bluuebunny/crossref_metadata_2025 huggingface dataset:
Discovery of anti-SARS-CoV-2 S2 protein antibody CV804 with broad-spectrum reactivity with various beta coronaviruses and analysis of its pharmacological properties in vitro and in vivo
Authors: Tsugawa Yoji , Furukawa Kentaro , Ise Tomoko , Takayama Masahiro , Ota Takeshi , Kuroda Takayuki , Shano Shinya , Hashimoto Takashi , Konishi Haruyo , Ishihara Takeshi , Sato Masaaki , Kamada Haruhiko , Fukao Keita , Shishido Takao , Takahashi Tatsuya , Nagata Satoshi
Published: March 2024

SARS-CoV-2 pandemic alerts us that spillovers of various animal coronaviruses to human in the future may bring us enormous damages. Thus, there is a significant need of antibody-based drugs to treat patients infected with previously unseen coronaviruses.CV804 against the S2 domain of the spike protein, which is less prone to mutations. CV804 shows not only broad cross-reactivities with representative 20 animal-origin coronaviruses but also with diseases-associated human beta coronaviruses including SARS-CoV, MERS-CoV, HCoV-OC43, HCoV-HKU1 and mutant strains of SARS-CoV-2. Other than that, the main characteristics of CV804 are that it has strong antibody-dependent cellular cytotoxicity (ADCC) activity to SARS-CoV2 spike protein-expressed cells in vitro and completely lacks virus-neutralization activity. Comprehensively in animal models, CV804 suppressed disease progression by SARS-CoV-2 infection. Structural studies using HDX-MS and point mutations of recombinant spike proteins revealed that CV804 binds to a unique epitope within the highly conserved S2 domain of the spike proteins of various coronaviruses. Based on the overall data, we suggest that the non-neutralizing CV804 antibody recognizes the conformational structure of the spike protein expressed on the surface of the infected cells and weakens the viral virulence by supporting host immune cells’ attack through ADCC activity in vivo. CV804 epitope identified in this study is not only useful for the design of pan-corona antibody therapeutics but also to design next-generation coronavirus vaccines and antiviral drugs.
Targeting Tuberculosis: Novel Scaffolds for Inhibiting Cytochrome bd Oxidase
Authors: Seitz Christian , Ahn Surl-Hee , Wei Haixin , Kyte Matson , Cook Gregory M. , Krause Kurt , McCammon J. Andrew
Published: March 2024

Discovered in the 1920s, cytochromebdis a terminal oxidase that has received renewed attention as a drug target since its atomic structure was first solved in 2016. Only found in prokaryotes, we study it here as a drug target forMycobacterium tuberculosis(Mtb). Most previous drug discovery efforts towards cytochromebdhave involved analogs of the canonical substrate quinone, known as Aurachin D. Here we report six new cytochromebdinhibitor scaffolds determined from a computational screen totaling over one million molecules and confirmed on target activity throughin vitrotesting. These scaffolds provide new avenues for lead optimization towardsMtbtherapeutics.
On-chip non-contact mechanical cell stimulation - quantification of SKOV-3 alignment to suspended microstructures
Authors: Onal Sevgi , Alkaisi Maan M. , Nock Volker
Published: March 2024

Although the accumulation of random genetic mutations have been traditionally viewed as the main cause of cancer progression, altered mechanobiological profiles of the cells and microenvironment also play a major role as a mutation-independent element. To probe the latter, we have previously reported a microfluidic cell-culture platform with an integrated flexible actuator and its application for sequential cyclic compression of cancer cells. The platform is composed of a control microchannel in a top layer for introducing external pressure, and a polydimethylsiloxane (PDMS) membrane from which a monolithically-integrated actuator protrudes downwards into a cell-culture microchannel. When actively actuated, the integrated actuator, referred to as micro-piston, transfers the pressure from the control channel as a mechanical force to the cells underneath. When not actuated, the micro-piston remains suspended above cells, separated from the latter via a liquid-filled gap of ∼108 µm. Despite the lack of direct physical contact between the micro-piston and cells in the latter arrangement, we observed distinct alignment of SKOV-3 ovarian cancer cells to the piston shape. To characterize this observation, micro-piston localization, shape, and size were adjusted and the directionality of a mono-layer of SKOV-3 cells relative to the suspended structure was probed. Cell alignment analysis was performed in a novel, label-free approach by measuring elongation angles of whole cell bodies with respect to micro-piston peripheries. Alignment of SKOV-3 cells to the structure outline was significant for circular, triangular and square micro-piston when compared to control areas without micro-piston on the same chip. The effect was present irrespective of whether cells were loaded with micro-pistons in static position (∼108 µm gap) or actively retracted using vacuum (>108 µm gap). Similar alignment was not observed for MCF7 cancer cells and MCF10A non-cancerous epithelial cells. The reported observation of directional movement and growth of SKOV-3 cells towards the region under micro-pistons point towards a to-date unexplored mechanotactic behaviour of these cells, warranting future investigations regarding the mechanisms involved and the role these may play in cancer.
Statistical design of a synthetic microbiome that clears a multi-drug resistant gut pathogen
Authors: Oliveira Rita A. , Pandey Bipul , Lee Kiseok , Yousef Mahmoud , Chen Robert Y. , Triebold Conrad , McSpadden Emma , Haro Fidel , Aksianiuk Valeryia , Ramanujam Ramaswamy , Kuehn Seppe , Raman Arjun S.
Published: March 2024

