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Barriers to developing treatments for human status epilepticus (SE) include the inadequacy of experimental animal models. In contrast, naturally-occurring canine epilepsy is similar to the human condition and can serve as a platform to translate research from rodents to humans. The objectives of this study were to characterize the pharmacokinetics (PK) of an intravenous (IV) dose of topiramate (TPM) in dogs with epilepsy, and evaluate its effect on intracranial electroencephalographic (iEEG) features. Five dogs with naturally occurring epilepsy were used for this study. Three were getting at least one antiseizure drug as maintenance therapy including phenobarbital (PB). Four (ID 1-4) were used for the 10 mg/kg IV TPM + PO TPM study, and three (ID 3-5) were used for the 20 mg/kg IV TPM study. IV TPM was infused over 5 minutes at both doses. The animals were observed for vomiting, diarrhea, ataxia, and lethargy. Blood samples were collected at scheduled pre- and post-dose times. Plasma concentrations were measured using a validated HPLC-MS method. Non-compartmental and population compartmental modeling were performed (Phoenix WinNonLin and NLME) using plasma concentrations from all dogs in the study. Intracranial EEG (iEEG) was acquired in one dog. The difference between averaged iEEG energy levels at 15 minutes pre- and post-dose was assessed using a Kruskal-Wallis test. No adverse events were noted. Topiramate concentration-time profiles were best fit by a two-compartment model. PB co-administration was associated with a 5.6 fold greater clearance and a ~4 fold shorter elimination half-life. iEEG data showed that TPM produced a significant energy increase at frequencies >4 Hz across all 16 electrodes within 15 minutes of dosing. Simulations suggested that dogs on an enzyme inducer would require 25 mg/kg, while dogs on non-inducing drugs would need 20 mg/kg to attain the target concentration (20-30 µg/mL) at 30-minutes post-dose.This study shows that IV TPM has a relatively rapid onset of action, loading doses appear safe, and the presence of PB necessitates a higher dose to attain targeted concentrations. Consequently, it is a good candidate for further evaluation for treatment of seizure emergencies in dogs and people.

IntroductionDeterioration of economic conditions, societal uncertainty, and negative expectations about the future have all been linked to delayed childbearing plans. All these negative circumstances can be related to epidemiological stress, which in turn becomes one of the culprits for changes in fertility plans. This study aims to analyze the individual factors that decrease the probability of wanting to have children after exposure to epidemiological stress from the coronavirus disease 2019 (COVID-19) pandemic.MethodsRecruitment was conducted between April and July 2021. Participants who were heterosexual, non-parent, and non-pregnant without a diagnosis of infertility completed an online, anonymous survey providing information on sociodemographic variables, COVID-19 exposure, COVID-19-related stress, and changes in their reproductive desires. Multiple logistic regression models were used to analyze the data. Participants were also given the opportunity to provide a descriptive explanation for changes in fertility desires due to the pandemic or the political situation (abortion restrictions coinciding with the pandemic in Poland), which was then used for qualitative analysis.ResultsA total of 706 participants completed the survey (mean age = 28.11, SD = 4.87, min = 19, max = 47). We found that (1) the desire to have children decreased in 43.3% of respondents, and (2) women with higher levels of epidemiological stress were more likely to report a decrease in their desired number of children than the less-stressed ones, after adjusting for potential covariates (aOR = 1.064, 95%CI = 1.03–1.10, p

BackgroundConsidering the role PARPs play in inflammation, we assessed the effect of PARP inhibition in an inflammatory skin condition, psoriasis, to explore novel avenues for the potential repurposing of PARP inhibitors that are currently used in tumour therapy.MethodsThe imiquimod (IMQ)-induced model of psoriasis was applied in BALB/c mice. Mice received daily intraperitoneal injection of either one of four PARP inhibitors or their vehicle prior to treatment of the shaved back skin of mice with IMQ-containing cream or control cream for four days. The appearance of the skin of mice was scored daily according to the extent of erythema, induration and scaling. The most effective PARP inhibitor was selected for detailed studies on mouse skin and in a human keratinocyte cell line.ResultsOf the PARP inhibitors, talazoparib and rucaparib improved the imiquimod-induced symptoms on mouse skin. Application of talazoparib in the psoriasis model resulted in maintained terminal differentiation and reduced proliferation of epidermal keratinocytes. Conversely, talazoparib also enhanced the production of pro-inflammatory chemokines in the skin of mice. These effects of talazoparib was associated with increased mitochondrial production of reactive oxygen species and a consequent activation of pro-apoptotic and pro-inflammatory pathways in keratinocytes.ConclusionPARP inhibition by talazoparib promotes terminal differentiation of epidermal keratinocytes that may be beneficial in psoriasis. Despite the fact that talazoparib exerted a pro-inflammatory effect in the skin, which is not unprecedented in anti-psoriatic therapy, these findings may advance the conduction of pre-clinical and clinical trials with PARP inhibitors in psoriasis management.

Hypoalbuminemia, defined as serum albumin levels below 35 g/L, is common in patients with conditions such as nephrotic syndrome, cirrhosis, or sepsis. This review examines the impact of hypoalbuminemia on the pharmacokinetics of selected drugs—such as antibiotics, immunosuppressants, antifungals, or anticonvulsants—emphasizing its role in drug efficacy and safety. Albumin is the main drug transporter and key binding protein, which influences the free drug concentration and drug activity. The review includes all studies available in the scientific literature found in the PubMed, Scopus, and Cochrane databases. The paper emphasizes the importance of therapeutic drug monitoring (TDM) in patients with hypoalbuminemia to avoid subtherapeutic or toxic drug levels. Many drugs need for dose adjustments to achieve therapeutic levels, especially in critically ill patients. The results of studies emphasize the need for individualized dosing regimens based on TDM to optimize drug therapy in patients with hypoalbuminemia. Our review is the first article to summarize the influence of hypoalbuminemia on the pharmacokinetic parameters of drugs and may be a useful tool for clinicians in their daily work.

IntroductionData science training has the potential to propel environmental health research efforts into territories that remain untapped and holds immense promise to change our understanding of human health and the environment. Though data science training resources are expanding, they are still limited in terms of public accessibility, user friendliness, breadth of content, tangibility through real-world examples, and applicability to the field of environmental health science.MethodsTo fill this gap, we developed an environmental health data science training resource, the inTelligence And Machine lEarning (TAME) Toolkit, version 2.0 (TAME 2.0).ResultsTAME 2.0 is a publicly available website that includes training modules organized into seven chapters. Training topics were prioritized based upon ongoing engagement with trainees, professional colleague feedback, and emerging topics in the field of environmental health research (e.g., artificial intelligence and machine learning). TAME 2.0 is a significant expansion upon the original TAME training resource pilot. TAME 2.0 specifically includes training organized into the following chapters: (1) Data management to enable scientific collaborations; (2) Coding in R; (3) Basics of data analysis and visualizations; (4) Converting wet lab data into dry lab analyses; (5) Machine learning; (6) Applications in toxicology and exposure science; and (7) Environmental health database mining. Also new to TAME 2.0 are “Test Your Knowledge” activities at the end of each training module, in which participants are asked additional module-specific questions about the example datasets and apply skills introduced in the module to answer them. TAME 2.0 effectiveness was evaluated via participant surveys during graduate-level workshops and coursework, as well as undergraduate-level summer research training events, and suggested edits were incorporated while overall metrics of effectiveness were quantified.DiscussionCollectively, TAME 2.0 now serves as a valuable resource to address the growing demand of increased data science training in environmental health research. TAME 2.0 is publicly available at: https://uncsrp.github.io/TAME2/.

5-Lipoxygenase (5-LO), encoded by the gene ALOX5, is implicated in several pathologies. As key enzyme in leukotriene biosynthesis, 5-LO plays a central role in inflammatory diseases, but the 5-LO pathway has also been linked to development of certain hematological and solid tumor malignancies. Of note, previous studies have shown that the leukemogenic fusion protein MLL-AF4 strongly increases ALOX5 gene promoter activity. Here, we investigate the upregulation of ALOX5 gene expression by MLL-AF4. Using reporter assays, we first identified the tandem GC box within the ALOX5 promotor sequence as the main target of MLL-AF4. Subsequently, we narrowed down the domains within the MLL-AF4 protein responsible for ALOX5 promoter activation. Our findings indicate that MLL-AF4 binds to the ALOX5 promoter via its CXXC domain and that the AF9ID, pSER and CHD domains redundantly activate transcriptional elongation. Knockdown of the MLL-AF4 gene in the human B cell line SEM revealed that MLL-AF4 is an inducer of ALOX5 gene expression in leukemic cells with lymphoid properties. Finally, we found that the MLL-AF4-related protein MLL-AF9, a driver of acute myeloid leukemia, similarly acts on the ALOX5 promoter. Taken together, we show that two prominent MLL fusion proteins are ALOX5 gene inducers in cells with lymphoid features.

