bluuebunny/crossref_metadata_2025 huggingface dataset:
Financing sustainable development goals in Sub‐Saharan Africa: Does international capital flows matter?
Authors: Slimani Sana , Omri Anis , Abbassi Abdessalem
Published: May 2024

This study investigates the role of international capital flows in financing the Sustainable Development Goals (SDGs) in Sub‐Saharan Africa (SSA). Using data from 41 SSA countries from 2000 to 2018 and employing the System Generalized Method of Moments (System GMM), the research examines the impact of Foreign Direct Investment (FDI) and remittances on the SDGs across disaggregated levels (economic, social, and environmental sustainability) and the aggregated level (SDGI). The findings underscore the crucial significance of international capital flows as essential financing sources for SSA countries. FDI emerges as a contributor to economic and social sustainability at the disaggregated level, yet it exhibits negative effects on environmental sustainability. Conversely, remittances are shown to positively contribute to economic and social sustainability at the disaggregated level. However, the impact of international capital flows on the aggregate SDGI is found to be insignificantly positive. These results highlight the necessity for policymakers in SSA to devise strategies that maximize the benefits of FDI while addressing its adverse effects on environmental sustainability. Furthermore, they emphasize the importance of strengthening policies aimed at directing remittances towards sustainable investments, thereby advancing the achievement of the SDGs. Governments are urged to prioritize enhancing regulatory capacities in environmental matters through investments in modern technologies and appropriate standards, aiming to strike a balance between environmental protection and economic needs. Additionally, they should prioritize transparency, public participation, and robust enforcement mechanisms. Encouraging environmentally friendly foreign investments and promoting regional and international cooperation are also crucial steps towards effectively managing local environmental challenges.
Circular economy and waste production models for sustainable development goals 12 and 14: Evidence from cruise sustainability reporting
Authors: Di Vaio Assunta , Dell'Amura Giuseppe , Chhabra Meghna , Garofalo Antonio
Published: May 2024

The relationship between the practices and initiatives governing “waste production models” (sustainable development goal [SDG]12) and marine biodiversity goals (SDG14) is relatively unexplored. Aiming to bridge this gap by drawing on stakeholder and legitimacy theories, this study examines onboard cruise ships' circular economy (CE)‐based waste management practices and initiatives, correlating SGDs 12 and 14. Consequently, Carnival Corporation Plc's 2020–2022 sustainability reports are analyzed using content analysis by both Leximancer software (ver. 5.0) and manual methods. The results highlight the corporation's increasing commitment to green technologies for “waste production models” to achieve SDG14. However, its sustainability reports provide unclear evidence of the impact on marine biodiversity. Findings implies that practitioners should partner and invest in green technologies for “waste production models” to achieve SDG14. Besides being the first to explore the link between the two SDGs within the CE framework, this study advances insights into waste management within “waste production models,” enhancing the understanding of sustainable practices.
Eco‐Friendly Analytical Approaches for the Quantification of Molnupiravir and Favipiravir Using Capillary Zone Electrophoresis and Derivative Ratio Spectrophotometry
Authors: Nasr Mohamed S. , Talaat Wael , Kaddah Mohamed M. Y. , Omran G. , Morshedy S.
Published: May 2024

Designing new validated analytical procedures with a focus on many objectives, such as simplicity, environmental friendliness, analytical effectiveness, and sustainability, has grown to be a top priority in quality control departments. Applying green and white analytical chemistry concepts is no longer a luxury. In this report, two new approaches, Capillary Zone Electrophoresis (CZE) with Photo Diode Array (PDA) detection and derivative ratio spectrophotometric methods, are established and validated for the simultaneous analysis of molnupiravir (MLP) and favipiravir (FAV) in bulk, single dosage forms, and their expected combined dosage forms. For the two drugs, linearity ranges of 5–50 μg/mL and 1–30 μg/mL were achieved using the CZE and spectrophotometric methods, respectively. Both techniques have been validated and used for the estimation of the two medications in lab‐made capsules in accordance with the International Council for Harmonization's (ICH) recommendations. Seven assessment models were used to evaluate the greenness and sustainability of the introduced approaches compared to three previously published HPLC, chemometric, and HPTLC techniques. ChlorTox and BAGI tools are applied for the first time for the evaluation of an analytical procedure. Higher green and sustainable qualities were declared by suggested approaches than by earlier ones.
Vanadium Single Atoms Embedded in MoS2 Enabled Gut‐Brain Axis Neurotransmitter Detection at pM Levels
Authors: Sun Linxuan , Xu Hengyue , Bai Yichao , Chang Liang , Gao Jianxiang , Zhao Mingchuang , Huang Arthur Tran , Ma Lan , Lei Yu , Kang Feiyu , Terrones Mauricio
Published: May 2024

