bluuebunny/crossref_metadata_2025 huggingface dataset:
Eculizumab administration for myasthenia gravis also stabilizes thrombogenicity of catastrophic antiphospholipid syndrome
Authors: Takahashi Sunao , Sanjo Nobuo , Koike Ryuji , Yokota Takanori
Published: April 2024

Background

The co‐occurrence of myasthenia gravis and primary antiphospholipid syndrome (APS) is rare. Notably, both the diseases share common complement‐mediated mechanisms.

Case Presentation

A 36‐year‐old woman, who was previously diagnosed with myasthenia gravis and APS, developed multiple embolisms, involving the brain, kidney and spleen, with severe anemia and platelet reduction. She was diagnosed as catastrophic APS, and intensive immunotherapies, including plasma exchange, high‐dose corticosteroid and rituximab, were introduced. After these therapies, symptoms of both APS and myasthenia gravis worsened, consistent with elevation of immunoglobulin G anti‐beta‐2‐glycoprotein‐I antibody and anti‐acetylcholine receptor antibody. We started eculizumab, which resulted in stabilizing the disease activity of both diseases without notable adverse events.

Conclusions

Eculizumab can be effective for controlling multiple complement‐mediated pathophysiology.
Real‐time Neural Rendering of Dynamic Light Fields
Authors: Coomans Arno , Dominci Edoardo A. , Döring Christian , Mueller Joerg H. , Hladky Jozef , Steinberger Markus
Published: April 2024

Synthesising high‐quality views of dynamic scenes via path tracing is prohibitively expensive. Although caching offline‐quality global illumination in neural networks alleviates this issue, existing neural view synthesis methods are limited to mainly static scenes, have low inference performance or do not integrate well with existing rendering paradigms. We propose a novel neural method that is able to capture a dynamic light field, renders at real‐time frame rates at 1920×1080 resolution and integrates seamlessly with Monte Carlo ray tracing frameworks. We demonstrate how a combination of spatial, temporal and a novel surface‐space encoding are each effective at capturing different kinds of spatio‐temporal signals. Together with a compact fully‐fused neural network and architectural improvements, we achieve a twenty‐fold increase in network inference speed compared to related methods at equal or better quality. Our approach is suitable for providing offline‐quality real‐time rendering in a variety of scenarios, such as free‐viewpoint video, interactive multi‐view rendering, or streaming rendering. Finally, our work can be integrated into other rendering paradigms, e.g., providing a dynamic background for interactive scenarios where the foreground is rendered with traditional methods.
Single‐Image SVBRDF Estimation with Learned Gradient Descent
Authors: Luo X. , Scandolo L. , Bousseau A. , Eisemann E.
Published: April 2024

Recovering spatially‐varying materials from a single photograph of a surface is inherently ill‐posed, making the direct application of a gradient descent on the reflectance parameters prone to poor minima. Recent methods leverage deep learning either by directly regressing reflectance parameters using feed‐forward neural networks or by learning a latent space of SVBRDFs using encoder‐decoder or generative adversarial networks followed by a gradient‐based optimization in latent space. The former is fast but does not account for the likelihood of the prediction, i.e., how well the resulting reflectance explains the input image. The latter provides a strong prior on the space of spatially‐varying materials, but this prior can hinder the reconstruction of images that are too different from the training data. Our method combines the strengths of both approaches. We optimize reflectance parameters to best reconstruct the input image using a recurrent neural network, which iteratively predicts how to update the reflectance parameters given the gradient of the reconstruction likelihood. By combining a learned prior with a likelihood measure, our approach provides a maximum a posteriori estimate of the SVBRDF. Our evaluation shows that this learned gradient‐descent method achieves state‐of‐the‐art performance for SVBRDF estimation on synthetic and real images.
Pan‐striatal reduction in the expression of the astrocytic dopamine transporter precedes the development of dorsolateral striatum dopamine‐dependent incentive heroin seeking habits
Authors: Hynes Tristan , Fouyssac Maxime , Puaud Mickaël , Joshi Dhaval , Chernoff Chloe , Stiebahl Sonja , Michaud Lola , Belin David
Published: April 2024

The emergence of compulsive drug‐seeking habits, a hallmark feature of substance use disorder, has been shown to be predicated on the engagement of dorsolateral striatal control over behaviour. This process involves the dopamine‐dependent functional coupling of the anterior dorsolateral striatum (aDLS) with the nucleus accumbens core, but the mechanisms by which this coupling occurs have not been fully elucidated. The striatum is tiled by a syncytium of astrocytes that express the dopamine transporter (DAT), the level of which is altered in individuals with heroin use disorder. Astrocytes are therefore uniquely placed functionally to bridge dopamine‐dependent mechanisms across the striatum. Here we tested the hypothesis that exposure to heroin influences the expression of DAT in striatal astrocytes across the striatum before the development of DLS‐dependent incentive heroin seeking habits. Using Western‐blot, qPCR, and RNAscope™, we measured DAT protein and mRNA levels in whole tissue, culture and in situ astrocytes from striatal territories of rats with a well‐established cue‐controlled heroin seeking habit and rats trained to respond for heroin or food under continuous reinforcement. Incentive heroin seeking habits were associated with a reduction in DAT protein levels in the anterior aDLS that was preceded by a heroin‐induced reduction in DAT mRNA and protein in astrocytes across the striatum. Striatal astrocytes were also shown to be susceptible to direct dopamine‐ and opioid‐induced downregulation of DAT expression. These results suggest that astrocytes may critically regulate the striatal dopaminergic adaptations that lead to the development of incentive heroin seeking habits.
Not an immune cell, but they may act like one—cells with immune properties outside the immune system
Authors: Typiak Marlena , Żurawa‐Janicka Dorota
Published: April 2024