IntroductionTumor-infiltrating lymphocytes are both prognostic and predictive biomarkers for immunotherapy response. However, less is known about the survival benefits oftheir subpopulations.MethodsUsing machine learning models, we assessed the clinical association of the CD8+, PD1+, TCF1+ cel l subset by multiplex immunohistochemistry using tissue microarrays in 553 non-small cell lung cancer (NSCLC) patients and its correlation with other immune cell biomarkers.ResultsWe observed positive correlations between TCF1 and CD20 (r=0.37), CD3 (r=0.45)and CD4 (r=0.33). Notably, triple positive (CD8+PD1+TCF1+) were rare, only observed in 29 of 553 patients (5%). Our analysis revealed that cells coexpressing TCF1 with either CD8+ or PD1+ were independent prognostic markers of disease-specific survival in multivariable analysis (HR=0.728, p=0.029 for CD8+TCF1+, and HR=0.612, p=0.002 for PD1+TCF1+). To pilot the subtype of abundant CD8-TCF1+ cells, we explored an immune cell infiltrated whole slideimage and found the majority to be CD4+.DiscussionOverall, these findings suggest that assessment of CD8+, PD1+, TCF1+ could serve as a potential prognostic biomarker in NSCLC.

BackgroundPlacenta previa is the abnormal implantation of the placenta into the lower segment of the uterus, is associated with adverse maternal and fetal outcomes such as placenta accreta spectrum disorders, antepartum and postpartum hemorrhage, fetal growth restriction, prematurity, stillbirth and neonatal death, thrombophlebitis, and septicemia. The aim of the study was to assess retrospectively how the later onset of placenta previa affects the microRNA expression profile in the whole peripheral blood during the first trimester of gestation.MethodsRegarding the occurrence of the association between aberrant microRNA expression profiles at early stages of gestation and later onset of various pregnancy-related complications, we selected for the study pregnancies developing placenta previa as the only pregnancy-related disorder. In total, 24 singleton pregnancies diagnosed with placenta previa that underwent first-trimester prenatal screening and delivered on-site within the period November 2012–May 2018 were included in the study. Overall, 80 normal pregnancies that delivered appropriate-for-gestational age newborns after completing 37 weeks of gestation were selected as the control group based on the equality of the length of biological sample storage.ResultsDownregulation of multiple microRNAs (miR-20b-5p, miR-24-3p, miR-26a-5p, miR-92a-3p, miR-103a-3p, miR-130b-3p, miR-133a-3p, miR-145-5p, miR-146a-5p, miR-155-5p, miR-181a-5p, miR-195-5p, miR-210-3p, miR-342-3p, and miR-574-3p) was observed in pregnancies destined to develop placenta previa. The combination of seven microRNAs (miR-130b-3p, miR-145-5p, miR-155-5p, miR-181a-5p, miR-210-3p, miR-342-3p, and miR-574-3p) showed the highest accuracy (AUC 0.937, p

BackgroundVasculopathy is a hallmark of systemic sclerosis (SSc) putting patients at an increased risk of cardiovascular disease. Approximately 20–25% of all SSc patients show prolonged elevated C-reactive protein (CRP) levels and thus signs of chronic low-grade inflammation. While CRP−positivity is an independent predictor of cardiovascular disease in non-SSc populations, the relationship between CRP−positivity and cardiovascular health/atherosclerosis in SSc patients is only incompletely understood. Here, we aimed to assess (1) which general, SSc disease-specific and cardiovascular parameters are associated with CRP−positivity in a cohort of SSc patients with prolonged CRP elevations (CRP+ SSc group) relative to SSc patients without CRP elevations (CRP− SSc group). In addition (2), we aimed to investigate whether prolonged CRP−positivity in SSc patients is associated with a higher cardiovascular risk and an increased atherosclerotic burden. We also aimed to (3) identify via random forest classification modeling which combined cardiovascular and/or SSc-specific parameters could differentiate best between SSc patients with elevated CRP levels (the so-called “inflammatory SSc subtype”) and SSc patients without increased CRP levels.MethodsSixty-five SSc patients were recruited and assigned to the CRP+ SSc group (n = 20) if their CRP levels were > 5 mg/L in at least three half-yearly visits within 2 years before enrolment or to the CRP− SSc group (n = 45), respectively. All patients underwent an anamnesis, physical examination, blood draw, and bilateral carotid ultrasound in order to assess arteriosclerotic burden including the presence, number and height of plaques, and carotid intima–media thickness (CIMT) as well as lipid profiles. 10-year ASCVD risk was estimated via the ASCVD risk estimator plus. Statistical evaluation included Spearman’s correlations, logistic regression and random forest modeling under 5-fold cross-validation, and permutation testing to determine combinations of cardiovascular variables highly discriminatory for CRP−positivity.ResultsSSc groups showed comparable mean age, height, and extent of SSc organ involvement. Regarding cardiovascular health, CRP+ SSc patients exhibited a significantly altered HDL-, LDL-, and triglyceride profile (0.001 ≤ p ≤ 0.017) and a significantly higher 10-year ASCVD risk (p = 0.047), relative to CRP− SSc patients. Additionally, within the subgroup of CRP+ SSc patients, positive correlations between CRP levels and CIMT right (ρ = 0.657, p = 0.002) and mean CIMT left and right (ρ = 0.497, p = 0.026) were seen. Combined ROC models identified the four lipid components (HDL, LDL, total cholesterol, and triglycerides) or the SSc duration and ASCVD category to differentiate with high cross-validated ROC-AUCs (AUC: 0.83 ± 0.15, and AUC: 0.86 ± 0.09, p

IntroductionThe International Classification of Functioning, Disability, and Health (ICF) has been widely adopted in academic health profession education and is part of bachelor curricula since its introduction by the WHO in 2001. In this context, interprofessional exchange among health professionals from a biopsychosocial perspective has become increasingly important and is now a key part of bachelor's program curricula to learn with, about, and from each other regarding students’ curiosity about interprofessional collaboration (IPC). This pilot study describes initial teaching experiences within an interprofessional elective module for health professions focused on patient-centeredness. It uses the ICF model to exemplify interprofessional exchange based on real patient experiences from the “DIPEx” database, which stands for “Database of Individual Patients’ Experiences.”MethodsBachelor students from four healthcare professions learned in small interprofessional groups and selected case-related content from excerpts of real patient narratives from qualitative interviews in the DIPEx database. In a peer-to-peer process, students structured, analyzed, and reflected on selected patient experiences and presented their findings using the ICF model.OutcomeDevelop a shared understanding of the case from a biopsychosocial perspective using the ICF model to communicate and reflect on patient-centeredness in interprofessional groups for a common care strategy rooted in patient-centeredness.ConclusionThis study illustrates how the shared analysis of a patient's experience of illness can lead to different perspectives on professional concepts for practice. The ICF model serves as a guiding structure and analysis tool. The core of the IPC, patient-centeredness, becomes the focus of the collaborative actions of the health professions.

BackgroundThe autonomic nervous system (ANS) plays a significant role in atrial fibrillation (AF). Catheter ablation (CA) is a well-established treatment method for AF and significantly affects the ANS, including baroreceptor (BR) function. However, little is known about the changes in BR function caused by radiofrequency (RF) or cryoballoon energy (CB) and its impact on future AF recurrences.PurposeTo assess 1-year efficacy of CA of AF in relation to BR function modification and type of ablation energy used.MethodsThe study group consisted of 78 patients (25 females, mean age 58 ± 9 years) with paroxysmal AF and first CA (39 patients in the RF group and 39 in the CB group). The BR function was assessed non-invasively, using tilt testing before and after CA, and three BR parameters were calculated: event count (BREC) depicting overall BR activity, slope mean depicting BR sensitivity (BRS), and BR effectiveness index (BEI). The efficacy of CA was assessed during 1-year follow-up, which consisted of ambulatory visits and 24-h Holter ECG recordings at 3, 6, and 12 months after CA. The quality of life was assessed by using a dedicated scale [University of Toronto Atrial Fibrillation Severity Scale (AFSS)].ResultsThe two groups did not show differences in terms of clinical or demographic data. One-year follow-up was completed for 35 (89.7%) patients from the CB group and for 34 (87.2%) from the RF group. The rates of efficacy of CB and RF were similar [31/35 (88.6%) vs. 26/34 (76.5%), respectively]. After CA, the BR function decreased in both groups, with a significantly greater decrease in the CB group. The changes in BR parameters were similar in both responders and non-responders after CA in the whole group [BREC 10.0 (2.0–24.0) vs. 12.0 (4.0–21.5), p = 0.939; BRS 5.4 (3.7–6.5) vs. 4.8 (3.6–7.2), p = 0.809; BEI 24.8 (15.9–27.4) vs. 17.5 (8.9–27.5), p = 0.508, respectively]. According to the AFSS, the AF symptoms were significantly reduced in both groups to a similar extent.ConclusionsCA for AF significantly decreased the BR function, especially in patients undergoing CB. There was no correlation between CA-induced changes in BR parameters and ablation outcome.

