bluuebunny/crossref_metadata_2025 huggingface dataset:
A self-sustaining serpentinization mega-engine feeds the fougerite nanoengines implicated in the emergence of guided metabolism
Authors: Russell Michael J.
Published: May 2023

The demonstration by Ivan Barnes et al. that the serpentinization of fresh Alpine-type ultramafic rocks results in the exhalation of hot alkaline fluids is foundational to the submarine alkaline vent theory (AVT) for life’s emergence to its ‘improbable’ thermodynamic state. In AVT, such alkaline fluids ≤ 150°C, bearing H2 > CH4 > HS−—generated and driven convectively by a serpentinizing exothermic mega-engine operating in the ultramafic crust—exhale into the iron-rich, CO2> > > NO3−-bearing Hadean ocean to result in hydrothermal precipitate mounds comprising macromolecular ferroferric-carbonate oxyhydroxide and minor sulfide. As the nanocrystalline minerals fougerite/green rust and mackinawite (FeS), they compose the spontaneously precipitated inorganic membranes that keep the highly contrasting solutions apart, thereby maintaining redox and pH disequilibria. They do so in the form of fine chimneys and chemical gardens. The same disequilibria drive the reduction of CO2 to HCOO− or CO, and the oxidation of CH4 to a methyl group—the two products reacting to form acetate in a sequence antedating the ‘energy-producing’ acetyl coenzyme-A pathway. Fougerite is a 2D-layered mineral in which the hydrous interlayers themselves harbor 2D solutions, in effect constricted to ~ 1D by preferentially directed electron hopping/tunneling, and proton Gröthuss ‘bucket-brigading’ when subject to charge. As a redox-driven nanoengine or peristaltic pump, fougerite forces the ordered reduction of nitrate to ammonium, the amination of pyruvate and oxalate to alanine and glycine, and their condensation to short peptides. In turn, these peptides have the flexibility to sequester the founding inorganic iron oxyhydroxide, sulfide, and pyrophosphate clusters, to produce metal- and phosphate-dosed organic films and cells. As the feed to the hydrothermal mound fails, the only equivalent sustenance on offer to the first autotrophs is the still mildly serpentinizing upper crust beneath. While the conditions here are very much less bountiful, they do offer the similar feed and disequilibria the survivors are accustomed to. Sometime during this transition, a replicating non-ribosomal guidance system is discovered to provide the rules to take on the incrementally changing surroundings. The details of how these replicating apparatuses emerged are the hard problem, but by doing so the progenote archaea and bacteria could begin to colonize what would become the deep biosphere. Indeed, that the anaerobic nitrate-respiring methanotrophic archaea and the deep-branching Acetothermia presently comprise a portion of that microbiome occupying serpentinizing rocks offers circumstantial support for this notion. However, the inescapable, if jarring conclusion is drawn that, absent fougerite/green rust, there would be no structured channelway to life.
Comparative genomics of Stutzerimonas balearica (Pseudomonas balearica): diversity, habitats, and biodegradation of aromatic compounds
Authors: Salvà-Serra Francisco , Pérez-Pantoja Danilo , Donoso Raúl A. , Jaén-Luchoro Daniel , Fernández-Juárez Víctor , Engström-Jakobsson Hedvig , Moore Edward R. B. , Lalucat Jorge , Bennasar-Figueras Antoni
Published: May 2023

Stutzerimonas balearica (Pseudomonas balearica) has been found principally in oil-polluted environments. The capability of S. balearica to thrive from the degradation of pollutant compounds makes it a species of interest for potential bioremediation applications. However, little has been reported about the diversity of S. balearica. In this study, genome sequences of S. balearica strains from different origins were analyzed, revealing that it is a diverse species with an open pan-genome that will continue revealing new genes and functionalities as the genomes of more strains are sequenced. The nucleotide signatures and intra- and inter-species variation of the 16S rRNA genes of S. balearica were reevaluated. A strategy of screening 16S rRNA gene sequences in public databases enabled the detection of 158 additional strains, of which only 23% were described as S. balearica. The species was detected from a wide range of environments, although mostly from aquatic and polluted environments, predominantly related to petroleum oil. Genomic and phenotypic analyses confirmed that S. balearica possesses varied inherent capabilities for aromatic compounds degradation. This study increases the knowledge of the biology and diversity of S. balearica and will serve as a basis for future work with the species.
Isolation of a highly virulent Metarhizium strain targeting the tea pest, Ectropis obliqua
Authors: Zhao Jie , Chen Yuxi , Keyhani Nemat O. , Wang Cong , Li Yichen , Pu Huili , Li Jincheng , Liu Sen , Lai Pengyu , Zhu Mengjia , He Xueyou , Cai Shouping , Guan Xiayu , Qiu Junzhi
Published: May 2023

Introduction

Tea is one of the most widely consumed beverages around the world. Larvae of the moth, Ectropis obliqua Prout (Geometridae, Lepidoptera), are one of the most destructive insect pests of tea in China. E. obliqua is a polyphagus insect that is of increasing concern due to the development of populations resistant to certain chemical insecticides. Microbial biological control agents offer an environmentally friendly and effective means for insect control that can be compatible with “green” and organic farming practices.

Methods

To identify novel E. obliqua biological control agents, soil and inset cadaver samples were collected from tea growing regions in the Fujian province, China. Isolates were analyzed morphologically and via molecular characterization to identity them at the species level. Laboratory and greenhouse insect bioassays were used to determine the effectiveness of the isolates for E. obliqua control.

