bluuebunny/crossref_metadata_2025 huggingface dataset:
Progress in the Application of Porous Tantalum Metal in Hip Joint Surgery
Authors: Ma Kaiming , Ma Zhijie , Cheng Liangliang , Zhao Dewei
Published: October 2024

Porous tantalum metal is a new orthopedic implant material made of tantalum metal that has been processed by porous treatment. This material has various advantages, including high hardness, good ductility, good biocompatibility, and strong bone integration ability. Porous tantalum metal has performed well in clinical application, demonstrating excellent medium‐ to long‐term curative effects. The use of implant products made of porous tantalum metal, such as porous tantalum rods, porous tantalum hip prostheses, and porous tantalum augments (MAs), is gradually increasing in the clinical application of hip surgery, and these products have achieved excellent therapeutic effects in the middle and late stages of various hip diseases. In recent years, the combined application of porous tantalum metal and three‐dimenional (3D) printing technology to create personalized 3D‐printed porous tantalum metal has led to new development directions for the treatment of complex hip joint surgical diseases. This review presents a summary of the application of porous tantalum metal in hip surgery in recent years, including clinical treatment effects and existing problems. In addition, the prospect of progress in this field is promoted.
Analysis of Risk Factors on Patellofemoral Osteoarthritis: Distribution Characteristics and Radiographic Parameters of Patellofemoral Joint
Authors: Zhao Jianlin , Liu Jinsong , Han Jing , Wan Xiaoyu , Xu Wenqian , Zhang Zengrui , Xu Yingxing
Published: October 2024

Objective

The risk factors for the degeneration of the patellofemoral joint (PFJ) have not been adequately and thoroughly studied. This study aimed to analyze the population distribution characteristics of patients with patellofemoral osteoarthritis (PFOA) and assess the correlation between PFOA and radiological parameters, including patella morphology, PFJ congruity, and patellar alignment. Moreover, the risk factors across various demographic groups were further analyzed.

Methods

A retrospective analysis was conducted to examine the population distribution characteristics of PFOA patients from September 2020 to September 2023. Radiological parameters of the PFJ were measured from the anteroposterior and lateral views of knee joint as well as axial view of patella using X‐ray imaging and the PACS imaging system at the First Affiliated Hospital of Kunming Medical University. These parameters included patella morphology (patella type, width, thickness, and Wiberg index), PFJ congruity (patella height, Wiberg angle, sulcus angle, and lateral patella angle), and patellofemoral alignment (patella tilt angle, displacement, and lateral patellofemoral angle). PFOA severity was classified according to the Iwano PFJ radiological classification, and its correlation with the aforementioned parameters was examined. Additionally, risk factors for PFOA across different populations were further evaluated.

Results

The study included 1080 patients according to the inclusion and exclusion criteria. Age, female gender, overweight or obesity, and manual workers were significantly associated with PFOA. Moreover, type III patella (OR = 3.03, p < 0.05), greater patella width (OR = 1.12, p = 0.01), sulcus angle (OR = 1.04, p < 0.01), patella tilt angle (OR = 1.13, p < 0.01), and patella displacement (OR = 1.22, p < 0.01) as well as smaller patella thickness (OR = 0.87, p < 0.01), Insall–Salvati index (OR = 0.24, p = 0.04), and lateral patellofemoral angle (OR = 0.93, p = 0.02) were identified as risk factors for PFOA. Furthermore, greater patella thickness (OR = 1.17, p < 0.05) and smaller patella displacement (OR = 0.79, p < 0.01) correlated with higher Kujala patellofemoral scores. Discrepancies in risk factors across different populations were also observed.

Conclusions

Older age, female gender, obesity, manual workers, and specific aberrations in patellofemoral parameters are predictive factors for PFOA. Additionally, greater patella thickness and smaller patella displacement were associated with increased severity of clinical symptoms. Thus, more attention should be paid to the discrepancies that exist in different populations.
Prognostic Value of Burst Pacing Inducibility Post‐Radiofrequency Versus Cryoablation for Paroxysmal Atrial Fibrillation
Authors: Sekimoto Satoru , Hachiya Kenta , Ichihashi Taku , Yoshida Takayuki , Wada Yasuaki , Murakami Yoshimasa , Seo Yoshihiro
Published: October 2024

Background

Atrial fibrillation (AF) inducibility with burst pacing (BP) after radiofrequency ablation (RFA) has been reported to be associated with AF recurrence. In contrast, the relevance of inducibility and recurrence after cryoablation (CRA) is unclear.

Methods

We investigated 367 patients undergoing initial ablation for paroxysmal AF (RFA: 174, CRA: 193). Propensity score matching was conducted, retaining 134 patients in each group. Following pulmonary vein isolation (PVI), the inducibility by BP was tested. Inductions at 250 ppm were defined as low‐frequency burst pacing (LFBP) positive, and those at 300 ppm were classified as medium‐frequency burst pacing (MFBP) positive. They were followed for 600 days.

