Journals
2025 EN
Nishikura Toshi · Kitamura Kaori · Watanabe Yumi
+10 more
ABSTRACT Aim Individuals with depressive symptoms have been reported to have an increased risk of falls; however, information on whether the association is severity‐dependent is lacking. This study aimed to examine associations of depressive symptoms with recurrent fall risk in middle‐aged and older people. Methods This 5‐year cohort study included 6703 community‐dwelling Japanese people aged 40–74 years. A baseline self‐administrated questionnaire survey was conducted in 2011–2013. Depressive symptoms were evaluated using the 11‐item Center for Epidemiologic Studies Depression Scale ( CES ‐D). CES ‐D scores were categorized as < 7 (normal), ≥ 7 to < 9, and ≥ 9. Information on falls in the year preceding the 5‐year survey was collected, wherein falls occurring two or more times were classified as recurrent falls. Multiple logistic regression analysis was used to obtain odds ratios ( ORs ) adjusted for potential confounders. Results The mean age of participants was 59.7 years, and 256 recurrent falls were reported. Higher CES ‐D scores were associated with higher recurrent fall risk (adjusted P for trend < 0.0001), with the highest CES ‐D score group having a significantly higher OR (1.97, 95% CI : 1.44–2.70) than the reference. When stratified by sex and age, higher CES ‐D scores were associated with higher recurrent fall risk in both men and women (adjusted P for trend = 0.0275 and 0.0001, respectively) and in < 65‐year and ≥ 65‐year groups (Adjusted P for trend = 0.0006 and 0.0144, respectively). Conclusion Depressive symptoms are severity‐dependently associated with higher recurrent fall risk in middle‐aged and older Japanese people. This association remained robust when analyzed by sex and age.
John Wiley & Sons Australia
Journals
2025 EN
Naganuma Atsushi · Kakizaki Satoru · Hatanaka Takeshi
+45 more
Abstract Aim This study aimed to evaluate the impact of infusion timing of time‐of‐day on clinical outcomes in patients with unresectable hepatocellular carcinoma (HCC) treated with atezolizumab plus bevacizumab combination therapy. Methods A retrospective analysis was conducted using data from 751 unresectable HCC patients treated with atezolizumab plus bevacizumab between September 2020 and April 2024. Patients were categorized into morning (AM; n = 351) and afternoon (PM; n = 400) groups based on infusion timing of time‐of‐day. Outcomes, including progression‐free survival (PFS), overall survival, objective response rate, and disease control rate, were assessed using Kaplan–Meier survival analysis and Cox regression analysis. Results The PFS was significantly longer in the AM group (8.6 months, 95% CI 7.6–10.5) compared with the PM group (6.0 months, 95% CI 5.4–7.0; p = 0.006). In contrast, overall survival was similar between the groups (AM: 24.7 months vs. PM: 21.4 months; p = 0.99). Cox regression analysis revealed that morning infusion was an independent favorable predictor of PFS (HR 1.23, 95% CI 1.04–1.45). Additionally, the AM group demonstrated superior objective response rate and disease control rate compared with the PM group, suggesting better tumor control. Conclusion Morning infusion of atezolizumab plus bevacizumab is associated with improved PFS and response rates in unresectable HCC patients, highlighting the potential for optimizing treatment outcomes through circadian timing.