Microbiomes perform critical functions across many environments on Earth1–3. However, elucidating principles of their design is immensely challenging4–7. Using a diverse bank of human gut commensal strains and clearance of multi-drug resistantKlebsiella pneumoniaeas a target, we engineered a functional synthetic microbiome using a process that was agnostic to mechanism of action, bacterial interactions, or compositions of natural microbiomes. Our strategy was a modified ‘Design-Build-Test-Learn’ approach (‘DBTL+’) coupled with statistical inference that learned design principles by considering only the strain presence-absence of designed communities. In just a single round of DBTL+, we converged on a generative model ofK. pneumoniaesuppression. Statistical inference performed on our model identified 15 strains that were key for community function. Combining these strains into a community (‘SynCom15’) suppressedK. pneumoniaeacross unrelatedin vitroenvironments and matched the clearance ability of a whole stool transplant in a pre-clinically relevant mouse model of infection. Considering metabolic profiles of communities instead of strain presence-absence yielded a poor generative model, demonstrating the advantage of using strain presence-absence for deriving principles of community design. Our work introduces the concept of ‘statistical design’ for engineering synthetic microbiomes, opening the possibility of synthetic ecology more broadly.
Atlastin-1 regulates endosomal tubulation and lysosomal proteolysis in human cortical neurons
Authors: Zlamalova Eliska , Rodger Catherine , Greco Francesca , Kleniuk Julia , Nadadhur Aishwarya G. , Kadlecova Zuzana , Reid Evan
Published: March 2024

Mutation of theATL1gene is one of the most common causes of hereditary spastic paraplegia (HSP), a group of genetic neurodegenerative conditions characterised by distal axonal degeneration of the corticospinal tract axons. Atlastin-1, the protein encoded byATL1, is one of three mammalian atlastins, which are homologous dynamin-like GTPases that control endoplasmic reticulum (ER) morphology by fusing tubules to form the three-way junctions that characterise ER networks. However, it is not clear whether atlastin-1 is required for correct ER morphology in human neurons and if so what the functional consequences of lack of atlastin-1 are. Using CRISPR-inhibition we generated human cortical neurons lacking atlastin-1. We demonstrate that ER morphology was altered in these neurons, with a reduced number of three-way junctions. Neurons lacking atlastin-1 had longer endosomal tubules, suggestive of defective tubule fission. This was accompanied by reduced lysosomal proteolytic capacity. As well as demonstrating that atlastin-1 is required for correct ER morphology in human neurons, our results indicate that lack of a classical ER-shaping protein such as atlastin-1 may cause altered endosomal tubulation and lysosomal proteolytic dysfunction. Furthermore, they strengthen the idea that defective lysosome function contributes to the pathogenesis of a broad group of HSPs, including those where the primary localisation of the protein involved is not at the endolysosomal system.
Hachiman is a genome integrity sensor
Authors: Tuck Owen T. , Adler Benjamin A. , Armbruster Emily G. , Lahiri Arushi , Hu Jason J. , Zhou Julia , Pogliano Joe , Doudna Jennifer A.
Published: March 2024

Hachiman is a broad-spectrum antiphage defense system of unknown function. We show here that Hachiman comprises a heterodimeric nuclease-helicase complex, HamAB. HamA, previously a protein of unknown function, is the effector nuclease. HamB is the sensor helicase. HamB constrains HamA activity during surveillance of intact dsDNA. When the HamAB complex detects DNA damage, HamB helicase activity liberates HamA, unleashing nuclease activity. Hachiman activation degrades all DNA in the cell, creating ‘phantom’ cells devoid of both phage and host DNA. We demonstrate Hachiman activation in the absence of phage by treatment with DNA-damaging agents, suggesting that Hachiman responds to aberrant DNA states. Phylogenetic similarities between the Hachiman helicase and eukaryotic enzymes suggest this bacterial immune system has been repurposed for diverse functions across all domains of life.
Glycerol degradation in the thermoacidophilic crenarchaeonSulfolobus acidocaldariusinvolves an unusual glycerol-3-phosphate dehydrogenase
Authors: Schmerling Christian , Schroeder Carsten , Zhou Xiaoxiao , Busche Tobias , Kalinowski Jörn , Montero Lidia , Schmitz Oliver , Kaschani Farnusch , Ninck Sabrina , Kaiser Markus , Bost Jan , Waßmer Bianca , Albers Sonja V. , Siebers Bettina , Bräsen Christopher
Published: March 2024

Glycerol is highly abundant in nature and serve as carbon source for many organisms. Also, several Archaea have the genetic capacity to grow on glycerol but its degradation has so far only been studiedHaloferax volcanii.Herein, the thermoacidophilic crenarchaeonSulfolobus acidocaldariuswas shown to grow with glycerol as sole carbon and energy source. After uptake likely involving facilitated diffusion, glycerol is degraded via phosphorylation to glycerol-3-phosphate followed by oxidation to dihydroxyacetone phosphate (DHAP) catalyzed by glycerol kinase (GK) by an unusual quinone reducing FAD-dependent glycerol-3-phosphate dehydrogenase (G3PDH), respectively. TheS. acidocaldariusgenome harbors two paralogous copies of each GK and G3PDH. However, only one of these GK-G3PDH couples (Saci_2031-2033) is highly upregulated on glycerol. Deletion of thesaci_2033gene encoding GK abolished growth on glycerol and GK activity in crude extracts. In contrast, deletion of the second GK gene (saci_1117) had only minor effects indicating that only one of the two GK-G3PDH couples is essential. Biochemical characterization revealed that both isoenzymes of each, GK and G3PDH, were functionally similar. Whereas the GKs showed high similarity to known enzymes from Bacteria and Eukaryotes, the G3PDHs represent unusual homologues of the bacterial GlpA subunit of the GlpABC complex with remarkable C-terminal sequence differences and a novel type of membrane anchoring via a CoxG-like protein (Saci_2031). Further sequence analyzes discovered a higher versatility of G3PDHs in Archaea with respect to interacting proteins, electron transfer, and membrane anchoring likely reflecting tailored evolutionary solutions to meet different requirements caused by life styles and electron acceptors.
Considerations for Rearing and MaintainingAnophelesin the Laboratory
Authors: Leite Laura N. , Bascuñán Priscila , Dotson Ellen M. , Benedict Mark Q.
Published: March 2024

