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Phosphaturic mesenchymal tumor (PMT) is a rare tumor causing bone complications and myopathy. Histologically, PMT displays a mix of spindled cells, osteoclast-like giant cells, basophilic matrix, and flocculent or “grungy” calcification. Here we describe a case of PMT in the right hip and proximal femur, initially suspected to be multiple myeloma, presenting with osteolytic lesions and elevated alkaline phosphatase. Tests for malignancy were negative, but a subsequent biopsy confirmed PMT. The patient underwent hip biopsy, femur resection, and hemiarthroplasty, with follow-up MRI recommended.

This paper presents the process of conducting the structural analysis of AlAinSat-1 CubeSat through a numerical solution using Siemens NX. AlAinSat-1 is a 3U remote-sensing CubeSat carrying two earth observation payloads. The CubeSat is scheduled for launch on SpaceX Falcon 9 rocket. To ensure the success of the mission and its ability to withstand the launch environment, several scenarios should be analyzed. For AlAinSat-1 model the finite element analysis (FEA) method is used, and four types of structural analyses are considered: modal, quasi-static, buckling, and random vibration analyses. The workflow cycle includes idealizing, meshing, assembling, applying connections and boundary conditions, and eventually running the simulation utilizing the Siemens Nastran solver. The simulation results of all analysis types indicate that the model can safely withstand the loads exerted during launch. Also, the numerical results of the Command and Data Handling Subsystem (CDHS) module of AlAinSat-1 are experimentally validated through a vibration test conducted using an LV8 shaker system. The module successfully passed the test based on the test success criteria provided by the launcher.

Conflict of interest: No Introduction and Objectives: Hypothermic machine perfusion using ECMO devices has emerged as a promising technique to enhance the viability of marginal liver grafts. This study aims to present the clinical outcomes of a series of 100 liver grafts subjected to this advanced preservation methods. Patients / Materials and Methods: A prospective analysis between October 2022 and May 2024 was conducted on 100 consecutive liver perfusion cases involving hypothermic perfusion with an ECMO device, followed by a subgroup comparison of regular and marginal grafts. Post-transplantation, key outcomes such as liver functionality, early complications, and overall survival were monitored in all patients. Statistical analyses included T-tests and Fisher's exact tests to evaluate differences in means and frequencies between groups. Results and Discussion: Three grafts were discarded due to severe steatosis. The patient cohort had a mean MELD Na score of 29.0 ± 8.72. The one-year survival rate was 82.7%. The major complication was infectious, observed in 57.7% of cases. The mean ICU and hospital stay was 10.98 ± 14.29 and 28.24 ± 24.78 days, respectively. Eighty-one liver grafts were categorized as regular (83.5%) and 16 as marginal (16.4%). Vascular complications were significantly more frequent in marginal grafts compared to regular grafts. No statistically significant differences in other clinical outcomes were observed between the regular and marginal graft groups (Table 1). Conclusions: The findings suggest that hypothermic perfusion using ECMO devices facilitates the safe utilization of marginal liver grafts. While the overall clinical outcomes are promising and comparable to international standards, the high incidence of infectious complications and extended ICU and hospital stays highlight significant areas for improvement. These challenges appear to be more related to the severity of the patient's conditions, as indicated by the elevated average MELD Na score, rather than the quality of the grafts. Therefore, hypothermic perfusion represents a viable strategy for expanding liver graft selection criteria in transplantation.

Conflict of interest: No Introduction and Objectives: Pts with ACLF should be assessed for liver transplant (LT) due to the high mortality without LT (28-day mortality: grade 1 = 14.6%, 2 = 32%, 3 = 78.6%). There is a survival benefit for ACLF grades 2-3 with LT (85-89% at 3-months and 70-80% at 3-years). Grade 2, and specially grade 3 ACLF pts remain a challenge for LT teams. New scoring systems (eg. SALT-M) have been developed to assist decision-making. There is limited data on this topic in Chile and Latin America. Aim: To characterize ACLF pts who underwent LT in our center between January 2020 and March 2024. Patients / Materials and Methods: Observational retrospective study. Clinical and laboratory data were collected. The cohort was divided into 3 groups based on ACLF grade. We calculated ACLF scores and assessed outcomes at 28-days and 3-months after LT. Results and Discussion: A total of 100 LT were performed between January 2020 and March 2024. 31 pts (31%) had ACLF before LT. Table 1 shows general data of ACLF LT pts. Alcohol and autoimmune were the most frequent etiologies. Infection was the most frequent extrahepatic comorbidity before and after LT (80.7% and 93.6% respectively). Length of stay (LOS) was influenced by the grade of ACLF, with grade 3 patients having the longest ICU stay (20.92 days). 28-day and 3-month survival rates were 90.3% and 87.1%, respectively. Only grade 3 ACLF LT pts showed a difference between 28-day and 3-month survival. Multi organ dysfunction syndrome (MODS) was the main reported cause of death (75%). Conclusions: Short term outcomes were consistent with national and international data. Infections were the main complication before and after LT. SALT-M score correlates with ACLF severity but would not have changed the decision to perform LT. A prolonged LOS is expected in ACLF LT pts.

Summary: Background: Post-traumatic stress disorder (PTSD) and depression are common after mild traumatic brain injury (mTBI), but their biological drivers are uncertain. We therefore explored whether polygenic risk scores (PRS) derived for PTSD and major depressive disorder (MDD) are associated with the development of cognate TBI-related phenotypes. Methods: Meta-analyses were conducted using data from two multicenter, prospective observational cohort studies of patients with mTBI: the CENTER-TBI study (ClinicalTrials.gov ID NCT02210221) in Europe (December 2014–December 2017) and the TRACK-TBI study in the US (March 2014–July 2018). In both cohorts, the most common causes of injury were road traffic accidents and falls. Primary outcomes, specifically probable PTSD and depression, were defined at 6 months post-injury using scores ≥33 on the PTSD Checklist-5 and ≥15 on the Patient Health Questionnaire-9, respectively. We calculated PTSD-PRS and MDD-PRS for patients aged ≥17 years who had a Glasgow Coma Scale score of 13–15 upon hospital arrival and assessed their association with PTSD and depression following TBI. We also evaluated the transferability of the findings in a cohort of African Americans. Findings: Overall, 11.8% (219/1869) and 6.7% (124/1869) patients were classified as having probable PTSD and depression, respectively. The PTSD-PRS was significantly associated with higher adjusted odds of PTSD in both cohorts, with a pooled odds ratio (OR) of 1.55 [95% confidence interval (CI) 1.30–1.84, p

Study region:: Ceará (Brazil). Study focus:: Considerable intra- and inter-annual variability of rainfall in this semi-arid region lead to strong temporal variations in water availability. To store and supply water in times of water scarcity, tens of thousands of freshwater reservoirs have been built over time, most of which are unmonitored. Here, we develop a hydrological forecasting system for the entire state of Ceará which integrates satellite-based monitoring of reservoir water storage, bias-corrected seasonal weather forecasts and hydrological modeling of freshwater availability. We test and demonstrate the applicability of this system by conducting experiments with historic data, hindcasts and forecasts. New hydrological insights for the region:: The assimilation of in-situ and Sentinel-1 based observations of reservoir fillings into the hydrological model WASA-SED proved to be feasible and an important step in the modeling of available water resources dynamics. Hydrological simulations for January to June from 1990–2019 based on meteorological observations resulted in a median average NRMSE between observed and modeled reservoir fillings of strategic reservoirs of 29.51%. The comparison of observed and predicted precipitation from two different seasonal forecasting systems were in the same order of magnitude (i.e. 19.51% and 24.52%). Hindcast experiments suggested the superposition of uncertainties of different model components. Efforts are currently being made to further test and improve the developed integrated framework as part of the operational service.