Journals
2025 EN
Matono Tomomitsu · Tada Toshifumi · Kumada Takashi
+47 more
ABSTRACT Aim To investigate the prognostic impact of the neutrophil‐to‐lymphocyte ratio (NLR) on outcomes in patients with hepatocellular carcinoma (HCC) treated with durvalumab plus tremelimumab (Dur/Tre). Methods A total of 182 patients with HCC who received Dur/Tre were included in the analysis. Univariate and multivariate survival analyses were conducted. Additionally, hazard ratio (HR) spline curve analysis was used to determine the optimal NLR cut‐off values for predicting overall survival (OS). Results The median progression‐free survival (PFS) was 3.5 months (95% confidence interval [CI]: 2.7–4.4), whereas the median OS was not reached (95% CI: 12.1 months–not reached). Multivariate analysis demonstrated that treatment with Dur/Tre as a second‐line therapy or beyond was independently associated with worse PFS (HR: 1.819; 95% CI: 1.230–2.688; p = 0.003). Furthermore, an NLR of ≥ 2.56 was identified as an independent predictor of reduced OS (HR: 1.919; 95% CI: 1.033–3.566; p = 0.039). The median OS was not reached (95% CI: 12.3 months–not reached) in patients with an NLR of < 2.56, compared with 12.1 months (95% CI: 9.0 months–not reached) in those with an NLR of ≥ 2.56 ( p = 0.016). A Sankey diagram illustrating post‐treatment outcomes revealed that a significantly larger proportion of patients with high NLRs did not proceed to subsequent therapies but instead received best supportive care ( p = 0.046). Spline curve analysis showed that an NLR range of approximately 2.3–3.0 represents an appropriate cut‐off for predicting OS. Conclusions The NLR is a significant prognostic biomarker for OS in patients with HCC treated with Dur/Tre.
Journals
2025 EN
Matono Tomomitsu · Tada Toshifumi · Kumada Takashi
+49 more
ABSTRACT Aim To evaluate the safety and efficacy of durvalumab plus tremelimumab (Dur/Tre) in older adults with unresectable hepatocellular carcinoma (HCC). Methods A total of 345 patients with HCC who received Dur/Tre were included in this study. Using propensity score matching, we compared outcomes between older (aged ≥ 75 years; n = 120) and younger individuals ( n = 120). Results The median progression‐free survival (PFS) was 3.3 months in the older group and 4.5 months in the younger group ( p = 0.271). The median overall survival (OS) was 17.0 months in older individuals and 19.2 months in younger individuals ( p = 0.598). No statistically significant differences were observed in the therapeutic response between the two groups ( p = 0.264). Additionally, the incidence of immune‐mediated adverse events (AEs) did not differ significantly between older and younger individuals. Multivariate analyses revealed that age group (older vs. younger) was not an independent prognostic factor for PFS ( p = 0.250) or OS ( p = 0.489). In a subgroup analysis stratifying older individuals into three age categories (75–79, 80–84, and ≥ 85 years), no significant differences were observed in the cumulative OS or PFS across the subgroups ( p = 0.308 and 0.783). Similarly, the incidence of immune‐mediated AEs did not differ significantly among the age categories. Conclusions Dur/Tre appears to be a safe and effective treatment option for patients with HCC, regardless of age. Dur/Tre appears to be a safe and effective treatment option for patients with unresectable HCC, regardless of age.
Journals
2025 EN
Fernandes Georgina · Chappell Elizabeth · Goetghebuer Tessa
+23 more
Abstract Objectives This survey was conducted to describe current European postnatal prophylaxis (PNP) and infant feeding policies with the aim of informing future harmonized guidelines. Methods A total of 32 senior clinicians with relevant expertise, working in 20 countries within the European Region, were invited to complete a REDCap questionnaire between July and September 2023. Results Twenty‐three of the 32 invited paediatricians responded, representing 16/20 countries. There were multiple respondents from the same country for Italy ( n = 5), the UK ( n = 2), Germany ( n = 2) and France ( n = 2). All countries use risk stratification to guide PNP regimen selection. Nine out of 16 countries reported three risk categories, six out of 16 reported two, and one country reported differences in categorization. Criteria used to stratify risk varied between and within countries. For the lowest risk category, the PNP regimen reported ranged from no PNP to up to four weeks of one drug; the drug of choice reported was zidovudine, apart from one country which reported nevirapine. For the highest risk category, the most common regimen was zidovudine/lamivudine/nevirapine (20/23 respondents); regimen duration varied from two to six weeks with variation in recommended dosing. Guidelines support breastfeeding for infants born to people living with HIV in eight out of 16 countries; in the other eight, guidelines do not support/specify. Conclusions Guidelines and practice for PNP and infant feeding vary substantially across Europe and within some countries, reflecting the lack of robust evidence. Effort is needed to align policies and practice to reflect up‐to‐date knowledge to ensure the vertical transmission risk is minimized and unnecessary infant HIV testing and PNP avoided, while simultaneously supporting families to make informed decisions on infant feeding choice.
