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The utility of brewery spent grain (BSG), a byproduct of the beer production process, for the synthesis of polyhydroxyalkanoates (PHAs), is a significant advancement towards sustainable and cost-effective biopolymer production. This paper reviews the upcycling potential of BSG as a substrate for PHA production, utilizing various biotechnological approaches to convert this abundant waste material into high-value biodegradable polymers. Through a comprehensive review of recent studies, we highlight the biochemical composition of BSG and its suitability for microbial fermentation processes. This research delves into different methodologies for PHA production from BSG, including the use of mixed microbial cultures (MMCs) for the synthesis of volatile fatty acids (VFAs), a critical precursor in PHA production, and solid-state fermentation (SSF) techniques. We also examine the optimization of process parameters such as pH, temperature, and microbial concentration through the application of the Doehlert design, revealing the intricate relationships between these factors and their impact on VFA profiles and PHA yields. Additionally, this paper discusses challenges and future perspectives for enhancing the efficiency and economic viability of PHA production from BSG. By harnessing the untapped potential of BSG, this research contributes to the development of a circular economy model, emphasizing waste valorization and the creation of sustainable alternatives to conventional plastics.

We revisit, and document new facts regarding, the financialization of U.S. energy markets in 2000–2010. We show that, after controlling for macroeconomic factors and physical energy market fundamentals, the strength of energy markets’ co-movements with the U.S. stock market is positively related to the energy paper market activity of hedge funds that trade both asset classes. This relation weakens when credit risk is elevated. We find, in contrast, no link with the aggregate positions of commodity index traders in energy futures markets. Our findings have implications for the ongoing debate regarding the financialization of commodities.

Abstract To explore the diversity of scenarios in nature, animals have evolved tools to interact with different environmental conditions. Chemoreceptors are an important interface component and among them, olfactory receptors (ORs) and gustatory receptors (GRs) can be used to find food and detect healthy resources. Drosophila is a model organism in many scientific fields, in part due to the diversity of species and niches they occupy. The contrast between generalists and specialists Drosophila species provides an important model for studying the evolution of chemoreception. Here, we compare the repertoire of chemoreceptors of different species of Drosophila with that of D. incompta, a highly specialized species whose ecology is restricted to Cestrum flowers, after reporting the preferences of D. incompta to the odor of Cestrum flowers in olfactory tests. We found evidence that the chemoreceptor repertoire in D. incompta is smaller than that presented by species in the Sophophora subgenus. Similar patterns were found in other non-Sophophora species, suggesting the presence of underlying phylogenetic trends. Nevertheless, we also found autapomorphic gene losses and detected some genes that appear to be under positive selection in D. incompta, suggesting that the specific lifestyle of these flies may have shaped the evolution of individual genes in each of these gene families.

Abstract Extent of resection after surgery is one of the main prognostic factors for patients diagnosed with glioblastoma. To achieve this, accurate segmentation and classification of residual tumor from post-operative MR images is essential. The current standard method for estimating it is subject to high inter- and intra-rater variability, and an automated method for segmentation of residual tumor in early post-operative MRI could lead to a more accurate estimation of extent of resection. In this study, two state-of-the-art neural network architectures for pre-operative segmentation were trained for the task. The models were extensively validated on a multicenter dataset with nearly 1000 patients, from 12 hospitals in Europe and the United States. The best performance achieved was a 61% Dice score, and the best classification performance was about 80% balanced accuracy, with a demonstrated ability to generalize across hospitals. In addition, the segmentation performance of the best models was on par with human expert raters. The predicted segmentations can be used to accurately classify the patients into those with residual tumor, and those with gross total resection.

Abstract This study tests the generalisability of three Brain Tumor Segmentation (BraTS) challenge models using a multi-center dataset of varying image quality and incomplete MRI datasets. In this retrospective study, DeepMedic, no-new-Unet (nn-Unet), and NVIDIA-net (nv-Net) were trained and tested using manual segmentations from preoperative MRI of glioblastoma (GBM) and low-grade gliomas (LGG) from the BraTS 2021 dataset (1251 in total), in addition to 275 GBM and 205 LGG acquired clinically across 12 hospitals worldwide. Data was split into 80% training, 5% validation, and 15% internal test data. An additional external test-set of 158 GBM and 69 LGG was used to assess generalisability to other hospitals’ data. All models’ median Dice similarity coefficient (DSC) for both test sets were within, or higher than, previously reported human inter-rater agreement (range of 0.74–0.85). For both test sets, nn-Unet achieved the highest DSC (internal = 0.86, external = 0.93) and the lowest Hausdorff distances (10.07, 13.87 mm, respectively) for all tumor classes (p

