bluuebunny/crossref_metadata_2025 huggingface dataset:
Cervical angle as a possible predictor of abnormal placental position in women with endometriosis
Authors: Higeta Daisuke , Kitahara Yoshikazu , Tanaka Ayuko , Morita Akihito , Sato Tatsuya , Inoue Maki , Soda Masayuki , Iwase Akira
Published: January 2024

Background

We aimed to examine the effects of endometriosis on the rate of abnormal placentation by comparing the data of pregnant women with and without endometriosis.

Methods

A case–control study was conducted to compare the perinatal outcomes between women with and without endometriosis. In the subgroup analysis, magnetic resonance imaging (MRI) scans of pregnant women with placenta previa were used to measure the cervical angle and its relationship with endometriosis. The cervical angle was measured as the angle between the cervical glands and the line perpendicular to the spinal column in each sagittal MRI section.

Results

We retrospectively analyzed data from 3453 cases of singleton deliveries between 2015 and 2019 at two study facilities. Among them, 159 had clinically or surgically confirmed endometriosis. The odds ratio (OR) for abnormal placental position was significantly higher in pregnant women with endometriosis (OR. 2.82; 95% confidence interval [CI], 1.58–5.04). The OR was 3.21 (95% CI, 1.57–6.55) in the endometriosis‐surgery group (91 patients) and 2.32 (95% CI, 0.91–5.88) in the non‐surgery group (68 patients). Furthermore, 44 women who underwent pelvic MRI after 30 weeks of gestation were included to examine the cervical angle. Then, we compared the date of pregnant women with (n = 6) and without endometriosis (n = 38). Regardless of placental attachment position, the cervical angle was significantly lower in the group with than in the group without a history of endometriosis.

Conclusion

Pregnant women with a history of endometriosis may have stronger uterine retroversion, which could potentially contribute to abnormal placental positioning.
Adaptive divergence of seasonal heart plasticity between Canadian and Spanish pumpkinseed sunfish populations
Authors: Procopio S. M. , Studden B. M. , Axelrod C. J. , Laberge F. , Robinson B. W.
Published: January 2024

Laboratory experiments suggest that reversible changes in the heart ventricle phenotype of fish accompany acclimation to temperature change to maintain cardiac function, but related work in fish living in natural conditions is scant. We investigated seasonal variation in heart ventricular mass and collagen content in pumpkinseed sunfish (Lepomis gibbosus) living in outdoor ponds where they experienced high seasonality conditions. Additionally, we compared populations adapted to high and low seasonality to evaluate potential divergence in seasonal heart plasticity. Heart ventricular mass decreased in the summer compared to colder seasons only in populations adapted to high seasonality. The absence of seasonal variation in ventricular mass in sunfish adapted to low seasonality was not due to changes in foraging activity, suggesting a loss of ventricle size plasticity due to either costs of plasticity or relaxed selection. Seasonal variation in ventricle collagen content also occurred, with the highest collagen content in summer regardless of population adaptation to high or low seasonality. Only the proportion of thick collagen fibres changed across seasons. We conclude that natural seasonal cues induce plastic responses in some functional heart traits and propose that these responses can rapidly diverge among populations under different seasonal regimes.
Commercial policies, unilateral versus bilateral foreign ownership, and welfare
Authors: Chang Yang‐Ming , Dong Quan
Published: January 2024

This paper examines how cross‐border ownership and restrictions affect commercial policies optimally chosen by the government of an importing country. Focusing on import competition in an oligopoly market served by two local producers and a foreign firm, we study and compare two partial ownership arrangements without corporate control: unilateral ownership by the foreign firm over a local producer and bilateral ownership between the two entities. The main findings are as follows: (i) When foreign ownership is unilateral, the optimal trade and industrial policies are an import tariff and a production subsidy, respectively. (ii) When foreign ownership is bilateral, the trade policy can be an import subsidy, and the industrial policy is a production subsidy. These results differ from the benchmark equilibrium without ownership, under which the optimal policy mix consists of an import tariff and a production subsidy. (iii) Unilateral foreign ownership always reduces domestic welfare. However, bilateral foreign ownership can increase domestic welfare when local producers' cost disadvantages are substantially high. (iv) Considering the usual lump‐sum transfer for a balanced budget, bilateral ownership entails a lower public burden than two other scenarios for the government to finance its strategic use of trade and industrial policies.
Can professional nursing value claims be refused? Might nursing values be accepted provisionally and tentatively?
Authors: Lipscomb Martin
Published: January 2024

Value–act relationships are less secure than is commonly supposed and this insecurity is leveraged to address two questions. First, can nurses refuse professional value claims (e.g., claims regarding care and compassion)? Second, even when value claims are accepted, might values be held provisionally and tentatively? These questions may seem absurd. Nurses deliver care and nursing is, we are told, a profession the members of which hold and share values. However, focusing attention on the problematic nature of professional value claims qua claims permits a more conciliatory and realistic stance to be taken towards nurses holding alternative values and value interpretations. This could prove beneficial.
Nothapodytes burmanica (Icacinaceae), a new species from Kachin State, Myanmar
Authors: Shen Si‐Ke , Ding Hong‐Bo , Tan Yun‐Hong
Published: January 2024