Giant congenital pigmented nevi constitute an extremely diverse group of skin lesions with varying morphologies. These nevi are often associated with many clinical implications, such as increased risk of melanoma and the presence of neurocutaneous melanosis, with melanoma being the primary concern. We present a rare case of a 62-year-old patient with a giant congenital birthmark who reported to the oncology department due to a tumor in the lower abdomen detected during an ultrasound examination. A biopsy of the lesion showed the presence of melanoma metastasis. Four independent dermatologists performed a dermoscopic examination of the patient’s skin and mucous membranes. In the PET/CT examination, apart from the previously described change in the lower abdomen, no metabolically active foci with features of malignant growth were found. The patient underwent surgical removal of the lesion in the lower abdomen. The postoperative histopathological examination confirmed the presence of metastasis of melanoma in the subcutaneous tissue of the abdomen with no connection to the epidermis. The BRAFV600 mutation was not found in the molecular test. For stage IV R0 melanoma with distant metastasis, with stage T0N0M1a, the only adjuvant treatment option following radical resection is nivolumab. After a rheumatological consultation, the patient was qualified for adjuvant treatment with nivolumab.

IntroductionThis study aimed to establish efficient, cost-effective, and early predictive models for adverse pregnancy outcomes based on the combinations of a minimum number of miRNA biomarkers, whose altered expression was observed in specific pregnancy-related complications and selected maternal clinical characteristics.MethodsThis retrospective study included singleton pregnancies with gestational hypertension (GH, n = 83), preeclampsia (PE, n = 66), HELLP syndrome (n = 14), fetal growth restriction (FGR, n = 82), small for gestational age (SGA, n = 37), gestational diabetes mellitus (GDM, n = 121), preterm birth in the absence of other complications (n = 106), late miscarriage (n = 34), stillbirth (n = 24), and 80 normal term pregnancies. MiRNA gene expression profiling was performed on the whole peripheral venous blood samples collected between 10 and 13 weeks of gestation using real-time reverse transcription polymerase chain reaction (RT-PCR).ResultsMost pregnancies with adverse outcomes were identified using the proposed approach (the combinations of selected miRNAs and appropriate maternal clinical characteristics) (GH, 69.88%; PE, 83.33%; HELLP, 92.86%; FGR, 73.17%; SGA, 81.08%; GDM on therapy, 89.47%; and late miscarriage, 84.85%). In the case of stillbirth, no addition of maternal clinical characteristics to the predictive model was necessary because a high detection rate was achieved by a combination of miRNA biomarkers only [91.67% cases at 10.0% false positive rate (FPR)].ConclusionThe proposed models based on the combinations of selected cardiovascular disease-associated miRNAs and maternal clinical variables have a high predictive potential for identifying women at increased risk of adverse pregnancy outcomes; this can be incorporated into routine first-trimester screening programs. Preventive programs can be initiated based on these models to lower cardiovascular risk and prevent the development of metabolic/cardiovascular/cerebrovascular diseases because timely implementation of beneficial lifestyle strategies may reverse the dysregulation of miRNAs maintaining and controlling the cardiovascular system.

The purpose of this case report is to present a poorly differentiated sarcoma in a pet rat. A veterinarian detected a small-sized nodular lesion in the ventral region of the neck during a follow-up visit related to another ailment. The anatomical structures found in the neck region in the rat and the differential diagnosis when deformities are palpated in this body part are discussed in detail. The patient underwent a total of four surgical procedures, as well as radiotherapy and chemotherapy. The rat survived in good condition for 144 days after finding the tumor.

Wild gadoids are known to have close associations with open-net fish farms, leading to concerns about changes in natural fish distribution and feeding patterns. However, the nature of the relationships between non-pelagic fish and mobile benthic invertebrates and aquaculture facilities remains poorly documented, even though this group contains widespread commercial North Atlantic species. This study utilizes baited remote and towed underwater video surveys to resolve the ecosystem-level effects of open salmon aquaculture cages and organic enrichment on the spatial structure and relative abundance of demersal fish and crustacean communities. Towed camera surveys were carried out 50 to >600 m downstream of three farms producing finfish in Western Finnmark and four in the Frøya region of Norway. Towed camera surveys were paired with baited remote underwater video surveys at the four Frøya farms. The declining enrichment gradient with distance downstream of the farm cages was confirmed by modeled and observed depositional flux measurements and benthic infaunal community composition. The community structure of wild demersal fish and crustaceans in close association with the seafloor varied with the distance from the aquaculture sites. In addition to the established pattern of the attraction of gadoids, the edible crab (Cancer pagurus) and flatfish (Pleuronectes platessa and Microstomus kitt) showed a preference for areas 10–150 m from farm cages where organically enriched sediments contain a rich food source of opportunistic polychaetes. In contrast, the cuckoo wrasse (Labrus mixtus) and the common hermit crab (Pagurus bernhardus) exhibited higher numbers in locations over 600 m from the farms. Findings show how changes in the benthic food web from aquaculture enrichment can affect the spatial distribution of poorly studied but commercially important fish and crustaceans. Such changes in distribution can impact the availability of these species to coastal fisheries, especially in dense aquaculture regions.

In the past decade we have seen new advances and thus remarkable progress in the therapeutic options for non-small cell lung cancer (NSCLC). Among cytostatic therapies with new approaches in molecularly targeted therapies, we see new developments in a wide range of applications for immunotherapies. In this review we discuss the new potential modalities for the use of immune checkpoint inhibitors (ICIs) in the frontlines, including in early-stage (perioperative) and metastatic settings. The perioperative use of ICIs in both neoadjuvant and adjuvant settings may show benefits for patients. In early-stage NSCLC (from stage IIB and above) a multimodality approach is recommended as the gold standard for the treatment. After surgical resection platinum-based adjuvant chemotherapy has been the standard of care for many years. Based on the benefit of disease-free survival, the approval of adjuvant atezolizumab and adjuvant pembrolizumab was a significant breakthrough. In the metastatic setting, the use of immune checkpoint inhibitors with chemotherapy, regardless of PD-L1 expression or ICI alone (PD-L1 expression equal to or greater than 50%) also improves overall survival and progression-free survival.

Participation in non-formal adult education (NFE) is considered an essential part of lifelong learning, aiming to foster the development of individuals and societies. This significance is particularly evident today, given the era of extensive digitalization and disruptive technological advances. Nevertheless, not all adults participate in organized learning and have equal chances. Therefore, this study addresses the absence of up-to-date comparative findings on participation in NFE in the post-COVID-19 world. To this end, we examine current trends in NFE participation in four European countries: Sweden, Germany, the United Kingdom, and the Czech Republic (RQ1), where we explore the impact of key micro (social and behavioral), meso (job-related), and macro-level (country-specific) factors on this participation (RQ2). Our findings indicate that NFE participation remained relatively stable in 2022 compared to 2016, except for Sweden and Germany, which achieved higher participation rates. However, differences in participation between countries are diminishing. Simultaneously, NFE participation is becoming increasingly job-oriented and receives more support from employers. However, it is important to note that inequality in access to NFE persists, as the main predictors of NFE participation, such as learning intentions, educational attainment, economic and occupational status, remain consistent, regardless of the participants’ economic activity and country of birth. This underscores the enduring significance of a key concept behind this study: the willingness to engage in organized NFE exhibits a complex structure with multiple layers.

Indigenous Peoples in Canada have endured many genocidal efforts, such as residential schools. Across the country, initiatives to promote critical historical education about residential schools are underway, ranging in duration, content, and immersion. In this study, we tested whether a promising high-immersion approach, a virtual reality residential school, could improve non-Indigenous participants' attitudes and feelings toward Indigenous people. We compared the effects of the virtual residential school to a transcript condition, in which participants read the transcripts of the narration that accompanied the virtual residential school, and an empty control condition. The study had three time points: Baseline (N = 241), intervention (N = 241), and follow-up (N = 132). Immediately following the intervention, what participants learned about the residential school, both through virtual reality and reading the transcripts, increased non-Indigenous participants' empathy, political solidarity, and outgroup warmth for Indigenous people, relative to the control. The virtual reality school, but not transcripts, also increased privity relative to the control. These effects decreased over time. In summary, though both written and virtual reality forms of critical historical education were effective in the short term, to maintain the long-term effects of critical historical education, ongoing or recurring education is likely necessary. These results extend the virtual reality literature to unstudied concepts (political solidarity, privity) and critical historical education literature to a new form of media (virtual reality). We discuss the findings in relation to literature on critical historical education and virtual reality as well as outline future directions.