Anophelesmosquitoes can transmit several human pathogens, including viruses such as o'nyong-nyong and parasites includingPlasmodiumspp. andWuchereriaspp., which cause malaria and filariasis, respectively. RearingAnophelesspecies of medical importance under laboratory conditions allows researchers to carry out experiments to better understand their genetics, physiology, and behavior. However,Anophelesspecies vary in how easily they can be reared in the laboratory, and some species have been difficult to colonize. Once established, members of the important AfricanAnopheles gambiaecomplex thrive following a standard protocol and are predictable in growth and development rates. Here, we provide useful basic information and guidance to successfully maintain colonies ofA. gambiaeand other species ofAnophelesin a laboratory setting. We also provide an example of a 3-wk rearing schedule that produces sufficient numbers of mosquitoes while minimizing the work required during weekends. In the accompanying protocols, we detail efficient methods and techniques suitable for several species of this genus at the egg, larva, pupae, and adult stages; however, it will be necessary for researchers to adjust methods as needed based on site-specific rearing observations of their particular strains.
Development of theDrosophilaOptic Lobe
Authors: Zhang Yu , Li Xin
Published: March 2024

TheDrosophilavisual system has been a great model to study fundamental questions in neurobiology, such as neural fate specification, axon guidance, circuit formation, and information processing. TheDrosophilavisual system is composed of the compound eye and the optic lobe. The optic lobe is divided into four neuropils—namely, the lamina, medulla, lobula, and lobula plate. There are around 200 types of optic lobe neurons, which wire together to form a complex neural structure to processes visual information. These neurons are derived from two neuroepithelial structures—namely, the outer proliferation center (OPC) and the inner proliferation center (IPC), in the larval brain. Recent work on theDrosophilaoptic lobe has revealed basic principles underlying the development of this complex neural structure, and immunostaining has been a key tool in these studies. Here, we provide a brief overview of theDrosophilaoptic lobe structure and development, as revealed by immunostaining. First, we introduce the structure of the adult optic lobe. Then, we summarize recent advances in the study of neural fate specification during development of different parts of the optic lobe. Last, we briefly summarize general aspects of axon guidance and neuropil assembly in the optic lobe. With this review, we aim to familiarize readers with this complex neural structure and highlight the power of this great model to study neural development to facilitate further developmental and functional studies using this system.
How the use of alternative information in risk management fintech platforms influences SME lending: a qualitative case study
Authors: Yan Jie
Published: March 2024

Purpose

The purpose of the study is to examine the use of alternative information in bank lending to small and medium enterprises (SMEs). Understanding alternative information and its use in bank lending to SMEs is important because it has become a growing part of the future of SME finance. The results and findings of my study not only enrich the finance literature but, more importantly, also address the use of Fintech in the risk management of SME lending, a new and complex problem that is specific to both the information technology and finance field.

Design/methodology/approach

To answer the research question, the author used a case study approach that relies upon qualitative data and analysis. By iterating between the existing literature, theoretical pieces and empirical findings, the author explain and interpret in detail how the use of alternative information impacts loan outcomes and develop insights to guide future research.

Findings

The case is outlined in two time periods including the prepartnership period and the postpartnership period. It highlights the establishment of a partnership between LoanBank and FintechInc (pseudonym), aimed at SME-focused Fintech lending. The findings underscore how the partnership has enabled a mutually beneficial situation where LoanBank and FintechInc leverage each other’s strengths to provide efficient and effective lending services. The adoption of alternative information in the risk management Fintech (RMF) platform of FintechInc has transformed LoanBank’s lending processes, showcasing how technological innovations can enhance SME lending practices.

Originality/value

The study’s originality mainly lies in the three detailed insights regarding alternative information’s impact on SME lending: information, platform properties and financial inclusion. The information part demonstrates that RMF platforms expand the information used for lending decisions, shifting from traditional hard and soft data to incorporating various alternative information sources. The platform properties part suggests that location, openness and technology also play a pivotal role in shaping lending outcomes. Finally, the financial inclusion part proposes that the use of alternative information has the potential to improve financial inclusion and offer better credit terms to previously underserved borrowers.
Stress‐induced anisotropy in Gulf of Mexico sandstones and the prediction of in situ stress
Authors: Sayers Colin M. , Leaney W. Scott , Bratton Tom R.
Published: March 2024