Nothapodytes burmanica Y.H.Tan & S.K.Shen, sp. nov. (Icacinaceae) from Kachin State, Myanmar is described and illustrated. It belongs to Nothapodytes due to the lorate hairy petals being connate at the base and a fleshy foliaceous disk divided into five leaflike lobes. Morphological and phylogenetic evidence indicates that it is close to N. pittosporoides. Morphologically, both species have oblanceolate or oblong leaf blades that are adaxially sparsely pubescent, but the new species is distinguished by its leaf base usually being oblique, and the paniculate inflorescence that has more numerous but smaller flowers with shorter petals. Phylogenetic results indicate that N. burmanica is deeply nested within the genus and forms a sister group of N. pittosporoides.
Effect of clarithromycin in a case of infantile bullous pemphigoid
Authors: Ghaoui Nohra , Hamie Lamiaa
Published: January 2024

Although rare, cases of infantile or childhood bullous pemphigoid are increasingly being reported in the literature. Treatment challenges, which are amplified in infancy, necessitate balancing efficacy and avoiding long‐term risks. In this report, clarithromycin was successfully used to establish and maintain disease remission, offering insights into its immunomodulatory effects, making it a compelling steroid‐sparing choice with a favorable side effect profile.
Analyzing secretory proteins in human dermal fibroblast‐conditioned medium for angiogenesis: A bioinformatic approach
Authors: Suh Sang Bum , Suh Ji Youn , Cho Sung Bin
Published: January 2024

Background

The conditioned medium from human dermal fibroblasts (dermal fibroblast‐conditioned medium; DFCM) contains a diverse array of secretory proteins, including growth factors and wound repair‐promoting proteins. Angiogenesis, a crucial process that facilitates the infiltration of inflammatory cells during wound repair, is induced by a hypoxic environment and inflammatory cytokines.

Methods

In this study, we conducted a comprehensive bioinformatic analysis of 337 proteins identified through proteomics analysis of DFCM. We specifically focused on 64 DFCM proteins with potential involvement in angiogenesis. These proteins were further classified based on their characteristics, and we conducted a detailed analysis of their protein–protein interactions.

Results

Gene Ontology protein classification categorized these 64 DFCM proteins into various classes, including metabolite interconversion enzymes (N = 11), protein modifying enzymes (N = 10), protein‐binding activity modulators (N = 9), cell adhesion molecules (N = 6), extracellular matrix proteins (N = 6), transfer/carrier proteins (N = 3), calcium‐binding proteins (N = 2), chaperones (N = 2), cytoskeletal proteins (N = 2), RNA metabolism proteins (N = 1), intercellular signal molecules (N = 1), transporters (N = 1), scaffold/adaptor proteins (N = 1), and unclassified proteins (N = 9). Furthermore, our protein–protein interaction network analysis of DFCM proteins revealed two distinct networks: one with medium confidence level interaction scores, consisting of 60 proteins with significant connections, and another at a high confidence level, comprising 52 proteins with significant interactions.

Conclusions

Our bioinformatic analysis highlights the presence of a multitude of secretory proteins in DFCM that form significant protein–protein interaction networks crucial for regulating angiogenesis. These findings underscore the critical roles played by DFCM proteins in various stages of angiogenesis during the wound repair process.
The MdCBF1/2‐MdTST1/2 module regulates sugar accumulation in response to low temperature in apple
Authors: Li Baiyun , Qu Shengtao , Kang Jiayi , Peng Yunjing , Yang Nanxiang , Ma Baiquan , Ruan Yong‐Ling , Ma Fengwang , Li Mingjun , Zhu Lingcheng
Published: January 2024

Soluble sugar content is a key component in controlling fruit flavor, and its accumulation in fruit is largely determined by sugar metabolism and transportation. When the diurnal temperature range is greater, the fleshy fruits accumulated more soluble sugars and become more sweeter. However, the molecular mechanism underlying this response remains largely unknown. In this study, we verified that low‐temperature treatment promoted soluble sugar accumulation in apple fruit and found that this was due to the upregulation of the Tonoplast Sugar Transporter genes MdTST1/2. A combined strategy using assay for transposase‐accessible chromatin (ATAC) sequencing and gene expression and cis‐acting elements analyses, we identified two C‐repeat Binding Factors, MdCBF1 and MdCBF2, that were induced by low temperature and that might be upstream transcription factors of MdTST1/2. Further studies established that MdCBF1/2 could bind to the promoters of MdTST1/2 and activate their expression. Overexpression of MdCBF1 or MdCBF2 in apple calli and fruit significantly upregulated MdTST1/2 expression and increased the concentrations of glucose, fructose, and sucrose. Suppression of MdTST1 and/or MdTST2 in an MdCBF1/2‐overexpression background abolished the positive effect of MdCBF1/2 on sugar accumulation. In addition, simultaneous silencing of MdCBF1/2 downregulated MdTST1/2 expression and apple fruits failed to accumulate more sugars under low‐temperature conditions, indicating that MdCBF1/2‐mediated sugar accumulation was dependent on MdTST1/2 expression. Hence, we concluded that the MdCBF1/2‐MdTST1/2 module is crucial for sugar accumulation in apples in response to low temperatures. Our findings provide mechanistic components coordinating the relationship between low temperature and sugar accumulation as well as new avenues to improve fruit quality.
The degradation of a nonylphenol isomer in water and soil of typical sewage irrigation area in China
Authors: Liu Min , Zhao Liangyuan , Deng Wei , Zhang Caixiang , Liao Xiaoping , Huang Huawei , Han Cheng , Hu Yuan , Wu Mengmeng
Published: January 2024

