Journals
2024 EN
Nagato Toshihiro · Komatsuda Hiroki · Hayashi Ryusuke
+15 more
In CD70‐expressing tumors, the interaction of CD70 on tumor cells with its lymphocyte receptor, CD27, is thought to play a role in immunosuppression in the tumor microenvironment and elevated serum levels of soluble CD27 (sCD27). Previous studies showed that CD70 is expressed in nasopharyngeal carcinoma (NPC), an Epstein–Barr virus (EBV)‐related malignancy. However, the association between intratumoral CD70/CD27 expression and serum levels of sCD27 in NPC remains unclear. In the present study, we show that CD70 is primarily expressed by tumor cells in NPC and that CD27‐positive lymphocytes infiltrate around tumor cells. NPC patients with CD27‐positive lymphocytes had significantly better prognosis than patients lacking these cells. In addition, high CD70 expression by tumor cells tended to be correlated with shorter survival in NPC patients with CD27‐positive lymphocytes. Serum sCD27 levels were significantly increased in patients with NPC and provided good diagnostic accuracy for discriminating patients from healthy individuals. The concentration of serum sCD27 in patients with CD70‐positive NPC with CD27‐positive lymphocytes was significantly higher than in patients with tumors negative for CD70 and/or CD27, indicating that the intratumoral CD70/CD27 interaction boosts the release of sCD27. Furthermore, positive expression of CD70 by NPC cells was significantly correlated with EBV infection. Our results suggest that CD70/CD27‐targeted immunotherapies may be promising treatment options and that sCD27 may become an essential tool for evaluating the applicability of these therapies by predicting the intratumoral CD70/CD27 interaction in NPC.
Journals
2024 EN
Sales Érika Nayara Benício Gonçalves · Barbosa Filho Valter Cordeiro · Maciel Gabriel Pereira
+3 more
Purpose Understanding self‐rated health in young people can help orient global health actions, especially in regions of social vulnerability. The present study analysed individual and contextual factors associated with self‐rated health in a sample of Brazilian adolescents. Design and Methods Cross‐sectional data from 1272 adolescents (aged 11–17; 48.5% of girls) in low human development index (HDI) neighbourhoods were analysed (HDI from 0.170 to 0.491). The outcome variable was self‐rated health. Independent variables relating to individual factors (biological sex, age and economic class) and lifestyle (physical activity, alcohol, tobacco consumption and nutritional state) were measured using standardised instruments. The socio‐environmental variables were measured using neighbourhood registered data where the adolescents studied. Multilevel regression was used to estimate the regression coefficients and their 95% confidence intervals (CI). Results Good self‐rated health prevalence was of 72.2%. Being male (B: −0.165; CI: −0.250 to −0.081), age (B: −0.040; CI: −0.073 to −0.007), weekly duration of moderate to vigorous physical activity (B: 0.074; CI: 0.048–0.099), body mass index (B: −0.025; CI: −0.036 to −0.015), number of family healthcare teams in the neighbourhood (B: 0.019; CI: 0.006–0.033) and dengue incidence (B: −0.001; CI: −0.002; −0.000) were factors associated with self‐rated health among students from vulnerable areas. Conclusions/Practical Implications Approximately three in every 10 adolescents in areas of social vulnerability presented poor self‐rated health. This fact was associated with biological sex and age (individual factors), physical activity levels and BMI (lifestyle) and the number of family healthcare teams in the neighbourhood (contextual).
Journals
2024 EN
Alfaro Villanueva Lucia Alejandra · Junior Roberto Meirelles · Rangel Érika Bevilaqua
+7 more
Background Graft loss increases the risk of patient death after simultaneous pancreas‐kidney (SPK) transplantation. The relative risk of each graft failure is complex due to the influence of several competing events. Methods This retrospective, single‐center study compared 4‐year patient survival according to the graft status using Kaplan‐Meier (KM) and Competing Risk Analysis (CRA). Patient survival was also assessed according to five eras (Era 1: 2001–2003; Era 2: 2004–2006; Era 3: 2007–2009; Era 4: 2010–2012; Era 5: 2012–2015). Results Between 2000 and 2015, 432 SPK transplants were performed. Using KM, patient survival was 86.5% for patients without graft loss ( n = 333), 93.4% for patients with pancreas graft loss ( n = 46), 43.7% for patients with kidney graft loss ( n = 16), and 25.4% for patients with pancreas and kidney graft loss ( n = 37). Patient survival was underestimated using KM versus CRA methods in patients with pancreas and kidney graft losses (25.4% vs. 36.2%), respectively. Induction with lymphocyte depleting antibodies was associated with 81% reduced risk (HR.19, 95% CI.38–.98, p = .0048), while delayed kidney function (HR 2.94, 95% CI 1.09–7.95, p = .033) and surgical complications (HR 2.94, 95% CI 1.22–7.08, p = .016) were associated with higher risk of death. Four‐year patient survival increased from Era 1 to Era 5 (79% vs. 87.9%, p = .047). Conclusion In this cohort of patients, kidney graft loss, with or without pancreas graft loss, was associated with higher mortality after SPK transplantation. Compared to CRA, the KM model underestimated survival only among patients with pancreas and kidney graft losses. Patient survival increased over time.