The detection of monoamine neurotransmitters is of paramount importance as the neurotransmitters are the chemical messengers regulating the gut‐brain axis (GBA). It requires real‐time, ultrasensitive, and selective sensing of the neurotransmitters in the gastric/intestinal fluid. However, multi‐components present in the gastric/intestinal fluid make sensing challenging to achieve in terms of ultra‐high sensitivity and selectivity. Herein, an approach is introduced to utilize vanadium single atom catalytic (SAC) centers in van der Waals MoS2 (V‐MoS2) to selectively detect real‐time serotonin (5‐HT) in artificial gastric/intestinal fluid. The synergetic effect of V‐SACs and the surface S‐bonds on the MoS2 surface, enables an extremely wide range of 5‐HT detection (from 1 pM to 100 µM), with optimum selectivity and interference resistance. By combining density functional theory calculations and scanning transmission electron microscopy, it is concluded that the V‐SACs embedded in the MoS2 network create active sites that greatly facilitate the charge exchange between the material and the 5‐HT molecules. This result allows the 5‐HT detection in GBA studies to be more reliable, and the material tunability provides a general platform to achieve real‐time and multi‐component detection of other monoamine neurotransmitters in GBA such as dopamine and norepinephrine.
Programmable Optoelectronic Synaptic Transistors Based on MoS2/Ta2NiS5 Heterojunction for Energy‐Efficient Neuromorphic Optical Operation
Authors: An Junru , Zhang Nan , Tan Fan , Zhao Xingyu , Chang Chunlu , Lanza Mario , Li Shaojuan
Published: May 2024

The optoelectronic synaptic transistors with various functions, broad spectral perception, and low power consumption are an urgent need for the development of advanced optical neural network systems. However, it remains a great challenge to realize the functional diversification of the systems on a single device. 2D van der Waals (vdW) materials can combine unique properties by stacking with each other to form heterojunctions, which may provide a strategy for solving this problem. Herein, an all‐2D vdW heterojunction‐based programmable optoelectronic synaptic transistor based on MoS2/Ta2NiS5 heterojunctions is demonstrated. The device implements reconfigurable, multilevel non‐volatile memory (NVM) states through sequential modulation of multiple optical and electrical stimuli to achieve broadband (532–808 nm), energy‐efficient (17.2 fJ), hetero‐synaptic functionality in a bionic manner. The intrinsic working mechanisms of the photogating effect caused by band alignment and the interfacial trapping defect modulation induced by gate voltage are revealed by Kelvin‐probe force microscopy (KPFM) measurements and carrier transport analysis. Overall, the (opto)electronic synaptic weight controllability for combined in‐sensor and in‐memory logic processors is realized by the heterojunction properties. The proposed findings facilitate the technical realization of generic all 2D hetero‐synapses for future artificial vision systems, opto‐logical systems, and Internet of Things (IoT) entities.
Koo‐Kleinstreuer‐Li magneto‐nanofluid model for non‐Newtonian micropolar fluid through porous channel
Authors: Lone Showkat Ahmad , Bilal Muhammad , Mehmood Yasir , Sajid Tanveer , Nadeem Muhammad
Published: May 2024

The primary concern of writing this article is to study the rheological properties of the micropolar non‐Newtonian nanofluid flowing through the porous medium along with magnetic field effects. In it, the outer boundary of the sheet is heated by applying an external heat source. The insertion of aluminum oxide nanoparticles in water turned it into a nanofluid. Together with the viscous dissipation phenomena, adding a magnetic field has another effect known as a Joule heating impact that is considered in the energy equation. To investigate the impact of viscosity and thermal conductivity on flow patterns, we considered the Koo‐Kleinstreuer‐Li model. A generalized Proudman‐Johnson equation is obtained by using similarity transformation on Navier‐Stokes equations. The well‐known classical shooting method is used to get the numerical solution to the said problem. Graphical results are portrayed for variant rheological parameters lke power law index, Reynolds number, volume fraction, Prandtl number, expansion ratio, and Hartmann number on the velocity and temperature of nanofluids.
Cattaneo–Christov heat and mass flux model and thermal enhancement in three‐dimensional MHD Jeffrey hybrid nanofluid flow over a bi‐directional stretching sheet with convective boundary conditions
Authors: Hussain Zawar , Ayaz Muhammad , Islam Saeed
Published: May 2024

Inspired by the progressive relaxation characteristics of the Jeffrey model and its applied advantages in the rheological modeling of various dynamic fluids, the current study is focused to investigate the heat and mass transfer of magnetohydrodynamic (MHD) Jeffrey hybrid nanofluid flow over bi‐directional stretching sheet with convective boundary conditions. Additionally, the Cattaneo–Christov model of heat and mass flux is employed to take into consideration the time relaxation effects. The energy and concentration equation are taken into account to explore the effects of thermophoresis and Brownian motion. Homotopy analysis method (HAM) is employed for the solution of the current problem. Solution methodology is verified by comparing present results with those already published in open literature. The physical aspects of obtained graphical and numerical results are explained in detail to justify acquired trends. From the investigation, it is inferred that the magnetic and viscoelastic factors have a reducing influence on the flow profile along primary and secondary directions, while the stretching parameter has an increasing behavior on the flow profile in the secondary direction. Furthermore, the Brownian motion, magnetic parameter, and thermophoretic parameter have an escalating behavior on thermal distribution; however, the Brownian motion has a declining consequence on the concentration profile. The larger Biot number heightens the thermal and concentration distributions.
Constructing a Comprehensive Discourse
Authors: Ghaly Mohammed
Published: May 2024