The cells presented in this work are not classified as cells that make up the immune system. They, however, present functions and molecules, which are characteristic of immune cells. These characteristic functions are, for example, sensing threat, performing phagocytosis, presentation of foreign antigens, cytokine release or enhancing immune memory. The enlisted immune response mechanisms are carried out by the possession of molecules such as Toll‐like receptors, receptors for the Fc fragment of IgG, major histocompatibility complex class II molecules, costimulatory CD80/CD86 proteins and molecules needed for NLRP3 (NOD‐like family pyrin domain containing 3) inflammasome activation. Thanks to these properties, the described nonimmune cells play an important role in the local immune response and support of the entire body in the fight against pathogens. They constitute the first line of defense of tissues and organs against pathogens and molecules recognized as harmful. The cells described in this article are particularly important in immunologically privileged places (e.g. the Bowman's capsule in the kidney), where “typical” immune cells normally do not have access. In this paper, we present immune‐like functions and molecule suites of resident kidney cells (podocytes and mesangial cells), cochlear resident cells, fibrocytes and fibroblasts, as well as some stem cells (mesenchymal stem cells and umbilical cord Wharton's jelly–derived cells).
Mpox vaccination routes: prevalence, correlates and adverse effects of subcutaneous versus intradermal vaccination at a mass vaccination clinic in Sydney, Australia
Authors: Pollack Alisa , Lo Winston , Imamura Hanaho , Caterson Ian
Published: April 2024

The Royal Prince Alfred Hospital Mpox Vaccination Clinic opened in response to the 2022 multicountry mpox outbreak. A total of 9500 vaccinations were administered intradermally and subcutaneously during the first 16 weeks of clinic operation. The rate of adverse events was 0.1%. Compared to people who received the vaccine intradermally, those who received it subcutaneously were more likely to be aged 30–39 years (P = 0.047), sexual partners of gay and bisexual men (P < 0.001), eligible for Medicare (P < 0.001) and born in the Philippines (P = 0.01) or Malaysia (P = 0.04).
Proteomic studies in VWA1‐related neuromyopathy allowed new pathophysiological insights and the definition of blood biomarkers
Authors: Athamneh Mohammed , Daya Nassam , Hentschel Andreas , Gangfuss Andrea , Ruck Tobias , Marina Adela Della , Schara‐Schmidt Ulrike , Sickmann Albert , Güttsches Anne‐Katrin , Deschauer Marcus , Preusse Corinna , Vorgerd Matthias , Roos Andreas
Published: April 2024

Bi‐allelic variants in VWA1, encoding Von Willebrand Factor A domain containing 1 protein localized to the extracellular matrix (ECM), were linked to a neuromuscular disorder with manifestation in child‐ or adulthood. Clinical findings indicate a neuromyopathy presenting with muscle weakness. Given that pathophysiological processes are still incompletely understood, and biomarkers are still missing, we aimed to identify blood biomarkers of pathophysiological relevance: white blood cells (WBC) and plasma derived from six VWA1‐patients were investigated by proteomics. Four proteins, BET1, HNRNPDL, NEFM and PHGDH, known to be involved in neurological diseases and dysregulated in WBC were further validated by muscle‐immunostainings unravelling HNRNPDL as a protein showing differences between VWA1‐patients, healthy controls and patients suffering from neurogenic muscular atrophy and BICD2‐related neuromyopathy. Immunostaining studies of PHGDH indicate its involvement in apoptotic processes via co‐localisation with caspase‐3. NEFM showed an increase in cells within the ECM in biopsies of all patients studied. Plasma proteomics unravelled dysregulation of 15 proteins serving as biomarker candidates among which a profound proportion of increased ones (6/11) are mostly related to antioxidative processes and have even partially been described as blood biomarkers for other entities of neuromuscular disorders before. CRP elevated in plasma also showed an increase in the extracellular space of VWA1‐mutant muscle. Results of our combined studies for the first time describe pathophysiologically relevant biomarkers for VWA1‐related neuromyopathy and suggest that VWA1‐patient derived blood might hold the potential to study disease processes of clinical relevance, an important aspect for further preclinical studies.
Macrophage‐derived extracellular vesicles alter cardiac recovery and metabolism in a rat heart model of donation after circulatory death
Authors: Graf Selianne , Biemmi Vanessa , Arnold Maria , Segiser Adrian , Müller Anja , Méndez‐Carmona Natalia , Egle Manuel , Siepe Matthias , Barile Lucio , Longnus Sarah
Published: April 2024

