bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tgfbr1regulates lateral plate mesoderm and endoderm reorganization during the trunk to tail transition
Authors: Lozovska Anastasiia , Casaca Ana , Nóvoa Ana , Kuo Ying-Yi , Jurberg Arnon D. , Martins Gabriel G. , Hadjantonakis Anna-Katerina , Mallo Moises 
Published: August 2023

ABSTRACTDuring the trunk to tail transition the mammalian embryo builds the outlets for the intestinal and urogenital tracts, lays down the primordia for the hindlimb and external genitalia, and switches from the epiblast/primitive streak to the tailbud as the driver of axial extension. Genetic and molecular data indicate thatTgfbr1is a key regulator of the trunk to tail transition.Tgfbr1has been shown to control the switch of the neuro mesodermal-competent cells from the epiblast to the chordo-neural hinge to generate the tail bud. We now show that Tgfbr1 signaling also controls the remodeling of the lateral plate mesoderm (LPM) and of the embryonic endoderm associated with the trunk to tail transition. In the absence ofTgfbr1the two LPM layers do not converge at the end of the trunk, extending instead as separate layers enclosing the celomic cavity until the caudal embryonic extremity, and failing to activate markers of primordia for the hindlimb and external genitalia. However, this extended LPM, does not exhibit the molecular signatures characteristic of this tissue in the trunk. The vascular remodeling involving the dorsal aorta and the umbilical artery leading to the connection between embryonic and extraembryonic circulation was also affected in theTgfbr1mutant embryos. Similar alterations in the LPM and vascular system were also observed inIsl1null mutants, indicating that this factor acts in the regulatory cascade downstream ofTgfbr1in LPM-derived tissues. In addition, in the absence ofTgfbr1the embryonic endoderm fails to expand to form the endodermal cloaca and to extend posteriorly to generate the tail gut. We present evidence suggesting that the remodeling activity ofTgfbr1in the LPM and endoderm results from the control of the posterior primitive streak fate after its regression during the trunk to tail transition. Our data, together with previously reported observations, placeTgfbr1at the top of the regulatory processes controlling the trunk to tail transition.
Prognostic Utility of Total Kidney Volume for Chronic Kidney Disease Risk Prediction: An Observational and Mendelian Randomization Study
Authors: Wu Jianhan , Wang Yifan , Vlasschaert Caitlyn , Lali Ricky , Feiner James , Gaheer Pukhraj , Yang Serena , Perrot Nicolas , Chong Michael , Lanktree Matthew B. , Paré Guillaume 
Published: August 2023

AbstractImportanceLow total kidney volume (TKV) is a risk factor for chronic kidney disease (CKD). However, evaluations of causal inference and prognostic utility beyond traditional biomarkers are lacking.ObjectiveTo investigate the observational and Mendelian randomization (MR) association of TKV with kidney and cardiovascular traits and assess improvement in CKD risk prediction when TKV is added to estimated glomerular filtration rate (eGFR) and urine albumin creatinine ratio (uACR).DesignCase-control study based on UK Biobank and two-sample MR analysis.Setting22 assessment centers, United Kingdom.ParticipantsIndividuals of European ancestry with kidney volume assessment derived from magnetic resonance imaging. Exclusion criteria include records of kidney transplantation, excision, congenital malformation, and cystic kidney disease.ExposuresTKV, height adjusted (htTKV), and body surface area adjusted TKV (BSA-TKV).Main OutcomesObservational and bidirectional MR association estimates of TKV with CKD risk. Incident CKD stage G3 or worse prediction performance using likelihood ratio, C-statistic, calibration, and category-free net absolute reclassification index (NARI).ResultsObservational analysis included 34,595 individuals [median (IQR) age 64 (12) years, 17,835 (51.6%) females]. Adjusted for confounders and risk factors including eGFR and uACR, a 10 mL decrease in TKV was associated with 7% increase in the risk of incident CKD stage G3 or worse (HR 1.07, 95% CI 1.04 to 1.10, P < 0.001). Addition of prognostically significant BSA-TKV thresholds of 119 and 145 mL/m2led to the greatest improvement in prediction performance beyond eGFR and uACR across likelihood ratio, discrimination (C-statistic 0.87, 95% CI 0.85 to 0.89, P = 0.017), calibration, and reclassification (NARI 228 per 1,000, P < 0.001). In MR, a 10 mL decrease in genetically predicted TKV was associated with 10% increase in CKD risk (OR 1.10, 95% CI 1.05 to 1.15, P < 0.001). Reciprocally, an increased risk of genetically predicted CKD by 2-fold was associated with an 8.75 mL reduction in TKV (95% CI -10.8 to -6.66, P < 0.001). There were no significant observational or MR associations of TKV with cardiovascular complications.ConclusionsA bidirectional relationship exists between TKV and CKD. Addition of TKV thresholds to eGFR and uACR can improve CKD risk stratification.
Synaptic inhibitory dynamics drive benzodiazepine response in paediatric status epilepticus
Authors: Fedele Tommaso , Burman Richard J. , Steinberg Anne , Selmin Giorgio , Ramantani Georgia , Rosch Richard E. 
Published: August 2023

