bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of testosterone replacement therapy on lower urinary tract symptoms: A systematic review and network meta‐analysis
Authors: Yuan Xiang , Xiong Xingyu , Xue Jianxin
Published: July 2024

Objective

In this study, we aimed to perform a network meta‐analysis (NMA) to investigate the effects of different testosterone replacement therapy (TRT) administration routes on lower urinary tract symptoms (LUTS) in aging men with late‐onset hypogonadism (LOH).

Methods

A systematic search of PubMed, Embase, The Cochrane Library, CNKI, WanFang Data, and VIP was conducted to identify randomized controlled trials (RCTs) reporting data on International Prostate Symptom Score (IPSS), prostate‐specific antigen (PSA) level, or prostate volume. NMA was performed, and subgroup analysis was conducted to assess the impact of TRT duration on outcomes.

Results

A total of 21 RCTs involving 2453 participants were included. For pairwise meta‐analysis, p values for TRT delivered by transdermal, intramuscular, and oral routes were as follows: IPSS: 0.93, 0.20, and 0.76; PSA level: 0.20, 0.27, and 0.98; prostate volume: 0.18, 0.04, and 0.16. There were no significant differences in IPSS, PSA level, or prostate volume between TRT routes. In subgroup analysis, long‐term intramuscular TRT significantly decreased IPSS (p = 0.03), short‐term transdermal TRT increased PSA levels (p < 0.001), and short‐term intramuscular TRT increased the prostate volume (p = 0.04). Other forms of TRT showed no significant change in IPSS, PSA level, and prostate volume compared with the placebo. Indirect comparison of the three administration routes demonstrated no significant differences in IPSS, PSA level, and prostate volume. Nevertheless, surface under the cumulative ranking curve analysis indicated that intramuscular TRT had an 83% probability of being the best method for decreasing IPSS.

Conclusions

The results demonstrate that TRT does not worsen LUTS regardless of the administration route. Intramuscular TRT may be the preferred treatment for aging men with LOH and LUTS. Intramuscular TRT may be the preferred treatment for men with LOH and LUTS. Further research is warranted to validate these findings and optimize TRT management strategies.
Efficiency and equity: A general equilibrium analysis of rent‐seeking
Authors: Heijdra Ben J. , Heijnen Pim
Published: July 2024

We study the rent‐seeking phenomenon using a simple, static general equilibrium model. The economy consists of two sectors, both employing a constant returns‐to‐scale technology with labor as its sole input. One of the sectors is a monopoly, where a continuum of agents compete for a share of monopoly profits (i.e. rent). Agents are heterogeneous in labor productivity and rent‐seeking ability: they face a choice between engaging in (productive) work or vying for a share of the rent (i.e., a contest against other rent‐seekers). At the aggregate level, rent‐seeking reduces the available amount of labor in the economy and thereby lowers output and welfare (rent‐seeking is inefficient). At the individual level, rent‐seeking shifts income towards rent‐seekers. Consequently, an economy with few rent‐seekers tends to have high income inequality: an effect that is exacerbated by the fact that rent is decreasing in the number of rent‐seekers (low levels of rent‐seeking increase inequity). This tradeoff between efficiency and equity is the primary focus of this paper. We investigate how the distribution of rent‐seeking ability and the correlation between labor productivity and rent‐seeking ability shape this tradeoff.
Mesenchymal stem cells derived from hard palate: An attractive alternative for regenerative medicine
Authors: Zhang Hui , Jiang Zhiwei , Ye Yuer , Pan Yiqi , Yu Mengjia , Yang Guoli , Wang Ying
Published: July 2024

Objective

The palatal mucosa exhibits a notable ability to regenerate without causing scarring during the process of wound healing, rendering it a highly valuable reservoir of mesenchymal stem cells (MSCs). The aim of this review is to summarize the different sources of MSCs derived from hard palatal (PMSCs), thereby presenting a promising avenue for the utilization of regenerative medicine.

Materials and Methods

Pertinent literatures focused on the sources, identification methods, and advantageous characteristics of PMSCs are obtained from PubMed and Web of Science.

Results

PMSCs, originating from the hard palate periosteum, subepithelial adipose tissue, and lamina propria, have been successfully isolated and characterized, with positive markers for MSCs and negative markers for hematopoietic stem cells. Moreover, PMSCs demonstrate resistance to inflammatory stimuli, enabling uninterrupted osteogenesis in the presence of inflammation. Additionally, PMSCs possess a notable migratory capacity, facilitating prompt arrival at the site of injury. Furthermore, PMSCs exhibit various advantageous inherent in stem cells, including clonogenicity, self‐renewal capability, and pluripotent differentiation potential.