Nonylphenols (NPs), one of the known endocrine disrupting organic pollutants, had received full attention for their estrogenic potency and ubiquitous distribution in the environment. Due to its chemical properties and compositions of technical nonylphenols (tNPs), which was persistent and soil environments for a long time and affect the ecosystem vigorously, degradation behaviour of a nonylphenol isomer (NP38) and the para‐substituded nonylphenols (4‐NPs) in water and soil was compared in this study. The results showed that the 4‐NPs and NP38 could be degraded under the mercury lamp in ultrapure water, 90% of 4‐NPs and NP38 were photodegradated in 2 h, but the removal rate of the 4‐NPs was slightly faster than the NP38. The NP38 was almost completely decay under the UV in 120 min. The active species (NO3− and Fe3+) were benefit for the photogradation of NP38 and presented higher efficiency under the higher concentration. The biodegradable curves of the 4‐NPs and NP38 in the SS (The soil from sewage irrigation area) were similar, 84% of the NP38 was removed after 20 days later in SS, the 62.25% of the NP38 was remained after 60 days later in CS (the soil was from the groundwater irrigation area), but the removal rate of the NP38 was nearly two times to the 4‐NPs in the CS, and the structure of the nonylphenol isomers with α‐quaternary had influenced on its degradation in soils. The study was helpful for better understanding the migration and transformation behaviour of NPs and provided scientific basis for accurate assessment of environmental risk of NPs from the sewage irrigation area.
Iron oxide nanoparticles produced by the laser ablation technique and analyzed by x-ray photoelectron spectroscopy
Authors: David Gonzalez E. , Botero M. A. , Ospina R.
Published: January 2024

The study of iron nanoparticles is one of the most researched areas in recent times due to the potential applications they have and because the study of iron by XPS is one of the most debated elements. In this work, we provide investigation data of iron oxide nanoparticles produced using the laser ablation technique, which were characterized using x-ray photoelectron spectroscopy. Survey spectra, C 1s, O 1s, and Fe 2p core levels spectra were acquired. Results showed the presence of Fe+3 and Fe+2 elements that constitute hematite and magnetite with differences in their concentrations depending on the fitting method. In addition, the presence of adventitious carbon and carbon from impurities was detected.
Global, and local optimization beamforming for broadband sources
Authors: Goudarzi Armin
Published: January 2024

This paper presents an alternative energy function for global optimization (GO) beamforming, tailored to acoustic broadband sources. Given that properties, such as the source location, multipole rotation, or flow conditions, are parameterized over the frequency, a cross spectral matrix-fitting can be performed for all frequencies at once. A numerical analysis shows that the nonlinear energy function for the standard GO problem is equivalent to the source's point spread function (PSF) and contains local minima at the locations of the grating lobes and side lobes. The energy function is improved with the proposed broadband energy, as it averages the PSF. Further, it simplifies the process of identifying sources and reconstructing their spectra from the results. The paper shows that the method is superior on synthetic monopoles compared to standard GO and CLEAN based on source coherence (CLEAN-SC). For real-world data, the results of the proposed method and CLEAN-SC are similar, and outperform standard GO. The main difference is that source assumption violations cause noisy maps for CLEAN-SC and cause wrong spectral estimations of the proposed method. By using reasonable initial values, the GO problem reduces to a local optimization problem with similar results. Further, the proposed method is able to identify synthetic multipoles with different pole amplitudes and unknown pole rotations.
Deterministic reprogramming of neutrophils within tumors
Authors: Ng Melissa S. F. , Kwok Immanuel , Tan Leonard , Shi Changming , Cerezo-Wallis Daniela , Tan Yingrou , Leong Keith , Calvo Gabriel F. , Yang Katharine , Zhang Yuning , Jin Jingsi , Liong Ka Hang , Wu Dandan , He Rui , Liu Dehua , Teh Ye Chean , Bleriot Camille , Caronni Nicoletta , Liu Zhaoyuan , Duan Kaibo , Narang Vipin , Ballesteros Iván , Moalli Federica , Li Mengwei , Chen Jinmiao , Liu Yao , Liu Lianxin , Qi Jingjing , Liu Yingbin , Jiang Lingxi , Shen Baiyong , Cheng Hui , Cheng Tao , Angeli Veronique , Sharma Ankur , Loh Yuin-han , Tey Hong Liang , Chong Shu Zhen , Iannacone Matteo , Ostuni Renato , Hidalgo Andrés , Ginhoux Florent , Ng Lai Guan
Published: January 2024

Neutrophils are increasingly recognized as key players in the tumor immune response and are associated with poor clinical outcomes. Despite recent advances characterizing the diversity of neutrophil states in cancer, common trajectories and mechanisms governing the ontogeny and relationship between these neutrophil states remain undefined. Here, we demonstrate that immature and mature neutrophils that enter tumors undergo irreversible epigenetic, transcriptional, and proteomic modifications to converge into a distinct, terminally differentiated dcTRAIL-R1
+
state. Reprogrammed dcTRAIL-R1
+
neutrophils predominantly localize to a glycolytic and hypoxic niche at the tumor core and exert pro-angiogenic function that favors tumor growth. We found similar trajectories in neutrophils across multiple tumor types and in humans, suggesting that targeting this program may provide a means of enhancing certain cancer immunotherapies.
Hyperglycosylation of prosaposin in tumor dendritic cells drives immune escape
Authors: Sharma Pankaj , Zhang Xiaolong , Ly Kevin , Kim Ji Hyung , Wan Qi , Kim Jessica , Lou Mumeng , Kain Lisa , Teyton Luc , Winau Florian
Published: January 2024

