bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of inorganic iron and haem on the human gut microbiota; An in vitro batch-culture approach
Authors: Monteagudo-Mera Andrea , Shalunkhe Arvindkumar , Duhduh Amro , Walton Gemma E. , Gibson Glenn R. , Pereira Dora I. , Wijeyesekera Anisha , Andrews Simon C.
Published: February 2023

Although iron is an essential nutrient for humans, as well as for almost all other organisms, it is poorly absorbed (~15%) from the diet such that most passes through the upper gut into the large intestine. The colonic microbiota is thus exposed to, and potentially influenced by, such residual iron which could have an impact on human health. The aim of the research described here is to determine how the major forms of dietary iron (inorganic iron and haem) influence metabolic activity and composition of the human gut microbiota by utilizing an in vitro parallel, pH-controlled anaerobic batch culture approach. Controlled iron provision was enabled by the design of a ‘modified’ low-iron gut-model medium whereby background iron content was reduced from 28 to 5 μM. Thus, the impact of both low and high levels of inorganic and haem iron (18–180 μM and 7.7–77 μM, respectively) could be explored. Gut-microbiota composition was determined using next generation sequencing (NGS) based community profiling (16S rRNA gene sequencing) and flow-fluorescent in situ hybridization (FISH). Metabolic-end products (organic acids) were quantified using gas chromatography (GC) and iron incorporation was estimated by inductively coupled plasma optical emission spectroscopy (ICP-OES). Results showed that differences in iron regime induced significant changes in microbiota composition when low (0.1% w/v) fecal inoculation levels were employed. An increase in haem levels from 7.7 to 77 μM (standard levels employed in gut culture studies) resulted in reduced microbial diversity, a significant increase in Enterobacteriaceae and lower short chain fatty acid (SCFA) production. These effects were countered when 18 μM inorganic iron was also included into the growth medium. The results therefore suggest that high-dietary haem may have a detrimental effect on health since the resulting changes in microbiota composition and SCFA production are indicators of an unhealthy gut. The results also demonstrate that employing a low inoculum together with a low-iron gut-model medium facilitated in vitro investigation of the relationship between iron and the gut microbiota.
Survey of mosquito species and mosquito-borne viruses in residential areas along the Sino–Vietnam border in Yunnan Province in China
Authors: Tian Fengjuan , He Jimin , Shang Shanlin , Chen Zhongyan , Tang Yumei , Lu Man , Huang Changzhi , Guo Xiaofang , Tong Yigang
Published: February 2023

Mosquitoes are capable of carrying complex pathogens, and their feeding habits on the mammalian blood can easily mediate the spread of viruses. Surveillance of mosquito-based arbovirus enables the early prevention and control of mosquito-borne arboviral diseases. The climate and geography of Yunnan Province in China are ideal for mosquitoes. Yunnan shares borders with several other countries; therefore, there exists a high risk of international transmission of mosquito-mediated infectious diseases. Previous studies have focused more on the Sino–Laos and Sino–Myanmar borders. Therefore, we focused on the neighborhoods of Malipo and Funing counties in Wenshan Prefecture, Yunnan Province, China, which are located along the Sino–Vietnam border, to investigate the species of mosquitoes and mosquito-borne viruses in the residential areas of this region. This study collected 10,800 mosquitoes from 29 species of 8 genera and grouped to isolate mosquito-borne viruses. In total, 62 isolates were isolated and classified into 11 viral categories. We demonstrated a new distribution of mosquito-borne viruses among mosquitoes in border areas, including Tembusu and Getah viruses, which can cause animal outbreaks. In addition, Dak Nong and Sarawak viruses originating from Vietnam and Malaysia, respectively, were identified for the first time in China, highlighting the complexity of mosquito-borne viruses in the Sino–Vietnam border region. The awareness of the importance of viral surveillance and prevention measures in border areas should be further encouraged to prevent future outbreaks of potentially infectious diseases.
Effect of fertilization combination on cucumber quality and soil microbial community
Authors: Wang Mei , Xu Yu , Ni Haiping , Ren Shiai , Li Ni , Wu Yuxia , Yang Yan , Liu Yumin , Liu Zongzheng , Liu Yingchun , Shi Jing , Zhang Youming , Jiang Lihua , Tu Qiang
Published: February 2023

Due to the lack of scientific guidance on the usage of fertilizer, the overuse of chemical and organic fertilizer is commonly witnessed all over the world, which causes soil degradation and leads to environmental pollution. The effect of fertilizer strategies on soil properties, cucumber nutrients, and microbial community was investigated in this study with the aim to explore an optimized and enhanced fertilizer strategy. There were five fertilizer strategies conducted including CK (no fertilizer), M (cow dung manure only), NPK (chemical fertilizer only), NPKM (chemical fertilizer combined with manure), and DNPKM (30%-reducing chemical fertilizer combined with manure). It was found that different fertilizer strategies significantly affected the soil organic matter and nutrient levels and cucumber production and nutrient contents of the experimental field. Different fertilizer strategies showed dramatic effects on the alpha- and beta-diversity of soil microbial communities. Moreover, NPKM and DNPKM groups could significantly improve the bacterial abundance and fungal diversity. In addition, the structure of microbial communities was significantly changed in the presence of manure, chemical fertilizer, and their combination. Optimized combination of NPK with M improved the abundance of aerobic, biofilm formation-related, and Gram-negative bacteria and suppressed the anaerobic and Gram-positive bacteria. The presence of saprotrophs fungi was enhanced by all fertilizer strategies, especially the plethora of Gymnoascus. The combination of manure with chemical fertilizer could improve the availability of nutrients, and therefore reduce the adverse effects and potential risks induced by excessive fertilizer application. In conclusion, the new fertilization approach can not only meet the growth requirements of cucumber after reduced fertilization, but also protect soil health, which provides a new candidate for the eco-friendly technology to satisfy the topic of carbon neutrality.
Ethyl lauroyl arginate: An update on the antimicrobial potential and application in the food systems: a review
Authors: Ma Yunfang , Ma Yanqing , Chi Lei , Wang Shaodan , Zhang Dianhe , Xiang Qisen
Published: February 2023

