The Association between Discrepancies in Parental Emotional Expressivity, Adolescent Loneliness and Depression: A Multi-Informant Study Using Response Surface Analysis.

Incongruent perceptions of parental emotional expressivity between parents and adolescents may signify relational challenges, potentially impacting adolescents' socioemotional adjustment. Direct evidence is still lacking and father-adolescent discrepancies are overlooked. This study employed a multi-informant design to investigate whether both mother-adolescent and father-adolescent discrepancies in perceptions of parental expressivity are related to adolescents' mental well-being, specifically focusing on loneliness and depression. Analyzing data from 681 families (mean age of adolescents = 15.5 years old, 51.2% girls, 40% only-children) in China revealed that adolescents tended to perceive paternal and maternal emotional expressivity more negatively than their parents, particularly fathers. Polynomial regression and response surface analysis showed significant links between parent-adolescent congruence and incongruence and adolescent loneliness. (In)Congruence between adolescents and mothers or fathers predicted later adolescent depression, mediated by adolescent loneliness and varied by the dimension of emotional expressivity. These findings provide insights into the roles of mothers' and fathers' emotional expressivity in shaping children's mental well-being during adolescence.

Structural analysis and in vitro fermentation characteristics of an Avicennia marina fruit RG-I pectin as a potential prebiotic.

Avicennia marina (Forssk.) Vierh. is a highly salt-tolerant mangrove, and its fruit has been traditionally used for treating constipation and dysentery. In this study, a pectin (AMFPs-0-1) was extracted and isolated from this fruit for the first time, its structure was analyzed, and the effects on the human gut microbiota were investigated. The results indicated that AMFPs-0-1 with a molecular weight of 798 kDa had a backbone consisting of alternating →2)-α-L-Rhap-(1→ and →4)-α-D-GalpA-(1→ residues and side chains composed of →3-α-L-Araf-(1→-linked arabinan with a terminal ß-L-Araf, →5-α-L-Araf-(1→-linked arabinan, and →4)-ß-D-Galp-(1→-linked galactan that linked to the C-4 positions of all α-L-Rhap residues in the backbone. It belongs to a type I rhamnogalacturonan (RG-I) pectin but has no arabinogalactosyl chains. AMFPs-0-1 could be consumed by human gut microbiota and increase the abundance of some beneficial bacteria, such as Bifidobacterium, Mitsuokella, and Megasphaera, which could help fight digestive disorders. These findings provide a structural basis for the potential application of A. marina fruit RG-I pectic polysaccharides in improving human intestinal health.

Secretion of IFN-γ by specific T cells in HCMV infection.

One major risk for recipients undergoing allogeneic hematopoietic stem cell transplants (allo-HSCTs) is infection with the human cytomegalovirus (HCMV). For HCMV treatment, it is especially crucial to be able to differentiate between recipients who are at high risk of reactivation and those who are not. In this study, HCMV-DNA was collected from 60 HLA-A*02 allo-HSCT recipients before and after transplantation. After transplantation, the release of interferon (IFN)-γ by T cells specific to HCMV was assessed using the enzyme-linked immunospot assay (ELISPOT). The results show that the median viral load (VL) was significantly higher in the HCMV persistent-infection group compared to the non-persistent-infection group (p = 0.002), and that the late-infection rate was considerably higher in the high-VL group compared to the low-VL group (p = 0.014). The uninfected group had a considerably higher median IFN-γ spot-forming cell (SFC) count than the persistent-infection group (p = 0.001), and IFN-γ SFC counts correlated negatively and linearly with VLs (r = -0.397, p = 0.002). The immune-response groups showed significantly difference in median VL (p = 0.018), and the high immune response group had a reduced late-infection rate than the no/low immune response groups (p = 0.049). Our study showed that allo-HSCT recipients with a high VL at an early transplantation stage were at high risk for late HCMV infection. Further HCMV reactivation can be prevented by HCMV-specific T cells secreting enough IFN-γ.

