bluuebunny/crossref_metadata_2025 huggingface dataset:
Innovative gamification and outreach tools to raise awareness about antimicrobial resistance
Authors: Tarín-Pelló Antonio , Marco-Crespo Elisa , Suay-García Beatriz , Galiana-Roselló Carolina , Bueso-Bordils José I. , Pérez-Gracia María-Teresa
Published: September 2022

Since 2017, the SWICEU team has developed various informative actions and innovative gamification supports to educate and raise awareness about antimicrobial resistance (AMR) and the correct use of antibiotics among the general population especially among young people. This case study presents the results obtained in the last 5 years with the strategies carried out by this team, composed of students and professors of Health Sciences, Industrial Design Engineering, and Communication Sciences at CEU Cardenal Herrera University (CEU UCH) in Valencia (Spain). Over the past 5 years, playful educational supports have been developed to make the health problem of bacterial resistance and the action of antibiotics more understandable among young people. The dissemination media used, with the same objective of teaching and raising awareness about AMR in a creative and innovative way, have been selected according to the trends in digital communication and use of scientific and health content provided by the most recent studies carried out among the Spanish population. These strategies have included decalogues or “tips” with useful advice, infographics, YouTube videos, Twitter threads, online challenges on Kahoot, stories on Instagram, use of QR codes, etc. These actions have also obtained diffusion in the media and have been awarded by different national and international entities. The good results obtained in the case under study allow us to establish recommendations for the design of innovative educational gamification and dissemination supports on AMR, especially aimed at younger audiences.
Prevalence and antibiotics resistance of Ureaplasma species and Mycoplasma hominis in Hangzhou, China, from 2013 to 2019
Authors: Song Jingjuan , Wu Xuanlan , Kong Yingying , Jin Hong , Yang Ting , Xie Xinyou , Zhang Jun
Published: September 2022

Ureaplasma spp. and Mycoplasma hominis, frequent colonizers in the lower urogenital tract, have been implicated in various infections, with antibiotic resistance growing and varying regionally. This study aims to investigate the prevalence and antibiotic resistance profiles of Ureaplasma spp. and M. hominis in outpatients in Hangzhou, China, from 2013 to 2019. A total of 135,263 outpatients were examined to determine the prevalence of Ureaplasma spp. and M. hominis, including 48,638 males and 86,625 females. Furthermore, trends in antibiotic susceptibility of Ureaplasma spp. and M. hominis during 1999–2019 were analyzed. The cultivation, identification, and antibiotic susceptibility of the bacteria (ofloxacin, ciprofloxacin, erythromycin, clarithromycin, azithromycin, josamycin, tetracycline, doxycycline, and pristinamycin) were determined using the Mycoplasma IST2 kit. Our study indicated that the overall prevalence of total Ureaplasma spp./M. hominis was 38.1% from 2013 to 2019. Ureaplasma spp. were the most frequently isolated species (overall prevalence, 31.3%), followed by Ureaplasma spp./M. hominis coinfection (6.0%) and single M. hominis infection (0.8%). The prevalence of Ureaplasma spp. and M. hominis was significantly higher in females than in males, and the highest positive rates of total Ureaplasma spp./M. hominis were observed in both female and male outpatients aged 14–20 years. During 2013–2019, josamycin, tetracycline, doxycycline, and pristinamycin maintained exceptionally high activity (overall resistance rates, <5%) against both Ureaplasma spp. and M. hominis, but ofloxacin and ciprofloxacin showed limited activity (overall resistance rates, >70%). During 1999–2019, the rates of resistance to ofloxacin and ciprofloxacin increased against both Ureaplasma spp. and M. hominis but decreased to erythromycin, clarithromycin, azithromycin, tetracycline, and doxycycline against Ureaplasma spp. In conclusion, our study demonstrates a high prevalence of Ureaplasma spp. compared to M. hominis and Ureaplasma spp./M. hominis, and their distribution was associated with sex and age. Josamycin, doxycycline, and tetracycline are promising antibiotics that have remarkable activity against Ureaplasma species and M. hominis.
TMT-based quantitative proteomics analysis reveals the role of Notch signaling in FAdV-4-infected LMH cell
Authors: Niu Yujuan , Liu Zhiyang , Wang Mengyu , Du Ke , Chang Kaihui , Ding Yonghe
Published: September 2022

Fowl adenovirus serotype 4 (FAdV-4) is recognized as a pathogen that causes hydropericardium syndrome. Irrespective of the pathway used by the virus to invade the chicken, the pathological characteristics of the disease include degeneration and necrosis of hepatocytes, formation of intranuclear inclusions, as well as inflammatory cell infiltration. Liver dysfunction constitutes one of the critical factors leading to death. Therefore, it is vital to investigate the virus-mediated severe pathological liver damage to further understand the pathogenesis of FAdV-4. Here, proteomics, a tandem mass tag (TMT)-based approach to directly analyze protein expression, was used to determine the protein expression during FAdV-4 proliferation in leghorn male hepatoma (LMH) cells. We identified 177 differentially expressed proteins associated with various biological processes and pathways. The functional enrichment analysis revealed that FAdV-4 could downregulate some signaling pathways in LMH cells, including NOD-like receptor signaling, RIG-I-like receptor signaling, NF-κB signaling, TNF signaling pathway, and Notch signaling, FoxO signaling, PI3K-Akt signaling, and autophagy. The results of proteomics screening suggested an association between FAdV-4 infection and Notch signaling in LMH in vitro, indicating that Notch signaling regulated the expression of inflammatory cytokines and interferons but not viral replication in LMH cells. These data contributed to the understanding of the immunopathogenesis and inflammopathogenesis of FAdV-4 infection and also provided valuable information for the further analysis of the molecular mechanisms underlying viral pathogenesis.
Repulsive response of Meloidogyne incognita induced by biocontrol bacteria and its effect on interspecific interactions
Authors: Zhao Yanli , Zhou Qinying , Zou Chenggang , Zhang Keqin , Huang Xiaowei
Published: September 2022

