bluuebunny/crossref_metadata_2025 huggingface dataset:
Management of patented ‘circular innovation’ in view of the circular economy
Authors: Valero‐Gil Jesús , Scarpellini Sabina
Published: February 2024

This study mainly aims to analyse whether innovation related to the circular economy's principles, defined as ‘circular innovation’, is closely linked to environmental disclosure and contributes to the generation of improvements in environmental performance. The article also aims to test whether waste patents, as a specific indicator of circular innovation, are more valuable assets that need specific strategic management due to their level of novelty, complexity, and radicalness being higher than other green or conventional innovations. The empirical analysis uses a rich firm‐level dataset of worldwide companies for the 2011–2015 period, with 1330 observations to show that environmental disclosure and environmental performance are positively associated with circular innovation. This innovation is in fact, more intensive in patent claims and patent citation generation, indicating a higher economic value for companies. The article contributes to this new line of inquiry on defining circular innovation, as well as providing some environmental determinants and consequences from the stakeholders' perspective in relation to circular business models.
Application of multi‐layer porcine small intestinal submucosa for the reconstruction of deep corneal defects in cats
Authors: Luo JingWen , Zhou ZhenLei
Published: February 2024

Objective

This study documented the application of porcine small intestinal submucosa (SIS) as a stand‐alone scaffold for treating deep corneal defects in cats.

Methods

Medical records of 20 cats with deep stromal ulcers, perforations, or corneal sequestra that underwent surgical treatment with SIS grafts between 2021 and 2022 were retrospectively reviewed. Data on re‐epithelialization time, corneal transparency score, and complications were collected to analyze the reconstruction of deep corneal defects after SIS biomaterial implantation.

Results

All cats were unilaterally affected. The corneal defects varied in size, with a median diameter of 8.3 mm (range: 3–15 mm). Re‐epithelialization of the SIS graft was completed 16–32 days after surgery (median, 22.3 days). No, mild, or moderate corneal transparency was detected in 90% of the cases. Complications were observed in eight cases (40%), including aqueous leakage (10%), partial SIS malacia (25%), and persistent bullous keratopathy (5%). The follow‐up period ranged 90–725 days, with a median duration of 255 days. The SIS graft was successfully applied as a single scaffold in 17 of 20 cases (85%).

Conclusion

The results of this study suggest that the application of commercial SIS is an effective surgical technique for managing deep corneal defects in cats.
The Interaction of Turbulent Spots With Low-Speed Streaks
Authors: Suryanarayanan Saikishan , Settlemier Anthony , Goldstein David B.
Published: February 2024

Turbulent spots are regions of turbulence surrounded by laminar flow that appear during the late stages of boundary layer transition. While turbulent spots are often studied in isolation, they usually occur near low-speed streaks and other disturbances during transition. This paper investigates the interaction between a turbulent spot and a subcritical low-speed streak using direct numerical simulations. The results, analyzed from streak instability and vorticity points of view, reveal mechanisms of the destabilization of the streak by the spot and provide insights into spot evolution in a realistic environment. Additional simulations involving intentional local control of portions of the streak provide further insight into the interaction mechanisms and potential transition mitigation strategies.
Enhancing Axial Flow Fan Performance in Air-Cooled Condensers: Tip Vortex Manipulators and Comparative Analysis of Numerical Simulation and Experimental Testing
Authors: Pretorius Johannes P. , van der Spuy Sybrand J.
Published: February 2024

Direct dry-cooled power plants typically operate numerous large-diameter axial flow fans in air-cooled condensers (ACCs) to facilitate the condensation of steam in the plant's thermodynamic cycle. Enhanced fan efficiency may, at scale, lead to significant parasitic power reductions and subsequent increases in plant power output. The performance of these fans may be increased by adding blade-tip modifications, which act to control blade-tip leakage flow. Previous studies have shown that manipulating the tip leakage vortex (TLV) increases the blade-to-air momentum transfer and stabilizes the air flow structures as it traverses the fan blade. This paper takes a step toward the development of improved tip vortex manipulators for an ACC fan. Three-dimensional computational fluid dynamics (CFD) simulations, and experimental testing of the modified and unmodified fan within an ISO test facility are performed. The results are then utilized to assess the accuracy of the simulation model, visualize the manipulated flow structures at the blade tip, and ultimately quantify the effect of the endplate designs on fan performance. Excellent correlation between numerical and test results for the unmodified fan is observed, and the benefit of blade-tip modification on fan performance is again confirmed experimentally. The simulation model, however, fails to predict improvements in fan performance under modification, and simulated tip leakage flows are investigated for clarification. It is hypothesized that deflection of tip endplates under operation account for differences between simulation and experiment, and that fluid–structure interaction analyses could potentially resolve discrepancies.
Bias voltage influence on the a-SiCx:H interlayer deposition using tetramethylsilane: Decorative applications of a-C:H thin films on steel
Authors: Goldbeck Michael C. , Piroli Vanessa , Weber Jennifer S. , Boeira Carla D. , Perotti Bruna L. , Fukumasu Newton K. , Alvarez Fernando , Figueroa Carlos A. , Michels Alexandre F.
Published: February 2024