Ethyl lauroyl arginate (ELA), a cationic surfactant with low toxicity, displays excellent antimicrobial activity against a broad range of microorganisms. ELA has been approved as generally recognized as safe (GRAS) for widespread application in certain foods at a maximum concentration of 200 ppm. In this context, extensive research has been carried out on the application of ELA in food preservation for improving the microbiological safety and quality characteristics of various food products. This study aims to present a general review of recent research progress on the antimicrobial efficacy of ELA and its application in the food industry. It covers the physicochemical properties, antimicrobial efficacy of ELA, and the underlying mechanism of its action. This review also summarizes the application of ELA in various foods products as well as its influence on the nutritional and sensory properties of such foods. Additionally, the main factors influencing the antimicrobial efficacy of ELA are reviewed in this work, and combination strategies are provided to enhance the antimicrobial potency of ELA. Finally, the concluding remarks and possible recommendations for the future research are also presented in this review. In summary, ELA has the great potential application in the food industry. Overall, the present review intends to improve the application of ELA in food preservation.
Transcriptome analysis of Ganoderma lingzhi (Agaricomycetes) response to Trichoderma hengshanicum infection
Authors: Wang Tiantian , Li Xiaobin , Zhang Chunlan , Xu Jize
Published: February 2023

Green mold caused by Trichoderma spp. has become one of the most serious diseases which threatening the production of Ganoderma lingzhi. To understand the possible resistance mechanism of the G. lingzhi response to T. hengshanicum infection, we examined the G. lingzhi transcript accumulation at 0, 12, and 24 h after T. hengshanicum inoculation. The gene expression analysis was conducted on the interaction between G. lingzhi and T. hengshanicum using RNA-seq and digital gene expression (DGE) profiling methods. Transcriptome sequencing indicated that there were 162 differentially expressed genes (DEGs) at three infection time points, containing 15 up-regulated DEGs and 147 down-regulated DEGs. Resistance-related genes thaumatin-like proteins (TLPs) (PR-5s), phenylalanine ammonia-lyase, and Beta-1,3-glucan binding protein were significantly up-regulated. At the three time points of infection, the heat shock proteins (HSPs) genes of G. lingzhi were down-regulated. The down-regulation of HSPs genes led to the inhibition of HSP function, which may compromise the HSP-mediated defense signaling transduction pathway, leading to G. lingzhi susceptibility. Pathway enrichment analyses showed that the main enriched pathways by G. lingzhi after infection were sphingolipid metabolism, ether lipid metabolism, and valine, leucine and isoleucine degradation pathway. Overall, the results described here improve fundamental knowledge of molecular responses to G. lingzhi defense and contribute to the design of strategies against Trichoderma spp.
Binding of RPR260243 at the intracellular side of the hERG1 channel pore domain slows closure of the helix bundle crossing gate
Authors: Zangerl-Plessl Eva-Maria , Wu Wei , Sanguinetti Michael C. , Stary-Weinzinger Anna
Published: February 2023

The opening and closing of voltage-dependent potassium channels is dependent on a tight coupling between movement of the voltage sensing S4 segments and the activation gate. A specific interaction between intracellular amino- and carboxyl-termini is required for the characteristically slow rate of channel closure (deactivation) of hERG1 channels. Compounds that increase hERG1 channel currents represent a novel approach for prevention of arrhythmia associated with prolonged ventricular repolarization. RPR260243 (RPR), a quinoline oxo-propyl piperidine derivative, inhibits inactivation and dramatically slows the rate of hERG1 channel deactivation. Here we report that similar to its effect on wild-type channels, RPR greatly slows the deactivation rate of hERG1 channels missing their amino-termini, or of split channels lacking a covalent link between the voltage sensor domain and the pore domain. By contrast, RPR did not slow deactivation of C-terminal truncated hERG1 channels or D540K hERG1 mutant channels activated by hyperpolarization. Together, these findings indicate that ability of RPR to slow deactivation requires an intact C-terminus, does not slow deactivation by stabilizing an interaction involving the amino-terminus or require a covalent link between the voltage sensor and pore domains. All-atom molecular dynamics simulations using the cryo-EM structure of the hERG1 channel revealed that RPR binds to a pocket located at the intracellular ends of helices S5 and S6 of a single subunit. The slowing of channel deactivation by RPR may be mediated by disruption of normal S5-S6 interactions.
Sex differences in amygdalohippocampal oscillations and neuronal activation in a rodent anxiety model and in response to infralimbic deep brain stimulation
Authors: Vila-Merkle Hanna , González-Martínez Alicia , Campos-Jiménez Rut , Martínez-Ricós Joana , Teruel-Martí Vicent , Lloret Ana , Blasco-Serra Arantxa , Cervera-Ferri Ana
Published: February 2023

Introduction

Depression and anxiety are highly comorbid mental disorders with marked sex differences. Both disorders show altered activity in the amygdala, hippocampus, and prefrontal cortex. Infralimbic deep brain stimulation (DBS-IL) has anxiolytic and antidepressant effects, but the underlying mechanisms remain unclear. We aimed to contribute to understanding sex differences in the neurobiology of these disorders.