Tumors develop strategies to evade immunity by suppressing antigen presentation. In this work, we show that prosaposin (pSAP) drives CD8 T cell–mediated tumor immunity and that its hyperglycosylation in tumor dendritic cells (DCs) leads to cancer immune escape. We found that lysosomal pSAP and its single-saposin cognates mediated disintegration of tumor cell–derived apoptotic bodies to facilitate presentation of membrane-associated antigen and T cell activation. In the tumor microenvironment, transforming growth factor–β (TGF-β) induced hyperglycosylation of pSAP and its subsequent secretion, which ultimately caused depletion of lysosomal saposins. pSAP hyperglycosylation was also observed in tumor-associated DCs from melanoma patients, and reconstitution with pSAP rescued activation of tumor-infiltrating T cells. Targeting DCs with recombinant pSAP triggered tumor protection and enhanced immune checkpoint therapy. Our studies demonstrate a critical function of pSAP in tumor immunity and may support its role in immunotherapy.
Designing metainterfaces with specified friction laws
Authors: Aymard Antoine , Delplanque Emilie , Dalmas Davy , Scheibert Julien
Published: January 2024

Many devices, including touchscreens and robotic hands, involve frictional contacts. Optimizing these devices requires fine control of the interface’s friction law. We lack systematic methods to create dry contact interfaces whose frictional behavior satisfies preset specifications. We propose a generic surface design strategy to prepare dry rough interfaces that have predefined relationships between normal and friction forces. Such metainterfaces circumvent the usual multiscale challenge of tribology by considering simplified surface topographies as assemblies of spherical asperities. Optimizing the individual asperities’ heights enables specific friction laws to be targeted. Through various centimeter-scaled elastomer-glass metainterfaces, we illustrate three types of achievable friction laws, including linear laws with a specified friction coefficient and unusual nonlinear laws. This design strategy represents a scale- and material-independent, chemical-free pathway toward energy-saving and adaptable smart interfaces.
Synthetic dioxygenase reactivity by pairing electrochemical oxygen reduction and water oxidation
Authors: Hoque Md. Asmaul , Gerken James B. , Stahl Shannon S.
Published: January 2024

The reactivity of molecular oxygen is crucial to clean energy technologies and green chemical synthesis, but kinetic barriers complicate both applications. In synthesis, dioxygen should be able to undergo oxygen atom transfer to two organic molecules with perfect atom economy, but such reactivity is rare. Monooxygenase enzymes commonly reductively activate dioxygen by sacrificing one of the oxygen atoms to generate a more reactive oxidant. Here, we used a manganese-tetraphenylporphyrin catalyst to pair electrochemical oxygen reduction and water oxidation, generating a reactive manganese-oxo at both electrodes. This process supports dioxygen atom transfer to two thioether substrate molecules, generating two equivalents of sulfoxide with a single equivalent of dioxygen. This net dioxygenase reactivity consumes no electrons but uses electrochemical energy to overcome kinetic barriers.
A family history of the Universe
Transient and Strange: Notes on the Science of Life
Nell Greenfieldboyce
Norton, 2024. 224 pp.
Authors: Hannibal Mary Ellen
Published: January 2024

Musings on natural phenomena merge with tales from a science journalist’s personal life
Covid’s cold cousins
Authors: Cohen Jon
Published: January 2024

Four largely ignored coronaviruses circulate in humans without causing great harm and may portend the future for SARS-CoV-2
Mysterious seismic swarm led up to Japan quake
Authors: Normile Dennis
Published: January 2024

Researchers study connection of rising fluids and quake flurry to magnitude 7.5 monster
In vitro
activity of manogepix and comparators against infrequently encountered yeast and mold isolates from the SENTRY Surveillance Program (2017–2022)
Authors: Pfaller Michael , Huband Michael , Bien Paul A. , Carvalhaes Cecilia G. , Klauer Abby , Castanheira Mariana
Published: January 2024

Manogepix is a potent new antifungal agent targeting the fungal Gwt1 enzyme. Manogepix has previously demonstrated potent
in vitro
activity against clinical isolates of both
Candida
(except
Candida krusei
) and
Aspergillus
species. This study determined the
in vitro
activity of manogepix and comparators against a large collection of infrequently encountered yeast and molds. Manogepix demonstrated potent
in vitro
activity against infrequently encountered yeasts exhibiting elevated MIC values to other drug classes, including
Candida
spp. (MIC
50/90
, 0.008/0.12 mg/L),
Saprochaete clavata
(
Magnusiomyces clavatus
) (MIC
50/90
, 0.03/0.06 mg/L),
Magnusiomyces capitatus
(MIC
range
, 0.016-0.06 mg/L),
Rhodotorula minuta
(MIC, 0.016 mg/L), and
Rhodotorula mucilaginosa
(MIC
50/90
, 0.03/0.12 mg/L). Similarly, manogepix was active against infrequently encountered mold isolates and strains exhibiting elevated MIC/MEC values to echinocandins, azoles, and amphotericin B, including
Coprinopsis cinerea
(MEC, 0.004 mg/L),
Fusarium
spp. (MEC
50/90
, 0.016/0.06 mg/L),
Fusarium
(
Gibberella
)
fujikuroi
species complex (MEC
50/90
, 0.016/0.03 mg/L),
Lomentospora prolificans
(MEC
50/90
, 0.03/0.06 mg/L),
Microascus cirrosus
(MEC, 0.008 mg/L),
Paecilomyces
spp. (MEC
50/90
, ≤0.008/0.016 mg/L),
Pleurostomophora richardsiae
(MEC, 0.06 mg/L),
Sarocladium kiliense
(MEC range, 0.016–0.12 mg/L), and
Scedosporium
spp. (MEC
50/90
, 0.03/0.06 mg/L). Manogepix demonstrated potent activity against a majority of the infrequently encountered yeast and mold isolates tested including strains with elevated MIC/MEC values to other drug classes. Additional clinical development of manogepix (fosmanogepix) in difficult-to-treat, resistant fungal infections is warranted.
Syntrophic microbes involved in the oxidation of short-chain fatty acids in continuous-flow anaerobic digesters treating waste activated sludge with hydrochar
Authors: Shi Zhijian , Zhang Chen , Tan Xuejun , Xie Li , Luo Gang
Published: January 2024