Conditions to which the cardiac graft is exposed during transplantation with donation after circulatory death (DCD) can trigger the recruitment of macrophages that are either unpolarized (M0) or pro‐inflammatory (M1) as well as the release of extracellular vesicles (EV). We aimed to characterize the effects of M0 and M1 macrophage‐derived EV administration on post‐ischaemic functional recovery and glucose metabolism using an isolated rat heart model of DCD. Isolated rat hearts were subjected to 20 min aerobic perfusion, followed by 27 min global, warm ischaemia or continued aerobic perfusion and 60 min reperfusion with or without intravascular administration of EV. Four experimental groups were compared: (1) no ischaemia, no EV; (2) ischaemia, no EV; (3) ischaemia with M0‐macrophage‐dervied EV; (4) ischaemia with M1‐macrophage‐derived EV. Post‐ischaemic ventricular and metabolic recovery were evaluated. During reperfusion, ventricular function was decreased in untreated ischaemic and M1‐EV hearts, but not in M0‐EV hearts, compared to non‐ischaemic hearts (p < 0.05). In parallel with the reduced functional recovery in M1‐EV versus M0‐EV ischaemic hearts, rates of glycolysis from exogenous glucose and oxidative metabolism tended to be lower, while rates of glycogenolysis and lactate release tended to be higher. EV from M0‐ and M1‐macrophages differentially affect post‐ischaemic cardiac recovery, potentially by altering glucose metabolism in a rat model of DCD. Targeted EV therapy may be a useful approach for modulating cardiac energy metabolism and optimizing graft quality in the setting of DCD.
Identification of PPAR‐related differentially expressed genes liver hepatocellular carcinoma and construction of a prognostic model based on data analysis and molecular docking
Authors: Wang Yumeng , Li Shuqiang , Liu Zihang , Li Xuanzheng , Yu Yifan , Liu Hao
Published: April 2024

Liver hepatocellular carcinoma (LIHC) is a significant global health issue with limited treatment options. In this study, single‐cell RNA sequencing (scRNA‐seq) data were used to explore the molecular mechanisms of LIHC development and identify potential targets for therapy. The expression of peroxisome proliferator‐activated receptors (PPAR)‐related genes was analysed in LIHC samples, and primary cell populations, including natural killer cells, T cells, B cells, myeloid cells, endothelial cells, fibroblasts and hepatocytes, were identified. Analysis of the differentially expressed genes (DEGs) between normal and tumour tissues revealed significant changes in gene expression in various cell populations. PPAR activity was evaluated using the ‘AUCell’ R software, which indicated higher scores in the normal versus the malignant hepatocytes. Furthermore, the DEGs showed significant enrichment of pathways related to lipid and glucose metabolism, cell development, differentiation and inflammation. A prognostic model was then constructed using 8 PPARs‐related genes, including FABP5, LPL, ACAA1, PPARD, FABP4, PLIN1, HMGCS2 and CYP7A1, identified using least absolute shrinkage and selection operator‐Cox regression analysis, and validated in the TCGA‐LIHC, ICGI‐LIRI and GSE14520 datasets. Patients with low‐risk scores had better prognosis in all cohorts. Based on the expression of the eight model genes, two clusters of patients were identified by ConsensusCluster analysis. We also predicted small‐molecule drugs targeting the model genes, and identified perfluorohexanesulfonic acid, triflumizole and perfluorononanoic acid as potential candidates. Finally, wound healing assay confirmed that PPARD can promote the migration of liver cancer cells. Overall, our study offers novel perspectives on the molecular mechanisms of LIHC and potential areas for therapeutic intervention, which may facilitate the development of more effective treatment regimens.
An enhanced hybrid model for batch sugar crystallization based on the pattern recognition for overall heat transfer coefficient using a machine learning approach
Authors: Azizi Mohammad , Mosharaf‐Dehkordi Mehdi , Fouladi Nourbaksh , Kazanci Caner
Published: April 2024

A hybrid model is developed and evaluated to simulate the heat and mass transfer in the crystallization unit of a sugar factory. While the mass transfer is modeled by using the kinetic growth rate model, the heat transfer is simulated by applying the energy balance to the model. Here, the overall convection heat transfer coefficient of the crystallizer's heat exchanger is considered as a temperature‐dependent function. As this makes the governing equations more realistic, it can help to increase the model accuracy. Additionally, a thorough examination of key practical equations and principles governing the sugar crystallization process is presented. A regression learner method is applied to extract the pattern of the overall heat transfer coefficient. According to our results, the regression learning model successfully predicts the heat transfer coefficient with an average 7% deviation from experimental results. For the hybrid model, an average deviation of about 10% is observed. The crystallizer's behavior is somehow linear, indicating a constant growth rate of sugar crystals. Furthermore, the heat transfer in the crystallizer is improved by increasing the working temperatures.

Practical applications

The method and obtained results of this work could be used in the following practical purposes: to find the optimum working temperatures of crystallizers used in sugar industry and to predict total working time of batch crystallizers versus working parameters.
Correspondent Banking, Systemic Risk, and the Panic of 1893
Authors: COTTER CHRISTOPHER , ROUSSEAU PETER L.
Published: April 2024

During the U.S. National Banking Period (1863–1913), a network of correspondent bank relationships created vulnerabilities to bank failures and financial panics. Using data on correspondent relationships for all national, state, savings, and private banks just before the Panic of 1893, along with the precise dates of bank suspensions, we show that prior suspensions of both upstream and downstream correspondents increased the likelihood that a given bank would itself suspend, and that these effects varied over the Panic. Conditional on suspension, banks with prior correspondent suspensions were also more likely to reopen. New York Clearinghouse banks, despite low incidences of actual failure, saw significant balance sheet weakening early in the Panic when downstream respondents suspended, and falling stock prices throughout.
A perspective on automated rapid eye movement sleep assessment
Authors: Baumert Mathias , Phan Huy
Published: April 2024