Methods

In male and female rats, we recorded neural oscillations along the dorsoventral axis of the hippocampus and the amygdala in response to an anxiogenic drug, FG-7142. Following this, we applied DBS-IL.

Results

Surprisingly, in females, the anxiogenic drug failed to induce most of the changes observed in males. We found sex differences in slow, delta, theta, and beta oscillations, and the amygdalo-hippocampal communication in response to FG-7142, with modest changes in females. Females had a more prominent basal gamma, and the drug altered this band only in males. We also analyzed c-Fos expression in both sexes in stress-related structures in response to FG-7142, DBS-IL, and combined interventions. With the anxiogenic drug, females showed reduced expression in the nucleus incertus, amygdala, septohippocampal network, and neocortical levels. In both experiments, the DBS-IL reversed FG-7142-induced effects, with a more substantial effect in males than females.

Discussion

Here, we show a reduced response in female rats which contrasts with the higher prevalence of anxiety in women but is consistent with other studies in rodents. Our results open compelling questions about sex differences in the neurobiology of anxiety and depression and their study in animal models.
The reasons for not returning to work and health-related quality of life among young and middle-aged patients with stroke: A cross-sectional study
Authors: Pan Xi , Wang Zhi , Yao Lin , Xu Lan
Published: February 2023

Objectives

This study aimed to explore the reasons and influencing factors for non-return to work (non-RTW) within 1 year among young and middle-aged patients with stroke and to assess their health-related quality of life (HRQoL) at 1 year across different reasons.

Methods

The study was conducted as a telephone-based cross-sectional survey. Seven hundred eighty-nine young and middle-aged patients with stroke aged between 18 and 54 years for men and 18 and 49 years for women in the electronic medical system were included. Data collection included demographic characteristics, socioeconomic status, behavioral habits, history of chronic diseases, work status, reasons for non-RTW, and HRQoL.

Results

Of 789 patients, 435 (55.1%) (mean [SD] age, 47.7 [7.8] years) did not return to work within 1 year after stroke. Among the patients who did not RTW, 58.9% were unable to work, 9.7% retired early, 11.03% became full-time homemakers or were unemployed, and 20.5% were reluctant to work. The disordered multiclass logistic regression model showed that the factors influencing the reasons for non-RTW included age, gender, education, income, health insurance, diabetes comorbidity, ability to perform activities of daily living, and mobility of the right upper extremity. Furthermore, patients who were unable to work had significantly lower HRQoL compared to those who had RTW, followed by those who retired early.

Conclusions

More than half did not RTW within 1 year in our study. The results will help inform future research to identify interventions to promote RTW and improve HRQoL for young and middle-aged patients with stroke.
Rodent behavior following a dural inflammation model with anti-CGRP migraine medication treatment
Authors: Reducha Philip V. , Bömers Jesper P. , Edvinsson Lars , Haanes Kristian A.
Published: February 2023

Background

Migraine is a widespread and prevalent disease with a complex pathophysiology, of which neuroinflammation and increased pain sensitivity have been suggested to be involved. Various studies have investigated the presence of different inflammatory markers in migraineurs and investigated the role of inflammation in inflammatory models with complete Freund's adjuvant (CFA) or inflammatory soup added to the dura mater.

Objective

The aim of the current study was to examine whether application of CFA to the dura mater would cause behavioral alterations that are migraine relevant. In addition, we investigated the potential mitigating effects of fremanezumab, a CGRP (calcitonin gene-related peptide) specific antibody, following CFA application.

Methods

Male Sprague-Dawley rats were randomly divided into six groups: fresh (n = 7), fresh + carprofen (n = 6), fresh + anti-CGRP (n = 6), sham (n = 7), CFA (n = 16), CFA + anti-CGRP (n = 8). CFA was applied for 15 min on a 3 × 3 mm clearing of the skull exposing the dura mater of male Sprague-Dawley rats. We applied the Light/Dark box and Open Field test, combined with the electronic von Frey test to evaluate outcomes. Finally, we observed CGRP immunoreactivity in the trigeminal ganglion.

Results

No differences were observed in the Light/Dark box test. The Open Field test detected behavior differences, notably that sham rats spend less time in the central zone, reared less and groomed more than fresh + carprofen rats. The other groups were not significantly different compared to sham rats, indicating that activation of the TGVS is present in sham surgery and cannot be exacerbated by CFA. However, for the allodynia, we observed specific periorbital sensitization, not observed in the sham animals. This could not be mitigated by fremanezumab, although it clearly reduced the amount of CGRP positive fibers.