The strong sensitivity of velocity to stress observed in many sandstones originates from the response of stress‐sensitive discontinuities such as grain contacts and microcracks to a change in effective stress. If the change in stress is anisotropic, then the change in elastic wave velocities will also be anisotropic. Characterization of stress‐induced elastic anisotropy in sandstones may enable estimation of the in situ three dimensional stress tensor with important application in solving problems occurring during drilling, such as borehole instability, and during production, such as sanding and reservoir compaction. Other applications include designing hydraulic fracture stimulations and quantifying production‐induced stresses which may lead to rock failure. Current methods for estimating stress anisotropy from acoustic anisotropy rely on third‐order elasticity, which ignores rock microstructure and gives elastic moduli that vary linearly with strain. Elastic stiffnesses in sandstones vary non‐linearly with stress. Using P‐ and S‐wave velocities measured on Gulf of Mexico sandstones, this non‐linearity is found to be consistent with a micromechanical model in which the discontinuities are represented by stress‐dependent normal and shear compliances. Stress‐induced anisotropy increases with increasing stress anisotropy at small stress but then decreases at larger stresses as the discontinuities close and their compliance decreases. When the ratio of normal‐to‐shear compliance of the discontinuities is unity, the stress‐induced anisotropy is elliptical, but for values different from unity, the stress‐induced anisotropy becomes anelliptic. Although vertical stress can be obtained by integrating the formation's bulk density from the surface to the depth of interest, and minimum horizontal stress can be estimated using leak‐off tests or hydraulic fracture data, maximum horizontal stress is more difficult to estimate. Maximum horizontal stress is overpredicted based on third‐order elasticity using measured shear moduli, with estimates of pore pressure, vertical stress and minimum horizontal stress as input. The non‐linear response of grain contacts and microcracks to stress must be considered to improve such estimates.
Food web structures of irrigated rice fields estimated from carbon and nitrogen stable isotopes: Special reference to the role of filamentous green algae as a food resource of aquatic consumers
Authors: Yasuno Natsuru , Kanaya Gen , Kikuchi Eisuke
Published: March 2024

Rice fields are characterized by high algal production and dense mats of filamentous green algae, and they function as habitats for various aquatic organisms. However, how algal production supports the secondary production of aquatic consumers in rice fields has not been assessed. Herein, aquatic food web structures in two adjacent rice fields in northeastern Japan were examined using carbon and nitrogen stable isotope analyses. Filamentous algae often showed higher δ13C values (mean, −23.1‰ to −21.4‰) than other organic matter sources, including particulate organic matter, benthic microalgae, and soil organic matter (−30.1‰ to −25.4‰). A δ13C‐based isotopic mixing model estimated that among 19 taxa of herbivores and omnivores, most taxa depended on filamentous algae‐derived carbon (ca. >30%). Particularly, Peltodytes intermedius larvae, a specialist feeder for filamentous algae, showed the highest reliance (mean, 66.7%–80.0%). The microcrustacean, Ostracoda sp. also utilized a diet consisting of a substantial proportion of filamentous algae‐derived carbon (57.6%). Seven out of 10 carnivorous taxa showed reliance on filamentous algae‐derived carbon by >30%. Particularly, larvae of beetles (Berosus sp., Enochrus sp., and Hydrochara affinis) showed the highest reliance (40.2%–44.3%). They could assimilate filamentous algae‐based carbon by consuming herbivores, such as P. intermedius. Because fresh filamentous green algae were eaten less by aquatic consumers, the herbivores could consume decomposed filamentous algae rather than fresh ones. Our results suggest that filamentous algae are one of the major organic matter sources supporting secondary production in rice field food webs.
Development of a PMA‐LAMP visual detection assay for viable Cronobacter sakazakii
Authors: Chen Qiming , Yu Yang , Chen Xiaodi , Tu Fangming , Wang Peng , Huang Junyi , Liu Zhanmin
Published: March 2024

Cronobacter sakazakii in powdered infant formula (PIF) can infect infants with a mortality rate of up to 80%. In this study, a propidium monoazide–loop‐mediated isothermal amplification (PMA‐LAMP) assay was developed for fast and cost‐effective visual detection of viable C. sakazakii. The detection could be finished in 75 min and the results could be identified by the naked eye. The detection limits of the assay were as low as 1.2 × 101 cfu/mL and 1.2 × 102 cfu/mL for gel electrophoresis and naked eyes respectively. Finally, the assay also showed good reliability in the artificially contaminated PIF.
Vaginal misoprostol versus vaginal dinoprostone for cervical ripening and induction of labour: An individual participant data meta‐analysis of randomised controlled trials
Authors: Patabendige Malitha , Chan Fei , Vayssiere Christophe , Ehlinger Virginie , Van Gemund Nicolette , le Cessie Saskia , Prager Martina , Marions Lena , Rozenberg Patrick , Chevret Sylvie , Young David C. , Le Roux Paul A. , Gregson Sarah , Waterstone Mark , Rolnik Daniel L. , Mol Ben W. , Li Wentao
Published: March 2024

Background

Induction of labour (IOL) is common practice and different methods carry different effectiveness and safety profiles.

Objectives

To compare the effectiveness, and maternal and perinatal safety outcomes of IOL with vaginal misoprostol versus vaginal dinoprostone using individual participant data from randomised clinical trials.

Search strategy

The following databases were searched from inception to March 2023: CINAHL Plus, ClinicalTrials.gov, Cochrane Pregnancy and Childbirth Group Trial Register, Ovid Embase, Ovid Emcare, Ovid MEDLINE, Scopus and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP).

Selection criteria

Randomised controlled trials (RCTs), with viable singleton gestation, no language restrictions, and all published and unpublished data.

Data collection and analysis

An individual participant data meta‐analysis was carried out.

