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In this article, we describe multiannual variations of the atmospheric aerosol optical depth values in the widely understood area of the Baltic Sea. We present the trends in the changes and depict unusual aerosol situations. As a result of analyses, we focus on 2019, since unusually high values of aerosol optical depth were recorded in several stations around the Baltic. We match the high aerosol levels with an unusually high number of wildfires across Europe in spring and summer, which emitted large quantities of aerosols into the atmosphere that were distributed over vast European areas in part by the wind. We then connect this case with the climate change consequences. Since aerosols influence the radiative budget of the planet by directly affecting the atmospheric radiation budget, it is obvious that human well-being is in danger due to wildfires, as well as from the atmospheric perspective. Climate change will lead to more frequent fires; thus, humans need to develop solutions to decrease the risk of fire outbreaks. [ABSTRACT FROM AUTHOR]

Microglia activity can drive excessive synaptic loss during the prodromal phase of Alzheimer's disease (AD) and is associated with lowered cyclic adenosine monophosphate (cAMP) due to cAMP phosphodiesterase 4B (PDE4B). This study aimed to investigate whether long-term inhibition of PDE4B by A33 (3 mg/kg/day) can prevent synapse loss and its associated cognitive decline in APPswe/PS1dE9 mice. This model is characterized by a chimeric mouse/human APP with the Swedish mutation and human PSEN1 lacking exon 9 (dE9), both under the control of the mouse prion protein promoter. The effects on cognitive function of prolonged A33 treatment from 20 days to 4 months of age, was assessed at 7–8 months. PDE4B inhibition significantly improved both the working and spatial memory of APPswe/PSdE9 mice after treatment ended. At the cellular level, in vitro inhibition of PDE4B induced microglial filopodia formation, suggesting that regulation of PDE4B activity can counteract microglia activation. Further research is needed to investigate if this could prevent microglia from adopting their 'disease-associated microglia (DAM)' phenotype in vivo. These findings support the possibility that PDE4B is a potential target in combating AD pathology and that early intervention using A33 may be a promising treatment strategy for AD. [ABSTRACT FROM AUTHOR]

The glycolysis process of flexible polyurethane foams containing styrene–acrylonitrile and calcium carbonate as fillers was explored in detail. The use of DABCO as a catalyst allowed us to reduce the catalyst concentration and the polyurethane-to-glycol mass ratio to 0.1% and 1:1, respectively. The glycolysis process allowed us to obtain a high-purity polyol (99%), which can totally replace raw polyols in the synthesis of new flexible polyurethane foams, maintaining the standard mechanical properties of the original one and modifying the ratio of isocyanates employed to correct the closed cell structure caused by the impurities present in the recovered polyol. This isocyanate mixture was also optimized, resulting in a ratio of 30 and 70% of the isocyanates TDI80 and TDI65, respectively. Additionally, the fillers incorporated in the glycolyzed foams were recovered. Both recovered fillers, styrene–acrylonitrile and calcium carbonate, were fully characterized, showing a quality very similar to that of commercial compounds. Finally, the replacement of commercial fillers by the recovered ones in the synthesis of new polyurethane foams was studied, demonstrating the feasibility of using them in the synthesis of new foams without significantly altering their properties. [ABSTRACT FROM AUTHOR]

Four weeks before competition in the 2023 Marathon des Sables, a 6-stage, ~250 km running event in the Sahara Desert, we examined the effects of a 7-day intake of New Zealand blackcurrant extract (210 mg anthocyanins per day) on 1 h treadmill running-induced physiological and metabolic responses in the heat (~34 °C, relative humidity: ~30%) in non-acclimatized amateur female and male athletes (age: 23, 38 yrs, BMI: 24.2, 28.4 kg·m−2, body fat%: 29.2, 18.8%, V ˙ O2max: 50.1, 52.1 mL·kg−1·min−1). During the 1 h run at 50% V ˙ O2max (speed female: 7.3, male: 7.5 km·h−1), indirect calorimetry was used, and heart rate was recorded at 15 min intervals with core temperature monitoring (0.05 Hz). The 1 h runs took place 3 h after a light breakfast and 2 h after intake of the final dose of New Zealand blackcurrant extract with water allowed ad libitum during the run. The New Zealand blackcurrant extract had no effects on the female athlete. The respiratory exchange ratio (RER) of the female athlete in the non-supplement control condition was 0.77 ± 0.01, indicating an existing ~77% contribution of fat oxidation to the energy requirements. In the male athlete, during 1 h of running, fat oxidation was higher by 21% (p < 0.01), carbohydrate oxidation was 31% lower (p = 0.05), RER was 0.03 units lower (p = 0.04), and core temperature was 0.4 °C lower (p < 0.01) with no differences for heart rate, minute ventilation, oxygen uptake, and carbon dioxide production for the New Zealand blackcurrant condition compared to the non-supplement control condition. Seven-day intake of New Zealand blackcurrant extract (210 mg anthocyanins per day) provided beneficial physiological and metabolic responses during exertional heat stress by 1 h of indoor (~34 °C) treadmill running in a male Marathon des Sables athlete 4 weeks before competition. Future work is required to address whether New Zealand blackcurrant provides a nutritional ergogenic effect for Marathon des Sables athletes during long-duration running in the heat combined with personalized nutrition. [ABSTRACT FROM AUTHOR]

Background: Mitral valve prolapse (MVP) and mitral annular disjunction (MAD) are common valvular abnormalities that have been associated with ventricular arrhythmias (VA). Cardiac magnetic resonance imaging (CMR) has a key role in risk stratification of VA, including assessment of late gadolinium enhancement (LGE). Methods: Single-center retrospective analysis of patients with MVP or MAD who had >1 CMR and >1 24 h Holter registration available. Data are presented in detail, including evolution of VA and presence of LGE over time. Results: A total of twelve patients had repeated CMR and Holter registrations available, of which in four (33%) patients, it was conducted before and after minimal invasive mitral valve repair (MVR). After a median of 4.7 years, four out of eight (50%) patients without surgical intervention had new areas of LGE. New LGE was observed in the papillary muscles and the mid to basal inferolateral wall. In four patients, presenting with syncope or high-risk non-sustained ventricular tachycardia (VT), programmed ventricular stimulation was performed and in two (50%), sustained monomorphic VT was easily inducible. In two patients who underwent MVR, new LGE was observed in the basal inferolateral wall of which one presented with an increased burden of VA. Conclusions: In patients with MVP and MAD, repeat CMR may show new LGE in a small subset of patients, even shortly after MVR. A subgroup of patients who presented with an increase in VA burden showed new LGE upon repeat CMR. VA in patients with MVP and MAD are part of a heterogeneous spectrum that requires further investigation to establish risk stratification strategies. [ABSTRACT FROM AUTHOR]

Simple Summary: Nowadays, tumor tests to analyze DNA in tumor cells from epithelial tubal/ovarian cancers (EOCs) are performed in many centers to detect tumor pathogenic variants (TPVs) in the BRCA1/2 genes. Information on the presence of these TPVs guides treatment options and further genetic testing in patients and relatives. However, there is no standardization of testing procedures, and information about how testing is performed is limited. Therefore, we described how BRCA1/2 tumor testing is performed in 999 EOC patients in the Netherlands in 2019 using real-world clinical data. Tumor tests were performed for 502 patients (50.2%) and TPVs were detected in 14.7% of the tests. This study shows that there is variability in the execution of BRCA1/2 tumor tests, but there were no indications for quality differences. Adequate reporting and quality monitors are essential to ensure that all centers perform reliable tumor tests to ultimately identify all patients with BRCA1/2 TPVs. Analyzing BRCA1/2 tumor pathogenic variants (TPVs) in epithelial tubal/ovarian cancers (EOCs) has become an essential part of the diagnostic workflow in many centers to guide treatment options and genetic cascade testing. However, there is no standardization of testing procedures, including techniques, gene assays, or sequencers used, and data on the execution of tumor tests remains scarce. Therefore, we evaluated characteristics of BRCA1/2 tumor testing in advanced-stage EOC with real-world national data. Pathology reports of patients diagnosed with EOC in 2019 in the Netherlands were obtained from the Dutch Pathology Registry (PALGA), and data regarding histological subtype and BRCA1/2 tumor tests were extracted. A total of 999 patients with advanced-stage EOC were included. Tumor tests were performed for 502 patients (50.2%) and BRCA1/2 TPVs were detected in 14.7%. Of all tests, 48.6% used hybrid capture techniques and 26.5% used PCR-based techniques. More than half of the tests (55.0%) analyzed other genes in addition to BRCA1/2. Overall, this study highlights the heterogeneity in the execution of BRCA1/2 tumor tests. Despite a lack of evidence of quality differences, we emphasize that adequate reporting and internal and external quality monitors are essential for the high-quality implementation and execution of reliable BRCA1/2 tumor testing, which is crucial for identifying all patients with BRCA1/2 TPVs. [ABSTRACT FROM AUTHOR]

