bluuebunny/crossref_metadata_2025 huggingface dataset:
The Prevalence and Clinical Relevance of the DFS Immunofluorescence Staining Pattern in a Large ANA-Positive Cohort
Authors: Deng Chuiwen , Wang Anqi , Hu Chaojun , Zhang Wen , Zeng Xiaofeng , Fei Yunyun
Published: May 2022

Background

Although the dense fine speckled (DFS) immunofluorescence staining pattern has been studied by various researchers in recent years, its clinical associations remain unspecified. Thus, we performed a retrospective study in a non-selective population to explore the prevalence of this enigmatic antinuclear antibody (ANA) pattern and to determine its possible clinical associations with any identifiable pathology.

Methods

We retrieved the results of ANA testing ordered by various departments in 2019 to study the prevalence of DFS pattern. Demographic characteristics and clinical features of these participants were also collected from the electronic medical record system. Correlation analysis was made to study its clinical associations and a p-value < 0.05 was considered statistically significant.

Results

The prevalence of ANA positivity was 37.4% among 72,204 serum samples of which the median age was 44 (interquartile range: 31, 56) years old and 68.0% were women. The prevalence of the DFS staining pattern was 1.1% in the total population and accounted for 3.1% in the ANA-positive population. There were 97.6% of these cases displaying the DFS pattern with a low titer of ANA (≤1:320; starting serum dilution: 1:100). We found that this pattern correlated with several pathological conditions, such as skin disorders (25.1%), alopecia (4.6%), and obstetric complications (6.6%).

Conclusion

The presence of the DFS immunofluorescence staining pattern may accompany several pathological conditions and may be a signal of localized inflammation within certain organs or tissues, especially the skin.
Transcriptomic Analysis Revealed an Important Role of Peroxisome-Proliferator-Activated Receptor Alpha Signaling in Src Homology Region 2 Domain-Containing Phosphatase-1 Insufficiency Leading to the Development of Renal Ischemia-Reperfusion Injury
Authors: Yan Sijia , Sui Mingxing , Tian Hongzhe , Fu Jiazhao , Li Yanfeng , Chen Jing , Zeng Li , Ding Xianting
Published: May 2022

In kidney transplantation, the donor kidney inevitably undergoes ischemia-reperfusion injury (IRI). It is of great importance to study the pathogenesis of IRI and find effective measures to attenuate acute injury of renal tubules after ischemia-reperfusion. Our previous study found that Src homology region 2 domain-containing phosphatase-1 (SHP-1) insufficiency aggravates renal IRI. In this study, we systematically analyzed differences in the expression profiles of SHP-1 (encoded by Ptpn6)-insufficient mice and wild-type mice by RNA-seq. We found that a total of 161 genes showed at least a twofold change, with a false discovery rate <0.05 in Ptpn6 +/mev mice after IRI and 42 genes showing more than a fourfold change. Of the eight genes encoding proteins with immunoreceptor tyrosine-based inhibitory motifs (ITIMs) that bind to Ptpn6, three were upregulated, and five were downregulated. We found that for the differentially expressed genes (DEGs) with a fold change >2, the most significantly enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were the cell division pathway and peroxisome-proliferator activated receptor PPARα signaling pathways. Furthermore, the downregulated genes of the PPARα signaling pathway were mainly related to fatty acid absorption and degradation. Using an agonist of the PPARα signaling pathway, fenofibrate, we found that renal IRI was significantly attenuated in Ptpn6 +/mev mice. In summary, our results show that insufficiency of SHP-1 inhibits the expression of genes in the PPARα signaling pathway, thereby leading to increased reactive oxygen species (ROS) and exacerbating the renal IRI. The PPARα signaling agonist fenofibrate partially attenuates renal IRI induced by SHP-1 insufficiency.
Gender Matters: Understanding Transitions in Surgical Education
Authors: Offiah Gozie , Cable Stuart , Rees Charlotte E. , Schofield Susie J.
Published: May 2022

Introduction

Diverse transitions are elemental to medical career trajectories. The effective navigation of such transitions influences a sense of belonging and wellbeing, positive relationships, and good engagement and attainment within new contexts. Using Multiple and Multidimensional Transitions (MMT) theory as an analytical lens, this paper aims to answer the research question: “What gendered transitions do female surgeons experience, and how do these gendered transitions impact them?”