Conclusions

PMSCs have stem cell‐related properties and can be used for regenerative medicine of cells and tissues in the future.
Improving detached tiller culture for doubled haploid production in wheat (T. aestivum L.) by post‐pollination fungicides application and UV radiation treatment
Authors: Goyal Prinka , Thind Sanjeev K. , Srivastava Puja , Sharma Achla
Published: July 2024

This work aims at improving the proven protocol for doubled haploid production in wheat. This procedure has some deficits, for example, microbial infection of ears as well as of the nutrient culture medium. In the present study, the potential effect of sterilization by detached tiller culture fungicides of ears as well as of nutrient medium to control microbial infection, and its effect on the formation of caryopses and embryos (CFF, EFF) was studied. In a further experiment, the UV‐light was used as physical sterilant for the nutrient medium. All of the fungicides and their concentrations studied were found to be effective to control infection on ears except the concentration 0.05% tilt. 0.1% tilt gave the highest CFF (79.5%) followed by 0.1% Bayleton (78.0%). The lowest CFF was recorded in control treatment (48.8%). Among Bavistin treatments, the 0.2% Bavistin gave maximum CFF (68.5%) as well as EFF (29.1%) followed by 0.1% Bavistin (64.9%, 23.7%). The higher concentration of tilt (0.2%) showed detrimental effects on EFF (17.5%). Bavistin in tiller culture nutrient medium reduced infection in medium and was shown to improve CFF and EFF (67.4%, 29.8%).
A generation divided: The politics of Generation X
Authors: Fisher Patrick
Published: July 2024

Generation X often receives less attention in generational analysis due to its perceived lack of distinctiveness compared to preceding and succeeding generations in the contemporary United States. Politically, there is little justification for distinguishing Generation X as it is commonly defined, yet it harbors significant political divergence between its older and younger cohorts. In terms of partisanship, ideology, and public policy preferences, Generation X is markedly divided, essentially comprising two distinct political generations. Generation X can thus be viewed as the in‐between generation representing the political dividing line between young and old. The dividing point is the birth year of 1973. Due to the considerable differences in the political climate during their formative years, those Gen Xers born before 1973 lean considerably more conservative and Republican than those born in 1973 and afterward.

Related Articles

Fisher, Patrick. 2020. “Generational Replacement and the Impending Transformation of the American Electorate.” Politics & Policy 48(1): 38–68. https://doi.org/10.1111/polp.12340.

Shaykhutdinov, Renat. 2019. “Socialization, Rationality, and Age: Generational Gaps and the Attitudes toward the Chechen War in Russia.” Politics & Policy 47(5): 931–55. https://doi.org/10.1111/polp.12323.

Stockemer, Daniel. 2016. “Is the Turnout Function in Democracies and Nondemocracies Alike or Different?” Politics & Policy 44(5): 889–915. https://doi.org/10.1111/polp.12174.
Onion‐pathogenic Burkholderia species: Role and regulation of characterized virulence determinants
Authors: Paudel Sujan , Dutta Bhabesh , Kvitko Brian
Published: July 2024

Members of the bacterial genus Burkholderia are a routine threat to onion production worldwide. In addition to the common onion‐pathogenic species, Burkholderia cepacia, Burkholderia orbicola and Burkholderia gladioli, other Burkholderia species have the potential to cause onion disease. Despite their impacts and long‐known association with onion disease, the virulence mechanisms of onion‐pathogenic Burkholderia are far less well understood than Burkholderia in human and murine infection models. In this review, we will focus on genetically characterized virulence factors in species that contribute to symptom production in onion and other plant hosts. Specifically, we will focus on the variable roles of specialized protein secretion systems (T2SS, T3SS and T4SS) and secreted proteins, thiosulphinate tolerance gene (TTG) clusters and the well‐characterized phytotoxin toxoflavin in virulence. The regulation and roles of LuxI/LuxS quorum‐sensing system and IclR‐type transcriptional regulator, qsmR, as master regulators of secondary metabolite production and virulence factors will also be discussed. The TTG clusters, involved in bacterial tolerance to thiosulphinate defence compounds, exhibit onion tissue‐specific contributions to virulence. This suggests that Burkholderia onion pathogens have tissue‐specific virulence strategies for causing disease.
Expression and function analysis of phenylalanine ammonia‐lyase genes involved in Bamboo lignin biosynthesis
Authors: Sun Huayu , Li Hui , Huang Mei , Gao Zhimin
Published: July 2024

Bamboo, renowned as the fastest‐growing plant globally, matures within an astonishingly short period of 40–50 days from shoots, reaching heights of 10–20 meters. Moreover, it can be harvested for various uses within 3–5 years. Bamboo exhibits exceptional mechanical properties, characterized by high hardness and flexibility, largely attributed to its lignin content. Phenylalanine ammonia‐lyase (PAL) catalyzes the crucial initial step in lignin biosynthesis, but its precise role in bamboo lignification processes remains elusive. Thus, elucidating the functions of PAL genes in bamboo lignification processes is imperative for understanding its rapid growth and mechanical strength. Here, we systematically identified and classified PAL genes in Moso bamboo, ensuring nomenclature consistency across prior studies. Subsequently, we evaluated PAL gene expression profiles using publicly available transcriptome data. The downregulation of PePALs expression in Moso bamboo through in planta gene editing resulted in a decrease in PAL activity and a subsequent reduction in lignin content. In contrast, overexpression of PePAL led to enhanced PAL activity and an increase in lignin content. These findings highlight the critical role of PAL in the lignin biosynthesis process of Moso bamboo, which will help to unravel the mechanism underpinning bamboo's rapid growth and mechanical strength, with a specific emphasis on elucidating the functions of PAL genes.
Nascent policy subsystems in polycentric governance networks: The case of sea‐level rise governance in the San Francisco Bay Area
Authors: Pozzi Tara , Zufall Elise , Gmoser‐Daskalakis Kyra , Vantaggiato Francesca
Published: July 2024