The aversive behavior of Caenorhabditis elegans is an important strategy that increases their survival under pathogen infection, and the molecular mechanisms underlying this behavior have been described. However, whether this defensive response occurs in plant-parasitic nematodes (PPNs), which have quite different life cycles and genomic sequences from the model nematode, against biocontrol microbes and affects interspecific interactions in ecological environments remains unclear. Here, we showed that Meloidogyne incognita, one of the most common PPNs, engaged in lawn-leaving behavior in response to biocontrol bacteria such as Bacillus nematocida B16 and B. thuringiensis Bt79. Genomic analysis revealed that the key genes responsible for the aversive behavior of C. elegans, such as serotonin-and TGF-β-related genes in canonical signaling pathways, were homologous to those of M. incognita, and the similarity between these sequences ranged from 30% to 67%. Knockdown of the homologous genes impaired avoidance of M. incognita to varying degrees. Calcium ion imaging showed that the repulsive response requires the involvement of the multiple amphid neurons of M. incognita. In situ hybridization specifically localized Mi-tph-1 of the serotonin pathway to ADF/NSM neurons and Mi-dbl-1 of the TGF-β pathway to AVA neurons. Our data suggested that the repulsive response induced by different biocontrol bacteria strongly suppresses the invasion of tomato host plants by M. incognita. Overall, our study is the first to clarify the pathogen-induced repulsive response of M. incognita and elucidate its underlying molecular mechanisms. Our findings provide new insights into interspecific interactions among biocontrol bacteria, PPNs, and host plants.
Long-term gamma transcranial alternating current stimulation improves the memory function of mice with Alzheimer’s disease
Authors: Wu Linyan , Cao Tiantian , Li Sinan , Yuan Ye , Zhang Wenlong , Huang Liang , Cai Chujie , Fan Liming , Li Long , Wang Jingyun , Liu Tian , Wang Jue
Published: September 2022

Background

The main manifestation of Alzheimer’s disease (AD) in patients and animal models is impaired memory function, characterized by amyloid-beta (Aβ) deposition and impairment of gamma oscillations that play an important role in perception and cognitive function. The therapeutic effect of gamma band stimulation in AD mouse models has been reported recently. Transcranial alternating current stimulation (tACS) is an emerging non-invasive intervention method, but at present, researchers have not completely understood the intervention effect of tACS. Thus, the intervention mechanism of tACS has not been fully elucidated, and the course of treatment in clinical selection also lacks theoretical support. Based on this issue, we investigated the effect of gamma frequency (40 Hz) tACS at different durations in a mouse model of AD.

Materials and methods

We placed stimulating electrodes on the skull surface of APP/PS1 and wild-type control mice (n = 30 and n = 5, respectively). Among them, 20 APP/PS1 mice were divided into 4 groups to receive 20 min 40 Hz tACS every day for 1–4 weeks. The other 10 APP/PS1 mice were equally divided into two groups to receive sham treatment and no treatment. No intervention was performed in the wild-type control mice. The short-term memory function of the mice was examined by the Y maze. Aβ levels and microglia in the hippocampus were measured by immunofluorescence. Spontaneous electroencephalogram gamma power was calculated by the average period method, and brain connectivity was examined by cross-frequency coupling.

Results

We found that the long-term treatment groups (21 and 28 days) had decreased hippocampal Aβ levels, increased electroencephalogram spontaneous gamma power, and ultimately improved short-term memory function. The treatment effect of the short-term treatment group (7 days) was not significant. Moreover, the treatment effect of the 14-day treatment group was weaker than that of the 21-day treatment group.

Conclusion

These results suggest that long-term gamma-frequency tACS is more effective in treating AD by reducing Aβ load and improving gamma oscillation than short-term gamma-frequency tACS.
Addressing skepticism of the critical brain hypothesis
Authors: Beggs John M.
Published: September 2022