Characterize the Growth and Metabolism of Acidithiobacillus ferrooxidans under Electroautotrophic and Chemoautotrophic Conditions.

Acidophiles are capable of surviving in extreme environments with low pH. Acidithiobacillus ferrooxidans is a typical acidophilic bacterium that has been extensively studied when grown chemoautotrophically, i.e., when it derives energy from oxidation of Fe2+ or reduced inorganic sulfur compounds (RISCs). Although it is also known to grow with electrons supplied by solid electrodes serving as the sole source of energy, the understanding of its electroautotrophic growth is still limited. This study aimed to compare the growth characteristics of A. ferrooxidans under electroautotrophic (ea) and chemoautotrophic (ca) conditions, with an attempt to elucidate the possible mechanism(s) of extracellular electron flow into the cells. Jarosite was identified by Raman spectroscopy, and it accumulated when A. ferrooxidans used Fe2+ as the electron donor, but negligible mineral deposition occurred during electroautotrophic growth. Scanning electron microscopy (SEM) showed that A. ferrooxidans possesses more pili and extracellular polymeric substances (EPSs) under electroautotrophic conditions. A total of 493 differentially expressed genes (DEGs) were identified, with 297 genes being down-regulated and 196 genes being up-regulated in ea versus ca conditions. The genes known to be essential for chemoautotrophic growth showed a decreased expression in the electroautotrophic condition; meanwhile, there was an increased expression of genes related to direct electron transfer across the cell's outer/inner membranes and transmembrane proteins such as pilin and porin. Joint analysis of DEGs and differentially expressed metabolites (DEMs) showed that galactose metabolism is enhanced during electroautotrophic growth, inducing A. ferrooxidans to produce more EPSs, which aids the cells in adhering to the solid electrode during their growth. These results suggested that electroautotrophy and chemoautotrophy of A. ferrooxidans have different extracellular electron uptake (EEU) pathways, and a model of EEU during electroautotrophic growth is proposed. The use of extracellular electrons as the sole energy source triggers A. ferrooxidans to adopt metabolic and subsequently phenotypic modifications.

Mechanisms of sleep disturbances in long-term cancer survivors: a childhood cancer survivor study report.

BACKGROUND: Sleep problems following childhood cancer treatment may persist into adulthood, exacerbating cancer-related late effects and putting survivors at risk for poor physical and psychosocial functioning. This study examines sleep in long-term survivors and their siblings to identify risk factors and disease correlates. METHODS: Childhood cancer survivors (≥5 years from diagnosis; n = 12 340; 51.5% female; mean [SD] age = 39.4 [9.6] years) and siblings (n = 2395; 57.1% female; age = 44.6 [10.5] years) participating in the Childhood Cancer Survivor Study completed the Pittsburgh Sleep Quality Index (PSQI). Multivariable Poisson-error generalized estimating equation compared prevalence of binary sleep outcomes between survivors and siblings and evaluated cancer history and chronic health conditions (CHC) for associations with sleep outcomes, adjusting for age (at diagnosis and current), sex, race/ethnicity, and body mass index. RESULTS: Survivors were more likely to report clinically elevated composite PSQI scores (>5; 45.1% vs 40.0%, adjusted prevalence ratio [PR] = 1.20, 95% CI = 1.13 to 1.27), symptoms of insomnia (38.8% vs 32.0%, PR = 1.26, 95% CI = 1.18 to 1.35), snoring (18.0% vs 17.4%, PR = 1.11, 95% CI = 1.01 to 1.23), and sleep medication use (13.2% vs 11.5%, PR = 1.28, 95% CI = 1.12 to 1.45) compared with siblings. Within cancer survivors, PSQI scores were similar across diagnoses. Anthracycline exposure (PR = 1.13, 95% CI = 1.03 to 1.25), abdominal radiation (PR = 1.16, 95% CI = 1.04 to 1.29), and increasing CHC burden were associated with elevated PSQI scores (PRs = 1.21-1.48). CONCLUSIONS: Among survivors, sleep problems were more closely related to CHC than diagnosis or treatment history, although longitudinal research is needed to determine the direction of this association. Frequent sleep-promoting medication use suggests interest in managing sleep problems; behavioral sleep intervention is advised for long-term management.