This study explores ways to reduce industrial waste from technological development in Indonesia. Indonesia's industrial sector's rapid growth has had positive and negative impacts on other sectors. On the positive side, industrial expansion has significantly contributed to economic growth by creating numerous jobs and facilitating the application of new technologies across various fields. However, the negative impact is evident in industrial waste, including liquid, solid, and gaseous by-products that contain harmful environmental substances. Given the detrimental effects of industrial waste, companies must implement effective waste management strategies.In this study, waste cooking oil (WCO) was neutralized using 5 % sulfuric acid up to 10 % of the sample weight. The transesterification process was conducted in a 250 mL beaker. WCO was added to the beaker, which already contained an Amberlite 62i catalyst, with the oil-to-methanol molar ratio set at 6:1. The catalyst concentration was varied at 5 %, 10 %, 15 %, and 20 % by oil weight. SEM and FT-IR analyses were performed to evaluate the reusability of the catalyst. The highest biodiesel conversion achieved was 82 % at 60 °C using 20 % catalyst, while the maximum flash point recorded was 162 °C at the same temperature and catalyst concentration.

Coffee is a vital industrial crop that generates significant economic value across the globe. The poor standard of production management from Thai entrepreneurs has caused significant issues in agricultural planning and the coffee supply chain. This research aims to design a method for measuring the performance of the coffee supply chain using axiomatic design and a business model canvas, and to create a sustainability measurement model for a hill tribe's coffee production in northern Thailand. Axiomatic design (AD) was used to help analyze and design customer requirements. In order to identify the real needs of customers, a business model canvas (BMC) was applied to develop a Thai coffee sustainability measurement model. A developed sustainability measurement model for the Thai coffee supply chain was applied to generate the design of matrices and indicators through economic, environmental, and social indicators. The results showed that the farmers’ profit from sorted cherry coffee could be increased by 77–80 %. The farmers could significantly reduce their reliance on chemical pesticides and fertilizers by up to 65–75 % in coffee plantations, and community participation increases from 60 to 70 % to 80–90 %. According to the methods and management practices described, entrepreneurs could adopt the techniques to run their businesses sustainably and achieve high production efficiency in the future.

Researchers employ many different approaches to study transitions towards more sustainable futures, of which Sustainability Transitions Research and Social Practice Theory are often used. These approaches offer complementary concepts that are helpful to analyse, explain, forecast, and drive sustainability transitions, e.g. heuristics on changing institutions (Sustainability Transitions Research) or dynamics to change behaviour through practice development (Social Practice Theory). However, despite first attempts, it remains unclear how the approaches can be used together. Therefore, the aim of this paper is to expose crossover frameworks in which these approaches are used together, elaborating on conditions that make this possible, and the strengths and weaknesses of specific crossover frameworks. A systematic literature review has been conducted, investigating the potentials and the limitations for crossovers between Social Practice Theory and Sustainability Transitions Research by analysing the approaches according to the different ontologies and theories and then analysing frameworks that have been created so far. This research elaborates on six crossover frameworks that have been created that all have diverse strengths, such as the ability to conceptualize early transitional changes or finding points of resistance in transitions. All the found crossover frameworks made use of either the multilevel perspective or transition management. Other frameworks of transition research have not been found. This research shows that there has been surprisingly little research to crossover frameworks that incorporate an element of time. The exposition following from this study is interesting for researchers and policymakers working on sustainability transitions and sets an agenda for further framework development.

Exploring non-coding regions is increasingly gaining importance in the diagnosis of inherited retinal dystrophies. Deep-intronic variants causing aberrant splicing have been identified, prompting the development of antisense oligonucleotides (ASOs) to modulate splicing. We performed a screening of five previously described USH2A deep-intronic variants among USH2A monoallelic patients with Usher syndrome (USH) or isolated retinitis pigmentosa. Sequencing of entire USH2A or USH genes was then conducted in unresolved or newly monoallelic cases. The splicing impact of identified variants was assessed using minigene assays, and ASOs were designed to correct splicing. The screening allowed to diagnose 30.95% of the studied patients. The sequencing of USH genes revealed 16 new variants predicted to affect splicing, with four confirmed to affect splicing through minigene assays. Two of them were unreported deep-intronic variants and predicted to include a pseudoexon in the pre-mRNA, and the other two could alter a regulatory cis-element. ASOs designed for three USH2A deep-intronic variants successfully redirected splicing in vitro. Our study demonstrates the improvement in genetic characterization of IRDs when analyzing non-coding regions, highlighting that deep-intronic variants significantly contribute to USH2A pathogenicity. Furthermore, successful splicing modulation through ASOs highlights their therapeutic potential for patients carrying deep-intronic variants.

Introduction: The primary aim was to describe the outcome, the compliance with inclusion criteria and the characteristics of patients who underwent extracorporeal cardiopulmonary resuscitation (ECPR) for out-of-hospital cardiac arrest (OHCA). The secondary aim was to calculate the cost of ECPR for the patients and the public Belgian healthcare system. Methods: Single-centre retrospective cohort study in Antwerp University Hospital. We included all patients who underwent ECPR for OHCA from 2018 to 2020. Medical records were assessed to determine the clinical outcome and invoices were assessed to calculate the charged fees. We collected all relevant cost components at the most detailed level (micro costing technique). Results: Sixty-five patients who received ECPR for OHCA were included. Thirty-eight patients (58%) died within one week after ECPR initiation. After one year, twelve patients (18.5%) were still alive of which ten (15.4%) had a good neurological outcome (Cerebral Performance Category (CPC) 1 or 2). Forty-nine patients (75.4%) met the ECPR inclusion criteria. A total of 2,552,498.34 euro was charged. The patients and the public Belgian healthcare system contributed to a 255,250 euro cost for each survivor after one year with good neurological outcome. Conclusion: Our analysis highlights the complex interplay between clinical efficacy and financial implications in the utilization of ECPR. While ECPR demonstrates potential in improving survival rates and neurological outcomes among cardiac arrest patients, its adoption presents substantial economic challenges. Inappropriate patient selection may lead to significant increases in resource utilisation without improved outcome.

The COVID-19 pandemic presented the greatest challenge to modern intensive care medicine since its founding as a specialty in 1952, with its effects felt across health care services in all regions, including low-resourced settings. A paucity of data remains regarding the provision of intensive care medicine across the globe, particularly after the COVID-19 pandemic. To determine the broad state of critical care medicine after the pandemic in the Asia-Pacific region, the inaugural Asia-Pacific Critical Care Societies Summit was held in Singapore as a satellite meeting of the Asia-Pacific Intensive Care Symposium on August 18, 2023. This article summarizes this summit and provides key health and economic data for representative countries before detailing the resolutions and planned actions arising from this initiative. Fourteen critical care societies participated in the inaugural summit and consented to publication of societal reports. Common challenges and priorities for participating societies included issues around education and training, specialty and workforce advocacy, and collaboration and research. As a result of this summit, societies resolved to establish an Asia-Pacific education forum, to encourage the development of Asia-Pacific critical care trials, and to support engagement in multinational studies. A second Asia-Pacific Critical Care Societies Summit will be convened in 2024, with a focus on safety and quality challenges within ICUs represented by the societies present and discussion of the listed priority areas.

The growing threat of viral infections requires innovative therapeutic approaches to safeguard human health. Nanomaterials emerge as a promising solution to overcome the limitations associated with conventional therapies. The eco-friendly synthesis of silver nanoparticles (AgNPs) currently represents a method that guarantees antimicrobial efficacy, safety, and cost-effectiveness. This study explores the use of AgNPs derived from the peel (Lp-AgNPs) and juice (Lj-AgNPs) Citrus limon “Ovale di Sorrento”, cultivars of the Campania region. The antiviral potential was tested against viruses belonging to the Coronaviridae and Herpesviridae. AgNPs were synthesized by reduction method using silver nitrate solution mixed with aqueous extract of C. limon peel and juice. The formation of Lp-AgNPs and Lj-AgNPs was assessed using a UV–Vis spectrophotometer. The size, ζ-potential, concentration, and morphology of AgNPs were evaluated by dynamic light scattering (DLS), nanoparticle tracking analysis (NTA), and field emission-scanning electron microscopy (FE-SEM). Cytotoxicity was evaluated in a concentration range between 500 and 7.8 µg/mL on VERO-76 and HaCaT cells, with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium test bromide (MTT). Antiviral activity consisted of virus pre-treatment, co-treatment, cellular pre-treatment, and post-infection tests versus HSV-1 and SARS-CoV-2 at a multiplicity of infections (MOI) of 0.01. Plaque reduction assays and real-time PCR provided data on the antiviral potential of tested compounds. Lp-AgNPs and Lj-AgNPs exhibited spherical morphology with respective diameters of 60 and 92 nm with concentrations of 4.22 and 4.84 × 1010 particles/mL, respectively. The MTT data demonstrated minimal cytotoxicity, with 50 % cytotoxic concentrations (CC50) of Lp-AgNPs and Lj-AgNPs against VERO cells of 754.6 and 486.7 µg/mL. Similarly, CC50 values against HaCaT were 457.3 µg/mL for Lp-AgNPs and 339.6 µg/mL for Lj-AgNPs, respectively. In the virus pre-treatment assay, 90 % inhibitory concentrations of HSV-1 and SARS-CoV-2 were 8.54–135.04 µg/mL for Lp-AgNPs and 6.13–186.77 µg/mL for Lj-AgNPs, respectively. The molecular investigation confirmed the antiviral data, recording a reduction in the UL54 and UL27 genes for HSV-1 and in the Spike (S) gene for SARS-CoV-2, following AgNP exposure. The results of this study suggest that Lp-AgNPs and Lj-AgNPs derived from C. Limon could offer a valid ecological, natural, local and safe strategy against viral infections.