The hypothesis that living neural networks operate near a critical phase transition point has received substantial discussion. This “criticality hypothesis” is potentially important because experiments and theory show that optimal information processing and health are associated with operating near the critical point. Despite the promise of this idea, there have been several objections to it. While earlier objections have been addressed already, the more recent critiques of Touboul and Destexhe have not yet been fully met. The purpose of this paper is to describe their objections and offer responses. Their first objection is that the well-known Brunel model for cortical networks does not display a peak in mutual information near its phase transition, in apparent contradiction to the criticality hypothesis. In response I show that it does have such a peak near the phase transition point, provided it is not strongly driven by random inputs. Their second objection is that even simple models like a coin flip can satisfy multiple criteria of criticality. This suggests that the emergent criticality claimed to exist in cortical networks is just the consequence of a random walk put through a threshold. In response I show that while such processes can produce many signatures criticality, these signatures (1) do not emerge from collective interactions, (2) do not support information processing, and (3) do not have long-range temporal correlations. Because experiments show these three features are consistently present in living neural networks, such random walk models are inadequate. Nevertheless, I conclude that these objections have been valuable for refining research questions and should always be welcomed as a part of the scientific process.
Abnormal decrement on high-frequency repetitive nerve stimulation in congenital myasthenic syndrome with GFPT1 mutations and review of literature
Authors: An Ran , Chen Huijiao , Lei Song , Li Yi , Xu Yanming , He Chengqi
Published: September 2022

Objectives

Congenital myasthenic syndrome (CMS) is a clinically and genetically heterogeneous group of inherited disorders characterized by neuromuscular junction defects. Mutations in GFPT1 have been shown to underlie CMS. An increasing number of patients with CMS due to mutations in GFPT1 have been reported. However, a comprehensive review of clinical and genetic analyses of GFPT-related CMS worldwide is lacking, especially, given that the common or hotspot mutations in GFPT1 have not been reported. Here, we described the clinical and genetic findings of three patients with GFPT1 mutations from southwestern China and reviewed the clinical and genetic features of patients with GFPT1-related CMS worldwide.

Methods

Clinical, laboratory, electrophysiological, myopathological, and genetic analyses of three patients with GFPT1-related CMS from southwestern China were conducted, and a review of previously published or reported cases about congenital myasthenic syndrome with GFPT1 mutations in the PubMed database was made.

Results

The clinical, laboratory, electrophysiological, and myopathological features by muscle biopsy of three patients with GFPT1-related CMS were consistent with those of previously reported patients with GFPT1 mutations. Additionally, an abnormal decrement in high-frequency RNS was found. Two different homozygous missense mutations (c.331C>T, p.R111C; c.44C>T, p.T15M) were detected by whole-exome sequencing (WES) or targeted neuromuscular disorder gene panels.

Conclusion

A distinct decremental response to high-frequency RNS was found in three patients with GFPT1-related CMS from southwestern China, which has never been reported thus far. In addition, the location and degree of tubular aggregates (TAs) seemed to be associated with the severity of clinical symptoms and serum creatine kinase levels, further expanding the phenotypic spectrum of GFPT1-related CMS. Lastly, some potential hotspot mutations in GFPT1 have been found in GFPT1-CMS worldwide.
Case report: Monoclonal CGRP-antibody treatment in a migraine patient with a mutation in the mitochondrial single-strand binding protein (SSBP1)
Authors: Kaltseis Katharina , Indelicato Elisabetta , Broessner Gregor , Boesch Sylvia
Published: September 2022

Background

There is a growing body of mitochondrial disorders that are associated with headaches, albeit only one of them is currently listed in the latest International Classification of Headache Disorders, 3rd edition (ICHD-3). Headache frequency and headache presentation can vary widely in this respective patient group. Acute and preventive migraine treatment can be quite challenging—the use of several established medications is often limited due to their side effects in the setting of mitochondrial dysfunction and multi-organ disease.

Case presentation

Along with a review of the literature on treatment options in patients with mitochondrial disorders and migraine headaches, we present the case of a 23-year-old male with a homozygous mutation in the mitochondrial single-strand binding protein (SSBP1) with chronic migraine with aura. After failing several standard of care prophylactics due to either side effects or inefficacy, he was successfully treated with a monoclonal anti-CGRP-antibody as a preventive migraine treatment. The monoclonal antibody was well tolerated and showed adequate efficacy with a sustained > 50% reduction in monthly headache days after 3 years of treatment.

Conclusion

Migraine is often challenging to treat in patients with mitochondriopathy due to therapy-limiting comorbidities. Monoclonal CGRP-antibodies might be a safe treatment option in the prevention of migraine headaches in patients with a mitochondrial disorder.
A flexible data-driven audiological patient stratification method for deriving auditory profiles
Authors: Saak Samira , Huelsmeier David , Kollmeier Birger , Buhl Mareike
Published: September 2022

For characterizing the complexity of hearing deficits, it is important to consider different aspects of auditory functioning in addition to the audiogram. For this purpose, extensive test batteries have been developed aiming to cover all relevant aspects as defined by experts or model assumptions. However, as the assessment time of physicians is limited, such test batteries are often not used in clinical practice. Instead, fewer measures are used, which vary across clinics. This study aimed at proposing a flexible data-driven approach for characterizing distinct patient groups (patient stratification into auditory profiles) based on one prototypical database (N = 595) containing audiogram data, loudness scaling, speech tests, and anamnesis questions. To further maintain the applicability of the auditory profiles in clinical routine, we built random forest classification models based on a reduced set of audiological measures which are often available in clinics. Different parameterizations regarding binarization strategy, cross-validation procedure, and evaluation metric were compared to determine the optimum classification model. Our data-driven approach, involving model-based clustering, resulted in a set of 13 patient groups, which serve as auditory profiles. The 13 auditory profiles separate patients within certain ranges across audiological measures and are audiologically plausible. Both a normal hearing profile and profiles with varying extents of hearing impairments are defined. Further, a random forest classification model with a combination of a one-vs.-all and one-vs.-one binarization strategy, 10-fold cross-validation, and the kappa evaluation metric was determined as the optimal model. With the selected model, patients can be classified into 12 of the 13 auditory profiles with adequate precision (mean across profiles = 0.9) and sensitivity (mean across profiles = 0.84). The proposed approach, consequently, allows generating of audiologically plausible and interpretable, data-driven clinical auditory profiles, providing an efficient way of characterizing hearing deficits, while maintaining clinical applicability. The method should by design be applicable to all audiological data sets from clinics or research, and in addition be flexible to summarize information across databases by means of profiles, as well as to expand the approach toward aided measurements, fitting parameters, and further information from databases.
A framework for application of consumer neuroscience in pro-environmental behavior change interventions
Authors: Leeuwis Nikki , van Bommel Tom , Alimardani Maryam
Published: September 2022