METTL3-mediated m6A RNA methylation was involved in aluminum-induced neurotoxicity.

Aluminum (Al) exposure has been linked to the development of a variety of neurodegenerative diseases. However, whether m6A RNA methylation participated in Al-induced neurotoxicity remain to be defined. In this study, mice were administrated with aluminum-lactate at dose of 220 mg/kg. bw by gavage for 3 months. Meanwhile, the primary hippocampal neurons were isolated and treated with 0, 50, 100, 150 µM aluminum-lactate, respectively for 7 days. Al exposure caused neuronal shrinkage, decreased Nissl bodies, and increased apoptosis. In accordance, in vitro studies also showed that Al exposure led to neuronal apoptosis in a dose-dependent manner, together with the decline in m6A RNA methylation levels. Moreover, the mRNA expression of Mettl3, Mettl14, Fto, and Ythdf2 were decreased upon Al exposure. Notably, the protein expression of METTL3 was dramatically down-regulated by 42% and 35% in Al-treated mice and neurons, suggesting METTL3 might exert a crucial role in Al-induced neurotoxicity. We next established a mouse model with hippocampus-specific overexpressing of Mettl3 gene to confirm the regulatory role of RNA methylation and found that METTL3 overexpression relieved the neurological injury induced by Al. The integrated MeRIP-seq and RNA-seq analysis elucidated that 631 genes were differentially expressed at both m6A RNA methylation and mRNA expression. Notably, EGFR tyrosine kinase inhibitor resistance, Rap1 signaling pathway, protein digestion and absorption might be involved in Al-induced neurotoxicity. Moreover, VEGFA, Thbs1, and PDGFB might be the central molecules. Collectively, our findings provide the novel sight into the role of m6A RNA methylation in neurodegenerative disease induced by Al.

Financial hardship among siblings of long-term survivors of childhood cancer: A Childhood Cancer Survivor Study report.

BACKGROUND: Siblings of children with cancer may experience adverse household economic consequences, but their financial outcomes in adulthood are unknown. METHODS: A total of 880 siblings (aged 18-64 years) of adult-aged childhood cancer survivors were surveyed to estimate the prevalence of financial hardship by three established domains (behavioral, material, and psychological). For individual financial hardship items matching the contemporaneous National Health Interview Survey or Behavioral Risk Factor Surveillance System, siblings were compared with the general population by calculating adjusted prevalence odds ratios (ORs) to sample-weighted responses. Multivariable logistic regression models examined associations between sibling characteristics and each hardship domain and between sibling hardship and survivors' cancer/treatment characteristics. RESULTS: Behavioral, material, and psychological hardship was reported by 24%, 35%, and 28%, respectively. Compared with national survey respondents, siblings were more likely to report worries about medical bills (OR, 1.14; 95% confidence interval [CI], 1.06-1.22), difficulty affording nutritious foods (OR, 1.79; 95% CI, 1.54-2.07), and forgoing needed medical care (OR, 1.38; 95% CI, 1.10-1.73), prescription medications (OR, 2.52; 95% CI, 1.99-3.20), and dental care (OR, 1.34; 95% CI, 1.15-1.57) because of cost. Sibling characteristics associated with reporting financial hardship in one or more domains included female sex, older age, chronic health conditions, lower income, not having health insurance, high out-of-pocket medical expenditures, and nonmedical/nonhome debt. No survivor cancer/treatment characteristics were associated with sibling financial hardship. CONCLUSIONS: Adult siblings of childhood cancer survivors were more likely to experience financial hardship compared with the general population. Childhood cancer may adversely affect entire households, with potentially lasting implications.

Identification of Fangchinoline as a novel autophagy inhibitor with an adjuvant of chemotherapy against lung cancer.