Chapter two constructs a comprehensive ethical framework to facilitate the analysis of intricate bioethical issues like incidental findings (IFs) in genomics. Drawing from both secular and Islamic traditions, it synthesizes Robert Veatch's multi-layered approach to bioethics and the recommendation by Muslim ethicists to engage diverse scholarly disciplines. The “Theoretical Level” section explores Islamic metaethics rooted in theology and legal theory, centering on aligning human actions with God’s will to achieve benefit and avert harm. It examines the process of religio-ethical reasoning (ijtihād) employed by Muslim scholars to discern divine guidance on novel issues. The “Practical Level” section outlines the fivefold classification scheme for categorizing human acts based on their moral value within the Islamic tradition: prohibited, obligatory, reprehensible, recommended, and permissible. Distinct from secular schemes, this classification’s theological foundations, definitions, and moral dimensions are elucidated. Bridging theory and practice, the chapter proposes utilizing this fivefold scheme as a nuanced tool to evaluate the ethical management of IFs. It advocates a dynamic approach, acknowledging how evolving scientific understanding may shift the categorization of specific IFs over time. The chapter lays the groundwork for the subsequent analysis, where representative cases illustrating each ethical category are examined through the synthesized Islamic ethical lens, fostering constructive dialogue between religious and secular bioethical discourses on this complex issue.
Dynamic changes in RNA m6A and 5 hmC influence gene expression programs during macrophage differentiation and polarisation
Authors: Pinello Natalia , Song Renhua , Lee Quintin , Calonne Emilie , Duan Kun-Long , Wong Emilie , Tieng Jessica , Mehravar Majid , Rong Bowen , Lan Fei , Roediger Ben , Ma Cheng-Jie , Yuan Bi-Feng , Rasko John E. J. , Larance Mark , Ye Dan , Fuks François , Wong Justin J.-L.
Published: May 2024

RNA modifications are essential for the establishment of cellular identity. Although increasing evidence indicates that RNA modifications regulate the innate immune response, their role in monocyte-to-macrophage differentiation and polarisation is unclear. While m6A has been widely studied, other RNA modifications, including 5 hmC, remain poorly characterised. We profiled m6A and 5 hmC epitranscriptomes, transcriptomes, translatomes and proteomes of monocytes and macrophages at rest and pro- and anti-inflammatory states. Transcriptome-wide mapping of m6A and 5 hmC reveals enrichment of m6A and/or 5 hmC on specific categories of transcripts essential for macrophage differentiation. Our analyses indicate that m6A and 5 hmC modifications are present in transcripts with critical functions in pro- and anti-inflammatory macrophages. Notably, we also discover the co-occurrence of m6A and 5 hmC on alternatively-spliced isoforms and/or opposing ends of the untranslated regions (UTR) of mRNAs with key roles in macrophage biology. In specific examples, RNA 5 hmC controls the decay of transcripts independently of m6A. This study provides (i) a comprehensive dataset to interrogate the role of RNA modifications in a plastic system (ii) a resource for exploring different layers of gene expression regulation in the context of human monocyte-to-macrophage differentiation and polarisation, (iii) new insights into RNA modifications as central regulators of effector cells in innate immunity.
CD200R activation on naïve T cells by B cells induces suppressive activity of T cells via IL-24
Authors: Chu Kuan-Hua , Chiang Bor-Luen
Published: May 2024

CD200 is an anti-inflammatory protein that facilitates signal transduction through its receptor, CD200R, in cells, resulting in immune response suppression. This includes reducing M1-like macrophages, enhancing M2-like macrophages, inhibiting NK cell cytotoxicity, and downregulating CTL responses. Activation of CD200R has been found to modulate dendritic cells, leading to the induction or enhancement of Treg cells expressing Foxp3. However, the precise mechanisms behind this process are still unclear. Our previous study demonstrated that B cells in Peyer’s patches can induce Treg cells, so-called Treg-of-B (P) cells, through STAT6 phosphorylation. This study aimed to investigate the role of CD200 in Treg-of-B (P) cell generation. To clarify the mechanisms, we used wild-type, STAT6 deficient, and IL-24 deficient T cells to generate Treg-of-B (P) cells, and antagonist antibodies (anti-CD200 and anti-IL-20RB), an agonist anti-CD200R antibody, CD39 inhibitors (ARL67156 and POM-1), a STAT6 inhibitor (AS1517499), and soluble IL-20RB were also applied. Our findings revealed that Peyer’s patch B cells expressed CD200 to activate the CD200R on T cells and initiate the process of Treg-of-B (P) cells generation. CD200 and CD200R interaction triggers the phosphorylation of STAT6, which regulated the expression of CD200R, CD39, and IL-24 in T cells. CD39 regulated the expression of IL-24, which sustained the expression of CD223 and IL-10 and maintained the cell viability. In summary, the generation of Treg-of-B (P) cells by Peyer’s patch B cells was through the CD200R-STAT6-CD39-IL-24 axis pathway.
Circulating tumour cells predict recurrences and survival in head and neck squamous cell carcinoma patients
Authors: Zhang Xi , Weeramange Chameera Ekanayake , Hughes Brett G. M. , Vasani Sarju , Liu Zhen Yu , Warkiani Majid , Hartel Gunter , Ladwa Rahul , Thiery Jean Paul , Kenny Liz , Breik Omar , Punyadeera Chamindie
Published: May 2024

Patients with head and neck squamous cell carcinoma (HNSCC) are at a high risk of developing recurrence and secondary cancers. This study evaluates the prognostic and surveillance utilities of circulating tumour cells (CTCs) in HNSCC. A total of 154 HNSCC patients were recruited and followed up for 4.5 years. Blood samples were collected at baseline and follow-up. CTCs were isolated using a spiral microfluid device. Recurrence and death due to cancer were assessed during the follow-up period. In patients with HNSCC, the presence of CTCs at baseline was a predictor of recurrence (OR = 8.40, p < 0.0001) and death (OR= ∞, p < 0.0001). Patients with CTCs at baseline had poor survival outcomes (p < 0.0001). Additionally, our study found that patients with CTCs in a follow-up appointment were 2.5 times more likely to experience recurrence or death from HNSCC (p < 0.05) prior to their next clinical visit. Our study highlights the prognostic and monitoring utilities of CTCs’ in HNSCC patients. Early identification of CTCs facilitates precise risk assessment, guiding treatment choices and ultimately enhancing patient outcomes.
Effects of beam power and feed rate in the process of cutting fresh wood with a CO2 laser on water contact angle on the cut surface
Authors: Maciak Adam , Aniszewska Monika , Zychowicz Witold , Zowczak Włodzimierz , Danielewski Hubert
Published: May 2024

