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Background Accurate assessment and enhancement of health-related skills among oncology patients are pivotal for optimizing cancer care. The Patient Activation Measure (PAM-13), a questionnaire designed to reflect an individual’s knowledge, skills, and confidence in self-healthcare management, has been validated across diverse countries and settings. Concerns have been raised regarding the cross-situational applicability, as patients with specific diseases and cultural backgrounds interpret questionnaire items differently. This study aimed to examine the structural validity and psychometric properties of the PAM-13 in an oncological patient cohort. Methods Baseline data from a longitudinal non-randomized controlled study involving cancer out-patients ( n  = 1,125) from Comprehensive Cancer Centres in Southern Germany were analysed. The German version of the PAM-13 was employed. With classical test and item response theory methods data quality, reliability, convergent and structural validity, as well as psychometric properties were assessed. Exploratory (EFA) and confirmatory factor analyses (CFA) were employed to investigate the postulated unidimensionality of the underlying construct. With a partial credit model (PCM) we examined item fit, targeting, local independence and differential item functioning. Results Participants were predominantly female (73.0%) with a breast cancer diagnosis (41.3%). While items were generally well-accepted, ceiling effects were observed and a high mean PAM-13 score (69.7, SD = 14.2) was noted, potentially compromising responsiveness to interventions. Reliability was adequate (Cronbach’s α = 0.81), person and item separation reliability were good to excellent (0.81 and 0.99, respectively). Explorations of the unidimensionality of the construct (EFA, CFA, PCM) yielded inconclusive results, hinting towards a two-factor solution. Item difficulty rankings deviated from the original. No differential item functioning was identified, and local independence was confirmed. Conclusions While the PAM-13 serves as a valuable instrument for comprehending and promoting health-related skills in cancer patients, the identification of ceiling effects, disordered item-difficulty rankings, and inconclusive findings regarding unidimensionality contribute to the expanding body of evidence, emphasizing the dependency of PAM-13’s validity and reliability on distinctive characteristics within the population under investigation. Future research should prioritize refining or adding PAM-13 items to better capture the specific health-related challenges within diverse populations, paving the way for more effective patient engagement strategies in oncology. Trial registration number DRKS00021779

Conducting a process evaluation is essential to understand how health interventions work in different healthcare settings. Particularly in the case of complex interventions, it is important to find out whether the intervention could be carried out as planned and which factors had a beneficial or hindering effect on its implementation. The aim of this study is to present the detailed protocol of the process evaluation embedded in the controlled implementation study CCC-Integrativ aiming to implement an interprofessional counselling program for cancer patients on complementary and integrative health care (CIH). This mixed methods study will draw upon the \"Consolidated Framework for Implementation Research\" (CFIR) combined with the concept of \"intervention fidelity\" to evaluate the quality of the interprofessional counselling sessions, to explore the perspective of the directly and indirectly involved healthcare staff, as well as to analyze the perceptions and experiences of the patients. The qualitative evaluation phase consists of analyzing audio-recorded counselling sessions, as well as individual and group interviews with the involved persons. The quantitative evaluation phase applies questionnaires which are distributed before (T0), at the beginning (T1), in the middle (T2) and at the end (T3) of the intervention delivery. This protocol provides an example of how a process evaluation can be conducted parallel to a main study investigating and implementing a complex intervention. The results of this mixed methods research will make it possible to identify strengths and weaknesses of the team-based intervention, and to target more specifically the key factors and structures required to implement healthcare structures to meet patients' unmet needs in the context of CIH. To our knowledge, this study is the first applying the CFIR framework in the context of interprofessional CIH counselling, and its results are expected to provide comprehensive and multidisciplinary management of cancer patients with complex supportive healthcare needs.

Complementary and integrative healthcare (CIH) is increasingly recognized as a valuable approach to empowering and activating cancer patients. Studies have shown that higher patient activation is positively associated with improved health outcomes and reduced healthcare costs. The CCC-Integrativ study aimed to assess the implementation of an evidence-based counseling service on CIH at four Comprehensive Cancer Centers (CCC) in Germany. In this controlled implementation study, the patient-level intervention included three CIH consultations within a 3-month period delivered by interprofessional teams of physicians and nurses. The primary endpoint was patient activation using the PAM-13 at baseline (T1) and post-intervention (T2), and compared between control (CO, receiving routine care) and the intervention group (IG) using an analysis of covariance. Missing data were handled with multiple imputations. Maintenance effects at 6-month follow-up (T3) were investigated using a linear mixed model. A total of n = 1128 oncology patients (CO = 443, IG = 685) with diverse tumor entities and cancer stages were included in the study. The overall mean baseline PAM-13 score was 69.74 (SD = 14.24) ( n = 959 (85.0 %)). A statistically significant between-group difference in post-intervention PAM-13 scores was observed (F group(1, 1866.82) = 8.634, P = 0.003), with an adjusted mean difference of 2.22 PAM-points. Age, gender, tumor entity, disease stage, or CCC study site did not significantly predict post-treatment PAM-13 scores. The maintenance effect of the intervention was not statistically significant (F timeXgroup(1, 3316.04) = 2.337, P = 0.096). Individually tailored counseling on CIH, offered by specifically trained, interprofessional teams, significantly improved patient activation. Given the established positive effects of higher patient activation, the implementation of such a program at cancer centers may yield beneficial outcomes for both patients and the healthcare system.