Most consumers are aware that climate change is a growing problem and admit that action is needed. However, research shows that consumers’ behavior often does not conform to their value and orientations. This value-behavior gap is due to contextual factors such as price, product design, and social norms as well as individual factors such as personal and hedonic values, environmental beliefs, and the workload capacity an individual can handle. Because of this conflict of interest, consumers have a hard time identifying the true drivers of their behavior, as they are either unaware of or unwilling to acknowledge the processes at play. Therefore, consumer neuroscience methods might provide a valuable tool to uncover the implicit measurements of pro-environmental behavior (PEB). Several studies have already defined neurophysiological differences between green and non-green individuals; however, a behavior change intervention must be developed to motivate PEB among consumers. Motivating behavior with reward or punishment will most likely get users engaged in climate change action via brain structures related to the reward system, such as the amygdala, nucleus accumbens, and (pre)frontal cortex, where the reward information and subsequent affective responses are encoded. The intensity of the reward experience can be increased when the consumer is consciously considering the action to achieve it. This makes goal-directed behavior the potential aim of behavior change interventions. This article provides an extensive review of the neuroscientific evidence for consumer attitude, behavior, and decision-making processes in the light of sustainability incentives for behavior change interventions. Based on this review, we aim to unite the current theories and provide future research directions to exploit the power of affective conditioning and neuroscience methods for promoting PEB engagement.
The hunt for hidden hearing loss in humans: From preclinical studies to effective interventions
Authors: Valderrama Joaquin T. , de la Torre Angel , McAlpine David
Published: September 2022

Many individuals experience hearing problems that are hidden under a normal audiogram. This not only impacts on individual sufferers, but also on clinicians who can offer little in the way of support. Animal studies using invasive methodologies have developed solid evidence for a range of pathologies underlying this hidden hearing loss (HHL), including cochlear synaptopathy, auditory nerve demyelination, elevated central gain, and neural mal-adaptation. Despite progress in pre-clinical models, evidence supporting the existence of HHL in humans remains inconclusive, and clinicians lack any non-invasive biomarkers sensitive to HHL, as well as a standardized protocol to manage hearing problems in the absence of elevated hearing thresholds. Here, we review animal models of HHL as well as the ongoing research for tools with which to diagnose and manage hearing difficulties associated with HHL. We also discuss new research opportunities facilitated by recent methodological tools that may overcome a series of barriers that have hampered meaningful progress in diagnosing and treating of HHL.
Resting-state occipito-frontal alpha connectome is linked to differential word learning ability in adult learners
Authors: Huang Yan , Deng Yao , Jiang Xiaoming , Chen Yiyuan , Mao Tianxin , Xu Yong , Jiang Caihong , Rao Hengyi
Published: September 2022

Adult language learners show distinct abilities in acquiring a new language, yet the underlying neural mechanisms remain elusive. Previous studies suggested that resting-state brain connectome may contribute to individual differences in learning ability. Here, we recorded electroencephalography (EEG) in a large cohort of 106 healthy young adults (50 males) and examined the associations between resting-state alpha band (8–12 Hz) connectome and individual learning ability during novel word learning, a key component of new language acquisition. Behavioral data revealed robust individual differences in the performance of the novel word learning task, which correlated with their performance in the language aptitude test. EEG data showed that individual resting-state alpha band coherence between occipital and frontal regions positively correlated with differential word learning performance (p = 0.001). The significant positive correlations between resting-state occipito-frontal alpha connectome and differential world learning ability were replicated in an independent cohort of 35 healthy adults. These findings support the key role of occipito-frontal network in novel word learning and suggest that resting-state EEG connectome may be a reliable marker for individual ability during new language learning.
Cerebellar transcranial current stimulation – An intraindividual comparison of different techniques
Authors: Herzog Rebecca , Berger Till M. , Pauly Martje G. , Xue Honghu , Rueckert Elmar , Münchau Alexander , Bäumer Tobias , Weissbach Anne
Published: September 2022