The paper describes a study on the effects of beam power and feed rate in the process of cutting fresh wood with a CO2 laser on water contact angle on the cut surface. The study involved several broadleaved tree species (oak, birch, alder, plum, and apple tree) and one coniferous species (pine). Samples were cut with a Trumpf TLC1005 laser equipped with a TruFlow 6000 CO2 resonator at a wavelength of 10.6 μm at three power output settings (1 kW, 2 kW, and 3 kW) and one feed rate (0.4 m∙min− 1). Contact angle was measured by pipetting a drop of distilled water on the wood surface and recording the process with a camera. Subsequently, images of the drop were analyzed over one minute at 10 s intervals to determine changes in contact angle for each of the cases examined. It was not possible to measure the contact angle on saw-cut samples as the water was immediately absorbed, while water drops placed on laser-cut samples remained on the surface for over 60 s, with the contact angle decreasing over time for the examined species from an average of 90° to 40°. The higher beam power settings (2 or 3 kW) were found to be preferable for the hardwood species (oak, birch, alder, and apple tree). In turn, in the case of the softwood species (pine), the laser power output did not matter, as both at the low (1 kW) and high (3 kW) settings the drop did not spread over the surface quickly. Finally, the optimum beam power for plum tree wood was found to be 1 kW.
Heterogeneity of glycaemic phenotypes in type 1 diabetes
Authors: Fagherazzi Guy , Aguayo Gloria A. , Zhang Lu , Hanaire Hélène , Picard Sylvie , Sablone Laura , Vergès Bruno , Hamamouche Naïma , Detournay Bruno , Joubert Michael , Delemer Brigitte , Guilhem Isabelle , Vambergue Anne , Gourdy Pierre , Hadjadj Samy , Velayoudom Fritz-Line , Guerci Bruno , Larger Etienne , Jeandidier Nathalie , Gautier Jean-François , Renard Eric , Potier Louis , Benhamou Pierre-Yves , Sola Agnès , Bordier Lyse , Bismuth Elise , Prévost Gaëtan , Kessler Laurence , Cosson Emmanuel , Riveline Jean-Pierre ,   on behalf of the SFDT1 study team
Published: May 2024

Aims/hypothesis

Our study aims to uncover glycaemic phenotype heterogeneity in type 1 diabetes.

Methods

In the Study of the French-speaking Society of Type 1 Diabetes (SFDT1), we characterised glycaemic heterogeneity thanks to a set of complementary metrics: HbA1c, time in range (TIR), time below range (TBR), CV, Gold score and glycaemia risk index (GRI). Applying the Discriminative Dimensionality Reduction with Trees (DDRTree) algorithm, we created a phenotypic tree, i.e. a 2D visual mapping. We also carried out a clustering analysis for comparison.

Results

We included 618 participants with type 1 diabetes (52.9% men, mean age 40.6 years [SD 14.1]). Our phenotypic tree identified seven glycaemic phenotypes. The 2D phenotypic tree comprised a main branch in the proximal region and glycaemic phenotypes in the distal areas. Dimension 1, the horizontal dimension, was positively associated with GRI (coefficient [95% CI]) (0.54 [0.52, 0.57]), HbA1c (0.39 [0.35, 0.42]), CV (0.24 [0.19, 0.28]) and TBR (0.11 [0.06, 0.15]), and negatively with TIR (−0.52 [−0.54, −0.49]). The vertical dimension was positively associated with TBR (0.41 [0.38, 0.44]), CV (0.40 [0.37, 0.43]), TIR (0.16 [0.12, 0.20]), Gold score (0.10 [0.06, 0.15]) and GRI (0.06 [0.02, 0.11]), and negatively with HbA1c (−0.21 [−0.25, −0.17]). Notably, socioeconomic factors, cardiovascular risk indicators, retinopathy and treatment strategy were significant determinants of glycaemic phenotype diversity. The phenotypic tree enabled more granularity than traditional clustering in revealing clinically relevant subgroups of people with type 1 diabetes.

Conclusions/interpretation

Our study advances the current understanding of the complex glycaemic profile in people with type 1 diabetes and suggests that strategies based on isolated glycaemic metrics might not capture the complexity of the glycaemic phenotypes in real life. Relying on these phenotypes could improve patient stratification in type 1 diabetes care and personalise disease management.