A policy subsystem is a system of relations between actors within the context of a specific, territorially bounded policy issue. Mature policy subsystems feature well‐established, easily distinguishable, confrontational coalitions. Recent literature has explored the behavior of nascent subsystems, which emerge in response to novel policy challenges and feature developing, rather than fully fledged, coalitions. However, as yet, we lack an empirical approach to identify and analyze the structural characteristics of nascent subsystems and assess their implications for theoretical and subsystem development. How do we recognize a nascent policy subsystem when we see one? What are the drivers of its nascent coalitional structure? We answer these questions using social network analysis in the empirical case of the governance network of adaptation to sea‐level rise in the San Francisco Bay Area, using original data collected in 2018. We find that the network portrays a nascent subsystem developing out of pre‐existing coalitions focused on two facets of environmental advocacy: environmental protection and environmental justice. We conclude with recommendations for future research on policy subsystem development.
Influence of additive and maternal effects on production and reproduction traits in Murrah buffaloes: Insights from Bayesian analysis
Authors: Sharma Rohit , Dahiya Satpal , Bangar Yogesh Chandrakant , Yadav Dipin Chander
Published: July 2024

The aim of this research was to assess genetic parameters for first lactation production and reproduction traits in Murrah buffaloes by employing additive and maternal effects. Data on pedigree and specific traits of 640 Murrah buffaloes were gathered from 1997 to 2020. These traits encompassed first lactation milk yield (FLMY), 305‐day first lactation milk yield (305FLMY), first lactation length (FLL), first lactation peak yield (FPY), first service period (FSP), first calving interval (FCI) and first dry period (FDP). Genetic evaluations employed six univariate animal models, accounting for both direct and maternal effects, facilitated by THRGIBBS1F90 and POSTGIBBSF90 programs. Fixed factors included in the analysis were period of calving, season of calving and age at first calving. The Bayesian estimates for direct heritability, derived from the most suitable model, were as follows: FLMY: 0.28 ± 0.01, 305FLMY: 0.30 ± 0.01, FLL: 0.19 ± 0.01, FPY: 0.18 ± 0.01, FSP: 0.12 ± 0.01, FCI: 0.14 ± 0.01 and FDP: 0.12 ± 0.01. Maternal effects were found significant, ranging from 5% to 10%, in first lactation traits under Model 2 and Model 5. Additionally, positive and significant genetic and phenotypic correlations were observed among the studied traits. In conclusion, selection based on 305‐day first lactation milk yield suggests potential for genetic enhancement in Murrah buffaloes, advocating its inclusion in breeding programmes to bolster early performance. Also, consideration of maternal influences is necessary for genetic progress of animals.
International attractiveness of cities: The drivers of urban FDI
Authors: Bono Pierre‐Henri , David Quentin , Desbordes Rodolphe
Published: July 2024

Foreign direct investment (FDI) nowadays mostly corresponds to activities in urban areas. This study provides the first global analysis of the determinants of urban FDI (UFDI). We assemble and exploit a unique database on the location choices of multinational enterprises in urban areas worldwide to investigate the relevance of local, national, and dynamic drivers of cities' international attractiveness. We find that attractive cities are large, productive, endowed with transport infrastructure able to move goods and people within and beyond their borders, abundant in educated people, and embedded in attractive national spaces. Cities combining all these attributes tend to attract service activities. Attractiveness is persistent but can evolve depending on economic dynamism. A variance decomposition analysis indicates that the location choices of UFDI are mainly driven by city‐level determinants, notably transport infrastructure.
Investigating spatiotemporal patterns and determinants of land resource misallocation in prefecture‐level China
Authors: Zhang Junfeng , He Sanwei , Weng Yuwei , Ding Jiancheng
Published: July 2024

The misallocation of land resources is an important factor restricting the high‐quality development of China's economy. Based on the perspective of supply and demand matching, this study proposed a measurement method for the spatial misallocation of land resources and constructed two models for the testing and decomposition of factors affecting land resource spatial misallocation. We used this measurement method and these two models to explore the spatiotemporal characteristics and determinants of the spatial misallocation of land resources in China from 2000 to 2018 with the aim of providing policy recommendations for the correction of land resource misallocation in China and other developing countries. The results showed that the spatial misallocation of land resources in China showed an upward trend with evident spatial differentiation and the proportion of cities with high and severe misallocation increased. Industrial isomorphism and market misallocation are the main driving factors of land misallocation. Government misallocation and factor market abnormal development aggravate land resource misallocation. Extensive economic development and excessive factor agglomeration have a small effect on land resource spatial misallocation. Therefore, strengthening the land supply‐side reform, and implementing differentiated land allocation policies are effective pathways to control land resource misallocation in China.
Maize lipid droplet‐associated protein 2 is recruited by a virus to enhance viral multiplication and infection through regulating cellular fatty acid metabolism
Authors: Wang Siyuan , Wang Xinyu , Li Siqi , Sun Xi , Xue Mingshuo , Di Dianping , Zhang Aihong , Zhang Yongjiang , Xia Yiji , Zhou Tao , Fan Zaifeng
Published: July 2024