Autophagy is a fundamental recycling pathway that enhances cellular resilience, promoting survival. However, this survival mechanism can impede anti-cancer treatment strategies designed to induce cell death. In this study, we identified a novel autophagy inhibitor, Fangchinoline (Fan) isolated from the traditional Chinese medicine Stephania tetrandra. We speculated that when Fan blocks autophagy, cancer cells lose substantial self-preservation abilities during treatment. Firstly, we examined in detail the mechanism through which Fan inhibits autophagy. Specifically, Fan induced a significant increase in autophagosomes, as indicated by GFP-LC3 labeling, confirmed by the up-regulation of LC3-II. The autophagy receptor protein p62 was also up-regulated, suggesting a potential inhibition of autophagy flux. We further ruled out the possibility of fusion barriers between lysosomes and autophagosomes, as confirmed by their co-localization in double fluorescence staining. However, the lysosomal acid environment might be compromised, as suggested by the diminished fluorescence of acidity-sensitive dyes in the lysosomes and the corresponding decrease in mature forms of lysosomal cathepsin. To test the anti-cancer potential of Fan, we combined it with Cisplatin (Cis) or Paclitaxel (PTX) for lung cancer cell treatment. This combined treatment demonstrated a synergistically enhanced killing effect. These promising anti-tumor results were also replicated in a xenografted tumor model. The significance of this research lies in the identification of Fan as a potent autophagy inhibitor and its potential to enhance the efficacy of existing anti-cancer drugs. By unraveling the mechanisms of Fan's action on autophagy and demonstrating its synergistic effect in combination therapies, our study provides valuable insights for developing novel strategies to overcome autophagy-mediated resistance in cancer treatment.

Untapped talents: insight into the ecological significance of methanotrophs and its prospects.

The deep ocean is a rich reservoir of unique organisms with great potential for bioprospecting, ecosystem services, and the discovery of novel materials. These organisms thrive in harsh environments characterized by high hydrostatic pressure, low temperature, and limited nutrients. Hydrothermal vents and cold seeps, prominent features of the deep ocean, provide a habitat for microorganisms involved in the production and filtration of methane, a potent greenhouse gas. Methanotrophs, comprising archaea and bacteria, play a crucial role in these processes. This review examines the intricate relationship between the roles, responses, and niche specialization of methanotrophs in the deep ocean ecosystem. Our findings reveal that different types of methanotrophs dominate specific zones depending on prevailing conditions. Type I methanotrophs thrive in oxygen-rich zones, while Type II methanotrophs display adaptability to diverse conditions. Verrumicrobiota and NC10 flourish in hypoxic and extreme environments. In addition to their essential role in methane regulation, methanotrophs contribute to various ecosystem functions. They participate in the degradation of foreign compounds and play a crucial role in cycling biogeochemical elements like metals, sulfur, and nitrogen. Methanotrophs also serve as a significant energy source for the oceanic food chain and drive chemosynthesis in the deep ocean. Moreover, their presence offers promising prospects for biotechnological applications, including the production of valuable compounds such as polyhydroxyalkanoates, methanobactin, exopolysaccharides, ecotines, methanol, putrescine, and biofuels. In conclusion, this review highlights the multifaceted roles of methanotrophs in the deep ocean ecosystem, underscoring their ecological significance and their potential for advancements in biotechnology. A comprehensive understanding of their niche specialization and responses will contribute to harnessing their full potential in various domains.

Financial Hardship in Childhood Cancer Survivors Treated with Hematopoietic Cell Transplantation: A Report from the Childhood Cancer Survivor Study.