Main results

Ten of 52 eligible trials provided individual participant data, of which two were excluded after checking data integrity. The remaining eight trials compared low‐dose vaginal misoprostol versus dinoprostone, including 4180 women undergoing IOL, which represents 32.8% of all participants in the published RCTs. Of these, 2077 were assigned to low‐dose vaginal misoprostol and 2103 were assigned to vaginal dinoprostone. Compared with vaginal dinoprostone, low‐dose vaginal misoprostol had a comparable rate of vaginal birth. Composite adverse perinatal outcomes did not differ between the groups. Compared with vaginal dinoprostone, composite adverse maternal outcomes were significantly lower with low‐dose vaginal misoprostol (aOR 0.80, 95% CI 0.65–0.98, P = 0.03, I2 = 0%).

Conclusions

Low‐dose vaginal misoprostol and vaginal dinoprostone for IOL are comparable in terms of effectiveness and perinatal safety. However, low‐dose vaginal misoprostol is likely to lead to a lower rate of composite adverse maternal outcomes than vaginal dinoprostone.
Conversations across international divides: Children learning through empathy about climate change
Authors: Satchwell Candice , Walley Bob , Dodding Jacqueline , Lagi Marily Daphine Audrey
Published: March 2024

Primary school curricula often largely avoid the climate crisis, and teachers feel ill‐equipped to teach it. In the secondary school curriculum, the climate crisis is generally addressed only in specific subjects such as science or geography. Our own and others’ research indicates that children are curious about climate change and become less anxious when they feel agentic in facing its effects. The challenges of everyday life for children in parts of the world severely affected by the rapidly changing climate are seldom included in educational contexts. This article reports on a project that linked a school in a UK town with a school on a Fijian island to explore a holistic approach to understanding the impacts of climate change. The children aged 9 to 11 built friendships across the globe through film messages, email, written letters, and drawings. As part of getting to know one another, the children asked and answered questions about their lives. Those questions and other creative activities revealed children’s interests and priorities and the extent of their local and global knowledge and enabled us to consider a personalised approach to climate justice. By co‐creating and exchanging their stories the children could begin to understand the social and emotional impacts as well as the science of climate change. We discuss the role of empathy in children’s learning about climate change, and consider how connections across international divides can be facilitated.
Current status of innate immune responses in Malpighian tubules of insects: A review focusing on the Toll signaling pathway
Authors: Khan Shahidul Ahmed , Han Yeon Soo
Published: March 2024

Innate immunity is the immediate and exclusive defense mechanism in invertebrates. It acts against foreign agents and pathogens. In insects, this defense mechanism involves a combination of humoral and cellular responses, orchestrated by specific recognition receptors and the activation of various signaling pathways. Remarkably, Toll and Toll‐related proteins play a pivotal role in insect immunity by inducing the production of antimicrobial peptides (AMPs) in response to pathogen attacks. Toll receptors, which are type I transmembrane proteins, significantly affect insect development and the innate immune response, primarily via the nuclear factor kappa‐B signaling pathway. The Malpighian tubules of insects play a crucial role in waste elimination, hemostasis maintenance, and immune defense. The Toll signaling pathway in Malpighian tubules is mainly involved in the production of AMPs. This review provides valuable insights into the mechanisms of the Toll signaling pathway and the morphological and physiological attributes of Malpighian tubules. Moreover, it discusses the classification and functionalities of AMPs synthesized in Malpighian tubules in response to pathogens, thereby contributing to our understanding of innate immunity in insects.
Construction of a versatile in vitro cultivation screening platform using human oral microbiota
Authors: Sasaki Kengo , Takeshima Yasunobu , Fujino Ayami , Yamashita Junya , Kimoto Akira , Sasaki Daisuke , Kondo Akihiko , Akashi Masaya , Okumura Ryo
Published: March 2024

We developed a simulation model of human oral microbiota using Bio Palette oral medium (BPOM) containing 0.02% glucose and lower bacterial nitrogen sources, derived from saliva and dental plaque. By decreasing the concentration of Gifu anaerobic medium (GAM) from 30 to 10 g L−1, we observed increased ratios of target pathogenic genera, Porphyromonas and Fusobacterium from 0.5% and 1.7% to 1.2% and 3.5%, respectively, in the biofilm on hydroxyapatite (HA) discs. BPOM exhibited the higher ratios of Porphyromonas and Fusobacterium, and amplicon sequence variant number on HA, compared with GAM, modified GAM and basal medium mucin. Mixing glycerol stocks of BPOM culture solutions from four human subjects resulted in comparable ratios of these bacteria to the original saliva. In this simulation model, sitafloxacin showed higher inhibitory effects on P. gingivalis than minocycline hydrochloride at a low dosage of 0.1 μg mL−1. Probiotics such as Streptococcus salivarius and Limosilactobacillus fermentum also showed significant decreases in Porphyromonas and Fusobacterium ratios on HA, respectively. Overall, the study suggests that BPOM with low carbon and nutrients could be a versatile platform for assessing the efficacy of antibiotics and live biotherapeutics in treating oral diseases caused by Porphyromonas and Fusobacterium.
The United States–China ‘tech war’: Decoupling and the case of Huawei
Authors: Ryan Maria , Burman Stephen
Published: March 2024