Conclusion

CFA surgically administered to the dura causes periorbital allodynia and increases CGRP positive fibers in the trigeminal ganglion. Fremanezumab does not reduce periorbital allodynia even though it reduces CGRP positive fibers in the TG. Further work is needed to investigate whether CFA administered to the dura could be used as a non-CGRP inflammatory migraine model.
Circadian rhythm in restless legs syndrome
Authors: Tang Mingyang , Sun Qingqing , Zhang Yanan , Li Huimin , Wang Dong , Wang Ying , Wang Zan
Published: February 2023

Restless legs syndrome (RLS) is a sensorimotor disorder with a obvious circadian rhythm, as its symptoms often occur or worsen only in the evening or at night. The mechanisms behind the rhythms of RLS have not yet been fully elucidated. This review explores possible causes for the circadian fluctuations of the symptomatology, including the levels of iron, dopamine, melatonin, melanocortin, and thyroid-stimulating hormone in the brain, as well as conditions such as peripheral hypoxia and microvascular function disorders. The metabolic disturbances of the substances above can create a pathological imbalance, which is further aggravated by physiological fluctuations of circadian rhythms, and results in the worsening of RLS symptoms at night. The review concludes with the suggestions for RLS treatment and research directions in the future.
Diagnosis, differential diagnosis, and treatment for sudden sensorineural hearing loss: Current otolaryngology practices in China
Authors: Chen Nishan , Karpeta Niki , Ma Xin , Ning Xianhui , Liu Xiaoling , Song Jijun , Jiang Zigang , Ma Xiulan , Liu Xiuli , Zhong Shixun , Sun Qing , Liu Jun , Chen Ganggang , Duan Maoli , Yu Lisheng
Published: February 2023

Introduction

Although sudden sensorineural hearing loss (SSNHL) has been attempted to be understood for 70 years, diagnosis and treatment strategies still have strong heterogeneity worldwide, which are reflected in the guidelines issued by countries and the clinical practice of otolaryngologists.

Methods

Questionnaires were sent to registered otolaryngologists nationwide via an online questionnaire system. We investigated the current views and clinical practices of otolaryngologists in mainland China about the diagnosis, examination, and treatment strategies of SSNHL.

Results

Most otolaryngologists supported diagnostic classification via audiograms. Regional economic situation and hospital grade affected application strategies for differential diagnosis. Regarding corticosteroid therapy, 54.9% of respondents opted to discontinue the drug 5 days after systemic administration. Both intratympanic therapy and post-auricular injections were selected by more than half of the respondents as initial and salvage treatments.

Discussion

Chinese otolaryngologists exhibit heterogeneity in clinical practices for SSNHL, including distinct approaches to combination therapy and local application of steroids. This study pointed out Chinese doctors' similarities, differences, and unique strategies in diagnosing and treating SSNHL and analyzed the possible reasons to help the world understand the current otolaryngology practices in China.
Assessing vestibular function using electroencephalogram rhythms evoked during the caloric test
Authors: Han Yutong , Bai Yanru , Liu Qiang , Zhao Yuncheng , Chen Taisheng , Wang Wei , Ni Guangjian
Published: February 2023

Introduction

The vestibular system is responsible for motion perception and balance preservation in the body. The vestibular function examination is useful for determining the cause of associated symptoms, diagnosis, and therapy of the patients. The associated cerebral cortex processes and integrates information and is the ultimate perceptual site for vestibular-related symptoms. In recent clinical examinations, less consideration has been given to the cortex associated with the vestibular system. As a result, it is crucial to increase focus on the expression of the cortical level while evaluating vestibular function. From the viewpoint of neuroelectrophysiology, electroencephalograms (EEG) can enhance the assessments of vestibular function at the cortex level.

Methods

This study recorded nystagmus and EEG data throughout the caloric test. Four phases were considered according to the vestibular activation status: before activation, activation, fixation suppression, and recovery. In different phases, the distribution and changes of the relative power of the EEG rhythms (delta, theta, alpha, and beta) were analyzed, and the correlation between EEG characteristics and nystagmus was also investigated.

Results

The results showed that, when the vestibule was activated, the alpha power of the occipital region increased, and the beta power of the central and top regions and the occipital region on the left decreased. The changes in the alpha and beta rhythms significantly correlate with nystagmus values in left warm stimulation.

Discussion

Our findings offer a fresh perspective on cortical electrophysiology for the assessment of vestibular function by demonstrating that the relative power change in EEG rhythms can be used to assess vestibular function.
Prognostic models for survival and consciousness in patients with primary brainstem hemorrhage
Authors: Zhou Jingyi , Wang Rui , Mao Jizhong , Gu Yichen , Shao Anwen , Liu Fengqiang , Zhang Jianmin
Published: February 2023

Objectives

Primary brainstem hemorrhage (PBSH) is one of the most catastrophic spontaneous intracerebral hemorrhage diseases, with a mortality rate of 70–80%. We explored the predictive factors for survival and consciousness in patients with PBSH (ClinicalTrials.gov ID: NCT04910490).

Methods

We retrospectively reviewed 211 patients with PBSH admitted to our institution between January 2014 and October 2020. Clinical outcomes included the 30-day survival rate and the 90-day consciousness rate as evaluated by the National Institutes of Health Stroke Scale score. Multiple logistic regression analysis was performed.