Background: Successful catheter ablation of ventricular tachycardia (VT) in repaired tetralogy of Fallot (TOF) can be achieved by targeting 1 or more anatomical isthmuses. However, significant interindividual variability in the size and location of surgical patches means careful mapping is required to design ablation lines to block the isthmus. Intracardiac echocardiography (ICE) may assist ablation by accurate identification of individual TOF anatomy. Objectives: The authors hypothesized ICE-guided VT ablation improved isthmus recognition, ablation, and procedural outcomes. Methods: Retrospective study of adults with repaired TOF undergoing VT ablation between January 1, 2017 and December 31, 2022. ICE integration was compared to a strategy using electroanatomical mapping only to identify anatomic boundaries. All cases underwent ablation and had proven isthmus block as the procedural endpoint. Results: Twenty-three patients (age 47 ± 14 years; 61% male) underwent 27 VT ablations (ICE: 16/27 [59%]; no ICE: 11/27 [41%]). ICE improved the ability to localize and ablate the anatomical isthmus (ICE: 13/15 [87%] vs no ICE: 4/11 [36%]; P = 0.014); however, there was no difference in long-term freedom from VT (ICE: 9/12 [75%] vs no ICE: 8/11 [73%]; P = 0.901). ICE had no impact on procedural times (ICE: 173 ± 48 minutes vs no ICE: 157 ± 47 minutes; P = 0.399), fluoroscopy time (ICE: 30 ± 16 minutes vs no ICE: 29 ± 10 minutes; P = 0.864), or major complications (ICE: 1/16 [6%] vs no ICE 0/11; P = 1.000). Conclusions: ICE improves ablation of the anatomical isthmus for sustaining VT in patients with repaired TOF by demonstrating the individual anatomy but does not improve long-term outcomes.

This study examines the effect of road infrastructure and regional finance on regional economic growth in the recently designated capital city of Indonesia. The empirical data employed in this study originates from ten regencies/cities in East Kalimantan and has been observed from 2013 to 2022. This investigation utilises a moderated mediation model. The analysis tool employs the structural equation partial least squares (PLS) approach, utilising the Warp 8.0 software. Regional finance acts as a full mediator between road infrastructure and regional economic growth. The moderating effect of road infrastructure on this relationship is −0.434, indicating that it significantly reduces the influence of regional finance on regional economic growth. Furthermore, the study identified a threshold between the impact of regional finance on economic growth, which is depicted in the S curve. This study contributes to the existing literature on endogenous economic growth.

Summary: Background: Early host immunity to acute respiratory infections (ARIs) is heterogenous, dynamic, and critical to an individual's infection outcome. Due to limitations in sampling frequency/timepoints, kinetics of early immune dynamics in natural human infections remain poorly understood. In this nationwide prospective cohort study, we leveraged a Tasso-SST based self-blood collection and stabilization tool (homeRNA) to profile detailed kinetics of the presymptomatic to convalescence host immunity to contemporaneous respiratory pathogens. Methods: We enrolled non-symptomatic adults with recent exposure to ARIs who subsequently tested negative (exposed-uninfected) or positive for respiratory pathogens. Participants self-collected blood and nasal swabs daily for seven consecutive days followed by weekly blood collection for up to seven additional weeks. Symptom burden was assessed during each collection. Nasal swabs were tested for SARS-CoV-2 and common respiratory pathogens. 92 longitudinal blood samples spanning the presymptomatic to convalescence phase of eight participants with SARS-CoV-2 infection and 40 interval-matched samples from four exposed-uninfected participants were subjected to high-frequency longitudinal profiling of 785 immune genes. Generalized additive mixed models (GAMM) were used to identify temporally dynamic genes from the longitudinal samples and linear mixed models (LMM) were used to identify baseline differences between exposed-infected (n = 8), exposed-uninfected (n = 4), and uninfected (n = 13) participant groups. Findings: Between June 2021 and April 2022, 68 participants across 26 U.S. states completed the study and self-collected a total of 691 and 466 longitudinal blood and nasal swab samples along with 688 symptom surveys. SARS-CoV-2 was detected in 17 out of 22 individuals with study-confirmed respiratory infection, of which five were still presymptomatic or pre-shedding, enabling us to profile detailed expression kinetics of the earliest blood transcriptional response to contemporaneous variants of concern. 51% of the genes assessed were found to be temporally dynamic during COVID-19 infection. During the pre-shedding phase, a robust but transient response consisting of genes involved in cell migration, stress response, and T cell activation were observed. This is followed by a rapid induction of many interferon-stimulated genes (ISGs), concurrent to onset of viral shedding and increase in nasal viral load and symptom burden. Finally, elevated baseline expression of antimicrobial peptides was observed in exposed-uninfected individuals. Interpretation: We demonstrated that unsupervised self-collection and stabilization of capillary blood can be applied to natural infection studies to characterize detailed early host immune kinetics at a temporal resolution comparable to that of human challenge studies. The remote (decentralized) study framework enables conduct of large-scale population-wide longitudinal mechanistic studies. Funding: This study was funded by R35GM128648 to ABT for in-lab developments of homeRNA and data analysis, a Packard Fellowship for Science and Engineering from the David and Lucile Packard Foundation to ABT for the study execution, sample collection, and analysis, and R01AI153087 to AW for data analysis.

Background: The ethnomedicinal uses of Picralima nitida is partly due to its antidiabetic properties. Purpose: In this study, the antioxidant and total reducing power, as well as the carbohydrate hydrolysing enzymes’ inhibition potentials of the root, leaf, and seed of P. nitida were compared. Methods: The antioxidant reducing power of P. nitida as well as its ability to inhibit selected enzymes of carbohydrate hydrolysis were evaluated using standard experimental methods. Results: Methanol extract of P. nitida leaves exhibited the strongest reducing power (653.52 mgASC/g) followed by the seed extract (620.11 mgASC/g). The free radical scavenging powers of the extracts were concentration dependent. P. nitida seed extract exhibited the highest scavenging ability (IC50 = 190.7 µg/ml) as compared to the root extract (IC50 = 470.40 µg/ml) and leaf extract (IC50 = 560.65 µg/ml). However, the seed extract had the highest ABTS radical scavenging ability (IC50 = 174.02 ± 0.75 µg/ml) in comparison with the root extract (IC50 = 181.83 ± 1.01 µg/ml) and leaf extract (IC50 = 279.87 ± 1.39 µg/ml). Alpha-amylase and alpha-glucosidase inhibitory properties of the extracts increased steadily with increasing concentration, as that of glibenclamide. The methanolic extract of P. nitida seed had the highest inhibitory activity (95.70 %) as compared to that of the root (92.39 %) and leaf (83.58 %) extracts. Conclusion: P. nitida show strong reducing as well as enzyme inhibitory properties which are concentration dependent and compares favourably with glibenclamide. Comparatively, the methanolic extract of the leaf of P. nitida exhibited the highest reducing power and inhibition of α-amylase, while the methanolic seed extract exhibited the highest ability to fight free radicals and inhibit the activity of α-glucosidase.

