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Abstract Background Patients with psoriasis often suffer from obesity. However, only limited data are available on the efficacy of brodalumab 210 mg, a fully human monoclonal immunoglobulin IgG2 antibody binding to the human interleukin 17 receptor subunit A, in obese patients in daily practice, to date. Objectives A subgroup analysis from the LIBERO study was conducted to compare the effectiveness of brodalumab in patients weighing ≤100 and >100 kg after ~12 weeks (W) and ~52 W. Methods LIBERO is a large prospective, multicenter, non‐interventional, real‐world‐evidence study including adult patients with plaque psoriasis treated with brodalumab 210 mg. Results Four hundred and sixty‐one patients with a body weight up to 100 kg (nonobese) and 161 patients with >100 kg body weight (obese) were included in this subgroup analysis. At baseline, the majority of patients in both groups had very severe (12.6%; 15.7%) or severe (49.4%; 55.0%) psoriasis, as assessed by Physician Global Assessment (PGA). As of W2, a significant reduction of the mean PASI could be achieved in both groups. In patients weighing ≤100 kg mean PASI decreased from 16.9 to 9.0 and further improved to 2.6 at ~W12 (p 100 kg, the PASI decreased from 17.9 to 10.2 at ~W2 (p 100 kg than in patients ≤100 kg (68.4% vs. 80.5%, p = 0.006); there was no statistically significant difference between the groups at ~W52/last visit any more in any of the effectiveness parameters with, for example, a PGA0/1 response of 82.3% versus 86.5% (p = 0.6089), respectively. Conclusions This subgroup analysis of LIBERO confirmed, that in daily practice brodalumab can be equally beneficial patients with >100 and ≤100 kg in the long‐term management of psoriasis.

Background: New-onset postoperative atrial fibrillation is associated with adverse clinical outcomes in older adults. Poor preoperative sleep quality is a putative modifiable risk factor. The relationships between new-onset postoperative atrial fibrillation and preoperative sleep structure in older adults undergoing elective cardiac surgery were investigated at a single center. Methods: This was a prespecified substudy within a prospective observational study of perioperative electroencephalographic markers (ClinicalTrials.gov; NCT03291626). We analyzed preoperative sleep recordings from 71 cardiac surgical patients aged ≥60 years without a prior history of atrial fibrillation. Overnight recordings were acquired using a consumer-grade headband and underwent manual sleep staging. Electroencephalographic slow wave activity (power in the 0.5-4 Hz frequency band) was computed in 1-minute intervals for non-rapid eye movement sleep stages. Associations between new-onset postoperative atrial fibrillation incidence and sleep measures were evaluated using univariate logistic regression models and multivariate logistic regression models including age and sex. Results: New-onset postoperative atrial fibrillation was present in 22 of 71 (31%) patients. A higher preoperative percentage of total sleep time in non-rapid eye movement stage 1 was associated with new-onset postoperative atrial fibrillation (median difference of 5.4%, P = .0002, Mann-Whitney U-test), independent of age and sex. No associations were observed between new-onset postoperative atrial fibrillation and other sleep metrics, including slow wave activity (all P > .05, Mann-Whitney U-test). Conclusions: Excess preoperative non-rapid eye movement stage 1 sleep, consistent with greater sleep fragmentation, is a potential modifiable target for mitigating new-onset postoperative atrial fibrillation risk in older adults undergoing elective cardiac surgery requiring cardiopulmonary bypass.

Stoneflies are well known as indicators of water quality. Their presence in running waters, glacial meltwaters, and large oligotrophic lakes is rapidly declining the world over. In the USA, states partner with the U.S. Fish and Wildlife Service to protect habitat and wildlife through the development of State Wildlife Action Plans (SWAPs). Plants and wildlife species often enter these SWAPs as Species in Greatest Conservation Need (SGCN). Arkansas currently lists nine stonefly species as SGCNs and has funded research on them through SWAP grants. However, these nine species were initially chosen based on the small amount of data from a few papers. A more comprehensive assessment using museum specimen data is necessary to assess completeness of sampling, the relative rarity and endemicity of species, temporal changes in distribution, and the conservation status of species in Arkansas. Herein, we publish a data paper and preliminary dataset comprised of specimen data primarily from the Illinois Natural History Survey Insect Collection, Canadian National Collection, Western Kentucky University, P. N. Hogan Personal Collection, and from existing literature sources. These data are made publicly available by the Global Biodiversity Information Facility (GBIF) to allow for comprehensive assessment of the Arkansas Plecoptera assemblage. More recent occurrence data are needed to accurately assess imperilment of Arkansas stonefly species; these data will be provided through targeted collecting, collaboration with others in Arkansas, and through investigation of additional museum collections.This dataset includes > 3,500 specimen records (ethanol vials or pins with or without catalog numbers) and accounts for 84 stonefly species in Arkansas, six more species than indicated in published records. Perlidae contributed 29 of these species followed distantly by Perlodidae (15), Capniidae (14), Taeniopterygidae (9), Leuctridae (7), Chloroperlidae (5), Nemouridae (4), and Pteronarcyidae (1). A species accumulation curve predicts that sampling of species is nearly complete with a Chao1 estimate of 88.0 ± 3.7 species. Our data demonstrate that 25 species are known from ≤ five records, suggesting that many more than the nine recognized stonefly SGCNs in Arkansas may meet standards for inclusion.

Abstract The Crimean-Congo hemorrhagic fever virus (CCHFV) causes Crimean-Congo hemorrhagic fever (CCHF), a widely distributed disease with significant morbidity and mortality. The virus has high genetic diversity correlated with geographic distribution but limited temporal evolution within regions. Despite this, cases of CCHF within a region present as a spectrum of disease from often unrecognized asymptomatic infections to severe, fatal viral hemorrhagic fever, suggesting host factors may play a role in disease outcome. We investigated the effect of host genetic diversity on the outcome of CCHFV infection in the genetically diverse Collaborative cross (CC)-mouse model. Infected mice recapitulated the full spectrum of disease recognized in humans, and similar to human disease, virus replication, tissue pathology, and inflammatory responses were associated with disease severity. Our study demonstrates that host genetics contribute to disease outcome in CCHF infection and establishes the CC mouse resource as a model to understand how host genetic diversity contributes to CCHF outcome.

Abstract Background Advanced head and neck malignancies with underlying bony involvement often require aggressive oncological resection of large segments of the oral cavity including the mandible. These patients require vascularized donor osseous free tissue transfer to reconstruct significant defects. Traditionally, the donor bone is harvested on its vascular supply and shaped to the defect in a free hand fashion (FHS). However, virtual surgical planning (VSP) has emerged as a method to optimize reconstructive outcomes and decrease operative time. The goals of this study are to assess superiority of VSP to FHS by comparing bony union rates at 12 months, short and long-term complication rates, reconstruction accuracy, quality of life (QOL), functional outcomes, and economic analysis. Methods This is a multicenter phase II/III study randomizing four hundred twenty head and neck patients undergoing mandibulectomy in a 1:1 ratio between VSP and FHS. Intention-to-treat analysis will be performed for patients enrolled but unable to undergo VSP-aided reconstruction. The primary endpoint is bony-union rates at 1 year post-operatively. Secondary outcomes include complication rates, QOL, functional outcomes, and economic burden. Discussion This study will provide an assessment of two different surgical approaches to the reconstructive methods of mandible defects using fibular or scapular free flaps on bony-union rates, complications, QOL and economics. Trial registration Clinicaltrials.gov identifier: NCT05429099. Date of registration: June 23, 2022. Current version: 1.0 on March 6, 2024.