Transcranial current stimulation (tCS) techniques have been shown to induce cortical plasticity. As an important relay in the motor system, the cerebellum is an interesting target for plasticity induction using tCS, aiming to modulate its excitability and connectivity. However, until now it remains unclear, which is the most effective tCS method for inducing plasticity in the cerebellum. Thus, in this study, the effects of anodal transcranial direct current stimulation (tDCS), 50 Hz transcranial alternating current stimulation (50 Hz tACS), and high frequency transcranial random noise stimulation (tRNS) were compared with sham stimulation in 20 healthy subjects in a within-subject design. tCS was applied targeting the cerebellar lobe VIIIA using neuronavigation. We measured corticospinal excitability, short-interval intracortical inhibition (SICI), short-latency afferent inhibition (SAI), and cerebellar brain inhibition (CBI) and performed a sensor-based movement analysis at baseline and three times after the intervention (post1 = 15 min; post2 = 55 min; post3 = 95 min). Corticospinal excitability increased following cerebellar tACS and tRNS compared to sham stimulation. This effect was most pronounced directly after stimulation but lasted for at least 55 min after tACS. Cortico-cortical and cerebello-cortical conditioning protocols, as well as sensor-based movement analyses, did not change. Our findings suggest that cerebellar 50 Hz tACS is the most effective protocol to change corticospinal excitability.
Purification, structural characterization and immunological activity of Sibiraea laexigata (L.) Maxim polysaccharide
Authors: Yang Xuhua , Liu Honghai , Yang Jutian , Ma Zhongren , Guo Penghui , Chen Hong , Gao Dandan
Published: September 2022

Sibiraea laexigata (L.) Maxim (SLM) has been used as an herbal tea for treating stomach discomfort and indigestion for a long time in china. Polysaccharides have been identified as one of the major bioactive compounds in the SLM. In the present paper, ultrasonic-assisted enzymatic extraction (UAEE) method was employed in polysaccharides extraction derived from SLM using polyethylene glycol (PEG) as extraction solvent, two SLM polysaccharides (SLMPs) fractions (SLMPs-1-1 and SLMPs-2-1) were purified by DEAE Cellulose-52 and Sephadex G-100 chromatography in sequence. Then, the preliminarily structure of the two factions were characterized by chemical composition analysis, molecular weight measurement, UVS, HPLC-PMP, FT-IR, nuclear magnetic resonance (NMR) spectra analysis and SEM. The results showed that SLMPs-1-1 and SLMPs-2-1 with different molecular weights of 1.03 and 1.02 kDa, mainly composed of glucose (46.76 and 46.79%), respectively. The results of structural characterization from FT-IR, 1H NMR, and SEM revealed that SLMPs-1-1 and SLMPs-2-1 contained the typical pyranoid polysaccharide with α-glycosidic bond and β-glycosidic bond. Furthermore, it was found that SLMPs-1-1 could increase the levels of tumor necrosis factor-α (TNF-α) and interleukin-2 (IL-2), and alleviated the immune organs tissue damage of cyclophosphamide (Cy)-treated mice. RT-qPCR and Western-Blot analysis showed that SLMPs-1-1 could significantly up-regulated the levels of NF-κB, TLR4, which revealed that SLMPs-1-1 could participate in immunosuppressive protection of Cy-treated mice. These findings suggested that the potential of SLMPs-1-1 as an alternative immunostimulator could be used in food and pharmaceutical industries.
The antidepressant effects and serum metabonomics of bifid triple viable capsule in a rat model of chronic unpredictable mild stress
Authors: Bu Qinpeng , Zhang Jingkai , Guo Xiang , Feng Yifei , Yan Huan , Cheng Weimin , Feng Zhitao , Cao Meiqun
Published: September 2022

Background

Probiotics have shown potential antidepressant effects. This study evaluated the effect and probable mechanisms of bifid triple viable capsules (BTVCs) on a rat model of chronic unpredictable mild stress (CUMS).

Materials and methods

Rats were randomly divided into Normal, CUMS model, fluoxetine hydrochloride (FLX), BTVCs, and FLX+BTVCs groups. Depressive-like behaviours, pathological changes in the hippocampus, changes in serum metabolites and potential biomarkers, and metabolic pathways were detected via behavioural tests, haematoxylin-eosin staining, nissl staining, non-targetted metabolomics, and ingenuity pathway analysis (IPA).

Results

The rats displayed depressive-like behaviours after CUMS exposure, but BTVCs ameliorated the depressive-like behaviours. In addition, the pathological results showed that the hippocampal tissue was damaged in rats after CUMS exposure and that the damage was effectively alleviated by treatment with BTVCs. A total of 20 potential biomarkers were identified. Treatment with BTVCs regulated D-phenylalanine, methoxyeugenol, (±)-myristoylcarnitine, 18:3 (6Z, 9Z, 12Z) /P-18:1 (11Z), propionyl-L-carnitine, and arachidonic acid (AA) concentrations, all compounds that are involved with biosynthesis of unsaturated fatty acids, glycerophospholipid metabolism, linoleic acid metabolism and AA metabolism. The IPA demonstrated that endothelin-1 signalling and cyclic adenosine monophosphate response element binding protein (CREB) signalling in neurons may be involved in the development of depression.