The rapid degradation of short-chain fatty acids (SCFAs) is an essential issue of anaerobic digestion (AD), in which SCFA oxidizers could generally metabolize in syntrophy with methanogens. The dynamic responses of active metagenome-assembled genomes to low concentrations of propionate and acetate were analyzed to identify specific syntrophic SCFA oxidizers and their metabolic characteristics in continuous-flow AD systems treating waste activated sludge with and without hydrochar. In this study, hydrochar increased methane production by 19%, possibly due to hydrochar enhancing acidification and methanogenesis processes. A putative syntrophic propionate oxidizer and two acetate oxidizers contributed substantially to the syntrophic degradation of SCFAs, and hydrochar positively regulated their functional gene expressions. A significant relationship was established between the replication rate of SCFA oxidizers and their stimulation-related transcriptional activity. Acetate was degraded in the hydrochar group, which might be mainly through the syntrophic acetate oxidizer from the genus
Desulfallas
and methanogens from the genus
Methanosarcina
.

IMPORTANCE

Short-chain fatty acid (SCFA) degradation is an important process in the methanogenic ecosystem. However, current knowledge of this microbial mechanism is mainly based on studies on a few model organisms incubated as mono- or co-cultures or in enrichments, which cannot provide appropriate evidence in complex environments. Here, this study revealed the microbial mechanism of a hydrochar-mediated anaerobic digestion (AD) system promoting SCFA degradation at the species level and identified key SCFA oxidizing bacteria. Our analysis provided new insights into the SCFA oxidizers involved in the AD of waste activated sludge facilitated by hydrochar.
Nutrition of
Escherichia coli
within the intestinal microbiome
Authors: Doranga Sudhir , Krogfelt Karen A. , Cohen Paul S. , Conway Tyrrell
Published: January 2024

In this chapter, we update our 2004 review of “The Life of Commensal
Escherichia coli
in the Mammalian Intestine” (
https://doi.org/10.1128/ecosalplus.8.3.1.2
), with a change of title that reflects the current focus on “Nutrition of
E. coli
within the Intestinal Microbiome.” The earlier part of the previous two decades saw incremental improvements in understanding the carbon and energy sources that
E. coli
and
Salmonella
use to support intestinal colonization. Along with these investigations of electron donors came a better understanding of the electron acceptors that support the respiration of these facultative anaerobes in the gastrointestinal tract. Hundreds of recent papers add to what was known about the nutrition of commensal and pathogenic enteric bacteria. The fact that each biotype or pathotype grows on a different subset of the available nutrients suggested a mechanism for succession of commensal colonizers and invasion by enteric pathogens. Competition for nutrients in the intestine has also come to be recognized as one basis for colonization resistance, in which colonized strain(s) prevent colonization by a challenger. In the past decade, detailed investigations of fiber- and mucin-degrading anaerobes added greatly to our understanding of how complex polysaccharides support the hundreds of intestinal microbiome species. It is now clear that facultative anaerobes, which usually cannot degrade complex polysaccharides, live in symbiosis with the anaerobic degraders. This concept led to the “restaurant hypothesis,” which emphasizes that facultative bacteria, such as
E. coli
, colonize the intestine as members of mixed biofilms and obtain the sugars they need for growth locally through cross-feeding from polysaccharide-degrading anaerobes. Each restaurant represents an intestinal niche. Competition for those niches determines whether or not invaders are able to overcome colonization resistance and become established. Topics centered on the nutritional basis of intestinal colonization and gastrointestinal health are explored here in detail.
Aerobic glycolysis of bronchial epithelial cells rewires
Mycoplasma pneumoniae
pneumonia and promotes bacterial elimination
Authors: He Jun , Xiu Feichen , Chen Yiwen , Yang Yan , Liu Hongwei , Xi Yixuan , Liu Lu , Li Xinru , Wu Yueyue , Luo Haodang , Chen Liesong , Ding Nan , Hu Jun , Chen En , You Xiaoxing
Published: January 2024

The immune response to
Mycoplasma pneumoniae
infection plays a key role in clinical symptoms. Previous investigations focused on the pro-inflammatory effects of leukocytes and the pivotal role of epithelial cell metabolic status in finely modulating the inflammatory response have been neglected. Herein, we examined how glycolysis in airway epithelial cells is affected by
M. pneumoniae
infection in an
in vitro
model. Additionally, we investigated the contribution of ATP to pulmonary inflammation. Metabolic analysis revealed a marked metabolic shift in bronchial epithelial cells during
M. pneumoniae
infection, characterized by increased glucose uptake, enhanced aerobic glycolysis, and augmented ATP synthesis. Notably, these metabolic alterations are orchestrated by adaptor proteins, MyD88 and TRAM. The resulting synthesized ATP is released into the extracellular milieu via vesicular exocytosis and pannexin protein channels, leading to a substantial increase in extracellular ATP levels. The conditioned medium supernatant from
M. pneumoniae
-infected epithelial cells enhances the secretion of both interleukin (IL)-1β and IL-18 by peripheral blood mononuclear cells, partially mediated by the P2X7 purine receptor (P2X7R).
In vivo
experiments confirm that addition of a conditioned medium exacerbates pulmonary inflammation, which can be attenuated by pre-treatment with a P2X7R inhibitor. Collectively, these findings highlight the significance of airway epithelial aerobic glycolysis in enhancing the pulmonary inflammatory response and aiding pathogen clearance.
Increased privatization of a public resource leads to spread of cooperation in a microbial population
Authors: Raj Namratha , Saini Supreet
Published: January 2024