This systematic review considered evidence of children’s and adolescents' typical brain connectivity development studied through resting-state functional magnetic resonance imaging (rs-fMRI). With aim of understanding the state of the art, what has been researched thus far and what remains unknown, this paper reviews 58 studies from 2013 to 2023. Considering the results, rs-fMRI stands out as an appropriate technique for studying language and attention within cognitive domains, and personality traits such as impulsivity and empathy. The most used analyses encompass seed-based, independent component analysis (ICA), the amplitude of the low frequency fluctuations (ALFF), and fractional ALFF (fALFF). The findings highlight key themes, including age-related changes in intrinsic connectivity, sex-specific patterns, and the relevance of the Default Mode Network (DMN). Overall, there is a need for longitudinal approaches to trace the typical developmental trajectory of neural networks from childhood through adolescence with fMRI at rest.

Summary: Background: Traumatic brain injury is conventionally categorised as mild, moderate, or severe on the Glasgow Coma Scale (GCS). Recently developed biomarkers can provide more objective and nuanced measures of the extent of brain injury. Methods: Exposure–response relationships were investigated in 2479 patients aged ≥16 enrolled in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) prospective observational cohort study. Neurofilament protein-light (NFL), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), and glial fibrillary acidic protein (GFAP) were assayed from serum sampled in the first 24 h; concentrations were divided into quintiles within GCS severity groups. Relationships with the Glasgow Outcome Scale-Extended were examined using modified Poisson regression including age, sex, major extracranial injury, time to sample, and log biomarker concentration as covariates. Findings: Within severity groups there were associations between biomarkers and outcomes after adjustment for covariates: GCS 13–15 and negative CT imaging (relative risks [RRs] from 1.28 to 3.72), GCS 13–15 and positive CT (1.21–2.81), GCS 9–12 (1.16–2.02), GCS 3–8 (1.09–1.94). RRs were associated with clinically important differences in expectations of prognosis. In patients with GCS 3 (RRs 1.51–1.80) percentages of unfavourable outcome were 37–51% in the lowest quintiles of biomarker levels and reached 90–94% in the highest quintiles. Similarly, for GCS 15 (RRs 1.83–3.79), the percentages were 2–4% and 19–28% in the lowest and highest biomarker quintiles, respectively. Interpretation: Conventional TBI severity classification is inadequate and underestimates heterogeneity of brain injury and associated outcomes. The adoption of circulating biomarkers can add to clinical assessment of injury severity. Funding: European Union 7th Framework program (EC grant 602150), Hannelore Kohl Stiftung, One Mind, Integra LifeSciences, Neuro-Trauma Sciences, NIHR Rosetrees Trust.

Achieving full-spectrum lighting is a major challenge for phosphor-converted light-emitting diodes (pc-LEDs), which are crucial for solid-state lighting. This study presents the synthesis of polycrystalline Eu-doped Y3Al5O12 (YAG) phosphors through a sol-gel method and flame synthesis process, leading to XRD amorphous microspheres. The amorphous nature of the microspheres allows the reduction of Eu3+ to Eu2+ at a significantly lower temperature (800 °C) than the reduction of crystalline samples described in the literature (1400 °C). The presence of Eu2+ in the YAG lattice was confirmed by X-ray photoelectron spectroscopy (XPS). The X-ray diffraction (XRD) of samples annealed in reducing atmosphere confirmed partial crystallization of pure YAG in all examined samples. The Eu-doped YAG phosphor embedded in residual glass microspheres exhibited a broadband emission spectrum over the wavelength range 450–800 nm peaking at 565 nm, corresponding to the 4f65d1→ 4f7 electron transition within the Eu2+ ions.

We will present exact solutions for three variations of the stochastic Korteweg de Vries–Burgers (KdV–Burgers) equation featuring variable coefficients. In each variant, white noise exhibits spatial uniformity, and the three categories include additive, multiplicative, and advection noise. Across all cases, the coefficients are time-dependent functions. Our discovery indicates that solving certain deterministic counterparts of KdV–Burgers equations and composing the solution with a solution of stochastic differential equations leads to the exact solution of the stochastic Korteweg de Vries–Burgers (KdV–Burgers) equations.

Spinocerebellar Ataxia Type 7 (SCA7) is an autosomal dominantly inherited disorder, primarily characterized by cerebellar ataxia and visual loss. SCA7 is caused by a CAG repeat expansion in exon 3 of the ATXN7 gene. We generated human induced pluripotent stem cells (hiPSCs) from peripheral blood-derived erythroblasts from two SCA7 patients (LUMCi051-A,B and LUMCi052-A,B,C) using integration-free episomal vectors. All hiPSC clones express pluripotency factors, show a normal karyotype, and can differentiate into the three germ layers. These lines can be used for in vitro disease modeling and therapy testing.

One of the most striking attacks on a commercial passenger airliner was the bombing of Pan Am Flight 103 (PA103) on 21 December 1988. Shortly after departure, the Boeing 747 “Clipper Maid of the Seas” broke apart over the Scottish town of Lockerbie. All 259 passengers and crew were killed, along with 11 residents of Lockerbie. The bombing of flight PA103 is still subject to controversy. The origin of a crucial piece of evidence, a fragment of circuit board, is highly questioned. One of the reasons for this ongoing controversy is probably that circumstantial evidence, that led to the conviction of a Libyan, is not supported by other evidence. Almost nothing is published in the forensic literature regarding the survivability of components that make up an improvised explosive device (IED). To gain insight into the survivability of IED components, suitcases, their contents, and luggage containers, a series of controlled experiments were carried out in which suitcase bombs, positioned in different configurations in aluminium LD3 luggage containers, were detonated. From the results, it could be seen that the major part of the suitcases, their contents and the LD3 containers survived the explosion. Also, almost all components of the IED itself survived the explosion to a greater or lesser extent.

The paper presents both non-destructive and destructive experimental tests on steel-reinforced concrete beams subjected to electrochemical corrosion. To examine the condition and behavior of the specimens, destructive tests were carried out, i.e., a three-point bending together with a modulated ultrasonic wave test. In addition, a series of non-destructive experiments were conducted, such as the potential measurement method, low-frequency vibrations, and ultrasonic wave propagation. A three-point bending test was conducted to examine the behavior of specimens under applied quasi-static force, together with a modulated ultrasonic wave test. The force-displacement relation, capacity, failure displacement, flexural stiffness, and failure mode were determined for each specimen. A modulated ultrasonic wave test was also performed during the flexural test. Prior to this, the specimens were visually inspected to check if any cracks occurred and a series of non-destructive tests such as potential measurement, low-frequency vibrations, and ultrasonic wave propagation were then performed.

Arboviruses such as West Nile Virus (WNV) and Usutu Virus (USUV) are emerging pathogens that circulate between mosquitoes and birds, occasionally spilling over into humans and horses. Current serological screening methods require access to a well-equipped laboratory and are not currently available for on-site analysis. As a proof of concept, we propose here a species-independent lateral flow microarray immunoassay (LMIA) able to quickly detect and distinguish between WNV Non-Structural 1 (NS1) and USUV NS1-specific antibodies. A double antigen approach was used to test sera collected from humans, horses, European jackdaws (Corvus monedula), and common blackbirds (Turdus merula). Optimization of the concentration of capture antigen spotted on the LMIA membrane and the amount of detection antigen conjugated to detector particles indicated that maximizing both parameters increased assay sensitivity. Upon screening of a larger serum panel, the optimized LMIA showed significantly higher spot intensity for a homologous binding event. Using a Receiver Operating Characteristics (ROC) curve, WNV NS1 LMIA results in humans, horses, and C. monedula showed good correlation when compared to “gold standard” WNV FRNT90. The most optimal derived sensitivity and specificity of the WNV NS1 LMIA relative to corresponding WNV FRNT90-confirmed sera were determined to be 96% and 86%, respectively. While further optimization is required, this study demonstrates the feasibility of developing a species-independent LMIA for on-site analysis of WNV, USUV, and other arboviruses. Such a tool would be useful for the on-site screening and monitoring of relevant species in more remote or low-income regions.

