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The Golgi apparatus, a crucial organelle involved in protein processing, including glycosylation, exhibits complex sub-structures, i.e., cis-, medial, and trans-cisternae. This study investigated the distribution of glycosyltransferases within the Golgi apparatus of mammalian cells via 3D super-resolution imaging. Focusing on human glycosyltransferases involved in N-glycan modification, we found that even enzymes presumed to coexist in the same Golgi compartment exhibit nuanced variations in localization. By artificially making their N-terminal regions [composed of a cytoplasmic, transmembrane, and stem segment (CTS)] identical, it was possible to enhance the degree of their colocalization, suggesting the decisive role of this region in determining the sub-Golgi localization of enzymes. Ultimately, this study reveals the molecular codes within CTS regions as key determinants of glycosyltransferase localization, providing insights into precise control over the positioning of glycosyltransferases, and consequently, the interactions between glycosyltransferases and substrate glycoproteins as cargoes in the secretory pathway. This study advances our understanding of Golgi organization and opens avenues for programming the glycosylation of proteins for clinical applications. Key words: Golgi apparatus, glycosyltransferase, 3D super-resolution imaging, N-glycosylation

Background and objective: Focal therapy (FT) is increasingly recognized as a promising approach for managing localized prostate cancer (PCa), notably reducing treatment-related morbidities. However, post-treatment anatomical changes present significant challenges for surveillance using current imaging techniques. This study aimed to evaluate the inter-reader agreement and efficacy of the Prostate Imaging after Focal Ablation (PI-FAB) scoring system in detecting clinically significant prostate cancer (csPCa) on post-FT multiparametric magnetic resonance imaging (mpMRI). Methods: A retrospective cohort study was conducted involving patients who underwent primary FT for localized csPCa between 2013 and 2023, followed by post-FT mpMRI and a prostate biopsy. Two expert genitourinary radiologists retrospectively evaluated post-FT mpMRI using PI-FAB. The key measures included inter-reader agreement of PI-FAB scores, assessed by quadratic weighted Cohen’s kappa (κ), and the system’s efficacy in predicting in-field recurrence of csPCa, with a PI-FAB score cutoff of 3. Additional diagnostic metrics including sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and overall accuracy were also evaluated. Key findings and limitations: Scans from 38 patients were analyzed, revealing a moderate level of agreement in PI-FAB scoring (κ = 0.56). Both radiologists achieved sensitivity of 93% in detecting csPCa, although specificity, PPVs, NPVs, and accuracy varied. Conclusions and clinical implications: The PI-FAB scoring system exhibited high sensitivity with moderate inter-reader agreement in detecting in-field recurrence of csPCa. Despite promising results, its low specificity and PPV necessitate further refinement. These findings underscore the need for larger studies to validate the clinical utility of PI-FAB, potentially aiding in standardizing post-treatment surveillance. Patient summary: Focal therapy has emerged as a promising approach for managing localized prostate cancer, but limitations in current imaging techniques present significant challenges for post-treatment surveillance. The Prostate Imaging after Focal Ablation (PI-FAB) scoring system showed high sensitivity for detecting in-field recurrence of clinically significant prostate cancer. However, its low specificity and positive predictive value necessitate further refinement. Larger, more comprehensive studies are needed to fully validate its clinical utility.

A presença do invasor mexilhão dourado em águas brasileiras acarreta em impactos ecológicos ou econômicos. Uma alternativa de controle populacional é promissora: a imersão de uma espécie geneticamente modificada com o objetivo de, em contato com o molusco selvagem, produzir gerações inférteis. Uma proposta de modelo matemático que contemple tal competição torna-se importante, uma vez que pode fornecer informações para nortear futuros experimentos. Contudo, o modelo de competição necessita de uma dinâmica de crescimento bem estabelecida. Este trabalho apresenta dois modelos para a dinâmica do mexilhão selvagem, estudados de forma analítica. O estudo expõe as soluções de equilíbrio, sua estabilidade local nos pontos estacionários e uma análise de sensibilidade do números de reprodução basal (R_0's). Com isso, define-se o modelo mais adequado para receber as parcelas que modelem a competição. São realizadas simulações numéricas a fim de aferir possíveis desfechos da competição, utilizando o método de Runge-Kutta de quarta ordem. O estudo é capaz de apresentar dois pontos conclusivos importantes: que através da competição planejada a erradicação pode ser atingida e que há necessidade de vantagens competitivas para que a estratégia funcione. Este estudo ressalta a necessidade de vantagens competitivas para o mexilhão modificado. Das possíveis vantagens, o trabalho indica a eficiência reprodutiva e a taxa de mortalidade do mexilhão modificado como as mais promissoras. À vista de um tópico tão importante, este trabalho é necessário para que essa estratégia de controle populacional seja estudada e testada para auxiliar no desenvolvimento da espécie modificada de forma a respeitar a ecologia.