Methods

We conducted a qualitative study drawing on narrative inquiry, with face-to-face and online semi-structured interviews with 29 female surgeons across nine surgical specialities in Ireland and Scotland. This paper is part of a larger study including male surgeons, other colleagues and patients of female surgeons. The female surgeons in this paper were purposively sampled using maximum variation sampling across several levels (consultants, trainees and middle-grade doctors), as well as six who had transitioned out of surgery. Framework analysis was employed to interrogate the interview data.

Results

Five overarching types of transitions were identified across surgical education but only three of these transitions—work, culture and health—were primarily experienced by female surgeons (not male surgeons so were considered gendered), thereby impacting social, academic, and psychological domains. The remaining two types of transition—education and geography—were seemingly experienced equally by female and male surgeons, so are beyond the scope of this paper focused on female surgeons’ gendered experiences.

Conclusion

This novel qualitative study drawing on MMT theory illustrates how multiple gendered transitions interact and impact female surgeons across the surgical education continuum. Aligned with MMT theory, family members and others are also purportedly affected by female surgeons’ transitions. Healthcare educators, leaders and policymakers need to better understand gendered transitions and their impacts to improve support for female surgical trainees on their educational journeys.
Functional Analysis of the C-5 Sterol Desaturase PcErg3 in the Sterol Auxotrophic Oomycete Pathogen Phytophthora capsici
Authors: Wang Weizhen , Cui Tongshan , Zhang Fan , Xue Zhaolin , Zhang Borui , Liu Xili
Published: May 2022

Although sterols play an important role in most eukaryotes, some oomycetes, including Phytophthora spp., have lost the sterol synthesis pathway. Nevertheless, the ERG3 gene encoding C-5 sterol desaturase in the sterol synthesis pathway is still present in the genomes of Phytophthora spp. Phytophthora capsici, a destructive pathogen with a broad range of plant hosts, poses a significant threat to the production of agriculture. This study focused on the ERG3 gene in P. capsici (PcERG3) and explored its function in this pathogen. It showed that the PcERG3 gene could be expressed in all tested developmental stages of P. capsici, with sporangium and mycelium displaying higher expression levels. A potential substrate of Erg3 (stellasterol) was used to treat the P. capsici wild-type strain and a PcERG3Δ transformant, and their sterol profiles were determined by GC-MS. The wild-type strain could convert stellasterol into the down-stream product while the transformant could not, indicating that PcErg3 retains the C-5 sterol desaturase activity. By comparing the biological characteristics of different strains, it was found that PcERG3 is not important for the development of P. capsici. The pathogenicity of the PcERG3Δ transformants and the wild-type strain was comparable, suggesting that PcERG3 is not necessary for the interaction between P. capsici and its hosts. Further investigations revealed that the PcERG3Δ transformants and the wild-type strain displayed a similar level of tolerance to external adversities such as unsuitable temperatures, high osmotic pressures, and intemperate pH, signifying that PcERG3 is not essential for P. capsici to cope with these environmental stresses.
Differential Responses of the Catalytic Efficiency of Ammonia and Nitrite Oxidation to Changes in Temperature
Authors: Taylor Anne E. , Mellbye Brett L.
Published: May 2022

Microbially mediated nitrification plays an important role in the nitrogen (N) cycle, and rates of activity have been shown to change significantly with temperature. Despite this, the substrate affinities of nitrifying bacteria and archaea have not been comprehensively measured and are often assumed to be static in mathematical models of environmental systems. In this study, we measured the oxidation kinetics of ammonia- (NH3) oxidizing archaea (AOA), NH3-oxidizing bacteria (AOB), and two distinct groups of nitrite (NO2–)-oxidizing bacteria (NOB), of the genera Nitrobacter and Nitrospira, by measuring the maximum rates of apparent activity (Vmax(app)), the apparent half-saturation constant (Km(app)), and the overall catalytic efficiency (Vmax(app)/Km(app)) over a range of temperatures. Changes in Vmax(app) and Km(app) with temperature were different between groups, with Vmax(app) and catalytic efficiency increasing with temperature in AOA, while Vmax(app), Km(app), and catalytic efficiency increased in AOB. In Nitrobacter NOB, Vmax(app) and Km(app) increased, but catalytic efficiency decreased significantly with temperature. Nitrospira NOB were variable, but Vmax(app) increased while catalytic efficiency and Km(app) remained relatively unchanged. Michaelis–Menten (MM) and Haldane (H) kinetic models of NH3 oxidation and NO2– oxidation based on the collected data correctly predict nitrification potential in some soil incubation experiments, but not others. Despite previous observations of coupled nitrification in many natural systems, our results demonstrate significant differences in response to temperature strategies between the different groups of nitrifiers; and indicate the need to further investigate the response of nitrifiers to environmental changes.
Hybrid Sequencing Resolved Inverted Terminal Repeats in the Genome of Megavirus Baoshan
Authors: Xia Yucheng , Cheng Huanyu , Zhong Jiang
Published: May 2022