Results

Eleven isolates corresponding to ten different species of Metarhizium were identified according to morphological and molecular analyses from soil and/or insect cadavers found on tea plants and/or in the surrounding soil sampled from eight different regions within the Fujian province, China. Four species of Metarhizium including M. clavatum, M. indigoticum, M. pemphigi, and M. phasmatodeae were documented for the first time in China, and the other species were identified as M. anisopliae, M. brunneum, M. lepidiotae, M. majus, M. pinghaense, and M. robertsii. Insect bioassays of the eleven isolates of Metarhizium revealed significant variation in the efficacy of each isolate to infect and kill E. obliqua. Metarhizium pingshaense (MaFZ-13) showed the highest virulence reaching a host target mortality rate of 93% in laboratory bioassays. The median lethal concentration (LC50) and median lethal time (LT50) values of M. pingshaense MaFZ-13 were 9.6 × 104 conidia/mL and 4.8 days, respectively. Greenhouse experiments and a time-dose-mortality (TDM) models were used to further evaluate and confirm the fungal pathogenic potential of M. pingshaense MaFZ-13 against E. obliqua larvae.

Discussion

Isolation of indigenous microbial biological control agents targeting specific pests is an effective approach for collecting resources that can be exploited for pest control with lowered obstacles to approval and commercialization. Our data show the presence of four different previously unreported Metarhizium species in China. Bioassays of the eleven different Metarhizium strains isolated revealed that each could infect and kill E. obliqua to different degrees with the newly isolated M. pingshaense MaFZ-13 strain representing a particularly highly virulent isolate potentially applicable for the control of E. obliqua larvae.
Advances in cellular and molecular predatory biology of Bdellovibrio bacteriovorus six decades after discovery
Authors: Lai Ting F. , Ford Rhian M. , Huwiler Simona G.
Published: May 2023

Since its discovery six decades ago, the predatory bacterium Bdellovibrio bacteriovorus has sparked recent interest as a potential remedy to the antibiotic resistance crisis. Here we give a comprehensive historical overview from discovery to progressive developments in microscopy and molecular mechanisms. Research on B. bacteriovorus has moved from curiosity to a new model organism, revealing over time more details on its physiology and fascinating predatory life cycle with the help of a variety of methods. Based on recent findings in cryo-electron tomography, we recapitulate on the intricate molecular details known in the predatory life cycle including how this predator searches for its prey bacterium, to how it attaches, grows, and divides all from within the prey cell. Finally, the newly developed B. bacteriovorus progeny leave the prey cell remnants in the exit phase. While we end with some unanswered questions remaining in the field, new imaging technologies and quantitative, systematic advances will likely help to unravel them in the next decades.
Gut microbiota assemblages of generalist predators are driven by local- and landscape-scale factors
Authors: Saqib Hafiz Sohaib Ahmed , Sun Linyang , Pozsgai Gabor , Liang Pingping , Goraya Mohsan Ullah , Akutse Komivi Senyo , You Minsheng , Gurr Geoff M. , You Shijun
Published: May 2023

The gut microbiomes of arthropods have significant impact on key physiological functions such as nutrition, reproduction, behavior, and health. Spiders are diverse and numerically dominant predators in crop fields where they are potentially important regulators of pests. Harnessing spiders to control agricultural pests is likely to be supported by an understanding of their gut microbiomes, and the environmental drivers shaping microbiome assemblages. This study aimed to deciphering the gut microbiome assembly of these invertebrate predators and elucidating potential implications of key environmental constraints in this process. Here, we used high-throughput sequencing to examine for the first time how the assemblages of bacteria in the gut of spiders are shaped by environmental variables. Local drivers of microbiome composition were globally-relevant input use system (organic production vs. conventional practice), and crop identity (Chinese cabbage vs. cauliflower). Landscape-scale factors, proportion of forest and grassland, compositional diversity, and habitat edge density, also strongly affected gut microbiota. Specific bacterial taxa were enriched in gut of spiders sampled from different settings and seasons. These findings provide a comprehensive insight into composition and plasticity of spider gut microbiota. Understanding the temporal responses of specific microbiota could lead to innovative strategies development for boosting biological control services of predators.
Adverse events after the transjugular intrahepatic portal shunt are linked to serum metabolomic changes following the procedure
Authors: Chen Quan , Bao Li , Yue Zhendong , Wang Lei , Fan Zhenhua , Liu Fuquan
Published: May 2023

Background and Objective: Transjugular intrahepatic portal shunt (TIPS) insertion could promote weight gain and muscle and fat mass increase in patients with cirrhosis. However, few studies have focused on metabolic changes after TIPS. This study aims to explore metabolic changes after TIPS and potential biomarkers of adverse events.

Methods: Peripheral and portal serum samples were collected before and after TIPS insertion. Untargeted metabolomics was performed using ultra-high-performance liquid chromatography-mass spectrometry. Spearman’s correlation analysis was used to determine the relationship between metabolites and clinical parameters. Metabolite set enrichment analysis was performed to explore enriched pathways. The predictive value of the metabolites was calculated by receiver operating characteristic curve (ROC) analysis.

Results: Metabolites in the peripheral and portal serum significantly changed early after TIPS. Some lipid metabolites were significantly correlated with liver function parameters. Both elevated and depleted metabolites were mainly enriched in amino acid metabolism. Nine and 12 portal metabolites have moderate predictive value in post-TIPS liver function decline and hepatic encephalopathy (HE), separately (area under curve >0.7).