Long-term survivors of childhood cancer are at risk for financial hardship. However, it is not known if HCT leads to an incremental change in financial hardship for survivors who received it versus those who did not. We examined financial outcomes among adult survivors of childhood cancer who had undergone HCT. Using a cross-sectional survey in the Childhood Cancer Survivor Study population between 2017 and 2019, self-reported financial hardship was compared between survivors who received HCT, survivors treated without HCT ("non-HCT"), and siblings and categorized into 3 domains: material hardship/financial sacrifices, behavioral, and psychological hardship. The standardized score of each domain of financial hardship was calculated by adding the item responses and dividing by the standard deviation among siblings. Multivariable linear and logistic regression were used to evaluate associations between sociodemographic characteristics, cancer diagnosis, post-treatment complications, and financial hardship among survivors. The mean adjusted score for each hardship domain was not significantly different between HCT survivors (n = 133) and non-HCT survivors (n = 2711); mean differences were .18 (95% confidence interval [CI], -.05 to .41) for material hardship/financial sacrifices, .07 (95% CI, -.18 to .32) for behavioral hardship, and .19 (95% CI, -.04 to .42) for psychological hardship. Within specific items, a higher proportion of survivors treated with HCT reported greater financial hardship compared to non-HCT survivors. HCT survivors also had significantly higher mean domain scores compared to sibling controls (n = 1027) in all domains. Household income and chronic health conditions, but not HCT, were associated with financial hardship among all survivors. Adult survivors of childhood cancer treated with HCT do not report greater overall financial hardship compared to non-HCT survivors but do report greater overall financial hardship compared to sibling controls. Surveillance and intervention may be necessary for all survivors regardless of HCT status.

Application of Transcranial Magnetic Stimulation with Electroencephalography in the Evaluation of Brain Function Changes after Stroke.

Objective: Based on transcranial magnetic stimulation (TMS) with electroencephalography technology, this study analyzed the rehabilitation mechanism of patients' motor function reconstruction and nerve remodeling after stroke. It revealed the function of the cerebral cortex network at a deeper level and established a set of prognostic marker evaluation indicators for the reconstruction of motor function after stroke. Methods: Twenty-one patients treated at the Beijing Rehabilitation Hospital of Capital Medical University because of ischemic stroke in the territory supplied by the middle cerebral artery were selected as the experimental group. Neurophysiological evaluation, motor function evaluation, and clinical evaluation were performed 30 and 180 d after the onset of ischemic stroke. In the control group, neurophysiological evaluation was also performed as a reference index to evaluate the changes in cortical patterns after stroke. Results: The brain topographic map showed the changes in energy or power spectral density (PSD) at 1,000 ms after stimulation as compared with before stimulation, but no difference was detected in these patients. The time-frequency analysis showed that when the left primary motor cortex (M1) area was stimulated using TMS, the PSD values of the left and right M1 and posterior occipital cortex areas produced an 8-40 Hz wave band in patients S1-S11. There was no significant energy change in patients S12-S16. Conclusions: For patients with different injury types, degrees of injury, and different onset periods, individualized intervention methods should be adopted. The evaluation methods should be as diverse as possible, and the rehabilitation effects of patients should be assessed from multiple perspectives to avoid the limitations of single factors. Possible mechanism: After brain injury, the nervous system can change its structure and function through different ways and maintain it for a certain period of time. This plasticity change will change with the course of the disease.

The Effect of W Content on the Microstructure, Mechanics and Electrical Performance of an FeCrCo Alloy.

In this paper, FeCrCoW alloys with different W contents (0.4, 2.1 and 3.4 at%) are designed and studied in order to overcome the existing shortcomings of resistance materials. These resistance materials have high resistivity and a low temperature coefficient of resistivity. It is observed that the addition of W has a remarkable effect on the phase structure of the alloy. In particular, when the W content is 3.4 at%, the single BCC phase of the alloy can be transformed into the BCC and FCC phase. Meanwhile, when analyzed by transmission electron microscopy, there are stacking faults and martensite in FeCrCoW alloy with W content of 3.4 at%. These features are related to excessive W content. In addition, the strength of the alloy can be improved, and the ultimate tensile strength and yield strength are both very high, which are considered as grain-boundary strengthening and solid solution strengthening, caused by the addition of W. The electrical resistivity of the FeCrCoW alloys decreases when the content of W is more than 2.1 at%. The maximum resistivity of the alloy is 170 ± 1.5 µΩ·cm. Moreover, the unique properties of the transition metal allow the alloy to have a low temperature coefficient of resistivity in the temperature range of 298~393 K. The temperature coefficient of resistivity values of the W0.4, W2.1 and W3.4 alloys are -0.0073, -0.0052 and -0.0051 ppm/K. Therefore, this work provides a vision for resistance alloys, which can achieve highly stable resistivity and high strengths in a certain temperature range.