Rapid eye movement sleep is associated with distinct changes in various biomedical signals that can be easily captured during sleep, lending themselves to automated sleep staging using machine learning systems. Here, we provide a perspective on the critical characteristics of biomedical signals associated with rapid eye movement sleep and how they can be exploited for automated sleep assessment. We summarise key historical developments in automated sleep staging systems, having now achieved classification accuracy on par with human expert scorers and their role in the clinical setting. We also discuss rapid eye movement sleep assessment with consumer sleep trackers and its potential for unprecedented sleep assessment on a global scale. We conclude by providing a future outlook of computerised rapid eye movement sleep assessment and the role AI systems may play.
Association between dietary protein intake and constipation: Data from the National Health and nutrition examination survey 2005–2010
Authors: Li Yi , Tong Wei‐Dong
Published: April 2024

Background

The association between dietary protein intake and constipation remains inconclusive. The aim of this study was to investigate whether dietary protein intake is associated with constipation.

Methods

This cross‐sectional study included 13,941 adults from the 2005 to 2010 National Health and Nutrition Examination Survey. A weighted logistic regression analysis was used to control for confounding factors. In addition, weighted interaction and stratified analyses were conducted to ascertain the potential modifying factors.

Results

The prevalence of constipation was 7.5% when constipation was defined by stool consistency and 3.5% when constipation was defined by stool frequency. After adjusting for covariates, an increase in dietary protein intake of 10 g was not associated with constipation, as defined by stool frequency (OR = 0.94, 95% CI = 0.54, 1.62) or stool consistency (OR = 1.02, 95% CI = 0.75, 1.39). Subgroup analyses revealed that dietary protein intake was associated with an increase in constipation defined by stool consistency risk in participants who consumed a low amount of carbohydrates (OR = 1.08, 95% CI = 1.02–1.14 for every 10‐g increase in protein intake), but a decrease in risk in participants in the moderate‐carbohydrate group (OR = 0.94, 95% CI = 0.89–0.99 for every 10‐g increase in protein intake), suggesting a significant interaction (p = 0.001).

Conclusion & Inferences

Dietary protein intake is not associated with stool consistency or frequency‐defined constipation. However, the association between dietary protein intake and constipation defined by stool consistency in participants with a low carbohydrate intake differed from that in participants with a moderate carbohydrate intake.
He who controls Clostridia and Bacteroidia controls the gut microbiome: The concept of targeted probiotics to restore the balance of keystone taxa in irritable bowel syndrome
Authors: Pokrotnieks Juris , Sitkin Stanislav
Published: April 2024

This article describes the concept of probiotics for patients with irritable bowel syndrome to target functionally active bacteria predominantly belonging to the Clostridia and Bacteroidia, which play a key role in maintaining the balance of the gut microbiota.
MicroRNA164e suppresses NAC100 transcription factor‐mediated synthesis of seed storage proteins in chickpea
Authors: Chakraborty Anirban , Singh Baljinder , Pandey Vimal , Parida Swarup K. , Bhatia Sabhyata
Published: April 2024

Development of protein‐enriched chickpea varieties necessitates an understanding of specific genes and key regulatory circuits that govern the synthesis of seed storage proteins (SSPs).

Here, we demonstrated the novel involvement of Ca‐miR164e‐CaNAC100 in regulating SSP synthesis in chickpea.

Ca‐miRNA164e was significantly decreased during seed maturation, especially in high‐protein accessions. The miRNA was found to directly target the transactivation conferring C‐terminal region of a nuclear‐localized transcription factor, CaNAC100 as revealed using RNA ligase‐mediated‐rapid amplification of cDNA ends and target mimic assays. The functional role of CaNAC100 was demonstrated through seed‐specific overexpression (NACOE) resulting in significantly augmented seed protein content (SPC) consequential to increased SSP transcription. Further, NACOE lines displayed conspicuously enhanced seed weight but reduced numbers and yield. Conversely, a downregulation of CaNAC100 and SSP transcripts was evident in seed‐specific overexpression lines of Ca‐miR164e that culminated in significantly lowered SPC. CaNAC100 was additionally demonstrated to transactivate the SSP‐encoding genes by directly binding to their promoters as demonstrated using electrophoretic mobility shift and dual‐luciferase reporter assays.

Taken together, our study for the first time established a distinct role of CaNAC100 in positively influencing SSP synthesis and its critical regulation by CamiR164e, thereby serving as an understanding that can be utilized for developing SPC‐rich chickpea varieties.
Clinical conundrums in pediatric kidney transplantation: What we know about the role of angiotensin II type I receptor antibodies in pediatric kidney transplantation and the path forward
Authors: Pearl Meghan H.
Published: April 2024