Conclusion: Metabolites in the peripheral and portal veins significantly changed after TIPS. Some metabolic changes might be ascribed to liver function decline early after TIPS. Nine and 12 portal metabolites might be potential biomarkers in prediction of liver function decline and HE, separately.
Comparing synaptic proteomes across five mouse models for autism reveals converging molecular similarities including deficits in oxidative phosphorylation and Rho GTPase signaling
Authors: Carbonell Abigail U. , Freire-Cobo Carmen , Deyneko Ilana V. , Dobariya Saunil , Erdjument-Bromage Hediye , Clipperton-Allen Amy E. , Page Damon T. , Neubert Thomas A. , Jordan Bryen A.
Published: May 2023

Specific and effective treatments for autism spectrum disorder (ASD) are lacking due to a poor understanding of disease mechanisms. Here we test the idea that similarities between diverse ASD mouse models are caused by deficits in common molecular pathways at neuronal synapses. To do this, we leverage the availability of multiple genetic models of ASD that exhibit shared synaptic and behavioral deficits and use quantitative mass spectrometry with isobaric tandem mass tagging (TMT) to compare their hippocampal synaptic proteomes. Comparative analyses of mouse models for Fragile X syndrome (Fmr1 knockout), cortical dysplasia focal epilepsy syndrome (Cntnap2 knockout), PTEN hamartoma tumor syndrome (Pten haploinsufficiency), ANKS1B syndrome (Anks1b haploinsufficiency), and idiopathic autism (BTBR+) revealed several common altered cellular and molecular pathways at the synapse, including changes in oxidative phosphorylation, and Rho family small GTPase signaling. Functional validation of one of these aberrant pathways, Rac1 signaling, confirms that the ANKS1B model displays altered Rac1 activity counter to that observed in other models, as predicted by the bioinformatic analyses. Overall similarity analyses reveal clusters of synaptic profiles, which may form the basis for molecular subtypes that explain genetic heterogeneity in ASD despite a common clinical diagnosis. Our results suggest that ASD-linked susceptibility genes ultimately converge on common signaling pathways regulating synaptic function and propose that these points of convergence are key to understanding the pathogenesis of this disorder.
Emerging epigenetic dynamics in gut-microglia brain axis: experimental and clinical implications for accelerated brain aging in schizophrenia
Authors: Ben-Azu Benneth , del Re Elisabetta C. , VanderZwaag Jared , Carrier Micaël , Keshavan Matcheri , Khakpour Mohammadparsa , Tremblay Marie-Ève
Published: May 2023

Brain aging, which involves a progressive loss of neuronal functions, has been reported to be premature in probands affected by schizophrenia (SCZ). Evidence shows that SCZ and accelerated aging are linked to changes in epigenetic clocks. Recent cross-sectional magnetic resonance imaging analyses have uncovered reduced brain reserves and connectivity in patients with SCZ compared to typically aging individuals. These data may indicate early abnormalities of neuronal function following cyto-architectural alterations in SCZ. The current mechanistic knowledge on brain aging, epigenetic changes, and their neuropsychiatric disease association remains incomplete. With this review, we explore and summarize evidence that the dynamics of gut-resident bacteria can modulate molecular brain function and contribute to age-related neurodegenerative disorders. It is known that environmental factors such as mode of birth, dietary habits, stress, pollution, and infections can modulate the microbiota system to regulate intrinsic neuronal activity and brain reserves through the vagus nerve and enteric nervous system. Microbiota-derived molecules can trigger continuous activation of the microglial sensome, groups of receptors and proteins that permit microglia to remodel the brain neurochemistry based on complex environmental activities. This remodeling causes aberrant brain plasticity as early as fetal developmental stages, and after the onset of first-episode psychosis. In the central nervous system, microglia, the resident immune surveillance cells, are involved in neurogenesis, phagocytosis of synapses and neurological dysfunction. Here, we review recent emerging experimental and clinical evidence regarding the gut-brain microglia axis involvement in SCZ pathology and etiology, the hypothesis of brain reserve and accelerated aging induced by dietary habits, stress, pollution, infections, and other factors. We also include in our review the possibilities and consequences of gut dysbiosis activities on microglial function and dysfunction, together with the effects of antipsychotics on the gut microbiome: therapeutic and adverse effects, role of fecal microbiota transplant and psychobiotics on microglial sensomes, brain reserves and SCZ-derived accelerated aging. We end the review with suggestions that may be applicable to the clinical setting. For example, we propose that psychobiotics might contribute to antipsychotic-induced therapeutic benefits or adverse effects, as well as reduce the aging process through the gut-brain microglia axis. Overall, we hope that this review will help increase the understanding of SCZ pathogenesis as related to chronobiology and the gut microbiome, as well as reveal new concepts that will serve as novel treatment targets for SCZ.
Emerging role of gut microbiota dysbiosis in neuroinflammation and neurodegeneration
Authors: Solanki Riddhi , Karande Anjali , Ranganathan Prathibha
Published: May 2023