METTL3-mediated m6A mRNA modification was involved in cadmium-induced liver injury.

Cadmium is an environmental pollutant that has extensive deleterious effects. However, the mechanisms underlying the hepatotoxicity induced by long-term exposure to cadmium remained undefined. In the present study, we explored the role of m6A methylation in the development of cadmium-induced liver disease. We showed a dynamic change of RNA methylation in liver tissue from mice administrated with cadmium chloride (CdCl2) for 3, 6 and 9 months, respectively. Particularly, the METTL3 expression was declined in a time-dependent manner, associated with the degree of liver injury, indicating the involvement of METTL3 in hepatotoxicity induced by CdCl2. Moreover, we established a mouse model with liver-specific over-expression of Mettl3 and administrated these mice with CdCl2 for 6 months. Notably, METTL3 highly expressed in hepatocytes attenuated CdCl2-induced steatosis and liver fibrosis in mice. In vitro assay also showed METTL3 overexpression ameliorated the CdCl2-induced cytotoxicity and activation of primary hepatic stellate cells. Furthermore, transcriptome analysis identified 268 differentially expressed genes both in mice liver tissue treated with CdCl2 for 3 months and 9 months. Among them, 115 genes were predicted to be regulated by METTL3 determined by m6A2Target database. Further analysis revealed the perturbation of metabolic pathway, glycerophospholipid metabolism, ErbB signaling pathway, Hippo signaling pathway, and choline metabolism in cancer, and circadian rhythm, led to hepatotoxicity induced by CdCl2. Collectively, our findings reveal new insight into the crucial role of epigenetic modifications in hepatic diseases caused by long-term exposure to cadmium.

Tailor-Made Autophagy Cascade Amplification Polymeric Nanoparticles for Enhanced Tumor Immunotherapy.

Chemotherapeutics can induce immunogenic cell death (ICD) by triggering autophagy and mediate antitumor immunotherapy. However, using chemotherapeutics alone can only cause mild cell-protective autophagy and be incapable of inducing sufficient ICD efficacy. The participation of autophagy inducer is competent to enhance autophagy, so the level of ICD is promoted and the effect of antitumor immunotherapy is highly increased. Herein, tailor-made autophagy cascade amplification polymeric nanoparticles STF@AHPPE are constructed to enhance tumor immunotherapy. Arginine (Arg), polyethyleneglycol-polycaprolactone, and epirubicin (EPI) are grafted onto hyaluronic acid (HA) via disulfide bond to form the AHPPE nanoparticles and autophagy inducer STF-62247 (STF) is loaded. When STF@AHPPE nanoparticles target to tumor tissues and efficiently enter into tumor cells with the help of HA and Arg, the high glutathione concentration leads to the cleavage of disulfide bond and the release of EPI and STF. Finally, STF@AHPPE induces violent cytotoxic autophagy and strong ICD efficacy. As compared to AHPPE nanoparticles, STF@AHPPE nanoparticles kill the most tumor cells and show the more obvious ICD efficacy and immune activation ability. This work provides a novel strategy for combining tumor chemo-immunotherapy with autophagy induction.

Effective extraction of the metabolites of toluene and xylene based on a postsynthetic-modified magnetic covalent organic polymer.