Abstract Background Listeriosis, caused by Listeria monocytogenes, poses significant health risks globally, particularly among pregnant women. Despite its established impact in other regions, its prevalence and antibiotic susceptibility patterns in Uganda, especially among women experiencing spontaneous abortion, remain understudied. Objective This cross-sectional study aimed to determine the prevalence, antibiotic susceptibility, and associated risk factors of listeriosis among women admitted with spontaneous abortion in Ugandan tertiary hospitals. Methods A total of 384 women from Jinja and Kayunga Regional Referral Hospitals were included. Data on socio-demographic characteristics, obstetric history, and dietary habits were collected using structured interviews and high vaginal swab cultures. Antibiotic susceptibility testing was performed using the disk diffusion method, and logistic regression analysis was used to assess risk factors. Results The prevalence of listeriosis among participants was 11.2%. L. monocytogenes showed high susceptibility to Vancomycin (88.37%) and Clindamycin (81.40%), but significant resistance to Ampicillin (81.40%) and Amoxicillin (76.74%). Risk factors significantly associated with listeriosis included lack of formal education (adjusted odds ratio [aOR] = 7.0, 95% CI: 1.779–27.655), multiple abortions (aOR = 3.3, 95% CI: 1.486–7.427), and consumption of soft cheese, ice cream, yogurt, or ghee (aOR = 4.3, 95% CI: 1.331–14.082). Conclusion This study provides critical insights into the prevalence, antibiotic resistance patterns, and risk factors for listeriosis among Ugandan women with spontaneous abortion. Findings underscore the need for targeted public health interventions and antibiotic stewardship to mitigate the impact of this infection.

Abstract Background The discovery of cellular tumor networks in glioblastoma, with routes of malignant communication extending far beyond the detectable tumor margins, has highlighted the potential of supramarginal resection strategies. Retrospective data suggest that these approaches may improve long-term disease control. However, their application is limited by the proximity of critical brain regions and vasculature, posing challenges for validation in randomized trials. Anterior temporal lobectomy (ATL) is a standardized surgical procedure commonly performed in patients with pharmacoresistant temporal lobe epilepsy. Translating the ATL approach from epilepsy surgery to the neuro-oncological field may provide a model for investigating supramarginal resection in glioblastomas located in the anterior temporal lobe. Methods The ATLAS/NOA-29 trial is a prospective, multicenter, multinational, phase III randomized controlled trial designed to compare ATL with standard gross-total resection (GTR) in patients with newly-diagnosed anterior temporal lobe glioblastoma. The primary endpoint is overall survival (OS), with superiority defined by significant improvements in OS and non-inferiority in the co-primary endpoint, quality of life (QoL; “global health” domain of the European organization for research and treatment of cancer (EORTC) QLQ-C30 questionnaire). Secondary endpoints include progression-free survival (PFS), seizure outcomes, neurocognitive performance, and the longitudinal assessment of six selected domains from the EORTC QLQ-C30 and BN20 questionnaires. Randomization will be performed intraoperatively upon receipt of the fresh frozen section result. A total of 178 patients will be randomized in a 1:1 ratio over a 3-year recruitment period and followed-up for a minimum of 3 years. The trial will be supervised by a Data Safety Monitoring Board, with an interim safety analysis planned after the recruitment of the 57th patient to assess potential differences in modified Rankin Scale (mRS) scores between the treatment arms 6 months after resection. Assuming a median improvement in OS from 17 to 27.5 months, the trial is powered at > 80% to detect OS differences with a two-sided log-rank test at a 5% significance level. Discussion The ATLAS/NOA-29 trial aims to determine whether ATL provides superior outcomes at equal patients’ Qol compared to GTR in anterior temporal lobe glioblastoma, potentially establishing ATL as the surgical approach of choice for isolated temporal glioblastoma and redefining the standard of care for this patient population. Trial registration German Clinical Trials Register (DRKS00035314), registered on October 18, 2024.

Abstract Exploration is an important strategy for reducing the uncertainty that pervades daily life. Yet the evolutionary roots of adaptive exploration are poorly understood. We harness and adapt the human decisions-from-experience paradigm to investigate exploration under uncertainty in chimpanzees. In our study, chimpanzees (N = 15; eight females) are simultaneously confronted with an uncertain option (with outcome variance) and a safe option (without outcome variance) and tested in both stable and changing environments. Results reveal that, as in human exploration, how and how much chimpanzees explore depends on the environment. One key environmental property is change: Chimpanzees explore more across trials in changing than in stable conditions. Consistent with the assumption of classic economic models that variance indicates risk, chimpanzees also explore more when they experience variance in the options’ outcomes. Individual risk and uncertainty preferences did not have a statistically significant effect on exploratory efforts. These findings suggest that chimpanzees and humans share key similarities in the way they respond to risk and uncertainty.

Abstract Background Little attention has been paid to the generalizability of cohort studies in bipolar disorder (BD) to patient with BD in everyday clinical practice. Methods A sample of patients with bipolar I disorder (BD-I) treated at a Dutch outpatient clinic for BD were compared with Dutch participants with BD-I of four clinical cohort studies, and participants with BD-I in a general population study in the Netherlands, on sociodemographic and clinical characteristics. Results On many variables participants from the outpatient sample matched with those of the included studies. However, compared with participants of several of the clinical cohort studies, these outpatients were significantly younger, had an earlier age of onset of mood symptoms, and had a shorter duration of illness. Compared with participants in the general population study, outpatients had significant higher levels of education and less often lived together or were married. One cohort study reported much lower comorbidity rates of alcohol use disorders, drug use disorders, and anxiety disorders than in the outpatient sample. In contrast, comorbidity rates were higher in the population study. Limitations Due to methodological differences between studies, comparisons between several variables was limited, and for some variables data was lacking. Conclusions Our findings suggest that many findings from cohort studies and general population study in BD-I are generalizable to everyday clinical practice, especially mood disorder outpatient centers. However, differences between samples indicate some selection and referral bias.

Abstract Clear cell renal cell carcinoma (ccRCC), a metabolic disease originating from renal proximal convoluted tubule (PCT) epithelial cells, remains incompletely understood in terms of its initiating signaling events. Here, we identify γ-butyrobetaine hydroxylase 1 (BBOX1), a key enzyme in carnitine synthesis predominantly expressed in PCT cells, as a tumor suppressor in ccRCC. BBOX1 expression is lost during ccRCC malignant transformation, and its restoration reduces cell viability in physiological medium and inhibits xenograft tumor growth. Transcriptomic analyses reveal that BBOX1 suppresses critical metabolic pathways including mTORC1 signaling and glycolysis in ccRCC. Further, we identify TANK-binding kinase 1 (TBK1) as an essential mediator of mTORC1 and glycolysis activation and as a target of BBOX1-mediated tumor suppression. Mechanistically, BBOX1 disrupts TBK1 activation by preventing its interaction with the upstream activator doublecortin-like kinase 2 (DCLK2). This BBOX1-DCLK2-TBK1 axis unveils an important mechanism in ccRCC metabolic dysregulation and highlights potential therapeutic strategies.