Pathogen infection induces massive reprogramming of host primary metabolism. Lipid and fatty acid (FA) metabolism is generally disrupted by pathogens and co‐opted for their proliferation. Lipid droplets (LDs) that play important roles in regulating cellular lipid metabolism are utilized by a variety of pathogens in mammalian cells. However, the function of LDs during pathogenic infection in plants remains unknown. We show here that infection by rice black streaked dwarf virus (RBSDV) affects the lipid metabolism of maize, which causes elevated accumulation of C18 polyunsaturated fatty acids (PUFAs) leading to viral proliferation and symptom development. The overexpression of one of the two novel LD‐associated proteins (LDAPs) of maize (ZmLDAP1 and ZmLDAP2) induces LD clustering. The core capsid protein P8 of RBSDV interacts with ZmLDAP2 and prevents its degradation through the ubiquitin–proteasome system mediated by a UBX domain‐containing protein, PUX10. In addition, silencing of ZmLDAP2 downregulates the expression of FA desaturase genes in maize, leading to a decrease in C18 PUFAs levels and suppression of RBSDV accumulation. Our findings reveal that plant virus may recruit LDAP to regulate cellular FA metabolism to promote viral multiplication and infection. These results expand the knowledge of LD functions and viral infection mechanisms in plants.
External Debt and Economic Vulnerability: An International Evidence
Authors: Dau Nam Huong , Pham Thanh , Luu Hiep Ngoc , Nguyen Dinh Trung
Published: July 2024

This paper examines the influence of external debt on economic vulnerability. Using an international sample of 96 countries over the period from 1990 to 2018, we find that external debts contribute to spurring economic vulnerability. In particular, we show that a higher level of external debt is associated with a greater economic vulnerability through accelerating the scale and the likelihood of external shocks in the economy. However, this finding is only hold for long-term external debt. Short-term external debt, on the other hand, can actually reduce economic vulnerability. We further examine the distribution of external debt and find that public external debt has a negative impact on economic stability, while private external debt appears to have no apparent impact. Overall, our results have important implications for authorities responsible for ensuring the resilience of the economy.
On the Potential of Manufacturing Multi-Material Components With Micro/Nanocellular Structures Via the Hybrid Process of Electromagnetic Forming Injection Foaming
Authors: Pirani Mahdi , Hahn Marlon , Joghan Hamed Dardaei , Tekkaya A. Erman , Farahani Saeed
Published: July 2024

Multimaterial design with a combination of solid and foam structures offers a promising avenue for reducing component weight while enhancing their functionalities. However, the complexity of multistage manufacturing processes poses significant challenges to adopting such approaches. To address these challenges, this paper introduces an innovative concept known as Electromagnetic Forming Injection Foaming (EFIF), which integrates injection molding, forming, and foaming processes into a single hybrid process. This process begins with a simultaneous filling-forming phase, followed by supercritical fluid (SCF) assisted foaming controlled by electromagnetic forming. Through a series of experimental and analytical studies, this work investigates the feasibility and effectiveness of EFIF. First, the impact of pressure drop rate and pressure drop on cell size and density is examined through a specialized experimental setup enabling performing injection, forming, and foaming processes in a single operation. The potential influence of electromagnetic forming on foam injection molding is explored through experiments focusing on the effects of a polymer layer between sheet metal blank and the electromagnetic coils. Additionally, an analytical study evaluates the EFIF process by calculating expected pressure drop rates under different processing conditions and their influence on cell nucleation rates. The results showed the possibility of achieving pressure drop rates up to 1.5 × 105 bar/sec, resulting in nucleation rates up to 1.77 × 109 nuclei/cm3sec. Overall, this paper highlights the potential of EFIF to merge existing technologies into a scalable solution for manufacturing multimaterial components with micro- to nanocellular polymer foams.
Reliability Assessment and Multiphysics Simulation of Additively Printed Wearable Humidity Sensor With Supercapacitive Material for Astronaut in Extreme Condition
Authors: Lall Pradeep , Jang Hyesoo , Hill Curtis
Published: July 2024

Additive technologies, such as aerosol jet printing (AJP) and direct write printing, are increasingly being used in the production of printed circuit boards because they eliminate the need for costly tooling, such as photomasks or etching containers. This is because additive methods allow for the direct deposition of printing materials onto a substrate. A design and manufacturing approach based on software also enables production flexibility, as well as speedier tool adjustments and design development. Moreover, additive printing methods could be used on a wide range of materials, including fabrics, vehicles, and polymers with various surfaces and forms. This versatility in a broad variety of applications allows engineers to create diverse applications, such as sensing devices with electro-cardiogram sensors, pulse-oxygen sensors, galvanic skin response sensors, body temperature sensors, humidity sensors, and so on. Due to its potential for adaptability and integration, the development of additively printed humidity sensors has been the subject of several prior investigations. There are still issues with the reliability of current humidity sensor technology when flexing force is coupled with the humidity sensor. For the avoidance of stability issues, it is required to develop a better printing technique, process recipe, and sensing material encapsulation. In this research, the direct-write (D-write) printing approach with an nScrypt printer was employed to print the humidity sensor as a test vehicle in a laboratory setting. The sensor was characterized by analyzing the print recipe and its interaction with humidity in regard to resistance and humidity sensitivity. Additionally, the characterization of sensor accuracy, hysteresis, linearity, and stability in relation to temperature and humidity variation has been measured. Furthermore, a multiphysics simulation model was created in order to comprehend the electrochemical processes that occur when the humidity sensor is exposed to a very humid environment.
Characteristics of a hybrid radio frequency capacitively and inductively coupled plasma using hydrogen gas
Authors: Ohtsu Yasunori , Tabaru Tatsuo , Schulze Julian
Published: July 2024