Research evidence indicating common metabolic mechanisms through which type 2 diabetes mellitus (T2DM) increases risk of late-onset Alzheimer's dementia (LOAD) has accumulated over recent decades. The aim of this systematic review is to provide a comprehensive review of common mechanisms, which have hitherto been discussed in separate perspectives, and to assemble and evaluate candidate loci and epigenetic modifications contributing to polygenic risk linkages between T2DM and LOAD. For the systematic review on pathophysiological mechanisms, both human and animal studies up to December 2023 are included. For the qualitative meta-analysis of genomic bases, human association studies were examined; for epigenetic mechanisms, data from human studies and animal models were accepted. Papers describing pathophysiological studies were identified in databases, and further literature gathered from cited work. For genomic and epigenomic studies, literature mining was conducted by formalised search codes using Boolean operators in search engines, and augmented by GeneRif citations in Entrez Gene, and other sources (WikiGenes, etc.). For the systematic review of pathophysiological mechanisms, 923 publications were evaluated, and 138 gene loci extracted for testing candidate risk linkages. 3 57 publications were evaluated for genomic association and descriptions of epigenomic modifications. Overall accumulated results highlight insulin signalling, inflammation and inflammasome pathways, proteolysis, gluconeogenesis and glycolysis, glycosylation, lipoprotein metabolism and oxidation, cell cycle regulation or survival, autophagic-lysosomal pathways, and energy. Documented findings suggest interplay between brain insulin resistance, neuroinflammation, insult compensatory mechanisms, and peripheral metabolic dysregulation in T2DM and LOAD linkage. The results allow for more streamlined longitudinal studies of T2DM-LOAD risk linkages.

Seaweeds are a valuable component of marine biodiversity that play multiple essential roles in Indonesia's coastal ecology and economy. This systematic review (1993–2023) aimed to provide an updated overview of seaweed distribution, biodiversity, cultivation, and industry in Indonesia. The literature search derived from major databases, Scopus, Web of Science (WoS) and ResearchGate (RG), and Google Scholar (GS) retrieved 794 studies, after removing 80 duplicates, identified 646 studies passed title and abstract screening that satisfied all criteria: Indonesia, seaweed, seaweed biodiversity and composition, which consisted of 80 exclusion studies. Full text screening decided 194 studies were selected based on the specific inclusion criteria (at least two criteria passed: seaweed distribution site, species, cultivation, and habitat). After additional filtering, 137 studies were included for extraction and analysis. We found that Indonesia is rich in seaweed biodiversity, with at least 325 identified species consisting of 103 Chlorophyceae (green algae), 167 Rhodophyceae (red algae), and 55 Phaeophyceae (brown algae), respectively. Seaweed distribution and abundance in Indonesia are influenced by environmental factors, including nutrients, grazing, competition, physical tolerance, light intensity, and degree of water circulation. Seaweed species are predominantly found in mangrove forests and coral reefs on the islands of Sumatra, Java, Kalimantan, and Sulawesi. This review provides an up-to-date and comprehensive overview of the distribution and biodiversity of seaweeds in Indonesia, highlighting the ecological, economic, and cultivation of marine resources. In addition, we identify knowledge gaps and areas for further research, which can inform sustainable seaweed management and utilization in Indonesia. This review also emphasizes the significance of this marine resource to Indonesia's environment and economy.

Background: Cannabis use has increased in Canada and can be associated with adverse cardiovascular events. Given increased use and accessibility to cannabis, there is a need among clinicians to better understand cannabis use in adults with congenital heart disease. Methods: A cross-sectional survey (May to September 2018) was used to investigate cannabis use among 252 patients with adult congenital heart disease in a quaternary care centre. Results: Of the 252 patients, 53 (21%) reported using cannabis. The majority of cannabis users were men (62%), between the ages of 25 and 39 years (mean age = 32 ± 16 years), and more likely to use tobacco (n = 9, 17%; P = 0.001) and alcohol (n = 37, 60%; P = 0.001). Significant differences (P = 0.011) were found between the age of onset for tobacco use among cannabis users (mean age: 16 ± 8 years) and non-cannabis users (mean age: 20 ± 3 years). Users reported consuming cannabis for recreational purposes (n = 29, 55%), anxiety (n = 22, 42%), depression (n = 15, 28%), and pain management (n = 4, 8%). Conclusions: This study supports our clinical experience that a high proportion of patients with adult congenital heart disease use cannabis. Cannabis users represent a patient population who may demonstrate less optimal health behaviours, including tobacco and alcohol use. Assessment of cannabis use should be an integral part of risk behaviour and cardiovascular risk profile at each clinic visit. Given the current legalization of cannabis in Canada and the growing increase of cannabis use, educational support should be provided to patients and caregivers. Résumé: Contexte: La consommation de cannabis, en hausse au Canada, a été associée à des manifestations cardiovasculaires indésirables. Puisque l’usage et la disponibilité du cannabis ont augmenté, il est nécessaire pour les cliniciens de mieux comprendre cet usage chez les adultes qui présentent une cardiopathie congénitale. Méthodologie: Nous avons mené une enquête transversale (mai à septembre 2018) sur l’usage du cannabis auprès de 252 adultes atteints d’une cardiopathie congénitale dans un centre de soins quaternaires. Résultats: Cinquante-trois patients sur 252 (21 %) ont indiqué consommer du cannabis. Les utilisateurs de cannabis étaient en majorité des hommes (62 %), ils étaient âgés de 25 à 39 ans (âge moyen de 32 ans ± 16), et ils étaient plus susceptibles de consommer du tabac (n = 9; 17 %; p = 0,001) et de l’alcool (n = 37; 60 %; p = 0,001). Une différence significative a été notée entre l’âge au moment de commencer l’usage de tabac chez les utilisateurs de cannabis (âge moyen de 16 ± 8 ans) et chez les non-utilisateurs (âge moyen de 20 ± 3 ans). Les personnes consommaient du cannabis pour un usage récréatif (n = 29; 55 %), ou pour la prise en charge de l’anxiété (n = 22; 42 %), de la dépression (n = 15; 28 %) ou de la douleur (n = 4; 8 %). Conclusion: Notre étude corrobore notre expérience clinique, selon laquelle une proportion importante des adultes atteints d’une cardiopathie congénitale consomment du cannabis. Les patients qui font usage de cannabis constituent une population qui pourrait adopter des comportements moins favorables pour la santé, comme la consommation d’alcool et de produits de tabac. Une évaluation de l’usage de cannabis devrait faire partie intégrante du profil de comportements à risque et du risque cardiovasculaire réalisé à chacune des visites des patients. Étant donné la légalisation du cannabis au Canada et l’augmentation constante de son usage, un soutien éducatif devrait être offert aux patients et à leurs proches.

Mass closure with a continuous suture using large bite stitching technique has been widely accepted for midline laparotomy wound closures. However, emerging evidence suggests the use of small bite technique to reduce rates of incisional ventral hernia, surgical site infection (SSI) and burst abdomen. This meta-analysis aims to compare small versus large bite stitching techniques to assess complication rates in midline laparotomy wound closures. A comprehensive multi-database search (OVID EBM Reviews, OVID Medline, EMBASE, Scopus) was conducted from database inception to 11th October 2021 according to PRISMA guidelines. We included studies comparing post-operative complication rates of small bite versus large bite stitching techniques for midline laparotomy wound closure. Extracted data was pooled for meta-analysis evaluating rates of incisional ventral hernia, SSI and burst abdomen. We included five randomized controlled trials (RCT) in the meta-analysis and three prospective cohort studies for qualitative analysis. A total of 1977 participants composed of 961 small bite and 1016 large bite technique patients were included from the five RCTs. There was a significant reduction in the rates of incisional ventral hernia and SSI with the small bite stitch technique with odds ratios (OR) of 0.39 (95% CI [0.21–0.71]) and 0.68 (95% CI [0.51–0.91]) respectively, and a trend in favour of reduced incidence of burst abdomen with OR of 0.60 (95% CI [0.15–2.48]). Small bite stitch technique in midline laparotomy wound closure may be superior over conventional mass closure using the large bite stitch technique, with statistically significant lower rates of incisional ventral hernia and SSI.