Hydrogenated amorphous carbon (a-C:H) is a type of coating vastly applied on steel alloys due to its low friction coefficient, high hardness, and chemical inertness. Also, its characteristic brilliant black color like onyx stone is desirable for decorative applications. Despite the beneficial properties conferred to ferrous substrates, the adhesion of a-C:H films is weakened by its residual stress. In order to improve the adhesion of a-C:H films/steel alloy structures, one adopted strategy is the addition of an interlayer. This research investigated the influence of the bias voltage applied on the deposition of hydrogenated amorphous silicon carbide (a-SiCx:H) interlayers, with tetramethylsilane (TMS) as the precursor, to promote adhesion in a-C:H/a-SiCx:H/ferrous alloy structures for decorative applications. The thicker interlayer was achieved at −600 V. Two regimes were proposed to explain this behavior considering ionization rates and resputtering rates and chemical reactions in plasma. The chemical structure in different regions of the a-SiCx:H interlayer was analyzed in detail. An increase in the applied bias voltage leads to oxygen incorporation at the a-C:H/a-SiCx:H interface. Higher bias voltages result in lower silicon content at the a-SiCx:H/steel interface, which is correlated to the −800 V sample’s poor adhesion. Finally, we have included a discussion about a new range of loads when a decorative piece is held by the hand where the critical loads for delamination of a-C:H coatings measured here are good enough for decorative applications.
Silicon nanowires analyzed by x-ray photoelectron spectroscopy
Authors: Farid Ghulam , Chaitoglou Stefanos , Amade Roger , Ospina Rogelio , Bertran-Serra Enric
Published: February 2024

Silicon nanowires were characterized by x-ray photoelectron spectroscopy with an Al Kα (1486.6 eV) excitation source. The sample was fixed to a stainless-steel sample holder with a copper double-sided adhesive tape. Survey spectrum and C 1s, O 1s, and Si 2p core-level spectra were acquired.
FEFF analysis of americium oxides
Authors: Tobin J. G. , Yu S.-W. , Shuh D. K. , Butorin S. M.
Published: February 2024

The Am N4,5 (4d3/2 and 4d5/2) and Am O4,5 (5d3/2 and 5d5/2) x-ray absorption spectroscopy (XAS) of americium sesquioxide (Am2O3) and americium dioxide (AmO2) has been evaluated with FEFF, a Green's function–based, multiple scattering code. Taking guidance from the intermediate coupling model (ICM), applicable to local and nonmagnetized samples, it is possible to completely reconstruct the experimental results for the N4,5 spectra, including the observed differences between the Am2O3 and the AmO2 cases. Although complicated by a more asymmetric line shape and difficult background variations, the FEFF analysis confirms the absence of core hole angular momentum coupling in Am O4,5 spectroscopy.
Colocalization of protein and microRNA markers reveals unique extracellular vesicle subpopulations for early cancer detection
Authors: Li Zongbo , Guo Kaizhu , Gao Ziting , Chen Junyi , Ye Zuyang , Cao Minghui , Wang Shizhen Emily , Yin Yadong , Zhong Wenwan
Published: February 2024

Extracellular vesicles (EVs) play important roles in cell-cell communication but are highly heterogeneous, and each vesicle has dimensions smaller than 200 nm with very limited amounts of cargos encapsulated. The technique of NanOstirBar (NOB)–EnabLed Single Particle Analysis (NOBEL-SPA) reported in the present work permits rapid inspection of single EV with high confidence by confocal fluorescence microscopy, thus enables colocalization assessment for selected protein and microRNA (miRNA) markers in the EVs produced by various cell lines, or present in clinical sera samples. EV subpopulations marked by the colocalization of unique protein and miRNA combinations were discovered to be able to detect early-stage (stage I or II) breast cancer (BC). NOBEL-SPA can be adapted to analyze other types of cargo molecules or other small submicron biological particles. Study of the sorting of specific cargos to heterogeneous vesicles under different physiological conditions can help discover distinct vesicle subpopulations valuable in clinical examination and therapeutics development and gain better understanding of their biogenesis.
Structural analysis of PTPN21 reveals a dominant-negative effect of the FERM domain on its phosphatase activity
Authors: Chen Lu , Qian Zijun , Zheng Yuyuan , Zhang Jie , Sun Jie , Zhou Chun , Xiao Haowen
Published: February 2024

PTPN21 belongs to the four-point-one, ezrin, radixin, moesin (FERM) domain–containing protein tyrosine phosphatases (PTP) and plays important roles in cytoskeleton-associated cellular processes like cell adhesion, motility, and cargo transport. Because of the presence of a WPE loop instead of a WPD loop in the phosphatase domain, it is often considered to lack phosphatase activity. However, many of PTPN21’s biological functions require its catalytic activity. To reconcile these findings, we have determined the structures of individual PTPN21 FERM, PTP domains, and a complex between FERM-PTP. Combined with biochemical analysis, we have found that PTPN21 PTP is weakly active and is autoinhibited by association with its FERM domain. Disruption of FERM-PTP interaction results in enhanced ERK activation. The oncogenic HPV18 E7 protein binds to PTP at the same location as PTPN21 FERM, indicating that it may act by displacing the FERM domain from PTP. Our results provide mechanistic insight into PTPN21 and benefit functional studies of PTPN21-mediated processes.
Cryo-EM analysis of
S. aureus
TarL, a polymerase in wall teichoic acid biogenesis central to virulence and antibiotic resistance
Authors: Li Franco K. K. , Worrall Liam J. , Gale Robert T. , Brown Eric D. , Strynadka Natalie C. J.
Published: February 2024