Cylinder-pressure-based control is a key enabler for advanced pre-mixed combustion concepts. In addition to guaranteeing robust and safe operation, it allows for cylinder pressure and heat release shaping. This requires fast control-oriented combustion models. Over the years, mean-value models have been proposed that can predict combustion metrics (e.g., gross indicated mean effective pressure ( IMEP g ), or the crank angle where 50% of the total heat is released (CA50)) or models that predict the full in-cylinder pressure. However, these models are not able to capture cycle-to-cycle variations. The inclusion of the cycle-to-cycle variations is important in the control design for combustion concepts, like reactivity-controlled compression ignition, that can suffer from large cycle-to-cycle variations. In this study, the in-cylinder pressure and cycle-to-cycle variations are modelled using a data-based approach. The in-cylinder conditions and fuel settings are the inputs to the model. The model combines principal component decomposition and Gaussian process regression. A detailed study is performed on the effects of the different hyperparameters and kernel choices. The approach is applicable to any combustion concept, but is most valuable for advance combustion concepts with large cycle-to-cycle variation. The potential of the proposed approach is successfully demonstrated for a reactivity-controlled compression ignition engine running on diesel and E85. The average prediction error of the mean in-cylinder pressure over a complete combustion cycle is 0.051 bar and of the corresponding mean cycle-to-cycle variation is 0.24 bar2. This principal-component-decomposition-based approach is an important step towards in-cylinder pressure shaping. The use of Gaussian process regression provides important information on cycle-to-cycle variation and provides next-cycle control information on safety and performance criteria. [ABSTRACT FROM AUTHOR]

Background: Cardiac resynchronization therapy (CRT) has evolved into an established therapy for patients with chronic heart failure and a wide QRS complex. Data on long-term outcomes over time are scarce and the criteria for implantation remain a subject of investigation. Methods: An international, multicenter, retrospective registry includes 2275 patients who received CRT between 30 November 2000 and 31 December 2019, with a mean follow-up of 3.6 ± 2.7 years. Four time periods were defined, based on landmark trials and guidelines. The combined endpoint was a composite of all-cause mortality, heart transplantation, or left ventricular assist device implantation. Results: The composite endpoint occurred in 656 patients (29.2%). The mean annual implantation rate tripled from 31.5 ± 17.4/year in the first period to 107.4 ± 62.4/year in the last period. In the adjusted Cox regression analysis, the hazard ratio for the composite endpoint was not statistically different between time periods. When compared to sinus rhythm with left bundle branch block (LBBB), a non-LBBB conduction pattern (sinus rhythm: HR 1.51, 95% CI 1.12–2.03; atrial fibrillation: HR 2.08, 95% CI 1.30–3.33) and a QRS duration below 130 ms (HR 1.64, 95% CI 1.29–2.09) were associated with a higher hazard ratio. Conclusions: Despite innovations, an adjusted regression analysis revealed stable overall survival over time, which can at least partially be explained by a shift in patient characteristics. [ABSTRACT FROM AUTHOR]

Chronic lower back pain caused by intervertebral disc degeneration and osteoarthritis (OA) are highly prevalent chronic diseases. Although pain management and surgery can alleviate symptoms, no disease-modifying treatments are available. mRNA delivery could halt inflammation and degeneration and induce regeneration by overexpressing anti-inflammatory cytokines or growth factors involved in cartilage regeneration. Here, we investigated poly(amidoamine)-based polymeric nanoparticles to deliver mRNA to human joint and intervertebral disc cells. Human OA chondrocytes, human nucleus pulposus (NP) cells, human annulus fibrosus (AF) cells, fibroblast-like synoviocytes (FLS) and M1-like macrophages were cultured and transfected with uncoated or PGA-PEG-coated nanoparticles loaded with EGFP-encoding mRNA. Cell viability and transfection efficiency were analyzed for all cell types. Nanoparticle internalization was investigated in FLS and M1-like macrophages. No significant decrease in cell viability was observed in most conditions. Only macrophages showed a dose-dependent reduction of viability. Transfection with either nanoparticle version resulted in EGFP expression in NP cells, AF cells, OA chondrocytes and FLS. Macrophages showed internalization of nanoparticles by particle–cell co-localization, but no detectable expression of EGFP. Taken together, our data show that poly (amidoamine)-based nanoparticles can be used for mRNA delivery into cells of the human joint and intervertebral disc, indicating its potential future use as an mRNA delivery system in OA and IVDD, except for macrophages. [ABSTRACT FROM AUTHOR]

The "can do, do do" framework combines measures of poor and normal physical capacity (PC, measured by a 6 min walking test, can do/can't do) and physical activity (PA, measured by accelerometer, do do/don't do) into four domains and is able to categorize patient subgroups with distinct clinical characteristics, including fall and fracture risk factors. This study aims to explore the association between domain categorization and prospective fall, fracture, and mortality outcomes. This 6-year prospective study included patients visiting a Fracture Liaison Service with a recent fracture. Outcomes were first fall (at 3 years of follow-up, measured by fall diaries), first subsequent fracture, and mortality (at 6 years). Cumulative incidences of all three outcomes were calculated. The association between domain categorization and time to the three outcomes was assessed by uni- and multivariate Cox proportional hazard analysis with the "can do, do do" group as reference. The physical performance of 400 patients with a recent fracture was assessed (mean age: 64 years; 70.8% female), of whom 61.5%, 20.3%, and 4.9% sustained a first fall, sustained a subsequent fracture, or had died. Domain categorization using the "can do, do do" framework was not associated with time to first fall, subsequent fracture, or mortality in the multivariate Cox regression analysis for all groups. "Can't do, don't do" group: hazard ratio [HR] for first fall: 0.75 (95% confidence interval [CI]: 0.45–1.23), first fracture HR: 0.58 (95% CI: 0.24–1.41), and mortality HR: 1.19 (95% CI: 0.54–6.95). Categorizing patients into a two-dimensional framework seems inadequate to study complex, multifactorial outcomes. A personalized approach based on known fall and fracture risk factors might be preferable. [ABSTRACT FROM AUTHOR]

Liver diseases represent a considerable burden to patients and healthcare systems. Hydrogels play an important role in the engineering of soft tissues and may be useful for embedding hepatocytes for different therapeutic interventions or the development of in vitro models to study the pathogenesis of liver diseases or testing of drugs. Here, we developed two types of hydrogels by crosslinking hydrazide-functionalized gelatin with either oxidized dialdehyde hyaluronan or alginate through the formation of hydrazone bonds. Gel formulations were studied through texture analysis and rheometry, showing mechanical properties comparable to those of liver tissue while also demonstrating long-term stability. The biocompatibility of hydrogels and their ability to host hepatocytes was studied in vitro in comparison to pure gelatin hydrogels crosslinked by transglutaminase using the hepatocellular line HepG2. It was found that HepG2 cells could be successfully embedded in the hydrogels, showing no signs of gel toxicity and proliferating in a 3D environment comparable to pure transglutaminase cross-linked gelatin hydrogels used as control. Altogether, hydrazide gelatin in combination with oxidized polysaccharides makes stable in situ gelling systems for the incorporation of hepatocytes, which may pave the way for use in liver tissue engineering and drug testing. [ABSTRACT FROM AUTHOR]