AbstractPaediatric status epilepticus (SE) is a medical emergency associated with significant morbidity. Benzodiazepines (BZPs) are the current first-line treatment, but do not work in over a third of children presenting with SE. Animal studies have shown that SE can cause changes in synaptic inhibition signalling which can ultimately lead to BZPs becoming ineffective. However, the relevance of these mechanisms in paediatric patients with SE remains unknown. To test this hypothesis, we combine clinical EEG recordings with dynamic causal modelling (DCM). This approach allows model-based inference of cortical synaptic coupling parameters based on EEG recorded across distinct oscillatory states. Our DCM revealed that dynamic changes in inhibitory synaptic coupling explain differences in EEG power spectra associated with BZP-treatment responsiveness, and guide the transition from ictal to interictal state. Furthermore,in silicosimulations demonstrate that there are alternative routes to seizure termination even in cortical circuit models unresponsive to the BZPs. Together, our findings confirm that alterations in synaptic inhibition underlie BZP response during paediatric SE. More broadly this work further demonstrates the utility of computational modelling to validate insights from basic science in clinically accessible recordings in neurological disorders characterised by abnormal brain states.
Comparison of the performance of two targeted metagenomic virus capture probe-based methods using synthetic viral sequences and clinical samples
Authors: Mourik Kees , Sidorov Igor , Carbo Ellen C. , van der Meer David , Boot Arnoud , Kroes Aloysius C. M. , Claas Eric C.J. , Boers Stefan A. , de Vries Jutte J.C. 
Published: August 2023

AbstractViral enrichment by probe hybridization has been reported to significantly increase the sensitivity of viral metagenomics.This study compares the analytical performance of two targeted metagenomic virus capture probe-based methods: i) SeqCap EZ HyperCap by Roche (ViroCap) and ii) Twist Comprehensive Viral Research Panel workflow, for diagnostic use. Sensitivity, specificity, limit of detection, and effect of human background DNA were analysed, using synthetic viral sequences, clinical and reference samples with known viral loads.Sensitivity and specificity were 95% and higher for both methods. Combining thresholds for viral sequence read counts and genome coverage (respectively 500 reads per million and 10% coverage) resulted in optimal prediction of true positive results. Limits of detection were approximately 50-500 copies/ml for both methods. Increasing proportions of spike-in cell free human background sequences did not negatively affect viral detection.These data show analytical performances in ranges applicable to clinical samples, for both probe hybridization metagenomic approaches. This study supports further steps towards more widespread use of viral metagenomics for pathogen detection, in clinical and surveillance settings using low biomass samples.
COVID-19 self-testing: Countries accelerating policies ahead of WHO guidelines during pandemics: A Global Survey
Authors: Sakala Melody , Johnson Cheryl , Chirombo James , Sacks Jilian A. , Baggaley Rachel , Divala Titus 
Published: August 2023