Abstract Background It is well established in the literature that active learning instruction in introductory STEM courses results in many desired student outcomes. Yet, regular use of high-quality active learning is not the norm in many STEM departments. Using results of a national survey, we identified 16 departments where multiple instructors reported using high levels of active learning in their introductory chemistry, mathematics, or physics courses. We conducted interviews with 27 instructors in these 16 departments to better understand the characteristics of such departments. Results Using grounded theory methodology, we developed a model that highlights relevant characteristics of departments with high use of active learning instruction in their introductory courses. According to this model, there are four main, interconnected characteristics of such departments: motivated people, knowledge about active learning, opportunities, and cultures and structures that support active learning. These departments have one or more people who are motivated to promote the use of active learning. These motivated people have knowledge about active learning as well as access to opportunities to promote the use of active learning. Finally, these departments have cultures and structures that support the use of active learning. In these departments, there is a positive feedback loop that works iteratively over time, where motivated people shape cultures/structures and these cultures/structures in turn increase the number and level of commitment of the motivated people. A second positive feedback loop was found between the positive outcome of using active learning instruction and the strengthening of cultures/structures supportive of active learning. Conclusions According to the model, there are two main take-away messages for those interested in promoting the use of active learning. The first is that all four components of the model are important. A weak or missing component may limit the desired outcome. The second is that desired outcomes are obtained and strengthened over time through two positive feedback loops. Thus, there is a temporal aspect to change. In all of the departments that were part of our study, the changes took at minimum several years to enact. While our model was developed using only high-use of active learning departments and future work is needed to develop the model into a full change theory, our results do suggest that change efforts may be made more effective by increasing the robustness of the four components and the connections between them.

The primary aim of this study was to establish the feasibility of implementing a larger RCT designed to evaluate the effect of financial incentives on HCV treatment initiation among persons receiving opioid agonist therapy and/or who have injected drugs in the prior six months. ETHOS Engage is an observational cohort of participants recruited from drug treatment and needle and syringe programs in Australia. Among 11 drug and alcohol clinics, participants who were HCV RNA-positive were randomized (1:1) to receive standard of care or a AUD $60 gift card at treatment initiation. Regarding feasibility, 100% (57/57) of eligible participants enrolled to take part. Twenty-eight participants were randomised to the financial incentive arm (AUD $60 gift card) plus standard of care and 29 participants to the standard of care arm. In this pilot RCT (n = 57), median age was 42 years (IQR 37–49), 63% were male (n = 36), 35% Indigenous (n = 20) and 36% (n = 21) reported injecting drugs daily in the past month. Twelve weeks post-study enrolment, 11 (39%) participants in the financial incentive arm and 17 (59%) participants in the standard of care arm initiated HCV treatment. Findings indicate high feasibility among people who inject drugs to be randomised to receive financial incentives to initiate HCV treatment.

Network analysis has become a well-recognized methodology in physics education research (PER), with study topics including student performance and persistence, faculty change, and the structure of conceptual networks. The social network analysis side of this work has focused on quantitative analysis of whole-network cases, such as the structure of networks in single classrooms. Egocentric or personal network approaches are largely unexplored, and qualitative methods are underdeveloped. In this paper, we outline theoretical and practical differences between two major network paradigms—whole-network and egocentric—and introduce theoretical frameworks and methodological considerations for egocentric studies. We also describe qualitative and mixed-methods approaches that are currently missing from the PER literature. We identify areas where these additional network methods may be of particular interest to physics education researchers and end by discussing example cases and implications for new PER studies.