Vertebral and spinal cord anomalies are well known in veterinary medicine. However, nerve root anomalies are seldomly reported. In human patients, nerve root anomalies can cause back pain and radicular pain. In human medicine, nerve root anomalies are more often found in cadaveric studies than in imaging studies, representing the lack of advanced imaging in the past and the unawareness about these pathologies. Additionally, nerve root anomalies can mimic other pathologies in imaging studies. It is important to know about the anatomy of the individual patient not only for correctly localizing the pathology but also for surgical planning and to prevent iatrogenic trauma to the patient. Conjoined nerve roots are a type of nerve root anomaly described in human medicine and are defined as two nerve roots that either share a common dural envelope at some point during their course from the dural sac or that have their origin very close together in the dural sac. In humans, lumbosacral nerve roots are most commonly conjoined, and signs of pain may be associated with this anomaly. We report the magnetic resonance imaging finding of right-sided conjoined L7 and S1 nerve roots in a dog that presented with lumbosacral hyperesthesia. We postulate that it is possible that the conjoined nerve roots played a role in the clinical signs of this dog. This is an anomaly that has not been reported before in veterinary medicine. [ABSTRACT FROM AUTHOR]

The document titled "Second Edition of the German-Austrian S3 Guideline 'Infarction-Related Cardiogenic Shock: Diagnosis, Monitoring and Treatment'" provides recommendations for the diagnosis, monitoring, and treatment of infarction-related cardiogenic shock (ICS). The guideline was developed by German and Austrian medical societies and includes 95 recommendations and 7 algorithms. It emphasizes the importance of monitoring blood pressure, cardiac output, and oxygen balance to guide hemodynamic therapy. The document also discusses the timing and type of revascularization for patients with acute myocardial infarction (MI) complicated by cardiogenic shock. It recommends prompt intervention with primary percutaneous coronary intervention (PCI) within 90 minutes of first medical contact and suggests that PCI with a drug-eluting stent is the reperfusion technique of choice for most patients. The text also discusses the use of mechanical circulatory support (MCS) devices as an alternative treatment for severe, refractory cardiogenic shock. The choice of MCS device depends on various factors, including the type of shock and available resources. The document also covers aspects of critical care medicine for patients with ICS, including invasive ventilation, management of acute kidney injury, transfusion strategies, nutrition, and glucose control. The recommendations provided aim to improve patient outcomes based on available evidence. [Extracted from the article]

Exercise is a recommended part of phase IV cardiovascular rehabilitation (CR). The 1 km treadmill walk test (1-KTWT) is a submaximal continuous exercise test to predict cardiorespiratory fitness in patients with cardiovascular disease. We examined physiological, metabolic and subjective responses in patients with cardiovascular disease with self-selected, unchanging walking speed for two 1-KTWTs. Fifteen men (age: 65 ± 9 yr, height: 174 ± 5 cm, body mass: 86 ± 17 kg, BMI: 28.5 ± 5.5 kg·m−2, body fat%: 27.7 ± 7.5%, 10 on beta-blockers) were recruited from phase IV CR groups in the United Kingdom. Participants established a self-selected walking speed for the 1-KTWT and performed the 1-KTWT on separate days with recording of physiological responses to predict V ˙ O2peak with equations. For the two 1-KTWTs, no differences existed for walking speed, mean and maximal heart rates, oxygen uptake, predicted V ˙ O2peak (1st 1-KTWT (range: 41–78% V ˙ O2peak, 95%CI, 53–65; 2nd 1-KTWT range: 43–78% V ˙ O2peak, 95%CI, 52–65) and rating of perceived exertion. In phase IV cardiac patients, the 1-KTWT with self-selected, unchanging walking speed can be used for V ˙ O2peak prediction without the need for a full familiarisation. The self-selected constant walking speed for the first 1-KTWT can be used to support nonsupervised physical activity for phase IV CR patients. [ABSTRACT FROM AUTHOR]

Background: Survival following cardiac arrest (CA) remains poor after conventional cardiopulmonary resuscitation (CCPR) (6–26%), and the outcomes after extracorporeal cardiopulmonary resuscitation (ECPR) are often inconsistent. Poor survival is a consequence of CA, low-flow states during CCPR, multi-organ injury, insufficient monitoring, and delayed treatment of the causative condition. We developed a new strategy to address these issues. Methods: This all-comers, multicenter, prospective observational study (69 patients with in- and out-of-hospital CA (IHCA and OHCA) after prolonged refractory CCPR) focused on extracorporeal cardiopulmonary support, comprehensive monitoring, multi-organ repair, and the potential for out-of-hospital cannulation and treatment. Result: The overall survival rate at hospital discharge was 42.0%, and a favorable neurological outcome (CPC 1+2) at 90 days was achieved for 79.3% of survivors (CPC 1+2 survival 33%). IHCA survival was very favorable (51.7%), as was CPC 1+2 survival at 90 days (41%). Survival of OHCA patients was 35% and CPC 1+2 survival at 90 days was 28%. The subgroup of OHCA patients with pre-hospital cannulation showed a superior survival rate of 57.1%. Conclusions: This new strategy focusing on repairing damage to multiple organs appears to improve outcomes after CA, and these findings should provide a sound basis for further research in this area. [ABSTRACT FROM AUTHOR]

Simple Summary: In Western countries, Hepatitis E virus (HEV) can infect humans when they consume contaminated food. In most cases, the infection resolves on its own with mild symptoms. However, for some individuals, especially those with weakened immune systems, it can lead to severe and long-lasting health problems. Currently, primary detection of the virus RNA in food is performed, but it does not allow for distinguishing between infectious and inactivated viruses. Another approach consists in detecting virus growth in vitro, but it is presently slow and requires specific skills. All these render the assessment of effectively inactivated HEV challenging. In our research, we explored (1) in vitro HEV cultivation methods and (2) alternative molecular methods that can distinguish between intact and damaged viruses. These newly developed methods will help to assess the virus infectivity along the food chain, thereby identifying risk factors and mitigation strategies (e.g., food processing techniques) enhancing food safety. Hepatitis E virus is a prominent cause of viral hepatitis worldwide. In Western countries, most infections are asymptomatic. However, acute self-limiting hepatitis and chronic cases in immunocompromised individuals can occur. Studying HEV is challenging due to its difficulty to grow in cell culture. Consequently, the detection of the virus mainly relies on RT-qPCR, which cannot differentiate between infectious and non-infectious particles. To overcome this problem, methods assessing viral integrity offer a possible solution to differentiate between intact and damaged viruses. This study aims at optimizing existing HEV cell culture models and RT-qPCR-based assays for selectively detecting intact virions to establish a reliable model for assessing HEV infectivity. In conclusion, these newly developed methods hold promise for enhancing food safety by identifying approaches for inactivating HEV in food processing, thereby increasing food safety measures. [ABSTRACT FROM AUTHOR]

Addressing equity in healthcare is fundamental for delivering safe care to vulnerable patients, especially during COVID-19. This paper aims to identify barriers and enabling factors for general practitioners (GPs) in delivering safe and equitable care during the COVID-19 pandemic. Semi-structured interviews took place during May–July 2020 among 18 Flemish and 16 Dutch GPs. Thematic analysis of the interviews demonstrated that while GPs acknowledged a smooth information flow by governments and professional organizations on care guidelines, the fast-changing information challenged them to stay up to date. Media communication facilitated information dissemination but also fueled misinformation and miscommunication, creating unrealistic patient expectations. Certain guidelines and patient reluctance delayed necessary care. A shortage of personal protective equipment made GPs concerned about patient safety during face-to-face contacts. Teleconsultations became a popular alternative, but posed increased patient safety risks. GPs struggled to identify and reach vulnerable patients. Equitable care was hindered by time constraints; thus, having the appropriate materials facilitated such care. An interprofessional collaboration involving paramedical, social, and city services benefited patient safety and equity in healthcare. However, limitations in this collaboration pressured GPs. The unprecedented and resource-constrained environment challenged GPs' capacity to provide the healthcare quality they aspired to deliver. A well-structured collaborative network involving all stakeholders could benefit safe and equitable care in future pandemics. [ABSTRACT FROM AUTHOR]

In this study, we grew radish (Raphanus raphanistrum subsp. sativus L.) and broad beans (Vicia faba L.) in a greenhouse on soils spiked with a mixture of 15 per- and polyfluoroalkyl substances (PFASs) and investigated the association between accumulated ∑PFAS concentrations, growth, and hormone levels. Short-chained PFASs dominated aboveground tissues, whereas long-chained PFASs were most abundant in the plant roots. Our results showed that the presence or absence of exodermal Casparian strips, as well as the hydrophobicity and anion exchange capacities of PFASs, could explain the translocation of PFASs within plants. Significant associations found between accumulated PFAS concentrations and levels of gibberellins (GA1 and GA15), methionine, and indole-3-acetic acid (IAA) imply potential effects of PFASs on plant development and growth. This study provides the first evidence of associations between PFAS accumulation in plants and growth hormone levels, possibly leading to growth reduction of the apical dome and effects on the cell cycle in pericycle cells and methionine metabolism in plants. [ABSTRACT FROM AUTHOR]