Results

Forty‐eight patients (18%) had AF recurrence. There was no significant difference in the recurrence rate between RFA and CRA (17% vs. 19%, Log‐rank p = 0.79). In RFA, significant differences were observed for both LFBP (Log‐rank p < 0.001) and MFBP (Log‐rank p < 0.001). In contrast, in CRA, there were no significant differences for either LFBP (Log‐rank p = 0.39) or MFBP (Log‐rank p = 0.19). Multivariable analysis revealed that LFBP‐positive (hazards ratio [HR] = 5.75, 95% confidence interval [CI] 2.41–13.7, p < 0.001) was an independent predictor for recurrence with RFA. Acute reconnection (HR = 2.73, 95% CI 1.13–6.56, p = 0.025) was an independent predictor for recurrence with CRA.

Conclusion

The inducibility by BP after RFA predicted recurrence at both low and medium frequencies. LFBP‐positive was an independent predictor of recurrence in multivariable analysis. In contrast, the inducibility by BP after CRA was not a predictor of recurrence.

Trail Registration

This study did not require clinical trial registration.
Belowground systems in tropical savanna: Fabaceae morphoanatomical traits and their relation to fire
Authors: Leal A. S. , Fidelis A. , de Araujo M. A. , Cozin B. B. , Martins A. R.
Published: October 2024

Post‐fire regeneration characterizes woody vegetation of the Cerrado. Several species (e.g., from the Fabaceae) can resprout after fire due to the presence of storage bud‐bearing belowground structures, such as xylopodia, having the capacity to rapidly allocate resources for the formation of new aboveground shoots, an advantage in fire‐prone ecosystems. Therefore, we evaluated the morphoanatomical structure of the belowground organs, buds and their storage to elucidate fire‐related functional traits in relation to regeneration. Besides the strong capacity of plants with xylopodia to resprout and/or their associated root suckers to propagate laterally, they also provide protection against pathogens, through the presence of defence compounds.

We evaluated the morphoanatomy and performed histochemical tests with the belowground organs of eight legume species collected in open savannas in Central Brazil.

Two species presented a taproot tuber and the six remaining species had a xylopodium as belowground organ. All xylopodia had buds on their upper portion. These organs were basically composed of lignified tissue, containing defence (phenolic compounds and lipidic substances), and storage (starch) substances. All xylopodia were associated to tuberous roots, and in two species these roots were also root suckers.

Thus, the presence of belowground storage organs, in combination with stored defence compounds, likely facilitates the persistence of the investigated legumes in fire‐prone ecosystems.
Probiotics as adjuvants to mitigate adverse reactions and enhance effectiveness in Food Allergy Immunotherapy
Authors: Lamminpää Ingrid , Niccolai Elena , Amedei Amedeo
Published: October 2024

In the past decades, food allergies became increasingly dominant since early childhood, leading to a lower quality of life and to increasing costs addressed by the health care system. Beside standard avoidance of specific allergens and drug treatments following allergen exposure, a great deal of research has lately focused on Food Allergy Allergen Immunotherapy (FA‐AIT). SCIT and EPIT (Subcutaneous and Epicutaneous Immunotherapy), OIT (Oral Immunotherapy), and SLIT (Sublingual Immunotherapy) consist in gradual exposure to allergens to desensitize and achieve tolerance once therapy has ended. Although promising, FA‐AIT may bring acute local and systemic adverse reactions. To enhance efficacy, safety and convenience of AIT, the quest of potential adjuvants to mitigate the adverse reactions becomes crucial. Immunomodulatory activities, such as that of increasing the regulatory T cells and decreasing the IgE, have been observed in specific probiotics' strains and multiple studies elucidated the role of gut microbiota as a major interplayer among the host and its immune system. In this review, the microbiome modulation is shown as potential AIT adjuvant, nevertheless the need of more clinical studies in the near future is pivotal to assess the efficacy of targeted bacterial therapies and faecal microbiota transplantation.
Revisiting inter‐Korean events and South Koreans’ perception on unification
Authors: Kwon Yewon , Lee Kyung Suk
Published: October 2024

Objective

This study aims to examine how inter‐Korean events influence South Korean public opinion on unification. It seeks to understand the impact of various political events, including South‐North contacts and North Korean nuclear provocations, on South Koreans' attitudes towards unification.

Methods

Using annual survey data from the Institute for Peace and Unification Studies at Seoul National University (IPUS), this study creates a novel time‐series dataset spanning from 2007 to 2021. We test how each of the inter‐Korean political events affects support for unification and how key individual dispositions moderate the level of support.

Results

The empirical findings reveal that inter‐Korean summits and family reunions positively affect unification sentiment, with family reunions showing surprisingly stronger impacts than inter‐Korean summits. Regarding North Korea's provocations, nuclear tests negatively influence public support for unification, while ballistic missile launches do not significantly impact unification sentiment, likely due to public habituation.

Conclusion

This study contributes to existing literature by providing new empirical insights into the relationship between inter‐Korean political events and public opinion. The findings suggest that policymakers should focus on strategic short‐term initiatives, particularly increasing inter‐Korean contacts, to foster long‐term positive sentiment towards unification. However, it's important to note that individual variables become more influential in shaping public opinion over the long term.
Self-Presentation on Social Media: Sociological Research of Young People in the City of Split (Croatia)
Authors: Gudić Daniela , Lončar Marija , Vučica Zorana Šuljug
Published: October 2024