A hybrid combination of a radio frequency (RF) capacitively coupled plasma (CCP) equipped with a ring-shaped hollow powered electrode and an inductively coupled plasma (ICP) with a helical antenna is investigated in hydrogen gas. Characteristics of the RF hybrid plasma are measured by a Langmuir probe at a fixed position in the center between the RF powered and grounded electrode for various CCP powers of 50–150 W. The voltage drop across the CCP is found to be almost independent of the ICP power. The RF hybrid plasma attains a high ion density of the order of 1010 cm−3 between the electrodes even at a low CCP input power of 50 W. The plasma density is strongly affected by the CCP generator power, while the floating potential is controlled by the ICP power, whereas the electron temperature is independent of the ICP power for various CCP powers. The negative ion production is enhanced by increasing the ICP power, resulting in a decrease in the ratio of the negative to the positive charge saturation current detected by the Langmuir probe. The maximum ratio of the negative ion density to the electron density is approximately 8 at a CCP power of 50 W and an ICP power of 250 W.
Enhanced contact resistance reduction in MoS2 transistors via ultrathin LiPON electrode interface doping
Authors: Pan Ting , Wu Yonghuang , Shi Run , Liu Haowen , Tong Ruoyu , Peng Ruixuan , Zhao Bochen , Liu Kai , Zhang Yuegang
Published: July 2024

Two-dimensional (2D) semiconductors are considered one of the most promising channel materials in devices for the future development of integrated circuits with low power consumption and high integration. As the size of the device gradually decreases, a key challenge is to reduce the contact resistance of nanoscale devices. Doping is a crucial strategy to realize low contact resistances in 2D devices, but there is still lack of simple and compatible doping methods. Here, we report a simple and localized doping strategy that adopts an ultrathin lithium phosphorus oxynitride (LiPON) as the buffer layer of electrodes to reduce the contact resistance of MoS2 transistors. This ultrathin buffer layer induces strong n-doping in the electrode contact area, thereby achieving nearly Ohmic contact in the devices. The contact resistances of LiPON/Ti/Au electrodes for different channel carrier densities are all lower than those of Ti/Au electrodes because the Schottky barrier height (SBH) for the LiPON/Ti/Au electrodes is only 8% of the value for the Ti/Au electrodes. This work provides a simple and compatible strategy for the development of high-performance 2D devices and deepens the understanding of the important role of doping in 2D electrical contacts.
Organic photovoltaic biomaterial with fullerene derivatives for near-infrared light sensing in neural cells
Authors: Yuan Bowei , Jiang Xue , Xie Zijun , Zhang Xuanjun , Zhang Jiaxin , Hong Jing
Published: July 2024

Retinal degenerative diseases, which can lead to photoreceptor cell apoptosis, have now become the leading irreversible cause of blindness worldwide. In this study, we developed an organic photovoltaic biomaterial for artificial retinas, enabling neural cells to detect photoelectric stimulation. The biomaterial was prepared using a conjugated polymer donor, PCE-10, and a non-fullerene receptor, Y6, both known for their strong near-infrared light absorption capabilities. Additionally, a fullerene receptor, PC61BM, was incorporated, which possesses the ability to absorb reactive oxygen species. We conducted a comprehensive investigation into the microstructure, photovoltaic properties, and photothermal effects of this three-component photovoltaic biomaterial. Furthermore, we employed Rat adrenal pheochromocytoma cells (PC-12) as a standard neural cell model to evaluate the in vitro photoelectric stimulation effect of this photovoltaic biomaterial. The results demonstrate that the photovoltaic biomaterial, enriched with fullerene derivatives, can induce intracellular calcium influx in PC-12 cells under 630 nm (red light) and 780 nm (near-infrared) laser irradiation. Moreover, there were lower levels of oxidative stress and higher levels of mitochondrial activity compared to the non-PC61BM group. This photovoltaic biomaterial proves to be an ideal substrate for near-infrared photoelectrical stimulation of neural cells and holds promise for restoring visual function in patients with photoreceptor apoptosis.
Multi-year analysis of the global preclinical antibacterial pipeline: trends and gaps
Authors: Gigante Valeria , Alm Richard A. , Melchiorri Daniela , Rocke Tamarie , Arias Cesar A. , Czaplewski Lloyd , Fernandes Prabhavathi , Franceschi François , Harbarth Stephan , Kozlov Roman , Lienhardt Christian , Ohmagari Norio , Ogilvie Lesley A. , Paul Mical , Rex John H. , Silver Lynn L. , Spigelman Melvin , Sati Hatim , Cameron Alexandra M.
Published: July 2024