Journals
2025 EN
Keane Amy · Haberl Lila · Aho Inka
+7 more
Abstract Introduction A notable gap exists in research on HIV and breastfeeding in high‐income settings with continuous access to antiretroviral therapy (ART) and suppressed HIV viral loads. The Women Against Viruses in Europe (WAVE) initiative aimed to consolidate European guidelines on HIV and breastfeeding to better inform medical staff and people living with HIV in the decision‐making process for breastfeeding. Methods Representatives from 23 countries were contacted by WAVE to submit their guidelines on HIV and breastfeeding, translated into English. The initial contact was made on 20 April 2023, and the final response was received on 26 May 2023. The WAVE breastfeeding group summarized the guidelines into key topics related to breastfeeding for the purpose of this manuscript. Results A total of 19 guidelines from 20 countries were included in the review. While the majority of countries recommend formula feeding as the preferred feeding for infants born to mothers living with HIV, most provide recommendations to support parents who choose to breastfeed if certain criteria are met. Conclusion Despite recommendations being based on the same research, there is variation across guidelines. This review consolidates European guidelines, enabling us to learn from each other and pool our experiences to create a robust cohort for further research and guideline development for parents living with HIV and their infants.
Journals
2025 EN
Rezende Leandro Pereira · Oi Cintia Akemi · Ferreira Katia Maria
+2 more
Abstract The decline of insect populations worldwide has raised concerns about the negative impact on ecosystem services, particularly pollination. Among the vital pollinators, bees play a central role, with wild and solitary species often receiving less attention compared to commercially managed bees. In this study, we focused on investigating the genetic and morphometric variation found across urban populations of the solitary oil‐collecting bee Centris ( Heterocentris ) analis . We collected and examined 361 individuals (259 males, 102 females) from 26 different locations in Brazil between 2012 and 2018. First, we developed a model to identify potential climatic habitats for this species, which revealed its distribution ranging from Mexico and North America to southern Brazil and other countries in South America. Second, to assess the interpopulational genetic differentiation, we genotyped 266 individuals from 25 locations at 16 species‐specific microsatellite loci. Our analysis indicated no genetic structuring. Third, a geometric morphometrics analysis of the wings from 361 individuals showed a clear sexual size dimorphism, with centroid size (CS) of males bigger than CS of females, but low differentiation among samples from four phytogeographical regions (Amazonian Forest, Cerrado, Caatinga, and Atlantic Forest). Intranidal sociogenetic structure was assessed through microsatellite genotyping, confirming a monogyny‐monandry mating system. Our findings emphasise the importance of studying both male and female solitary bees in the wild and urban areas to better comprehend the impacts of human‐dominated habitats on insect population genetics, a critical step for proposing effective conservation and management strategies to preserve them. Understanding the population genetics of these species is a critical step in developing effective conservation and management strategies to preserve them. Moreover, C. analis is a vital pollinator of various plant families, and identifying the plant species most frequently visited by these pollinators and promoting their cultivation in urban landscapes are valuable initiatives to support conservation efforts.