Results

The overall 30-day survival rate of 211 patients with PBSH was 70%. Several predictive factors including hematoma volume, hematoma location, activated partial thromboplastin time (APTT) upon admission, and therapeutic strategy were significantly related to 30-day survival. Compared with conservative treatment, stereotactic aspiration in our prediction model is strongly associated with improved 30-day survival (odds ratio, 6.67; 95% confidence interval, 3.13–14.29; P < 0.001). The prognosis prediction model of 90-day consciousness including factors such as mydriasis, APTT value, hematoma location, and hematoma volume upon admission has a good predictive effect (AUC, 0.835; 95% confidence interval, 0.78–0.89; P < 0.001).

Conclusion

In patients with PBSH, conscious state upon admission, coagulation function, hematoma volume, hematoma location, and therapeutic strategy were significantly associated with prognosis. Stereotactic aspiration could significantly reduce the 30-day mortality rate.
Thunderclap headache revealing dural tears with symptomatic intracranial hypotension: Report of two cases
Authors: Antonescu-Ghelmez Dana , Butnariu Ioana , Antonescu Florian , Maier Cristina , Moraru Adriana , Bucur Amanda Ioana , Anghel Daniela Nicoleta , Tuţă Sorin
Published: February 2023

Cerebrospinal fluid (CSF) leakage is considered the cause of spontaneous intracranial hypotension (SIH), an important etiology for new daily persistent headaches and a potentially life-threatening condition. Minor traumatic events rarely lead to CSF leakage, contrasting with iatrogenic interventions such as a lumbar puncture or spinal surgery, which are commonly complicated by dural tears. Most meningeal lesions are found in the cervicothoracic region, followed by the thoracic region, and rarely in the lumbar region, and extremely rarely in the sacral region. We describe two patients admitted to our hospital for severe headaches aggravated in the orthostatic position, with a recent history of minor trauma and sustained physical effort, respectively. In the first case, a bone fragment pierced an incidental congenital meningocele creating a dural fistula. An extensive extradural CSF collection, spanning the cervicothoracic region (C4–T10), was described in the second case. In both patients, the clinical evolution was favorable under conservative treatment.
Sudden unexpected death in epilepsy: A bibliometric overview
Authors: Tong Fang , Lin Jian , Zeng Zixuan , Wang Qi , Yang Zhifang , Lv Yehui
Published: February 2023

The mechanism of sudden unexpected death in epilepsy (SUDEP) is elusive and many questions remain unanswered. Autopsy is generally unhelpful in providing evidence for the cause of death, as pathological changes may be on the molecular level. Although histopathological examination occasionally demonstrates pathology such as vascular malformation, old traumatic injury, and tumor, in most cases of SUDEP, the examination is negative. We examined the current status of SUDEP research by performing a bibliometric analysis of studies in the Web of Science Core Collection database published between 2002 and 2022. Our aim was to demonstrate areas of interest and frontiers of SUDEP research. A total of 1803 papers were included in the analysis. The number of published papers focused on SUDEP has been increasing since 2002. Main areas of interest include clinical manifestations, prevalence, treatment, and underlying mechanisms. Research teams from the United States and Europe are leading the way in SUDEP research, while Asia trails behind. Future studies regarding the mechanism and neuropathology of SUDEP are warranted.
Endocytosis is required for consolidation of pattern-separated memories in the perirhinal cortex
Authors: Piromalli Girado Dinka , Miranda Magdalena , Giachero Marcelo , Weisstaub Noelia , Bekinschtein Pedro
Published: February 2023

Introduction

The ability to separate similar experiences into differentiated representations is proposed to be based on a computational process called pattern separation, and it is one of the key characteristics of episodic memory. Although pattern separation has been mainly studied in the dentate gyrus of the hippocampus, this cognitive function if thought to take place also in other regions of the brain. The perirhinal cortex is important for the acquisition and storage of object memories, and in particular for object memory differentiation. The present study was devoted to investigating the importance of the cellular mechanism of endocytosis for object memory differentiation in the perirhinal cortex and its association with brain-derived neurotrophic factor, which was previously shown to be critical for the pattern separation mechanism in this structure.

Methods

We used a modified version of the object recognition memory task and intracerebral delivery of a peptide (Tat-P4) into the perirhinal cortex to block endocytosis.

Results

We found that endocytosis is necessary for pattern separation in the perirhinal cortex. We also provide evidence from a molecular disconnection experiment that BDNF and endocytosis-related mechanisms interact for memory discrimination in both male and female rats.

Discussion

Our experiments suggest that BDNF and endocytosis are essential for consolidation of separate object memories and a part of a time-restricted, protein synthesis-dependent mechanism of memory stabilization in Prh during storage of object representations.
A bibliometric and visual analysis of low carbohydrate diet
Authors: Lu Gang , Huang Xin , Lin Chun , Zou Lijuan , Pan Huashan
Published: February 2023

Introduction

Numerous studies have confirmed the effects of low carbohydrate diet (LChD) on metabolism and chronic diseases. However, there were no bibliometric studies on LChD. This study was conducted through a bibliometric analysis to investigate the current status, hotspots and frontiers trends.

Methods

We searched all research publications related to LChD from 2002 to 2021 on the Web of Scientific Core Collection (WoSCC). CiteSpace and VOSviewer software was used to analyze countries/regions, institutions, journals, authors, references, and keywords.