Alzheimer's disease (AD), is a chronic age-related progressive neurodegenerative disorder, characterized by neuroinflammation and extracellular aggregation of Aβ peptide. Alzheimer's affects every 1 in 14 individuals aged 65 years and above. Recent studies suggest that the intestinal microbiota plays a crucial role in modulating neuro-inflammation which in turn influences Aβ deposition. The gut and the brain interact with each other through the nervous system and chemical means via the blood-brain barrier, which is termed the Microbiota Gut Brain Axis (MGBA). It is suggested that the gut microbiota can impact the host's health, and numerous factors, such as nutrition, pharmacological interventions, lifestyle, and geographic location, can alter the gut microbiota composition. Although, the exact relationship between gut dysbiosis and AD is still elusive, several mechanisms have been proposed as drivers of gut dysbiosis and their implications in AD pathology, which include, action of bacteria that produce bacterial amyloids and lipopolysaccharides causing macrophage dysfunction leading to increased gut permeability, hyperimmune activation of inflammatory cytokines (IL-1β, IL-6, IL-8, and NLRP3), impairment of gut- blood brain barrier causing deposition of Aβ in the brain, etc. The study of micro-organisms associated with dysbiosis in AD with the aid of appropriate model organisms has recognized the phyla Bacteroidetes and Firmicutes which contain organisms of the genus Escherichia, Lactobacillus, Clostridium, etc., to contribute significantly to AD pathology. Modulating the gut microbiota by various means, such as the use of prebiotics, probiotics, antibiotics or fecal matter transplantation, is thought to be a potential therapeutic intervention for the treatment of AD. This review aims to summarize our current knowledge on possible mechanisms of gut microbiota dysbiosis, the role of gut brain microbiota axis in neuroinflammation, and the application of novel targeted therapeutic approaches that modulate the gut microbiota in treatment of AD.
Safe and effective implantation and use of vagal nerve stimulation in new-onset refractory status epilepticus in early pregnancy: a case report
Authors: Jindal Malaika , Delaj Laura , Winston Joel , Goel Rishu , Bhatti Sadia , Angelova-Chee Milena , Selway Richard , Mantoan Ritter Laura
Published: May 2023

Introduction

The management of new-onset refractory status epilepticus (NORSE) in pregnancy may be complicated by anti-seizure medication (ASM) polytherapy-associated teratogenicity. We aim to demonstrate the safety and efficacy of vagal nerve stimulation (VNS) in a pregnant patient presenting with NORSE.

Case description

A 30-year old female, at 5-weeks' gestation presented with drug-refractory myoclonic status epilepticus, responsive only to high levels of anesthetic agents. The severity of seizures did not allow extubation, and the patient remained ventilated and sedated. VNS was implanted 26 days after seizure onset. The immediate post-operative output was 0.25 mA, which was rapidly titrated up to 0.5 mA the next morning, and to 0.75 mA that afternoon. This was further increased to 1.0 mA on 3rd day post-operation, and to 1.25 mA 7 days post-op. Myoclonic jerks diminished significantly 7 days post-op, allowing extubation. Twenty days after VNS implantation, no myoclonic jerks were observed. There was also a notable neurological improvement including increased alertness and mobility, and ability to obey commands. Drug overdose was subsequently found to be the most likely etiology of her NORSE. An early pregnancy assessment 17 days after VNS implantation showed a normally sited pregnancy, normal fetal heart activity and crown-rump length. The patient remained seizure free, gained functional independence and delivered a premature but otherwise healthy baby at 33 weeks' gestation.

Conclusion

NORSE is challenging to manage, further compounded in pregnancy due to the teratogenicity of ASMs and ASM polytherapy. This is the first case-study to report the safe implantation and use of VNS during the first trimester of pregnancy for the management of NORSE.
Bridging the BCI illiteracy gap: a subject-to-subject semantic style transfer for EEG-based motor imagery classification
Authors: Kim Da-Hyun , Shin Dong-Hee , Kam Tae-Eui
Published: May 2023

Introduction

Brain-computer interfaces (BCIs) facilitate direct interaction between the human brain and computers, enabling individuals to control external devices through cognitive processes. Despite its potential, the problem of BCI illiteracy remains one of the major challenges due to inter-subject EEG variability, which hinders many users from effectively utilizing BCI systems. In this study, we propose a subject-to-subject semantic style transfer network (SSSTN) at the feature-level to address the BCI illiteracy problem in electroencephalogram (EEG)-based motor imagery (MI) classification tasks.

Methods

Our approach uses the continuous wavelet transform method to convert high-dimensional EEG data into images as input data. The SSSTN 1) trains a classifier for each subject, 2) transfers the distribution of class discrimination styles from the source subject (the best-performing subject for the classifier, i.e., BCI expert) to each subject of the target domain (the remaining subjects except the source subject, specifically BCI illiterates) through the proposed style loss, and applies a modified content loss to preserve the class-relevant semantic information of the target domain, and 3) finally merges the classifier predictions of both source and target subject using an ensemble technique.

Results and discussion

We evaluate the proposed method on the BCI Competition IV-2a and IV-2b datasets and demonstrate improved classification performance over existing methods, especially for BCI illiterate users. The ablation experiments and t-SNE visualizations further highlight the effectiveness of the proposed method in achieving meaningful feature-level semantic style transfer.
Preterm birth accelerates the maturation of spontaneous and resting activity in the visual cortex
Authors: Witteveen Isabelle F. , McCoy Emily , Holsworth Troy D. , Shen Catherine Z. , Chang Winnie , Nance Madelyn G. , Belkowitz Allison R. , Dougald Avery , Puglia Meghan H. , Ribic Adema
Published: May 2023