This paper offers an analysis of US strategy in the unfolding United States–China ‘tech war’ and its consequences. We argue that a tech war is now underway, and that Washington is the driving force behind it. Here, we focus on the most impactful policy so far: the placement of Huawei and over 150 of its affiliates on the sanctioned Entity List. As a result, a decoupling between high‐end US tech and Huawei Technologies is well underway, if not already complete. However, the consequences of the sanctions have not been what Washington intended or expected. The company appears to have maintained its position as one of the world's leading innovators in 5G technology and remains a leading supplier of 5G base stations. The United States risks undermining co‐operation with China in other critical policy areas because the tech war is viewed as aggressive in Beijing. It has also exposed the limits of US influence over allies and third countries, many of whom are opting for Huawei's cheaper 5G infrastructure. Nevertheless, the expansion of this approach by the Biden administration suggests that, in future, Washington may prioritise security interests over commercial ones as it seeks to preserve as much US primacy as possible.
Transcriptomic and intervention evidence reveals domestic dogs as a promising model for anti‐inflammatory investigation
Authors: Zeng Min , Zhou Tong , Li Zhiyu , Li Guimei , Zhang Shurun , Wang Lu , Huang Qing‐Guo , Li Ju‐Dong , Samarawickrama P. Nadeeshika , He Yonghan , Wang Guo‐Dong
Published: March 2024

Domestic dogs have great potential to expand our understanding of the determinants of aging. To understand the aging pattern of domestic dogs and evaluate whether they can be used as an aging model, we performed RNA sequencing on white blood cells from domestic dogs aged 1–9 years and treated aged dogs with classical antiaging approaches. We obtained 30 RNA sequencing libraries and identified 61 age‐associated genes with dynamic changes, the majority of which were related to metabolism and immune function, which may be predominant biomarkers for aging in dogs. We next treated aged dogs with canine mesenchymal stem cells (cMSCs), nicotinamide mononucleotide, and rapamycin to determine whether and how they responded to the antiaging interventions. The results showed that these treatments can significantly reduce the level of inflammatory factors (IL‐6 and TNF‐α). MSCs effectively improved the heart functions of aged dogs. Three key potential age‐related genes (PYCR1, CCRL2, and TOX) were reversed by MSC treatment, two of which (CCRL2 and TOX) are implicated in immunity. Overall, we profiled the transcriptomic pattern of domestic dogs and revealed that they may be a good model of aging, especially in anti‐inflammatory investigations.
Effects from medications on functional biomarkers of aging in three longitudinal studies of aging in Sweden
Authors: Lopes De Oliveira Thaís , Tang Bowen , Bai Ge , Sjölander Arvid , Jylhävä Juulia , Finkel Deborah , Pedersen Nancy L. , Hassing Linda B. , Reynolds Chandra A. , Karlsson Ida K. , Hägg Sara
Published: March 2024

Antihypertensive, lipid‐lowering, and blood glucose‐lowering drugs have slowed down the aging process in animal models. In humans, studies are limited, have short follow‐up times, and show mixed results. Therefore, this study aimed to estimate the effects of commonly used medications on functional aging, cognitive function, and frailty. We included information on individuals from three Swedish longitudinal population‐based studies collected between 1986 and 2014. Our exposures were the 21 most used groups of medications among individuals aged 65 years and older in the Swedish population in 2022. Functional aging index (n = 1191), cognitive function (n = 1094), and frailty index (n = 1361) were the outcomes of interest. To estimate the medication effects, we used a self‐controlled analysis, where each individual is his/her own control, thereby adjusting for all time‐stable confounders. The analysis was additionally adjusted for time‐varying confounders (chronological age, Charlson Comorbidity Index, smoking, body mass index, and the number of drugs). The participants were 65.5–82.8 years at the first in‐person assessment. Adrenergics/inhalants (effect size = 0.089) and lipid‐modifying agents/plain (effect size = 0.082) were associated with higher values of cognitive function (improvement), and selective calcium channel blockers with mainly vascular effects (effect size = −0.129) were associated with lower values of the functional aging index (improvement). No beneficial effects were found on the frailty index. Adrenergics/inhalants, lipid‐modifying agents/plain, and selective calcium channel blockers with mainly vascular effects may benefit functional biomarkers of aging. More research is needed to investigate their clinical value in preventing adverse aging outcomes.
Efficacy and feasibility of the RADA16 self‐assembling peptide, PuraStat® for haemostasis in laparoscopic gynaecological surgery: A pilot study
Authors: Hall Philip
Published: March 2024

Bleeding after laparoscopic gynaecological surgery remains a potential complication. We assessed RADA16 (PuraStat®), a topical self‐assembling peptide haemostatic agent, in a pilot study of 46 women undergoing laparoscopic gynaecological surgery. The primary outcome was intraoperative haemostatic efficacy for resection site bleeding. Haemostasis was achieved in all intraoperative bleeding situations (40/40 participants: 100%) with no clinically significant surgical bed bleeding or complications. Mean volume and time required to achieve haemostasis were 6 mL and 14 sec, respectively. This study suggests that PuraStat® is a safe, effective haemostatic agent in laparoscopic gynaecological surgery. Randomised controlled trials are warranted to confirm these findings.
Colposcopy performance in the new primary HPV screening in Australia: How to determine colposcopy competency?
Authors: Tan Jeffrey H.J. , Neesham Deborah , Szabo Rebecca A. , Khomko Natalia , Yap Desiree , Wrede C. David H.
Published: March 2024

Aims

To assess colposcopic performance and determine indicators for competency within the new Australian primary human papillomavirus (HPV) cervical screening program.