Results

A total of 6938 papers were included, with an increasing trend of annual publication. LChD categories mainly included nutrition, endocrinology, and neurosciences which reflected the interdisciplinary characteristics. USA was with the largest number and the world science center in LChD field. Universities were main research institutions and five of the top 10 institutions were from USA. Eric Heath Kossoff had 101 publications and ranked first. Nutrients was the leading journal. “A randomized trial of a low-carbohydrate diet for obesity” and “Obesity” were considered to be the most co-cited and cited reference respectively. The hotspots of LChD are four aspects, “ketogenic diet”, “metabolism disease”, “cardiovascular disease” and “cancer”. We summarized that “oxidative stress”, “gut microbiota”, and “inflammation factors” are becoming frontiers trends of LChD research in the future and deserve further study.

Discussion

Over the past 20 years research on LChD has gained great attention. To better explore LChD field, multilevel mechanism studies will be required in the future.
Effect of vitamin K2 in the treatment of nocturnal leg cramps in the older population: Study protocol of a randomized, double-blind, controlled trial
Authors: Li Ying , Zhu Rui , Wang Li , Tan Jing
Published: February 2023

Introduction

Nocturnal leg cramps (NLCs) are sudden contractions of the leg muscles, usually in the posterior calf muscles at night, affecting sleep quality. Because the precise pathophysiology of NCLs is unclear, different interventions have been proposed. There is conflicting evidence regarding the efficacy of conventional interventions in preventing cramps. Thus, the present study aims to investigate the effects of vitamin K2 for NLCs in a prospective randomized, double-blind, controlled trial.

Methods and analysis

This multicenter, randomized, double-blind, placebo-controlled clinical study will enroll older age (≥65-year-old) with two or more documented episodes of NLCs during 2 weeks of screening. Participants will be randomized to receive vitamin K2 or a similar-looking placebo for 8 weeks in a 1:1 ratio. Follow-up visits will be scheduled each week at the beginning of 4-week intervention, then participants will be visited semimonthly. The primary outcome is the difference in the mean number of NLCs per week in the vitamin K2 and placebo arms. The secondary outcomes include the severity and duration of NLCs in the vitamin K2 and placebo arms. Two hundred patients will be needed, for this two-treatment parallel design study, to achieve a probability is 90% that the study will detect a treatment difference at a two-sided 0.04 significance level, if the difference between treatments is 3.6 (difference in means between treatment arms) NLC events.

Discussion

Nocturnal Leg Cramps (NLCs) are a common musculoskeletal disorder in the general population, but effective and safe interventions have not been established. Our previous study has shown vitamin K2 was effective to reduce the frequency, severity, and duration of dialysis-related muscle cramps with a good safety profile. This randomized controlled trial (RCT) of rigorous methodological design will help to establish the effectiveness of vitamin K2 for the management of NLCs in older population. The findings of this RCT will encourage the studies of vitamin K2 in musculoskeletal disorders.

Clinical Trial Registration

www.ClinicalTrials.gov, identifier, NCT05547750.
Geriatric assessment for older patients with breast cancer: A single-institution study
Authors: Lin Yan , Xu Ying , Wang Changjun , Song Yu , Xu Yali , Zhang Xiaohui , Huang Xin , Sun Qiang
Published: February 2023

Introduction

Although geriatric assessment (GA) has been used for a long time in the field of geriatrics and internal medicine, there are few studies on its application in the field of breast surgery. Therefore, the utility of specific GA domains for the assessment of older patients with breast cancer remains unclear. The aim of the present study was to evaluate the association between specific GA domains and the survival rate of older patients with breast cancer.

Methods

We used the database of Peking Union Medical College Hospital to identify older patients who were newly diagnosed with breast cancer between 2012 and 2018 and retrospectively analysed the data of 541 patients aged ≥65 years. Patients with metastatic cancer and those with missing vital status data were excluded. The primary outcomes were overall survival (OS) and breast cancer-specific survival. The GA domains used in this study included functional status, comorbidities, and psychological state. Multivariate regression analysis was used to estimate hazard ratios for these three domains.

Results

After a median follow-up of 72 months, we observed a significant relationship between functional impairment and mortality (adjusted HR: 3.06, 95% confidence interval [CI]: 1.83-5.10, P<0.001). Similarly, patients with severe comorbidities (adjusted HR: 2.35; 95% CI: 1.16-4.75, P=0.017) and an impaired psychological state (adjusted HR: 2.82, 95% CI: 1.45-5.50, P=0.002) showed worse OS rates. Accordingly, addition of the three GA domains to the basic model, which included age, tumour stage, lymph node stage, and intrinsic molecular subtype as baseline variables, yielded higher C‐statistics for mortality analysis (from 0.713 to 0.740).