Internet usage is a salient developmental factor in adolescents' lives. Although relevant correlates of Internet use have been documented earlier, there is a lack of information on lower socioeconomic status groups. This is important, as these adolescents have increased risk of negative online experiences. The current survey aimed to explore Internet use and parental involvement amongst adolescents from areas of socio-economic disadvantage in 30 urban schools across five European countries. A total of 2594 students participated, of whom 90% were 14–16 years. Virtually all adolescents of socioeconomic disadvantage had Internet access, with 88.5% reporting spending more than two hours per day online, often on apps such as Instagram, Snapchat, and YouTube. Almost one-third of adolescents did not talk with their parents about their Internet use and almost two-thirds indicated that their parents were only a little or not interested in their Internet use. A consistent finding across countries was that girls more often talked with their parents about their Internet use and more often reported that their parents were interested in their Internet use than boys. The results suggest that parents have an important task in explicitly showing interest in their adolescents' Internet use, with special attention needed for boys. [ABSTRACT FROM AUTHOR]

Purpose: Pelvic fractures in older adults are a major public health problem and socioeconomic burden. The standard of care has changed over the past years, and there is limited consensus on which patients benefit from surgical fixation. There is currently no nationwide treatment protocol to guide the decision-making process. Therefore, the aim of this survey was to provide more insight into if, when, and why patients with a fragility fracture of the pelvis (FFPs) would be considered for additional imaging and surgical fixation by treating physicians. Methods: An online clinical vignette-based survey of hypothetical scenarios was sent out to all orthopedic and trauma surgeons in the Netherlands. The questionnaire comprised multiple-choice questions and radiographic images. Differences between subgroups were calculated using the X2 test or the Fisher exact test. Results: 169 surgeons responded to the survey, with varying levels of experience and working in different types of hospitals. In a patient with a simple pubic ramus fracture and ASA 2 or ASA 4, 32% and 18% of the respondents would always advise a CT scan for further analysis. In the same patients, 11% and 31% of the respondents would not advise a CT scan, respectively. When presented with three cases of increasing severity of co-morbidity (ASA) and/or increasing age and/or different clinical presentation of an FFP type 3c on a CT scan, an increasing number of respondents would not consider surgical fixation. There was significant variation in practice patterns between the respondents who do not work in a hospital performing pelvic and acetabular (P&A) fracture surgery and those who do work in a P&A referral hospital. Most respondents (77%) refer patients 1–5 times a year to an expert center for surgical fixation. Conclusion: There is currently a wide variety of clinical practices regarding the imaging and management of FFPs, which seems to be influenced by the type of hospital the patients are presented to. A regional or national evidence-based treatment protocol should be implemented to ensure a more uniform approach. [ABSTRACT FROM AUTHOR]

Background: Left atrial posterior wall isolation (LAPWI) may improve rhythm control in addition to pulmonary vein isolation (PVI) in persistent atrial fibrillation (persAF) patients undergoing catheter ablation (CA). However, LAPWI may be challenging when using thermal energy sources. Objective: This study aimed to investigate the efficacy and safety of LAPWI performed by non-thermal pulsed field ablation (PFA) in CA for persAF. Methods: Consecutive persAF patients from two German centers were prospectively enrolled. There were two study cohorts: (1) the LAPWI cohort, which included PFA-guided (re-)PVI with LAPWI for first-time and/or repeat ablation procedures; and (2) a comparative persAF cohort with a PFA PVI-only approach without LAPWI for first-time ablation within the same timeframe. Patients were followed up by routine Holter ECGs. Results: In total, 79 persistent AF patients were included in the study: 59/79 patients were enrolled in the LAPWI cohort, including 16/59 index (27%) and 43/59 repeat ablation procedures (73%). Sixteen patients (16/79; 21%) were in the PVI-only cohort without LAPWI. Of the patients treated with LAPWI, procedure time and fluoroscopy time was 91 ± 30 min and 15 ± 7 min, respectively. The acute PVI rate was 100% in all first-time ablation patients (32 patients (16 PVI only, 16 PVI plus LAPWI), 196/196 PVs). Of the 43 re-do patients in the LAPWI cohort, re-PVI was necessary in 33% (14/43) of patients (27 PVs; 1.9 PV per-patient); in 67% (29/43), all PVs were isolated, and antral ablation of the PV ostia was performed in 48% (14/29). LAPWI was performed successfully in all 59 (100%) patients of the LAPWI cohort. Two minor complications occurred. No esophageal lesion was detected in the LAPWI cohort (n = 33/59 (56%) patients underwent endoscopy). After 354 ± 197 days of follow-up, freedom from atrial arrhythmias was 79.3% (95-CI: 62–95%) in the complete LAPWI cohort (n = 14/59 (24%) on AAD: class Ic n = 9, class III n = 5). There was no difference regarding acute procedural and clinical outcome compared to the PVI-only cohort. Conclusion: LAPWI guided by PFA is feasible and safe in patients undergoing CA for persAF and shows favorable outcomes. In the context of durable PVI, PFA-guided LAPWI may be an effective adjunctive treatment option. [ABSTRACT FROM AUTHOR]

Drought can have a significant impact on both society and the economy, resulting in issues such as scarcity of water and shortages of food and energy, as well as elevated health risks. However, as global temperatures continue to rise, the impact of drought events is increasingly exacerbated, manifested by an increase in the frequency, intensity, duration, and spatial extent of their effects. Therefore, studying the changing characteristics of drought events with the background of climate change is of great significance. Based on the high-precision and high-resolution CN05.1 dataset, this study obtained the monthly Standardized Precipitation Evapotranspiration Index (SPEI) dataset from 1961 to 2020, and then identified regional drought events in China using the Intensity–Area–Duration (IAD) method, which considers both temporal continuity and spatial dynamics. On this basis, the spatiotemporal variations in frequency, intensity, duration, and affected area of drought events in China and its seven subregions were analyzed. The results showed that the subregions located in the northern region of China generally have lower mean, maximum, and minimum temperatures than those located in the southern region, but the associated interannual change rate of the subregions in the north is higher than that in the south. As for the annual total precipitation, results show a clear pattern of decreasing southeast–northwest gradient, with an increasing trend in the northern subregions and a decreasing trend in the southern subregions except for the subregion south China (SC). The northeast of China (NE), SC, the southwest of China (SW) and north China (NC) are the regions with a high frequency of drought events in China, while the frequency of drought events in NW and Qinghai–Tibetan Plateau (QTP), although lower, is on a significantly increasing trend, and the increasing rate is higher than for the other regions. For drought intensity, Xinjiang (XJ) and QTP had greater drought intensity, and the change rate of these regions with greater drought intensity was also greater. The drought impact area in China showed a significant increasing trend, mainly concentrated in QTP, NW and NE. Particular attention needs to be focused on the southwest of QTP, where drought events in this region show a significant increase in frequency, intensity, duration and impact area. [ABSTRACT FROM AUTHOR]

Background and aim: The presence of mechanical dyssynchrony on echocardiography is associated with reverse remodelling and decreased mortality after cardiac resynchronization therapy (CRT). Contrarily, myocardial scar reduces the effect of CRT. This study investigated how well a combined assessment of different markers of mechanical dyssynchrony and scarring identifies CRT responders. Methods: In a prospective multicentre study of 170 CRT recipients, septal flash (SF), apical rocking (ApRock), systolic stretch index (SSI), and lateral-to-septal (LW-S) work differences were assessed using echocardiography. Myocardial scarring was quantified using cardiac magnetic resonance imaging (CMR) or excluded based on a coronary angiogram and clinical history. The primary endpoint was a CRT response, defined as a ≥15% reduction in LV end-systolic volume 12 months after implantation. The secondary endpoint was time-to-death. Results: The combined assessment of mechanical dyssynchrony and septal scarring showed AUCs ranging between 0.81 (95%CI: 0.74–0.88) and 0.86 (95%CI: 0.79–0.91) for predicting a CRT response, without significant differences between the markers, but significantly higher than mechanical dyssynchrony alone. QRS morphology, QRS duration, and LV ejection fraction were not superior in their prediction. Predictive power was similar in the subgroups of patients with ischemic cardiomyopathy. The combined assessments significantly predicted all-cause mortality at 44 ± 13 months after CRT with a hazard ratio ranging from 0.28 (95%CI: 0.12–0.67) to 0.20 (95%CI: 0.08–0.49). Conclusions: The combined assessment of mechanical dyssynchrony and septal scarring identified CRT responders with high predictive power. Both visual and quantitative markers were highly feasible and demonstrated similar results. This work demonstrates the value of imaging LV mechanics and scarring in CRT candidates, which can already be achieved in a clinical routine. [ABSTRACT FROM AUTHOR]