The phenomenon of cooperation is prevalent at all levels of life. In one such manifestation of cooperation in microbial communities, some cells produce costly extracellular resources that are freely available to others. These resources are referred to as public goods.
Saccharomyces cerevisiae
secretes invertase (public good) in the periplasm to hydrolyze sucrose into glucose and fructose, which are then imported by the cells. After hydrolysis of sucrose, a cooperator retains only 1% of the monosaccharides, while 99% of the monosaccharides diffuse into the environment and can be utilized by any cell. The non-producers of invertase (cheaters) exploit the invertase-producing cells (cooperators) by utilizing the monosaccharides and not paying the metabolic cost of producing the invertase. In this work, we investigate the evolutionary dynamics of this cheater-cooperator system. In a co-culture, if cheaters are selected for their higher fitness, the population will collapse. On the other hand, for cooperators to survive in the population, a strategy to increase fitness would likely be required. To understand the adaptation of cooperators in sucrose, we performed a coevolution experiment in sucrose. Our results show that cooperators increase in fitness as the experiment progresses. This phenomenon was not observed in environments which involved a non-public good system. Genome sequencing reveals duplication of several
HXT
transporters in the evolved cooperators. Based on these results, we hypothesize that increased privatization of the monosaccharides is the most likely explanation of spread of cooperators in the population.

IMPORTANCE

How is cooperation, as a trait, maintained in a population? In order to answer this question, we perform a coevolution experiment between two strains of yeast—one which produces a public good to release glucose and fructose in the media, thus generating a public resource, and the other which does not produce public resource and merely benefits from the presence of the cooperator strain. What is the outcome of this coevolution experiment? We demonstrate that after ~200 generations of coevolution, cooperators increase in frequency in the co-culture. Remarkably, in all parallel lines of our experiment, this is obtained via duplication of regions which likely allow greater privatization of glucose and fructose. Thus, increased privatization, which is intuitively thought to be a strategy against cooperation, enables spread of cooperation.
Human carriage of ESBL/pAmpC-producing
Escherichia coli
and
Klebsiella pneumoniae
in relation to the consumption of raw or undercooked vegetables, fruits, and fresh herbs
Authors: Meijs A. P. , Rozwandowicz M. , Hengeveld P. D. , Dierikx C. M. , de Greeff S. C. , van Duijkeren E. , van Dissel J. T.
Published: January 2024

We investigated to what extent the consumption of raw or undercooked vegetables, fruits, and fresh herbs influences carriage rates of ESBL/pAmpC-producing
Escherichia coli
and
Klebsiella pneumoniae
(ESBL-E/K) in the general population. We assessed long-term carriage and changes in ESBL-E/K prevalence over time, by comparing the results to findings in the same population 5 years earlier. Between July and December 2021, participants sent in two fecal samples and questionnaires, 3 months apart. Food frequency questionnaires were sent on a monthly basis. Fecal samples were cultured and screened for ESBL-E/K, and phenotypically positive isolates were sequenced. Multivariable logistic regression models were established to assess the association between the consumption of fresh produce and ESBL-E/K carriage. The ESBL-E/K prevalence was 7.6% [41/537; 95% confidence interval (CI): 5.7–10.2] in the first sampling round and 7.0% (34/489; 95% CI: 5.0–9.6) in the second. Multivariable models did not result in statistical significance for any of the selected fruit and vegetable types. Trends for increased carriage rates were observed for the consumption of raspberry and blueberry in the summer period. ESBL-E/K prevalence was comparable with the prevalence in the same cohort 5 years earlier (7.5%; 95% CI: 5.6–10.1%). In six persons (1.2%) a genetically highly homologous ESBL-E/K was found. In conclusion, the contribution of the consumption of raw fruits, vegetables, and herbs to ESBL-E/K carriage in humans in the Netherlands is probably low. Despite COVID-19 containment measures (e.g., travel restrictions, social distancing, and hygiene) the ESBL-E/K prevalence was similar to 5 years earlier. Furthermore, indications for long-term carriage were found.

IMPORTANCE

ESBL-producing bacteria are resistant against important classes of antibiotics, including penicillins and cephalosporines, which complicates treatment of infections. Food is one of the main routes of transmission for carriage of these bacteria in the general population. Although fruits, vegetables, and herbs are generally less frequently contaminated with ESBL-producing bacteria compared to meat, exposure might be higher since these products are often eaten raw or undercooked. This research showed that the contribution of the consumption of raw or undercooked fresh produce to ESBL-E/K carriage in the general Dutch population was low. No specific types of fruit or vegetables could be identified that gave a higher risk of carriage. In addition, we demonstrated the presence of genetically highly homologous ESBL-E/K in six persons after a period of 5 years, indicative for long-term carriage.
Heterotrophic bacteria in drinking water: evaluating antibiotic resistance and the presence of virulence genes
Authors: Molale-Tom Lesego G. , Olanrewaju Oluwaseyi S. , Kritzinger Rinaldo K. , Fri Justine , Bezuidenhout Cornelius C.
Published: January 2024

Heterotrophic bacteria, impacting those with infections or compromised immunity, pose heightened health risks when resistant to antibiotics. This study investigates heterotrophic plate count bacteria in water from North West-C (NWC) and North West-G (NWG) facilities, revealing prevalent β-hemolysis (NWC 82.5%, NWG 86.7%), enzyme production (98%), and antibiotic resistance, especially in NWC. NWG exhibits variations in hemolysin (
P
= 0.013), lipase (
P
= 0.009), and DNase activity (
P
= 0.006). Antibiotics, including ciprofloxacin, persist throughout treatment, with high resistance to β-lactams and trimethoprim (47%–100%), predominantly in NWC. Multiple antibiotic resistance index indicates that 90% of values exceed 0.20, signifying isolates from high antibiotic usage sources. Whole genome sequencing reveals diverse antibiotic resistance genes in heterotrophic strains, emphasizing their prevalence and health risks in water.