Abstract Essential oils (EO) are known for their antibacterial and anti-inflammatory properties and can be used as an alternative to reduce the reliance on antimicrobials in dairy cattle. While many studies have explored the beneficial properties of EO in vitro, their effects on milk quality and milk microbiota, when applied directly to the udder skin, remain relatively unknown. This study aimed to investigate the impact of Thymus capitatus essential oil (TCEO), known for its high antibacterial and antioxidant properties, on milk microbiota using 16S rRNA sequencing, the lipidomic profile via liquid chromatography-quadrupole time-of-flight mass spectrometry, udder skin microbiota, and inflammatory biomarkers of dairy cows at the end of lactation. Sixteen-quarters of 12 Holstein cows were selected, and TCEO was topically applied to the udder skin twice a day for 7 days. Milk was collected aseptically on days 0, 7, 21, and 28 before morning farm milking. The results showed no significant changes in microbiota composition after the EO treatment in alpha and beta diversity or taxonomical composition at the phylum and genus levels. TCEO induced limited changes in the milk lipidome, primarily affecting diacylglycerols at T21. The treatment did not affect inflammatory biomarkers, milk sensory properties, or quality. Our study is the first to demonstrate that a local application of 10% TCEO on cow’s quarters does not significantly alter milk quality or microbiota composition in milk and skin. More studies should be conducted to ensure the safe use of TCEO in dairy cows and explore its potential benefits on antibiotic-resistant bacteria as an alternative or support for antibiotic therapy.

Abstract Background Based on current guidelines, surgical treatment of hepatic oligometastases in patients with pancreatic ductal adenocarcinoma (PDAC) is not primarily recommended. Systematic chemotherapy is the therapy of choice for these patients. The relevance of subsequent surgical resection after chemotherapy remains unclear. This multicentre, randomized, controlled phase III trial is planned to evaluate whether resection of the primary tumor and liver metastases can improve overall survival in patients with PDAC with hepatic oligometastases in a multimodal treatment setting. Methods After an induction therapy with eight cyles of mFOLFIRINOX and a response assessment after four and eight cycles, patients will be randomized to either Arm 1 (perioperative mFOFIRINOX plus resection of the primary tumor with resection or ablation of all hepatic metastases) or Arm 2 (continuation of 4 cycles of the standard-of-care mFOLFIRINOX chemotherapy). This clinical trial will focus on a well-defined patient group with metastatic disease limited to the liver as the target organ, with a maximum of three metastases. Discussion METAPANC is the first international, randomized, controlled, open-label, multicentre, phase III clinical trial for curative intended surgical therapy of oligometastatic pancreatic cancer in Europe and America. The multimodal surgical treatment of patients with oligometastatic pancreatic cancer could significantly extend the overall survival of this patient group. A possible recommendation of this multimodal treatment regimen outside of clinical trials requires data from randomized controlled trials first. To identify patient subgroups that might benefit from multimodal surgical therapy, additional information on tumor genetics could supplement valid parameters. Trial registration EU Clinical Trials No. 2023-503558-10-00.

Abstract Although variation in effect sizes and predicted values among studies of similar phenomena is inevitable, such variation far exceeds what might be produced by sampling error alone. One possible explanation for variation among results is differences among researchers in the decisions they make regarding statistical analyses. A growing array of studies has explored this analytical variability in different fields and has found substantial variability among results despite analysts having the same data and research question. Many of these studies have been in the social sciences, but one small “many analyst” study found similar variability in ecology. We expanded the scope of this prior work by implementing a large-scale empirical exploration of the variation in effect sizes and model predictions generated by the analytical decisions of different researchers in ecology and evolutionary biology. We used two unpublished datasets, one from evolutionary ecology (blue tit, Cyanistes caeruleus, to compare sibling number and nestling growth) and one from conservation ecology (Eucalyptus, to compare grass cover and tree seedling recruitment). The project leaders recruited 174 analyst teams, comprising 246 analysts, to investigate the answers to prespecified research questions. Analyses conducted by these teams yielded 141 usable effects (compatible with our meta-analyses and with all necessary information provided) for the blue tit dataset, and 85 usable effects for the Eucalyptus dataset. We found substantial heterogeneity among results for both datasets, although the patterns of variation differed between them. For the blue tit analyses, the average effect was convincingly negative, with less growth for nestlings living with more siblings, but there was near continuous variation in effect size from large negative effects to effects near zero, and even effects crossing the traditional threshold of statistical significance in the opposite direction. In contrast, the average relationship between grass cover and Eucalyptus seedling number was only slightly negative and not convincingly different from zero, and most effects ranged from weakly negative to weakly positive, with about a third of effects crossing the traditional threshold of significance in one direction or the other. However, there were also several striking outliers in the Eucalyptus dataset, with effects far from zero. For both datasets, we found substantial variation in the variable selection and random effects structures among analyses, as well as in the ratings of the analytical methods by peer reviewers, but we found no strong relationship between any of these and deviation from the meta-analytic mean. In other words, analyses with results that were far from the mean were no more or less likely to have dissimilar variable sets, use random effects in their models, or receive poor peer reviews than those analyses that found results that were close to the mean. The existence of substantial variability among analysis outcomes raises important questions about how ecologists and evolutionary biologists should interpret published results, and how they should conduct analyses in the future.

Abstract Background Histological chorioamnionitis (HCA) is a significant global threat to maternal and fetal health, with an increasing prevalence in resource-limited settings. However, data on its burden and predictors remain scarce in Africa, including Uganda. This study aimed to determine the prevalence and predictors of HCA among mothers with premature rupture of membranes (PROM) at three tertiary hospitals in Uganda. Methods This multicenter cross-sectional study was conducted over a three-month period, from July to October 2023, at three tertiary hospitals in Uganda. A total of 106 women diagnosed with PROM were consecutively enrolled. Data were collected using a structured questionnaire that captured routine history-taking and physical examinations. Key information gathered included the history of liquor drainage, clinical signs of chorioamnionitis (fever, uterine tenderness, and foul-smelling liquor), labor history, and placental samples obtained after delivery for histopathological analysis. Descriptive statistics and binary logistic regression analyses were performed using STATA version 14.2. Statistical significance was set at P

DNN (deep neural network) and CNN (convolution neural network) have been widely used in real-time artificial intelligent (AI) applications, particularly image or video recognitions, because they have been proved physically in many occasions. However, most prior AI hardware works either suffered from high on-silicon area cost or low usage thereof. This investigation presents a power efficient and high performance implementation of a digital logic accelerator (DLA) for the real-time underwater object recognition. The proposed DLA is also featured with 2-dimensional PE (processing element) array to increase the processing throughput by the enhancement of parallelism. The DLA design was realized and fabricated using TSMC 40-nm CMOS process. Not only the post-layout simulation results are shown, the on-silicon measurement outcome as well as the system validation in water are also demonstrated to prove the function correctness and the performance. The area efficiency (GOPS/mm2) is 4.562, and the power efficiency (TOPS/W) is 0.5668 on silicon, which both are the best to date.

Target tracking algorithms commonly use structured dynamic models which require prior training of fixed model parameters. These trackers have reduced accuracy if the target behaviour does not match the dynamic model. This work develops an algorithm that can infer target dynamic behaviour online, allowing the target dynamic to be time-varying as well. A time-varying target dynamic allows the target to change its level of maneuverability continuously through the trajectory, so the trajectory may have highly variable levels of agility. The developed tracker assumes the target dynamic can be described by an autoregressive model with time-varying parameters and constant, but unknown innovation variance. The autoregressive coefficients and innovation variance are then inferred online while simultaneously tracking the target. A data-association model is included to allow for clutter in the target measurements. This tracker is then compared against common structured trackers and is shown that it can approximate these models, while also showing better state filtering and prediction accuracy for an agile target.