Sarcomas are rare and heterogeneous malignancies that are difficult to treat. Approximately 50% of patients diagnosed with sarcoma develop metastatic disease with so far very limited treatment options. The transmembrane protein B7-H3 reportedly is expressed in various malignancies, including different sarcoma subtypes. In several cancer entities B7-H3 expression is associated with poor prognosis. In turn, B7-H3 is considered a promising target for immunotherapeutic approaches. We here report on the preclinical characterization of a B7-H3xCD3 bispecific antibody in an IgG-based format, termed CC-3, for treatment of different sarcoma subtypes. We found B7-H3 to be expressed on all sarcoma cells tested and expression on sarcoma patients correlated with decreased progression-free and overall survival. CC-3 was found to elicit robust T cell responses against multiple sarcoma subtypes, resulting in significant activation, release of cytokines and effector molecules. In addition, CC-3 promoted T cell proliferation and differentiation, resulting in the generation of memory T cell subsets. Finally, CC-3 induced potent target cell lysis in a target cell restricted manner. Based on these results, a clinical trial evaluating CC-3 in soft tissue sarcoma is currently in preparation.

Psoriasis is a common, life-long skin disease with a significant negative health and societal impact. Data on rates of disease control and treatment strategies are lacking in Central and Eastern European countries. We aimed to describe the real-world disease severity, control, and treatment strategies for psoriasis in patients from Central and Eastern European countries. CRYSTAL (EUPAS36459) was a cross-sectional, retrospective study in adults (18–75 years) from Bulgaria, Estonia, Hungary, Latvia, Lithuania, Romania, and Russia. We enrolled patients with moderate-to-severe psoriasis receiving continuous systemic treatment for ≥24 weeks. We used the Psoriasis Area and Severity Index (PASI) to describe disease severity and the Dermatology Life Quality Index (DLQI) to assess quality of life (QoL) and collected other outcomes [psoriasis work productivity and activity impairment (WPAI-PSO), patient satisfaction] at enrollment. Analyses were descriptive. A total of 690 patients were included in the analyses. Median disease duration was 11.8 years. Current treatment was monotherapy for most patients (95.8%) with either biological (BIO group; 88.4%) or conventional (NON-BIO group; 7.4%) agents. Mean (± standard deviation) absolute PASI scores were 3.5 ± 5.7, 3.1 ± 5.3, and 6.6 ± 7.4 in the overall population, the BIO group, and the NON-BIO group, respectively. Among patients treated with monotherapy, absolute PASI scores ≤1, ≤3, and ≤5 were observed for 44.1%, 72.0%, and 82.6% of BIO patients and 21.6%, 33.3%, and 49.0% of NON-BIO patients. Mean DLQI total score was 3.3 ± 5.1; higher scores were noted for higher absolute PASI. The most impacted WPAI-PSO domain was presenteeism; for all domains, impact increased with increased absolute PASI. A total of 91.8% of BIO patients and 74.5% of NON-BIO patients were satisfied with the current treatment. We observed a better disease control in BIO than NON-BIO patients. However, around half of BIO patients did not reach clear skin status and reported an impact on QoL. An improvement in treatment strategies is still needed in Central and Eastern European countries to optimize outcomes of moderate-to-severe psoriasis.

Tacrolimus is metabolized in the liver with the participation of the CYP3A4 and CYP3A5 enzymes. Proton pump inhibitors are used in kidney transplant patients to prevent duodenal and gastric ulcer disease due to glucocorticoids. Omeprazole, unlike famotidine, is a substrate and inhibitor of the enzymes CYP2C19, CYP3A4, CYP3A5. The aim of this study was to compare the impact of omeprazole and famotidine on the pharmacokinetics of tacrolimus. A randomized, non-blinded study involving 22 stabilized adult kidney transplant patients was conducted. Patients received the standard triple immunosuppression regimen and omeprazole 20 mg (n = 10) or famotidine 20 mg (n = 12). The study material consisted of blood samples in which tacrolimus concentrations were determined using the Chemiluminescent Microparticle Immuno Assay method. A single administration of omeprazole increased tacrolimus concentrations at 2 h (day 2) = 11.90 ± 1.59 ng/mL vs. 2 h (day 1 — no omeprazole administration) = 9.40 ± 0.79 ng/mL (p = 0.0443). AUC0-6 amounted to 63.07 ± 19.46 ng × h/mL (day 2) vs. 54.23 ± 10.48 ng × h/mL (day 1), (p = 0.0295). AUC2-6 amounted to 44.32 ± 11.51 ng × h/mL (day 2) vs. 38.68 ± 7.70 ng × h/mL (day 1), (p = 0.0130). Conversely, no significant changes in values of pharmacokinetic parameters were observed for famotidine. Omeprazole significantly increases blood exposure of tacrolimus. The administration of famotidine instead of omeprazole seems safer for patients following kidney transplantation.Clinical Trial Registration:clinicaltrials.gov, identifier NCT05061303

ObjectiveSmart sensing has the potential to make psychotherapeutic treatments more effective. It involves the passive analysis and collection of data generated by digital devices. However, acceptance of smart sensing among psychotherapy patients remains unclear. Based on the unified theory of acceptance and use of technology (UTAUT), this study investigated (1) the acceptance toward smart sensing in a sample of psychotherapy patients (2) the effectiveness of an acceptance facilitating intervention (AFI) and (3) the determinants of acceptance.MethodsPatients (N = 116) were randomly assigned to a control group (CG) or intervention group (IG). The IG received a video AFI on smart sensing, and the CG a control video. An online questionnaire was used to assess acceptance of smart sensing, performance expectancy, effort expectancy, facilitating conditions and social influence. The intervention effects of the AFI on acceptance were investigated. The determinants of acceptance were analyzed with structural equation modeling (SEM).ResultsThe IG showed a moderate level of acceptance (M = 3.16, SD = 0.97), while the CG showed a low level (M = 2.76, SD = 1.0). The increase in acceptance showed a moderate effect in the intervention group (p

Ruminant production systems in the arid and semi-arid regions of Sub-Saharan Africa confront severe challenges due to recurring droughts and the intensifying effects of climate change (CC). These systems grapple with numerous stress factors, including poor animal nutrition, water scarcity, gastrointestinal (GIT) parasite burdens, and heat stress, which contribute to below optimal animal productivity and a high environmental footprint. Addressing these issues urgently, by creating livestock systems resilient to CC that also promote better animal health, enhanced productivity, and reduced environmental impact, is paramount to safeguarding the livelihoods of the rural population. This 50-day study aimed to evaluate the effects of improved feeding and nutritional management in sheep, focusing on GIT parasite infections, feed intake and digestibility, liveweight (LW) gain, and enteric methane (CH4) emissions. We investigated the legume forage tree, Calliandra (Calliandra calothyrsus), as a high-quality feed source because of its rich crude protein content and its potential as a remedy for gastrointestinal tract (GIT) parasite infections, attributed to its high condensed tannin (CT) content. Twenty-eight Dorper lambs underwent random allocation across four treatments, each consisting of seven lambs. These treatments combined either a trickle infection or no infection with Haemonchus contortus with a supplementation (40% of diet on a dry matter basis or lack thereof) of the basal diet (Rhodes grass hay) with dried Calliandra leaflets. The treatments were: UnHay (uninfected, fed on hay-only), InHay (infected, fed on hay-only), InHay+Cal (infected, fed on hay plus Calliandra), and InHay+Cal+PEG [infected, fed on hay, Calliandra, and polyethylene glycol (PEG)]. The latter was to evaluate the potential effects of Calliandra’s condensed tannins. The results show that lambs in the InHay+Cal treatment exhibited a higher packed cell volume (PCV) and lower faecal egg counts (FEC) compared to the InHay group. No effects of infection on the other measured variables were observed in unsupplemented lambs. Calliandra supplementation increased total feed dry matter intake (DMI) by 20% (61.8 vs. 51.7 g DM/kg LW0.75) (InHay+Cal vs. InHay) and enhanced LW gain (7.2 g/d) in the InHay+Cal group, whereas the unsupplemented infected group (InHay) experienced LW loss (-26.6 g/d). Calliandra supplementation to infected lambs reduced daily CH4 emission by 15% (13.9 vs. 16.2 g/d) and CH4 yield (g/kg DMI) by 30% (18.7 vs. 26.5 g/kg DMI), compared to emissions from unsupplemented infected lambs. Nonetheless, Calliandra supplementation decreased the digestibility of crude protein and fibre and raised the faecal nitrogen (N) output to N intake (FN/NI) ratio. The effects of PEG supplementation on CT activity remained inconclusive. The study concludes that a 40% replacement of a protein-deficient basal diet with Calliandra may be excessive. However, the findings underscore the considerable advantages of integrating Calliandra into farming systems. Such nature-based solution control GIT parasite infections and their lifecycle, bolster the nutritional value of a deficient basal diet, improve animal productivity cost-effectively, and mitigate enteric methane emissions both in absolute terms and intensity.