Purpose: Gain of chromosome 8q has been associated with poor prognosis in uveal melanoma (UM), and an increase in the absolute number of 8q-copies correlated with an even shorter survival. Splicing factor 3b subunit 1 (SF3B1)-mutated (SF3B1MUT) tumors display structural chromosomal anomalies and frequently show a partial gain of chromosome 8qter. A recent subset of SF3B1MUT UM with early-onset metastases has been identified, prompting the investigation of the relationship between survival, 8q gain, and SF3B1MUT UM. Design: Retrospective cohort study. Subjects: Patients diagnosed with UM who underwent enucleation or received a biopsy at the Erasmus MC Cancer Institute or the Rotterdam Eye Hospital, The Netherlands were included. Methods: Fifty-nine patients with SF3B1MUT tumors and 211 patients with BRCA1 associated protein 1 (BAP1)-mutated (BAP1MUT) tumors were included in this study. Copy number status and gene expression were assessed using either a single nucleotide polymorphism array, fluorescence in situ hybridization, and karyotyping, or a combination of these techniques. Disease-free survival was determined and a cut-off of 60 months was used to define early-onset metastatic disease. Main Outcome Measures: Disease-free survival. Results: Forty-eight patients with SF3B1MUT UM (81%) had chromosome 8q gain (3 copies, 78%; 4 copies, 22%). Kaplan–Meier analysis of SF3B1MUT UM did not indicate a difference in survival in patients with or without gain of 8q (P = 0.99). Furthermore, the number of 8q copies was not associated with survival when comparing early (P = 0.97) versus late (P = 0.23) metastases group. In contrast, the presence of 8q gain (86%) was correlated with a decreased survival in BAP1MUT UM (P = 0.013). Conclusions: We did not find a correlation between 8q gain and early-onset metastasis in SF3B1MUT tumors. Gain of 8q has no additional predictive value in SF3B1MUT tumors. In contrast, 8q gain is predictive of a worse prognosis in patients with BAP1MUT tumors. Thus, gain of chromosome 8q has additional predictive value for BAP1MUT tumors, but not for SF3B1MUT tumors. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Purpose: Technological progress of machine learning and natural language processing has led to the development of large language models (LLMs), capable of producing well-formed text responses and providing natural language access to knowledge. Modern conversational LLMs such as ChatGPT have shown remarkable capabilities across a variety of fields, including medicine. These models may assess even highly specialized medical knowledge within specific disciplines, such as radiation therapy. We conducted an exploratory study to examine the capabilities of ChatGPT to answer questions in radiation therapy. Methods and Materials: A set of multiple-choice questions about clinical, physics, and biology general knowledge in radiation oncology as well as a set of open-ended questions were created. These were given as prompts to the LLM ChatGPT, and the answers were collected and analyzed. For the multiple-choice questions, it was checked how many of the answers of the model could be clearly assigned to one of the allowed multiple-choice-answers, and the proportion of correct answers was determined. For the open-ended questions, independent blinded radiation oncologists evaluated the quality of the answers regarding correctness and usefulness on a 5-point Likert scale. Furthermore, the evaluators were asked to provide suggestions for improving the quality of the answers. Results: For 70 multiple-choice questions, ChatGPT gave valid answers in 66 cases (94.3%). In 60.61% of the valid answers, the selected answer was correct (50.0% of clinical questions, 78.6% of physics questions, and 58.3% of biology questions). For 25 open-ended questions, 12 answers of ChatGPT were considered as “acceptable,” “good,” or “very good” regarding both correctness and helpfulness by all 6 participating radiation oncologists. Overall, the answers were considered “very good” in 29.3% and 28%, “good” in 28% and 29.3%, “acceptable” in 19.3% and 19.3%, “bad” in 9.3% and 9.3%, and “very bad” in 14% and 14% regarding correctness/helpfulness. Conclusions: Modern conversational LLMs such as ChatGPT can provide satisfying answers to many relevant questions in radiation therapy. As they still fall short of consistently providing correct information, it is problematic to use them for obtaining medical information. As LLMs will further improve in the future, they are expected to have an increasing impact not only on general society, but also on clinical practice, including radiation oncology.

Summary: Background: Sleeve gastrectomy is the most performed metabolic surgical procedure worldwide. However, conflicting results offer no clear evidence about its long-term clinical comparability to Roux-en-Y gastric bypass. This study aims to determine their equivalent long-term weight loss effects. Methods: This randomised open-label controlled trial was conducted from 2012 until 2017 in two Dutch bariatric hospitals with a 5-year follow-up (last follow-up July 29th, 2022). Out of 4045 patients, 628 were eligible for metabolic surgery and were randomly assigned to sleeve gastrectomy or Roux-en-Y gastric bypass (intention-to-treat). The primary endpoint was weight loss, expressed by percentage excess body mass index (BMI) loss. The predefined clinically relevant equivalence margin was −13% to 13%. Secondary endpoints included percentage total kilograms weight loss, obesity-related comorbidities, quality of life, morbidity, and mortality. This trial is registered with Dutch Trial Register NTR4741: https://onderzoekmetmensen.nl/nl/trial/25900. Findings: 628 patients were randomised between sleeve gastrectomy (n = 312) and Roux-en-Y gastric bypass (n = 316) (mean age 43 [standard deviation (SD), 11] years; mean BMI 43.5 [SD, 4.7]; 81.8% women). Excess BMI loss at 5 years was 58.8% [95% CI, 55%–63%] after sleeve gastrectomy and 67.1% [95% CI, 63%–71%] after Roux-en-Y gastric bypass (difference 8.3% [95% CI, −12.5% to −4.0%]). This was within the predefined margin (P

Summary: Nano-vesicular carriers are promising tissue-specific drug delivery platforms. Here, biomimetic proteolipid vesicles (BPLVs) were used for delivery of glycosylphosphatidylinositol (GPI)-anchored proteins to GPI deficient paroxysmal nocturnal hemoglobinuria (PNH) cells. BPLVs were assembled as single unilamellar monodispersed (polydispersity index, 0.1) negatively charged (ζ-potential, −28.6 ± 5.6 mV) system using microfluidic technique equipped with Y-shaped chip. GPI-anchored and not-GPI proteins on BPLV surface were detected by flow cytometry. Peripheral blood mononuclear cells (PBMCs) from healthy and PNH subjects were treated with BPLVs (final concentration, 0.5 mg/mL), and cells displayed an excellent protein uptake, documented by flow cytometry immunophenotyping and confocal microscopy. BPLV-treated cells stressed with complement components showed an increased resistance to complement-mediated lysis, both healthy and PNH PBMCs. In conclusion, BPLVs could be effective nanocarriers for protein transfer to targeted cells to revert protein deficiency, like in PNH disease. However, further in vivo studies are required to validate our preclinical in vitro results.

Summary: Consumption of fructo- (FOS) and galacto-oligosaccharides (GOS) has health benefits which have been linked in part to short-chain fatty acids (SCFA) production by the gut microbiota. However, detailed knowledge of this process in the human intestine is lacking. We aimed to determine the acute fermentation kinetics of a FOS:GOS mixture in healthy males using a naso-intestinal catheter for sampling directly in the ileum or colon. We studied the fate of SCFA as substrates for glucose and lipid metabolism by the host after infusion of 13C-SCFA. In the human distal ileum, no fermentation of FOS:GOS, nor SCFA production, or bacterial cross-feeding was observed. The relative composition of intestinal microbiota changed rapidly during the test day, which demonstrates the relevance of postprandial intestinal sampling to track acute responses of the microbial community toward interventions. SCFA were vividly taken up and metabolized by the host as shown by incorporation of 13C in various host metabolites.

With increasing numbers of chemicals used in modern society, assessing human and environmental exposure to them is becoming increasingly difficult. Recent advances in wastewater-based epidemiology enable valuable insights into public exposure to data-poor compounds. However, measuring all >26,000 chemicals registered under REACH is not just technically unfeasible but would also be incredibly expensive. In this paper, we argue that estimating emissions of chemicals based on usage data could offer a more comprehensive, systematic and efficient approach than repeated monitoring. Emissions of 29 active pharmaceutical ingredients (APIs) to wastewater were estimated for a medium-sized city in the Netherlands. Usage data was collected both on national and local scale and included prescription data, usage in health-care institutions and over-the-counter sales. Different routes of administration were considered as well as the excretion and subsequent in-sewer back-transformation of conjugates into respective parent compounds. Results suggest model-based emission estimation on a city-level is feasible and in good agreement with wastewater measurements obtained via passive sampling. Results highlight the need to include excretion fractions in the conceptual framework of emission estimation but suggest that the choice of an appropriate excretion fraction has a substantial impact on the resulting model performance.