Abstract Background With Direct Acting Antivirals for Hepatitis C virus (HCV), cure is possible in > 95% including those with HIV/HCV co-infection. Achieving strategic targets for cure requires addressing barriers including suboptimal care engagement. We adapted Data to Care (D2C), a public health strategy designed to identify and link persons out of care (OOC) for HIV, for persons with HIV/HCV co-infection untreated for HCV. Methods In partnership with Connecticut Department of Public Health (DPH), persons OOC for HIV (defined as no HIV surveillance laboratory tests from 10/1/2018–10/1/2019) were matched to a list of persons co-infected with HIV/HCV (through 12/31/2019). We used a three-phase follow-up approach (pre-work, case conferencing, and Disease Intervention Specialist (DIS) follow-up) to track outreach outcomes and re-engagement/HCV cure success. Results There were 90 HIV/HCV co-infected persons who were OOC for HIV. The pre-work and case conferencing phases determined that 33 (36.7%) had previous HCV cure or were in treatment. There were 41 eligible for DIS-follow-up of which 21 (51%) were successfully contacted and 7 (33%) successfully re-engaged (kept appointment with HCV provider). No new HCV treatment initiations were recorded. Conclusions Using a D2C approach, we identified and conducted outreach to persons who were OOC for HIV to promote HCV treatment. This approach resulted in intensive data clean-up and outreach efforts which produced modest re-engagement and no HCV treatment initiations. Future studies should develop alternative and complementary interventions to promote effective re-engagement and HCV treatment.

Abstract While all native tRNAs undergo extensive post-transcriptional modifications as a mechanism to regulate gene expression, mapping these modifications remains challenging. The critical barrier is the difficulty of readthrough of modifications by reverse transcriptases (RTs). Here we use Induro—a new group-II intron-encoded RT—to map and quantify genome-wide tRNA modifications in Induro-tRNAseq. We show that Induro progressively increases readthrough over time by selectively overcoming RT stops without altering the misincorporation frequency. In a parallel analysis of Induro vs. a related RT, we provide comparative datasets to facilitate the prediction of each modification. We assess tRNA modifications across five human cell lines and three mouse tissues and show that, while the landscape of modifications is highly variable throughout the tRNA sequence framework, it is stabilized for modifications that are required for reading of the genetic code. The coordinated changes have fundamental importance for development of tRNA modifications in protein homeostasis.

Abstract Background To determine the feasibility, acceptability, and preliminary efficacy of a 6-month tailored non-linear progressive physical activity intervention (PAI) for lymphoma patients undergoing chemotherapy. Methods Patients newly diagnosed with lymphoma (non-Hodgkin (NHL) or Hodgkin (HL)) were randomized into the PAI or healthy living intervention (HLI) control (2:1). Feasibility was assessed by examining accrual, adherence, and retention rates. Participants completed assessments of exercise capacity (VO2 peak and 6-min walk distance (6MWD)), objective and self-reported levels of physical activity, MRI-derived cardiovascular functioning (Left Ventricular Ejection Fraction [LVEF], stroke volume, and cardiac output), and self-reported health-related and disease-specific quality of life and self-efficacy for exercise at baseline, 3, and 6 months. Results One hundred and forty-five individuals were screened with 23 of 84 eligible patients agreeing to participate (27%). Three participants withdrew before baseline testing. Out of the 20 participants randomized to the PAI (n = 13) and HLI groups (n = 7), 18 completed the intervention resulting in an overall retention rate of 78%. The adherence rates to the PAI and HLI were 85% and 87%, respectively. One non-serious adverse event was registered. VO2 peak ranged from 15.5–28.0 ml/kg/min at baseline and participants in both groups improved by 6 months. Physical activity levels and cardiovascular function were reduced prior to treatment but did not deteriorate further. Conclusions Implementing a tailored PAI in adults with lymphoma during active treatment is feasible, was well received by participants and shows preliminary efficacy for limiting a decline in function during treatment. Potential Implications for Cancer Survivors: Physical activity may be beneficial for improving exercise capacity and health-related quality of life in patients undergoing chemotherapy. Trial registration #NCT01719562 ClinicalTrials.gov. Registered July 2, 2019—retrospectively registered.

Modulated Model Predictive Control (MMPC) techniques can be applied to enhance matrix converter (MC) performance in the linear modulation zone (LMZ). However, extending the converter operation in the overmodulation zone (OMZ) remains a problem. A key limitation of existing control methods in the OMZ is using the duty cycles calculated for the LMZ without considering the voltage or current reference vectors. This approach can lead to inaccurate calculations and a slower transient response when switching between the two operational zones. To overcome this challenge, a novel reference vector calculation method is proposed in this paper. The proposed approach simplifies the duty cycle calculation and ensures optimal performance in the OMZ by introducing new vector calculations and dividing the OMZ into two subzones. This method also minimizes the transition time between LMZ and OMZs to maximize the usable operating range of MCs. Simulation and experimental results validate the proposed method outperforms two other MMPC methods in improving the MC performance, reducing the transition times between operational zones, and maximizing the converter utilization.

In a longitudinal study in a first-level hospital in Luanda, Angola, we found rifampin-resistant and multidrug-resistant tuberculosis (TB) in 38 (8%, 95% CI 5.7–10.8) of 474 patients with no previous history of TB. Of note, 2 patients (0.4%, 95% CI 0.1–1.5) demonstrated pre–extensively drug-resistant TB.

Background: Phosphorylated alpha-synuclein (P-aSyn) is a biomarker for Parkinson’s disease (PD), with potential relevance in intestinal inflammatory disorders. Objectives: This study examines the distribution of P-aSyn in colonic tissues of patients with diverticular disease (DD) compared to age-matched controls. Methods: P-aSyn distribution was analyzed in colon samples of 45 patients with diverticulitis (D-itis), 12 with diverticulosis (D-osis), and 30 controls via immunohistochemistry. Results: P-aSyn immunoreactivity was found along enteric neurons of the myenteric and submucosal plexus in 93.1 % of participants, with similar distribution across D-itis, D-osis, and controls. Elevated reactivity appeared in 16.7 % of D-osis, 19.6 % of D-itis, and 30.0 % of controls. Conclusion: P-aSyn presence in colonic tissue did not significantly differ between DD patients and controls, suggesting that DD-related inflammation does not notably affect P-aSyn expression. Further research is warranted to explore aSyn roles within the enteric nervous system in intestinal inflammatory disorders and their relation with neurodegenerative diseases.

Hepatocellular adenoma (HCA) represents a rare benign liver tumor occurring predominantly in females of reproductive age and taking oral contraceptives. They are associated with various conditions. We report the case of a male patient with hepatic adenomas who has an association with long-term antiepileptic drugs in treatment for seizures of Rasmussen's encephalitis without a history of anabolic steroid use or any underlying hyperestrogenism. MRI findings show multiple hepatic nodules with mainly intermediate signal on T2, intratumoral fat content without diffusion restriction, and intense enhancement in the arterial phase with and without washout in portal and equilibrium phases. The imaging characteristics of these adenomas are indicative of the HNF1 alpha-inactivated subtype. No therapeutic interventions have been performed so far. This association is rare, and few cases have been reported in the literature. This case aims to reaffirm and remind people of the association of hepatic adenomas with antiepileptic drug use and make an additional analysis of the new molecular subtypes of hepatic adenoma, described recently in the literature. Exhaustive literature research reveals few case reports.