Toluene and xylene are volatile organic compounds, and long-term exposure to toluene and xylene may cause brain structure and nervous system damage. To evaluate exposure to toluene and xylene in the environment, it is usually possible to monitor their metabolites in organisms, hippuric acid (HA) and methylhippuric acid (MHA). In this work, we designed a new magnetic solid phase extraction (MSPE) sorbent, zirconium postsynthetic-modified magnetic covalent organic polymer (Fe3O4@COP-COOZr), for purifying and enriching HA and 4-MHA. Zirconium ions were immobilized on the magnetic COP surface by postsynthetic modification without the use of additional coating layers or chelating ligands. The developed Fe3O4@COP-COOZr interacted with HA and 4-MHA through the π-π stacking effect and electrostatic interactions, as well as strong chelation with coordinatively unsaturated zirconium sites. The promising affinity material of Fe3O4@COP-COOZr in MSPE had high stability and recyclability. The established MSPE-HPLC-UV method showed low sorbent consumption (10 mg) and high sensitivity (LODs less than 0.1 µg L-1), and can be used for the analysis of HA and 4-MHA in real samples. The recoveries of the proposed method in real urine samples for the simultaneous determination of HA and 4-MHA were in the range of 83.5-103.2 %, and the RSDs were 0.9-7.1 %.

Ideal vs Actual Timing of Palliative Care Integration for Children With Cancer in Latin America.

Importance: Early integration of pediatric palliative care (PPC) for children with cancer is critical for the quality of life of both patient and family. To improve access to PPC in resource-limited settings, barriers to early integration must be understood. Objectives: To evaluate the ideal vs actual timing of PPC integration for children with cancer and to uncover barriers to early integration identified by physicians in Latin America. Design, Setting, and Participants: The Assessing Doctors' Attitudes on Palliative Treatment (ADAPT) survey was distributed electronically from August 1, 2020, to January 31, 2021, to physicians who treat children with cancer in 17 countries in Latin America. Main Outcomes and Measures: The ADAPT survey queried for understanding of ideal vs actual timing of PPC for children with cancer and for identification of barriers to PPC integration. Descriptive statistics were used to summarize the data. For secondary analyses, a comparison of the associations of previous palliative care training with physician specialty was performed using the Pearson χ2 test or the Fisher exact test. The McNemar test was used to assess responses regarding the actual vs ideal timing of PPC consultation. Analysis of variance was used to compare mean values for perceived barriers by country income level. Answers to open-ended questions were analyzed qualitatively. Results: A total of 831 physicians (578 women [69.6%]; 275 physicians [33.1%] aged <35 years and 556 physicians [66.9%] aged ≥35 years) from 17 countries participated, with an overall response rate of 37.9% (831 of 2193) and a median country response rate of 51.4% (range, 22.2%-88.9%). Most respondents (572 [68.8%]) said that PPC should be involved from diagnosis, but only 117 (14.1%) stated that this occurred at their institution (P < .001). The most significantly ranked barriers to PPC were lack of home-based services (713 [85.8%]), personnel (654 [78.7%]), and knowledge about PPC (693 [83.4%]), along with physician (676 [81.3%]) and family (603 [72.6%]) discomfort about PPC involvement. In addition, these barriers were rated as more important in lower-middle income countries compared with upper-middle income countries and high-income countries. Conclusions and Relevance: This study highlights the discrepancy between ideal and actual timing of PPC for children with cancer and barriers to early PPC integration in Latin America. Interventions addressing access to PPC resources, didactic training, and clinical education (with a particular focus on equitable access to basic resources and support) are critical to improve the timing and quality of PPC in the region.

An international multicenter survey reveals health care providers' knowledge gap in childhood central nervous system tumors.