Prematurity is among the leading risks for poor neurocognitive outcomes. The brains of preterm infants show alterations in structure and electrical activity, but the underlying circuit mechanisms are unclear. To address this, we performed a cross-species study of the electrophysiological activity in the visual cortices of prematurely born infants and mice. Using electroencephalography (EEG) in a sample of healthy preterm (N = 29) and term (N = 28) infants, we found that the maturation of the aperiodic EEG component was accelerated in the preterm cohort, with a significantly flatter 1/f slope when compared to the term infants. The flatter slope was a result of decreased spectral power in the theta and alpha bands and was correlated with the degree of prematurity. To determine the circuit and cellular changes that potentially mediate the changes in 1/f slope after preterm birth, we used in vivo electrophysiology in preterm mice and found that, similar to infants, preterm birth results in a flattened 1/f slope. We analyzed neuronal activity in the visual cortex of preterm (N = 6) and term (N = 9) mice and found suppressed spontaneous firing of neurons. Using immunohistochemistry, we further found an accelerated maturation of inhibitory circuits. In both preterm mice and infants, the functional maturation of the cortex was accelerated, underscoring birth as a critical checkpoint in cortical maturation. Our study points to a potential mechanism of preterm birth-related changes in resting neural activity, highlighting the utility of a cross-species approach in studying the neural circuit mechanisms of preterm birth-related neurodevelopmental conditions.
Long-term outcomes and potential mechanisms of offspring exposed to intrauterine hyperglycemia
Authors: Yan Yi-Shang , Feng Chun , Yu Dan-Qing , Tian Shen , Zhou Yin , Huang Yi-Ting , Cai Yi-Ting , Chen Jian , Zhu Miao-Miao , Jin Min
Published: May 2023

Diabetes mellitus during pregnancy, which can be classified into pregestational diabetes and gestational diabetes, has become much more prevalent worldwide. Maternal diabetes fosters an intrauterine abnormal environment for fetus, which not only influences pregnancy outcomes, but also leads to fetal anomaly and development of diseases in later life, such as metabolic and cardiovascular diseases, neuropsychiatric outcomes, reproduction malformation, and immune dysfunction. The underlying mechanisms are comprehensive and ambiguous, which mainly focus on microbiota, inflammation, reactive oxygen species, cell viability, and epigenetics. This review concluded with the influence of intrauterine hyperglycemia on fetal structure development and organ function on later life and outlined potential mechanisms that underpin the development of diseases in adulthood. Maternal diabetes leaves an effect that continues generations after generations through gametes, thus more attention should be paid to the prevention and treatment of diabetes to rescue the pathological attacks of maternal diabetes from the offspring.
The association of dietary inflammatory potential with skeletal muscle strength, mass, and sarcopenia: a meta-analysis
Authors: Xie Haibin , Wang Haochen , Wu Ziying , Li Wei , Liu Yanzhe , Wang Ning
Published: May 2023

Aims

Evidence suggested that dietary inflammatory potential may be associated with age-related skeletal muscle decline, but the results remained controversial. To summarize the evidence for the relationships between dietary inflammatory potential and skeletal muscle strength, mass, and sarcopenia in adults we conducted this meta-analysis.

Methods

Embase, Pubmed, and Web of Science were searched from inception up to 12 March 2023 for studies that evaluated the associations of dietary inflammatory potential [estimated by the Dietary inflammatory index (DII)] with skeletal muscle strength, mass, and sarcopenia. A meta-analysis was then performed to calculate the pooled regression coefficient (β) and odds ratio (OR). The non-linear dose-response relation between DII and sarcopenia was assessed using random-effects dose-response meta-analysis.

Results

This meta-analysis included 24 studies involving 56,536 participants. It was found that high DII was associated with low skeletal muscle strength [OR 1.435, 95% confidence interval (CI) 1.247–1.651, P < 0.001, I2 = 4.97%]. There was a negative association of DII with skeletal muscle strength (β−0.031, 95% CI −0.056 to −0.006, P = 0.017, I2 = 72.69%). High DII was also associated with low skeletal muscle mass (OR 1.106, 95% CI 1.058–1.157, P < 0.001, I2 = 0%). DII had a negative relationship with skeletal muscle mass with high heterogeneity (β−0.099, 95% CI −0.145 to −0.053, P < 0.001, I2 = 88.67%); we downgraded the inconsistency in the subgroup analysis of overweight/obese participants (β−0.042, 95% CI −0.065 to −0.019, I2 = 12.54%). Finally, the pooled results suggested that high DII was significantly associated with sarcopenia with significant heterogeneity (OR 1.530, 95% CI 1.245–1.880, P < 0.001, I2 = 69.46%); age and BMI may contribute partially to the heterogeneity since heterogeneity was decreased in the subgroup of older age (OR 1.939, 95% CI 1.232–3.051, I2 = 0%) and the group of overweight/obesity (OR 1.853, 95% CI 1.398–2.456, I2 = 0%). There was a non-linear dose-response association between DII and sarcopenia (P = 0.012 for non-linearity).