Wall teichoic acid (WTA), a covalent adduct of Gram-positive bacterial cell wall peptidoglycan, contributes directly to virulence and antibiotic resistance in pathogenic species. Polymerization of the
Staphylococcus aureus
WTA ribitol-phosphate chain is catalyzed by TarL, a member of the largely uncharacterized TagF-like family of membrane-associated enzymes. We report the cryo–electron microscopy structure of TarL, showing a tetramer that forms an extensive membrane-binding platform of monotopic helices. TarL is composed of an amino-terminal immunoglobulin-like domain and a carboxyl-terminal glycosyltransferase-B domain for ribitol-phosphate polymerization. The active site of the latter is complexed to donor substrate cytidine diphosphate–ribitol, providing mechanistic insights into the catalyzed phosphotransfer reaction. Furthermore, the active site is surrounded by electropositive residues that serve to retain the lipid-linked acceptor for polymerization. Our data advance general insight into the architecture and membrane association of the still poorly characterized monotopic membrane protein class and present molecular details of ribitol-phosphate polymerization that may aid in the design of new antimicrobials.
Chemical and genetic basis of orange flavor
Authors: Fan Zhen , Jeffries Kristen A. , Sun Xiuxiu , Olmedo Gabriela , Zhao Wei , Mattia Matthew R. , Stover Ed , Manthey John A. , Baldwin Elizabeth A. , Lee Seonghee , Gmitter Frederick G. , Plotto Anne , Bai Jinhe
Published: February 2024

Sweet orange (
Citrus sinensis
) exhibits limited genetic diversity and high susceptibility to Huanglongbing (HLB). Breeding HLB-tolerant orange-like hybrids is in dire need. However, our understanding of the key compounds responsible for orange flavor and their genetic regulation remains elusive. Evaluating 179 juice samples, including oranges, mandarins,
Poncirus trifoliata
, and hybrids, distinct volatile compositions were found. A random forest model predicted untrained samples with 78% accuracy and identified 26 compounds crucial for orange flavor. Notably, seven esters differentiated orange from mandarin flavor. Cluster analysis showed six esters with shared genetic control. Differential gene expression analysis identified
C. sinensis alcohol acyltransferase 1
(
CsAAT1
) responsible for ester production in orange. Its activity was validated through overexpression assays. Phylogeny revealed the functional allele was inherited from pummelo. A SNP-based DNA marker in the coding region accurately predicted phenotypes. This study enhances our understanding of orange flavor compounds and their biosynthetic pathways and expands breeding options for orange-like cultivars.
Modulating tumoral exosomes and fibroblast phenotype using nanoliposomes augments cancer immunotherapy
Authors: Freag May S. , Mohammed Mostafa T. , Kulkarni Arpita , Emam Hagar E. , Maremanda Krishna P. , Elzoghby Ahmed O.
Published: February 2024

Cancer cells program fibroblasts into cancer associated fibroblasts (CAFs) in a two-step manner. First, cancer cells secrete exosomes to program quiescent fibroblasts into activated CAFs. Second, cancer cells maintain the CAF phenotype via activation of signal transduction pathways. We rationalized that inhibiting this two-step process can normalize CAFs into quiescent fibroblasts and augment the efficacy of immunotherapy. We show that cancer cell–targeted nanoliposomes that inhibit sequential steps of exosome biogenesis and release from lung cancer cells block the differentiation of lung fibroblasts into CAFs. In parallel, we demonstrate that CAF-targeted nanoliposomes that block two distinct nodes in fibroblast growth factor receptor (FGFR)–Wnt/β-catenin signaling pathway can reverse activate CAFs into quiescent fibroblasts. Co-administration of both nanoliposomes significantly improves the infiltration of cytotoxic T cells and enhances the antitumor efficacy of αPD-L1 in immunocompetent lung cancer–bearing mice. Simultaneously blocking the tumoral exosome-mediated activation of fibroblasts and FGFR-Wnt/β-catenin signaling constitutes a promising approach to augment immunotherapy.
From salt water to bioceramics: Mimic nature through pressure-controlled hydration and crystallization
Authors: Liu Jia-hua , Huang Changxiong , Wu Haikun , Long Yunchen , Tang Xinxue , Li Hongkun , Shen Junda , Zhou Binbin , Zhang Yibo , Xu Zhengtao , Fan Jun , Zeng Xiao Cheng , Lu Jian , Li Yang Yang
Published: February 2024

Modern synthetic technology generally invokes high temperatures to control the hydration level of ceramics, but even the state-of-the-art technology can still only control the overall hydration content. Magically, natural organisms can produce bioceramics with tailorable hydration profiles and crystallization traits solely from amorphous precursors under physiological conditions. To mimic the biomineralization tactic, here, we report pressure-controlled hydration and crystallization in fabricated ceramics, solely from the amorphous precursors of purely inorganic gels (PIGs) synthesized from biocompatible aqueous solutions with most common ions in organisms (Ca
2+
, Mg
2+
, CO
3
2−
, and PO
4
3−
). Transparent ceramic tablets are directly produced by compressing the PIGs under mild pressure, while the pressure regulates the hydration characteristics and the subsequent crystallization behaviors of the synthesized ceramics. Among the various hydration species, the moderately bound and ordered water appears to be a key in regulating the crystallization rate. This nature-inspired study offers deeper insights into the magic behind biomineralization.
An ingestible self-propelling device for intestinal reanimation
Authors: Srinivasan Shriya S. , Dosso Julien , Huang Hen-Wei , Selsing George , Alshareef Amro , Kuosmanen Johannes , Ishida Keiko , Jenkins Joshua , Madani Wiam Abdalla Mohammed , Hayward Alison , Traverso Giovanni
Published: February 2024