IntroductionThe notion of satisfaction with the use of one’s time has not been operationalized previously. Based on qualitative interviews, we propose a concept of positive time use comprised by four components: self-congruence of daily activities, balance between activities, efficient use of time, and a sense of mastery over one’s time.MethodsUsing data from two UK adult samples (N = 173 and N = 357), we developed a new measure, Positive Time Use Inventory (PTUI), and investigated its structural and convergent validity.Results and discussionThe associations of positive time use with balanced time perspective, affect balance, satisfaction with life, sense of coherence, and self-reported satisfaction with time use indicate convergent and discriminant validity of the new measure. Positive time use partially explained the associations of balanced time perspective with subjective well-being and fully mediated the effects of future time perspective and time management on subjective well-being. We propose positive time use as a new model of temporal well-being, which brings together the notions of work-life balance, time efficiency, and time mastery in a single comprehensive framework, helping to inform the time management coaching interventions.

To decipher the evolution of the hominoid brain and its functions, it is essential to conduct comparative studies in primates, including our closest living relatives. However, strong ethical concerns preclude in vivo neuroimaging of great apes. We propose a responsible and multidisciplinary alternative approach that links behavior to brain anatomy in non-human primates from diverse ecological backgrounds. The brains of primates observed in the wild or in captivity are extracted and fixed shortly after natural death, and then studied using advanced MRI neuroimaging and histology to reveal macro- and microstructures. By linking detailed neuroanatomy with observed behavior within and across primate species, our approach provides new perspectives on brain evolution. Combined with endocranial brain imprints extracted from computed tomographic scans of the skulls these data provide a framework for decoding evolutionary changes in hominin fossils. This approach is poised to become a key resource for investigating the evolution and functional differentiation of hominoid brains.

Neural stem cells (NSCs) hold a very significant promise as candidates for cell therapy due to their robust neuroprotective and regenerative properties. Preclinical studies using NSCs have shown enough encouraging results to perform deeper investigations into more potential clinical applications. Nevertheless, our knowledge regarding neurogenesis and its underlying mechanisms remains incomplete. To understand them better, it seems necessary to characterize all components of neural stem cell niche and discover their role in physiology and pathology. Using NSCs in vivo brings challenges including limited cell survival and still inadequate integration within host tissue. Identifying overlooked factors that might influence these outcomes becomes pivotal. In this review, we take a deeper examination of the influence of a fundamental element that is present in the brain, the cerebrospinal fluid (CSF), which still remains relatively unexplored. Its role in neurogenesis could be instrumental to help find novel therapeutic solutions for neurological disorders, eventually advancing our knowledge on central nervous system (CNS) regeneration and repair.

Pancreatic cancer is a highly lethal disease with limited treatment options. Hence, there is a considerable medical need for novel treatment strategies. Monoclonal antibodies (mAbs) have significantly improved cancer therapy, primarily due to their ability to stimulate antibody-dependent cellular cytotoxicity (ADCC), which plays a crucial role in their therapeutic efficacy. As a result, significant effort has been focused on improving this critical function by engineering mAbs with Fc regions that have increased affinity for the Fc receptor CD16 expressed on natural killer (NK) cells, the major cell population that mediates ADCC in humans. Here we report on the preclinical characterization of a mAb directed to the target antigen B7-H3 (CD276) containing an Fc part with the amino acid substitutions S239D/I332E to increase affinity for CD16 (B7-H3-SDIE) for the treatment of pancreatic cancer. B7-H3 (CD276) is highly expressed in many tumor entities, whereas expression on healthy tissues is more limited. Our findings confirm high expression of B7-H3 on pancreatic cancer cells. Furthermore, our study shows that B7-H3-SDIE effectively activates NK cells against pancreatic cancer cells in an antigen-dependent manner, as demonstrated by the analysis of NK cell activation, degranulation and cytokine release. The activation of NK cells resulted in significant tumor cell lysis in both short-term and long-term cytotoxicity assays. In conclusion, B7-H3-SDIE constitutes a promising agent for the treatment of pancreatic cancer.

BackgroundAnesthetic skills are usually learned through continuous supervision by experienced trainers who observe, advise and challenge students. Current educational techniques rely less on live animal training and include the use of simulations and models for teaching and assessment of surgical and anesthetic skills.ObjectiveTo evaluate the development of anesthetic skills of veterinary students having different levels of previous experience using simulation. An additional aim was to evaluate the impact of the simulation training on students with no anesthesia experience.Study designSingle group periinterventional and postinterventional study.MethodsInitial and final anesthesia simulation training recording were obtained from 53 randomly selected veterinary students. Seven faculty members blinded to previous student anesthesia experience reviewed the simulation recording and scored student performance using a rubric, results were recorded and analyzed.ResultsAll students participating in an anesthesia and surgery course reached higher proficiency levels on fundamental anesthesia skills regardless of their previous amount of experience with anesthesia. Simulation based learning positively influenced the final score in veterinary students having no previous anesthesia training, suggesting that it is possible for veterinary students to achieve a level of competence in anesthesia skills with simulation-based training.Main limitationsSample size, group simulation, multiple reviewers bias.ConclusionStudents having no experience with clinical anesthesia demonstrated remarkable improvement in their skills, achieving a score that was similar to students having extensive prior clinical anesthesia experience. Despite this clear improvement students having no prior clinical anesthesia experience required more time to complete all anesthesia tasks and may require more training sessions to acquire the speed demonstrated by peers who had significant prior clinical anesthesia experience. Overall, all participants reached a higher proficiency level performing fundamental anesthesia skills at the end of the course.

BackgroundPediatric acute myeloid leukemia (AML) therapy is associated with substantial short- and long-term treatment-related cardiotoxicity mainly due to high-dose anthracycline exposure. Early left ventricular systolic dysfunction (LVSD) compromises anthracycline delivery and is associated with inferior event-free and overall survival in de novo pediatric AML. Thus, effective cardioprotective strategies and cardiotoxicity risk predictors are critical to optimize cancer therapy delivery and enable early interventions to prevent progressive LVSD. While dexrazoxane-based cardioprotection reduces short-term cardiotoxicity without compromising cancer survival, liposomal anthracycline formulations have the potential to mitigate cardiotoxicity while improving antitumor efficacy. This overview summarizes the rationale and methodology of cardiac substudies within AAML1831, a randomized Children's Oncology Group Phase 3 study of CPX-351, a liposomal formulation of daunorubicin and cytarabine, in comparison with standard daunorubicin/cytarabine with dexrazoxane in the treatment of de novo pediatric AML.Methods/designChildren (age

IntroductionAs emerging infectious diseases (EIDs) increase, examining the underlying social and environmental conditions that drive EIDs is urgently needed. Ecological niche modeling (ENM) is increasingly employed to predict disease emergence based on the spatial distribution of biotic conditions and interactions, abiotic conditions, and the mobility or dispersal of vector-host species, as well as social factors that modify the host species’ spatial distribution. Still, ENM applied to EIDs is relatively new with varying algorithms and data types. We conducted a systematic review (PROSPERO: CRD42021251968) with the research question: What is the state of the science and practice of estimating ecological niches via ENM to predict the emergence and spread of vector-borne and/or zoonotic diseases?MethodsWe searched five research databases and eight widely recognized One Health journals between 1995 and 2020. We screened 383 articles at the abstract level (included if study involved vector-borne or zoonotic disease and applied ENM) and 237 articles at the full-text level (included if study described ENM features and modeling processes). Our objectives were to: (1) describe the growth and distribution of studies across the types of infectious diseases, scientific fields, and geographic regions; (2) evaluate the likely effectiveness of the studies to represent ecological niches based on the biotic, abiotic, and mobility framework; (3) explain some potential pitfalls of ENM algorithms and techniques; and (4) provide specific recommendation for future studies on the analysis of ecological niches to predict EIDs.ResultsWe show that 99% of studies included mobility factors, 90% modeled abiotic factors with more than half in tropical climate zones, 54% modeled biotic conditions and interactions. Of the 121 studies, 7% include only biotic and mobility factors, 45% include only abiotic and mobility factors, and 45% fully integrated the biotic, abiotic, and mobility data. Only 13% of studies included modifying social factors such as land use. A majority of studies (77%) used well-recognized ENM algorithms (MaxEnt and GARP) and model selection procedures. Most studies (90%) reported model validation procedures, but only 7% reported uncertainty analysis.DiscussionOur findings bolster ENM to predict EIDs that can help inform the prevention of outbreaks and future epidemics.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier (CRD42021251968).