Youth self-presentation represents the creative expression of personality, interests, and attitudes through the formation of an online identity on social media, which is an indispensable component of young people's lives nowadays. Just as Goffman's actor presents himself on stage in everyday life, people on social media have unique modes of expression that include filtering, editing, and selective sharing of content in order to present themselves in the best light and impress their target online audience. This sociological research aims to gain an insight into how young people present themselves to their online audience by examining why and how often they use and post on social media, as well as how they create and edit content on Instagram, Facebook, and TikTok as the most popular social media. An online survey was used in 2023 to gather data from a sample of 283 young people in Split (Croatia), who were between the ages of 20 and 34. The study's findings indicate that young people follow posts and stories of others every day and that women spend more time both following and posting content on social media than men. In comparison with Facebook and TikTok, they prefer to use Instagram. Compared to men who use social media because of its popularity or in order to make new acquaintances, women use it for entertainment (Facebook) and to follow and create content (Instagram). At the same time, women are more inclined to use various options and tools when creating and editing content on social media.
Approximation properties of torsion classes
Authors: Cox Sean , Poveda Alejandro , Trlifaj Jan
Published: October 2024

We strengthen a result of Bagaria and Magidor (Trans. Amer. Math. Soc. 366 (2014), no. 4, 1857–1877)  about the relationship between large cardinals and torsion classes of abelian groups, and prove that

the Maximum Deconstructibility principle introduced in Cox (J. Pure Appl. Algebra 226 (2022), no. 5) requires large cardinals; it sits, implication‐wise, between Vopěnka's Principle and the existence of an ‐strongly compact cardinal.

While deconstructibility of a class of modules always implies the precovering property by Saorín and Šťovíček (Adv. Math. 228 (2011), no. 2, 968–1007), the concepts are (consistently) nonequivalent, even for classes of abelian groups closed under extensions, homomorphic images, and colimits.
Pain tolerance and the thresholds of human sensory and motor axons to single and repetitive bursts of kilohertz‐frequency stimulation
Authors: Luu Billy L. , Trinh Terry , Finn Harrison T. , Aplin Felix P. , Gandevia Simon C. , Héroux Martin E. , Butler Jane E.
Published: October 2024

Transcutaneous electrical stimulation with repetitive bursts of a kilohertz carrier frequency is thought to be less painful than conventional pulsed currents by reducing the sensitivity of pain receptors. However, no purported benefit has been shown unequivocally. We compared the effects of carrier‐frequency stimulation and conventional stimulation on pain tolerance and the thresholds for sensory and motor axons in twelve participants. The ulnar nerve was stimulated transcutaneously with a conventional single pulse and 5 and 10 kHz carrier‐frequency waveforms that had 5 and 10 pulses, respectively, when delivered in bursts of ∼1 ms duration. Phase durations were adjusted across waveform types to match the total charge for a given current amplitude. Single bursts of stimulation were delivered from 1 mA up until no longer tolerable. This was repeated with repetitive bursts of stimulation at 20 Hz for 1 s. Participants tolerated higher current amplitudes with both carrier‐frequency waveforms than conventional stimulation, with repetitive bursts more painful than single bursts. However, compared to conventional stimulation, carrier‐frequency waveforms required more current to produce sensory and motor‐threshold responses and to obtain a maximal motor response (Mmax). When the current at pain tolerance was normalised to the current at Mmax, participants tolerated lower stimulus intensities with carrier‐frequency waveforms than conventional stimulation. These findings indicate that there is little to no benefit in using carrier‐frequency waveforms to minimise the discomfort from electrical stimulation as the increase in stimulus intensity at pain tolerance is more than offset by reduced effectiveness in the activation of sensory and motor axons.

image

Key points

Transcutaneous electrical stimulation with repetitive bursts of a kilohertz carrier‐frequency waveform is thought to be less painful than conventional pulsed currents.

For ulnar nerve stimulation, when stimulus waveforms were matched for total phase charge, participants tolerated higher current amplitudes with carrier‐frequency stimulation than conventional stimulation.

However, compared to conventional stimulation, carrier‐frequency waveforms required more current to produce a threshold response in both sensory and motor axons and to produce a maximal motor response (Mmax).

When current at pain tolerance was normalised to current at Mmax, participants tolerated lower stimulus intensities with carrier‐frequency waveforms than conventional stimulation.

Carrier‐frequency waveforms provide little to no benefit in minimising the discomfort from transcutaneous electrical stimulation as the increase in stimulus intensity at pain tolerance is more than offset by reduced effectiveness in activating sensory and motor axons.
CURRENT STATUS OF SCABIOSA ISETENSIS POPULATIONS IN CENTRAL KAZAKHSTAN
Authors: Turzhanova S. , Ishmuratova M. , Tleukenova S. , Gavrilkova E.
Published: October 2024

The paper presents the results of studying the structure of 6 populations of Scabiosa isetensis growing in Central Kazakhstan. The floristic composition of communities, the ratio of life forms, ecological groups and age spectrum were evaluated. The floristic composition of the populations was 79 species from 56 genera and 23 families, of which the leading are the families of Asteraceae and Fabaceae. Herbaceous perennials predominate among life forms, mesophytes and xerophytes by ecological groups. Such a spectrum of families in populations with Scabiosa isetensis and ecological and biomorphic composition is a vivid indicator of the degree of habitat heterogeneity. Analysis of Jaccard's similarity indices showed similarity in species composition between populations 4 and 5; 1 and 2; 3 and 6, which is explained by similar habitat conditions. All studied populations are characterized by a single type of ontogenetic spectrum - left-handed type with predominance of juvenile individuals, i.e. populations with Scabiosa isetensis are young, developing, and suitable for practical use.
Global Antiviral Peptide Research: A Bibliometric Analysis from 1951 to 2022
Authors: Putri Wahyu Aristyaning , Setiawan Jajar , Sofyantoro Fajar , Mafiroh Wulan Usfi , Priyono Dwi Sendi , Septriani Nur Indah , Siregar Abdul Rahman , Purwestri Yekti Asih , Wibowo Anjar Tri , Nuringtyas Tri Rini
Published: October 2024