Background Conducting a process evaluation is essential to understand how health interventions work in different healthcare settings. Particularly in the case of complex interventions, it is important to find out whether the intervention could be carried out as planned and which factors had a beneficial or hindering effect on its implementation. The aim of this study is to present the detailed protocol of the process evaluation embedded in the controlled implementation study CCC-Integrativ aiming to implement an interprofessional counselling program for cancer patients on complementary and integrative health care (CIH). Methods This mixed methods study will draw upon the “Consolidated Framework for Implementation Research” (CFIR) combined with the concept of “intervention fidelity” to evaluate the quality of the interprofessional counselling sessions, to explore the perspective of the directly and indirectly involved healthcare staff, as well as to analyze the perceptions and experiences of the patients. The qualitative evaluation phase consists of analyzing audio-recorded counselling sessions, as well as individual and group interviews with the involved persons. The quantitative evaluation phase applies questionnaires which are distributed before (T0), at the beginning (T1), in the middle (T2) and at the end (T3) of the intervention delivery. Discussion This protocol provides an example of how a process evaluation can be conducted parallel to a main study investigating and implementing a complex intervention. The results of this mixed methods research will make it possible to identify strengths and weaknesses of the team-based intervention, and to target more specifically the key factors and structures required to implement healthcare structures to meet patients’ unmet needs in the context of CIH. To our knowledge, this study is the first applying the CFIR framework in the context of interprofessional CIH counselling, and its results are expected to provide comprehensive and multidisciplinary management of cancer patients with complex supportive healthcare needs.

Predictability on seasonal time scales over the North Atlantic–Europe region is assessed using a seasonal prediction system based on an initialized version of the Max Planck Institute Earth System Model (MPI-ESM). For this region, two of the dominant predictors on seasonal time scales are El Niño–Southern Oscillation (ENSO) and sudden stratospheric warming (SSW) events. Multiple studies have shown a potential for improved North Atlantic predictability for either predictor. Their respective influences are however difficult to disentangle, since the stratosphere is itself impacted by ENSO. Both El Niño and SSW events correspond to a negative signature of the North Atlantic Oscillation (NAO), which has a major influence on European weather. This study explores the impact on Europe by separating the stratospheric pathway of the El Niño teleconnection. In the seasonal prediction system, the evolution of El Niño events is well captured for lead times of up to 6 months, and stratospheric variability is reproduced with a realistic frequency of SSW events. The model reproduces the El Niño teleconnection through the stratosphere, involving a deepened Aleutian low connected to a warm anomaly in the northern winter stratosphere. The stratospheric anomaly signal then propagates downward into the troposphere through the winter season. Predictability of 500-hPa geopotential height over Europe at lead times of up to 4 months is shown to be increased only for El Niño events that exhibit SSW events, and it is shown that the characteristic negative NAO signal is only obtained for winters also containing major SSW events for both the model and the reanalysis data.

Craniofacial microsomia (CFM; also known as Goldenhar syndrome), is a craniofacial developmental disorder of variable expressivity and severity with a recognizable set of abnormalities. These birth defects are associated with structures derived from the first and second pharyngeal arches, can occur unilaterally and include ear dysplasia, microtia, preauricular tags and pits, facial asymmetry and other malformations. The inheritance pattern is controversial, and the molecular etiology of this syndrome is largely unknown. A total of 670 patients belonging to unrelated pedigrees with European and Chinese ancestry with CFM, are investigated. We identify 18 likely pathogenic variants in 21 probands (3.1%) in FOXI3 . Biochemical experiments on transcriptional activity and subcellular localization of the likely pathogenic FOXI3 variants, and knock-in mouse studies strongly support the involvement of FOXI3 in CFM. Our findings indicate autosomal dominant inheritance with reduced penetrance, and/or autosomal recessive inheritance. The phenotypic expression of the FOXI3 variants is variable. The penetrance of the likely pathogenic variants in the seemingly dominant form is reduced, since a considerable number of such variants in affected individuals were inherited from non-affected parents. Here we provide suggestive evidence that common variation in the FOXI3 allele in trans with the pathogenic variant could modify the phenotypic severity and accounts for the incomplete penetrance. Most cases of craniofacial microsomia are sporadic but familial cases have been reported. Here the authors report that variants in FOXI3 can cause a small fraction of cases with different modes of inheritance including autosomal dominant with reduced penetrance.