Journals
2024 EN
MakinoItou Hatsune · Yamatani Noriko · Okubo Akemi
+4 more
Abstract The development of new technologies opens new avenues in the research field. Gene knockout is a key method for analyzing gene function in mice. Currently, conditional gene knockout strategies are employed to examine temporal and spatial gene function. However, phenotypes are sometimes not observed because of the time required for depletion due to the long half‐life of the target proteins. Protein knockdown using an improved auxin‐inducible degron system, AID2, overcomes such difficulties owing to rapid and efficient target depletion. We observed depletion of AID‐tagged proteins within a few to several hours by a simple intraperitoneal injection of the auxin analog, 5‐Ph‐IAA, which is much shorter than the time required for target depletion using conditional gene knockout. Importantly, the loss of protein is reversible, making protein knockdown useful to measure the effects of transient loss of protein function. Here, we also established several mouse lines useful for AID2‐medicated protein knockdown, which include knock‐in mouse lines in the ROSA26 locus; one expresses TIR1(F74G), and the other is the reporter expressing AID‐mCherry. We also established a germ‐cell‐specific TIR1 line and confirmed the protein knockdown specificity. In addition, we introduced an AID tag to an endogenous protein, DCP2 via the CAS9‐mediated gene editing method. We confirmed that the protein was effectively eliminated by TIR1(F74G), which resulted in the similar phenotype observed in knockout mouse within 20 h.
Journals
2024 EN
Forte Maurizio · D'Ambrosio Luca · Schiattarella Gabriele G.
+14 more
Abstract Background Defects of mitophagy, the selective form of autophagy for mitochondria, are commonly observed in several cardiovascular diseases and represent the main cause of mitochondrial dysfunction. For this reason, mitophagy has emerged as a novel and potential therapeutic target. Methods In this review, we discuss current evidence about the biological significance of mitophagy in relevant preclinical models of cardiac and vascular diseases, such as heart failure, ischemia/reperfusion injury, metabolic cardiomyopathy and atherosclerosis. Results Multiple studies have shown that cardiac and vascular mitophagy is an adaptive mechanism in response to stress, contributing to cardiovascular homeostasis. Mitophagy defects lead to cell death, ultimately impairing cardiac and vascular function, whereas restoration of mitophagy by specific compounds delays disease progression. Conclusions Despite previous efforts, the molecular mechanisms underlying mitophagy activation in response to stress are not fully characterized. A comprehensive understanding of different forms of mitophagy active in the cardiovascular system is extremely important for the development of new drugs targeting this process. Human studies evaluating mitophagy abnormalities in patients at high cardiovascular risk also represent a future challenge.
Journals
2024 EN
Martins André Ribeiro · Bastos Douglas Aviz · Sousa Leandro Melo
+3 more
Metacommunity theory seeks to explain how local and regional processes contribute to the organisation of biological communities. Recent conceptual frameworks of this theory indicate that the dynamics of populations and communities are jointly established by dispersal, species responses to environmental conditions and biotic interactions dependent on species density. Here, we use hierarchical joint species distribution modelling to verify the effects of environmental factors (at multiple spatial scales), drainage network configuration, spatial autocorrelation and interspecific interactions on the structure of fish assemblages in terra‐firme streams in the Eastern Brazilian Amazon. Thirty streams were sampled in two field surveys, and 89 species were collected in total. Our results confirm the effects of limited dispersal, environmental conditions (at multiple scales) and the configuration of the drainage network on the dynamics of these assemblages. Furthermore, our results suggest that interspecific interactions are less relevant for the structuring of fish metacommunities in small Amazonian headwater streams. Abiotic factors like drainage networks and environmental heterogeneity were better predictors of species distributions than co‐occurrence patterns with potential competitors or predators.
Journals
2024 EN
Noda Tatsuhiro · Takeichi Takuya · Tanahashi Kana
+16 more
Autosomal recessive congenital ichthyoses (ARCI) is a genetically heterogeneous condition that can be caused by pathogenic variants in at least 12 genes, including ABCA12 . ARCI mainly consists of congenital ichthyosiform erythroderma (CIE), lamellar ichthyosis (LI) and harlequin ichthyosis (HI). The objective was to determine previously unreported pathogenic variants in ABCA12 and to update genotype–phenotype correlations for patients with pathogenic ABCA12 variants. Pathogenic variants in ABCA12 were detected using Sanger sequencing or a combination of Sanger sequencing and whole‐exome sequencing. To verify the pathogenicity of a previously unreported large deletion and intron variant, cDNA analysis was performed using total RNA extracted from hair roots. Genetic analyses were performed on the patients with CIE, LI, HI and non‐congenital ichthyosis with unusual phenotypes (NIUP), and 11 previously unreported ABCA12 variants were identified. Sequencing of cDNA confirmed the aberrant splicing of the variant ABCA12 in the patients with the previously unreported large deletion and intron variant. Our findings expand the phenotype spectrum of ichthyosis patients with ABCA12 pathogenic variants. The present missense variants in ABCA12 are considered to be heterogenous in pathogenicity, and they lead to varying disease severities in patients with ARCI and non‐congenital ichthyosis with unusual phenotypes (NIUP).