Postoperative ileus (POI) is the leading cause of prolonged hospital stay after abdominal surgery and is characterized by a functional paralysis of the digestive tract, leading to symptoms such as constipation, vomiting, and functional obstruction. Current treatments are mainly supportive and inefficacious and yield acute side effects. Although electrical stimulation studies have demonstrated encouraging pacing and entraining of the intestinal slow waves, no devices exist today to enable targeted intestinal reanimation. Here, we developed an ingestible self-propelling device for intestinal reanimation (INSPIRE) capable of restoring peristalsis through luminal electrical stimulation. Optimizing mechanical, material, and electrical design parameters, we validated optimal deployment, intestinal electrical luminal contact, self-propelling capability, safety, and degradation of the device in ex vivo and in vivo swine models. We compared the INSPIRE’s effect on motility in models of normal and depressed motility and chemically induced ileus. Intestinal contraction improved by 44% in anesthetized animals and up to 140% in chemically induced ileus cases. In addition, passage time decreased from, on average, 8.6 days in controls to 2.5 days with the INSPIRE device, demonstrating significant improvement in motility. Luminal electrical stimulation of the intestine via the INSPIRE efficaciously restored peristaltic activity. This noninvasive option offers a promising solution for the treatment of ileus and other motility disorders.
Endothelial cells drive organ fibrosis in mice by inducing expression of the transcription factor SOX9
Authors: Trogisch Felix A. , Abouissa Aya , Keles Merve , Birke Anne , Fuhrmann Manuela , Dittrich Gesine M. , Weinzierl Nina , Wink Elvira , Cordero Julio , Elsherbiny Adel , Martin-Garrido Abel , Grein Steve , Hemanna Shruthi , Hofmann Ellen , Nicin Luka , Bibli Sofia-Iris , Airik Rannar , Kispert Andreas , Kist Ralf , Quanchao Sun , Kürschner Sina W. , Winkler Manuel , Gretz Norbert , Mogler Carolin , Korff Thomas , Koch Philipp-Sebastian , Dimmeler Stefanie , Dobreva Gergana , Heineke Joerg
Published: February 2024

Fibrosis is a hallmark of chronic disease. Although fibroblasts are involved, it is unclear to what extent endothelial cells also might contribute. We detected increased expression of the transcription factor
Sox9
in endothelial cells in several different mouse fibrosis models. These models included systolic heart failure induced by pressure overload, diastolic heart failure induced by high-fat diet and nitric oxide synthase inhibition, pulmonary fibrosis induced by bleomycin treatment, and liver fibrosis due to a choline-deficient diet. We also observed up-regulation of endothelial SOX9 in cardiac tissue from patients with heart failure. To test whether SOX9 induction was sufficient to cause disease, we generated mice with endothelial cell–specific overexpression of
Sox9
, which promoted fibrosis in multiple organs and resulted in signs of heart failure. Endothelial
Sox9
deletion prevented fibrosis and organ dysfunction in the two mouse models of heart failure as well as in the lung and liver fibrosis mouse models. Bulk and single-cell RNA sequencing of mouse endothelial cells across multiple vascular beds revealed that SOX9 induced extracellular matrix, growth factor, and inflammatory gene expression, leading to matrix deposition by endothelial cells. Moreover, mouse endothelial cells activated neighboring fibroblasts that then migrated and deposited matrix in response to SOX9, a process partly mediated by the secreted growth factor CCN2, a direct SOX9 target; endothelial cell–specific
Sox9
deletion reversed these changes. These findings suggest a role for endothelial SOX9 as a fibrosis-promoting factor in different mouse organs during disease and imply that endothelial cells are an important regulator of fibrosis.
A multifunctional flavoprotein monooxygenase HspB for hydroxylation and C-C cleavage of 6-hydroxy-3-succinoyl-pyridine
Authors: Ouyang Xingyu , Liu Gongquan , Guo Lihua , Wu Geng , Xu Ping , Zhao Yi-Lei , Tang Hongzhi
Published: February 2024

Flavoprotein monooxygenases catalyze reactions, including hydroxylation and epoxidation, involved in the catabolism, detoxification, and biosynthesis of natural substrates and industrial contaminants. Among them, the 6-hydroxy-3-succinoyl-pyridine (HSP) monooxygenase (HspB) from
Pseudomonas putida
S16 facilitates the hydroxylation and C-C bond cleavage of the pyridine ring in nicotine. However, the mechanism for biodegradation remains elusive. Here, we refined the crystal structure of HspB and elucidated the detailed mechanism behind the oxidative hydroxylation and C-C cleavage processes. Leveraging structural information about domains for binding the cofactor flavin adenine dinucleotide (FAD) and HSP substrate, we used molecular dynamics simulations and quantum/molecular mechanics calculations to demonstrate that the transfer of an oxygen atom from the reactive FAD peroxide species (C4a-hydroperoxyflavin) to the C3 atom in the HSP substrate constitutes a rate-limiting step, with a calculated reaction barrier of about 20 kcal/mol. Subsequently, the hydrogen atom was rebounded to the FAD cofactor, forming C4a-hydroxyflavin. The residue Cys218 then catalyzed the subsequent hydrolytic process of C-C cleavage. Our findings contribute to a deeper understanding of the versatile functions of flavoproteins in the natural transformation of pyridine and HspB in nicotine degradation.