Antibodies to angiotensin II type 1 receptor (AT1R‐Abs) are among the most well‐studied non‐HLA antibodies in renal transplantation. These antibodies have been shown to be common in pediatric kidney transplantation and associated with antibody‐mediated rejection (AMR), vascular inflammation, development of human leukocyte donor‐specific antibodies (HLA DSA), and allograft loss. As AT1R‐Ab testing becomes more readily accessible, evidence to guide clinical practice for testing and treating AT1R‐Ab positivity in pediatric kidney transplant recipients remains limited. This review discusses the clinical complexities of evaluating AT1R‐Abs given the current available evidence.
Disentangling hydroxynitrile glucoside biosynthesis in a barley (Hordeum vulgare) metabolon provides access to elite malting barleys for ethyl carbamate‐free whisky production
Authors: Jørgensen Morten E. , Houston Kelly , Jørgensen Hans Jørgen L. , Thomsen Hanne C. , Tekaat Linda , Krogh Camilla Timmermann , Mellor Silas B. , Braune Katarzyna Birch , Damm Mette L. , Pedas Pai Rosager , Voss Cynthia , Rasmussen Magnus Wohlfahrt , Nielsen Kasper , Skadhauge Birgitte , Motawia Mohammed S. , Møller Birger Lindberg , Dockter Christoph , Sørensen Mette
Published: April 2024

Barley produces several specialized metabolites, including five α‐, β‐, and γ‐hydroxynitrile glucosides (HNGs). In malting barley, presence of the α‐HNG epiheterodendrin gives rise to undesired formation of ethyl carbamate in the beverage production, especially after distilling. Metabolite‐GWAS identified QTLs and underlying gene candidates possibly involved in the control of the relative and absolute content of HNGs, including an undescribed MATE transporter. By screening 325 genetically diverse barley accessions, we discovered three H. vulgare ssp. spontaneum (wild barley) lines with drastic changes in the relative ratios of the five HNGs. Knock‐out (KO)‐lines, isolated from the barley FIND‐IT resource and each lacking one of the functional HNG biosynthetic genes (CYP79A12, CYP71C103, CYP71C113, CYP71U5, UGT85F22 and UGT85F23) showed unprecedented changes in HNG ratios enabling assignment of specific and mutually dependent catalytic functions to the biosynthetic enzymes involved. The highly similar relative ratios between the five HNGs found across wild and domesticated barley accessions indicate assembly of the HNG biosynthetic enzymes in a metabolon, the functional output of which was reconfigured in the absence of a single protein component. The absence or altered ratios of the five HNGs in the KO‐lines did not change susceptibility to the fungal phytopathogen Pyrenophora teres causing net blotch. The study provides a deeper understanding of the organization of HNG biosynthesis in barley and identifies a novel, single gene HNG‐0 line in an elite spring barley background for direct use in breeding of malting barley, eliminating HNGs as a source of ethyl carbamate formation in whisky production.
Insights into U‐to‐C RNA editing from the lycophyte Phylloglossum drummondii
Authors: Kwok van der Giezen Farley M. , Viljoen Amy , Campbell‐Clause Leni , Dao Nhan Trong , Colas des Francs‐Small Catherine , Small Ian
Published: April 2024

The lycophyte Phylloglossum drummondii is the sole inhabitant of its genus in the Huperzioideae group and one of a small minority of plants which perform uridine to cytidine RNA editing. We assembled the P. drummondii chloroplast and mitochondrial genomes and used RNA sequence data to build a comprehensive profile of organellar RNA editing events. In addition to many C‐to‐U editing events in both organelles, we found just four U‐to‐C editing events in the mitochondrial transcripts cob, nad1, nad5 and rpl2. These events are conserved in related lycophytes in the genera Huperzia and Phlegmariurus. De novo transcriptomes for three of these lycophytes were assembled to search for putative U‐to‐C RNA editing enzymes. Four putative U‐to‐C editing factors could be matched to the four mitochondrial U‐to‐C editing sites. Due to the unusually few numbers of U‐to‐C RNA editing sites, P. drummondii and related lycophytes are useful models for studying this poorly understood mechanism.
Computed tomographic features of exocrine pancreatic carcinomas in dogs and cats
Authors: Dunn Alexandra , Rao Sangeeta , Husbands Brian , Petrovitch Nicholas , Loeber Samantha , Schwarz Tobias , Cline Kelsey , Mai Wilfried , Spain Heather , Curran Kaitlin , Vickery Kate , Marolf Angela
Published: April 2024

Exocrine pancreatic carcinomas are uncommon in dogs and cats, and diagnosis with diagnostic imaging can be challenging. This retrospective, multi‐institutional, descriptive study was performed to evaluate the CT features of exocrine pancreatic carcinomas. The CT examinations of 18 dogs and 12 cats with exocrine pancreatic carcinomas diagnosed by cytology or histopathology were reviewed. The CT features of exocrine pancreatic carcinomas included a well‐defined mass in 28/30 (93%) with contrast enhancement in 27/30 (90%), commonly heterogeneous 22/30 (73%); often with a nonenhancing fluid to soft tissue attenuating center 12/30 (40%). The right lobe of the pancreas was the most common location, 14/30 (47%), then the left lobe, 10/30 (33%), and the body, 6/30 (20%). Extrahepatic biliary duct dilation was present in six animals; 5/6 (83%) of the masses were located in the right pancreatic lobe. Additional findings included peripancreatic fat‐stranding 17/30 (57%), lymphadenopathy 16/30 (57%), peripancreatic soft tissue nodules 12/30 (40%), and free fluid 10/30 (33%). When comparing the imaging features of dogs and cats, there was a large overlap in imaging characteristics. There was a significant difference between the height of the masses, with dogs having larger masses (P‐value.0028). Lymphadenopathy was more likely in larger masses [increased height (P‐value.029)]. Cats were significantly older than dogs (P‐value.0355). Pancreatic carcinomas were commonly identified as masses with heterogeneous contrast enhancement and a nonenhancing fluid to soft tissue attenuating center with concurrent peripancreatic changes (fat‐stranding and/or soft tissue nodules) and lymphadenopathy.
Analysis of Ultimate Gas Recovery in Shale Reservoirs
Authors: Zhang Yiming , Kleit Andrew , Morgan Eugene , Wang John
Published: April 2024