Abstract Background Glioblastoma (GBM) is the most common primary, malignant brain tumour with a 5-year survival of 5%. If possible, a glioblastoma is resected and further treated with chemoradiation therapy (CRT), but resection is not feasible in about 30% of cases. Current standard of care in these cases is a biopsy followed by CRT. Magnetic resonance (MR) imaging-guided laser interstitial thermal therapy (LITT) has been suggested as a minimally invasive alternative when surgery is not feasible. However, high-quality evidence directly comparing LITT with standard of care is lacking, precluding any conclusions on (cost-)effectiveness. We therefore propose a multicenter randomized controlled study to assess the (cost-)effectiveness of MR-guided LITT as compared to current standard of care (EMITT trial). Methods and analysis The EMITT trial will be a multicenter pragmatic randomized controlled trial in the Netherlands. Seven Dutch hospitals will participate in this study. In total 238 patients will be randomized with 1:1 allocation to receive either biopsy combined with same-session MR-guided LITT therapy followed by CRT or the current standard of care being biopsy followed by CRT. The primary outcomes will be health-related quality of life (HR-QoL) (non-inferiority) using EORTC QLQ-C30 + BN20 scores at 5 months after randomization and overall survival (superiority). Secondary outcomes comprise cost-effectiveness (healthcare and societal perspective) and HR-QoL of life over an 18-month time horizon, progression free survival, tumour response, disease specific survival, longitudinal effects, effects on adjuvant treatment, ablation percentage and complication rates. Discussion The EMITT trial will be the first RCT on the effectiveness of LITT in patients with glioblastoma as compared with current standard of care. Together with the Dutch Brain Tumour Patient association, we hypothesize that LITT may improve overall survival without substantially affecting patients’ quality of life. Trial registration This trial is registered at ClinicalTrials.gov (NCT05318612).

Abstract GBM (Glioblastoma) is the most lethal CNS (Central nervous system) tumor in adults, which inevitably develops resistance to standard treatments leading to recurrence and mortality. TRIB1 is a serine/threonine pseudokinase which functions as a scaffold platform that initiates degradation of its substrates like C/EBPα through the ubiquitin proteasome system and also activates MEK and Akt signaling. We found that increased TRIB1 gene expression associated with worse overall survival of GBM patients across multiple cohorts. Importantly, overexpression of TRIB1 decreased RT/TMZ (radiation therapy/temozolomide)-induced apoptosis in patient derived GBM cell lines in vitro. TRIB1 directly bound to MEK and Akt and increased ERK and Akt phosphorylation/activation. We also found that TRIB1 protein expression was maximal during G2/M transition of cell cycle in GBM cells. Furthermore, TRIB1 bound directly to HDAC1 and p53. Importantly, mice bearing TRIB1 overexpressing tumors had worse overall survival. Collectively, these data suggest that TRIB1 induces resistance of GBM cells to RT/TMZ treatments by activating the cell proliferation and survival pathways thus providing an opportunity for developing new targeted therapeutics.

Introduction: Technical advances and the increasing role of interdisciplinary decision-making may warrant formal definitions of expertise in surgical neuro-oncology. Research question: The EANS Neuro-oncology Section felt that a survey detailing the European neurosurgical perspective on the concept of expertise in surgical neuro-oncology might be helpful. Material and methods: The EANS Neuro-oncology Section panel developed an online survey asking questions regarding criteria for expertise in neuro-oncological surgery and sent it to all individual EANS members. Results: Our questionnaire was completed by 251 respondents (consultants: 80.1%) from 42 countries. 67.7% would accept a lifetime caseload of >200 cases and 86.7% an annual caseload of >50 as evidence of neuro-oncological surgical expertise. A majority felt that surgeons who do not treat children (56.2%), do not have experience with spinal fusion (78.1%) or peripheral nerve tumors (71.7%) may still be considered experts. Majorities believed that expertise requires the use of skull-base approaches (85.8%), intraoperative monitoring (83.4%), awake craniotomies (77.3%), and neuro-endoscopy (75.5%) as well as continuing education of at least 1/year (100.0%), a research background (80.0%) and teaching activities (78.7%), and formal interdisciplinary collaborations (e.g., tumor board: 93.0%). Academic vs. non-academic affiliation, career position, years of neurosurgical experience, country of practice, and primary clinical interest had a minor influence on the respondents’ opinions. Discussion and conclusion: Opinions among neurosurgeons regarding the characteristics and features of expertise in neuro-oncology vary surprisingly little. Large majorities favoring certain thresholds and qualitative criteria suggest a consensus definition might be possible.