Conclusion

Our findings suggest that BTVCs can alleviate depressive-like behaviours, restore damage to the hippocampus in CUMS rats and regulate serum metabolism, which may be related to endothelin-1 signalling or CREB signalling in neurons.
Validation of GLIM criteria on malnutrition in older Chinese inpatients
Authors: Ji Tong , Li Yun , Liu Pan , Zhang Yaxin , Song Yu , Ma Lina
Published: September 2022

Objective

Malnutrition is a nutritional disorder and common syndrome that has a high incidence and is easily ignored in hospitalized older patients. It can lead to multiple poor prognoses, such as frailty. Early identification and correct evaluation of possible malnutrition and frailty are essential to improve clinical outcomes in older patients. Therefore, our objective was to explore the applicability and effectiveness of the Global Leadership Initiative on Malnutrition (GLIM) criteria for identifying malnutrition in older patients.

Methods

In total, 223 participants aged ≥60 years were involved. Nutrition was evaluated using the Mini Nutritional Assessment-Full Form (MNA-FF) and GLIM criteria, which adopt a two-step procedure. The first step was to use three different methods for the screening of nutritional risk: the Nutrition Risk Screening 2002, the Mini Nutritional Assessment Short Form (MNA-SF), and the Malnutrition Universal Screening Tool. The second step was to link a combination of at least one phenotypical criterion and one etiological criterion to diagnose malnutrition. The Clinical Frailty Scale was used to assess frailty. Sensitivity, specificity, Youden index, kappa values, and positive and negative predictive values were used to evaluate the validity of the GLIM criteria. Logistic regression models were used to assess whether there was a correlation between malnutrition, as defined by the GLIM criteria, and frailty.

Results

We found that 32.3–49.8% of our patient sample were at risk of malnutrition based on the GLIM diagnosis and using the three different screening tools; 19.3–27.8% of the patients were malnourished. GLIM criteria with MNA-SF as a diagnostic validation and MNA-FF as a reference showed high consistency (K = 0.629; p < 0.001), sensitivity (90.5%), and specificity (86.4%). Logistic regression analysis showed that malnutrition, using MNA-SF with the GLIM criteria, was relevant for a higher likelihood of frailty (OR = 1.887; 95% CI 1.184–2.589).

Conclusions

The incidence of GLIM-defined malnutrition was 19.3–27.8% using different screening tools. The consistency between the GLIM criteria using the MNA-SF and the MNA methods was high. Malnutrition, as diagnosed by the GLIM criteria with MNA-SF, was significantly correlated with frailty. GLIM criteria with MNA-SF may be a more reliable malnutrition assessment process in older inpatients.
Drastic sex-dependent etiological distribution in severe liver diseases from Gabon
Authors: Moussavou-Boundzanga Pamela , Itoudi Bignoumba Patrice Emery  , Mouinga-Ondeme Augustin , Iroungou Berthe Amelie , Bivigou-Mboumba Berthold , Marchio Agnès , Saibou Maryam , Moussavou Kombila Jean-Baptiste  , Pineau Pascal
Published: September 2022

Chronic liver diseases still represent a worrying public health issue in Sub-Saharan Africa. In this region, emphasis is generally made on hepatocellular carcinoma (HCC) albeit liver cirrhosis (LC) is also responsible for an important death toll. Very few studies have compared the presentation and etiologies of cancer and cirrhosis of the liver in Middle Africa. We conducted a comparative retrospective analysis of 74 and 134 cases of patients with HCC and LC treated in Libreville, Gabon. Viral or lifestyle risk factors, clinical symptoms, and biological features were compared. We observed that ages of diagnosis were 53.2 ± 15.7 years and 48.6 ± 18.6 years for HCC and LC with remarkably low M:F sex ratios (1.3–1.8). Ethanol consumption was highly prevalent in both disease types (65.0%–70.0%). Chronic viral infections with hepatitis B (HBV) or C (HCV) virus were also widespread with slight domination of the former in both diseases (43.4% vs. 34.3%, and 35.9% vs. 28.5%). Patients with HCC were presenting very late with a mean diameter of the main nodule of 84 ± 50 mm and a multifocal pattern in 72.7% of cases. HCC developed on a cirrhotic liver in 91.7% of cases. Serum AFP was frankly elevated (>400 ng/ml) in only 35.8% of HCC cases. The most striking feature of the HCC series was the contrasted contribution of distinct pathogenic etiologies involving sex, viral, metabolic, and toxic factors. A frequently dysmetabolic condition synergizing with hepatitis C (anti-HCV, 73.8% vs 22.7%, p < 0.0001) in females and a male cancer promoted by recreational toxicants and chronic hepatitis B (HBsAg, 83.5% vs 35.9%, p < 0.0001) were observed. Men with HCC were considerably younger than women (46.8 ± 14.5 years vs. 62.2 ± 12.2 years, p < 0.0001). Further studies are now warranted to identify routes of HCV transmission and if they are still fueling reservoirs of future patients. Public policies to prevent alcohol-related harm have also to be urgently implemented in Gabon.
A novel immune-related gene signature predicts the prognosis of hepatocellular carcinoma
Authors: He Shujiao , Qiao Jingqiao , Wang Lei , Yu Li
Published: September 2022