IMPORTANCE

Pseudomonas putida
S16 plays a pivotal role in degrading nicotine, a toxic pyridine derivative that poses significant environmental challenges. This study highlights a key enzyme, HspB (6-hydroxy-3-succinoyl-pyridine monooxygenase), in breaking down nicotine through the pyrrolidine pathway. Utilizing dioxygen and a flavin adenine dinucleotide cofactor, HspB hydroxylates and cleaves the substrate’s side chain. Structural analysis of the refined HspB crystal structure, combined with state-of-the-art computations, reveals its distinctive mechanism. The crucial function of Cys218 was never discovered in its homologous enzymes. Our findings not only deepen our understanding of bacterial nicotine degradation but also open avenues for applications in both environmental cleanup and pharmaceutical development.
Utilizing cost-effective portable equipment to enhance COVID-19 variant tracking both on-site and at a large scale
Authors: Park Sung Yong , Faraci Gina , Ward Pamela , Lee Ha Youn
Published: February 2024

Despite optimistic predictions on the eventual end of COVID-19 (Coronavirus Disease 2019), caution is necessary regarding the emergence of new variants to sustain a positive outlook and effectively address any potential future outbreaks. However, ongoing efforts to track COVID-19 variants are concentrated in developed countries and unique social practices and remote habitats of indigenous peoples present additional challenges. By combining small-sized equipment that is easily accessible and inexpensive, we performed SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) whole genome sequencing and measured the sample-to-answer time and accuracy of this portable variant tracking tool. Our portable design determined the variant of SARS-CoV-2 in an infected individual within 9 hours and 15 minutes without external power or internet connection, surpassing the speed of previous portable tools. It took only 16 minutes to complete sequencing run, whole genome assembly, and lineage determination using a single standalone laptop. We then demonstrated the capability to produce 289 SARS-CoV-2 whole genome sequences in a single portable sequencing run, representing a significant improvement over an existing throughput of 96 sequences per run. We verified the accuracy of portable sequencing by comparison with two other independent sequencing methods. We showed that our high-throughput data consistently represented the circulating variants in Los Angeles, United States, when compared with publicly available sequences. Our scheme is designed to be flexible, rapid, and accurate, making it a valuable tool for large-scale surveillance operations in low- and middle-income countries as well as targeted surveys for vulnerable populations in remote locations.

IMPORTANCE

There have been significant efforts to track COVID-19 (Coronavirus Disease 2019) variants, accumulating over 15 million SARS-CoV-2 sequences as of 2023. However, the distribution of global survey data is highly skewed, with nearly half of all countries having inadequate or low levels of genomic surveillance. In addition, indigenous peoples face more severe threats from COVID-19, due to their generally remote residence and unique social practices. Cost-effective portable sequencing tools have been used to investigate Ebola and Zika outbreaks. However, these tools have a sample-to-answer time of around 24 hours and require an internet connection for data transfer to an off-site cloud server. In our study, we rapidly determined COVID-19 variants using only small and inexpensive equipment, with a completion time of 9 hours and 15 minutes. Furthermore, we produced 289 near-full-length SARS-CoV-2 genome sequences from a single portable Nanopore sequencing run, representing a threefold increase in throughput compared with existing Nanopore sequencing methods.
The H9N2 avian influenza virus increases APEC adhesion to oviduct epithelia by viral NS1 protein-mediated activation of the TGF-β pathway
Authors: Han Jinjie , Chang Wenchi , Fang Junyang , Hou Xiaolan , Li Zhijun , Wang Jingyu , Deng Wen
Published: February 2024

H9N2 avian influenza is a low-pathogenic avian influenza circulating in poultry and wild birds worldwide and frequently contributes to chicken salpingitis that is caused by avian pathogenic
Escherichia coli
(APEC), leading to huge economic losses and risks for food safety. Currently, how the H9N2 virus contributes to APEC infection and facilitates salpingitis remains elusive. In this study,
in vitro
chicken oviduct epithelial cell (COEC) model and
in vivo
studies were performed to investigate the role of H9N2 viruses on secondary APEC infection, and we identified that H9N2 virus enhances APEC infection both
in vitro
and
in vivo
. To understand the mechanisms behind this phenomenon, adhesive molecules on the cell surface facilitating APEC adhesion were checked, and we found that H9N2 virus could upregulate the expression of fibronectin, which promotes APEC adhesion onto COECs. We further investigated how fibronectin expression is regulated by H9N2 virus infection and revealed that transforming growth factor beta (TGF-β) signaling pathway is activated by the NS1 protein of the virus, thus regulating the expression of adhesive molecules. These new findings revealed the role of H9N2 virus in salpingitis co-infected with APEC and discovered the molecular mechanisms by which the H9N2 virus facilitates APEC infection, offering new insights to the etiology of salpingitis with viral-bacterial co-infections.