Antimicrobial resistance (AMR) is a major global health threat estimated to have caused the deaths of 1.27 million people in 2019, which is more than HIV/AIDS and malaria deaths combined. AMR also has significant consequences on the global economy. If not properly addressed, AMR could immensely impact the world’s economy, further increasing the poverty burden in low- and middle-income countries. To mitigate the risk of a post-antibiotic society, where the ability to effectively treat common bacterial infections is being severely threatened, it is necessary to establish a continuous supply of new and novel antibacterial medicines. However, there are gaps in the current pipeline that will prove difficult to address, given the time required to develop new agents. To understand the status of upstream antibiotic development and the challenges faced by drug developers in the early development stage, the World Health Organization has regularly assessed the preclinical and clinical antibacterial development pipeline. The review identifies potential new classes of antibiotics or novel mechanisms of action that can better address resistant bacterial strains. This proactive approach is necessary to stay ahead of evolving resistance patterns and to support the availability of effective treatment options. This review examines the trends in preclinical development and attempts to identify gaps and potential opportunities to overcome the numerous hurdles in the early stages of the antibacterial research and development space.
Eosinophils as drivers of bacterial immunomodulation and persistence
Authors: Parrish Katelyn M. , Gestal Monica C.
Published: July 2024

Traditionally, eosinophils have been linked to parasitic infections and pathological disease states. However, emerging literature has unveiled a more nuanced and intricate role for these cells, demonstrating their key functions in maintaining mucosal homeostasis. Eosinophils exhibit diverse phenotypes and exert multifaceted effects during infections, ranging from promoting pathogen persistence to triggering allergic reactions. Our investigations primarily focus on
Bordetella
spp., with particular emphasis on
Bordetella bronchiseptica
, a natural murine pathogen that induces diseases in mice akin to pertussis in humans. Recent findings from our published work have unveiled a striking interaction between
B. bronchiseptica
and eosinophils, facilitated by the
btrS
-mediated mechanism. This interaction serves to enhance pathogen persistence while concurrently delaying adaptive immune responses. Notably, this role of eosinophils is only noted in the absence of a functional
btrS
signaling pathway, indicating that wild-type
B. bronchiseptica
, and possibly other
Bordetella
spp., possess such adeptness in manipulating eosinophils that the true function of these cells remains obscured during infection. In this review, we present the mounting evidence pointing toward eosinophils as targets of bacterial exploitation, facilitating pathogen persistence and fostering chronic infections in diverse mucosal sites, including the lungs, gut, and skin. We underscore the pivotal role of the master regulator of
Bordetella
pathogenesis, the sigma factor BtrS, in orchestrating eosinophil-dependent immunomodulation within the context of pulmonary infection. These putative convergent strategies of targeting eosinophils offer promising avenues for the development of novel therapeutics targeting respiratory and other mucosal pathogens.
Chikungunya virus release is reduced by TIM-1 receptors through binding of envelope phosphatidylserine
Authors: Reyes Ballista Judith M. , Hoover Ashley J. , Noble Joseph T. , Acciani Marissa D. , Miazgowicz Kerri L. , Harrison Sarah A. , Tabscott Grace Andrea L. , Duncan Avery , Barnes Don N. , Jimenez Ariana R. , Brindley Melinda A.
Published: July 2024

T-cell immunoglobin and mucin domain protein-1 (TIM-1) mediates entry of chikungunya virus (CHIKV) into some mammalian cells through the interaction with envelope phospholipids. While this interaction enhances entry, TIM-1 has been shown to tether newly formed HIV and Ebola virus particles, limiting their efficient release. In this study, we investigate the ability of surface receptors such as TIM-1 to sequester newly budded virions on the surface of infected cells. We established a luminescence reporter system to produce chikungunya viral particles that integrate nano-luciferase and easily quantify viral particles. We found that TIM-1 on the surface of host cells significantly reduced CHIKV release efficiency in comparison to other entry factors. Removal of cell surface TIM-1 through direct cellular knock-out or altering the cellular lipid distribution enhanced CHIKV release. Over the course of infection, CHIKV was able to counteract the tethering effect by gradually decreasing the surface levels of TIM-1 in a process mediated by the nonstructural protein 2. This study highlights the importance of phosphatidylserine receptors in mediating not only the entry of CHIKV but also its release and could aid in developing cell lines capable of enhanced vaccine production.

IMPORTANCE

Chikungunya virus (CHIKV) is an enveloped alphavirus transmitted by the bites of infectious mosquitoes. Infection with CHIKV results in the development of fever, joint pain, and arthralgia that can become chronic and last for months after infection. Prevention of this disease is still highly focused on vector control strategies. In December 2023, a new live attenuated vaccine against CHIKV was approved by the FDA. We aimed to study the cellular factors involved in CHIKV release, to better understand CHIKV’s ability to efficiently infect and spread among a wide variety of cell lines. We found that TIM-1 receptors can significantly abrogate CHIKV’s ability to efficiently exit infected cells. This information can be beneficial for maximizing viral particle production in laboratory settings and during vaccine manufacturing.
Epidemiology of cryptococcal meningitis and fluconazole heteroresistance in
Cryptococcus neoformans
isolates from a teaching hospital in southwestern China
Authors: Huang Yunfei , Zhang Yongqi , Yang Shuangshuang , Lu Hongling , Yu Hanbing , Wang Xingyue , Jia Xiaojiong , Tang Dijiao , Wu Linhong , Huang Shifeng , Yang Ping
Published: July 2024

Cryptococcal meningitis (CM), a common and serious opportunistic infection mostly caused by
Cryptococcus neoformans
, is primarily treated with fluconazole. Nevertheless,
Cryptococcus neoformans
strains that undergo repeated exposure to azoles can gradually acquire heteroresistance to fluconazole. The management of this specific CM infection poses a substantial challenge. Determining a globally accepted definition for fluconazole heteroresistance and developing effective and prompt methods for identifying heteroresistance is of utmost importance. We collected data on the clinical and epidemiological characteristics of patients diagnosed with CM. All the available
Cryptococcus neoformans
strains isolated from these patients were collected and subjected to antifungal susceptibility testing and evaluation of fluconazole heteroresistance. AIDS was present in 40.5% of the patients, whereas 24.1% did not have any underlying diseases. Patients with chronic diseases or impaired immune systems are susceptible to infection by
Cryptococcus neoformans
, a fungus that frequently (39.6%, 19/48) shows heteroresistance to fluconazole, as confirmed by population analysis profile (PAP).