Conclusion

This meta-analysis suggested that higher dietary inflammatory potential was significantly associated with lower skeletal muscle strength, mass, and risk of sarcopenia. Future studies with consistent assessment and standardized methodology are needed for further analysis.
A metabolic shift toward glycolysis enables cancer cells to maintain survival upon concomitant glutamine deprivation and V-ATPase inhibition
Authors: Lengauer Florian , Geisslinger Franz , Gabriel Antje , von Schwarzenberg Karin , Vollmar Angelika M. , Bartel Karin
Published: May 2023

It is widely known that most cancer cells display an increased reliance on glutaminolysis to sustain proliferation and survival. Combining glutamine deprivation with additional anti-cancer therapies is an intensively investigated approach to increase therapeutic effectiveness. In this study, we examined a combination of glutamine deprivation by starvation or pharmacological tools, with the anti-cancer agent archazolid, an inhibitor of the lysosomal V-ATPase. We show that glutamine deprivation leads to lysosomal acidification and induction of pro-survival autophagy, which could be prevented by archazolid. Surprisingly, a combination of glutamine deprivation with archazolid did not lead to synergistic induction of cell death or reduction in proliferation. Investigating the underlying mechanisms revealed elevated expression and activity of amino acid transporters SLC1A5, SLC38A1 upon starvation, whereas archazolid had no additional effect. Furthermore, we found that the export of lysosomal glutamine derived from exogenous sources plays no role in the phenotype as knock-down of SLC38A7, the lysosomal glutamine exporter, could not increase V-ATPase inhibition-induced cell death or reduce proliferation. Analysis of the cellular metabolic phenotype revealed that glutamine deprivation led to a significant increase in glycolytic activity, indicated by an elevated glycolytic capacity and reserve, when V-ATPase function was inhibited concomitantly. This was confirmed by increased glutamine uptake, augmented lactate production, and an increase in hexokinase activity. Our study, therefore, provides evidence, that glutamine deprivation induces autophagy, which can be prevented by simultaneous inhibition of V-ATPase function. However, this does not lead to a therapeutic benefit, as cells are able to circumvent cell death and growth inhibition by a metabolic shift toward glycolysis.
Association between dietary approaches to stop hypertension eating pattern and lung cancer risk in 98,459 participants: results from a large prospective study
Authors: Zhu Zhiyong , Peng Linglong , Gu Haitao , Tang Yunhao , Xiao Yi , He Hongmei , Yang Mingying , Xiang Ling , Wang Yaxu
Published: May 2023

Background

Dietary approaches to stop hypertension (DASH) eating pattern is linked to anti-inflammatory responses and antioxidation, which overlap with the pathogenesis of lung cancer. However, there is insufficient epidemiological evidence to link this dietary pattern to lung cancer risk conclusively.

Aim

To determine if adherence to the DASH diet is linked to a lower risk of developing lung cancer in a large prospective study.

Methodology

The data of participants were retrieved from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. A DASH score was calculated based on 8 dietary components to reflect adherence to DASH, with greater scores representing higher adherence. Three Cox proportional hazards models were constructed to analyze the association between DASH scores and lung cancer risk, including an unadjusted model and two adjusted models (model 1 for demographics and model 2 for fully confounding factors). A restricted cubic spline plot was utilized to illustrate the likelihood of developing lung cancer across the entire range of DASH scores. The association between each of the 8 DASH components and the risk of lung cancer was assessed separately. Several subgroup analyses were conducted to identify potential modifiers, and several sensitivity analyses were performed to verify the robustness of the findings.

Results

The study involved 98,459 individuals in total. The mean (standard deviation) DASH score was 24.00 (4.62) points, along with the mean follow-up period of 8.84 (1.94) years. Lung cancer was identified in 1642 cases over 869807.9 person-years of follow-up, and the overall incidence rate was 0.189 cases/100 person-years. Participants in the highest quartile in the fully adjusted model had a relatively decreased risk of developing lung cancer in comparison to those in the lowest quartile (HRquartile 4 versus 1: 0.647; 95% CI: 0.557, 0.752; Ptrend < 0.001). The restricted cubic spline plot demonstrated that DASH score and lung cancer risk were inversely associated and had a linear dose–response relationship (Pnon-linear = 0.944). According to subgroup analyses, those who were current or former smokers had a stronger inverse connection than those who never smoked (Pinteraction = 0.013). The results remained robust after several sensitivity analyses.

Conclusion

The risk of lung cancer was inversely associated with DASH scores in the US population. This suggests that following the DASH pattern can help prevent lung cancer, especially for current or former smokers. More epidemiological evidence from other regions and populations is needed to confirm our findings.
Imaging findings of primary epithelioid sarcoma of adrenal gland: a case report and literature review
Authors: Yin Hongyu , Zhang Yi , Wu Linyun , Zhang Ji
Published: May 2023

Epithelioid sarcoma (ES) is a rare soft tissue malignant tumor with an uncertain histogenetic origin. It usually arises in soft tissues of the extremities, while ES in adrenal gland is extremely rare. There is no special clinical manifestation in the early stage, so it may be misdiagnosed and delay the treatment. We reported a 69-year-old male with an adrenal ES. The tumor was completely resected, and two months later, positron emission tomography-computed tomography(PET/CT) noted recurrence at the tumor bed and multiple metastases. The patient has been treated with chemotherapy with good effects. We summarize the radiological findings and immunohistochemical indexes of primary epithelioid sarcoma of adrenal gland, which may be useful to promote disease awareness and help to distinguish among other lesions.
Orchestral role of lipid metabolic reprogramming in T-cell malignancy
Authors: Mehta Arundhati , Ratre Yashwant Kumar , Soni Vivek Kumar , Shukla Dhananjay , Sonkar Subhash C. , Kumar Ajay , Vishvakarma Naveen Kumar
Published: May 2023