AbstractIntroductionThe widespread use of antigen-detection rapid diagnostic tests (Ag-RDTs) has revolutionized SARS-CoV-2 (COVID-19) testing, particularly through the option of self-testing. The full extent of Ag-RDT utilization for self-testing, however, remains largely unexplored. To inform the development of WHO guidance on COVID-19 self-testing, we conducted a cross-sectional survey to gather the views and experiences of policy makers, researchers, and implementers worldwide.MethodsThe survey was shared through professional networks via email and social media, encouraging onward sharing. We used closed and open-ended questions related to policy and program information concerning the regulation, availability, target population, indications, implementation, benefits, and challenges of COVID-19 self-testing (C19ST). We defined self-testing as tests performed and interpreted by an untrained individual, often at home. Descriptive summaries, cross-tabulations, and proportions were used to calculate outcomes at the global level and by WHO region and World Bank income classifications.ResultsBetween 01 and 11 February 2022, 844 individuals from 139 countries responded to the survey, with 45% reporting affiliation with governments and 47% operating at the national level. 504 respondents from 101 countries reported policies supporting C19ST for a range of use cases, including symptomatic and asymptomatic populations. More respondents from low-and-middle-income countries (LMICs) than high-income countries (HICs) reported a lack of an C19ST policy (61 vs 11 countries) and low population-level reach of C19ST. Respondents with C19ST experience perceived that the tests were mostly acceptable to target populations, provided significant benefits, and highlighted several key challenges to be addressed for increased success. Reported costs varied widely, ranging from specific programmes enabling free access to certain users and others with high costs via the private sector.ConclusionBased on the survey responses, systems for the regulatory review, policy development and implementation of C19STappeared to be much more common in HIC when compared to LIC in early 2022, though most respondents indicated self-testing was available to some extent (101 out of 139 countries) in their country. Addressing such global inequities is critical for ensuring access to innovative and impactful interventions in the context of a public health emergency of international concern. The challenges and opportunities highlighted by survey respondents could be valuable to consider as future testing strategies are being set for outbreak-prone diseases.
An improved PDE6D inhibitor combines with Sildenafil to synergistically inhibit KRAS mutant cancer cell growth
Authors: Kaya Pelin , Schaffner-Reckinger Elisabeth , Manoharan Ganesh babu , Vukic Vladimir , Kiriazis Alexandros , Ledda Mirko , Burgos Maria , Pavic Karolina , Gaigneaux Anthoula , Glaab Enrico , Abankwa Daniel Kwaku 
Published: August 2023

AbstractThe trafficking chaperone PDE6D (or PDEƍ) was proposed as a surrogate target for K-Ras, leading to the development of a series of inhibitors that block its prenyl-binding pocket. These inhibitors suffered from low solubility and intracellular potency, preventing their clinical development.Here we developed a highly soluble PDE6D inhibitor (PDE6Di), Deltaflexin3, which has the currently lowest off-target activity, as we demonstrate in dedicated assays. We further increased the K-Ras focus, by exploiting that PKG2-mediated phosphorylation of Ser181 lowers K-Ras binding to PDE6D. Thus, the combination of Deltaflexin3 with the approved PKG2-activator Sildenafil synergistically inhibits cell- and microtumor growth. However, the overall cancer survival of the high PDE6D/ low PKG2 target population is higher than of the group with the opposite signature. Our results therefore suggest re-examining the interplay between PDE6D and K-Ras in cancer, while recommending the development of PDE6Di that ’plug’, rather than ’stuff’ the hydrophobic pocket of PDE6D.SignificanceCombinations of a novel PDE6D inhibitor with Sildenafil synergistically focus the inhibition on K-Ras, however, survival data of the target population suggest an interplay of K-Ras and PDE6D that needs further exploration.
SUPREM: an engineered non-site-specific m6A RNA methyltransferase with highly improved efficiency
Authors: Ochiai Yoshiki , Clifton Ben E. , Coz Madeleine Le , Terenzio Marco , Laurino Paola 
Published: August 2023