IMPORTANCE

This study’s findings are a stark reminder of a significant health concern: our water sources harbor antibiotic-resistant heterotrophic bacteria, which can potentially cause illness, especially in individuals with weakened immune systems or underlying infections. Antibiotic resistance among these bacteria is deeply concerning, as it threatens the effectiveness of antibiotics, critical for treating various infections. Moreover, detecting virulence factors in a notable proportion of these bacteria highlights their elevated risk to public health. This research underscores the immediate need for enhanced water treatment processes, rigorous water quality monitoring, and the development of strategies to combat antibiotic resistance in the environment. Safeguarding the safety of our drinking water is imperative to protect public health and mitigate the spread of antibiotic-resistant infections, making these findings a compelling call to action for policymakers and public health authorities alike.
Single-cell analysis reveals that cryptic prophage protease LfgB protects
Escherichia coli
during oxidative stress by cleaving antitoxin MqsA
Authors: Fernández-García Laura , Gao Xinyu , Kirigo Joy , Song Sooyeon , Battisti Michael E. , Garcia-Contreras Rodolfo , Tomas Maria , Guo Yunxue , Wang Xiaoxue , Wood Thomas K.
Published: January 2024

Although toxin/antitoxin (TA) systems are ubiquitous, beyond phage inhibition and mobile element stabilization, their role in host metabolism is obscure. One of the best-characterized TA systems is MqsR/MqsA of
Escherichia coli
, which has been linked previously to protecting gastrointestinal species during the stress it encounters from the bile salt deoxycholate as it colonizes humans. However, some recent whole-population studies have challenged the role of toxins such as MqsR in bacterial physiology since the
mqsRA
locus is induced over a hundred-fold during stress, but a phenotype was not found upon its deletion. Here, we investigate further the role of MqsR/MqsA by utilizing single cells and demonstrate that upon oxidative stress, the TA system MqsR/MqsA has a heterogeneous effect on the transcriptome of single cells. Furthermore, we discovered that MqsR activation leads to induction of the poorly characterized
yfjXY ypjJ yfjZF
operon of cryptic prophage CP4-57. Moreover, deletion of
yfjY
makes the cells sensitive to H
2
O
2
, acid, and heat stress, and this phenotype was complemented. Hence, we recommend
yfjY
be renamed to
lfgB
(
l
ess
f
atality
g
ene
B
). Critically, MqsA represses
lfgB
by binding the operon promoter, and LfgB is a protease that degrades MqsA to derepress
rpoS
and facilitate the stress response. Therefore, the MqsR/MqsA TA system facilitates the stress response through cryptic phage protease LfgB.

IMPORTANCE

The roles of toxin/antitoxin systems in cell physiology are few and include phage inhibition and stabilization of genetic elements; yet, to date, there are no single-transcriptome studies for toxin/antitoxin systems and few insights for prokaryotes from this novel technique. Therefore, our results with this technique are important since we discover and characterize a cryptic prophage protease that is regulated by the MqsR/MqsA toxin/antitoxin system in order to regulate the host response to oxidative stress.
Supplemental Material: A high-resolution sequence stratigraphic framework for the eastern Ellis Bay Formation, Canada: A record of Hirnantian sea-level change
Authors: Zimmt Joshua B. , et al.
Published: January 2024

The full carbon and oxygen isotopic data set is available online.
Early parenteral nutrition is associated with improved growth in very low birth weight infants: a retrospective study
Authors: Shen René Liang , Ritz Christian , Li Yanqi , Sangild Per Torp , Jiang Ping-Ping
Published: January 2024

Objective

To assess the association between early initiation of parenteral nutrition (PN) and body growth in preterm infants with very low birth weight (VLBW).

Design

Causal inference analysis with confounders preselected by causal diagram based on the NeoNutriNet cohort containing data of infants born between 2011 and 2014 from 13 hospitals from 5 continents.

Patients

Neonates with birth weight ≤1500 g.

Interventions

PN initiated within the first day of life (early PN) versus within day 2–5 (delayed PN).

Main outcome measures

The primary outcome was body weight z-scores at postmenstrual age (PMA) 36 weeks or early discharge or death, whichever comes first (WT z-score END). Secondary outcomes included WT z-scores at week 1 and 4 of life (WT z-scores CA1 and CA4), corresponding growth velocities (GVs), mortality and incidence of necrotising enterocolitis (NEC), and duration and episodes of antibiotic treatment.

Results

In total, 2151 infants were included in this study and 2008 infants were in the primary outcome analysis. Significant associations of early PN were found with WT z-score END (adjusted mean difference, 0.14 (95% CI 0.05 to 0.23)), CA4 (β, 0.09 (0.04 to 0.14)) and CA1 (0.04 (0.01 to 0.08)), and GV PMA 36 weeks (1.02 (0.46 to 1.58)) and CA4 (1.03 (0.56 to 1.49), all p<0.001), but not with GV CA1 (p>0.05). No significant associations with mortality, incidence of NEC or antibiotic use was found (all p>0.05).