Materials and methods

A retrospective observational study of 4542 women seen at The Royal Women's Hospital Colposcopy Clinic in Melbourne, from 1 December 2017 to 31 July 2020 after a higher‐risk cervical screening test (CST) result.

Results

Histological CIN2+ was detected in 25.1% up to two years from first colposcopy visit (FCV). The majority (86.7%) of CIN2+ was detected early within the first six months of presentation. Biopsy rate overall was 96.1% with abnormal colposcopic impression. Of four colposcopists with a lower biopsy rate, only one was able to achieve this early detection rate. Biopsy was also taken in over 30% of cases with negative reflex cytology and normal colposcopy, with CIN2+ detected in 5.0% among positive HPV16/18 and 3.8% with non‐16/18 HPV. Positive predictive value of high‐grade colposcopic impression at FCV averaged 66.4% (range: 54.9–81.6% among our colposcopists) and is poorly correlated with early detection rate of CIN2+. Overall accuracy of colposcopy is 84.5% (range: 78.7–90.3%), buoyed by high true negative colposcopic predictions secondary to high rates of negative reflex cytology referral with the new screening algorithm and is also unlikely to be a useful colposcopy indicator.

Conclusions

Early detection rate of CIN2+ within the first six months of presentation is a useful measure of colposcopy competency and we would encourage our National Cancer Screening Register to explore this with the participating colposcopists.
Value of the surgical pancreatic duct anatomy and associated outcomes in pancreatic cancer
Authors: Harris Mark Conor , Atanasov Georgi , Neo Eu Nice , Goldfinch Andrew , Ng Andrew Jin‐Hean , Tew Khimseng , Kuan Lilian , Trochsler Markus , Kanhere Harsh
Published: March 2024

Introduction

Pancreatic cancer recurrence following surgery is a significant challenge, and personalized surgical care is crucial. Topographical variations in pancreatic duct anatomy are frequent but often underestimated. This study aimed to investigate the potential importance of these variations in outcomes and patient survival after Whipple's procedures.

Methods

Data were collected from 105 patients with confirmed pancreatic head neoplasms who underwent surgery between 2008 and 2020. Radiological measurements of pancreatic duct location were performed, and statistical analysis was carried out using IBM SPSS.

Results

Inferior pancreatic duct topography was associated with an increased rate of metastatic spread and tumour recurrence. Additionally, inferior duct topography was associated with reduced overall and recurrence‐free survival. Posterior pancreatic duct topography was associated with decreased incidence of perineural sheet infiltration and improved overall survival.

Discussion

These findings suggest that topographical diversity of pancreatic duct location can impact outcomes in Whipple's procedures. Intraoperative review of pancreatic duct location could help surgeons define areas of risk or safety and deliver a personalized surgical approach for patients with beneficial or deleterious anatomical profiles. This study provides valuable information to improve surgical management by identifying high‐risk patients and delivering a personalized surgical approach with prognosis stratification.
CAMP‐B score predicts the risk of hepatocellular carcinoma in patients with chronic hepatitis B after HBsAg seroclearance
Authors: Lee Hye Won , Yip Terry Cheuk‐Fung , Wong Vincent Wai‐Sun , Lim Young‐Suk , Chan Henry Lik‐Yuen , Ahn Sang Hoon , Wong Grace Lai‐Hung , Choi Jonggi
Published: March 2024

Background

Risk of hepatocellular carcinoma (HCC) persists after hepatitis B surface antigen (HBsAg) seroclearance in patients with chronic hepatitis B (CHB).

Aims

To identify risk factors and construct a predictive model for HCC development.

Methods

We retrospectively analysed patients with CHB with HBsAg seroclearance. Primary outcome was HCC development. Factors identified from a multivariate Cox model in the training cohort, consisting of 3476 patients from two Korean hospitals, were used to construct the prediction model. External validation was performed using data from 5255 patients in Hong Kong.

Results

In the training cohort, HCC occurred in 102 patients during 24,019 person‐years of observation (0.43%/year). Risk scores were assigned to cirrhosis (C:3), age ≥50 years (A:2), male sex (M:3) and platelet count <150,000/mm3 (P:1); all were independently associated with an increased risk of HCC in multivariate analysis The time‐dependent area under receiver operating characteristic curves for 5, 10 and 15 years in the training and validation cohorts were 0.782, 0.817 and 0.825 and 0.785, 0.771 and 0.796, respectively. In the validation cohort, 85 patients developed HCC (0.24%/year). The corresponding incidence of HCC in the low‐, intermediate‐ and high‐risk groups were 0.07%, 0.37% and 0.90%, respectively.

Conclusions

The CAMP‐B score (cirrhosis, age ≥50 years, male sex and platelet count <150,000/mm3/L) was significantly associated with HCC development after HBsAg seroclearance. CAMP‐B score can be easily implemented in real‐world clinical practice and helps stratify HCC risk in patients with CHB following HBsAg seroclearance.
New frontiers in delivering public infrastructure
Authors: Brunet Maude , Jobidon Gabriel
Published: March 2024

Delivering infrastructure in a timely and efficient manner to provide public value remains challenging despite the theoretical developments that have been made. What do we know that could help to deliver quality and energy‐efficient infrastructure, what are current challenges and how could we overcome them? This State‐of‐the‐Art Review article attempts to uncover underlying themes, including the governance of large infrastructure projects, the importance of innovation and contractual arrangements, and social and environmental acceptability. A current review of major Canadian contributions is offered, and promising research avenues are proposed.
Optimising the management of peanut allergy by targeting immune plasticity
Authors: Nguyen Alan , du Toit George , Lack Gideon , Marrs Tom
Published: March 2024