Journals
2024 EN
Shen Minghua · van Klink Roel · Sagouis Alban
+117 more
ABSTRACT Motivation Freshwater ecosystems have been heavily impacted by land‐use changes, but data syntheses on these impacts are still limited. Here, we compiled a global database encompassing 241 studies with species abundance data (from multiple biological groups and geographic locations) across sites with different land‐use categories. This compilation will be useful for addressing questions regarding land‐use change and its impact on freshwater biodiversity. Main Types of Variables Contained The database includes metadata of each study, sites location, sample methods, sample time, land‐use category and abundance of each taxon. Spatial Location and Grain The database contains data from across the globe, with 85% of the sites having well‐defined geographical coordinates. Major Taxa and Level of Measurement The database covers all major freshwater biological groups including algae, macrophytes, zooplankton, macroinvertebrates, fish and amphibians.
Journals
2024 EN
Hatanaka Takeshi · Kakizaki Satoru · Hiraoka Atsushi
+44 more
Aim Elderly patients are believed to have a reduced immune capacity, which may make immunotherapy less effective. The aim of this study was to compare the therapeutic outcome of atezolizumab plus bevacizumab (Atez/Bev) and lenvatinib (LEN) for advanced hepatocellular carcinoma (HCC) in patients aged 80 years and older. Methods From March 2018 to July 2022, 170 and 92 elderly patients who received LEN and Atez/Bev as first‐line treatment, respectively, were retrospectively analyzed. Results The median ages of the Atez/Bev and LEN groups were 83.0 (8.01–86.0) and 83.0 (82.0–86.0) years ( p = 0.3), respectively. Men accounted for approximately 70% of the patients in both groups. The objective response rate was 35.9% in the LEN group and 33.7% in the Atez/Bev group ( p = 0.8), whereas the disease control rates in the LEN and Atez/Bev groups were 62.9% and 63.0%, respectively ( p = 1.0). The median progression‐free survival (PFS) in the LEN and Atez/Bev groups was 6.3 and 7.2 months, respectively, which were not significantly different ( p = 0.2). The median overall survival (OS) was 17.9 months in the LEN group and 14.0 months in the Atez/Bev group. This difference was not statistically significant ( p = 0.7). In multivariate analyses, the choice of treatment (LEN vs. Atez/Bev) showed no association with PFS or OS. The Atez/Bev group had a significantly higher rate of postprogression treatment (59.0% vs. 35.7%, p = 0.01) and a lower rate of discontinuation due to adverse events (69 [40.6%] vs. 19 [20.7%], p < 0.001) compared to the LEN group. Conclusions Atezolizumab plus bevacizumab showed comparable effectiveness to LEN in HCC patients aged 80 years and older. Given the results of postprogression treatment and discontinuation due to adverse events, Atez/Bev could serve as a first‐line treatment even for elderly HCC patients.
Journals
2024 EN
Tanaka Atsushi · Tsuji Keiji · Komiyama Yasuyuki
+14 more
Aim The diagnosis of drug‐induced liver injury (DILI) is challenging. We modified the revised electronic version of the Roussel Uclaf Causality Assessment Method (RUCAM) for the diagnosis of DILI (RECAM), the scoring system developed in US and Spanish cohorts in 2022, and developed RECAM‐J 2023 to align with the clinical practice in Japan. In the current study, we introduce RECAM‐J 2023 and verify its performance in the context of Japanese patients with DILI. Methods After translation of RECAM into Japanese, modifications were made to develop RECAM‐J 2023 without any alteration to the scores. To examine the validity and performance of RECAM‐J 2023, clinical information on DILI and non‐DILI cases in Japan were retrospectively collected. The diagnosis of DILI was made by expert's decision. Then we scored each case using RECAM‐J 2023, and calculated area under curve (AUC) values for identification for DILI. Results We collected data from 538 DILI and 128 non‐DILI cases. The sum of highly probable (HP) and probable (PR) cases categorized by RECAM‐J 2023 were only 206 (38%) in DILI cases. As the primary cause of low scores was the deduction with missing hepatitis virus markers, which is unlikely to be an issue in prospective applications, we rescored without these deductions. At this time, the sum of HP and PR was raised to 421 (78%). The AUCs of RECAM‐J 2023 without deductions were 0.70 and 0.88 for identifying at least HP, and at least PR, respectively. Conclusion RECAM‐J 2023, when prospectively used without any missing hepatitis virus markers, provides acceptable performance for identifying at least PR DILI cases in Japanese daily clinical practice.