Preview: / Ralph D. Ellis interviewed by Samuel Maruszewski / Ralph D. Ellis, one of the strongest advocates of the enactivist approach to consciousness and cognitive theory, began his academic career as a phenomenologist, earning the Ph.D. at Duquesne University under Andre Schuwer, John Sallis and Amedeo Giorgi, and has taught at Clark Atlanta University since 1985. He subsequently received a post-doctoral M.S. in Public Affairs at Georgia State University, and worked also as a social worker in both Pittsburgh and Atlanta. Partly as a result of those experiences, as well as being a life-long practitioner of Gene Gendlin’s focusing method, he gravitated toward emotion research and the intersection of philosophy, psychology and the brain sciences from the enactivist perspective, arguing that action, as opposed to mere reaction, has to be emotionally motivated, and that the understanding of all modalities of consciousness should include that perspective. The author of many books and articles on these topics, he is interested in integrating the social sciences with phenomenology, ethics, and philosophy of mind. He is now trying to integrate enactive consciousness theory with moral and social philosophy, with relevance to our current world-wide crisis of internet disinformation. The Moral Psychology of Internal Conflict (Cambridge University Press 2018) is an attempted beginning in that direction. His latest book, Action, Embodied Mind, and Life-World (SUNY Press 2022) is a continuation of that project. His various books in these areas are listed at the Ralph D. Ellis page of Amazon.com.

Abstract Background Type A acute aortic dissection (TAAAD) is a serious cardiovascular disease with a high mortality rate and prompt diagnosis is the key to survival. However, misdiagnosis is common in the Emergency Department (ED). The aim of this study is to evaluate the rate of misdiagnosis, factors associated with misdiagnosis and patient outcomes. Methods This retrospective cohort study recruited 91 patients with TAAAD at the ED of a tertiary university hospital in Hong Kong from 2013 to 2022. Patients were divided into the following two groups: correct diagnosis (60 patients) and misdiagnosis (31 patients) of TAAAD. Clinical symptoms, signs, and investigations were analyzed as factors associated with misdiagnosis by multivariate analysis. In‐patient mortality, 30‐day mortality, 1‐year mortality, and hospital length of stay (LOS) were compared between the two groups. Results The misdiagnosis rate of TAAAD was 34.1% (31/91). Absence of severe intensity pain (OR = 6.01, 95% confidence interval [CI] = 1.41–25.63, p = 0.015), less urgent triage category (OR = 4.46, 95% CI = 1.77–11.22, p = 0.002), and absence of point‐of‐care ultrasound exam (POCUS) (OR = 13.00, 95% CI = 3.05–55.40, p = 0.001) were associated with misdiagnosis. There were no statistically significant differences between correct diagnosis and misdiagnosis groups in patient outcomes including in‐hospital mortality (28.3% vs. 38.7%), 30‐day mortality (28.3% vs. 38.7%), 1‐year mortality (30.0% vs. 41.9%), or hospital LOS (15.5 ± 15.6 days vs. 14.7 ± 15.5 days). Conclusions One‐third of cases in our study were misdiagnosed. The absence of severe intensity pain, less urgent triage category, and absence of POCUS ultrasound exam were independent factors associated with misdiagnosis. More widespread use of POCUS of the aorta and heart may help to improve the diagnosis of TAAAD in the ED.

Abstract Plant endogenous signaling peptides shape growth, development and adaptations to biotic and abiotic stress. Here, we identify C-TERMINALLY ENCODED PEPTIDEs (CEPs) as immune-modulatory phytocytokines in Arabidopsis thaliana. Our data reveals that CEPs induce immune outputs and are required to mount resistance against the leaf-infecting bacterial pathogen Pseudomonas syringae pv. tomato. We show that effective immunity requires CEP perception by tissue-specific CEP RECEPTOR 1 (CEPR1) and CEPR2. Moreover, we identify the related RECEPTOR-LIKE KINASE 7 (RLK7) as a CEP4-specific CEP receptor contributing to CEP-mediated immunity, suggesting a complex interplay of multiple CEP ligands and receptors in different tissues during biotic stress. CEPs have a known role in the regulation of root growth and systemic nitrogen (N)-demand signaling. We provide evidence that CEPs and their receptors promote immunity in an N status-dependent manner, suggesting a previously unknown molecular crosstalk between plant nutrition and cell surface immunity. We propose that CEPs and their receptors are central regulators for the adaptation of biotic stress responses to plant-available resources.

Abstract Mitochondrial dysfunction is a central aspect of Parkinson’s disease (PD) pathology, yet the underlying mechanisms are not fully understood. This study investigates the link between α-Synuclein (α-Syn) pathology and the loss of translocase of the outer mitochondrial membrane 40 (TOM40), unraveling its implications for mitochondrial dysfunctions in neurons. We discovered that TOM40 protein depletion occurs in the brains of patients with Guam Parkinsonism-Dementia (Guam PD) and cultured neurons expressing α-Syn proteinopathy, notably, without corresponding changes in TOM40 mRNA levels. Cultured neurons expressing α-Syn mutants, with or without a mitochondria-targeting signal (MTS) underscores the role of α-Syn’s mitochondrial localization in inducing TOM40 degradation. PDe-related etiological factors, such as 6-hydroxydopamine or ROS/metal ions stress, which promotes α-Syn oligomerization, exacerbate TOM40 depletion in PD patient-derived cells with SNCA gene triplication. Although α-Syn interacts with both TOM40 and TOM20 in the outer mitochondrial membrane, degradation is selective for TOM40, which occurs via the ubiquitin-proteasome system (UPS) pathway. Our comprehensive analyses using Seahorse technology, mitochondrial DNA sequencing, and damage assessments, demonstrate that mutant α-Syn-induced TOM40 loss results in mitochondrial dysfunction, characterized by reduced membrane potential, accumulation of mtDNA damage, deletion/insertion mutations, and altered oxygen consumption rates. Notably, ectopic supplementation of TOM40 or reducing pathological forms of α-Syn using ADP-ribosylation inhibitors ameliorate these mitochondrial defects, suggesting potential therapeutic avenues. In conclusion, our findings provide crucial mechanistic insights into how α-Syn accumulation leads to TOM40 degradation and mitochondrial dysfunction, offering insights for targeted interventions to alleviate mitochondrial defects in PD.

Background/Objectives: Caring for patients at the end of life can involve issues that are ethically and legally fraught: withholding or withdrawing artificial nutrition and hydration, pain control that could hasten death, aggressive treatment that is continued when it seems only to be prolonging suffering, patients who request medical assistance in dying, and so forth. Clinicians may find that their deeply held ethical principles conflict with law, institutional policy, or patients’ choices. In these situations, they may consider either refusing to participate in procedures that they find morally abhorrent (conscientious refusal) or providing care that they believe to be ethically obligatory despite being contrary to law or policy (conscientious commitment). Methods: This paper reviews the ethical issues involved. Results: Each of the usual policies for handling conscientious refusals faces serious challenges. Conclusions: Healthcare providers who refuse to provide medical services should be expected to explain their reasons, make prompt referrals, and bear some of the resulting costs or burdens.

This publication examines the representation of information within test specifications and formulas defined in standards and directives. This information often pre-defines not only the tests and requirements to be conducted but also the information backflow within the execution. These results are crucial for the effective management of knowledge throughout the product development process as well as for the creation and maintenance of digital representations of a physical product or plant. However, the accessibility of this information is frequently hindered by its extensive and heterogenous definition across a multitude of standards, directives, and other technical regulations. Furthermore, the pre-defined information is typically documented and processed manually on a recurring basis. Given this challenge, the following article presents a holistic two-part approach for pre-defining the information backflow of subsequent physical instances. Initially, an analysis of multiple test specifications in standards and directives is conducted, resulting in the development of a generic data model to represent this Pre-defined Information Backflow (PdIB). The second step builds on the first and defines an optimized representation for machine readability and executability for the future design of standards and directives. The two parts are brought together and validated using representative examples, thereby demonstrating the practical applicability and effectiveness of the proposed approach. This enhances the accessibility and usability of information in test specifications and formulas, thereby establishing a foundation for enhancing the efficiency of knowledge work in product development and the creation of digital representations of products and plants.