Conclusion

To our knowledge, this is the first study to include specific GA domains in a prognostic model for older patients with breast cancer in China. Three domains, namely functional status, comorbidities, and psychological state, should be considered for survival analyses in this particular population. The full model including these three GA domains may be more accurate in predicting the survival of older patients with breast cancer.
Benefits of switching from intravenous to subcutaneous daratumumab: Perspectives from UK healthcare providers
Authors: Cook Gordon , Ashcroft John , Fernandez Mariana , Henshaw Sarah , Khalaf Zeyad , Pratt Guy , Tailor Anish , Rabin Neil
Published: February 2023

Daratumumab is a CD38-directed monoclonal antibody indicated to treat multiple myeloma (MM). Daratumumab was initially administered intravenously (IV), subsequently a subcutaneous (SC) formulation was developed to increase convenience of administration. The UK was an early adopter of SC daratumumab and, as such, this report provides consensus recommendations from a group of UK MM experts, with the aim of facilitating the transition from IV to SC daratumumab for other European healthcare providers. The switch from IV to SC daratumumab has been beneficial to patients and healthcare providers, as it simplifies treatment, reduces pressure on hospitals and can improve patients’ quality of life.
Macrophage – tumor cell interaction beyond cytokines
Authors: Kovaleva Olga , Sorokin Maxim , Egorova Anastasija , Petrenko Anatoly , Shelekhova Ksenya , Gratchev Alexei
Published: February 2023

Tumor cells communication with tumor associated macrophages is a highly important factor of tumor malignant potential development. For a long time, studies of this interaction were focused on a cytokine- and other soluble factors -mediated processes. Discovery of exosomes and regulatory RNAs as their cargo opened a broad field of research. Non-coding RNAs (ncRNAs) were demonstrated to contribute significantly to the development of macrophage phenotype, not only by regulating expression of certain genes, but also by providing for feedback loops of macrophage activation. Being a usual cargo of macrophage- or tumor cell-derived exosomes ncRNAs provide an important mechanism of tumor-stromal cell interaction that contributes significantly to the pathogenesis of various types of tumors. Despite the volume of ongoing research there are still many gaps that must be filled before the practical use of ncRNAs will be possible. In this review we discuss the role of regulatory RNAs in the development of macrophage phenotype. Further we review recent studies supporting the hypothesis that macrophages may affect the properties of tumor cells and vice versa tumor cells influence macrophage phenotype by miRNA and lncRNA transported between these cells by exosomes. We suggest that this mechanism of tumor cell – macrophage interaction is highly promising for the development of novel diagnostic and therapeutic strategies, though many problems are still to be solved.
A retrospective case-series of influence of chronic hepatitis B on synchronous liver metastasis of colorectal cancer
Authors: Zhu Lin , Gong Piqing , Liu Ye , Shi Yunjie , Wang Wenqiang , Zhang Wei , Hu Zhiqian , Li Xinxing
Published: February 2023

Main point

Our retrospective analysis of a large number of cases found in patients with primary colorectal cancer (CRC) carrying positive HBsAg inhibited the occurrence of synchronous liver metastases (SLM). However, liver cirrhosis caused by non-HBV factors promoted the occurrence of SLM.

Objectives

This study aimed to investigate the effect of HBV on the occurrence of synchronous liver metastases (SLM) of colorectal cancer (CRC).

Methods

Univariate and multivariate analyses were used to analyze the influence of clinical parameters on the occurrence of SLM.

Results

A total of 6, 020 patients with primary CRC were included in our study, of which 449 patients carrying HBsAg(+) accounted for 7.46%. 44 cases of SLM occurred in the HBsAg(+) group, accounting for 9.80%, which was much lower than 13.6% (758/5571) in the HBsAg(-) group (X=5.214, P=0.022). Among CRC patients with HBsAg(-), the incidence of SLM was 24.9% and 14.9% in the group with high APRI and FIB-4 levels, respectively, which were significantly higher than that in the compared groups (12.3% and 12.5%, all P<0.05). Compared with the control group, female patients, late-onset patients, and HBV-infective patients had lower risks of SLM (HR=0.737, 95%CI: 0.614-0.883, P<0.001; HR=0.752, 95%CI: 0.603-0.943, P=0.013; HR=0.682, 95%CI: 0.473-0.961, P=0.034).

Conclusions

The carriage of HBsAg(+) status inhibited the occurrence of SLM from CRC. HBV-causing liver cirrhosis did not further influence the occurrence of SLM, whereas non-HBV-factor cirrhosis promoted the occurrence of SLM. Nevertheless, this still required prospective data validation.
The role of targeted therapy and immune therapy in the management of non-small cell lung cancer brain metastases
Authors: Billena Cole , Lobbous Mina , Cordova Christine A. , Peereboom David , Torres-Trejo Alejandro , Chan Timothy , Murphy Erin , Chao Samuel T. , Suh John , Yu Jennifer S.
Published: February 2023

Brain metastases are a significant source of morbidity and mortality in patients with non-small cell lung cancer. Historically, surgery and radiation therapy have been essential to maintaining disease control within the central nervous system due to poorly penetrant conventional chemotherapy. With the advent of targeted therapy against actionable driver mutations, there is potential to control limited and asymptomatic intracranial disease and delay local therapy until progression. In this review paper, intracranial response rates and clinical outcomes to biological and immune therapies are summarized from the literature and appraised to assist clinical decision making and identify areas for further research. Future clinical trials ought to prioritize patient-centered quality of life and neurocognitive measures as major outcomes and specifically stratify patients based on mutational marker status, disease burden, and symptom acuity.
Targeted therapy for intractable cancer on the basis of molecular profiles: An open-label, phase II basket trial (Long March Pathway)
Authors: Jiao Xiao-Dong , Qin Bao-Dong , Wang Zhan , Liu Ke , Wu Ying , Ling Yan , Qin Wen-Xing , Wang Miao-Miao , Yuan Ling-Yan , Barreto Savio George , Kim Anthony W. , Mak Kimberley , Li Hao , Xu Yuan-Yuan , Qiu Xiao-Ming , Wu Min , Jin Min , Xu Li-Chao , Zhong Yi , Yang Hui , Chen Xue-Qin , Zeng Yu , Shi Jun , Zhu Wen-Yu , Ding Qing-Qing , Jia Wei , Liu Su-Fen , Zhou Jun-Jing , Shen Hong , Yao Shi-Hua , Guo Zhao-Ji , Li Ting , Zhou Pei-Juan , Dong Xue-Wei , Lu Wen-Feng , Coleman Robert L. , Akce Mehmet , Akladios Chérif , Puccetti Francesco , Zang Yuan-Sheng
Published: February 2023