Randomised controlled trials investigating the efficacy of oral tolerance induction to peanut have enabled detailed comparison of their clinical and immunological success. They have demonstrated that the regular consumption of peanut for at least 2 years by babies who are not allergic enables protection from developing peanut allergy. The LEAP study intervention tested the impact of regular peanut consumption for 4 years and demonstrated a sustained protection against the development of peanut allergy even after 12 months of peanut avoidance from 5 to 6 years of age. The PreventADALL trial introduced multiple allergens into babies' diets from early infancy and reduced the prevalence of food allergy at 3 years, especially by protecting against peanut allergy. Immunological studies from the LEAP cohort demonstrated that regular peanut consumption was associated with a prompt induction of peanut‐specific IgG4 and reduced manufacture of peanut and Ara h 2‐specific IgE. Even after stopping peanut consumption for 5 years, there continued to be a significant fall in peanut‐specific Ara h 2 IgE in the consumption group from 5 to 6 years of age (p < .01). Children who developed peanut allergy by 5 years started to develop increasing sensitisation to linear sequential peanut epitopes from 2.5 years of age, suggesting that putative disease‐modifying interventions should commence before 3 years. Data comparing clinical outcomes between children undergoing peanut immunotherapy from infancy suggest that younger children can consume higher portions of peanut without reaction on challenge whilst taking immunotherapy, have fewer side effects and are more likely to enjoy remission of PA. Peanut oral immunotherapy modulates T‐cell populations in order to bring about hypo‐responsiveness of allergy effector cells. Studies are now needed to characterise and compare different states of immunological tolerance. This will accelerate the design of interventions which can promote primary, secondary and tertiary levels of PA prevention across a range of age groups.
Cerebral dural arteriovenous fistulas in patients with PTEN‐related hamartoma tumor syndrome
Authors: Gerasimenko Anna , Mignot Cyril , Naggara Olivier , Coulet Florence , Ekram Samar , Heide Solveig , Sorato Clarisse , Mazowiecki Maxime , Perrin Laurence , Colas Chrystelle , Cusin Veronica , Caux Frédéric , Dardenne Antoine , El Chehadeh Salima , Verloes Alain , Maurey Hélène , Afenjar Alexandra , Petit Florence , Barete Stéphane , Boespflug‐Tanguy Odile , Bourrat Emmanuelle , Capri Yline , Ciorna Viorica , Deb Wallid , Doummar Diane , Perrier Alexandre , Guédon Alexis , Houdart Emmanuel , Isidor Bertrand , Jacquemont Marie‐Line , Buffet Camille , Mercier Sandra , Passemard Sandrine , Riquet Audrey , Ruaud Lyse , Schaefer Elise , Heron Delphine , Bisdorff Annouk , Benusiglio Patrick R.
Published: March 2024

Central nervous system (CNS) dural arteriovenous fistulas (DAVF) have been reported in PTEN‐related hamartoma tumor syndrome (PHTS). However, PHTS‐associated DAVF remain an underexplored field of the PHTS clinical landscape. Here, we studied cases with a PTEN pathogenic variant identified between 2007 and 2020 in our laboratory (n = 58), and for whom brain imaging was available. Two patients had DAVF (2/58, 3.4%), both presenting at advanced stages: a 34‐year‐old man with a left lateral sinus DAVF at immediate risk of hemorrhage, and a 21‐year‐old woman with acute intracranial hypertension due to a torcular DAVF. Interestingly, not all patients had 3D TOF/MRA, the optimal sequences to detect DAVF. Early diagnosis of DAVF can be lifesaving, and is easier to treat compared to developed, proliferative, or complex lesions. As a result, one should consider brain MRI with 3D TOF/MRA in PHTS patients at genetic diagnosis, with subsequent surveillance on a case‐by‐case basis.
The need for standardized perioperative care for patients undergoing bariatric and metabolic surgery in the United Kingdom
Authors: Lee Shiela , Courtney Michael
Published: March 2024

Enhanced recovery after surgery (ERAS) protocols are shown to improve patient outcomes and reduce length of hospital stay. However, there is currently limited consensus on the perioperative management of patients undergoing bariatric and metabolic surgery (BMS) in the United Kingdom. This study aims to survey the level of consistency in patient care undergoing BMS. Bariatric nurse specialists from 30 bariatric units completed an anonymised, online survey from 21 December 2022 to 21 February 2023. Most units (77%) have implemented a premade postoperative care bundle protocol including predetermined timing of oral intake (77%) and postoperative day 1 bloods (60%). 63% of units have also established pre‐set analgesia and anti‐emetic bundles. Date of discharge is variable, ranging from 1 day after surgery (50%) to a ‘two night stay’ protocol (33%) to within 4 days after surgery (17%). Most follow‐up clinics are either led by dietitians (33%) or both bariatric nurse specialists and dietitians collaboratively (57%). Patients are usually established on solid food 6 weeks after surgery in 53% (16/30) units. Chemical venous thromboembolism (VTE) prophylaxis was either given on day of surgery postoperatively (60%), day before (20%) or after (17%) surgery. Our study shows significant variability of care throughout the surgical pathway, in the study population. The results suggest a need for consensus guidelines outlining the best‐practice approach to managing patients undergoing BMS; due to the heterogeneity of the patient group, these guidelines should contain overarching generalisable recommendations that can then be tailored to individual patients.