Abstractm6A RNA methylation plays a key role in RNA processing and translational regulation, influencing both normal physiological and pathological processes. Yet, current techniques for studying RNA methylation struggle to isolate the effects of individual m6A modifications. Engineering of RNA methyltransferases (RNA MTases) could enable development of improved synthetic biology tools to manipulate RNA methylation, but it is challenging due to limited understanding of structure-function relationships in RNA MTases. Herein, using ancestral sequence reconstruction we explore the sequence space of the bacterial DNA methyltransferase EcoGII (M.EcoGII), a promising target for protein engineering due to its lack of sequence specificity and its residual activity on RNA. We thereby created an efficient non-specific RNA MTase termed SUPREM, which exhibits 8-fold higher expression levels, 7 °C higher thermostability, and 12-fold greater m6A RNA methylation activity compared with M.EcoGII. Immunofluorescent staining and quantitative LC/MS-MS analysis confirmed SUPREM’s higher RNA methylation activity compared with M.EcoGII in mammalian cells. Additionally, Nanopore direct RNA sequencing highlighted that SUPREM is capable of methylating a larger number of RNA methylation sites than M.EcoGII. Through phylogenetic and mutational analysis, we identified a critical residue for the enhanced RNA methylation activity of SUPREM. Collectively, our findings indicate that SUPREM holds promise as a versatile tool forin vivoRNA methylation and labeling.
Micropillar enhanced FRET-CRISPR biosensor for nucleic acid detection
Authors: Bao Mengdi , Dollery Stephen J. , Yuqing FNU , Tobin Gregory J. , Du Ke 
Published: August 2023

AbstractCRISPR technology has gained widespread adoption for pathogen detection due to its exceptional sensitivity and specificity. Although recent studies have investigated the potential of high-aspect-ratio microstructures in enhancing biochemical applications, their application in CRISPR-based detection has been relatively rare. In this study, we developed a FRET-based biosensor in combination with high-aspect-ratio microstructures and Cas12a-mediated trans-cleavage for detecting HPV 16 DNA fragments. Remarkably, our results show that micropillars with higher density exhibit superior molecular binding capabilities, leading to a tenfold increase in detection sensitivity. Furthermore, we investigated the effectiveness of two surface chemical treatment methods for enhancing the developed FRET assay. A simple and effective approach was also developed to mitigate bubble generation in microfluidic devices, a crucial issue in biochemical reactions within such devices. Overall, this work introduces a novel approach using micropillars for CRISPR-based viral detection and provides valuable insights into optimizing biochemical reactions within microfluidic devices.
Unveiling metaverse potential in supply chain management and overcoming implementation challenges: an empirical study
Authors: Bag Surajit , Rahman Muhammad Sabbir , Srivastava Gautam , Shrivastav Santosh Kumar 
Published: August 2023

PurposeThe metaverse is a virtual world where users can communicate with each other in a computer-generated environment. The use of metaverse technology has the potential to revolutionize the way businesses operate, interact with customers, and collaborate with employees. However, several obstacles must be addressed and overcome to ensure the successful implementation of metaverse technology. This study aims to examine the implementation of metaverse technology in the management of an organization's supply chain, with a focus on predicting potential barriers to provide suitable strategies.Design/methodology/approachCovariance-based structural equation modeling (CB-SEM) was used to test the model. In addition, artificial neural network modeling (ANN) was also performed.FindingsThe CB-SEM results revealed that a firm's technological limitations are among the most significant barriers to implementing metaverse technology in the supply chain management (SCM). The ANN results further highlighted that the firm's technological limitations are the most crucial input factors, followed by a lack of governance and standardization, integration challenges, poor diffusion through the network, traditional organizational culture, lack of stakeholder commitment, lack of collaboration and low perception of value by customers.Practical implicationsBecause metaverse technology has the potential to provide organizations with a competitive advantage, increase productivity, improve customer experience and stimulate creativity, it is crucial to discuss and develop solutions to implementation challenges in the business world. Companies can position themselves for success in this fascinating and quickly changing technological landscape by conquering these challenges.Originality/valueThis study provides insights to metaverse technology developers and supply chain practitioners for successful implementation in SCM, as well as theoretical contributions for supply chain managers aiming to implement such environments.
Supply chain performance: a novel integrated decision-making model
Authors: Zhong Jianlan , Cheng Han , Gholami Hamed , Letchumanan L. Thiruvarasu , Toptancı Şura 
Published: August 2023