Aims: Oral squamous cell carcinoma (OSCC) frequently invades the jaw. The exact mechanism of bone invasion remains unclear. This study investigates (premature) osteoclasts and the expression of its differentiation regulating proteins RANKL, OPG and RANK in patients with OSCC. Methods: Resection specimens from OSCC patients were divided into NI group (No Invasion), E group (Erosion) or I group (bone Invasion). Tissue sections were stained with Cathepsin K (osteoclast-counting), RANKL, OPG and RANK. The staining intensity was scored on different regions of the tumor: front, center, back and normal mucosa. Immunohistochemistry and qPCR for RANKL/OPG/RANK were performed on five head and neck squamous cell carcinoma (HNSCC) organoids. Results: The mean number of osteoclasts (I group) and premature osteoclasts (E group) was significantly higher compared to the NI group (p = 0.003, p = 0.036). RANKL expression was significantly higher in the tumor front and tumor center compared to normal mucosa (all groups). In the I group, RANKL and RANK expression was significantly higher in the tumor front compared to the tumor back and there was a trend of higher RANKL expression in the tumor front compared to the E group and NI group. qPCR showed a 20–43 times higher RANKL mRNA expression in three out of five tumor organoids compared to a normal squamous cell organoid line. There was no correlation between protein and mRNA expression in the HNSCC organoids. Conclusions: These findings suggest that OSCCs induce bone invasion by stimulating osteoclast activation by regulating the production of RANKL and RANK proteins. [ABSTRACT FROM AUTHOR]

The paper focuses on secondary bio streams which are not captured efficiently in the value supply chain. Specifically, roadside grass clippings were chosen, based on their logistical optimization potential, direct feasibility, locality, biomass potential, and economic valorization value. The main objective is to determine how this secondary flow can be brought to the "factory gate"—through road transport and inland shipping—and at what cost per unit. To this end, various scenarios were developed for a case study in East Flanders, considering multiple combinations of first collection points, secondary collection points, and processing points. The result is a generically applicable Excel-based tool that combines these variations with a solution considering both inland waterways and road transport. These scenarios become valuable in applying the tool for grass clippings and optimizing this value chain located in East Flanders. The results show that reducing the number of collection points is favorable for the utilization of inland waterways, as it reduces costs related to transshipment. Nevertheless, unimodal road transport is still the most cost-effective method for transporting this secondary material stream from the collection point to the processing point. Consequently, a lower weight and a higher density will lead to lower costs, which eventually bottom out, due to regulations and conditions that must be met. [ABSTRACT FROM AUTHOR]

Simple Summary: Intense selection has led to a significant increase in body weight of commercial turkeys. These successes have had some impact on the mobility of turkeys. There is a consensus about the negative genetic relationship between growth and mobility. Although it is reasonable to assume that such a relationship is likely to change with the rate of growth, little is known about the potential non-linearity of such association. To investigate the potential non-linear relationship between growth and mobility, the growth rates at three different age periods (0 to 12, 12 to 20, and 0 to 20 weeks) were calculated, and each bird was assigned to one of the quartiles of the growth rate distribution for each age period. Heritability estimates of walking ability ranged between 0.18 and 0.26 indicating the possibility for genetic improvement. The genetic correlations between adjacent growth rate quartiles were high and decayed as the interval between quartiles increased. There is no evidence to support that walking abilities across growth rate quartiles are different traits. However, the magnitude of the variation in the incidence of walking scores and genetic correlations across the different growth quartiles seem to point towards a potential non-linear relationship between growth and mobility. The aim of this study was to investigate the potential non-linear relationship between growth and walking ability (WA). The phenotypic data included body weights at 12 and 20 weeks and WA at 20 weeks of age measured on 276,059 male turkeys. The growth rate at three age periods (0 to 12, 12 to 20 and 0 to 20 weeks) was calculated. Each bird was assigned to one of the quartiles of the growth rate distribution for each age period. Between the first and fourth quartiles, the incidence of score 1 (bad WA) increased by 31, 18, and 33% for the first, second, and third age periods, respectively. For good WA (scores 4, 5, and 6), the incidence decreased by 55, 66, and 72% between the first and fourth quartiles for the first, second, and third age periods, respectively. Estimates of heritability of WA ranged between 0.18 and 0.26. The genetic correlations between adjacent growth rate quartiles were high and decayed as the interval between quartiles increased. The magnitude of the variation in the incidence of walking scores and genetic correlations across the growth rate quartiles point towards a non-linear relationship between growth and mobility suggesting other factors may affect walking ability. [ABSTRACT FROM AUTHOR]

Global drought patterns are substantially impacted by climate change, with far-reaching implications for socioeconomic and ecological systems. Existing global climate models (GCMs) are unable to accurately project precipitation and drought characteristics, particularly in countries or regions with complex topography and significant seasonal variability, such as China. Consequently, the purpose of this study is to assess the efficacy of GCMs, and their multi-model ensemble mean, as well as to investigate the seasonal drought characteristics in China using precipitation data from CMIP6 under various "possible future" scenarios. This study selected five GCMs with historical (1961–2014) and future (2015–2100) periods, namely CNRM-CM6-1, GFDL-ESM4, MPI-ESM1-2-HR, MPI-ESM1-2-LR, and NorESM2-MM, as well as their ensemble mean ENS-CGMMN. Based on the China Daily Precipitation Analysis Product (CPAP) as the reference precipitation, the performance of these models is evaluated using the DISO index and the quantile mapping (QM) method for calibration, as well as seasonal-scale drought using the standardized precipitation index (SPI) and spatiotemporal variability analysis methods. In comparison to other climate models and the ensemble mean, the calibrated MPI-ESM1-2-HR model can more precisely describe the actual precipitation conditions at the seasonal scale. Under four scenarios, China's climate will shift from arid to moist in the future period (2015–2100) (SSP126, SSP245, SSP370, and SSP585). Autumn and summer will see a considerable increase in China's moisture levels. During the autumn, winter, and spring, the moisture will generally increase in the northern subregions of China, including the Qinghai-Tibet Plateau (QTP), Xinjiang (XJ), Northwest (NW), Northeast (NE), and North China (NC). Dryness will decrease in southern subregions, such as the Southwest (SW) and South China (SC). In contrast to these three seasons, summer in XJ exhibits a distinct trend of aridity, especially in the SSP245 scenario, whereas the NE, NC, and SC exhibit a distinct trend of moisture. To be more specific, the aridity changes in subregions during various seasons under different future climate scenarios vary significantly. This study's findings can provide significant support for future research on climate change and drought, which can help improve the accuracy of future climate projections and serve as a reference for drought risk management and policy formulation. [ABSTRACT FROM AUTHOR]

The forensic application of phonetics relies on individuality in speech. In the forensic domain, individual patterns of verbal and paraverbal behavior are of interest which are readily available, measurable, consistent, and robust to disguise and to telephone transmission. This contribution is written from the perspective of the forensic phonetic practitioner and seeks to establish a more comprehensive concept of disfluency than previous studies have. A taxonomy of possible variables forming part of what can be termed disfluency behavior is outlined. It includes the "classical" fillers, but extends well beyond these, covering, among others, additional types of fillers as well as prolongations, but also the way in which fillers are combined with pauses. In the empirical section, the materials collected for an earlier study are re-examined and subjected to two different statistical procedures in an attempt to approach the issue of individuality. Recordings consist of several minutes of spontaneous speech by eight speakers on three different occasions. Beyond the established set of hesitation markers, additional aspects of disfluency behavior which fulfill the criteria outlined above are included in the analysis. The proportion of various types of disfluency markers is determined. Both statistical approaches suggest that these speakers can be distinguished at a level far above chance using the disfluency data. At the same time, the results show that it is difficult to pin down a single measure which characterizes the disfluency behavior of an individual speaker. The forensic implications of these findings are discussed. [ABSTRACT FROM AUTHOR]