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system. A better understanding of the mechanisms supporting brain plasticity in MS would help to develop targeted interventions to promote recovery. A total of 29 MS patients and 19 healthy volunteers underwent clinical assessment and multi-modal MRI acquisition [fMRI during serial reaction time task (SRT), DWI, T1w structural scans and ASL of resting perfusion] at baseline and after 4-weeks of SRT training. Reduction of functional hyperactivation was observed in MS patients following the training, shown by the stronger reduction of the BOLD response during task execution compared to healthy volunteers. The functional reorganization was accompanied by a positive correlation between improvements in task accuracy and the change in resting perfusion after 4 weeks’ training in right angular and supramarginal gyri in MS patients. No longitudinal changes in WM and GM measures and no correlation between task performance improvements and brain structure were observed in MS patients. Our results highlight a potential role for CBF as an early marker of plasticity, in terms of functional (cortical reorganization) and behavioral (performance improvement) changes in MS patients that may help to guide future interventions that exploit preserved plasticity mechanisms.

Psychological and physical factors are robustly associated with perceived social support. Drawing from the literature on attachment style in adults and psychophysiology, we examined the possibility that the interaction of attachment insecurity and resting heart rate variability (HRV) was associated with perceived social support in a diverse sample of young adults living in the U.S (N = 145, Mage = 20.45) that was majority Latino (n = 77). Analyses revealed three key findings. First, in the overall sample, attachment avoidance and attachment anxiety were negatively associated with perceived social support, but in the Latino sample, only attachment avoidance was negatively associated with perceived social support. Second, HRV was not associated with perceived social support in the overall sample nor in the Latino sample. Third, attachment insecurity and HRV interacted to predict perceived social support only in the Latino sample such that, for those with lower levels of HRV, attachment anxiety was positively associated with perceived social support. This study underscores the importance of examining both psychological and physiological processes with careful consideration of ethnicity/culture in order to better understand perceived social support.

BackgroundThere are usually multiple factors underlying dementia in old age. Somatic comorbidity is one important element that influences the progression of cognitive impairment.ObjectiveThe goal of this study was to assess the relationship between the progression of cognitive impairment and the presence and severity of comorbidities based on a four-year observation.MaterialOut of 128 patients from the Clinic for Outpatients in Gdansk, who were recruited into the study based on the criteria of the Working Group on Mild Cognitive Impairment, a total of 93 participants completed the four-year observation. Only the data from participants who completed the full period of observations were analysed. The mean age of the group was M = 75.93 (SD = 9.43). The level of progression of cognitive impairment was measured using the Clinical Dementia Rating Scale – Sum of Boxes, the severity of comorbidities was measured using the modified Cumulative Illness Rating Scale, and, additionally, at the time of inclusion in the study, participants were assessed using the MMSE scale and the Activity Scale, and sociodemographic data were collected. The Generalized Estimating Equations method was employed to fit a marginal model for analyzing the data collected in a repeated measures design. The tested model elucidated the role of the overall severity of comorbidities in explaining the progression of cognitive impairment, while controlling for everyday activity and basic demographic variables.ResultsDuring the four-year observation, a significant decline in cognitive function (B = 1.86, p

Objectives: To gain insight in the motives and determinants for the uptake of healthy lifestyles by South-Asian Surinamese people to identify needs and engagement strategies for healthy lifestyle support.Methods: We used a mixed-method design: first, focus groups with South-Asian Surinamese women; second, a questionnaire directed at their social network, and third, interviews with health professionals. Qualitative content analysis, basic statistical analyses and triangulation of data were applied.Results: Sixty people participated (n = 30 women, n = 20 social network, n = 10 professionals). Respondent groups reported similar motives and determinants for healthy lifestyles. In general, cardiometabolic prevention was in line with the perspectives and needs of South-Asian Surinamese. However, there seems to be a mismatch too: South-Asian Surinamese people missed a culturally sensitive approach, whereas professionals experienced difficulty with patient adherence. Incremental changes to current lifestyles; including the social network, and an encouraging approach seem to be key points for improvement of professional cardiometabolic prevention.Conclusion: Some key points for better culturally tailoring of preventive interventions would meet the needs and preferences of the South-Asian Surinamese living in the Netherlands.

ObjectivesPrevious studies have documented a decline in fertility desires and intentions following the COVID-19 outbreak, but the reasons for this decline are not well understood. This study examined whether childcare burden on mothers during the lockdown and quarantines, COVID-related stress, and COVID exposure were associated with a change in the desired number of children.MethodsThe survey was conducted online, in Poland from April to July 2021 on a sample of 622 non-pregnant mothers without diagnosed infertility.ResultsAssociations were observed between childcare responsibilities during the quarantine and fertility desires: mothers who solely or mainly took care of their children during the quarantine(s) were more likely to decrease their desired number of children ([adjusted] aOR = 1.91, 95% CI = 1.16–3.15). Mothers with higher levels of COVID-related stress (aOR = 1.81, 95% CI = 1.48–2.22) and a greater COVID exposure index (aOR = 1.39, 95% CI = 1.12–1.72) were more likely to decrease their fertility desires.ConclusionHigher childcare burden during quarantines was related to a lower desired number of children among mothers. Both greater COVID-related stress and COVID exposure were associated with fertility desires, regardless of childcare responsibilities during the pandemic.

Estimating the detection probability of small cetaceans using either visual or acoustic surveys is difficult because they do not surface or vocalise continuously and can be imperceptible to an observer or hydrophone. Animals seen at the surface may have lower vocalisation rates, while submerged individuals may be more vocally active. This study aims to estimate visual, acoustic and combined detection probability by using Mark-Recapture Distance Sampling (MRDS) methodology. We used vessel-based visual sightings and acoustic data (based on click identification) collected simultaneously during the ACCOBAMS Survey Initiative in summer 2018 onboard the R/V Song of the Whale. This study focused on small cetaceans in the Mediterranean Sea, including the most commonly-encountered species, the striped dolphin (Stenella coeruleoalba). We identified duplicate events between visual and acoustic platforms using a decision tree based on time and distance thresholds to estimate g(0) (the detection probability on the trackline) for small cetaceans. A total of 30 duplicate events were identified from 107 and 109 events identified by the visual and acoustic platforms respectively. We tested the models with two key functions. With a hazard-rate key function, the g(0) was estimated at 0.52 (CV=21.0%) for both platforms combined, 0.29 (CV=25.6%) for the visual platform and 0.32 (CV=25.1%) for the acoustic platform. With a half-normal key function, g(0) was estimated at 0.51 (CV = 21.7%) for both platforms combined, 0.29 (CV = 25.6%) for the visual platform and 0.33 (CV = 23.2%) for the acoustic platform. Our results illustrate that passive acoustic monitoring can be used as an independent platform in MRDS to estimate the detection probability. Our estimate of g(0) was well below 1, far from the perfect detection commonly assumed for abundance estimation. Without correction for detection biases, total abundance would be underestimated by a factor of two when using both acoustic and visual data. This highlights the importance of using dual-platform surveys to estimate detection probability in order to improve abundance estimates and conservation efforts.

BackgroundAdenosine administration for fractional flow reserve (FFR) measurement may induce heart pauses.AimsTo assess the accuracy and tolerability of direct wire pacing (DWP) during measurement of FFR.MethodsAdults with at least one intermediate coronary artery stenosis (40%–80%) were consecutively enrolled between June 2021 and February 2022 in this randomized, noninferiority, crossover trial (NCT04970082) carried out in France. DWP was applied (DWP) or not (standard method) through the pressure guidewire used for FFR measurement during adenosine-induced maximal hyperaemia. Subjects were randomly assigned to the allocation sequence (DWP first or standard first). A 2-minute washout period was observed between the two FFR measurements performed for each stenosis. The primary endpoint was the reproducibility of FFR measurements between methods.ResultsA total of 150 focal lesions, presented by 94 subjects, were randomized (ratio: 1:1). The FFR values obtained with each method were nearly identical (R = 0.98, p = 0.005). The mean FFR difference of 0.00054 (95% confidence interval: 0.004 to 0.003) showed the noninferiority of FFR measurement with DWP vs. that with the standard method. Higher levels of chest discomfort were reported with DWP than with the standard method (0.61 ± 0.84 vs. 1.05 ± 0.89, p

The vast majority of hormone positive and HER2 negative advanced breast cancers can be controlled well by endocrine therapy combined with the groundbreaking use of CDK4/6 inhibitors in the metastatic first-line setting. Approximately 50%–60% of these patients have “bone-only” metastatic disease. In oligometastatic cases or if a certain number of uncontrolled lesions develop during the aforementioned therapy, ablative radiotherapy can be delivered or, in symptomatic cases, urgent irradiation is needed with palliative intent. To achieve the most effective results, parallel with good quality of life, the timing of radiotherapy must be determined precisely, taking into account that different cell cycles are involved during different treatment modalities; therefore, optimization of treatment schedules ensures longer and safer post-progression overall survival. The key question is whether the two treatment modalities are safe concurrently or whether they should be administered separately, and if so, what is the optimal sequence and why? This manuscript aims to answer this important question, with a focus on quality of life. Existing publications focus on safety and toxicity profiles, and efficacy is detailed only tangentially and minimally.