Graphical Abstract
Key points of statistics for clinically oriented research
Authors: Laky Brenda ,   AGA Research Committee
Published: May 2024

Processing of research data is a crucial point in every scientific study. The basis of each statistical test is a clear research question and hypothesis. Then the scientist must consider which type of data are to be collected (nominal, ordinal, continuous). It is recommended that study-specific spreadsheets are developed before data collection, which consider the type of data being collected, how the data are to be analyzed, and which software will be used. Then, once the data have been gathered, tests for normality should be applied before proceeding with the specific statistical tests. This article provides a brief overview of common statistical tests based on fictional examples.
Testing for Granger causality in heterogeneous panels with cross-sectional dependence
Authors: Nazlioglu Saban , Karul Cagin
Published: May 2024

This paper proposes a panel Granger causality approach for heterogeneous panels with cross-sectional dependence. We define a panel VAR model with unobserved common factors and apply the PANIC procedure to obtain the de-factored data. We then estimate the lag augmented (LA)-VAR model for each cross section and construct the panel statistics based on the meta-analytic approach that combines the p-values of the individual statistics. The Monte Carlo simulations indicate that the combination tests show good size and power properties and appear suitable for the panels where cross sections may have different unit root or co-integration properties. We finally re-investigate Granger causality between export and economic growth in OECD countries. The results shed light on the importance of accounting for cross-sectional dependence within a factor model framework in determining direction of Granger causality for country-specific analysis. The results further reveal that export and economic growth do not cause each other in the majority of the European Union countries.
DESI-MSI-guided exploration of metabolic-phenotypic relationships reveals a correlation between PI 38:3 and proliferating cells in clear cell renal cell carcinoma via single-section co-registration of multimodal imaging
Authors: Zickuhr Greice M. , Um In Hwa , Laird Alexander , Harrison David J. , Dickson Alison L.
Published: May 2024

A workflow has been evaluated that utilizes a single tissue section to obtain spatially co-registered, molecular, and phenotypical information suitable for AI-enabled image analysis. Desorption electrospray ionization mass spectrometry imaging (DESI-MSI) was used to obtain molecular information followed by conventional histological staining and immunolabelling. The impact of varying DESI-MSI conditions (e.g., heated transfer line (HTL) temperature, scan rate, acquisition time) on the detection of small molecules and lipids as well as on tissue integrity crucial for integration into typical clinical pathology workflows was assessed in human kidney. Increasing the heated transfer line temperature from 150 to 450 °C resulted in a 1.8-fold enhancement in lipid signal at a scan rate of 10 scans/s, while preserving histological features. Moreover, increasing the acquisition speed to 30 scans/s yielded superior lipid signal when compared to 10 scans/s at 150 °C. Tissue morphology and protein epitopes remained intact allowing full histological assessment and further multiplex phenotyping by immunofluorescence (mIF) and immunohistochemistry (mIHC) of the same section. The successful integration of the workflow incorporating DESI-MSI, H&E, and immunolabelling on a single tissue section revealed an accumulation of ascorbic acid in regions of focal chronic inflammatory cell infiltrate within non-cancerous kidney tissue. Additionally, a strong positive correlation between PI 38:3 and proliferating cells was observed in clear cell renal cell carcinoma (ccRCC) showing the utility of this approach in uncovering molecular associations in disease pathology.

Graphical Abstract
Tandem gene duplication selected by activation of horizontally transferred gene in bacteria
Authors: Zhang Fangqing , Shi Xinxin , Xu Jian , Yuan Wen , Li Zhichao
Published: May 2024

Horizontal gene transfer occurs frequently in bacteria, but the mechanism driving activation and optimization of the expression of horizontally transferred genes (HTGs) in new recipient strains is not clear. Our previous study found that spontaneous tandem DNA duplication resulted in rapid activation of HTGs. Here, we took advantage of this finding to develop a novel technique for tandem gene duplication, named tandem gene duplication selected by activation of horizontally transferred gene in bacteria (TDAH), in which tandem duplication was selected by the activation of horizontally transferred selectable marker gene. TDAH construction does not contain any reported functional elements based on homologous or site-specific recombination and DNA amplification. TDAH only contains an essential selectable marker for copy number selection and 9-bp-microhomology border sequences for precise illegitimate recombination. One transformation and 3 days were enough to produce a high-copy strain, so its procedure is simple and fast. Without subsequent knockout of the endogenous recombination system, TDAH could also generate the relatively stable high-copy tandem duplication for plasmid-carried and genome-integrated DNA. TDAH also showed an excellent capacity for increase gene expression and worked well in different industrial bacteria. We also applied TDAH to select the optimal high copy number of ribA for vitamin B2 production in E. coli; the yield was improved by 3.5 times and remained stable even after 12 subcultures. TDAH is a useful tool for recombinant protein production and expression optimization of biosynthetic pathways.

Key points

• We develop a novel and efficient technique (TDAH) for tandem gene duplication in bacterium. TDAH is based on the mechanism of HTG rapid activation. TDAH does not contain any reported functional elements based on homologous recombination and DNA amplification. TDAH only contains an essential selectable marker for copy number selection, so its construction and procedure are very simple and fast.

• TDAH is the first reported selected and stable tandem-gene-duplication technique in which the selected high-copy plasmid-carried and genome-integrated DNA could remain stable without the subsequent knockout of recombination system.

• TDAH showed an excellent capacity for regulating gene expression and worked well in different industrial bacteria, indicating it is a useful tool for recombinant protein production and expression optimization of biosynthetic pathways.