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The study assessed the peptidomic profile of in-bag dry-aged (2 °C, RH 75 %, 0.5 m.s−1, n = 30) and wet-aged (-1.5 °C, n = 30) lamb with high and low levels of lipid oxidation. A total of 1056 low molecular weight peptides (< 10 kDa) were identified in aged lamb samples, using LC-MS/MS and label free quantification (data are available via ProteomeXchange with identifier PXD047738). Partial Least Squares – Discriminant analysis highlighted that all discriminating peptides in dry-aged lamb were from titin, whereas discriminating peptides in the wet-aged samples were predominantly from nebulin, myotilin, collagen type IV, LIM domain binding 3, and heat shock protein family B. Comparison of peptides from aged lamb meat with high- and low-levels of lipid oxidation showed that most discriminatory peptides within an ageing method are derived from oxidatively modified peptides from creatine kinase. These peptides could thus potentially be used as signature biomolecules to discriminate ageing techniques and indicate lipid oxidation levels.

Abstract Numerous policy and international frameworks consider that “destructive fishing” hampers efforts to reach sustainability goals. Though ubiquitous, “destructive fishing” is undefined and therefore currently immeasurable. Here we propose a definition developed through expert consultation: “Destructive fishing is any fishing practice that causes irrecoverable habitat degradation, or which causes significant adverse environmental impacts, results in long‐term declines in target or nontarget species beyond biologically safe limits and has negative livelihood impacts.” We show strong stakeholder support for a definition, consensus on many biological and ecological dimensions, and no clustering of respondents from different sectors. Our consensus definition is a significant step toward defining sustainable fisheries goals and will help interpret and implement global political commitments which utilize the term “destructive fishing.” Our definition and results will help reinforce the Food and Agricultural Organization's Code of Conduct and meaningfully support member countries to prohibit destructive fishing practices.

Variants in ATP-binding cassette transporter type A4 (ABCA4) have been linked to several forms of inherited retinal diseases (IRDs) besides the classically defined Stargardt disease (STGD), known collectively as ABCA4 retinopathies. ABCA4 is a sizable locus harboring 50 exons; thus, its analysis has revealed over 2,400 variants described, of which more than 2,000 are causal. Due to the clinical and genetic heterogeneity, diagnosing ABCA4 retinopathies is challenging. To date, no ABCA4-related retinopathy has been detected in Lebanon. Using next-generation sequencing, we analyzed our IRDs' cohort retrospectively (61 families) and identified five with ABCA4-related retinopathies, making it a relatively abundant cause of IRDs (about 8 %). Three families were diagnosed with rod-cone dystrophy (RCD), two with STGD, and one with cone-rod dystrophy (CRD). In conclusion, our study showed the presence of ABCA4 variants with a high degree of heterogeneity in Lebanon.

ABSTRACTAntigen-based rapid diagnostic tests (Ag-RDTs) were widely deployed to enhance SARS-CoV-2 testing capacity during the COVID-19 pandemic. Consistent with national guidance for low prevalence settings, positive Ag-RDTs were confirmed using nucleic acid amplification tests (NAATs) to avoid false positive results. However, increasing demands for positive Ag-RDT confirmation competed with other testing priorities in clinical laboratories. This work hypothesized that real-time RT-PCR without nucleic acid extraction (NAE) would be sufficiently sensitive to support positive Ag-RDT confirmation. Ag-RDT and NAAT results from community-based asymptomatic testing sites prior to the omicron variant wave were compared to calculate the weekly false positive rate (FPR) and false detection rate (FDR). Real-time RT-PCR was compared with and without NAE using 752 specimens previously tested positive for SARS-CoV-2 using commercial NAATs and 344 specimens from Ag-RDT-positive individuals. The impact of SARS-CoV-2 prevalence on laboratory resources required to sustain Ag-RDT confirmation was modeled for the RT-PCR with and without NAE. Overall, FPR was low [0.07% (222/330,763)] in asymptomatic testing sites, but FDR was high [30.7% (222/724)]. When RT-PCR was compared with and without NAE, 100% concordance was obtained with NAAT-positive specimens, including those from Ag-RDT-positive individuals. NAE-free RT-PCR significantly reduced time to results, human resources, and overall costs. A 30.7% FDR reaffirms the need for NAAT-based confirmation of positive Ag-RDT results during low SARS-CoV-2 prevalence. NAE-free RT-PCR was shown to be a simple and cost-sparing NAAT-based solution for positive Ag-RDT confirmation, and its implementation supported data-driven broader Ag-RDT deployment into communities, workplaces, and households.IMPORTANCERapid antigen testing for SARS-CoV-2 was widely deployed during the COVID-19 pandemic. In settings of low prevalence, national guidance recommends that positive antigen test results be confirmed with molecular testing. Given the high testing burden on clinical laboratories during the COVID-19 pandemic, the high volume of positive antigen tests submitted for confirmatory testing posed challenges for laboratory workflow. This study demonstrated that a simple PCR method without prior nucleic acid purification is an accurate and cost-effective solution for positive rapid antigen test confirmation. Implementing this method allowed molecular confirmatory testing for positive antigen tests to be sustained as antigen testing was expanded into large populations such as workplaces, schools, and households.