Childhood central nervous system (CNS) tumors have longer delays in diagnosis than do other pediatric malignancies because health care providers (HCPs) lack awareness about clinical presentation of these tumors. To evaluate the knowledge gap among HCPs, we conducted a global cross-sectional survey. The survey consisted of a set of CNS tumor knowledge questions focused on symptoms, signs, and imaging indications. The survey was disseminated to HCPs via email (November 2018-March 2020). Participants had to complete a pre-test survey, attend an education seminar on CNS tumors, and complete a post-test survey. The knowledge gap was evaluated using pre-test and post-test scores. We received 889 pre-test and 392 post-test responses. Most respondents were from Asia (73.1% of pre-test responses; 87.5% of post-test responses). The median pre-test score was 40.0% (range: 13.1-92.9%). A high percentage of correct answers were given in post-test responses (median score: 77.1%, range: 14.9-98.2%). In the pre-test, 18.7% of participants accurately responded that Cushing's triad was a less common symptom, and 15.0% recognized that children aged > 10 years are at risk of late diagnosis. Surprisingly, 21.9% falsely reported that patients with malignancy experienced the longest pre-diagnostic symptom interval, and 54.5% of respondents wrongly selected medulloblastoma as the most common CNS tumor. Overall, pediatricians demonstrated a greater knowledge gap on both surveys than did other specialties.  Conclusion: Pre- and post-test surveys revealed significant knowledge gaps in childhood CNS tumors among HCPs. Thus, raising professional awareness on clinical presentations of CNS tumors through educational strategies is important to address this knowledge deficit. What is Known: • Diagnostic delay in childhood central nervous system (CNS) tumors continues to be a significant problem that negatively impacts the quality of life and treatment sequelae. • Lack of medical education on CNS tumors is a contributing factor to this problem. What is New: • Most health care providers do not realize that low-grade tumors are the most common neoplasm in children. • Health care providers fail to recognize that teenagers and adolescents are a vulnerable age group for diagnostic delays, with the longest pre-diagnostic symptom interval.

Regional adaptation of the education in palliative and end-of-life Care Pediatrics (EPEC-Pediatrics) curriculum in Eurasia.

BACKGROUND: Pediatric palliative care (PPC) is a priority to improve pediatric hematology oncology (PHO) care in Eurasia. However, there are limited regional opportunities for PPC education. We describe the adaptation and implementation of a bilingual end-user Education in Palliative and End-of-Life Care (EPEC)-Pediatrics course for PHO clinicians in Eurasia. METHODS: Due to COVID-19, this course was delivered virtually, consisting of prerecorded, asynchronous lectures, and a bilingual workshop with interactive lectures and small group sessions. A pre-postcourse design was used to evaluate the knowledge acquisition of the participants including their knowledge alignment with World Health Organization (WHO) guidance, ideal timing of palliative care, and comfort in providing palliative care to their patients. Questions were mostly quantitative with multiple choice or Likert scale options, supplemented by free-text responses. RESULTS: A total of 44 (76%) participants from 14 countries completed all components of the course including pre- and postcourse assessments. Participant alignment with WHO guidance improved from 75% in the pre- to 90% in the postcourse assessments (p < 0.001). After participation, 93% felt more confident controlling the suffering of children at the end of life, 91% felt more confident in prescribing opioids and managing pain, and 98% better understood how to hold difficult conversations with patients and families. Most participants (98%) stated that they will change their clinical practice based on the skills and knowledge gained in this course. CONCLUSIONS: We present a successful regional adaptation of the EPEC-Pediatrics curriculum, including novel delivery of course content via a virtual bilingual format. This course resulted in significant improvement in participant attitudes and knowledge of PPC along with an understanding of the ideal timing of palliative care consultation and comfort in providing PPC to children with cancer. We plan to incorporate participant feedback to improve the course and repeat it annually to improve access to high-quality palliative care education for PHO clinicians in Eurasia.

Reactivation of occult hepatitis B virus infection in a renal transplant recipient.

We report a case of hepatitis B virus (HBV) reactivation in a renal transplant recipient. Reactivation manifested as an occult infection with detectable HBV-DNA and negativity for hepatitis B surface antigen (HBsAg). The anti-HBs antibody titre was above the protective threshold and continued to rise, to 951.36 mIU/ml, after HBV reactivation. Sequencing revealed multiple vaccine- and diagnostic-escape mutations in the major hydrophilic region of HBsAg. This case demonstrates both reactivation of an HBV escape mutant in a vaccinated patient and host immunity after virus mutation.