Purpose

We evaluated he effects of molecular guided-targeted therapy for intractable cancer. Also, the epidemiology of druggable gene alterations in Chinese population was investigated.

Materials and methods

The Long March Pathway (ClinicalTrials.gov identifier: NCT03239015) is a non-randomized, open-label, phase II trial consisting of several basket studies examining the molecular profiles of intractable cancers in the Chinese population. The trial aimed to 1) evaluate the efficacy of targeted therapy for intractable cancer and 2) identify the molecular epidemiology of the tier II gene alterations among Chinese pan-cancer patients.

Results

In the first stage, molecular profiles of 520 intractable pan-cancer patients were identified, and 115 patients were identified to have tier II gene alterations. Then, 27 of these 115 patients received targeted therapy based on molecular profiles. The overall response rate (ORR) was 29.6% (8/27), and the disease control rate (DCR) was 44.4% (12/27). The median duration of response (DOR) was 4.80 months (95% CI, 3.33−27.2), and median progression-free survival (PFS) was 4.67 months (95% CI, 2.33−9.50). In the second stage, molecular epidemiology of 17,841 Chinese pan-cancer patients demonstrated that the frequency of tier II gene alterations across cancer types is 17.7%. Bladder cancer had the most tier-II alterations (26.1%), followed by breast cancer (22.4%), and non-small cell lung cancer (NSCLC; 20.2%).

Conclusion

The Long March Pathway trial demonstrated a significant clinical benefit for intractable cancer from molecular-guided targeted therapy in the Chinese population. The frequency of tier II gene alterations across cancer types supports the feasibility of molecular-guided targeted therapy under basket trials.
Evaluation of a computational strategy to model transitory injection in rotating detonation combustors
Authors: Hellard Pierre , Gaillard Thomas , Davidenko Dmitry
Published: February 2023

The efficiency of a Rotating Detonation Combustor (RDC) strongly depends on the transitory injection process of fresh reactants in the combustion chamber: poor propellant mixing induces losses of combustion efficiency and consequently low detonation speed and unstable detonation propagation. Moreover, dilution of fresh reactants with burnt gases during injection increases the deflagration losses and decreases the pressure gain provided by the detonation. Numerical simulation can help design an efficient injector to reduce these losses. In this study, the modeling strategy previously proposed by ONERA to simulate the transitory injection process is applied to two existing experimental RDC (from Nagoya University and TU Berlin) and one in-development RDC from ONERA. The computational domain represents only one injection element, convenient for a parametric study at low computational cost. A custom initial condition is used to model the expansion process of burnt gases past a detonation wave. The initial condition parameters are discussed and a method is proposed to correctly set them. The TU Berlin RDC is studied in more detail: mixing efficiency up to 70% is obtained, and 5% of deflagration losses are estimated according to the assumptions of the simulation. Based on the numerical results, detonation speed was evaluated at various distances from the injection plane taking into account the heterogeneities of the fresh mixture. The measured speed lies within the predicted range.
School performance is impaired in children with both simple and complex congenital heart disease
Authors: Omann Camilla , Kristensen Rasmus , Tabor Ann , Gaynor J. William , Hjortdal Vibeke E. , Nyboe Camilla
Published: February 2023

Background

We do not know if children born with a simple or uncorrected congenital heart disease (CHD) have school performance issues and an increased need for special education compared to healthy peers. With this study we examine the school performance and the need for special education in children with both simple and complex CHD. Further, we evaluate if exposure to preeclampsia or smoking affects the need for special education.

Methods

In this nation-wide population based registry study, we included all Danish children with CHD born 1994–2012. In addition ten age and gender matched control per CHD child were included. Non-singletons and children born with a syndrome were excluded. Exposure was defined as having a CHD and the outcome was defined as needing special education service in the Danish primary and lower secondary school.

Results

The population consisted of 7,559 CHD children and 77,046 non-CHD children (controls). CHD children had a higher need for special education compared to non-CHD children, OR: 2.14 (95% CI: 2.00; 2.28), p < 0.001. The odds ratio was also increased when comparing children with a minor CHD to non-CHD children, OR: 1.99 (95% CI: 1.86; 2.14), p < 0.001. CHD children exposed to preeclampsia or smoking had a higher risk of receiving special education compared to unexposed CHD children.

Conclusion

We find that school performance is impaired in children born with CHD. This applies to both simple and complex CHD. If a child with CHD was exposed to preeclampsia or maternal smoking this further increased the need for special education.