Horizontal wells with multistage fracture treatments enabled economic gas production from shale gas reservoirs. Recovery from a typical shale reservoir is usually quite low as numerous factors can affect the ultimate recovery. However, recovery factors inside and outside the stimulated reservoir volume (SRV), especially the variations spatially and temporally, are not yet fully understood as the numerical simulation of shale gas production is still challenging. In this study, a dual-porosity, dual-permeability model was built to investigate ultimate gas recovery and its spatial variations throughout the production period. Parametric studies were conducted to evaluate the effect of matrix permeability, fracture conductivity, fracture half length, and operating conditions on recovery factors. Systematic and comprehensive numerical experiments were carried out to generate a probability distribution of ultimate recovery factors. The results presented in this article provide insight into the impact that key parameters have on these recovery factors in and outside the SRV and the range of recovery factors one can expect from shale gas reservoirs. Fracture conductivity has the most impact on recovery in the SRV while matrix permeability can affect the recovery outside the SRV significantly. The expected recovery in the SRV is 24% in shale reservoirs. The methodology in this study provides a foundation to develop more reliable models in accurately forecasting ultimate gas recoveries spatially for shale gas reservoirs. The new understanding can be applied to optimize field development, well spacing, and infill drilling to increase economic recovery.
An Underactuated Cable-Driven Parallel Robot for Marine Automated Launch and Recovery Operations
Authors: Angelini Michele , Ida’ Edoardo , Bertin Daniele , Mantovani Enrico , Bazzi Davide , Orassi Vincenzo , Carricato Marco
Published: April 2024

This article presents the feasibility study and preliminary testing of an underactuated cable-driven parallel robot for automated launch and recovery operations on the sea surface. The robot frame is mounted onto a primary vessel (PV) subject to sea-induced motions. During launch, the end-effector (EE) is required to deploy a secondary vessel (SV) by lowering it from the PV onto the sea surface. During recovery, the EE has to track and grasp a SV, and the EE-SV assembly needs to be stabilized during lifting from the sea surface to the PV. Sea conditions and the underactuated nature of the EE influence the operational feasibility and the overall robot performance. This article presents the conceptual design and the robot model, as well as the methodologies for winch dimensioning and robot control. An extensive simulation campaign is conducted to optimize performances and assess the system behavior. Finally, the operations are tested on a scaled prototype in a laboratory environment.
Azole resistance mechanisms and population structure of the human pathogen
Aspergillus fumigatus
on retail plant products
Authors: Wang Caroline , Miller Natalie , Vines Douglas , Severns Paul M. , Momany Michelle , Brewer Marin T.
Published: April 2024

Aspergillus fumigatus
is a ubiquitous saprotroph and human-pathogenic fungus that is life-threatening to the immunocompromised. Triazole-resistant
A. fumigatus
was found in patients without prior treatment with azoles, leading researchers to conclude that resistance had developed in agricultural environments where azoles are used against plant pathogens. Previous studies have documented azole-resistant
A. fumigatus
across agricultural environments, but few have looked at retail plant products. Our objectives were to determine if azole-resistant
A. fumigatus
is prevalent in retail plant products produced in the United States (U.S.), as well as to identify the resistance mechanism(s) and population genetic structure of these isolates. Five hundred twenty-five isolates were collected from retail plant products and screened for azole resistance. Twenty-four isolates collected from compost, soil, flower bulbs, and raw peanuts were pan-azole resistant. These isolates had the TR
34
/L98H, TR
46
/Y121F/T289A, G448S, and H147Y
cyp51A
alleles, all known to underly pan-azole resistance, as well as WT alleles, suggesting that non-cyp51A mechanisms contribute to pan-azole resistance in these isolates. Minimum spanning networks showed two lineages containing isolates with TR alleles or the F46Y/M172V/E427K allele, and discriminant analysis of principle components identified three primary clusters. This is consistent with previous studies detecting three clades of
A. fumigatus
and identifying pan-azole-resistant isolates with TR alleles in a single clade. We found pan-azole resistance in U.S. retail plant products, particularly compost and flower bulbs, which indicates a risk of exposure to these products for susceptible populations and that highly resistant isolates are likely distributed worldwide on these products.

IMPORTANCE

Aspergillus fumigatus
has recently been designated as a critical fungal pathogen by the World Health Organization. It is most deadly to people with compromised immune systems, and with the emergence of antifungal resistance to multiple azole drugs, this disease carries a nearly 100% fatality rate without treatment or if isolates are resistant to the drugs used to treat the disease. It is important to determine the relatedness and origins of resistant
A. fumigatus
isolates in the environment, including plant-based retail products, so that factors promoting the development and propagation of resistant isolates can be identified.
Complete genome sequences of
Aerococcus loyolae
ATCC TSD-300
T
,
Aerococcus mictus
ATCC TSD-301
T
, and
Aerococcus tenax
ATCC TSD-302
T
Authors: Choi Brian I. , Fontes Noronha Melline , Kaindl Jacob , Wolfe Alan J.
Published: April 2024

Previously identified under the single designation of
Aerococcus urinae
, three distinct taxonomic species have been distinguished as
Aerococcus loyolae, Aerococcus mictus,
and
Aerococcus tenax
. Here, we present the complete genome sequences of the type strains of these species assembled via a combination of short-read and long-read sequencing techniques.