Simple Summary: Immunotherapy is increasingly used in lymphoma strategy. Risk-adapted therapeutical management and set-up scores to -stratify the most vulnerable patients by risk are becoming major concerns. With the continuing upward trend of real-world data usage in addition to clinical trial data, it is possible to test the feasibility of using data from clinical data warehouses (CDWs) to identify new predictive factors for response or toxicity to immunotherapy. Based on a large set of biological and clinical factors, our results confirm already known predictors factors of CAR T (chimeric antigen receptor T) cells: age, elevated lactate dehydrogenase, and C-Reactive Protein at the time of infusion. Additionally male gender, low hemoglobin, and hypo- or hyperkalemia are demonstrated to be predictive factors for progression after CAR T cell therapy. Thus, the attractiveness of CDW for generating data by building ever larger cohorts is proven, enabling significant results to be obtained in line with those previously described in the literature. Immunotherapy (IT) is a major therapeutic strategy for lymphoma, significantly improving patient prognosis. IT remains ineffective for a significant number of patients, however, and exposes them to specific toxicities. The identification predictive factors around efficacy and toxicity would allow better targeting of patients with a higher ratio of benefit to risk. PRONOSTIM is a multicenter and retrospective study using the Clinical Data Warehouse (CDW) of the Greater Paris University Hospitals network. Adult patients with Hodgkin lymphoma or diffuse large-cell B lymphoma treated with immune checkpoint inhibitors or CAR T (Chimeric antigen receptor T) cells between 2017 and 2022 were included. Analysis of covariates influencing progression-free survival (PFS) or the occurrence of grade ≥3 toxicity was performed. In total, 249 patients were included. From this study, already known predictors for response or toxicity of CAR T cells such as age, elevated lactate dehydrogenase, and elevated C-Reactive Protein at the time of infusion were confirmed. In addition, male gender, low hemoglobin, and hypo- or hyperkalemia were demonstrated to be potential predictive factors for progression after CAR T cell therapy. These findings prove the attractiveness of CDW in generating real-world data, and show its essential contribution to identifying new predictors for decision support before starting IT. [ABSTRACT FROM AUTHOR]

Autophagy is a catabolic pathway capable of degrading cellular components ranging from individual molecules to organelles. Autophagy helps cells cope with stress by removing superfluous or hazardous material. In a previous work, we demonstrated that transcriptional upregulation of two autophagy-related genes, ATG5 and ATG7, in Arabidopsis thaliana positively affected agronomically important traits: biomass, seed yield, tolerance to pathogens and oxidative stress. Although the occurrence of these traits correlated with enhanced autophagic activity, it is possible that autophagy-independent roles of ATG5 and ATG7 also contributed to the phenotypes. In this study, we employed affinity purification and LC-MS/MS to identify the interactome of wild-type ATG5 and its autophagy-inactive substitution mutant, ATG5K128R Here we present the first interactome of plant ATG5, encompassing not only known autophagy regulators but also stress-response factors, components of the ubiquitin-proteasome system, proteins involved in endomembrane trafficking, and potential partners of the nuclear fraction of ATG5. Furthermore, we discovered post-translational modifications, such as phosphorylation and acetylation present on ATG5 complex components that are likely to play regulatory functions. These results strongly indicate that plant ATG5 complex proteins have roles beyond autophagy itself, opening avenues for further investigations on the complex roles of autophagy in plant growth and stress responses. [ABSTRACT FROM AUTHOR]

Simple Summary: Historically, patients with pancreatic ductal adenoma carcinoma were subjected to immediate surgical resection of the pancreatic tumor. Nowadays, more and more patients are treated with chemo(radio)therapy before surgical resection. It is known that patients with pancreatic cancer have a high risk of developing thrombosis. However, as patients underwent immediate surgery before, the incidence of thrombosis in patients with pancreatic cancer during neoadjuvant chemotherapy is understudied. Few studies have investigated the VTE incidence in this population and it is unclear whether these patients should use perioperative thromboprophylaxis to prevent thrombosis. This narrative review summarizes the evidence that is currently available. Recent studies have shown that patients with pancreatic ductal adenocarcinoma (PDAC) treated with neoadjuvant chemo(radio)therapy followed by surgery have an improved outcome compared to patients treated with upfront surgery. Hence, patients with PDAC are more and more frequently treated with chemotherapy in the neoadjuvant setting. PDAC patients are at a high risk of developing venous thromboembolism (VTE), which is associated with decreased survival rates. As patients with PDAC were historically offered immediate surgical resection, data on VTE incidence and associated preoperative risk factors are scarce. Current guidelines recommend primary prophylactic anticoagulation in selected groups of patients with advanced PDAC. However, recommendations for patients with (borderline) resectable PDAC treated with chemotherapy in the neoadjuvant setting are lacking. Nevertheless, the prevention of complications is crucial to maintain the best possible condition for surgery. This narrative review summarizes current literature on VTE incidence, associated risk factors, risk assessment tools, and primary thromboprophylaxis in PDAC patients treated with neoadjuvant chemo(radio)therapy. [ABSTRACT FROM AUTHOR]

Background: Perioral muscle function, which influences maxillofacial growth and tooth position, can be affected in patients with oral clefts due to their inherent anatomical characteristics and the multiple surgical corrections performed. This research aims to (1) compare the maximum oral muscle pressure of subjects with and without isolated cleft palate (CP) or unilateral cleft lip and palate (UCLP), (2) investigate its influence on their dentoalveolar characteristics, and (3) investigate the influence of functional habits on the maximum oral muscle pressure in patients with and without cleft. Material and methods: Subjects with and without CP and UCLP seeking treatment at the Department of Orthodontics of University Hospitals Leuven between January 2021 and August 2022 were invited to participate. The Iowa Oral Performance Instrument (IOPI) was used to measure their maximum tongue, lip, and cheek pressure. An imbalance score was calculated to express the relationship between tongue and lip pressure. Upper and lower intercanine (ICD) and intermolar distance (IMD) were measured on 3D digital dental casts, and the presence of functional habits was reported by the patients. The data were analyzed with multivariable linear models, correcting for age and gender. Results: 44 subjects with CP or UCLP (mean age: 12.00 years) and 104 non-affected patients (mean age: 11.13 years) were included. No significant differences in maximum oral muscle pressure or imbalance score were detected between controls and clefts or between cleft types. Significantly smaller upper ICDs and larger upper and lower IMDs were found in patients with clefts. A significant difference between controls and clefts was found in the relationship between oral muscle pressure and transversal jaw width. In cleft patients, the higher the maximum tongue pressure, the wider the upper and lower IMD, the higher the lip pressure, the smaller the upper and lower ICD and IMD, and the higher the imbalance score, the larger the upper and lower IMD and lower ICD. An imbalance favoring the tongue was found in cleft patients. The influence of functional habits on the maximum oral muscle pressure was not statistically different between clefts and controls. Conclusion: Patients with CP or UCLP did not present reduced maximum oral muscle pressure compared with patients without a cleft. In cleft patients, tongue pressure was consistently greater than lip pressure, and those who presented a larger maxillary width presented systematically higher imbalance scores (favoring the tongue) than those with narrow maxillae. Therefore, the influence of slow maxillary expansion on maximum oral muscle pressure in cleft patients should not be underestimated. [ABSTRACT FROM AUTHOR]