Journals
2025 EN
Janini Ana Cristina Padilha · Pelepenko Lauter Eston · Moraes Brenda Fornazaro
+10 more
Abstract Aim Calcium silicate‐based cements have been widely used in dentistry mainly due to their physicochemical and biological properties. Commercially available materials use radiopacifiers containing metals (bismuth, tantalum, tungsten and/or zirconium). To investigate volumetric changes, in vivo biocompatibility and systemic migration from eight commercially available materials, including powder/liquid and ‘ready‐to‐use’ presentations. Methodology After characterization, tubes were implanted in healthy Wistar rats' alveolar bone and subcutaneous tissues. Micro‐CT was used to evaluate volumetric change before/after 30 days of implantation. Histological and immunohistochemistry analysis were used to evaluate materials' biocompatibility. After euthanasia, kidney samples were retrieved, acidic digested and evaluated by inductively coupled plasma mass spectrometry (ICP‐MS) for bismuth, tantalum, tungsten and zirconium mass fractions. Statistical analysis compared the results for normality and comparisons adopted a level of significance of 0.05. Results Characterization photomicrographs and spectroscopy analysis revealed calcium, silicon and radiopacifiers for tested cements. Volumetric changes after implantation showed higher alteration in subcutaneous tissues than alveolar bone indicating that Biodentine, EndoSequence BC RRM Putty and ProRoot MTA were the most stable materials. Histological analysis found intense inflammation for NeoPUTTY and moderate for the other materials; osteocalcin and osteopontin were positively marked for all materials. Despite its volumetric stability, ProRoot MTA showed a 1000‐fold higher mass fraction of bismuth accumulation and MTA Repair HP a 37‐fold higher tungsten accumulation in kidney samples when compared with the nonexposed controls. All tantalum‐analysed samples indicated a similar mass fraction with the nonexposed controls. Biodentine exhibited a significant lower kidney mass fraction of zirconium accumulation when compared with this control. Conclusions Volumetric analysis revealed that Bio‐C Repair, NeoPUTTY and MTA Repair HP presented greater volumetric loss when implanted in the subcutaneous tissue. NeoPUTTY presented more intense inflammatory infiltrate. Systemic migration analysis highlighted the predominance of bismuth in the ProRoot MTA group. These results suggest that endodontic repair cements are affected by their chemical composition, the type of implant tissue and different clinical settings.
Journals
2025 EN
Trocin Cristina · Lee Gwanhoo · Bernardi Roberta
+1 more
Abstract Drawing upon an affordance‐actualisation perspective, we aim to advance our knowledge of the emergence of unintended consequences from the implementation of Electronic Health Record (EHR) systems. Prior research has not yet deeply understood how these unintended consequences unfold. We investigate how the (non‐)actualisation of affordances produces unintended consequences. Our exploratory case study of an EHR system implemented in Italy reveals four types of actions (flexing, bypassing, avoiding, and reorganising) through which different types of unintended consequences occur with the (non‐)actualisation of affordances. We explain and theorise how interactions among technology features and psychosocial and organisational constraints/enablers contribute to users' perception of affordances and technological constraints. This, in turn, influences different types of user actions, leading to unintended consequences. Our findings and insights contribute to the literature on unintended consequences and help organisations better manage implementing new systems.
Journals
2025 EN
Mutti Silvia · Cavalleri Alessia · Federici Stefania
+16 more
ABSTRACT Chronic Myeloid Leukaemia is driven by the BCR::ABL1 fusion gene. Although Tyrosine Kinase Inhibitors have significantly improved patient outcomes, drug resistance and disease persistence remain challenges, highlighting the need for effective preclinical models. We observed cellular heterogeneity among CML models in response to TKIs, influencing viability, metabolism, and molecular markers. With growing interest in extracellular vesicles as mediators of leukaemia progression via oncogenic cargo like BCR::ABL1, we explored whether EVs from different CML cell lines exhibit distinct features. EVs from K562 and KCL22 cells were characterised under basal conditions using Fourier Transform Infrared spectroscopy, Atomic Force Microscopy, dot blotting, and Nanoparticle Tracking Analysis. We assessed EV release and BCR::ABL1 content before and after treatment with imatinib, nilotinib, or dasatinib, alongside Ki67 expression to gauge proliferation. Fourier Transform Infrared Spectroscopy with Principal Component Analysis revealed distinct clustering of EVs by cell line. While untreated K562 and KCL22 cells showed similar EV output and BCR::ABL1 content, post‐treatment K562 cells released more EVs with elevated BCR::ABL1 transcripts. KCL22 cells showed earlier reduction in Ki67 expression. These findings highlight model‐dependent EV behaviour, reflecting patient heterogeneity and reinforcing the need for careful model selection in CML research.