Abstract The application of upconversion nanoparticles (UCNPs) for cell and tissue analysis requires a comprehensive understanding of their interactions with biological entities to prevent toxicity or harmful effects. Whereas most studies focus on cancer cells, this work addresses non-cancerous cells with their regular in vitro physiology. Since it is generally accepted that surface chemistry largely determines biocompatibility in general and uptake of nanomaterials in particular, two bilayer surface coatings with different surface shielding properties have been studied: (i) a phospholipid bilayer membrane (PLM) and (ii) an amphiphilic polymer (AP). Both surface modifications are applied to (12–33) nm core-shell UCNPs NaYF4(Yb, Er)@NaYF4, ensuring colloidal stability in biological media. The impact of UCNPs@AP and UCNPs@PLM on non-cancerous epithelial-like kidney cells in vitro was found to differ significantly. UCNPs@PLM did not exhibit any measurable effect on cell physiology, even with prolonged exposure. In contrast, UCNPs@AP caused changes in cell morphology and induced cell-death after approximately 30 h. These variations in toxicity are attributed to the distinct chemical stability of these particles, which likely influences their intracellular disintegration.

Abstract Despite decades of improvements in cytotoxic therapy, the current standard of care for locally advanced pancreatic cancer (LAPC) provides, on average, only a few months of survival benefit. Stereotactic Body Radiation Therapy (SBRT), a technique that accurately delivers high doses of radiation to tumors in fewer fractions, has emerged as a promising therapy to improve local control of LAPC; however, its effects on the tumor microenvironment and hypoxia remain poorly understood. To explore how SBRT affects pancreatic tumors, we combined an orthotopic mouse model of pancreatic cancer with an intravital microscopy platform to visualize changes to the in vivo tumor microenvironment in real-time. Mice received SBRT (5 × 8 Gy) or were left untreated, and were imaged before and 1, 4, 7, and 14 days after treatment (n = 7/group). A fluorescent human pancreatic cancer cell line (BxPC3-DsRed) engineered to express GFP under hypoxic conditions (driven by hypoxia-inducible factor, HIF) was used to monitor tumor hypoxia. Immunohistochemical staining was also performed on tissues to validate in vivo data. Our findings demonstrate a persistent decrease in pancreatic tumor hypoxia as early as one day after SBRT. This coincided with a decrease in both tumor cell proliferation and cell density in the SBRT group. Reduced demand for oxygen after SBRT (due to cell death and growth arrest from treatment) significantly contributed to reoxygenation of the pancreatic TME. Understanding how this reoxygenation phenomenon occurs in a dose-dependent manner will help improve dosing and fractionation schemes for clinical SBRT.

Abstract Diabetes is a pandemic disease that causes the loss of control of glucose regulation in the organism, in consequence of dysfunction of insulin production or functionality. In this work, the antidiabetic bioactivity of 182 fractions from 19 cyanobacteria strains derived from the LEGE Culture Collection were analysed using the 2-NBDG assay in zebrafish larvae. From this initial screening, two fractions (57 (06104_D) and 107 (03283_B)) were identified as promising insulin mimetics. These were further characterized by measuring glucose levels in whole larvae, the expression of glucose transporters (GLUT 1–3) using western blot, and the mRNA expression levels of the glut2, pepck, and insa genes using real-time qPCR. Both fractions showed a decrease in free glucose levels. Furthermore, exposure to fraction 06104_D decreased GLUT1 and increased insa mRNA levels. The chemical composition of these fractions was determined using LC-HRESIMS/MS and compared to inactive fractions of the same polarity in order to identify the unique bioactive molecules. The molecular networks constructed using the GNPS platform revealed that fraction 06104_D contained mass clusters primarily composed of chlorins, lipids, and terpenoids, while fraction 03283_B contained xanthophylls, peptides, and terpenoids. To correlate the observed activity with the chemical composition of fraction 06104_D, pheophorbide a was chosen as a representative of chlorophyll derivatives. Exposure to zebrafish larvae at 10 and 20 µM confirmed the increased glucose uptake on the 2-NBDG assay. These findings highlight the bioactivity of chlorophyll derivatives as insulin mimetic compounds, as well as cyanobacteria as a source of potential therapeutic diabetes applications.

Abstract Pathogenic activating mutations in the fibroblast growth factor receptor 3 (FGFR3) drive disease maintenance and progression in urothelial cancer. 10–15% of muscle-invasive and metastatic urothelial cancer (MIBC/mUC) are FGFR3-mutant. Selective targeting of FGFR3 hotspot mutations with tyrosine kinase inhibitors (e.g., erdafitinib) is approved for mUC and requires FGFR3 mutational testing. However, current testing assays (polymerase chain reaction or next-generation sequencing) necessitate high tissue quality, have long turnover time, and are expensive. To overcome these limitations, we develop a deep-learning model that detects FGFR3 mutations using routine hematoxylin-eosin slides. Encompassing 1222 cases, our study is a large-scale validation of a model prescreening FGFR3 mutations for MIBC and mUC patients. In this work, we demonstrate that our model achieves high sensitivity (>93%) on advanced and metastatic cases while reducing molecular testing by 40% on average, thereby offering a cost-effective and rapid pre-screening tool for identifying patients eligible for FGFR3 targeted therapies.

Abstract In the last three decades, ablation of atrial fibrillation (AF) has become an evidence‐based safe and efficacious treatment for managing the most common cardiac arrhythmia. In 2007, the first joint expert consensus document was issued, guiding healthcare professionals involved in catheter or surgical AF ablation. Mounting research evidence and technological advances have resulted in a rapidly changing landscape in the field of catheter and surgical AF ablation, thus stressing the need for regularly updated versions of this partnership which were issued in 2012 and 2017. Seven years after the last consensus, an updated document was considered necessary to define a contemporary framework for selection and management of patients considered for or undergoing catheter or surgical AF ablation. This consensus is a joint effort from collaborating cardiac electrophysiology societies, namely the European Heart Rhythm Association, the Heart Rhythm Society, the Asia Pacific Heart Rhythm Society, and the Latin American Heart Rhythm Society

Abstract The prediction of the risk of developing complications after colorectal surgery for colorectal carcinoma remains imprecise. Body composition measurements on a computed tomography (CT) scan can potentially contribute to a better preoperative risk assessment. The aim of this systematic review is to evaluate the evidence for the use of body composition measurements on CT scans to predict short‐term complications after colorectal cancer surgery. A literature search (in PubMed, Embase and Web of Science) was performed up to 1 August 2022. Two researchers independently screened the articles, extracted data and assessed the quality of the studies using the Quality in Prognosis Studies tool. The primary outcome measure was the occurrence of complications within 30 days after surgery. Meta‐analysis was conducted using a random‐effects model to synthesize a pooled odds ratio (OR). The study protocol was registered in PROSPERO (CRD42021281010). Forty‐five articles with a total of 16 537 patients were included. In total, 26 body composition measures were investigated: 8 muscle‐related measures, 11 adipose tissue measures, 4 combined muscle and adipose tissue measures, and 3 other measures. These were investigated as potential predictors for more than 50 differently defined postoperative complications. Meta‐analysis was only possible for two measurements and showed that higher amounts of visceral fat increase the risk of developing overall complications (OR: 2.52 [1.58–4.00], P