The immune function of normal T cells partially depends on the maneuvering of lipid metabolism through various stages and subsets. Interestingly, T-cell malignancies also reprogram their lipid metabolism to fulfill bioenergetic demand for rapid division. The rewiring of lipid metabolism in T-cell malignancies not only provides survival benefits but also contributes to their stemness, invasion, metastasis, and angiogenesis. Owing to distinctive lipid metabolic programming in T-cell cancer, quantitative, qualitative, and spatial enrichment of specific lipid molecules occur. The formation of lipid rafts rich in cholesterol confers physical strength and sustains survival signals. The accumulation of lipids through de novo synthesis and uptake of free lipids contribute to the bioenergetic reserve required for robust demand during migration and metastasis. Lipid storage in cells leads to the formation of specialized structures known as lipid droplets. The inimitable changes in fatty acid synthesis (FAS) and fatty acid oxidation (FAO) are in dynamic balance in T-cell malignancies. FAO fuels the molecular pumps causing chemoresistance, while FAS offers structural and signaling lipids for rapid division. Lipid metabolism in T-cell cancer provides molecules having immunosuppressive abilities. Moreover, the distinctive composition of membrane lipids has implications for immune evasion by malignant cells of T-cell origin. Lipid droplets and lipid rafts are contributors to maintaining hallmarks of cancer in malignancies of T cells. In preclinical settings, molecular targeting of lipid metabolism in T-cell cancer potentiates the antitumor immunity and chemotherapeutic response. Thus, the direct and adjunct benefit of lipid metabolic targeting is expected to improve the clinical management of T-cell malignancies.
Comprehensive genomic and immunohistochemical profiles and outcomes of immunotherapy in patients with recurrent or advanced cervical cancer
Authors: Kim Yoo-Na , Lee Kyunglim , Park Eunhyang , Park Junsik , Lee Yong Jae , Nam Eun Ji , Kim Sang Wun , Kim Sunghoon , Kim Young Tae , Lee Jung-Yun
Published: May 2023

Purpose

This study aimed to investigate genomic and immunohistochemical (IHC) profiles and immunotherapy outcomes in patients with cervical cancer.

Methods

Patients with recurrent cervical cancer who underwent tumor next-generation sequencing (NGS) with the TruSight Oncology 500 panel at Yonsei Cancer Center between June 2019 and February 2022, were identified. Patients who received treatment with checkpoint inhibitors during the same period were also identified. Clinical information, including histology, stage, human papillomavirus (HPV) genotype, IHCs profile, and therapy outcome, was reviewed.

Results

We identified 115 patients treated for recurrent cervical cancer, including 74 patients who underwent tumor NGS. Most of these 74 patients were initially diagnosed with advanced stage (63.6%) and had squamous cell histology (52.7%), and high-risk HPV (76.9%). Based on IHC analysis, the programmed death-ligand 1 combined positive score (PD-L1 CPS) was higher in patients with squamous cell carcinoma (SCC) than in those with adeno or mucinous types (P=0.020). HER2 receptor expression of 2+ and 3+ were identified in 5 and 1 patients, respectively, and significantly varied based on histology (p=0.002). Among the 74 patients, single nucleotide variants (SNVs) and copy number variations (CNVs) were identified in 60 (81.1%) and 13 patients (17.6%), respectively. The most common SNVs were PIK3CA, TP53, STK11, FAT1, and FBXW7 mutations. Mutations in PIK3CA, with two hotspot mutations, were frequently observed in patients with SCC histology, whereas mutations in TP53 were frequently observed in patients with non-SCC histology. Additionally, variations in FAT1 were exclusively identified in patients with SCC histology. Mutations in homologous recombination repair-associated genes were identified in 18 patients (24.3%). The most frequent CNV alteration was CCNE1 amplification. Moreover, among the 36 patients who underwent NGS and received immunotherapy, the tumor mutational burden and microsatellite instability were significantly correlated with immunotherapy duration. During this timeframe, 73 patients received pembrolizumab monotherapy, among whom a small portion showed a durable response.

Conclusion

Comprehensive genomic and IHC profiling may help identify potential candidates for targeted immunotherapy in patients with cervical cancer.
Dihydromyricetin functions as a tumor suppressor in hepatoblastoma by regulating SOD1/ROS pathway
Authors: Guo Tong , Wang Xitong , Zhang Gensheng , Xia Tian , Zhu Runzhi , Tou Jinfa
Published: May 2023

Background

Hepatoblastoma has an unsatisfactory prognosis, and traditional chemotherapy has strong side effects. Dihydromyricetin is a flavonoid extracted from a woody vine of the genus Serpentine in the family Vitaceae, with effects such as preventing alcoholic liver and reducing the incidence of liver cancer. However, the effect of DHM on hepatoblastoma and its specific pathway are still unclear.

Purpose

The purpose of this study was to investigate the effects of DHM on children's hepatoblastoma and its related mechanisms.

Methods

CCK-8 assays were used to measure proliferation. Apoptosis and reactive oxygen species (ROS) were analyzed by flow cytometry. Apoptotic cells were observed using Hoechst 33342 staining and fluorescence microscopy. Protein expression levels in HuH-6 and HepG2 cells were determined by western blotting.

Results

We found that DHM was able to inhibit the growth and increase cellular mortality in HuH-6 and HepG2 cells. Furthermore, DHM decreased the intracellular ROS level and increased the expression of SOD1. ROS scavenger NAC promoted apoptosis, while the use of SOD1 inhibitor LCS-1 weakened the ROS scavenging effect of DHM , and to some extent reduced the killing effect of DHM on hepatoblastoma cells.