The vinegar fly Drosophila melanogaster is a pivotal model for invertebrate development, genetics, physiology, neuroscience, and disease. The whole family Drosophilidae, which contains over 4,400 species, offers a plethora of cases for comparative and evolutionary studies. Despite a long history of phylogenetic inference, many relationships remain unresolved among the genera, subgenera, and species groups in the Drosophilidae. To clarify these relationships, we first developed a set of new genomic markers and assembled a multilocus data set of 17 genes from 704 species of Drosophilidae. We then inferred a species tree with highly supported groups for this family. Additionally, we were able to determine the phylogenetic position of some previously unplaced species. These results establish a new framework for investigating the evolution of traits in fruit flies, as well as valuable resources for systematics.

Abstract Background The objective of this study was to evaluate the behavioral determinants associated with exclusive use of arsenic-safe water in the community-led Strong Heart Water Study (SHWS) arsenic mitigation program. Methods The SHWS is a randomized controlled trial of a community-led arsenic mitigation program designed to reduce arsenic exposure among private well users in American Indian Great Plains communities. All households received point-of-use (POU) arsenic filters installed at baseline and were followed for 2 years. Behavioral determinants selected were those targeted during the development of the SHWS program, and were assessed at baseline and follow-up. Results Among participants, exclusive use of arsenic-safe water for drinking and cooking at follow-up was associated with higher self-efficacy for accessing local resources to learn about arsenic (OR: 5.19, 95% CI: 1.48–18.21) and higher self-efficacy to resolve challenges related to arsenic in water using local resources (OR: 3.11, 95% CI: 1.11–8.71). Higher commitment to use the POU arsenic filter faucet at baseline was also a significant predictor of exclusive arsenic-safe water use for drinking (OR: 32.57, 95% CI: 1.42–746.70) and cooking (OR: 15.90, 95% CI: 1.33–189.52) at follow-up. From baseline to follow-up, the SHWS program significantly increased perceived vulnerability to arsenic exposure, self-efficacy, descriptive norms, and injunctive norms. Changing one’s arsenic filter cartridge after installation was associated with higher self-efficacy to obtain arsenic-safe water for drinking (OR: 6.22, 95% CI: 1.33–29.07) and cooking (OR: 10.65, 95% CI: 2.48–45.68) and higher perceived vulnerability of personal health effects (OR: 7.79, 95% CI: 1.17–51.98) from drinking arsenic-unsafe water. Conclusions The community-led SHWS program conducted a theory-driven approach for intervention development and evaluation that allowed for behavioral determinants to be identified that were associated with the use of arsenic safe water and changing one’s arsenic filter cartridge. These results demonstrate that theory-driven, context-specific formative research can influence behavior change interventions to reduce water arsenic exposure. The SHWS can serve as a model for the design of theory-driven intervention approaches that engage communities to reduce arsenic exposure. Trial registration The SHWS is registered with ClinicalTrials.gov (Identifier: NCT03725592).

Abstract Background Glioblastoma (GBM), the most common glial primary brain tumour, is without exception lethal. Every year approximately 600 patients are diagnosed with this heterogeneous disease in The Netherlands. Despite neurosurgery, chemo -and radiation therapy, these tumours inevitably recur. Currently, there is no gold standard at time of recurrence and treatment options are limited. Unfortunately, the results of dedicated trials with new drugs have been very disappointing. The goal of the project is to obtain the evidence for changing standard of care (SOC) procedures to include whole genome sequencing (WGS) and consequently adapt care guidelines for this specific patient group with very poor prognosis by offering optimal and timely benefit from novel therapies, even in the absence of traditional registration trials for this small volume cancer indication. Methods The GLOW study is a prospective diagnostic cohort study executed through collaboration of the Hartwig Medical Foundation (Hartwig, a non-profit organisation) and twelve Dutch centers that perform neurosurgery and/or treat GBM patients. A total of 200 patients with a first recurrence of a glioblastoma will be included. Dual primary endpoint is the percentage of patients who receive targeted therapy based on the WGS report and overall survival. Secondary endpoints include WGS report success rate and number of targeted treatments available based on WGS reports and number of patients starting a treatment in presence of an actionable variant. At recurrence, study participants will undergo SOC neurosurgical resection. Tumour material will then, together with a blood sample, be sent to Hartwig where it will be analysed by WGS. A diagnostic report with therapy guidance, including potential matching off-label drugs and available clinical trials will then be sent back to the treating physician for discussing of the results in molecular tumour boards and targeted treatment decision making. Discussion The GLOW study aims to provide the scientific evidence for changing the SOC diagnostics for patients with a recurrent glioblastoma by investigating complete genome diagnostics to maximize treatment options for this patient group. Trial registration: ClinicalTrials.gov Identifier: NCT05186064.