Abstract Background Whole lung transpulmonary chemoembolization using a combination of doxorubicin (DXO) and degradable starch microspheres (DSM-TPCE) might be a promising treatment option in soft tissue sarcoma. To pave the way for clinical studies, this study aimed to evaluate the short-term effects of DSM-TPCE with DXO using an ex vivo isolated lung perfusion (ILP) model. Methods Nine lung specimens retrieved from patients undergoing lobectomy underwent ex vivo ILP. In groups of three, lung specimens were either treated with sole DXO, sole DSM, or combined substances (DSM + DXO). During ex vivo ILP, histological samples were obtained from each lung every 15 min. Quantitative DXO analysis and histopathological grading of possible tissue damage using a five-point Likert scale was performed. Two-way repeated measures ANOVA tested for differences between treatment groups and changes over time. Results We created a preclinical ex vivo ILP model to simulate the effects of DSM-TPCE. In histopathological analysis, only two specimens, treated with only DXO, showed an increase in parenchymal damage over time. No significant effect of time (3.3%, p = 0.305) or group (23.3; p = 0.331) was identified. Within the lung tissue, the DXO concentration ranged from 205 to 1,244 ng/g. No significant effects could be detected regarding different treatment groups (4.9% of total variation, p = 0.103). Conclusion In an ex vivo ILP model using human lung lobes, the physiological effects of DSM-TPCE with DXO could be tested. Neither increased DXO concentrations in lung tissue nor histopathological changes indicating early lung toxicity were observed. Relevance statement An ex vivo ILP model using human lung specimens did not show any signs of early lung toxicity after transpulmonary chemoembolization with DXO. These results support further evaluation of DSM-TPCE in phase I/II trials. Key Points Transpulmonary chemoembolization can be investigated in an ex vivo ILP model. DSM did not increase DXO in normal lung tissue. DSM did not increase parenchymal toxicity compared to the control groups. Graphical Abstract

Abstract Polyproline sequences are deleterious to cells because they stall ribosomes. In bacteria, EF-P plays an important role in overcoming such polyproline sequence-induced ribosome stalling. Additionally, numerous bacteria possess an EF-P paralog called EfpL (also known as YeiP) of unknown function. Here, we functionally and structurally characterize EfpL from Escherichia coli and demonstrate its role in the translational stress response. Through ribosome profiling, we analyze the EfpL arrest motif spectrum and find additional sequences beyond the canonical polyproline motifs that both EF-P and EfpL can resolve. Notably, the two factors can also induce pauses. We further report that EfpL can sense the metabolic state of the cell via lysine acylation. Overall, our work characterizes the role of EfpL in ribosome rescue at proline-containing sequences, and provides evidence that co-occurrence of EF-P and EfpL is an evolutionary driver for higher bacterial growth rates.

Introduction Tick-borne encephalitis (TBE) is rapidly spreading to new areas in many parts of Europe. While vaccination remains the most effective method of protection against the disease, vaccine uptake is low in many endemic countries.Areas covered We conducted a literature search of the MEDLINE database to identify articles published from 2018 to 2023 that evaluated the immunogenicity and effectiveness of TBE vaccines, particularly Encepur, when booster doses were administered up to 10 years apart. We searched PubMed with the MeSH terms ‘Encephalitis, Tick-Borne/prevention and control’ and ‘Vaccination’ for articles published in the English language.Expert opinion Long-term immunogenicity data for Encepur and real-world data on vaccine effectiveness and breakthrough infections following the two European TBE vaccines, Encepur and FSME-Immun, have shown that extending the booster interval from 3–5 years to 10 years does not negatively impact protection against TBE, regardless of age. Such extension not only streamlines the vaccination schedules but may also increase vaccine uptake and compliance among those living in endemic regions.

Background Recombinant protein vaccines are vital for broad protection against SARS-CoV-2 variants. This study assessed ReCOV as a booster in two Phase 2 trials.Research design and methods Study-1 involved subjects were randomized (1:1:1) to receive 20 μg ReCOV, 40 μg ReCOV, or an inactivated vaccine (COVILO®) in the United Arab Emirates. Study-2 participating individuals were randomized (1:1:1) to receive 20 μg ReCOV (pilot batch, ReCOV HA), 20 μg ReCOV (commercial batch, ReCOV TC), or 30 μg BNT162b2 (COMIRNATY®) in the Philippines. The primary immunogenicity objectives was to compare the geometric mean titer (GMT) and seroconversion rate (SCR) of neutralizing antibodies induced by one ReCOV booster dose with those of inactivated vaccine and BNT162b2, respectively, at 14 days post-booster.Results Heterologous ReCOV booster doses were safe and induced comparable immune responses to inactivated vaccines and BNT162b2 against Omicron variants and the prototype. They showed significant advantages in cross-neutralization against multiple SARS-CoV-2 variants, surpassing inactivated vaccines and BNT162b2, with good immune persistence.Conclusions Heterologous ReCOV boosting was safe and effective, showing promise in combating COVID-19. The study highlights ReCOV’s potential for enhanced protection, supported by strong cross-neutralization and immune persistence.Clinical Trial Registration Study-1, www.clinicaltrials.gov, identifier is NCT05323435; Study-2, www.clinicaltrials.gov, identifier is NCT05084989.

Abstract Background The prognosis of patients with anaplastic thyroid cancer (ATC) remains dismal. A small portion of patients experience longterm survival and need to be identified before treatment allocation. Survival scores may guide clinicians making more informed decisions about treatment options and improve the understanding of patients’ prognosis. The aim of this study was to validate two prognostic scores using an independent dataset to analyze which prognostic index is superior in discriminating survival. Methods Thirty-four patients with histologically confirmed ATC diagnosed between January 2009 and December 2019 were consecutively treated at our department and evaluated. Next generation sequencing was performed in 7 (21%) patients, but no druggable mutation was found. 50% of all patients received surgery and 56% were treated with chemoradiotherapy. The median radiation dose in equivalent dose in 2 Gy fractions (EQD2) was 50 Gy (SD:21 Gy). The study compared the discrimination of the Sugitani Prognostic Index (SPI) and the Marchand-Crety Prognostic Score (MCPS) using concordance statistics, area under the receiver-operating characteristics curve (AUC), net reclassification index, and integrated discrimination improvement for 6-month survival. Results The median survival of the entire cohort was 5 months (range: 1-133). The AUC for 6-month survival was 0.85 (95% confidence interval [CI]:0.72–0.97) for SPI and 0.69 (95% CI: 0.56–0.83) for MCPS (p

Abstract Introduction Direct oral anticoagulant (DOAC) dose adjustment is based on age, renal function, and body weight. There is a paucity of data describing the factors associated with the prescription of inappropriate dosage and their impact on clinical outcomes among patients receiving transcatheter aortic valve implantation (TAVI). Methods In a single-center study, 432 patients who were on long-term DOAC therapy and underwent TAVI between 2015 and 2022 were included. We analyzed the predictors and outcomes of inappropriate dosing of DOACs; namely apixaban, dabigatran, edoxaban, and rivaroxaban. A composite endpoint, including all-cause mortality, life-threatening/major bleeding, stroke, peripheral thromboembolic complications, or myocardial infarction, was assessed after 1 year. Results In this TAVI cohort, inappropriate DOAC dosing was observed in 20.6% of patients. Inappropriate DOAC dosage was related to female gender (adj. odds ratio [OR] 2.72, 95% confidence interval [CI] 1.64–4.51, p