Conclusions

For VLBW infants, PN initiated within the first day of life is associated with improved in-hospital growth.
Life outcomes after paediatric kidney transplantation: a qualitative, biographical study in long-term survivors
Authors: Ritschl Valentin , Stamm Tanja , Selzer Axana , Boesendorfer Anna , Eibensteiner Fabian , Kaltenegger Lukas , Mosor Erika , Omara Maisa , Vachuda Natalie , Sperl Lisa , Masel Eva K , Aufricht Christoph , Boehm Michael
Published: January 2024

Objective

The objective of this study was to analyse the narrative life stories of children with end-stage kidney disease (ESKD) and their families to determine how health professionals can effectively support these children to achieve better life outcomes.

Design

Qualitative narrative biographic study.

Setting

We invited every long-term survivor of paediatric kidney transplants and their families at the Medical University of Vienna between 2008 and 2013 to participate in this study.

Participants

Nineteen patients (women: n=8, 42%) and 34 family members (women: n=22, 65%) were interviewed. The patients had a mean age of 7.6 (SD±5.6) years at the time of transplantation and 22.2 (SD±5.4) at the time of interview.

Main outcome(s) measure(s)

A qualitative narrative biographical analysis was combined with computational structured topic models using the Latent Dirichlet Allocation.

Results

The overarching finding was the desire for normality in daily life in long-term survivors and their families but with different perceptions of what normality looks like and predominance of this aspect evolving. Different strategies were used by patients (focused on their advancement) and caregivers (normality for all family members). Siblings played a major role in supporting survivors’ social inclusion.

Conclusions

The strong desire for normality confirms recent findings of the Standardised Outcomes in Nephrology Group initiative, which proposes survival and life participation as core outcomes in children with chronic kidney disease. Our study should be a starting point for an international effort to identify typologies and stratified interventions for children with ESKD and their families, particularly siblings.
Cardiogeriatrics: the current state of the art
Authors: Gaur Akshay , Carr Fiona , Warriner David
Published: January 2024

It is estimated that by 2050, 17% of the world’s population will be greater than 85 years old, which, combined with cardiovascular disease (CVD) being the leading cause of death and disability, sets an unprecedented burden on our health and care systems. This perfect storm will be accompanied by a rise in the prevalence of CVD due to increased survival of patients with pre-existing CVD and the incidence of CVD that is associated with the process of ageing. In this review, we will focus on the diagnosis and management of common CVD conditions in old age, namely: heart failure (HF), coronary artery disease (CAD), atrial fibrillation (AF) and valvular heart disease (VHD). Despite limited evidence, clinical guidelines are increasingly considering the complexity of management of these conditions in the older person, which often coexist, for example, AF and HF or CAD and VHD. Furthermore, they, in turn, need specific consideration in the context of comorbidities, polypharmacy, frailty and impaired cognition found in this age group. Hence, the emerging role of the geriatric cardiologist is therefore vital in performing comprehensive geriatric assessment, attending multidisciplinary team meetings and ultimately considering the patient and the sum of their diseases in their totality. There have been recent advances in CVD management but how we apply these to deliver integrated care to the elderly population is key. This review article aims to bring together emerging studies and guidelines on assessment and management of CVD in the elderly, summarising latest definitions, diagnostics, therapeutics and future challenges.
PSCK9 inhibitors reduced early recurrent stroke in patients with symptomatic intracranial atherosclerotic stenosis
Authors: Wu Li , Zhang Bo , Li Chenghao , Zhuang Zhuolin , Liu Kang , Chen Hualin , Zhu Shuanggen , Zhu Juehua , Dai Zheng , Huang Huameng , Jiang Yongjun
Published: January 2024

Background

Symptomatic intracranial atherosclerotic stenosis (ICAS) is prone to cause early recurrent stroke (ERS). Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors lower low-density lipoprotein cholesterol (LDL-C) levels and prevent cardiovascular events. This multicentre, hospital-based prospective cohort study was designed to investigate whether PCSK9 inhibitors would prevent ERS in patients with symptomatic ICAS.

Methods

From 1 October 2020 to 30 September 2022, consecutive patients with acute ischaemic stroke attributed to ICAS admitted within 1 week after onset were enrolled and followed up for 1 month. Patients were divided into two groups, the PCSK9 inhibitors group receiving PCSK9 inhibitors add-on therapy, and the control group receiving statins and/or ezetimibe. The primary outcome was ERS. Cox proportional hazard models and Kaplan-Meier survival curve were used to estimate the association between PCSK9 inhibitors and ERS.

Results

At the end of follow-up, the LDL-C levels were further lowered by PCSK9 inhibitors add-on therapy (n=232, from 3.06±1.16 mmol/L to 2.12±1.19 mmol/L) than statins and/or ezetimibe treatment (n=429, from 2.91±1.05 mmol/L to 2.64±0.86 mmol/L, p<0.001). The Kaplan-Meier survival curves showed that PCSK9 inhibitors add-on therapy significantly reduced ERS (5.59%, 24/429, vs 2.16%, 5/232; log-rank test, p=0.044). The multivariate Cox regression analysis revealed that, after adjusting for confounders with a p value less than 0.05 in univariate analysis or of particular importance, the HR was 0.335 (95% CI 0.114 to 0.986, p=0.047), compared with the control group.

Conclusions

In our study, PCSK9 inhibitors add-on therapy further reduced LDL-C levels and ERS in patients with symptomatic ICAS.