• TDAH was applied to select the optimal high copy number of ribA for vitamin B2 production in E. coli; the yield was improved by 3.5-fold and remained stable even after 12 subcultures.
Flow-cytometry Assessment of DNA content and Immunophenotyping of Immune-cells in Lymph-node-specimens as a Potential Diagnostic Signature of Aggressiveness in B-Non-Hodgkin Lymphomas
Authors: Azoulay David , Tapuchi Tal , Ronen Ohad , Akria Luiza , Cohen Hector I. , Surio Celia , Chepa Svetlana Rodin , Eshel Elizabeth , Zarfati Moran , Stemer Galia , Horowitz Netanel A.
Published: May 2024

Flow-cytometry (FC) is a powerful tool that can assist in lymphoma diagnosis in lymph node (LN) specimens. Although lymphoma diagnosis and classification are mainly based on tumor cell characteristics, surrounding cells are less employed in this process. We retrospectively investigated alterations in the ploidy status, proliferative cell fraction (PF) and the percentages of surrounding immune cells in 62 consecutive LN specimens with B-Cell Non-Hodgkin Lymphoma (B-NHL) that were submitted for FC evaluation between 2019–2022. Compared with indolent B-NHLs, aggressive B-NHLs show increased DNA aneuploidy and PF, increased monocytes, immature-granulocytes, mature granulocytes, CD8+ T-cells, Double-Negative-T-cells and Double-Positive-T-cells, and decreased total CD45+ cells, total lymphocytes, CD4+ T-cells and CD4/CD8 ratio. Receiver operating characteristic analysis determined PF > 6.8% and immature-granulocytes > 0.9% as optimal cutoffs with highest specificity and sensitivity in differentiating aggressive and indolent B-NHLs. These findings further strength the diagnostic value of DNA content analysis by FC and suggest the utilization of tumor surrounding immune cells in NHL diagnosis and classification.
SA and NHP glucosyltransferase UGT76B1 affects plant defense in both SID2- and NPR1-dependent and independent manner
Authors: Zhang Wei , Maksym Rafał , Georgii Elisabeth , Geist Birgit , Schäffner Anton R.
Published: May 2024

Key message

The small-molecule glucosyltransferase loss-of-function mutant ugt76b1 exhibits both SID2- or NPR1-dependent and independent facets of enhanced plant immunity, whereupon FMO1 is required for the SID2 and NPR1 independence.

The small-molecule glucosyltransferase UGT76B1 inactivates salicylic acid (SA), isoleucic acid (ILA), and N-hydroxypipecolic acid (NHP). ugt76b1 loss-of-function plants manifest an enhanced defense status. Thus, we were interested how UGT76B1 genetically integrates in defense pathways and whether all impacts depend on SA and NHP. We study the integration of UGT76B1 by transcriptome analyses of ugt76b1. The comparison of transcripts altered by the loss of UGT76B1 with public transcriptome data reveals both SA-responsive, ISOCHORISMATE SYNTHASE 1/SALICYLIC ACID INDUCTION DEFICIENT 2 (ICS1/SID2)- and NON EXPRESSOR OF PR GENES 1 (NPR1)-dependent, consistent with the role of UGT76B1 in glucosylating SA, and SA-non-responsive, SID2/NPR1-independent genes. We also discovered that UGT76B1 impacts on a group of genes showing non-SA-responsiveness and regulation by infections independent from SID2/NPR1. Enhanced resistance of ugt76b1 against Pseudomonas syringae is partially independent from SID2 and NPR1. In contrast, the ugt76b1-activated resistance is completely dependent on FMO1 encoding the NHP-synthesizing FLAVIN-DEPENDENT MONOOXYGENASE 1). Moreover, FMO1 ranks top among the ugt76b1-induced SID2- and NPR1-independent pathogen responsive genes, suggesting that FMO1 determines the SID2- and NPR1-independent effect of ugt76b1. Furthermore, the genetic study revealed that FMO1, ENHANCED DISEASE SUSCEPTIBILITY 1 (EDS1), SID2, and NPR1 are required for the SA–JA crosstalk and senescence development of ugt76b1, indicating that EDS1 and FMO1 have a similar effect like stress-induced SA biosynthesis (SID2) or the key SA signaling regulator NPR1. Thus, UGT76B1 influences both SID2/NPR1-dependent and independent plant immunity, and the SID2/NPR1 independence is relying on FMO1 and its product NHP, another substrate of UGT76B1.
ESR Essentials: using the right scoring system in prostate MRI—practice recommendations by ESUR
Authors: Ponsiglione Andrea , Brembilla Giorgio , Cuocolo Renato , Gutierrez Patricia , Moreira Ana Sofia , Pecoraro Martina , Zawaideh Jeries , Barentsz Jelle , Giganti Francesco , Padhani Anwar R. , Panebianco Valeria , Puech Philippe , Villeirs Geert
Published: May 2024

MRI has gained prominence in the diagnostic workup of prostate cancer (PCa) patients, with the Prostate Imaging Reporting and Data System (PI-RADS) being widely used for cancer detection. Beyond PI-RADS, other MRI-based scoring tools have emerged to address broader aspects within the PCa domain. However, the multitude of available MRI-based grading systems has led to inconsistencies in their application within clinical workflows. The Prostate Cancer Radiological Estimation of Change in Sequential Evaluation (PRECISE) assesses the likelihood of clinically significant radiological changes of PCa during active surveillance, and the Prostate Imaging for Local Recurrence Reporting (PI-RR) scoring system evaluates the risk of local recurrence after whole-gland therapies with curative intent. Underlying any system is the requirement to assess image quality using the Prostate Imaging Quality Scoring System (PI-QUAL). This article offers practicing radiologists a comprehensive overview of currently available scoring systems with clinical evidence supporting their use for managing PCa patients to enhance consistency in interpretation and facilitate effective communication with referring clinicians.

Key Points

Assessing image quality is essential for all prostate MRI interpretations and the PI-QUAL score represents  the standardized tool for this purpose.

Current urological clinical guidelines for prostate cancer diagnosis and localization recommend adhering to the PI-RADS recommendations.