IMPORTANCE

Fluconazole heteroresistance poses a significant threat to the efficacy of fluconazole in treating cryptococcal meningitis (CM). Unfortunately, the standard broth microdilution method often misses the subtle percentages of subpopulations exhibiting heteroresistance. While the population analysis profile (PAP) method is esteemed as the gold standard, its time-consuming and labor-intensive nature makes it impractical for routine clinical use. In contrast, the Kirby-Bauer (KB) disk diffusion method offers a simple and effective screening solution. Our study highlights the value of KB over PAP and minimum inhibitory concentration (MIC) by demonstrating that when adjusting the inoculum concentration to 1.0 McFarland and subjecting samples to a 72-hour incubation period at 35°C, the KB method closely mirrors the outcomes of the PAP approach in detecting fluconazole heteroresistance. This optimization of the KB method not only enhances assay efficiency but also provides a blueprint for developing a timely and effective strategy for identifying heteroresistance.
Heat Capacity and Features of the Phonon Spectrum of Single Crystals of Solid Solutions of Yttrium–Lutetium Aluminum Garnets
Authors: Nikitov S. A. , Taranov A. V. , Khazanov E. N. , Charnaya E. V. , Likholetova M. V. , Shevchenko E. V.
Published: July 2024

The temperature dependences of the heat capacity were measured and the general patterns of the formation of the phonon spectrum of single crystals of solid solutions of yttrium-lutetium aluminum garnets Y3 – xLuxAl5O12 at 0 ≤ x ≤ 3 were investigated in the temperature range from 1.9 to 220 K. According to the data obtained at temperatures below 10 K, the Debye temperatures were calculated. The features of the phonon spectrum in the intermediate temperature range are interpreted as a superposition of optical modes for yttrium and lutetium garnets. It is shown that the low heat capacity values due to the contribution of acoustic phonons for Y2.25Lu0.75Al5O12 correlate with anomalies in the concentration dependences of the phonon transport, the absorption of acoustic waves, and the shape of the aluminum NMR line.
Effects of pre-existing type 1 diabetes mellitus on survival outcome following out-of-hospital cardiac arrest: a registry-based observational study in Sweden
Authors: Eken Berkan , Rawshani Araz , Rawshani Aidin , Mandalenakis Zacharias , Thunstrom Erik , Louca Antros , Petursson Petur , Angerås Oskar , Nadhir Sadek , Dworeck Christian , Råmunddal Truls
Published: July 2024

Background

It has been estimated that 80% of cases of out-of-hospital cardiac arrest (OHCA) are due to cardiac causes. It is well-documented that diabetes is a risk factor for conditions associated with sudden cardiac arrest. Type 1 diabetes (T1D) displays a threefold to fivefold increased risk of cardiovascular disease and death compared with the general population.

Objective

This study aims to assess the characteristics and survival outcomes of individuals with and without T1D who experienced an OHCA.Design: A registry-based nationwide observational study with two cohorts, patients with T1D and patients without T1D.Setting: All emergency medical services and hospitals in Sweden were included in the study.

Participants

Using the Swedish Cardiopulmonary Resuscitation Registry, we enrolled 54 568 cases of OHCA where cardiopulmonary resuscitation was attempted between 2010 and 2020. Among them, 448 patients with T1D were identified using International Classification of Diseases-code: E10.

Methods

Survival analysis was performed using Kaplan-Meier and logistic regression. Multiple regression was adjusted for age, sex, cause of arrest, prevalence of T1D and time to cardiopulmonary resuscitation.

Main outcome measures

The outcomes were discharge status (alive vs dead), 30 days survival and neurological outcome at discharge.

Results

There were no significant differences in patients discharged alive with T1D 37.3% versus, 46% among cases without T1D. There was also no difference in neurological outcome. Kaplan-Meier curves yielded no significant difference in long-term survival. Multiple regression showed no significant association with survival after accounting for covariates, OR 0.99 (95% CI 0.96 to 1.02), p value=0.7. Baseline characteristics indicate that patients with T1D were 5 years younger at OHCA occurrence and had proportionally fewer cases of heart disease as the cause of arrest (57.6% vs 62.7%).