Immune-related genes play a key role in regulating the cancer immune microenvironment, influencing the overall survival of patients with hepatocellular carcinoma (HCC). Along with the rapid development of immunotherapy, identifying immune-related genes with prognostic value in HCC has attracted increasing attention. Here, we aimed to develop a prognostic signature based on immune-related genes. By investigating the transcriptome landscape of 374 HCC and 160 non-HCC samples in silico, a total of 2251 differentially expressed genes were identified. Among which, 183 differentially expressed immune-related genes were subjected to a univariate Cox proportional hazard model to screen for genes with possible prognostic significance. A 10-gene prognostic signature, including HLA-G, S100A9, S100A10, DCK, CCL14, NRAS, EPO, IL1RN, GHR and RHOA, was generated employing a multivariate Cox proportional hazard model. Kaplan–Meier and Receiver Operator Characteristic (ROC) curves were used to evaluate the prognostic utility of the 10-gene signature. Moreover, the underlying mechanisms of these genes were analyzed via Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment. According to the Tumor Immune Estimation Resource (TIMER) database, our prognostic signature was significantly associated with tumor-infiltrating B cells, CD4 T cells, dendritic cells, macrophages and neutrophils. Our study provides a novel prognostic signature based on immune-related genes associated with clinical outco mes of HCC.
Analysis of “true extrauterine growth retardation” and related factors in very preterm infants—A multicenter prospective study in China
Authors: Shen Wei , Wu Fan , Mao Jian , Liu Ling , Chang Yan-Mei , Zhang Rong , Zheng Zhi , Ye Xiu-Zhen , Qiu Yin-Ping , Ma Li , Cheng Rui , Wu Hui , Chen Dong-Mei , Chen Ling , Xu Ping , Mei Hua , Wang San-Nan , Xu Fa-Lin , Ju Rong , Chen Chao , Tong Xiao-Mei , Lin Xin-Zhu
Published: September 2022

Objective

To investigate the incidence and related factors of extrauterine growth retardation (EUGR) and “true EUGR” in very preterm infants (VPI) from different regions of China.

Materials and methods

Clinical data of VPI were prospectively collected from 28 hospitals in seven different regions of China from September 2019 to December 2020. The infants were divided into a small for gestational age (SGA) group or non-SGA group at birth, with non-SGA infants at 36 weeks of gestation or at discharge being further divided into a EUGR group or a non-EUGR group. Infants in the EUGR and non-SGA group were defined as “true EUGR.” The general information of VPI, such as maternal complications during pregnancy, use of enteral nutrition and parenteral nutrition, and complications during hospitalization were compared between the groups.

Results

Among the 2,514 VPI included in this study, 47.3, 41.5, and 33.3% of VPI were below the 10th percentile, and 22.6, 22.4, and 16.0% of VPI were below the 3rd percentile for weight, height, and head circumference at 36 weeks of gestation or at discharge, respectively, by the percentile on the 2013 Fenton curve. The incidences of EUGR and “true EUGR” evaluated by weight were 47.3 and 44.5%, respectively. Univariate analysis showed that there were statistically significant differences in the aspects of perinatal and nutritional characteristics, treatment, and complications between the groups. Multivariate analysis showed that in non-SGA infants, the cumulative caloric intake during the first week was a protective factor for “true EUGR,” while days to reach total enteral nutrition, late initiation of human milk fortifier, and moderate to severe bronchopulmonary dysplasia were independent risk factors for “true EUGR.”

Conclusion

More attention should be paid to the nutritional management of VPI to prevent “true EUGR.” Cumulative caloric intake should be ensured and increased during the first week, total enteral nutrition should be achieved as early as possible, human milk fortifier should be added early, and moderate to severe bronchopulmonary dysplasia should be prevented. These strategies are very important for reducing the incidence of “true EUGR” in VPI.
Ameliorative effect of bayberry leaves proanthocyanidins on high sugar diet induced Drosophila melanogaster
Authors: Wang Mengting , Mao Haiguang , Chen Jianchu , Qi Lili , Wang Jinbo
Published: September 2022

Bayberry leaves proanthocyanidins (BLPs) were distributed in natural plant food, considered to have the potential for metabolic syndrome. In this study, we raised Drosophila melanogaster on high sugar diet (HSD) from the egg stage to induce hyperglycemia, and the ameliorative effect of BLPs was assessed based on this model. Phenotypical, biochemical, and molecular analyses related to diabetes mellitus pathogenesis were measured. Flies exposed to BLPs were found to suppress the HSD-induced high glucose and high triglycerides levels. Moreover, BLPs showed an inhibitory effect on carbohydrate digestive enzymes (α-amylase and α-glucosidase) activity and mRNA expression, exhibiting the potential for carbohydrate digestion retardation. Transcriptional levels of key genes associated with glycolipid metabolism were further evaluated, including dilp, InR, and downstream dAKT-dFOXO-PEPCK, together with E78, SREBP, FAS, and LSD genes, were all downregulated after BLPs-exposure, suggesting the ameliorative effect of BLPs on dysbiosis associated with the insulin signaling pathway. This study provided a new functional compound, which is beneficial to further antidiabetic therapy studies.
Regulation of CYP450 and drug transporter mediated by gut microbiota under high-altitude hypoxia
Authors: Bai Xue , Yang Jianxin , Liu Guiqin , Zhu Junbo , Wang Qian , Gu Wenqi , La Linli , Li Xiangyang
Published: September 2022