Antiviral peptides (AVPs) are small molecules that inhibit the replication of viruses in living cells. AVPs are being investigated as potential alternatives to traditional antiviral drugs. The development of novel antiviral agents is of the highest concern because some traditional antiviral medications can be ineffective and lead to resistant viruses emergence. We conducted a bibliometric study on the global distribution of AVP research to comprehend the trends and patterns in the field. For this analysis, we retrieved data from the Scopus database on AVP-related publications from 1951 to 2022, including the number of publications, citations, and authors. Overall, 10,279 papers were published, with an annual average of 146 publications. The United States released the most documents, followed by China, Germany, and the United Kingdom. Since 2001, there has been a substantial increase in global publications on AVPs, with prominent themes including virology, genetics, protease inhibitors, polypeptide antimicrobial agents, and viral entry. This bibliometric analysis can be used to guide future research in this field.
Cr2O3–NiO mixed oxides thin films for p-type transparent conductive electrodes
Authors: Almaev Aleksei , Kushnarev Bogdan , Korusenko Petr , Butenko Pavel , Kopyev Viktor , Koroleva Aleksandra , Chikiryaka Andrei , Zhizhin Evgeniy
Published: October 2024

The Cr2O3–NiO mixed oxides’ thin films were formed by means of the layer-by-layer magnetron sputtering deposition of Cr2O3, NiO, and Cr2O3 layers on c-plane sapphire substrates. These thin-film structures, subjected to subsequent annealing, constituted a combination of the monocrystalline (0001) Cr2O3 and nonordered nickel oxide phase, which was a mixture of NiO and Ni2O3. The annealing at 900 and 1000 °С in air facilitated the diffusion of Ni and Cr atoms into the layers. Varying the annealing time allowed us to control the uniformity of the Ni and Cr distribution, the microrelief of the film surface, the transmittance in the visible region, and the sheet resistance of the Cr2O3–NiO thin-film structures. Thus, the films annealed at 900 °C during 30 min were characterized by a uniform distribution, a relatively weakly developed surface, a low sheet resistance, and the highest Haacke's Figure of Merit of 1.49 × 10–9 Ω–1. The formation of mixed Cr2O3–NiO oxides by the proposed approach was found to be an effective way to improve the performances of Cr2O3 based p-type transparent conductive electrodes.
Deep cryogenic silicon etching for 3D integrated capacitors: A numerical perspective
Authors: Rudenko M. K. , Miakonkikh A. V. , Rudenko K. V.
Published: October 2024

One promising approach to increase the capacity density of integral microcapacitors, microsupercapacitors, and microbatteries is three-dimensional structure design, where electrodes are exposed in three dimensions instead of conventional in-plane electrodes. Such structures include nanowires, nanotubes, nanopillars, nanoholes, nanosheets, and nanowalls. In this work, a cryogenic silicon etching process suitable for fabrication of structures with high electrode area is proposed. A numeric model of this process is experimentally calibrated and used for pillar array structure sidewall area optimization. The use of adaptive Runge–Kutta–Fehlberg time integrator allows to achieve almost linear overall computation complexity as a function of simulated etching time, despite the linear increase in conductance computation complexity with depth. A rule for choosing optimal geometric structure parameters under technological constraints is formulated. An optimized trefoil-like structure is proposed, resulting in a total 5.5% increase in sidewall area with respect to the hexagonal array of circular pillars, resulting in 20.33 sidewall area per unit chip area for 30 min long etch or 31.80 for 60 min long etch.
Adhesion layers between piezoelectric and magnetostrictive layers in a MEMS magneto-sensor stack: Influence on the phase transformation of deposited Co/Fe multilayers to magnetostrictive CoxFe1−x phase
Authors: Honig H. , Töpfer H. , Schaaf P.
Published: October 2024

Magnetoelectric MEMS devices, such as magnetic field sensors, may be composed of a multilayer stack as a magnetostrictive layer, which is mechanically coupled to a piezoelectric film. Good adhesion and a stable rigid interface have to be maintained for such a sensor. Certain electric and magnetic properties, especially the magnetostriction, have to reach sufficiently high values, which can be achieved by selected phases or mixtures of phases. In this study, Co/Fe multilayers with varied bilayer periods are deposited onto AlN or Sc0.14Al0.86N coated Si substrates by DC magnetron sputtering with the optional insertion of a 5 nm thick adhesion layer of Cr or Zr to investigate its influence on the formation of the desired mixture of bcc and fcc Co0.7Fe0.3 phases, which are expected to yield a high magnetostrictive strain, after an RTA at 800 °C. A qualitative phase analysis is made by XRD in Bragg-Brentano geometry and shows that the bcc + fcc mixture can be achieved with a Cr interlayer. A sharp, void free, and undamaged interface for that case was observed in SEM images of cross sections prepared with FIB.
Observation of micropolar modes in the transmission of acoustic waves at oblique incidence by polystyrene plates
Authors: Meso C. , Franklin H. , Ogam E. , Fellah Z. E. A.
Published: October 2024