Abstract Waterbird population and species diversity maintenance are important outcomes of wetland conservation management, but knowledge gaps regarding waterbird movements affect our ability to understand and predict waterbird responses to management at appropriate scales. Movement tracking using satellite telemetry is now allowing us to fill these knowledge gaps for highly mobile waterbirds at continental scales, including in remote areas for which data have been historically difficult to acquire. We used GPS satellite telemetry to track the movements of 122 individuals of three species of ibis and spoonbills (Threskiornithidae) in Australia from 2016 to 2023. We analysed movement distances, residency periods and areas, and foraging-site fidelity. From this we derived implications for water and wetland management for waterbird conservation. This is the first multi-year movement tracking data for ibis and spoonbills in Australia, with some individuals tracked continuously for more than five years including from natal site to first breeding attempt. Tracking revealed both inter- and intra-specific variability in movement strategies, including residency, nomadism, and migration, with individuals switching between these behaviours. During periods of residency, areas used and distances travelled to forage were highly variable and differed significantly between species. Sixty-five percent of identified residency areas were not associated with wetlands formally listed nationally or internationally as important. Tracking the movements of waterbirds provides context for coordinated allocation of management resources, such as provision of environmental water at appropriate places and times for maximum conservation benefit. This study highlights the geographic scales over which these birds function and shows how variable waterbird movements are. This illustrates the need to consider the full life cycle of these birds when making management decisions and evaluating management impacts. Increased knowledge of the spatio-temporal interactions of waterbirds with their resource needs over complete life cycles will continue to be essential for informing management aimed at increasing waterbird numbers and maintaining long-term diversity.

In this article we provide the results of European insurers’ first time application of IFRS 17 ‘Insurance Contracts’. We have selected a sample of 24 large European insurers and analysed the disclosure in their 2023 annual reports of this first application of significantly changed principles in the accounting for insurance contracts. At the date of transition most insurance companies reported a decrease in opening equity, although the reasons for the difference are hard to compare due to the various policies that IFRS 4 allowed and the different transition approaches used. We identified areas of improvement with regard to a further disaggregation of groups of portfolios, analyses of the changes related to the insurance liabilities and sensitivity analyses disclosures. The comparability between insurers in our sample is impeded by the use of options provided by IFRS 17 and by the EU. Half of the companies in our sample presented an (adjusted) operating result as alternative performance (profit) measure in which area explanations can be improved.

This study examines the disclosure quality in the 2023 annual reports of the impact that climate-related matters have on the reporting of financial instruments within banks. The sample contains the 44 largest banks supervised by the European Central Bank. We find that banks have high quality disclosures regarding their objectives, policies and processes for managing the climate-related risk arising from financial instruments. In addition, the exposure to climate related risks is also disclosed, which is mostly fuelled by regulatory disclosure requirements. Banks can improve the quality of their disclosures regarding ESG features embedded in financial instruments and the impact of climate-related risk on the allowance for expected credit losses.

Abstract Family members of Asian Americans (AAs) hold enormous potential as health changemakers to help combat the growing non-communicable disease burden in the community. To inform the development of impactful family-based interventions, there is a need to disentangle the mechanisms behind family influences on health. This study aims to deconstruct how interactivity and closeness mediate the association of age and acculturation with how much AA young adults perceive themselves to influence the health behaviors of family members. 502 AA young adults (48.0% East Asian, 20.9% South Asian, 23.1% Southeast Asian) were recruited in March 2021 to participate in an online survey on family interaction patterns, providing data on 944 unique dyadic family relationships. Associations between age, acculturation, interactivity (shared family activities, living proximity, and interaction frequency), closeness (family connectedness and interaction quality), and family health influence (reflecting influence on diet, exercise, sleep, stress, substance use, and relationship building) were evaluated through structural equation modeling. The final model displayed strong fit (CFI:0.956, RMSEA:0.081, SRMR:0.041), and revealed that an increase in closeness compared to interactivity corresponded with a greater increase in family health influence, with both completely mediating the association between age and family health influence. Acculturation was not associated with closeness, and its effect on family health influence was only partially mediated through interactivity. In subgroup analyses, neither interactivity nor closeness mediated the relationship between age and family health influence among South Asians (unlike East and Southeast Asians). Findings suggest the importance of targeting interactivity and closeness separately when developing AA family-based health interventions, and considering how the age and acculturation profile of AA young adults may shape these dynamics.

Abstract The formation of water ice clouds or hazes on Mars imposes substantial limitations on the vertical transport of water into the middle-upper atmosphere, impacting the planet’s hydrogen loss. Recent observations made by the Mars Environmental Dynamics Analyzer instrument onboard Mars 2020 Perseverance rover have shown a marked decline in water ice abundance within the mesosphere (above 35-40 km) when Mars is near its aphelion (near the northern summer solstice), notably occurring during solar longitudes (Ls) between Ls 70∘ and 80∘. Orbital observations around the same latitudes indicate that temperatures between ~ 30-40 km reach a minimum during the same period. Using cloud microphysics simulations, we demonstrate that this decrease in temperature effectively increases the amount of water cold-trapped at those altitudes, confining water ice condensation to lower altitudes. Similarly, the reinforcement of the cold trap induced by the lower temperatures results in significant reductions in the water vapor mixing ratio above 35–40 km, explaining the confinement of water vapor observed around aphelion from orbiters.

Dit artikel is een vervolgstudie op de door mij gehouden oratie in 2006, die in december van dat jaar is opgenomen in dit maandblad. De essentie van het artikel is om situaties te analyseren waarin fair value een relevante, nuttige waarderingsgrondslag is voor de jaarrekening. Het gaat dan niet om een incidentele toepassing van fair value, zoals bij fusies en overnames, maar om een continu te gebruiken grondslag voor de waardering van activa of verplichtingen. Ten opzichte van 2006 wordt een extra situatie gevonden waarin historische kostprijzen beter niet kunnen worden gebruikt en dat betreft de situatie waarin de onderneming door rekeninghouders of beleggers gedwongen kan worden activa te verkopen. Het gemengde waarderingsmodel waarin historische kostprijzen en marktwaardes als grondslagen simultaan worden toegepast voor elk specifieke situaties, blijft de voorkeur verdienen vanuit het door het Conceptual Framework geformuleerde doel van de jaarrekening.

Abstract Background Diagnosing bipolar disorder (BD) is challenging, and adequate treatment is of major importance to minimalize the consequences of the illness. Early recognition is one way to address this. Although in clinical research the prodromal phase of BD is gaining interest, the perspective of patients with BD and their caregivers on prodromal symptoms is still lacking. The aim of this study is to gain insights in prodromal symptoms of patients with BD and their caregivers before the onset of a first manic episode. Methods A qualitative research method was used to investigate prodromal symptoms one year prior to a first manic episode. In-depth interviews were conducted with patients with BD type I and their caregivers. Only patients with a first manic episode in the previous five years were included. Results The prodromal symptoms from patients’ and caregivers’ perspectives could be clustered into seven themes, with underlying subthemes: behavior (increased activity, destructive behavior, disinhibited behavior, inadequate behavior, changes in appearance), physical changes (changes in sleep, physical signals, differences in facial expression), communication (reciprocity, process, changes in use of social media), thought (process and content), cognition (changes in attention and concentration, forgetfulness), emotions (positive emotions, more intense emotions, mood swings), and personality (more pronounced manifestation of existing personality traits). Conclusion Patients with bipolar I disorder and their caregivers described subsyndromal manic features one year prior to a first manic episode. In addition, they recognized mood lability, physical changes and more pronounced manifestation of existing personality traits. The results of this study confirm the presence of a prodromal phase. In clinical practice, monitoring of prodromal symptoms of BD can be useful in patients with depression, especially those with a familial risk of BD.