Registered at ClinicalTrials.gov (
NCT01166438
).
A novel cgMLST for genomic surveillance of
Yersinia enterocolitica
infections in France allowed the detection and investigation of outbreaks in 2017–2021
Authors: Le Guern Anne-Sophie , Savin Cyril , Chereau Fanny , Tessier Sabrina , Guglielmini Julien , Brémont Sylvie , Pizarro-Cerdá Javier
Published: April 2024

Enteric yersiniosis, the third most common food-borne zoonosis in Europe, is mainly caused by the pathogen
Yersinia enterocolitica
. In France
,
the yersiniosis microbiological surveillance is conducted at the
Yersinia
National Reference Laboratory (YNRL). Since 2017, isolates have been characterized by whole genome sequencing (WGS) followed by a 500-gene
Yersinia
-cgMLST. We report here the data of the WGS-based surveillance on
Y. enterocolitica
isolates for the 2017–2021 period. The YNRL characterized 7,642
Y. enterocolitica
strains distributed in 2,497 non-pathogenic isolates from lineages 1Aa and 1Ab, and 5,145 specimens belonging to 8 pathogenic lineages. Among pathogenic isolates, lineage 4 was the most common (87.2%) followed by lineages 2/3-9b (10.6%), 2/3-5a (1.2%), 2/3-9a (0.6%), 3-3b, 3-3c, 1B, and 3-3d (0.1% per each). Importantly, we developed a routine surveillance system based on a new typing method consisting of a 1,727-genes core genome Multilocus Sequence Typing (cgMLST) specific to the species
Y. enterocolitica
followed by isolate clustering. Thresholds of allelic distances (AD) were determined and fixed for the clustering of isolates: AD ≤ 5 for lineages 4, 2/3-5a, and 2/3-9a, and AD ≤ 3 for lineage 2/3-9b. Clustering programs were implemented in 2019 in routine surveillance to detect genomic clusters of pathogenic isolates. In total, 419 clusters with at least 2 isolates were identified, representing 2,504 of the 3,503 isolates characterized between 2019 and 2021. Most clusters (
n
= 325) comprised 2 to 5 isolates. The new typing method proved to be useful for the molecular investigation of unusual grouping of cases as well as for the detection of genomic clusters in routine surveillance.

IMPORTANCE

We describe here the new typing method used for molecular surveillance of
Yersinia enterocolitica
infections in France based on a novel core genome Multilocus Sequence Typing (cgMLST) specific to
Y. enterocolitica
species. This method can reliably identify the pathogenic
Y. enterocolitica
subspecies and compare the isolates with a high discriminatory power. Between 2017 and 2021, 5,145 pathogenic isolates belonging to 8 lineages were characterized and lineage 4 was by far the most common followed by lineage 2/3-9b. A clustering program was implemented, and detection thresholds were cross-validated by the molecular and epidemiological investigation of three unusual groups of
Y. enterocolitica
infections. The routine molecular surveillance system has been able to detect genomic clusters, leading to epidemiological investigations.
Misidentification and misreporting of antibiotic resistance in
Kluyvera
bacteremia by blood culture molecular identification panels
Authors: Vatterrodt Darrick , Lee Janelle , Ho Dooil , Stevig Craig , Chow Siu-Kei
Published: April 2024

The use of molecular identification panels has advanced the diagnosis for blood stream infections with fast turnaround time and high accuracy. Yet, this technology cannot completely replace conventional blood culture and standardized antibiotic susceptibility testing (AST) given its limitations and occasional false results. Here we present two cases of bacteremia caused by
Kluyvera
. Its identification and antibiotic resistance were at least partially mispresented by blood culture molecular identification panels on ePlex, Verigene, and Biofire. The detection of CTX-M resistance marker did not align with the susceptibility to the third generation cephalosporins among a wide range of antibiotics for this organism. Conventional extended-spectrum beta-lactamase (ESBL) testing was used to confirm the absence of ESBL. Caution should be taken when managing cases with CTX-M or ESBL detection in blood culture caused by uncommon pathogens. Conventional culture with microbial identification and standardized AST should continue to be the gold standard for routine patient care.

IMPORTANCE

This is the first report that highlights the limitations of blood culture molecular identification panels on identifying
Kluyvera
and its associated antibiotic resistance patterns. Both the false identification and overreporting of antibiotic resistance could mislead the treatment for bacteremia caused by this pathogen. Patient isolation could have been avoided due to the lack of extended-spectrum beta-lactamase (ESBL) activity of the organism. This report emphasizes the importance of confirming rapid identification and antibiotic resistance by molecular technologies with standardized methods. It also provides insight into the development of new diagnostic panels.
‘God protects us from death through faith and science’: a qualitative study on the role of faith leaders in combating the COVID-19 pandemic and in building COVID-19 vaccine trust in Addis Ababa, Ethiopia
Authors: Yibeltal Kalkidan , Workneh Firehiwot , Melesse Hanna , Wolde Habtamu , Kidane Workagegnhu Tarekegn , Berhane Yemane , Herzig van Wees Sibylle
Published: April 2024

Objective

This study explored faith leaders’ perspectives on the COVID-19 vaccine and their role in building COVID-19 vaccine trust in Addis Ababa, Ethiopia.