Conclusion

We conclude, with the current sample size, that there is no statistically significant difference in long-term or short-term survival between patients with and without T1D following OHCA.
Protocol for a longitudinal study examining the trajectory of COVID-19, post-COVID, multidimensional disadvantage and health-related quality of life in India: the IndiQol Project
Authors: Sinha Kompal , Gutacker Nils , Gu Yuanyuan , Haagsma Juanita , Kumar Kaushalendra , Aghdaee Mona
Published: July 2024

Introduction

The COVID-19 pandemic has raised concerns about the persistence of symptoms after infection, commonly referred to as ‘post-COVID’ or ‘long-COVID’. While countries in high-resource countries have highlighted the increased risk of disadvantaged communities, there is limited understanding of how COVID-19 and post-COVID conditions affect marginalised populations in low-income and middle-income countries. We study the longitudinal patterns of COVID-19, post-COVID symptoms and their impact on the health-related quality of life through the IndiQol Project.

Methods and analysis

The IndiQol Project conducts household surveys across India to collect data on the incidence of COVID-19 and multidimensional well-being using a longitudinal design. We select a representative sample across six states surveyed over four waves. A two-stage sampling design was used to randomly select primary sampling units in rural and urban areas of each State. Using power analysis, we select an initial sample of 3000 household and survey all adult household members in each wave. The survey data will be analysed using limited dependent variable models and matching techniques to provide insights into the impact of COVID-19 pandemic and post-COVID on health and well-being of individuals in India.

Ethics and dissemination

Ethics approval for the IndiQol Project was obtained from the Macquarie University Human Research Ethics Committee in Sydney, Australia and Institutional Review Board of Morsel in India. The project results will be published in peer-reviewed journals. Data collected from the IndiQol project will be deposited with the EuroQol group and will be available to use by eligible researchers on approval of request.
Aortic aneurysm sac filling with AneuFix injectable polymer during endovascular aneurysm repair: feasibility and safety trial study protocol
Authors: Smorenburg Stefan P M , Lely Rutger J , Jacobs Michael J , Hoksbergen Arjan W J
Published: July 2024

Introduction

Type II endoleaks (T2ELs) following endovascular aneurysm repair (EVAR) for abdominal aortic aneurysm (AAA) can lead to aneurysm growth, compromising the stent graft seal and risking rupture. Preventing these endoleaks during EVAR involves filling the AAA sac around the stent graft to exclude the aneurysm and block any arteries causing the endoleak. This study investigates the feasibility and safety of using AneuFix, a biocompatible injectable polymer developed by TripleMed (Geleen, the Netherlands), for aneurysmal sac filling during EVAR in high-risk T2EL patients.

Methods and analysis

A feasibility, single-arm, single-centre clinical trial will initially include five patients with infrarenal AAA, eligible for EVAR, and at high risk for T2EL based on the number of patent lumbar arteries and the cross-sectional area of the aortic lumen at the level of the inferior mesenteric artery. Postevaluation by the Data Safety and Monitoring Board, the study cohort will extend to 25 patients. During EVAR and after stent graft deployment, the aneurysm sac is filled with AneuFix polymer using a filling sheath positioned parallel to the contralateral limb with the tip inside the aneurysm sac. Primary outcome is technical success (successful AAA sac filling). The secondary outcomes include clinical success at 6 and 12 months (occurrence of T2ELs and AAA growth assessed with CT angiography), intraoperative and perioperative complications, all endoleaks, adverse events, re-interventions, aneurysm rupture and patient survival.

Ethics and dissemination

This trial was approved by the Dutch Authorities (Central Committee on Research Involving Human Subjects, IGJ), Amsterdam University Medical Centre Ethical Commission, and adheres to the Declaration of Helsinki and European Medical Device Regulation. Results will be shared at (inter)national conferences and in peer-reviewed journals.

Trial registration number

NCT04307992.
Defining the gaps in transitional care to adulthood for patients in paediatric surgical specialties: a scoping review protocol
Authors: Lu Daisy , Wang Zhi , Clar Monique , Shen Jesse
Published: July 2024

Introduction

Transitioning patients from their paediatric centres to adulthood is an important subject for many of these patients living with different chronic pathologies. There are few studies that assess its effectiveness in paediatric surgical pathologies. The overall objective of this scoping review is to assess the extent of the literature describing transitional programmes dedicated to young patients living with surgical conditions. The primary question will look to assess what transitional programmes are available for young patients living with surgical conditions either operated or not.

Methods and analysis

The proposed scoping review will follow guidelines described by the Joanna Briggs Institute manual described by Peterset alin 2020. This protocol will employ the Preferred Reporting Items for Systematic review and Meta-Analysis Protocols checklist. The concept that will be included in this review is the exposure of these patients to a transition of care pathway or care programmes. Patients between the ages of 16 and 30 with a surgical condition will be included. There will be no comparator. No specific outcomes will be assessed, however, the outcomes that will be found from the transition programmes will be reviewed. A knowledge synthesis librarian will search MEDLINE All (Ovid), Embase (Ovid), Web of Science Core Collection (Clarivate) and CINAHL Complete (EBSCOhost). The literature search will be limited to 2000 onwards publications. No language or age group limitation will be applied. The reference list of all included sources of evidence will be screened for additional studies. Screening of search results and data extraction from included studies will be completed in Covidence by two independent reviewers. We will also use the PAGER (Patterns, Advances, Gaps, Evidence for practice and Research recommendations) framework to report and summarise the results.

Ethics and dissemination

This review does not require ethics approval. Our dissemination strategy includes peer review publication, conference presentation, co-constructed guidelines with stakeholders and policymakers.

Trial registration

This review is registered on OSF