Objectives: The full-scale Russian invasion of Ukraine resulted in a refugee crisis. The terms of employment of Ukrainian Refugee background Medical Professionals (UKR-MPs) in the Polish healthcare system were liberalised. The aim of the study was to identify challenges in job seeking and the integration of Ukrainian war refugee healthcare workers into the Polish healthcare system.Methods: A qualitative, descriptive study based on content thematic analysis of Facebook content. We analyzed 1,700 posts published on two public Facebook groups intended for UKR-MPs.Results: The most common problems encountered by UKR-MPs were: 1) lack of easy-to-understand information about the list of documents necessary to apply for a work permit, 2) lack of feedback from those responsible for handling individual cases, and 3) long waiting time for the decision issued by the Ministry of Health.Conclusion: Despite the promptly implemented solutions enabling access to the job market by UKR-MPs, the refugees have encountered considerable administrative difficulties, as well as those arising from insufficient knowledge of the regulations on working as medical professionals in Poland under the EU law.

IntroductionAlthough impacts of physical activity on cognitive functions have been intensively investigated, they are still far from being completely understood. The aim of this study was to evaluate the effect of 12 weeks of the Nordic Walking training with BungyPump resistance poles (NW-RSA) on the amino acid and kynurenine profiles as well as selected myokine/exerkine concentrations, which may modify the interface between physical and cognitive functions.MethodsA group of 32 older adults participated in the study. Before and after the intervention, body composition, cognitive functions, and physical performance were assessed. Blood samples were taken before and 1 h after the first and last sessions of the NW-RSA training, to determine circulating levels of exercise-induced proteins, i.e., brain-derived neurotrophic factor (BDNF), irisin, kynurenine (KYN), metabolites, and amino acids.ResultsThe NW-RSA training induced a significant improvement in cognitive functions and physical performance as well as a reduction in fat mass (p = 0.05). Changes were accompanied by a decline in resting serum BDNF (p = 0.02) and a slight reduction in irisin concentration (p = 0.08). Still, changes in irisin concentration immediately after the NW-RSA intervention depended on shifts in kynurenine—irisin dropped as kynurenine increased. The kynurenine-to-tryptophan and phenylalanine-to-tyrosine ratios decreased significantly, suggesting their possible involvement in the amelioration of cognitive functions. No changes of glucose homeostasis or lipid profile were found. Shifts in the concentrations of selected amino acids might have covered the increased energy demand in response to the NW-RSA training and contributed to an improvement of physical performance.ConclusionRegular Nordic Walking training with additional resistance (BungyPump) improved cognitive functions and physical performance. These positive effects were associated with a reduced BDNF concentration and kynurenine-to-tryptophan ratio as well as changes in the amino acid profile.

The COVID-19 pandemic coincided with an already long-standing crisis in health systems around the world characterized by economic pressure and increasing staff shortage. “Crisis” became a global metaphor to convey collective experiences of the COVID-19 threat. Little is known on how crisis metaphors influence thought and speech on crisis management and the challenging staff situation of intensive care unit (ICU) clinicians in leadership positions and how they act. Therefore, we were interested in (1) which metaphorical concepts ICU clinicians in leadership use to express experiences and strategies in dealing with coinciding crises, (2) how these change over time, and (3) how metaphors in speech reveal self-images of crisis management. We conducted a systematic metaphor analysis focusing on data from three participants of a qualitative interview study with twenty-four healthcare professionals in ICUs in Germany. The participants were interviewed at two time points between April 2020 and March 2021. We identified and reconstructed metaphorical concepts of three interviewees (ICU clinicians in leadership) with regard to the pandemic management, and developed a typology based on the dimensions of mood, modus operandi, location, and scope. The typology consists of eight self-images (protagonists) for the crisis management of ICU clinicians in leadership, such as the figure of the soldier (“to unite everyone behind this flag”), the distributor (“sometimes it is a crazy patchwork [wahnsinniges Gestückel]”) or the critic (“we are the fool for everything”). They embody different qualities of a leader and refer to intra- and inter-role conflicts within multiple crisis conditions. Metaphor analysis reveals different self-images of ICU leadership clinicians in relation to crisis management. This illustrates that thinking and perceptions of crisis management may strongly differ between and within leaders and may change over the course of crises. Our findings highlight the need both to improve knowledge on challenges associated with leadership in crises and preparedness, and to support clinicians in their leadership by recognizing and addressing differences and changes in leaders’ self-image.

There has been a “territorial turn” in exploring sustainable development in the past two decades. Sustainability is increasingly seen as rooted in local resources, relationships, and values. Cultural and creative industries (CCIs) are a substantial local resource and participants of local development. One of the most important relationships of CCIs is with local municipalities, which usually have an overview of local resources, and a role of redefining national level policy ideas, including those pertaining to cultural and art activities. The paper examines place-based development in Valmiera County as a case of national cultural policy translation, grounded in interpretations of the availability of local resources for change. The paper argues that the trajectories of local cultural development are indeed strongly related to local development agents' interpretations of available local resources, including active CCIs. In negotiating the preferred development paths, the stakeholders tend to respond to one of two strategies carried out by the local municipality: Act (taking upon themselves the role of a cultural operator) or Wait-and-see (enabling other cultural operators, the private and non-governmental CCI sector). The paper also highlights the role of creative intermediaries in negotiation processes. The Wait-and-see approach is seen as preferable and more sustainable in the long run.

This study was based on the concept of teacher professional vision, in which professional reasoning plays a crucial role, and investigated how video with gaze overlay and heatmaps from the mobile eye tracker can support teachers’ professional self-reflection and professional vision development in higher education. Four university teachers wore a mobile eye tracker in a segment of one lecture. Their gaze distribution on classroom targets was analyzed together with their reflective comments when watching the recordings of their own behavior in the lecture. The results showed that mobile eye tracking data provided feedback on the distribution of teacher attention in different areas in the classroom and between students. Visualization of gaze distribution as heatmaps allowed teachers to reflect on how they perceived their gaze allocation and most of them realized that sometimes there was a difference between how they perceived their gaze allocation and how it was captured by the eye tracker. The study revealed where teachers most often diverted their attention, which encouraged them to reflect on why this happened, to think about their professional reasoning, and to analyze opportunities for improvement. Therefore, the heatmap analysis based on the data collected with the mobile eye trackers could be used to develop the professional vision of teachers in different educational contexts for engaging students through more balanced attention to every student in the classroom. Implications for using mobile eye tracker recording and gaze distribution heatmaps in video-based professional development for teachers are discussed.

This study investigated how university teachers’ (mis)conceptions of teaching and learning are related to their ability to notice and interpret pedagogically significant incidents in the classroom, that is their professional vision. Additionally, we examined whether university teachers can be supported in their development of conceptual understanding and professional vision through a short pedagogical training. A total of 32 university teachers who participated in this study completed a teacher conception questionnaire and an eye-tracking measurement with a stimulated retrospective recall (SRR) interview. A pre-test/post-test design was utilized. The findings indicate that in general, professional vision scores and (mis)conceptions of teaching and learning did not correlate. However, with regard to classroom incidents where teachers’ visual attention needed to be selectively allocated due to simultaneous interactions, university teachers with more misconceptions and less sophisticated conceptions of teaching and learning tended to focus on the teacher’s actions in the classroom. By contrast, university teachers with fewer misconceptions and with more sophisticated conceptions of teaching and learning tended to focus on students’ actions. University teachers’ less sophisticated conceptions became more sophisticated as a result of pedagogical training. Additionally, statistically significant improvements in participants’ noticing were identified, but interestingly not in their interpreting skills. The results emphasize the relevance of the need for pedagogical training and the development of conceptual understanding for university teachers in relation to learning theories in order to support their pedagogical expertise as well as their professional vision.