This study investigates micropolar plates through the analysis of transmitted acoustic waves at various incident angles. Using a combined theoretical and experimental approach, we explore the non-classical elasto-dynamic behavior of these materials. Theoretical transmission coefficients are tailored to highlight generalized Lamb modes and a new type of vibration mode called micropolar modes, considering the constant thickness of the plate and the effects of material micropolarity on linear elasticity. Overlaying diverse transmission coefficients for different angles provides insight into micropolar behavior, aiding in the understanding of mode evolution in the frequency domain and the estimation of the critical angle. We employ two types of low-density closed-cell foams made from polystyrene (expanded in one case, extruded in the other), covering a frequency range from 4 to 60 kHz using a tweeter loudspeaker and a microphone integrated with a National Instruments acquisition system. Identification of the first vibration mode of the plates is facilitated by the frequency range rich in low frequencies. Additionally, all responses exhibit supersonic velocities with substantial attenuations. The originality of this paper is twofold: it provides theoretical predictions of micropolar modes, along with their experimental observations above a critical angle of incidence. Consequently, this research enriches our understanding of micropolar materials and their potential contribution to effective noise reduction strategies in acoustic engineering.
Phasing out open net-pen salmon farming in British Columbia
Authors: Mather Charles
Published: October 2024

Canada has committed to banning salmon open net-pen aquaculture in British Columbia by 2029 and is transitioning the industry to closed containment technologies for salmon farming.
Levofloxacin activity at increasing doses in a murine model of fluoroquinolone-susceptible and -resistant tuberculosis
Authors: Maitre Thomas , Godmer Alexandre , Mory Céline , Chauffour Aurélie , Mai Thi Cuc , El Helali Najoua , Aubry Alexandra , Veziris Nicolas
Published: October 2024

High-dose levofloxacin was explored in a clinical trial against multidrug-resistant tuberculosis and failed to show increased efficacy. In this study, we used a murine model to explore the efficacy of a dose increase in levofloxacin monotherapy beyond the maximum dose evaluated in humans. A total of 120 4-week-old female BALB/c mice were intravenously infected with 10
6
CFU of
Mycobacterium tuberculosis
H37Rv wild-type (WT) or isogenic H37Rv mutants harboring GyrA A90V or D94G substitutions; the MICs were 0.25, 4, and 6 µg/mL, respectively. Levofloxacin 250 and 500 mg/kg were given every 12 h (q12h) orally for 4 weeks. Pharmacokinetic parameters were determined after five doses. These two regimens decreased lung bacillary load in mice infected with H37Rv WT but not in mice infected with the A90V and D94G mutants. Levofloxacin 250 mg/kg q12h in mice generated pharmacokinetic parameters equivalent to 1,000 mg/d in humans, whereas 500 mg/kg q12h generated a twofold greater exposure than the highest equivalent dose tested in humans (1,500 mg/d). In our dose–response model, the effective concentration at 50% (EC
50
) produced an AUC/MIC (AUC
0–24h
/MIC) ratio of 167.9 ± 27.5, and at EC
80
it was 281.2 ± 97.3. Based on this model, high-dose levofloxacin regimens above 1,000 mg/d are not expected to cause a significant increase in bactericidal activity. This study suggests no benefit of high-dose levofloxacin above 1,000 mg/d in the treatment of fluoroquinolone-susceptible or -resistant tuberculosis.
Genome editing in ubiquitous freshwater Actinobacteria
Authors: Bairagi Nachiketa , Keffer Jessica L. , Heydt Jordan C. , Maresca Julia A.
Published: October 2024

Development of genome-editing tools in diverse microbial species is an important step both in understanding the roles of those microbes in different environments, and in engineering microbes for a variety of applications. Freshwater-specific clades of Actinobacteria are ubiquitous and abundant in surface freshwaters worldwide. Here, we show that
Rhodoluna lacicola
and
Aurantimicrobium photophilum
, which represent widespread clades of freshwater Actinobacteria, are naturally transformable. We also show that gene inactivation via double homologous recombination and replacement of the target gene with antibiotic selection markers can be used in both strains, making them convenient and broadly accessible model organisms for freshwater systems. We further show that in both strains, the predicted phytoene synthase is the only phytoene synthase, and its inactivation prevents the synthesis of all pigments. The tools developed here enable targeted modification of the genomes of some of the most abundant microbes in freshwater communities. These genome-editing tools will enable hypothesis testing about the genetics and (eco)physiology of freshwater Actinobacteria and broaden the available model systems for engineering freshwater microbial communities.