The PRECISE and PI-RR scoring systems can be used for assessing radiological changes of prostate cancer during active surveillance and the likelihood of local recurrence after radical treatments respectively.
Comparative Physiological and Transcriptomic Profiling Reveals the Characteristics of Tissue Tolerance Mechanisms in the japonica Rice Landrace Under Salt Stress
Authors: Fauzia Anisa Nazera , Nampei Mami , Jiadkong Kamonthip , Shinta  , Sreewongchai Tanee , Ueda Akihiro
Published: May 2024

The aim of this study was to characterize the tissue tolerance mechanisms of rice under salt stress. Our preliminary experiment identified a japonica rice landrace Shuzenji-kokumai (SZK), which is considered to be tissue-tolerant because it can maintain better growth than salt-sensitive rice varieties while having a high-Na+ concentration in the shoots under salt stress. These mechanisms differ from those of most salt-tolerant rice varieties, which have low Na+ concentrations in the shoots. We compared the physiological and molecular characteristics of SZK with those of FL478, a salt-tolerant variety, and Kunishi, a salt-sensitive variety. Under salt stress conditions, SZK accumulated high levels of Na+ in the roots, leaf sheaths, and leaf blades, which were almost as high as those in the salt-sensitive Kunishi. Simultaneously, SZK maintained better growth and physiological status, as determined by its higher dry weight, lower electrolyte leakage ratio, and lower malondialdehyde concentration. Expressions of OsNHX1 and OsNHX2 were upregulated in the leaf sheaths of SZK, suggesting that Na+ might be compartmentalized in the vacuoles to avoid cytosolic Na+ toxicity. In contrast, FL478 showed upregulation of OsHKT1;5 and OsSOS1 in the roots, which may exclude Na+ from the shoots. RNA-seq analysis showed that 4623 and 1998 differentially expressed genes were detected in the leaf sheaths and leaf blades of SZK, respectively. Among them, the HSP (heat shock protein) gene expression was highly up-regulated only in SZK, indicating that SZK protects against the protein damage caused by Na+ toxicity. Our findings suggest that SZK has atypical survival mechanisms under salt stress conditions. These mechanisms offer potential traits for improving salt tolerance in rice in terms of tissue tolerance.
Anatomic parameters of omphaloceles and their association with anatomic, genetic, or syndromic malformations: a retrospective study
Authors: Parata Gallien , Vial Yvan , Addor Marie-Claude , Pellegrinelli Jean-Marie , Wildhaber Barbara E.
Published: May 2024

Purpose

This retrospective study aims to describe anatomical parameters of omphaloceles and to analyze their association with anatomical, genetic, or syndromic malformations.

Methods

Cases were selected from digital records of two university centers, a certified regional registry and personal records. Patients from 1998 to 2018 with omphalocele and live birth (LB), termination of pregnancy due to fetal anomaly (TOPFA) and fetal death (FD) were included. Cases born outside Western Switzerland and/or with upper or lower coelosomy were excluded.

Results

We analyzed 162 cases with the following distribution: 57 (35%) LB, 91 (56%) TOPFA and 14 (9%) FD. TOPFA was significantly more frequently performed in cases with non-isolated omphalocele, i.e., omphaloceles with associated major malformations (especially cardiovascular and genitourinary), genetic/chromosomal anomalies, or syndromes. For LB, associated anatomical malformations, genetic or chromosomal anomalies were not significantly associated with the size of the omphalocele or the liver involvement.

Conclusions

The proportion of cases resulting in TOPFA was higher among fetuses with major malformations, genetic or chromosomal anomalies. Despite the large size of this cohort, and in contrary to previous publications, the size of the omphalocele and/or liver involvement does not allow for conclusions regarding the presence or number of associated malformations, genetic or chromosomal anomalies.
The impact of different anticoagulants and antiplatelets regimens on acute epistaxis outcomes
Authors: Zloczower Elchanan , Pinhas Sapir , Allon Raviv , Syn-Hershko Adi , Raz Yarkoni Tom , Marom Maayan , Kiderman David , Cohen Oded , Warman Meir
Published: May 2024

Background

The impact of anticoagulants (AC) and antiplatelets (AP) on the management of acute epistaxis remains unclear. This study investigated the association between AC/AP therapy and treatment outcomes in patients with acute epistaxis.

Methodology

A retrospective analysis of patients presented to the otolaryngology emergency room with acute epistaxis (2014–2022). Patients were categorized based on their regular medications: AP, dual AP therapy (DAPT), new oral anticoagulants (NOAC), vitamin K antagonists (VKA), or no regular AC/AP use (control group). Outcome measures included rates of minor interventions (chemical or electrical cautery, nasal tamponade), major interventions (endoscopic ligation, embolization), recurrent emergency department visits, admission rates, and duration.

Results

786 patients were included with an average follow-up period of 52.56 ± 20.4 months. Compared to the control group, patients on AP, DAPT, or VKA had significantly higher rates of minor interventions (63.1% vs. 74.4%, 79.6%, and 77.3%, respectively, p < 0.05). DAPT users exhibited a higher rate of major interventions than the control (5.6% vs. 1.3%, p = 0.053). NOAC users showed no significant difference in minor interventions compared to control and required no major interventions. Both NOAC and VKA users had significantly higher rates of recurrent epistaxis events and prolonged hospitalization compared to the control (p < 0.01 and p < 0.05, respectively).