Mimivirus is a group of amoeba-infecting DNA viruses with linear double-strand genome. It is found to be ubiquitous in nature worldwide. Here, we reported the complete genome of a new member of Mimivirus lineage C isolated from a fresh water pond in Shanghai, China. Its 1,224,839-bp genome encoded 1,062 predicted ORFs. Combining the results of Nanopore, Illumina, and Sanger sequencing technologies, two identical 23,919 bp inverted terminal repeats (ITRs) were identified at both extremities of the viral linear genome, one of which was missing in the draft assembly based on Illumina data only. The discovery of ITRs of Mimivirus provided a new insight into Mimivirus genome structure.
Repurposing of FDA Approved Drugs Against SARS-CoV-2 Papain-Like Protease: Computational, Biochemical, and in vitro Studies
Authors: Kulandaisamy Rajkumar , Kushwaha Tushar , Dalal Anu , Kumar Vikas , Singh Deepa , Baswal Kamal , Sharma Pratibha , Praneeth Kokkula , Jorwal Pankaj , Kayampeta Sarala R. , Sharma Tamanna , Maddur Srinivas , Kumar Manoj , Kumar Saroj , Polamarasetty Aparoy , Singh Aekagra , Sehgal Deepak , Gholap Shivajirao L. , Appaiahgari Mohan B. , Katika Madhumohan R. , Inampudi Krishna K.
Published: May 2022

The pandemic caused by SARS-CoV-2 (SCoV-2) has impacted the world in many ways and the virus continues to evolve and produce novel variants with the ability to cause frequent global outbreaks. Although the advent of the vaccines abated the global burden, they were not effective against all the variants of SCoV-2. This trend warrants shifting the focus on the development of small molecules targeting the crucial proteins of the viral replication machinery as effective therapeutic solutions. The PLpro is a crucial enzyme having multiple roles during the viral life cycle and is a well-established drug target. In this study, we identified 12 potential inhibitors of PLpro through virtual screening of the FDA-approved drug library. Docking and molecular dynamics simulation studies suggested that these molecules bind to the PLpro through multiple interactions. Further, IC50 values obtained from enzyme-inhibition assays affirm the stronger affinities of the identified molecules for the PLpro. Also, we demonstrated high structural conservation in the catalytic site of PLpro between SCoV-2 and Human Coronavirus 229E (HCoV-229E) through molecular modelling studies. Based on these similarities in PLpro structures and the resemblance in various signalling pathways for the two viruses, we propose that HCoV-229E is a suitable surrogate for SCoV-2 in drug-discovery studies. Validating our hypothesis, Mefloquine, which was effective against HCoV-229E, was found to be effective against SCoV-2 as well in cell-based assays. Overall, the present study demonstrated Mefloquine as a potential inhibitor of SCoV-2 PLpro and its antiviral activity against SCoV-2. Corroborating our findings, based on the in vitro virus inhibition assays, a recent study reported a prophylactic role for Mefloquine against SCoV-2. Accordingly, Mefloquine may further be investigated for its potential as a drug candidate for the treatment of COVID.
Potential Fungi Isolated From Anti-biodegradable Chinese Medicine Residue to Degrade Lignocellulose
Authors: Cheng Min , Wijayawardene Nalin N. , Promputtha Itthayakorn , de Vries Ronald P. , Lan Yongzhe , Luo Gang , Wang Meizhu , Li Qirui , Guo Xinyao , Wang Feng , Liu Yanxia , Kang Yingqian
Published: May 2022