An intentional transfer of information is central to human communication. When comparing nonhuman primate communication systems to language, a critical challenge is to determine whether a signal is used in intentional, goal-oriented ways. As it is not possible to directly observe psychological states in any species, comparative researchers have inferred intentionality via behavioral markers derived from studies on prelinguistic human children. Recent efforts to increase consistency in nonhuman primate communication studies undervalue the effect of possible sources of bias: some behavioral markers are not generalizable across certain signal types (gestures, vocalizations, and facial expressions), contexts, settings, and species. Despite laudable attempts to operationalize first-order intentionality across signal types, a true “multimodal” approach requires integration across their sensory components (visual-silent, contact, audible), as a signal from a certain type can comprise more than one sensory component. Here we discuss how the study of intentional communication in nonlinguistic systems is hampered by issues of reliability, validity, consistency, and generalizability. We then highlight future research avenues that may help to understand the use of goal-oriented communication by opting, whenever possible, for reliable, valid, and consistent behavioral markers, but also taking into account sampling biases and integrating detailed observations of intraspecific communicative interactions.

ObjectiveThe prognostic value of left atrial (LA) dimensions may differ between patients with and without atrial fibrillation (AF).MethodsMEDLINE and EMBASE were searched for studies that investigated the association between LA echocardiographic parameters measured by transthoracic echocardiography and cardiovascular outcomes in patients with or without AF. Data were independently abstracted by two reviewers and pooled using random-effects meta-analysis. The primary outcome was incident stroke or thromboembolic events. Secondary outcomes were heart failure, all-cause mortality and major adverse cardiac events (MACE).ResultsTwenty-three studies of patients with AF (14 939 patients) and 68 studies of patients without AF (50 720 patients) in this systematic review. Increasing LA diameter was significantly associated with stroke and thromboembolic events in patients without AF (risk ratio (RR) 1.38, 95% CI 1.02 to 1.87; p=0.03), but not in patients with AF (RR 1.02, 95% CI 0.98 to 1.07; p=0.27; p for difference=0.05). Increasing LA diameter index was significantly associated with MACE in patients with AF (RR 1.13, 95% CI 1.09 to 1.17; p<0.001) and in patients without AF (RR 2.98, 95% CI 1.90 to 4.66; p<0.001), with stronger effects in non-AF populations (p for difference <0.001). Greater LA volume index was significantly associated with the risk of MACE in patients with AF (RR 1.01, 95% CI 1.00 to 1.02; p=0.03) and in non-AF populations (RR 1.08, 95% CI 1.05 to 1.10; p<0.001), the association being stronger in individuals without AF (p for difference <0.001).ConclusionsLarger LA parameters were associated with various adverse cardiovascular events. Many of these associations were stronger in individuals without AF, highlighting the potential importance of LA myopathy.

Most of the known approved drugs comprise functionalized heterocyclic compounds as subunits. Among them, non-fluorescent quinazolines with four different substitution patterns are found in a variety of clinically used pharmaceuticals, while 4,5,7,8-substituted quinazolines and those displaying their own specific fluorescence, favourable for cellular uptake visualization, have not been described so far. Here we report the development of a one-pot synthetic strategy to access these 4,5,7,8-substituted quinazolines, which are fluorescent and feature strong antiviral properties ( EC 50 down to 0.6±0.1 μM) against human cytomegalovirus (HCMV). Merging multistep domino processes in one-pot under fully metal-free conditions leads to sustainable, maximum efficient and high-yielding organic synthesis. Furthermore, generation of artesunic acid–quinazoline hybrids and their application against HCMV ( EC 50 down to 0.1±0.0 μM) is demonstrated. Fluorescence of new antiviral hybrids and quinazolines has potential applications in molecular imaging in drug development and mechanistic studies, avoiding requirement of linkage to external fluorescent markers. Heterocycles are ubiquitous in bioactive compounds and routes to different substitution patterns are important to access the full substrate space. Here the authors report a route to 4,5,7,8-substituted antiviral fluorescent quinazolines, to allow cellular uptake visualization without external marker.

Administration of spermidine, a polyamine whose concentration declines during ageing, extends lifespan in yeast, flies, worms and in human immune cells. Spermidine prevents early oxidative stress and necrotic cell death and increases the expression of autophagy genes by inhibiting histone acetyltransferases action on histone H3. Ageing results from complex genetically and epigenetically programmed processes that are elicited in part by noxious or stressful events that cause programmed cell death. Here, we report that administration of spermidine, a natural polyamine whose intracellular concentration declines during human ageing, markedly extended the lifespan of yeast, flies and worms, and human immune cells. In addition, spermidine administration potently inhibited oxidative stress in ageing mice. In ageing yeast, spermidine treatment triggered epigenetic deacetylation of histone H3 through inhibition of histone acetyltransferases (HAT), suppressing oxidative stress and necrosis. Conversely, depletion of endogenous polyamines led to hyperacetylation, generation of reactive oxygen species, early necrotic death and decreased lifespan. The altered acetylation status of the chromatin led to significant upregulation of various autophagy-related transcripts, triggering autophagy in yeast, flies, worms and human cells. Finally, we found that enhanced autophagy is crucial for polyamine-induced suppression of necrosis and enhanced longevity.