Conclusions

NOAC demonstrated more favorable outcomes than VKA in patients with acute epistaxis, and DAPT use was associated with an increased need for major interventions. These findings suggest a more conservative approach in NOAC users than other AC/AP agents.
Effectiveness of cannabis use and cannabis use disorder interventions: a European and international data synthesis
Authors: Connor Jason P. , Manthey Jakob , Hall Wayne , Stjepanović Daniel
Published: May 2024

This data synthesis examined the effectiveness of behavioural and pharmacological approaches for cannabis treatment. We integrated findings from high level evidence studies and prioritised data from Europe when available. The synthesis found that only a relatively small number of published behavioural and pharmacological studies on cannabis interventions have been conducted in Europe. Applying both European and non-European data, it was found that Cognitive Behavioural Therapy (CBT) and/or Motivational Enhancement Therapy (MET) improved short-term outcomes in the frequency of cannabis use and dependency severity, although abstinence outcomes were less consistent. These improvements were typically not maintained nine months after treatment. CBT and MET (or combined CBT + MET) treatments that extend beyond four sessions were more effective than fewer sessions over a shorter duration. Combining CBT or MET (or combined CBT + MET) with adjunctive Contingency Management (CM) improved therapeutic outcomes. No pharmacotherapies have been approved for the management of cannabis use, cannabis use disorders or cannabis withdrawal. Despite only weak evidence to support the use of pharmacological agents, some are used ‘off-label’ to manage withdrawal symptoms outside clinical trials.
Congenital central hypoventilation syndrome in korea: 20 years of clinical observation and evaluation of the ventilation strategy in a single center
Authors: Lee Min Jeong , Park Ji Soo , Kim Kyunghoon , Ko Jung Min , Park June Dong , Suh Dong In
Published: May 2024

Congenital central hypoventilation syndrome (CCHS) is a rare genetic disorder characterized by hypoventilation due to impaired breathing control by the central nervous system and other symptoms of autonomic dysfunction. Mutations in paired-like homeobox 2 B (PHOX2B) are responsible for most cases of CCHS. Patients with CCHS have various phenotypes and severities, making the diagnosis difficult. This study aimed to present a comprehensive single-center experience of patients with CCHS, including key clinical features, treatment strategies, and outcomes. A retrospective chart review was performed for patients diagnosed with CCHS between January 2001 and July 2023 at Seoul National University Children’s Hospital. Finally, we selected 24 patients and collected their demographic data, genotypes, ventilation methods, and clinical features related to autonomic dysfunction. The relationship between the clinical manifestations and genotypes was also examined. All patients used home ventilators, and tracheostomy was performed in 87.5% of patients. Fifteen (62.5%) patients had constipation and nine (37.5%) were diagnosed with Hirschsprung disease. Arrhythmia, endocrine dysfunction, and subclinical hypothyroidism were present in nine (37.5%), six patients (25.0%), and two patients (16.7%), respectively. A significant number of patients exhibited neurodevelopmental delays (19 patients, 79.2%). There was a correlation between the phenotype and genotype of PHOX2B in patients with CCHS. (r = 0.71, p < 0.001).

   Conclusion: There was a positive correlation between paired-like homeobox 2 B mutations (especially the number of GCN repeats in the polyalanine repeat mutations sequence) and clinical manifestations. This study also demonstrated how initial treatment for hypoventilation affects neurodevelopmental outcomes in patients with CCHS.

What is Known:• Congenital central hypoventilation syndrome is a rare genetic disorder characterized by hypoventilation and dysfunction of autonomic nervous system.• The disease-defining gene of CCHS isPHOX2Bgene – most of the cases have heterozygous PARMs and the number of GCN triplets varies among the patients(20/24 – 20/33).

What is New:• We have noted in the Korean patients with CCHS that there is a correlation between genotype (number of GCN repeats) and severity of phenotype.• National support for rare diseases allowed for a prompter diagnosis of patients with CCHS in Korean population.
Chemotherapy-induced febrile neutropenia (FN): healthcare resource utilization (HCRU) and costs in commercially insured patients in the US
Authors: Flanigan Jeanine A. , Yasuda Marie , Chen Chi-Chang , Li Edward C.
Published: May 2024

Purpose

Febrile neutropenia (FN) is a known side effect of chemotherapy, often requiring hospitalization. Economic burden increases with an FN episode and estimates of cost per episode should be updated from real-world data.

Methods

A retrospective claims analysis of FN episodes in patients with non-myeloid malignancies from 2014 to 2021 was performed in IQVIA PharMetrics® Plus database. FN episodes were defined as having same-day claims for neutropenia and fever or infection, plus antibiotic in outpatient settings, following a claim for chemotherapy; index date was defined as the first claim for neutropenia/fever/infection. Patients receiving bone marrow/stem cell transplant and CAR-T therapy were excluded, as were select hematologic malignancies or COVID-19. Healthcare utilization and costs were evaluated and described overall, by episode type (w/wo hospitalization), index year, malignancy type, NCI comorbidity score, and age group.

Results

7,033 FN episodes were identified from 6,825 patients. Most episodes had a hospitalization (91.2%) and 86% of patients had ≥1 risk factor for FN. Overall, FN episodes had a mean (SD) FN-related cost of $25,176 ($39,943). Episodes with hospitalization had higher average FN-related costs versus those without hospitalization ($26,868 vs $7,738), and costs increased with comorbidity score (NCI=0: $23,095; NCI >0-2: $26,084; NCI ≥2: $26,851).

Conclusions

FN continues to be associated with significant economic burden, and varied by cancer type, comorbidity burden, and age. In this analysis, most FN episodes were not preceded by GCSF prophylaxis. The results of this study highlight the opportunity to utilize GCSF in appropriate oncology scenarios.