Ellenberg indicator values (EIV) are widely used in vegetation ecology, but the values for many species in Southeastern Europe are not available due to incomplete knowledge of their ecology: it is therefore of paramount importance to estimate missing values in existing databases. The entire EIV set for a single species can be missing or a single EIV can be missing for species for which other indicator values are available. Our aim here is to provide a simple method to impute missing values for species who have missing data in a single or multiple EIV. For this purpose, we adopt a multiple imputation procedure and compare a number of imputation methods on the basis of two datasets: i) “indices”, the set of 9 Ellenberg indicators taken from literature, available for 10,824 species and ii) “vegetation”, a set describing the physical and climatic characteristics (Light, Temperature, Continentality, Soil moisture, Nitrogen, Soil pH, Hemeroby index, Humidity, Organic_matter) of 29,935 relevés from Southeastern Europe where at least one tree species is present. The imputation methods we considered are: k-Nearest Neighbour, multiple linear regression (with or without collinearity correction), Reprediction Algorithm, Weighted Averaging (WA) and Weighted Averaging Partial Least Squares (WAPLS) regression. The different methods of imputation were compared by looking at the output produced and its deviation from the “true” observed values for a set of species with known EIVs. We have considered a set of species with known EIVs and proceeded to multiple imputation using the methods above; as a measure of performance we adopted the mean squared error (MSE) estimate, and expert judgement of ecological consistency. Models based on Regression and k-Nearest Neighbour seem to outperform the others. On the contrary, Reprediction algorithm in its different forms: produced less satisfactory results.Imputation of missing values is generally based on expert knowledge or on some variant of weighted averaging (also known as Hill’s method). Here we show that other methods may be more effective and should be appropriately considered by vegetation scientists, since those may allow the application of EIVs in other biogeographic regions.

Background and aims: In low endemic countries, screening for hepatitis B surface antigen (HBsAg) in migrants is cost-effective in reducing the disease burden of hepatitis B virus (HBV) infections, but linkage to care (LTC) remains a challenge. This study aims to guide future screening initiatives, with 3 objectives: 1. to compare LTC between different ethnic groups screened for HBsAg with point-of-care testing (POCT) in an outreach setting; 2. to estimate the proportion of HBsAg seropositivity for ethnic minorities; and 3. to investigate the association between seropositivity and HBV risk factors. Methods: Opportunistic outreach screenings using finger prick HBsAg tests were performed at civic integration programmes between 11/2017 and 09/2022. If an individual tested positive, an appointment was given immediately at the outpatient hepatology clinic for follow-up and confirmation of HBsAg positivity in blood. Dedicated personnel contacted these individuals to motivate them for further LTC, which was defined as being assessed by a hepatologist, a blood test and an abdominal ultrasound. Results: A total of 677 people from different ethnicities (Asian, Middle Eastern and African) were serologically screened using POCT. The observed positivity for HBsAg was 3.4 % (95% CI 2.17-5.05, 23/677). Apart from ethnicity and male sex, none of the surveyed HBV risk factors were associated with HBsAg seropositivity. All HBsAg positive individuals were linked to care and assessed by a hepatologist, despite the COVID-19 pandemic increase in time to follow-up of 82 days (95% CI 51–112 days) vs. 24 days (95% CI 5–43 days, p = 0.008)).Among HBV-infected patients, 31.8% (7/22), 100 % (22/22) and 26.1% (6/23) met the criteria for treatment indication, intrafamilial transmission risk and need for hepatocellular carcinoma surveillance, respectively. Conclusion: The proportion of HBsAg seropositivity in ethnic minorities was 3.4%. POCT and commitment of dedicated personnel can overcome previously identified barriers resulting in a 100% LTC.

In the hierarchical model of soil aggregates, small soil microaggregates (small SMA; 40 μm up to 1700 μm in maximum. Our study on aggregation in wet-dry cycles revealed that the colloidal content has a controlling effect on the size distribution of resulting aggregates by acting as a binding agent and provides hereby new insights into the evolvement of aggregate hierarchy in soils.

In vitro cellular models denote a crucial part of drug discovery programs as they aid in identifying successful drug candidates based on their initial efficacy and potency. While tremendous headway has been achieved in improving 2D and 3D culture techniques, there is still a need for physiologically relevant systems that can mimic or alter cellular responses without the addition of external biochemical stimuli. A way forward to alter cellular responses is using physical cues, like 3D topographical inorganic substrates, to differentiate macrophage-like cells. Herein, protein secretion and gene expression markers for various macrophage subsets cultivated on a 3D topographical substrate are investigated. The results show that macrophages differentiate into anti-inflammatory M2-type macrophages, secreting increased IL-10 levels compared to the controls. Remarkably, these macrophage cells are differentiated into the M2d subset, making up the main component of tumour-associated macrophages (TAMs), as measured by upregulated Il-10 and Vegf mRNA. M2d subset differentiation is attributed to the topographical substrates with 3D fractal-like geometries arrayed over the surface, else primarily achieved by tumour-associated factors in vivo. From a broad perspective, this work paves the way for implementing 3D topographical inorganic surfaces for drug discovery programs, harnessing the advantages of in vitro assays without external stimulation and allowing the rapid characterisation of therapeutic modalities in physiologically relevant environments.

The mechanism governing pharmaceutical tablet disintegration is far from fully understood. Despite the importance of controlling a formulation's disintegration process to maximize the active pharmaceutical ingredient's bioavailability and ensure predictable and consistent release profiles, the current understanding of the process is based on indirect or superficial measurements. Formulation science could, therefore, additionally deepen the understanding of the fundamental physical principles governing disintegration based on direct observations of the process. We aim to help bridge the gap by generating a series of time-resolved X-ray micro-computed tomography (μCT) images capturing volumetric images of a broad range of mini-tablet formulations undergoing disintegration. Automated image segmentation was a prerequisite to overcoming the challenges of analyzing multiple time series of heterogeneous tomographic images at high magnification. We devised and trained a convolutional neural network (CNN) based on the U-Net architecture for autonomous, rapid, and consistent image segmentation. We created our own μCT data reconstruction pipeline and parameterized it to deliver image quality optimal for our CNN-based segmentation. Our approach enabled us to visualize the internal microstructures of the tablets during disintegration and to extract parameters of disintegration kinetics from the time-resolved data. We determine by factor analysis the influence of the different formulation components on the disintegration process in terms of both qualitative and quantitative experimental responses. We relate our findings to known formulation component properties and established experimental results. Our direct imaging approach, enabled by deep learning-based image processing, delivers new insights into the disintegration mechanism of pharmaceutical tablets.

Loss-of-function mutations in USH2A are among the most common causes of syndromic and non-syndromic retinitis pigmentosa (RP). We previously presented skipping of USH2A exon 13 as a promising treatment paradigm for USH2A-associated RP. However, RP-associated mutations are often private, and evenly distributed along the USH2A gene. In order to broaden the group of patients that could benefit from therapeutic exon skipping strategies, we expanded our approach to other USH2A exons in which unique loss-of-function mutations have been reported by implementing a protein domain-oriented dual exon skipping strategy. We first generated zebrafish mutants carrying a genomic deletion of the orthologous exons of the frequently mutated human USH2A exons 30–31 or 39–40 using CRISPR-Cas9. Excision of these in-frame combinations of exons restored usherin expression in the zebrafish retina and rescued the photopigment mislocalization typically observed in ush2a mutants. To translate these findings into a future treatment in humans, we employed in vitro assays to identify and validate antisense oligonucleotides (ASOs) with a high potency for sequence-specific dual exon skipping. Together, the in vitro and in vivo data demonstrate protein domain-oriented ASO-induced dual exon skipping to be a highly promising treatment option for RP caused by mutations in USH2A.