IMPORTANCE

To advance bioproduction or bioremediation in large, unsupervised environmental systems such as ponds, wastewater lagoons, or groundwater systems, it will be necessary to develop diverse genetically amenable microbial model organisms. Although we already genetically modify a few key species, tools for engineering more microbial taxa, with different natural phenotypes, will enable us to genetically engineer multispecies consortia or even complex communities. Developing genetic tools for modifying freshwater bacteria is particularly important, as wastewater, production ponds or raceways, and contaminated surface water are all freshwater systems where microbial communities are already deployed to do work, and the outputs could potentially be enhanced by genetic modifications. Here, we demonstrate that common tools for genome editing can be used to inactivate specific genes in two representatives of a very widespread, environmentally relevant group of Actinobacteria. These Actinobacteria are found in almost all tested surface freshwater environments, where they co-occur with primary producers, and genome-editing tools in these species are thus a step on the way to engineering microbial consortia in freshwater environments.
SARS-CoV-2 N protein coordinates viral particle assembly through multiple domains
Authors: Han Yuewen , Zhou Haiwu , Liu Cong , Wang Weiwei , Qin Yali , Chen Mingzhou
Published: October 2024

Increasing evidence suggests that mutations in the nucleocapsid (N) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may enhance viral replication by modulating the assembly process. However, the mechanisms governing the selective packaging of viral genomic RNA by the N protein, along with the assembly and budding processes, remain poorly understood. Utilizing a virus-like particles (VLPs) system, we have identified that the C-terminal domain (CTD) of the N protein is essential for its interaction with the membrane (M) protein during budding, crucial for binding and packaging genomic RNA. Notably, the isolated CTD lacks M protein interaction capacity and budding ability. Yet, upon fusion with the N-terminal domain (NTD) or the linker region (LKR), the resulting NTD/CTD and LKR/CTD acquire RNA-dependent interactions with the M protein and acquire budding capabilities. Furthermore, the presence of the C-tail is vital for efficient genomic RNA encapsidation by the N protein, possibly regulated by interactions with the M protein. Remarkably, the NTD of the N protein appears dispensable for virus particle assembly, offering the virus adaptive advantages. The emergence of N* (NΔN209) in the SARS-CoV-2 B.1.1 lineage corroborates our findings and hints at the potential evolution of a more streamlined N protein by the SARS-CoV-2 virus to facilitate the assembly process. Comparable observations have been noted with the N proteins of SARS-CoV and HCoV-OC43 viruses. In essence, these findings propose that β-coronaviruses may augment their replication by fine-tuning the assembly process.

IMPORTANCE

As a highly transmissible zoonotic virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to evolve. Adaptive mutations in the nucleocapsid (N) protein highlight the critical role of N protein-based assembly in the virus’s replication and evolutionary dynamics. However, the precise molecular mechanisms of N protein-mediated viral assembly remain inadequately understood. Our study elucidates the intricate interactions between the N protein, membrane (M) protein, and genomic RNA, revealing a C-terminal domain (CTD)-based assembly mechanism common among β-coronaviruses. The appearance of the N* variant within the SARS-CoV-2 B.1.1 lineage supports our conclusion that the N-terminal domain (NTD) of the N protein is not essential for viral assembly. This work not only enhances our understanding of coronavirus assembly mechanisms but also provides new insights for developing antiviral drugs targeting these conserved processes.
mSphere of Influence: Revisiting the central dogma, again!
Authors: Samir Parimal
Published: October 2024

Dr. Parimal Samir works in the field of host–pathogen interactions. In this mSphere of Influence article, he reflects on how the manuscript entitled “
De novo
gene synthesis by an antiviral reverse transcriptase” by Samuel Sternberg and colleagues made an impact by reminding him that there is still so much to discover in life sciences.
How geology and paleontology help build the magic of the Disneyland Resort (Anaheim, California, USA)
Authors: Sturmer* Daniel M. , Vice* Garrett S. , Sumida* Stuart , Mary* Michelle
Published: October 2024

The Disneyland Resort (Anaheim, California, USA) is one of the most iconic theme parks in the world, and is fortuitously located across the street from the 2024 GSA Connects meeting. Geology and paleontology have played an important role in the making of the resort, from initial design and layout to attraction and land conceptualization and design. On this walking tour, we will learn some of the history of the resort and how the geosciences have affected and influenced the design and evolution of several attractions at Disneyland Park, including the Disneyland Railroad, Pirates of the Caribbean, the Matterhorn Bobsleds, Big Thunder Mountain, and the new Star Wars: Galaxy’s Edge. We also include notes on the influence of geology on several of the attractions at Disney California Adventure. Ultimately, we hope participants gain insight and appreciation for the influence that the geosciences have had on the Disneyland Resort and the effort that Disney’s Imagineers put in to accurately incorporate elements of our natural world into the world(s) of the Disneyland Resort. The examples we will see show how incorporating real geology and paleontology into attraction conceptualization and construction results in more believable, engaging, and entertaining attractions for audiences.
Mechanism and management of acute femoral artery occlusion caused by suture-mediated vascular closure device following neurointervention
Authors: Fuga Michiyasu , Kan Issei , Shukuzawa Kota , Murayama Yuichi
Published: October 2024

Vascular closure devices (VCDs) show fewer complications related to the puncture site than manual compression but can cause stenosis or occlusion of the common femoral artery (CFA). A patient in her 30s who underwent suture-mediated VCD for haemostasis at the right CFA puncture site after neurointervention showed occlusion of the right CFA on postoperative day 2. Endovascular treatment retrieved the thrombus from the occlusion site, and surgical removal of a suture causing stenosis between the dissected posterior wall intima and anterior wall allowed the resumption of full flow through the right CFA. This complication occurred because the VCD insertion angle was less than 45°, which allowed the footplate to deploy more perpendicularly, causing its posterior foot to snag and dissect the posterior wall intima. To mitigate the risk of such complications caused by the suture-mediated VCD, the surgeon should ensure that the entry angle of the puncture is not less than 45°.
For which entrustable professional activities must medical students be prepared if unsupervised patient care without further training is an expectation? An international Global South study
Authors: ten Cate Olle , Nel Daniel , Hennus Marije P , Peters Susanne , Romao Gustavo Salata
Published: October 2024