Objectives: To compare the performance of the Malmgren index on 2D and 3D radiographs. Methods: Patients with a panoramic radiograph and a cone beam computed tomography (CBCT) taken at an interval of <3 months and presenting root resorption (RR) on at least one incisor and/or canine were retrospectively included. RR was scored twice by two observers using the Malmgren index in both the 2D and 3D sets, and intra-class correlation coefficient (ICC) was calculated. Results: 155 teeth were analyzed. The ICC was the lowest in 2D, followed by overall, transversal and sagittal 3D. Malmgren scores were systematically higher in 2D, which overestimated RR, especially in the transversal plane on all incisors and canines and in the sagittal plane on the maxillary incisors. 2D respectively leads to 28.0–34.8% of false positives and negatives when discriminating between RR or not. The early stages of RR are often misdiagnosed in 2D, while later stages are more accurate. Conclusions: The original Malmgren index is not suited for 3D images, especially axial, where using dichotomized values (resorption yes/no) leads to overestimation of RR. A low-dose CBCT of the upper incisors could detect RR with high diagnostic accuracy in the early stages of orthodontic treatment, especially in patients with dental trauma or familial RR history. [ABSTRACT FROM AUTHOR]

Highly filled plastics may offer a suitable solution within the production process for bipolar plates. However, the compounding of conductive additives and the homogeneous mixing of the plastic melt, as well as the accurate prediction of the material behavior, pose a major challenge for polymer engineers. To support the engineering design process of compounding by twin-screw extruders, this present study offers a method to evaluate the achievable mixing quality based on numerical flow simulations. For this purpose, graphite compounds with a filling content of up to 87 wt.-% were successfully produced and characterized rheologically. Based on a particle tracking method, improved element configurations were found for twin-screw compounding. Furthermore, a method to characterize the wall slip ratios of the compounded material system with different filler content is presented, since highly filled material systems often tend to wall slip during processing, which could have a very large influence on accurate prediction. Numerical simulations of the high capillary rheometer were conducted to predict the pressure loss in the capillary. The simulation results show a good agreement and were experimentally validated. In contrast to the expectation, higher filler grades showed only a lower wall slip than compounds with a low graphite content. Despite occurring wall slip effects, the developed flow simulation for the design of slit dies can provide a good prediction for both low and high filling ratios of the graphite compounds. [ABSTRACT FROM AUTHOR]

Simple Summary: Prognostic markers play an important role in the risk assessment and treatment of cancers in general. The aim of this systematic review was to assess the potential prognostic markers for the rare sinonasal intestinal-type adenocarcinoma. The results from this paper may help specialists to better understand the risks of this disease and provide more insight into the prognosis. We found twenty-one biomarkers. Whilst some had a significant negative effect on prognosis, none had a positive effect. Furthermore, the biomarkers found were analyzed within the hallmarks of cancer to provide more information considering the carcinogenesis of this carcinoma. This could help in the better treatment of sinonasal intestinal-type adenocarcinoma and better patient outcomes. One of the rare tumor entities present in the nose and paranasal sinuses is sinonasal (non-) intestinal-type adenocarcinoma (ITAC/non-ITAC). Currently, surgery with postoperative radiotherapy is the cornerstone of the treatment of these tumors. Systemic treatment is usually applied in a palliative setting. The prognosis of these tumors is very diverse. Biomarkers that may have prognostic value in these rare malignancies could help clinicians in decision-making. A systematic search of the literature was performed using the PubMed database. All studies investigating the prognostic significance of biomarkers in paranasal sinus ITAC/non-ITAC were retrieved. The findings were categorized within the hallmarks of cancer, to gain an understanding of the functions of possible prognostic biomarkers in the development of ITAC/non-ITAC. There were twenty-one studies reporting on twenty-one possible biomarkers included in the review. The expression of Mucin antigen sialosyl-Tn, C-erbB-2 oncoprotein, TIMP3 methylation, TP53, VEGF, ANXA2, MUC1 and the mucinous histological subtype were found to have a significant negative effect on survival. None of the biomarkers were found to have a positive effect on prognosis. The hallmarks 'activating invasion and metastasis' and 'sustaining proliferative signaling' seem to play the largest role in sinonasal (non-)ITAC. It could be concluded that there are multiple biomarkers foreboding a negative prognosis for ITAC/non-ITAC patients. [ABSTRACT FROM AUTHOR]

Background: The incidence of cardiac implantable electronic device (CIED)-related complications, as well as the prevalence of obesity, is rising worldwide. Transvenous laser lead extraction (LLE) has grown into a crucial therapeutic option for patients with CIED-related complications but the impact of obesity on LLE is not well understood. Methods and Results: All patients (n = 2524) from the GermAn Laser Lead Extraction RegistrY (GALLERY) were stratified into five groups according to their body mass index (BMI, <18.5; 18.5–24.9; 25–29.9; 30–34.9; ≥35 kg/m2). Patients with a BMI ≥ 35.0 kg/m2 had the highest prevalence of arterial hypertension (84.2%, p < 0.001), chronic kidney disease (36.8%, p = 0.020) and diabetes mellitus (51.1%, p < 0.001). The rates for procedural minor (p = 0.684) and major complications (p = 0.498), as well as procedural success (p = 0.437), procedure-related (p = 0.533) and all-cause mortality (p = 0.333) were not different between groups. In obese patients (BMI ≥ 30 kg/m2), lead age ≥10 years was identified as a predictor of procedural failure (OR: 2.99; 95% CI: 1.06–8.45; p = 0.038). Lead age ≥10 years (OR: 3.25; 95% CI: 1,31–8.10; p = 0.011) and abandoned leads (OR: 3.08; 95% CI: 1.03–9.22; p = 0.044) were predictors of procedural complications, while patient age ≥75 years seemed protective (OR: 0.27; 95% CI: 0.08–0.93; p = 0.039). Systemic infection was the only predictor for all-cause mortality (OR: 17.68; 95% CI: 4.03–77.49; p < 0.001). Conclusions: LLE in obese patients is as safe and effective as in other weight classes, if performed in experienced high-volume centers. Systemic infection remains the main cause of in-hospital mortality in obese patients. [ABSTRACT FROM AUTHOR]

We designed a Network Exfiltration Detection System (NEDS) to detect data exfiltration as occurring in ransomware attacks. The NEDS operates on aggregated metadata, which is more privacy-friendly and allows analysis of large volumes of high-speed network traffic. The NEDS aggregates metadata from multiple, sequential sessions between pairs of hosts in a network, which captures exfiltration by both stateful and stateless protocols. The aggregated metadata include averages per session of both packet count, request entropy, duration, and payload size, as well as the average time between sequential sessions and the amount of aggregated sessions. The NEDS applies a number of autoencoder models with unsupervised learning to detect anomalies, where each autoencoder model targets different protocols. We trained the autoencoder models with real-life data collected at network sensors in the National Detection Network as operated by the National Cyber Security Centre in the Netherlands, and configured the detection threshold by varying the false positive rate. We evaluated the detection performance by injecting exfiltration over different channels, including DNS tunnels and uploads to FTP servers, web servers, and cloud storage. Our experimental results show that aggregation significantly increases detection performance of exfiltration that happens over longer time, most notably, DNS tunnels. Our NEDS can be applied to detect exfiltration either in near-real-time data analysis with limited false positive rates, or in captured data to aid in post-incident analysis. [ABSTRACT FROM AUTHOR]

Urinary extracellular vesicles (EVs) are an attractive source of bladder cancer biomarkers. Here, a protein biomarker discovery study was performed on the protein content of small urinary EVs (sEVs) to identify possible biomarkers for the primary diagnosis and recurrence of non-muscle-invasive bladder cancer (NMIBC). The sEVs were isolated by ultrafiltration (UF) in combination with size-exclusion chromatography (SEC). The first part of the study compared healthy individuals with NMIBC patients with a primary diagnosis. The second part compared tumor-free patients with patients with a recurrent NMIBC diagnosis. The separated sEVs were in the size range of 40 to 200 nm. Based on manually curated high quality mass spectrometry (MS) data, the statistical analysis revealed 69 proteins that were differentially expressed in these sEV fractions of patients with a first bladder cancer tumor vs. an age- and gender-matched healthy control group. When the discriminating power between healthy individuals and first diagnosis patients is taken into account, the biomarkers with the most potential are MASP2, C3, A2M, CHMP2A and NHE-RF1. Additionally, two proteins (HBB and HBA1) were differentially expressed between bladder cancer patients with a recurrent diagnosis vs. tumor-free samples of bladder cancer patients, but their biological relevance is very limited. [ABSTRACT FROM AUTHOR]