الأهداف: الكشف عن درجة وعي طلبة الدراسات العليا في الجامعة الأردنيّة بتقنية إنترنت الأشياء واستخداماتها في العملية التعليمية، وأثر متغيرات مستوى البرنامج وتصنيف الكلية والعُمر على درجة الوعي. المنهجية: تم استخدام المنهج الوصفي المسحي، وتوزيع استبانة على عينة طبقية عشوائية تكونت من (362) فردا من طلبة الدراسات العليا المسجلين للفصل الثاني 2021/2022. النتائج: إن الدرجة الكلية لوعي الطلبة بتقنية إنترنت الأشياء واستخداماتها في العملية التعليمية كانت متوسطة، وأنه لا توجد فــروق ذات دلالة إحصائية لتقديرات أفراد عينة الدراسة تُعزى لمتغير مستوى البرنامج. وعلى الرغم من ذلك، يوجد فــروق ذات دلالة إحصائية تُعزى لمتغير تصنيف الكلية لصالح الكليات العلمية، وتُعزى لمتغير العُمر لصالح من أعمارهم 40 عاما فأقل. الخلاصة: زيادة وعي الطلبة -وخاصة في الكليات الإنسانية وكبار السن- بخدمات تقنية إنترنت الأشياء في العملية التعليمية من خلال عقد ورش تدريبية.

ABSTRACT: The use of plant resistance acts by intervening in the herbivore-host relationship, through morphological, physical or chemical factors of the plant. This study evaluated the oviposition and foliar consumption of Chrysodeixis includens (Walker [1858]) in soybean genotypes, in free- and no-choice tests, correlating them with the factors, density and size of trichomes. The experiments were carried out in laboratory (25 ± 2 °C; RH= 70 ± 10%; photoperiod 14h) using five cultivars (BRS 391, BRS 6203 RR, BMX Valente RR, Tec Irga 6070 RR, BMX Icone Ipro) and two isolines (PELBR 10-6000 and PELBR 10-6049). The trichomes reported were filiform tectors and claviform multicellular glandular. The density of glandular trichomes, in stages V2 and V5, was higher on BRS 6203 RR and BRS 391, respectively. The higher density of glandular trichomes was observed in V5 and a higher density of tector trichomes in V2. The lowest densities and the smallest sizes of trichomes in V2 and V5 stages was observed on PELBR 10-6049. The size of tector trichomes and the number of eggs did not differ among the cultivars. Foliar consumption was lower for on BMX Icone Ipro and Tec Irga 6070 RR. Trichome density influences the consumption and oviposition behavior of C. includens.

Use of the American Society of Anesthesiologists (ASA) physical status classification is important for periprocedural risk stratification. However, the collective effect after adjustment for the Society for Vascular Surgery (SVS) medical comorbidity grading system on long-term all-cause mortality, complications, and discharge disposition is unknown. We examined these associations in patients after thoracic endograft placement. Data from three thoracic endovascular aortic repair (TEVAR) trials through 5 years of follow-up were included. Patients with acute complicated type B dissection (n = 50), traumatic transection (n = 101), or descending thoracic aneurysm (n = 66) were analyzed. The patients were stratified into three groups according to the ASA class: I-II, III, and IV. Multivariable proportional hazards regression models were used to examine the effect of ASA class on 5-year mortality, complications, and rehospitalizations after adjustment for SVS risk score and potential confounders. The largest proportion of patients treated by TEVAR across the ASA groups (n = 217) was ASA IV (n = 97; 44.7%; P < .001), followed by ASA III (n = 83; 38.2%) and ASA I-II (n = 37; 17.1%). Among the ASA groups, the ASA I-II patients were, on average, 6 years younger than those with ASA III and 3 years older than those with ASA IV (ASA I-II: age, 54.3 ± 22.0 years; ASA III: age, 60.0 ± 19.7 years; ASA IV: age, 51.0 ± 18.4 years; P = .009). Multivariable adjusted 5-year outcome models showed that ASA class IV, independent of the SVS score, conferred an increased risk of mortality (hazard ratio [HR], 3.83; 95% confidence interval [CI], 1.19-12.25; P = .0239) and complications (HR, 4.53; 95% CI, 1.69-12.13; P = .0027) but not rehospitalization (HR, 1.84; 95% CI, 0.93-3.68; P = .0817) compared with ASA class I-II. Procedural ASA class is associated with long-term outcomes among post-TEVAR patients, independent of the SVS score. The ASA class and SVS score remain important to patient counseling and postoperative outcomes beyond the index operation.