Introduction

Training medical students requires objectives that are often translated into frameworks of competencies. Since the introduction of entrustable professional activities (EPAs), these tasks or ‘units of professional practice’, originally conceived for postgraduate training, define what residents must be prepared to do unsupervised. Nowadays, EPAs are also applied to undergraduate training, with the prospect of entering residency. However, in many countries, especially in the Global South, a substantial number of medical graduates will be working in healthcare with little or no supervision and no further training soon or ever. EPAs for these conditions cannot be copied from undergraduate medical education EPA frameworks in Global North countries.

Methods

We conducted a generative investigation to identify and elaborate EPAs for Global South countries who must train students for unsupervised general practice. We included 39 medical educators from 13 Global South countries and 17 specialties in either one of two online focus group sessions using a nominal group technique (NGT) or as Delphi panel member. Results from the two NGT sessions were merged and fed into the two-round Delphi investigation.

Results

A framework of 11 EPAs resulted, each with an elaborate description (specification, setting and limitations).

Conclusion

This framework of undergraduate medical education Global South EPAs differs in its nature and specifications from existing Global North EPAs. The authors do not pretend universality for all Global South countries with graduates who face expectations of unsupervised practice but present it to support countries that consider introducing the model of entrustable professional activities.
Risk factors for antenatal anxiety: a cross-sectional study in field antenatal clinics in Sri Lanka
Authors: Priyadarshanie Manathungei Nirmala , Waas Dulshika A , Goonewardena Sampatha , Balasuriya Aindralal , Senaratna Chamara V , Fernando Sharaine
Published: October 2024

Objectives

We aimed to determine the prevalence and factors affecting antenatal anxiety (AA) among Sri Lankan women.

Design

We conducted a cross-sectional analysis of first trimester data from a population-based cohort of antenatal women.

Setting

Field antenatal clinics of four field health areas in Colombo District, Sri Lanka.

Participants

Antenatal women (n=535) in the first trimester of pregnancy and aged ≥18 years were sequentially recruited when they attended antenatal clinics selected using random cluster sampling. Those with hearing difficulty, visual and speaking problems or currently on treatment for mental disorders were excluded.

Measures

We used an interviewer-administered questionnaire to collect data. The AA was identified using the validated Sinhala version of Perinatal Anxiety Screening Scale (PASS-S). Self-reported demographic and pregnancy-related information were verified against health records. Psychosocial risk factors were self-reported. We investigated the associations between potential risk factors and AA using regression models that included confounders identified through a directed acyclic graph and reported using adjusted odds ratios (ORs) with 95% confidence intervals (CIs).

Results

The prevalence of AA during the first trimester of pregnancy, identified using a PASS threshold of ≥20, was 34.4% (n=184). We found several novel risk factors for AA, namely, physical (OR 2.1; 95% CI 1.4 to 3.2) and mental health problems of self (OR 2.3; 95% CI 1.2 to 4.4), physical (OR 2.1; 95% CI 1.4 to 3.4) and mental health problems of parents/spouse (OR 6.7; 95% CI 2.8 to 16.2), traumatic life situations (OR 2.7; 95% CI 1.5 to 4.8), substance abuse by the spouse (OR 3.5; 95% CI 1.9 to 6.6) and the spouse being away (OR 2.0; 95% CI 1.1 to 3.7). The other risk factors that we identified included domestic violence among family members (OR 6.4; 95% CI 1.3 to 31.0), loss of family support (OR 2.2; 95% CI 1.0 to 5.2), financial hardships (OR 1.7; 95% CI 1.0 to 2.8), accommodation-related issues (OR 2.2; 95% CI 1.0 to 4.9), unplanned pregnancy (OR 3.7; 95% CI 1.9 to 7.3), difficulties due to pregnancy (OR 2.0; 95% CI 1.1 to 3.4), changed or stopped education (OR 2.9; 95% CI 1.7 to 5.1), recent loss of employment (OR 2.9; 95% CI 1.2 to 7.0), recent death of a loved one (OR 3.5; 95% CI 2.0 to 5.9) and sleep problems during pregnancy (OR 1.6; 95% CI 1.1 to 2.3).

Conclusions

The prevalence of antenatal anxiety is high in Sri Lanka and is associated with several risk factors, not previously described, which are potentially modifiable.
Effect of calcium channel blockers on influenza incidence: a population-based retrospective cohort study using administrative claims data in Japan
Authors: Imai Takanori , Hashimoto Hideki , Kanda Naoki , Sasabuchi Yusuke , Matsui Hiroki , Yasunaga Hideo , Hatakeyama Shuji
Published: October 2024

Objectives

Laboratory experiments have indicated that calcium channel blockers (CCBs) inhibit the entry and replication of influenza A virus in cells. However, no clinical studies have assessed the incidence of influenza among patients receiving CCBs. This study aimed to investigate the association between CCB use and the incidence of influenza among patients with hypertension using administrative claims data in Japan.

Design

Retrospective cohort study.