Hypoxia, an essential feature of high-altitude environments, has a significant effect on drug metabolism. The hypoxia–gut microbiota–CYP450/drug transporter axis is emerging as a vital factor in drug metabolism. However, the mechanisms through which the gut microbiota mediates the regulation of CYP450/drug transporters under high-altitude hypoxia have not been well defined. In this study, we investigated the mechanisms underlying gut microbial changes in response to hypoxia. We compared 16S ribosomal RNA gene sequences of the gut microbiota from plain and hypoxic rats. As a result, we observed an altered gut microbial diversity and composition in rats under hypoxia. Our findings show that dysregulated gut microbiota changes CYP3A1 and MDR1 expressions in high-altitude hypoxic environments. Thus, our study reveals a novel mechanism underlying the functioning of the hypoxia–gut microbiota–CYP450/drug transporter axis.
A bibliometric analysis of autophagy in atherosclerosis from 2012 to 2021
Authors: Zhang Fengwei , Wang Ruirui , Liu Baocheng , Zhang Lei
Published: September 2022

Background: Regulation of autophagy affects the progression of atherosclerosis. In recent years, research on autophagy in atherosclerosis has been widely concerned. However, there is no bibliometric analysis in this field.

Objective: The purpose of this study was to explore the general situation, hot spots, and trends of the research in this field through bibliometric analysis.

Methods: Articles related to autophagy in atherosclerosis from 2012 to 2021 were retrieved from the Web of Science Core Collection. VOSviewer and CiteSpace were used for data analysis and visualization of countries, institutions, authors, keywords, journals, and citations.

Results: A total of 988 articles were obtained in the last 10 years. The number of publications and citations increased rapidly from 2012 to 2021, especially after 2019. The most productive countries, institutions, journals, and authors were the People’s Republic of China, Shandong University, Arteriosclerosis Thrombosis and Vascular Biology, and Wim Martinet, respectively. The primary keywords were “oxidative stress,” “apoptosis,” “activated protein kinase,” and “inflammation.” The burst detection analysis of keywords found that “SIRT1” and “long non-coding RNA” might be regarded as the focus of future research.

Conclusion: This is the first bibliometric analysis of autophagy in atherosclerosis, which reports the hot spots and emerging trends. The interaction between oxidative stress and autophagy, programmed cell death, and activated protein kinases are considered to be the current research priorities. Molecular mechanisms and therapeutic target for the intervention of atherosclerosis by regulating autophagy will become an emerging research direction.
Everolimus pharmacokinetics and exposure-response relationship in Japanese patients with advanced breast cancer
Authors: Hirabatake Masaki , Mizuno Tomoyuki , Kato Hironori , Hashida Tohru
Published: September 2022

Background: Everolimus is one of the key drugs for the treatment of advanced breast cancer. The optimal target concentration range for everolimus therapy in patients with breast cancer has not yet been established. This study aimed to characterize everolimus pharmacokinetics (PK) and determine the relationship between blood concentration and efficacy as well as adverse events in patients with breast cancer.

Methods: This was a prospective, observational PK study. Patients receiving everolimus between November 2015 and November 2018 at our hospital were enrolled in this study. The whole blood samples for the everolimus assay were collected at least two weeks after initiation of treatment or the last everolimus dose change. PK parameters were estimated using Bayesian analysis. Statistical differences in everolimus trough concentrations between patient cohorts were assessed using the Mann–Whitney test. Progression-free survival was assessed using the Kaplan-Meier method and the log-rank test.

Results: Eighteen patients were enrolled in the study. The median follow-up period was 35 months. The most frequently observed adverse event was stomatitis (all grade 94%). There was high inter-individual variation in PK parameters such as clearance [range: 5.1–21.3 L/h/70 kg and co-efficient of variation (CV): 38.5%] and volume of distribution of the central compartment (range: 9.9–103.6 L/70 kg and CV: 57.8%). The trough concentrations at dose-limiting toxicities were significantly higher than trough concentrations in the absence of these toxicities (p = 0.0058). Progression-free survival was significantly longer in the 10–20 ng/ml group than in the other groups (p = 0.0078).

Conclusion: This study characterized the everolimus PK parameters in Japanese patients with breast cancer. High everolimus exposure was found to be associated with poor tolerability. Based on our data, trough concentrations in the range of 10–20 ng/ml may be associated with prolonged progression-free survival. Thus, determining the blood concentration of everolimus and subsequent dose adjustments will potentially reduce side effects and enhance the therapeutic effect in Japanese patients with advanced breast cancer.
Development of Rb fountain clock for time keeping
Authors: Weiliang Chen , Fang Fang , Kun Liu , Fasong Zheng , Shaoyang Dai , Yani Zuo , Tianchu Li
Published: September 2022

A new Rb fountain clock was built at the National Institute of Metrology with the aim to realize robustness and excellent long-term instability for time keeping. While some basic designs have been adopted from our Cs fountain clocks, new features have been included for improved performance. A double-metal interrogation microwave cavity with a thermal expansion self-compensating mechanism was used to reduce the clock sensitivity to temperature fluctuations for the first time, to our knowledge. Moreover, a compact optical system was developed to ensure robustness. These features dramatically increased the ambient temperature range. The developed Rb fountain clock achieved a typical fractional frequency instability of 1.49×10−13(τ/s)−1/2within 10 days of continuous operation without any intervention, demonstrating the potential for time keeping.