IMPORTANCE

H9N2 avian influenza virus (AIV) widely infects poultry and is sporadically reported in human infections. The infection in birds frequently causes secondary bacterial infections, resulting in severe symptoms like pneumonia and salpingitis. Currently, the mechanism that influenza A virus contributes to secondary bacterial infection remains elusive. Here we discovered that H9N2 virus infection promotes APEC infection and further explored the underlying molecular mechanisms. We found that fibronectin protein on the cell surface is vital for APEC adhesion and also showed that H9N2 viral protein NS1 increased the expression of fibronectin by activating the TGF-β signaling pathway. Our findings offer new information on how AIV infection promotes APEC secondary infection, providing potential targets for mitigating severe APEC infections induced by H9N2 avian influenza, and also give new insights on the mechanisms on how viruses promote secondary bacterial infections in animal and human diseases.
Ceramide-1-phosphate is a regulator of Golgi structure and is co-opted by the obligate intracellular bacterial pathogen
Anaplasma phagocytophilum
Authors: Read Curtis B. , Ali Anika N. , Stephenson Daniel J. , Macknight H. Patrick , Maus Kenneth D. , Cockburn Chelsea L. , Kim Minjung , Xie Xiujie , Carlyon Jason A. , Chalfant Charles E.
Published: February 2024

Many intracellular pathogens structurally disrupt the Golgi apparatus as an evolutionarily conserved promicrobial strategy. Yet, the host factors and signaling processes involved are often poorly understood, particularly for
Anaplasma phagocytophilum
, the agent of human granulocytic anaplasmosis. We found that
A. phagocytophilum
elevated cellular levels of the bioactive sphingolipid, ceramide-1-phosphate (C1P), to promote Golgi fragmentation that enables bacterial proliferation, conversion from its non-infectious to infectious form, and productive infection.
A. phagocytophilum
poorly infected mice deficient in ceramide kinase, the Golgi-localized enzyme responsible for C1P biosynthesis. C1P regulated Golgi morphology via activation of a PKCα/Cdc42/JNK signaling axis that culminates in phosphorylation of Golgi structural proteins, GRASP55 and GRASP65. siRNA-mediated depletion of Cdc42 blocked
A. phagocytophilum
from altering Golgi morphology, which impaired anterograde trafficking of
trans
-Golgi vesicles into and maturation of the pathogen-occupied vacuole. Cells overexpressing phosphorylation-resistant versions of GRASP55 and GRASP65 presented with suppressed C1P- and
A. phagocytophilum
-induced Golgi fragmentation and poorly supported infection by the bacterium. By studying
A. phagocytophilum
, we identify C1P as a regulator of Golgi structure and a host factor that is relevant to disease progression associated with Golgi fragmentation.

IMPORTANCE

Ceramide-1-phosphate (C1P), a bioactive sphingolipid that regulates diverse processes vital to mammalian physiology, is linked to disease states such as cancer, inflammation, and wound healing. By studying the obligate intracellular bacterium
Anaplasma phagocytophilum
, we discovered that C1P is a major regulator of Golgi morphology.
A. phagocytophilum
elevated C1P levels to induce signaling events that promote Golgi fragmentation and increase vesicular traffic into the pathogen-occupied vacuole that the bacterium parasitizes. As several intracellular microbial pathogens destabilize the Golgi to drive their infection cycles and changes in Golgi morphology is also linked to cancer and neurodegenerative disorder progression, this study identifies C1P as a potential broad-spectrum therapeutic target for infectious and non-infectious diseases.
Draft genome of three isolates of
Listeria monocytogenes
isolated from
Stenella coeruleoalba
in Italy
Authors: Scarpa Fabio , Grattarola Carla , Arillo Alessandra , Mattioda Virginia , Testori Camilla , Terracciano Giuliana , Senese Matteo , Giorda Federica , Zoppi Simona , Sanna Daria , Casu Marco , Peletto Simone
Published: February 2024

Listeria monocytogenes
is the etiological agent of the listeriosis. Here, we described three draft genome sequences of
L. monocytogenes
isolated in Italy from stranded individuals of the striped dolphin
Stenella coeruleoalba
. All the genomes have been molecular typed through the multilocus sequence typing to identify the phylogenetic lineage, clonal complex, sublineage, and serogroup.
Interpreting and reporting fission-track chronological data
Authors: Kohn Barry P. , Ketcham Richard A. , Vermeesch Pieter , Boone Samuel C. , Hasebe Noriko , Chew David , Bernet Matthias , Chung Ling , Danišík Martin , Gleadow Andrew J.W. , Sobel Edward R.
Published: February 2024

Fission-track dating is based on the analysis of tracks—linear damage trails—produced by the spontaneous fission of 238U in a range of natural accessory minerals and glasses. The retention of tracks is sensitive to elevated temperatures, and the data serve principally as a tool for recording thermal histories of rocks, potentially over the range of ~20–350 °C, depending on the specific minerals studied. As such, in most cases, fission-track data generally bear little or no direct relationship to the original formation age of the material studied. The age range of fission-track dating is related to the product of age and uranium content, and ages from several tens of years to older than 1 Ga are reported. Fission-track analysis led to the development of powerful modeling techniques. When used with appropriate geological constraints, these modeling techniques allow important geological processes to be addressed in a broad range of upper crustal settings.

Since early attempts to standardize the treatment of fission-track data and system calibration over more than 30 years ago, major advancements were made in the methodology, necessitating the development of new, updated data reporting requirements. Inconsistencies in reporting impede public data transparency, accessibility and reuse, Big Data regional syntheses, and interlaboratory analytical comparisons.