PurposeKnowledge management (KM) significantly affects supply chain management (SCM) and its performance in today's highly competitive corporate climate. It is crucial to consider this relationship to achieve optimal supply chain performance (SCP). This study aims to assess this impact by defining and examining the multi-dimensional relationships between KM Process Elements (KMPEs) and SCP Evaluation Criteria (SCPEC) within a comprehensive theoretical framework.Design/methodology/approachIntegrating KMPEs and SCPEC becomes an uncertain decision-making problem due to data deficiency and the vagueness of decision-makers’ judgments. To address uncertainties, this study uses interval-valued neutrosophic (IVN) sets and proposes an IVN model consisting of SWARA, which is one of the effective multi-criteria decision-making (MCDM) approaches, and house of quality (HOQ) methods. IVN-SWARA is used to weight the SCPEC while IVN-HOQ establishes relationships and prioritizes the KMPEs and SCPEC.FindingsThe results show that reliability is the most significant SCP evaluation criterion. Among the KMPEs, capitalization, sharing, and transfer exhibit stronger associations with the SCPEC compared to the other elements. Capitalization as one of the KMPEs was found to be the most critical one, and efficiency is the criterion most affected by all elements of the KM process.Originality/valueThis study uses innovative methodologies to evaluate the adoption of KM processes on SCP under uncertain environments and involving multi-decision-makers. The proposed integrated model demonstrates flexibility and practicality in combining KM and SCM, leading to improved SCP. Notably, this study presents the development of IVN-SWARA and the use of the integrated IVN-SWARA - IVN-HOQ decision tool, which are novel contributions to the existing literature.
New approaches to measuring welfare
Authors: Cooper Kristen , Fabian Mark , Krekel Christian 
Published: August 2023

AbstractEconomics has traditionally understood ‘welfare’ (what makes a life go well) as the satisfaction of preference. This conceptualisation of welfare is typically measured using revealed preferences, proxied through income and prices or stated in willingness‐to‐pay surveys. Recent decades have seen growing challenges to this paradigm. The climate crisis, among other phenomena, has called into question whether income and price data effectively proxy preferences, and willingness‐to‐pay surveys continue to struggle with accurately pricing important items such as biodiversity, digital goods, privacy and social connections. Preference satisfaction as a welfare criterion has also been challenged conceptually by psychologists and scholars working in the development space, among others. In this article, we review recent innovations in alternate ways of conceptualising and measuring welfare for the purposes of economic welfare analysis. We focus on using stated preferences over aspects of well‐being, life‐satisfaction scales and the WELLBY approach, and well‐being frameworks such as Bhutan's Gross National Happiness Index. While not without weaknesses, these approaches also have marked strengths relative to the traditional approach.
Proportion of unplanned tube replacements and complications following gastrostomy: A systematic review and meta‐analysis
Authors: Farrugia Emily , Semciw Adam Ivan , Bailey Shanelle , Cooke Zoe , Tuck Caroline 
Published: August 2023

AbstractAimsGastrostomy feeding represents a vital component of supportive care provided to people with swallowing or feeding difficulties; however, the rate of specific long‐term complications is currently unknown in the adult population. This study aimed to determine the prevalence of specific long‐term gastrostomy‐related complications and unplanned replacements in adults.MethodsA prospective systematic review of Medline, CINAHL and Embase databases was performed. Key complications of hypergranulation, infection and displacement among studies relevant to percutaneous endoscopic gastrostomy tubes, radiologically inserted gastrostomy tubes and balloon replacement tubes were critically appraised by two independent reviewers. Results were synthesised quantitatively in a meta‐analysis using random effects where the population and condition were sufficiently homogeneous.ResultsIn total, 453 studies were identified, of which 17 met inclusion criteria. 8.5% of adults with a gastrostomy were found to have had an infection ≥42 days after initial tube insertion (p < 0.01), while 13% had hypergranulation (p < 0.01). Displacement occurred in 10.8% of adults (p < 0.01), with age (p < 0.001) and sex (p < 0.001) presenting as a risk factor (R2 = 75%) following meta‐regression.ConclusionsApproximately 1 in 10 people with a gastrostomy will experience a complication related to either hypergranulation, infection or dislodgement. Age, in combination with sex, may provide a guide for risk of displacement among adult female cohorts, though further studies reporting prevalence of gastrostomy‐related complications along with participant demographics are required.