Conclusion

These results suggest that regulating SOD1/ROS pathway to induce apoptosis is one of the potential mechanisms of DHM as a tumor suppressor in hepatoblastoma. Therefore, DHM may be a novel candidate for inhibiting hepatoblastoma growth and deserves further study.
Burkholderia cepacia infection in children without cystic fibrosis: a clinical analysis of 50 cases
Authors: Shi Huixuan , Chen Xianrui , Chen Lili , Zhu Bizhen , Yan Weiyuan , Ma Xiaobo
Published: May 2023

Background

Burkholderia cepacia (B. cepacia) is an emerging pathogen of nosocomial infection in pediatric patient carrying cystic fibrosis. The clinical diagnosis and treatment of B. cepacia infection remains poorly studied. This study outlined the risk factors, antimicrobial susceptibility, and clinical characteristics aiming to improve the treatment of B. cepacia infection.

Methods

A retrospective study was conducted based on the 50 cases infection caused by B. cepacia in children without cystic fibrosis, which were diagnosed in the First Affiliated Hospital of Xiamen University, from January 1st, 2011 to December 31st, 2021.

Results

A total of 50 children were infected with B. cepacia, of whom 68% had an underlying health condition, such as cardiovascular disease (23.5%), respiratory disease (17.6%), nervous system disease (14.7%), and neoplastic disease (14.7%). At the onset of B. cepacia infection, 42 (84%) pediatric patients were in an intensive care unit (ICU), 33 (66%) underwent endotracheal intubation, and 32 (64%) had a central venous catheter (CVC). In addition, hospital-acquired cases were 46 (92%), and healthcare-acquired cases were 4 (12%). The most common infectious sites of B. cepacia were the respiratory tract (68%), followed by the blood (20%), and the urinary tract (12%). It indicated that B. cepacia was the most sensitive to ceftazidime (95.65%), followed by trimethoprim-sulfamethoxazole (88.68%), meropenem (82.98%), cefepime (77.78%), and levofloxacin (55.85%). The drug resistance rate of piperacillin-tazobactam, minocycline, aztreonam, cefoperazone-sulbactam and ceftriaxone was higher than 55%. 38 cases were cured or improved, eight had treatment terminated, and four died.

Conclusion

B. cepacia is an opportunistic pathogen normally found in immunocompromised pediatric patients and highly likely to lead to drug resistance. Nosocomial B. cepacia infections occurred mostly in patients in the ICU based on our observations. The surveillance of B. cepacia infections including changing epidemiology and increasing resistance of the microorganism is still very important. Treatment with effective antibiotics such as ceftazidime, meropenem, trimethoprim-sulfamethoxazole is associated with a favorable prognosis.
Leveraging the placenta to advance neonatal care
Authors: Mestan Karen K. , Leibel Sandra L. , Sajti Eniko , Pham Betty , Hietalati Samantha , Laurent Louise , Parast Mana
Published: May 2023

The impact of placental dysfunction and placental injury on the fetus and newborn infant has become a topic of growing interest in neonatal disease research. However, the use of placental pathology in directing or influencing neonatal clinical management continues to be limited for a wide range of reasons, some of which are historical and thus easily overcome today. In this review, we summarize the most recent literature linking placental function to neonatal outcomes, focusing on clinical placental pathology findings and the most common neonatal diagnoses that have been associated with placental dysfunction. We discuss how recent technological advances in neonatal and perinatal medicine may allow us to make a paradigm shift, in which valuable information provided by the placenta could be used to guide neonatal management more effectively, and to ultimately enhance neonatal care in order to improve our patient outcomes. We propose new avenues of clinical management in which the placenta could serve as a diagnostic tool toward more personalized neonatal intensive care unit management.
Impact of COVID-19 epidemic on antihypertensive drug treatment disruptions: results from a nationwide interrupted time-series analysis
Authors: Mathieu Clément , Bezin Julien , Pariente Antoine
Published: May 2023

Background: The COVID-19 epidemic has disrupted care and access to care in many ways. It was accompanied by an excess of cardiovascular drug treatment discontinuations. We sought to investigate a deeper potential impact of the COVID-19 epidemic on antihypertensive drug treatment disruptions by assessing whether the epidemic induced some changes in the characteristics of disruptions in terms of duration, treatment outcome, and patient characteristics.

Methods: From March 2018 to February 2021, a repeated cohort analysis was performed using French national health insurance databases. The impact of the epidemic on treatment discontinuations and resumption of antihypertensive medications was assessed using preformed interrupted time series analyses either on a quarterly basis.

Results: Among all adult patients on antihypertensive medication, we identified 2,318,844 (18.7%) who discontinued their antihypertensive treatment during the first blocking period in France. No differences were observed between periods in the characteristics of patients who interrupted their treatment or in the duration of treatment disruptions. The COVID-19 epidemic was not accompanied by a change in the proportion of patients who fully resumed treatment after a disruption, neither in level nor in trend/slope [change in level: 2.66 (−0.11; 5.42); change in slope: −0.67 (−1.54; 0.20)]. Results were similar for the proportion of patients who permanently discontinued treatment within 1 year of disruption [level change: −0.21 (−2.08; 1.65); slope change: 0.24 (−0.40; 0.87)].

Conclusion: This study showed that, although it led to an increase in cardiovascular drug disruptions, the COVID-19 epidemic did not change the characteristics of these. First, disruptions were not prolonged, and post-disruption treatment outcomes remained unchanged. Second, patients who experienced antihypertensive drug disruptions during the COVID-19 outbreak were essentially similar to those who experienced disruptions before it.