Abstract Glioma is the most common form of malignant primary brain tumours in adults. Their highly invasive nature makes the disease incurable to date, emphasizing the importance of better understanding the mechanisms driving glioma invasion. Glial fibrillary acidic protein (GFAP) is an intermediate filament protein that is characteristic for astrocyte- and neural stem cell-derived gliomas. Glioma malignancy is associated with changes in GFAP alternative splicing, as the canonical isoform GFAPα is downregulated in higher-grade tumours, leading to increased dominance of the GFAPδ isoform in the network. In this study, we used intravital imaging and an ex vivo brain slice invasion model. We show that the GFAPδ and GFAPα isoforms differentially regulate the tumour dynamics of glioma cells. Depletion of either isoform increases the migratory capacity of glioma cells. Remarkably, GFAPδ-depleted cells migrate randomly through the brain tissue, whereas GFAPα-depleted cells show a directionally persistent invasion into the brain parenchyma. This study shows that distinct compositions of the GFAPnetwork lead to specific migratory dynamics and behaviours of gliomas.

Rhynchonycteris is a monotypic genus of Embalonurid bats, whose geographic distribution extends from southern Mexico to tropical regions of the South American continent, including Trinidad and Tobago. Although species that have a wide geographic distribution are frequently revealed to be polytypic, to date, no study has evaluated the taxonomic status of populations of Rhynchonycteris naso. Thus, the aim of this study is to address the patterns of phylogeographic structure and taxonomic subdivision of R. naso using molecular phylogenetics, morphometric data and ecological niche modeling. Phylogenetic results recovered using the genes COI, Cytb, Chd1, Dby, and Usp9x, supported the monophyly of the genus Rhynchonycteris, in addition, a deep phylogeographic structure was revealed by the mitochondrial gene COI for the populations of Belize and Panama in comparison to those of South America. The PCA, and the linear morphometry indicated an apparent differentiation between the cis-Andean and trans-Andean populations. Furthermore, according to the skull morphology, at least two morphotypes were identified. Ecological niche modeling projections in the present have shown that the Andean cordillera acts as a climatic barrier between these two populations, with the depression of Yaracuy (Northwest Venezuela) being the only putative climatically suitable path that could communicate these two populations. On the other hand, projections for the last glacial maximum showed a drastic decrease in climatically suitable areas for the species, suggesting that cycles of lower temperatures played an important role in the separation of these populations.

Introduction: Lesion-symptom mapping is a key tool in understanding the relationship between brain structures and behavior. However, the behavioral consequences of lesions from different etiologies may vary because of how they affect brain tissue and how they are distributed. The inclusion of different etiologies would increase the statistical power but has been critically debated. Meanwhile, findings from lesion studies are a valuable resource for clinicians and used across different etiologies. Therefore, the main objective of the present study was to directly compare lesion-symptom maps for memory and language functions from two populations, a tumor versus a stroke population. Methods: Data from two different studies were combined. Both the brain tumor (N = 196) and stroke (N = 147) patient populations underwent neuropsychological testing and an MRI, pre-operatively for the tumor population and within three months after stroke. For this study, we selected two internationally widely used standardized cognitive tasks, the Rey Auditory Verbal Learning Test and the Verbal Fluency Test. We used a state-of-the-art machine learning-based, multivariate voxel-wise approach to produce lesion-symptom maps for these cognitive tasks for both populations separately and combined. Results: Our lesion-symptom mapping results for the separate patient populations largely followed the expected neuroanatomical pattern based on previous literature. Substantial differences in lesion distribution hindered direct comparison. Still, in brain areas with adequate coverage in both groups, considerable LSM differences between the two populations were present for both memory and fluency tasks. Post-hoc analyses of these locations confirmed that the cognitive consequences of focal brain damage varied between etiologies. Conclusion: The differences in the lesion-symptom maps between the stroke and tumor population could partly be explained by differences in lesion volume and topography. Despite these methodological limitations, both the lesion-symptom mapping results and the post-hoc analyses confirmed that etiology matters when investigating the cognitive consequences of lesions with lesion-symptom mapping. Therefore, caution is advised with generalizing lesion-symptom results across etiologies.