Setting

Administrative health insurance claims database of Kumamoto Prefecture, Japan.

Participants

360 515 patients with hypertension (10th edition of the International Classification of Diseases code I10) who were prescribed CCBs and 171 142 patients who were prescribed angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) between 2012 and 2016.

Primary outcome

We compared the incidence of influenza between the CCB and ACEI/ARB groups using high-dimensional propensity-score (HD-PS) matching.

Results

A total of 166 814 HD-PS matched pairs were obtained. Before HD-PS matching, the CCB group had a significantly lower influenza incidence than the ACEI/ARB group in the overall analysis (2.4% vs 2.5%, p=0.007; risk ratio 0.95, 95% CI 0.92 to 0.99). However, no significant difference was observed between the two groups after HD-PS matching (2.4% vs 2.5%, p=0.067; risk ratio 0.96, 95% CI 0.92 to 1.00); only in 2012 did the CCB group have a significantly lower likelihood of influenza than the ACEI/ARB group.

Conclusions

No significant difference was observed in the influenza incidence between the CCB and ACEI/ARB groups. A direct comparative study between background-matched patients with and without CCBs is warranted to confirm the effect of CCBs on reducing the incidence of influenza.
Impacts of the COVID-19 pandemic on deprivation-level differences in cardiovascular hospitalisations: a comparison of England and Denmark using the OpenSAFELY platform and National Registry Data
Authors: Costello Ruth E , Pedersen Lars , Henderson Alasdair D , Tazare John , Sorensen Henrik Toft , Vandenbroucke Jan P , Mansfield Kathryn E , Mahalingasivam Viyaasan , Zheng Bang , Carreira Helena , Bidulka Patrick , Piehlmaier Dominik Manuel , Wong Angel Yun Sum , Warren-Gash Charlotte , Hayes Joseph F , Quint Jennifer K , Katikireddi Srinivasa Vittal , Mackenna Brian , Mehrkar Amir , Bacon Sebastian , Goldacre Ben , Tomlinson Laurie A , Langan Sinead M , Mathur Rohini , Collaborative The LH&W NCS (or CONVALESCENCE) , Consortium The OpenSAFELY
Published: October 2024

Objectives

To examine the impact of the COVID-19 pandemic on deprivation-related inequalities in hospitalisations for cardiovascular disease (CVD) conditions in Denmark and England between March 2018 and December 2021.

Design

Time-series studies in England and Denmark.

Setting

With the approval of National Health Service England, we used English primary care electronic health records, linked to secondary care and death registry data through the OpenSAFELY platform and nationwide Danish health registry data.

Participants

We included adults aged 18 and over without missing age, sex or deprivation information. On 1 March 2020, 16 234 700 people in England and 4 491 336 people in Denmark met the inclusion criteria.

Primary outcome measures

Hospital admissions with the primary reason for myocardial infarction (MI), ischaemic or haemorrhagic stroke, heart failure and venous thromboembolism (VTE).

Results

We saw deprivation gradients in monthly CVD hospitalisations in both countries, with differences more pronounced in Denmark. Based on pre-pandemic trends, in England, there were an estimated 2608 fewer admissions than expected for heart failure in the most deprived quintile during the pandemic compared with an estimated 979 fewer admissions in the least deprived quintile. For all other outcomes, there was little variation by deprivation quintile. In Denmark, there were an estimated 1013 fewer admissions than expected over the pandemic for MI in the most deprived quintile compared with 619 in the least deprived quintile. Similar trends were seen for stroke and VTE, though absolute numbers were smaller. Heart failure admissions were similar to pre-pandemic levels with little variation by deprivation quintile.

Conclusions

Overall, we did not find that the pandemic substantially worsened pre-existing deprivation-related differences in CVD hospitalisations, though there were exceptions in both countries.
National review of end-of-life care withdrawal guidelines for non-invasive advanced respiratory support using document analysis
Authors: Wenzel David , Jeffery Thomas , Davies Rachel , Creese Jennifer , Wilson Eleanor , Faull Christina
Published: October 2024

Objectives

This study aims to understand the breadth of practice around end-of-life withdrawal of non-invasive advanced respiratory support (encompassing both continuous positive airway pressure and non-invasive ventilation) by analysing NHS-published guidelines and guidance for clinicians. This study seeks validity in the guidelines through a confluence of findings and reassurance of practice despite having little to no high-quality research to inform the content of the guidelines. Ultimately, where discordance is found between guidelines, there will be a strong mandate for future research.

Methods

Guidelines were gathered through snowball sampling and analysed using document analysis techniques. Analysis was mixed in inductive and deductive and facilitated across several authors using framework analysis. 20 guidelines were analysed but saturation was found after 15. Further guidelines were analysed beyond saturation to provide reassurance of the endpoint of the study.

Results

There were common components to the guidelines presented as themes: legal and ethical frameworks, decision-making around withdrawal, the process of withdrawal, post-withdrawal care and when to contact palliative care. There were significant areas of confluence, where multiple guidelines were in agreement on best practice. However, there was significant discordance in some key areas including the use of post-withdrawal oxygen therapy and pressure weaning practice.

Conclusion

This study provides reassurance through a confluence of findings for the majority of withdrawal practices. However, key areas of discordance highlight an urgent need for further research to support clinicians, patients and their families during challenging clinical events.