Despite knowing physics and astronomy doctoral programs are laden with identity-based inequities, they continue to push minoritized students to the margins. This qualitative social network analysis of 100 women and/or lesbian, gay, bisexual, transgender, queer, and more (LGBT+) physics and astronomy Ph.D.’s explores how minoritized physics and astronomy students utilize social networks to navigate departmental exclusion. Our findings indicate that many of the participants’ identities were often unacknowledged or negatively addressed within their graduate education, with only four participants reporting a positive or favorable experience during this period of their career. Direct support from peers, faculty, and identity-based affinity groups was necessary for participants to navigate their educations. This study demonstrated that generic best practices often cannot fully support the diverse range of persons who come to physics and that identity-neutral values in physics further isolate students by insinuating that their own minoritized experiences are not valid.

In this article, we summarize recent theoretical and experimental studies of the impedance and beam-induced heating of titanium-coated ceramic vacuum chambers used in the NSLS-II injection kickers. The impedance was calculated using the field matching theory assuming planar approximation and compared with the impedancewake2d code. For the coating thickness of a few microns, we demonstrated that the beam-induced power is dissipated in the titanium coating and that the longitudinally averaged two-dimensional power density is approximated by an analytical expression, thus allowing the use of a simplified model of the power density as input for the ansys code to simulate the temperature distribution with realistic nonuniform thickness of the Ti coating. For a few values of the NSLS-II beam current, we measured the beam-induced heating of two ceramic chambers using thermal sensors installed along the chamber and compared the measurement results with the simulations.

Multiple randomized controlled trials have extensively examined the therapeutic effectiveness of sodium-glucose cotransporter 2 (SGLT2) inhibitors, ushering in a transformative approach to treating individuals with type 2 diabetes mellitus (DM). Notably, emerging reports have drawn attention to the potential positive impacts of SGLT2 inhibitors in nondiabetic patients. In an effort to delve into this phenomenon, a comprehensive systematic literature review spanning PubMed (NLM), Medline (Ovid), and Cochrane Library, covering publications from 2000 to 2024 was undertaken. This systematic review encompassed twenty-six randomized control trials (RCTs) involving 35,317 participants. The findings unveiled a multifaceted role for SGLT2 inhibitors, showcasing their ability to enhance metabolic control and yield cardioprotective effects through a reduction in cardiovascular death (CVD) and hospitalization related to heart failure (HF). Additionally, a renalprotective effect was observed, evidenced by a slowdown in chronic kidney disease (CKD) progression and a decrease in albuminuria. Importantly, these benefits were coupled with an acceptable safety profile. The literature also points to various biological plausibility and underlying mechanistic pathways, offering insights into the association between SGLT2 inhibitors and these positive outcomes in nondiabetic individuals. Current research trends indicate a continual exploration of additional role for SGLT2 inhibitors in. Nevertheless, further research is imperative to fully elucidate the mechanisms and long-term outcomes associated with the nondiabetic use of SGLT2 inhibitors.

We investigated the impact of mesenchymal stem cell (MSC) therapy on treating bilateral human hip osteonecrosis, analyzing 908 cases. This study assesses factors such as tissue source and cell count, comparing core decompression with various cell therapies. This research emphasizes bone repair according to pre-treatment conditions and the specificities of cell therapy in osteonecrosis repair, indicating a potential for improved bone repair strategies in hips without femoral head collapse. This study utilized a single-center retrospective analysis to investigate the efficacy of cellular approaches in the bone repair of osteonecrosis. It examined the impact on bone repair of tissue source (autologous bone marrow concentrate, allogeneic expanded, autologous expanded), cell quantity (from none in core decompression alone to millions in cell therapy), and osteonecrosis stage and volume. Excluding hips with femoral head collapse, it focused on patients who had bilateral hip osteonecrosis, both pre-operative and post-operative MRIs, and a follow-up of over five years. The analysis divided these patients into seven groups based on match control treatment variations in bilateral hip osteonecrosis, primarily investigating the outcomes between core decompression, washing effect, and different tissue sources of MSCs. Younger patients (