Simple Summary: Around 30% of patients with stage III non-small cell lung cancer (NSCLC) receiving radical chemoradiotherapy will develop symptomatic brain metastases (BM) during the disease course. Identifying risk factors for BM can help improve the management of these patients. The aim of this current study was to identify clinical risk factors, including gross tumor volume (GTV) radiomics features, for developing BM in patients with radically treated stage III NSCLC. We found that age, NSCLC subtype, and GTV of lymph nodes (GTVn) were significant factors for BM. GTVn radiomics features provided higher predictive value than GTV of primary tumor (GTVp) and GTV. Therefore, GTVp and GTVn should be separated in clinical and research practice. Purpose: To identify clinical risk factors, including gross tumor volume (GTV) and radiomics features, for developing brain metastases (BM) in patients with radically treated stage III non-small cell lung cancer (NSCLC). Methods: Clinical data and planning CT scans for thoracic radiotherapy were retrieved from patients with radically treated stage III NSCLC. Radiomics features were extracted from the GTV, primary lung tumor (GTVp), and involved lymph nodes (GTVn), separately. Competing risk analysis was used to develop models (clinical, radiomics, and combined model). LASSO regression was performed to select radiomics features and train models. Area under the receiver operating characteristic curves (AUC-ROC) and calibration were performed to assess the models' performance. Results: Three-hundred-ten patients were eligible and 52 (16.8%) developed BM. Three clinical variables (age, NSCLC subtype, and GTVn) and five radiomics features from each radiomics model were significantly associated with BM. Radiomic features measuring tumor heterogeneity were the most relevant. The AUCs and calibration curves of the models showed that the GTVn radiomics model had the best performance (AUC: 0.74; 95% CI: 0.71–0.86; sensitivity: 84%; specificity: 61%; positive predictive value [PPV]: 29%; negative predictive value [NPV]: 95%; accuracy: 65%). Conclusion: Age, NSCLC subtype, and GTVn were significant risk factors for BM. GTVn radiomics features provided higher predictive value than GTVp and GTV for BM development. GTVp and GTVn should be separated in clinical and research practice. [ABSTRACT FROM AUTHOR]

Bioactive nanomaterials are increasingly being applied in oral health research. Specifically, they have shown great potential for periodontal tissue regeneration and have substantially improved oral health in translational and clinical applications. However, their limitations and side effects still need to be explored and elucidated. This article aims to review the recent advancements in nanomaterials applied for periodontal tissue regeneration and to discuss future research directions in this field, especially focusing on research using nanomaterials to improve oral health. The biomimetic and physiochemical properties of nanomaterials such as metals and polymer composites are described in detail, including their effects on the regeneration of alveolar bone, periodontal ligament, cementum and gingiva. Finally, the biomedical safety issues of their application as regenerative materials are updated, with a discussion about their complications and future perspectives. Although the applications of bioactive nanomaterials in the oral cavity are still at an initial stage, and pose numerous challenges, recent research suggests that they are a promising alternative in periodontal tissue regeneration. [ABSTRACT FROM AUTHOR]

Objective: To investigate in an unselected, systemic sclerosis (SSc) cohort if baseline laser speckle contrast analysis (LASCA) peripheral blood perfusion (PBP) measurements differ between 'early' SSc (without skin involvement, or 'limited' SSc—LSSc) and 'clinically overt' SSc (with skin involvement, limited cutaneous SSc—LcSSc and diffuse cutaneous SSc—DcSSc) in routine setting. Methods: A group of twenty consecutive 'early' SSc patients and forty consecutive 'clinically overt' SSc patients (twenty LcSSc and twenty DcSSc) underwent clinical and LASCA examinations (to assess the peripheral blood perfusion [PBP] of both hands volar). Results: No statistically significant difference in adjusted PBP was found in the 'early' versus the 'clinically overt' group (p = 0.77) when adjusted for possible confounding factors (e.g., vasoactive medication, active smoking, history of DTL and disease duration). A wide variability was noted when observing the individual datapoints of each subset. Conclusion: This study with an unselected SSc population in daily routine, non-research setting, showed there was no difference in adjusted PBP at baseline between 'early' SSc and 'clinically overt' SSc when corrected for possible confounding factors. Interestingly a wide variation of individual datapoints were observed in each subset, which emphasizes the heterogeneity of SSc. [ABSTRACT FROM AUTHOR]

Altered tibiofemoral contact forces represent a risk factor for osteoarthritis onset and progression, making optimization of the knee force distribution a target of treatment strategies. Musculoskeletal model-based simulations are a state-of-the-art method to estimate joint contact forces, but they typically require laboratory-based input and skilled operators. To overcome these limitations, ambulatory methods, relying on inertial measurement units, have been proposed to estimated ground reaction forces and, consequently, knee contact forces out-of-the-lab. This study proposes the use of a full inertial-capture-based musculoskeletal modelling workflow with an underlying probabilistic principal component analysis model trained on 1787 gait cycles in patients with knee osteoarthritis. As validation, five patients with knee osteoarthritis were instrumented with 17 inertial measurement units and 76 opto-reflective markers. Participants performed multiple overground walking trials while motion and inertial capture methods were synchronously recorded. Moderate to strong correlations were found for the inertial capture-based knee contact forces compared to motion capture with root mean square error between 0.15 and 0.40 of body weight. The results show that our workflow can inform and potentially assist clinical practitioners to monitor knee joint loading in physical therapy sessions and eventually assess long-term therapeutic effects in a clinical context. [ABSTRACT FROM AUTHOR]

The most common resistance mechanism to carbapenems is the production of carbapenemases. In 2021, the Pan American Health Organization warned of the emergence and increase in new carbapenemase combinations in Enterobacterales in Latin America. In this study, we characterized four Klebsiella pneumoniae isolates harboring blaKPC and blaNDM from an outbreak during the COVID-19 pandemic in a Brazilian hospital. We assessed their plasmids' transference ability, fitness effects, and relative copy number in different hosts. The K. pneumoniae BHKPC93 and BHKPC104 strains were selected for whole genome sequencing (WGS) based on their pulsed-field gel electrophoresis profile. The WGS revealed that both isolates belong to ST11, and 20 resistance genes were identified in each isolate, including blaKPC-2 and blaNDM-1. The blaKPC gene was present on a ~56 Kbp IncN plasmid and the blaNDM-1 gene on a ~102 Kbp IncC plasmid, along with five other resistance genes. Although the blaNDM plasmid contained genes for conjugational transfer, only the blaKPC plasmid conjugated to E. coli J53, without apparent fitness effects. The minimum inhibitory concentrations (MICs) of meropenem/imipenem against BHKPC93 and BHKPC104 were 128/64 and 256/128 mg/L, respectively. Although the meropenem and imipenem MICs against E. coli J53 transconjugants carrying the blaKPC gene were 2 mg/L, this was a substantial increment in the MIC relative to the original J53 strain. The blaKPC plasmid copy number was higher in K. pneumoniae BHKPC93 and BHKPC104 than in E. coli and higher than that of the blaNDM plasmids. In conclusion, two ST11 K. pneumoniae isolates that were part of a hospital outbreak co-harbored blaKPC-2 and blaNDM-1. The blaKPC-harboring IncN plasmid has been circulating in this hospital since at least 2015, and its high copy number might have contributed to the conjugative transfer of this particular plasmid to an E. coli host. The observation that the blaKPC-containing plasmid had a lower copy number in this E. coli strain may explain why this plasmid did not confer phenotypic resistance against meropenem and imipenem. [ABSTRACT FROM AUTHOR]

Parallel elastic actuation is a highly promising concept for assisting preplanned trajectories such as repetitive tasks in industrial machines and robots. Nevertheless, due to the persisting challenges on spring lifetime, its full potential has yet to be leveraged in the industry. We propose a novel adaptive magnetic spring as a fatigue-free spring mechanism to enable variable stiffness actuators in long lifetime applications. The spring is designed to flexibly deal with variations in operating conditions, i.e., mass customization. We propose a co-design methodology which simultaneously optimizes the sizing of the magnetic spring (for the given machine and its operating conditions), together with the controls and ideal dynamic response of the system. This mechanism and the methodology are applied to a design problem of a weaving machine drivetrain, where the benefits of the adaptive magnetic spring are highlighted with respect to a fixed stiffness magnetic spring, and the current industrial benchmark without springs. Experimentally validated findings show a consistent and considerable improvement with respect to energy consumption and peak torque reduction of up to 47% and 64%, respectively, when comparing to the current industrial benchmark. [ABSTRACT FROM AUTHOR]