Introduction: Treatment-limiting decisions (TLDs) can be inevitable severe traumatic brain injury (s-TBI) patients, but data on their use remain scarce. Research question: To investigate the prevalence, timing and considerations of TLDs in s-TBI patients. Material and methods: s-TBI patients between 2008 and 2017 were analysed retrospecively. Patient data, timing, location, involvement of proxies, and reasons for TLDs were collected. Baseline characteristics and in-hospital outcomes were compared between s-TBI patients with and without TLDs. Results: TLDs were reported in 117 of 270 s-TBI patients (43.3%) and 95.9% of deaths after s-TBI were preceded by a TLD. The majority of TLDs (68.4%) were categorized as withdrawal of therapy, of which withdrawal of organ-support in 64.1%. Neurosurgical intervention was withheld in 29.9%. The median time from admission to TLD was 2 days [IQR, 0–8] and 50.4% of TLDs were made within 3 days of admission. The main reason for a TLD was that the patients were perceived as unsalvageable (66.7%). Nearly all decisions were made multidisciplinary (99.1%) with proxies involvement (75.2%). The predicted mortality (CRASH-score) between patients with and without TLDs were 72.6 vs. 70.6%. The percentage of TLDs in s-TBI patients increased from 20.0% in 2008 to 42.9% in 2012 and 64.3% in 2017. Discussion and conclusion: TLDs occurred in almost half of s-TBI patients and were instituted more frequently over time. Half of TLDs were made within 3 days of admission in spite of baseline prognosis between groups being similar. Future research should address whether prognostic nihilism contributes to self-fulfilling prophecies.

Studies indicate that the amount of active travel among children is decreasing worldwide. The circumstances around travel modes and routes of children and young adolescents are less known if compared to adults’ walking or cycling. There is a growing interest in mobility patterns of children to school, especially. Active School Travel (AST) is decreasing in developed nations. This study explored which structural elements in the built environment of home and school locations influence AST of Dutch students. We used multinomial logistic regressions to study the effects of built environments on walking and cycling by students in the Netherlands. Findings about the design of environments around homes and schools suggest that variations in personal characteristics, temperature, destination proximity, traffic safety conditions, and urban form can influence AST. Safety conditions seem to play a spurious role in the relationship between built environments and AST, reflecting counterintuitive results if compared to adult travel research. Findings were mixed regarding directionality and significance levels between transport modes and variables, which highlights the importance of considering target groups, modes and locations of students and schools when planning for effective interventions. The findings can be valuable for both academia and policymakers, supporting strategies that could be adopted by municipalities and encouraged by parents or schools.

We describe the feasibility of covered endovascular reconstruction of the aortic bifurcation (CERAB) through a single femoral access and a steerable sheath. We present the technique, which we used for a patient with severe aortoiliac calcification and bilateral involvement of the common femoral artery. The patient underwent endarterectomy of the left common femoral artery plus CERAB with an aortic stent graft and bilateral covered stents for the common iliac artery with kissing dilatation with a steerable sheath using only left femoral access. CERAB can be performed using unilateral access with the aid of a steerable sheath, reducing the potential for access site complications.

A greenhouse study was conducted to characterize the drought response of eight high-yielding sugarcane varieties at tillering stage using polyethylene glycol 6000 (PEG6000) induced drought conditions. Plant height, stalk diameter, dry matter accumulation, root characteristics, stomatal conductance, chlorophyll fluorescence, SPAD, normalized difference vegetation index (NDVI), and canopy temperature were evaluated at 2.5 months after planting after four weeks of induced drought conditions. The study aimed to determine whether 1.0% PEG treatment would be able to produce significant differences among test genotypes and use it as a basis to determine drought-tolerant and susceptible varieties. Significant differences were observed among genotypes in PEG stress treatments. PEG stress resulted in significant reductions relative to non-PEG treatment in plant height (32.1%), leaf dry matter (31.6%), and stalk dry matter (49.5%) while total root length (11.8%), root surface area (7.8%) and root volume (19.6%) have generally increased. Reduced plant height, stalk diameter, and dry matter accumulation were observed in susceptible genotypes, while potential tolerant lines maintained or exhibited less reduction in these traits. Moreover, principal component analysis suggests that stalk dry matter, stomatal conductance, chlorophyll fluorescence plant height, SPAD, canopy temperature, and NDVI, highly contributed to the overall variation in the data (41.5%). With this, vars. 2289, 1011, 2569, and 1899 were identified to be potential drought-tolerant varieties while vars. 1763 and 2155 were potential drought susceptible varieties. Screening for drought tolerance under controlled conditions using PEG-induced drought stress offers a promising approach for sugarcane breeding especially when focusing on specific drought responses during important formative stages such as tillering stage. Being able to select genotypes of interest as early as the tillering stage would significantly hasten breeding cycles and will highly benefit the efforts towards drought stress tolerance in sugarcane.

Purpose: Myopia (nearsightedness) is a condition in which a refractive error (RE) affects vision. Although common variants explain part of the genetic predisposition (18%), most of the estimated 70% heritability is missing. Here, we investigate the contribution of rare genetic variation because this might explain more of the missing heritability in the more severe forms of myopia. In particular, high myopia can lead to blindness and has a tremendous impact on a patient and at the societal level. The exact molecular mechanisms behind this condition are not yet completely unraveled, but whole genome sequencing (WGS) studies have the potential to identify novel (rare) disease genes, explaining the high heritability. Design: Cross-sectional study performed in the Netherlands. Participants: We investigated 159 European patients with high myopia (RE > −10 diopters). Methods: We performed WGS using a stepwise filtering approach and burden analysis. The contribution of common variants was calculated as a genetic risk score (GRS). Main Outcome Measures: Rare variant burden, GRS. Results: In 25% (n = 40) of these patients, there was a high (> 75th percentile) contribution of common predisposing variants; that is, these participants had higher GRSs. In 7 of the remaining 119 patients (6%), deleterious variants in genes associated with known (ocular) disorders, such as retinal dystrophy disease (prominin 1 [PROM1]) or ocular development (ATP binding cassette subfamily B member 6 [ABCB6], TGFB induced factor homeobox 1 [TGIF1]), were identified. Furthermore, without using a gene panel, we identified a high burden of rare variants in 8 novel genes associated with myopia. The genes heparan sulfate 6-O-sulfotransferase 1 (HS6ST1) (proportion in study population vs. the Genome Aggregation Database (GnomAD) 0.14 vs. 0.03, P = 4.22E-17), RNA binding motif protein 20 (RBM20) (0.15 vs. 0.06, P = 4.98E-05), and MAP7 domain containing 1 (MAP7D1) (0.19 vs. 0.06, P = 1.16E-10) were involved in the Wnt signaling cascade, melatonin degradation, and ocular development and showed most biologically plausible associations. Conclusions: We found different contributions of common and rare variants in low and high grade myopia. Using WGS, we identified some interesting candidate genes that could explain the high myopia phenotype in some patients. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Purpose: To study the prevalence, level, and nature of sleep problems and fatigue experienced by Usher syndrome type 2a (USH2a) patients. Design: Cross-sectional study. Participants: Fifty-six genetically confirmed Dutch patients with syndromic USH2a and 120 healthy controls. Methods: Sleep quality, prevalence, and type of sleep disorders, chronotype, fatigue, and daytime sleepiness were assessed using 5 questionnaires: (1) Pittsburgh Sleep Quality Index, (2) Holland Sleep Disorders Questionnaire, (3) Morningness–Eveningness Questionnaire, (4) Checklist Individual Strength, and (5) Epworth Sleepiness Scale. For a subset of patients, recent data on visual function were used to study the potential correlation between the outcomes of the questionnaires and disease progression. Main Outcome Measures: Results of all questionnaires were compared between USH2a and control cohorts, and the scores of the patients were compared with disease progression defined by age, visual field size, and visual acuity. Results: Compared with the control population, patients with USH2a experienced a poorer quality of sleep, a higher incidence of sleep disorders, and higher levels of fatigue and daytime sleepiness. Intriguingly, the sleep disturbances and high levels of fatigue were not correlated with the level of visual impairment. These results are in accordance with the patients’ experiences that their sleep problems already existed before the onset of vision loss. Conclusions: This study demonstrates a high prevalence of fatigue and poor sleep quality experienced by patients with USH2a. Recognition of sleep problems as a comorbidity of Usher syndrome would be a first step toward improved patient care. The absence of a relationship between the level of visual impairment and the severity of reported sleep problems is suggestive of an extraretinal origin of the sleep disturbances. Financial Disclosure(s):: Proprietary or commercial disclosure may be found after the references.