This paper briefly reviews the fundamentals of fission-track dating and applications to provide context for recommended guidelines for reporting and supporting essential meta fission-track data for publication and methodological archiving in structured formats that conform with FAIR (Findable, Accessible, Interoperable, and Reusable) data principles. Adopting such practices will ensure that data can be readily accessed, interrogated, and reused, allowing for further integration with other numerical geoscience techniques.
Subduction erosion revealed by exhumed lower arc crustal rocks in an accretionary complex, northeastern China
Authors: Xu Mengyu , Xiao Wenjiao , Liu Kai , Wan Bo , Mitchell Ross N. , Rosenbaum Gideon , Wang Hao
Published: February 2024

Subduction erosion at convergent margins is a leading mechanism for the destruction (recycling and reworking) of continental crust. But because of the lack of direct evidence, it is not straightforward to identify erosive events and their intensities in fossil subduction zones. The Heilongjiang accretionary complex in northeastern China was formed during the early Mesozoic subduction of the Paleo-Pacific Ocean. We investigated amphibolites from this accretionary complex, whose protoliths (based on whole-rock trace elements and Sr-Nd-Hf isotopes) were mafic continental arc magmatic rocks (255–249 Ma; zircon core U-Pb ages) from the upper plate. Phase equilibria modeling constrained by mineral geochemistry indicates that the amphibolites and their wall rocks were first heated to low granulite facies (750–800 °C, ~7 kbar) at 251–244 Ma (zircon rim U-Pb ages) and then cooled to ~700 °C with increasing pressure (8–9 kbar) before 213–187 Ma (titanite and apatite U-Pb ages). To explain the occurrence of the lower arc crustal lithologies in the accretionary complex and their metamorphic history, we propose that the subducting plate strongly eroded the forearc crust, allowing the plate interface to advance landward and scrape the amphibolites and wall rocks formed under the old arc, which finally were exhumed along the subduction channel and became components of the complex. The case study exemplifies direct petrological evidence of strong subduction erosion occurring in an ancient orogen, thus implying that consumption of the entire forearc crust could occur within only ~50 m.y.
Supplemental Material: Deep resistivity geophysics of the San Juan–Silverton caldera complex, San Juan County, Colorado
Authors: Rodriguez Brian D. , al. et
Published: February 2024

Magnetotelluric data analysis: Includes introductions to electrical rock properties and the magnetotelluric method, data processing approach, profile model construction, inversion parameters, and topographic effects.  
Factors that impact second attempt success for neonatal intubation following first attempt failure: a report from the National Emergency Airway Registry for Neonates
Authors: Johnson Mitchell David , Tingay David Gerald , Perkins Elizabeth J , Sett Arun , Devsam Bianca , Douglas Ellen , Charlton Julia K , Wildenhain Paul , Rumpel Jennifer , Wagner Michael , Nadkarni Vinay , Johnston Lindsay , Herrick Heidi M , Hartman Tyler , Glass Kristen , Jung Philipp , DeMeo Stephen D , Shay Rebecca , Kim Jae H , Unrau Jennifer , Moussa Ahmed , Nishisaki Akira , Foglia Elizabeth E
Published: February 2024

Objective

To determine the factors associated with second attempt success and the risk of adverse events following a failed first attempt at neonatal tracheal intubation.

Design

Retrospective analysis of prospectively collected data on intubations performed in the neonatal intensive care unit (NICU) and delivery room from the National Emergency Airway Registry for Neonates (NEAR4NEOS).

Setting

Eighteen academic NICUs in NEAR4NEOS.

Patients

Neonates requiring two or more attempts at intubation between October 2014 and December 2021.

Main outcome measures

The primary outcome was successful intubation on the second attempt, with severe tracheal intubation-associated events (TIAEs) or severe desaturation (≥20% decline in oxygen saturation) being secondary outcomes. Multivariate regression examined the associations between these outcomes and patient characteristics and changes in intubation practice.

Results

5805 of 13 126 (44%) encounters required two or more intubation attempts, with 3156 (54%) successful on the second attempt. Second attempt success was more likely with changes in any of the following: intubator (OR 1.80, 95% CI 1.56 to 2.07), stylet use (OR 1.65, 95% CI 1.36 to 2.01) or endotracheal tube (ETT) size (OR 2.11, 95% CI 1.74 to 2.56). Changes in stylet use were associated with a reduced chance of severe desaturation (OR 0.74, 95% CI 0.61 to 0.90), but changes in intubator, laryngoscope type or ETT size were not; no changes in intubator or equipment were associated with severe TIAEs.

Conclusions

Successful neonatal intubation on a second attempt was more likely with a change in intubator, stylet use or ETT size.
Comparison of two bicycle handlebar trauma cases
Authors: Atkinson Cameron James , Rajagopalan Sriram
Published: February 2024

Handlebar injury is an uncommon mechanism of blunt injury with a recognised risk of injury to groin vasculature. We describe two cases involving bicycle handlebar injury to the groin and their different respective outcomes. Patient A sustained a significant limb-threatening injury following significant arterial and venous disruption. Surgical intervention was able to restore arterial flow via interpositional vein graft, while venous injuries were ligated. As a result, the patient was discharged with a viable limb and a non-disabling swelling from venous pathology. Patient B, of identical age, also sustained a bicycle handlebar injury to the groin but without the need for surgical intervention. Active observation and the use of repeat imaging suggested spontaneous cessation of any minor arterial bleeding; the patient made a rapid recovery and was discharged soon thereafter. These cases highlight the variability in outcome stemming from this injury mechanism and that early recognition is vital for limb viability.
Association between age-related macular degeneration and risk of incident cancer
Authors: Park Junhee , Jung Wonyoung , Han Kyungdo , Kim Bongseong , Lee Seung-Yeon , Yoon Je Moon , Lim Dong Hui , Shin Dong Wook
Published: February 2024

Background/aims

Age-related macular degeneration (AMD) and cancer may share similar risk factors, indicating possible common pathogenic pathways. We aimed to describe the site-specific cancer risk based on the relationship of AMD with visual disability (VD) status.