Design

A qualitative study with in-depth interviews and thematic analysis was conducted.

Participants

Twenty-one faith leaders from the seven religious groups represented in the Inter-Religious Council of Ethiopia participated in the study.

Setting

The study was conducted in Addis Ababa, Ethiopia.

Results

The thematic analysis revealed three themes. First, faith leaders were aware of the risks of the COVID-19 pandemic, although most ascribed a spiritual meaning to the advent of the pandemic. The pandemic seriously affected the faith communities, inflicting financial losses. Second, faith leaders were essential allies during the pandemic by effectively collaborating with government and health professionals in COVID-19 prevention activities and public health interventions using spiritual reasoning. They were actively informing the community about the importance of the COVID-19 vaccine, where many faith leaders were publicly vaccinated to build trust in the vaccine and act as role models. Third, despite this, they faced multiple questions from the congregation about the vaccine, including rumours.

Conclusions

This research showed that faith leaders played crucial roles in encouraging vaccine use but were limited in their persuasion power because of intense rumours and misinformation. Empowering faith leaders with the latest vaccine evidence needs to be prioritised in the future.
Epirubicin for the Treatment of Sepsis and Septic Shock (EPOS-1): study protocol for a randomised, placebo-controlled phase IIa dose-escalation trial
Authors: Thomas-Rüddel Daniel , Bauer Michael , Moita Luís Ferreira , Helbig Christiane , Schlattmann Peter , Ehler Johannes , Rahmel Tim , Meybohm Patrick , Gründling Matthias , Schenk Heiko , Köcher Thomas , Brunkhorst Frank M , Gräler Markus , Heger Ann-Julika , Weis Sebastian ,   EPOS-1 study group
Published: April 2024

Introduction

Sepsis remains the major cause of death among hospitalised patients in intensive care. While targeting sepsis-causing pathogens with source control or antimicrobials has had a dramatic impact on morbidity and mortality of sepsis patients, this strategy remains insufficient for about one-third of the affected individuals who succumb. Pharmacological targeting of mechanisms that reduce sepsis-defining organ dysfunction may be beneficial. When given at low doses, the anthracycline epirubicin promotes tissue damage control and lessens the severity of sepsis independently of the host–pathogen load by conferring disease tolerance to infection. Since epirubicin at higher doses can be myelotoxic, a first dose–response trial is necessary to assess the potential harm of this drug in this new indication.

Methods and analysis

Epirubicin for the Treatment of Sepsis and Septic Shock-1 is a randomised, double-blind, placebo-controlled phase 2 dose-escalation phase IIa clinical trial to assess the safety of epirubicin as an adjunctive in patients with sepsis. The primary endpoint is the 14-day myelotoxicity. Secondary and explorative outcomes include 30-day and 90-day mortality, organ dysfunction, pharmacokinetic/pharmacodynamic (PK/PD) and cytokine release. Patients will be randomised in three consecutive phases. For each study phase, patients are randomised to one of the two study arms (epirubicin or placebo) in a 4:1 ratio. Approximately 45 patients will be recruited. Patients in the epirubicin group will receive a single dose of epirubicin (3.75, 7.5 or 15 mg/m2depending on the study phase. After each study phase, a data and safety monitoring board will recommend continuation or premature stopping of the trial. The primary analyses for each dose level will report the proportion of myelotoxicity together with a 95% CI. A potential dose-toxicity association will be analysed using a logistic regression model with dose as a covariate. All further analyses will be descriptive.

Ethics and dissemination

The protocol is approved by the German Federal Institute for Drugs and Medical Devices. The results will be submitted for publication in peer-reviewed journals.

Trial registration number

NCT05033808.
Resonant detectors of gravitational wave in the linear and quadratic generalized uncertainty principle framework
Authors: Bhattacharyya Sukanta , Sen Soham , Gangopadhyay Sunandan
Published: April 2024

In this work, we consider a resonant bar detector of gravitational waves in the generalized uncertainty principle (GUP) framework with linear and quadratic momentum uncertainties. The phonon modes in these detectors vibrate due to the interaction with the incoming gravitational wave. In this uncertainty principle framework, we calculate the resonant frequencies and transition rates induced by the incoming gravitational waves on these detectors. We observe that the energy eigenstates and the eigenvalues get modified by the GUP parameters. We also observe non-vanishing transition probabilities between two adjacent energy levels due to the existence of the linear order momentum correction in the generalized uncertainty relation which was not present in the quadratic GUP analysis (Class Quantum Gravity 37:195006, 2020). We finally obtain bounds on the dimensionless GUP parameters using the form of the transition rates obtained during this analysis.
Sensing Using Terahertz Radiation
Authors: Shur Michael
Published: April 2024

Terahertz (THz) sensing technology enables 6G communication, detection of biological and chemical hazardous agents, cancer detection, monitoring of industrial processes and products, and detection of mines and explosives. THz sensors support security in buildings, airports, and other public spaces. They found important applications in radioastronomy and space research and, more recently, in Artificial Intelligence-driven THz sensing of MMICs and VLSI. Exploding demand for data transfers will require using the 300 GHz band after 2028 or even before and will make the deployment of THz sensing electronics inevitable. This paper discusses the new physics of THz sensing and THz sensing devices. It also reviews the THz sensing market, and key THz sensor companies.