A study was conducted with Red Maasai and Dorper lambs to evaluate the effects of infection with the gastrointestinal nematode (GIN) Haemonchus contortus on feed intake, liveweight gain (LWG), feed energy and nitrogen partitioning, and enteric methane (CH4) emissions. Six- to seven-month-old Red Maasai (n=12) and Dorper (n=12) lambs were randomly allocated to three treatments (n=8, four lambs per breed) in a 2×3 factorial cross-over study over two periods (P1 and P2) of 36 days each. The treatments consisted of three combinations of GIN infection and feeding level: Infected + ad libitum feeding (I-adlib), uninfected + ad libitum feeding (Un-adlib), and uninfected + restricted feeding (Un-restd), across the two breeds. Lambs in the I-adlib group were trickle-infected daily with 1,000 L3 stage larvae of H. contortus for four consecutive days (Days 1–4), whereas lambs in the other experimental treatments were kept GIN free. The feed intake was measured daily. Liveweight (LW), faecal egg counts (FEC), and packed cell volume (PCV) were measured on Day 1 and weekly thereafter. On Days 29–33 total faecal and urine outputs were determined in metabolic crates. The lambs were then housed in respiration chambers for three consecutive days (Days 34–36). There was a washout period of 21 days before P2 started. Uninfected lambs (Un-adlib and Un-restd) had undetectable FEC throughout the study. On Day 36, FEC did not differ between the breeds (P>0.05). Infected lambs (I-adlib) had lower PCV than uninfected (Un-adlib and Un-restd) lambs on day 36. Neither breed nor infection influenced feed and nutrient intake, but as expected, restricted-fed lambs had a lower intake (P0.05). Neither breed nor infection affected feed digestibility, nitrogen retention or energy metabolisability (P>0.05). However, feed restriction decreased feed intake, LWG and N retention, whereas feed digestibility and energy metabolisability were unaffected. Neither daily CH4 emissions nor yield (per unit of feed intake) were affected by experimental infection, but Un-restd lambs had lower CH4 emissions per day. Red Maasai lambs had consistently lower daily CH4 emissions and yields than Dorper (P

IntroductionThe emergence of carbapenem-resistant bacteria causing serious infections may lead to more frequent use of previously abandoned antibiotics like colistin. However, mobile colistin resistance genes (mcr) can jeopardise its effectiveness in both human and veterinary medicine. In Germany, turkeys have been identified as the food-producing animal most likely to harbour mcr-positive colistin-resistant Enterobacterales (mcr-Col-E). Therefore, the aim of the present study was to assess the prevalence of both mcr-Col-E and carbapenemase-producing Enterobacterales (CPE) in German turkey herds and humans in contact with these herds.MethodsIn 2018 and 2019, 175 environmental (boot swabs of turkey faeces) and 46 human stool samples were analysed using a combination of enrichment-based culture, PCR, core genome multilocus sequence typing (cgMLST) and plasmid typing.Resultsmcr-Col-E were detected in 123 of the 175 turkey farms in this study (70.3%). mcr-Col-E isolates were Escherichia coli (98.4%) and Klebsiella spp. (1.6%). Herds that had been treated with colistin were more likely to harbour mcr-Col-E, with 82.2% compared to 66.2% in untreated herds (p = 0.0298). Prevalence also depended on husbandry, with 7.1% mcr-Col-E in organic farms compared to 74.5% in conventional ones (p < 0.001). In addition, four of the 46 (8.7%) human participants were colonised with mcr-Col-E. mcr-Col-E isolates from stables had minimum inhibitory concentrations (MICs) from 4 to ≥ 32 mg/l, human isolates ranged from 4 to 8 mg/l. cgMLST showed no clonal transmission of isolates. For one farm, plasmid typing revealed great similarities between plasmids from an environmental and a human sample. No CPE were found in turkey herds or humans.DiscussionThese findings confirm that mcr-Col-E-prevalence is high in turkey farms, but no evidence of direct zoonotic transmission of clonal mcr-Col-E strains was found. However, the results indicate that plasmids may be transmitted between E. coli isolates from animals and humans.

Antimony selenide (Sb2Se3) is one of the emerging photovoltaic absorber materials possessing abundance and non-toxicity as the main attributes. Following CdTe technology, CdS is a widely used partner layer for Sb2Se3 solar cells. Related to CdS/Sb2Se3 device configuration, a number of studies reported findings and challenges regarding the intermixing phenomenon at the main interface and suitability of various annealing for CdS (and related interface) and still, significant room remains in developing strategies for interface optimization and understanding of the physiochemistry behind. In this perspective, this work provides a systematic investigation of the effect of vacuum and air annealing at temperatures between 200 and 400°C on the properties of CdS deposited by chemical bath deposition and combined with Sb2Se3 absorber obtained by close-spaced sublimation the direct impact of the CdS annealing on the device performance is illustrated. It is found that by varying the annealing temperature from 200 to 400°C in both, vacuum and air ambient, the morphology of CdS changes from highly dispersed small grain structure to sintered dense grains, the band gap decreases from 2.43 to 2.35 eV and the electron density drops from ∼1018 to ∼1011 cm−3. These changes were correlated with the changes in the CdS lattice and connected with the mobility of the OH group and the presence of secondary phases in CdS layers. 200°C air annealing of CdS was found as an optimal treatment resulting in 2.8% Sb2Se3/CdS cell efficiency - a 60% boost compared to the 1.8% performance of the device with as-deposited CdS. Material and device characterization analysis is performed, providing complementary insights on the interrelation between the physicochemical mechanism of the CdS annealing processes and device functionality.

Three-dimensional (3D) cell cultures, including organ-on-a-chip (OOC) devices, offer the possibility to mimic human physiology conditions better than 2D models. The organ-on-a-chip devices have a wide range of applications, including mechanical studies, functional validation, and toxicology investigations. Despite many advances in this field, the major challenge with the use of organ-on-a-chips relies on the lack of online analysis methods preventing the real-time observation of cultured cells. Mass spectrometry is a promising analytical technique for real-time analysis of cell excretes from organ-on-a-chip models. This is due to its high sensitivity, selectivity, and ability to tentatively identify a large variety of unknown compounds, ranging from metabolites, lipids, and peptides to proteins. However, the hyphenation of organ-on-a-chip with MS is largely hampered by the nature of the media used, and the presence of nonvolatile buffers. This in turn stalls the straightforward and online connection of organ-on-a-chip outlet to MS. To overcome this challenge, multiple advances have been made to pre-treat samples right after organ-on-a-chip and just before MS. In this review, we summarised these technological advances and exhaustively evaluated their benefits and shortcomings for successful hyphenation of organ-on-a-chip with MS.

India has a large, free-roaming dog population, encompassing both owned and stray dogs. Canine surgical neutering is often a central component of dog population management and rabies control initiatives. The provision of practical, surgical training opportunities remains a major challenge for veterinary educational establishments worldwide to ensure competency in this routine procedure. A 12-day educational programme, focusing on surgical neutering skills, was developed to address this need. A questionnaire comprising 26 questions covering surgical and clinical topics, and a self-assessment of confidence in undertaking five common surgical procedures, was completed immediately before and after finishing the programme. A total of 296 participants attended, with 228 achieving the inclusion criteria for the study. Total knowledge scores increased significantly after the training programme (mean score pre-18.94, 95% CI 18.13–19.74; post-28.11, 95% CI 27.44–28.77, p

Toxicology research has rapidly evolved, leveraging increasingly advanced technologies in high-throughput approaches to yield important information on toxicological mechanisms and health outcomes. Data produced through toxicology studies are consequently becoming larger, often producing high-dimensional data. These types of data hold promise for imparting new knowledge, yet inherently have complexities causing them to be a rate-limiting element for researchers, particularly those that are housed in “wet lab” settings (i.e., researchers that use liquids to analyze various chemicals and biomarkers as opposed to more computationally focused, “dry lab” researchers). These types of challenges represent topics of ongoing conversation amongst our team and researchers in the field. The aim of this perspective is to i) summarize hurdles in analyzing high-dimensional data in toxicology that require improved training and translation for wet lab researchers, ii) highlight example methods that have aided in translating data analysis techniques to wet lab researchers; and iii) describe challenges that remain to be effectively addressed, to date, in toxicology research. Specific aspects include methodologies that could be introduced to wet lab researchers, including data pre-processing, machine learning, and data reduction. Current challenges discussed include model interpretability, study biases, and data analysis training. Example efforts implemented to translate these data analysis techniques are also mentioned, including online data analysis resources and hands-on workshops. Questions are also posed to continue conversation in the toxicology community. Contents of this perspective represent timely issues broadly occurring in the fields of bioinformatics and toxicology that require ongoing dialogue between wet and dry lab researchers.