Methods

This was a population-based cohort study using data from the Korean National Health Insurance Service database (2009–2019) including patients who participated in a national health screening programme in 2009. The subjects were categorised based on the presence of AMD and VD. The occurrence of cancer was identified using principal diagnosis according to the International Classification of Disease, 10th revision codes in claims data. The Cox regression hazard model was used to compare HRs of site-specific cancer.

Results

Among 4 088 814 participants, 51 596 had AMD of which 3683 subjects had VD. The mean follow-up period was 9.6 years. The overall cancer risk was generally null, but the risk of hypervascular cancer such as thyroid cancer (adjusted HR (aHR) 1.10, 95% CI 1.00 to 1.20) and renal cancer (aHR 1.16, 95% CI 1.00 to 1.33) was higher and the risk of stomach cancer (aHR 0.89, 95% CI 0.84 to 0.94) was lower in the AMD group than in the non-AMD group.

Conclusion

This study demonstrated a possible association between AMD and several cancers. Increased renal and thyroid cancer risk among patients with AMD could indicate that AMD is associated with hypervascular cancer. Further studies in which additional databases are used and the underlying detailed mechanisms evaluated are needed to validate our results.
Relationship of posterior peripheral corneal layers and the trabecular meshwork: an immunohistological and anatomical study
Authors: Kepez Yildiz Burçin , Freitas Rui , Filippini Perla , Habroosh Fatima , Said Dalia G , Dua Harminder Singh , Sahay Prity
Published: February 2024

Background/Aim

With the popularity of endothelial keratoplasty (EK) procedures, Descemet membrane (DM) EK and pre-Descemet EK, considerable work has been done on understanding the posterior corneal anatomy. Most of the information available relates to the central cornea. We evaluated the peripheral cornea to explore the immunohistological and anatomical relationship between the pre-Descemet layer (PDL), DM and trabecular meshwork (TM).

Methods

Six donor human sclerocorneal discs were studied. PDL, DM and TM were examined by light microscopy, transmission electron microscopy (TEM) and immunohistology. The DM was peeled from the centre to the limit of its peripheral attachment, to reach the transition zone (TZ) between TM and peripheral cornea. Ten-micron sections were stained with antibodies against collagens 1, 2, 3, 4, 5, 6, 12, elastin, myocilin, wnt-1, aquaporin, tenascin C, laminin and integrin alpha 3.

Results

Collagens 2, 3, 4, laminin and myocilin were predominantly seen in the TZ between TM and peripheral cornea. Wnt-1, integrin alpha 3 and tenascin C were highly concentrated in TM. Collagen 1 was present predominantly in the corneal stroma. On TEM; DM was thinner with a denser banded structure spread throughout its thickness in the periphery compared with the central cornea where it presents as the distinct anterior banded layer.

Conclusion

The TZ between DM, PDL and TM shows a unique histological structure at the periphery. The collagen and elastin fibres of the TM are continuous with the PDL. The structures are firmly attached to each other. These findings provide structural information that is relevant to the preparation of DMEK donor tissue.
Model of multidisciplinary teamwork in hip fracture care: a qualitative interview study
Authors: Drew Sarah , Fox Fiona , Gregson Celia L , Gooberman-Hill Rachael
Published: February 2024

Objectives

Hip fractures are common injuries in older age with high mortality requiring multidisciplinary clinical care. Despite guidance, there is considerable variation in hip fracture services and patient outcomes; furthermore, little is known about how successful multidisciplinary working can be enabled. This study aimed to characterise professionals’ views about the core components of multidisciplinary teamwork in hip fracture care.

Design

The study comprised qualitative interviews with healthcare professionals delivering hip fracture care. Interviews were audio recorded, transcribed and analysed abductively: material was coded inductively and grouped into higher level concepts informed by theories and frameworks relating to teamwork.

Setting

Four hospitals in England.

Participants

Participants were 40 healthcare professionals including orthopaedic surgeons, orthogeriatricians, physiotherapists and service managers.

Results

Results identified four components of successful multidisciplinary teamwork: (1) defined roles and responsibilities, (2) information transfer processes, (3) shared goals and (4) collaborative leadership. These were underpinned by a single concept: shared responsibility. Defined roles and responsibilities were promoted through formal care pathways, reinforced through induction and training with clear job plans outlining tasks. Information transfer processes facilitated timely information exchange to appropriate individuals. Well-defined common purpose was hindered by complex interdisciplinary professional relationships, particularly between orthogeriatric and orthopaedic staff, and encouraged through multidisciplinary team meetings and training. Clinical service leads were integral to bridging interdisciplinary boundaries. Mutual trust and respect were based on recognition of the value of different professional groups. Teamwork depended on formal clinical leads with facilitative and motivational roles, and on hospital leadership that created an environment supporting collaboration. Shared responsibility for patients was encouraged by joint orthopaedic and orthogeriatric care models. Staff shared responsibility by assisting colleagues when needed.

Conclusions

Shared responsibility across the multidisciplinary team is fundamental to delivery of hip fracture care. Findings will inform development of clinical practice recommendations and training to build teamworking competencies.