Traditional Chinese medicine is one of the ancient medicines which is popular in Asian countries, among which the residue produced by the use of anti-biodegradables is endless, and causes significant adverse impacts on the environment. However, the high acidity of anti-biodegradable residues and some special biological activities make it difficult for microorganisms to survive, resulting in a very low degradation rate of lignocellulose in naturally stacked residues, which directly impedes the degradation of residues. We aimed to identify the fungal strains that efficiently biodegrade anti-biodegradable residue and see the possibility to improve the biodegradation of it and other agricultural wastes by co-cultivating these fungi. We isolated 302 fungal strains from anti-biodegradable residue to test hydrolysis ability. Finally, we foundConiochaetasp.,Fomitopsissp.,Nemaniasp.,Talaromycessp.,Phaeophlebiopsissp. which inhabit the anti-biodegradable residues are capable of producing higher concentrations of extracellular enzymes. Synergistic fungal combinations (viz.,Fomitopsissp. +Phaeophlebiopsissp.;Talaromycessp. +Coniochaetasp. +Fomitopsissp.;Talaromycessp. +Fomitopsissp. +Pilodermasp. andTalaromycessp. +Nemaniasp. +Pilodermasp.) have better overall degradation effect on lignocellulose. Therefore, these fungi and their combinations have strong potential to be further developed for bioremediation and biological enzyme industrial production.
Detoxification of Aflatoxin B1 by a Potential Probiotic Bacillus amyloliquefaciens WF2020
Authors: Chen Guojun , Fang Qian’an , Liao Zhenlin , Xu Chunwei , Liang Zhibo , Liu Tong , Zhong Qingping , Wang Li , Fang Xiang , Wang Jie
Published: May 2022

Microbial degradation is considered as an attractive method to eliminate exposure to aflatoxin B1 (AFB1), the most toxic mycotoxin that causes great economic losses and brings a serious threat to human and animal health, in food and feed. In this study, Bacillus amyloliquefaciens WF2020, isolated from naturally fermented pickles, could effectively degrade AFB1 ranging from 1 to 8 μg/ml, and the optimum temperature and pH value were 37–45°C and 8.0, respectively. Moreover, B. amyloliquefaciens WF2020 was considered to be a potential probiotic due to the synthesis of active compounds, absence of virulence genes, susceptibility to various antibiotics, and enhanced lifespan of Caenorhabditis elegans. Extracellular enzymes or proteins played a major role in AFB1 degradation mediated by B. amyloliquefaciens WF2020 into metabolites with low or no mutagenicity and toxicity to C. elegans. AFB1 degradation by the cell-free supernatant was stable up to 70°C, with an optimal pH of 8.0, and the cell-free supernatant could still degrade AFB1 by 37.16% after boiling for 20 min. Furthermore, B. amyloliquefaciens WF2020 caused a slight defect in fungal growth and completely inhibited AFB1 production when co-incubated with Aspergillus flavus. Additionally, B. amyloliquefaciens WF2020 suppressed the expression of 10 aflatoxin pathway genes and 2 transcription factors (alfR and alfS), suggesting that B. amyloliquefaciens WF2020 might inhibit AFB1 synthesis in A. flavus. These results indicate that B. amyloliquefaciens WF2020 and/or its extracellular enzymes or proteins have a promising potential to be applied in protecting food and feed from AFB1 contamination.
Activation and Characterization of Lanthomicins A–C by Promoter Engineering in Streptomyces chattanoogensis L10
Authors: Liu Xiao-Fang , Wang Jun-Xiao , Chen Xin-Ai , Liu Yu , Li Yong-Quan
Published: May 2022

The emergence of drug resistance highlights the importance of new drug discovery. Microbial secondary metabolites encoded in biosynthetic gene clusters (BGCs) are a prolific source of drugs, whereas most of these BGCs are cryptic. Thus, taking strategies to activate these cryptic BGCs is of great importance for potential drug discovery. In this work, three novel pentangular polyphenols lanthomicin A–C were identified by activating a cryptic aromatic polyketide BGC through promoter engineering combined with optimization of fermentation conditions. We further confirmed the involvement of lanthomicin (ltm) BGC in biosynthesis by CRISPR-Cpf1-assisted gene editing. Based on functional analysis of homologous genes, a putative biosynthetic pathway was proposed for the three lanthomicins. Particularly, lanthomicin A showed antiproliferative activity with IC50 0.17 μM for lung cancer cell line A-549. The discovery of lanthomicins brings new members to the pentangular polyphenol subclade of aromatic polyketide and demonstrates the potential of Streptomyces as a source for drug discovery.
Identification of Immune Hub Genes Associated With Braak Stages in Alzheimer’s Disease and Their Correlation of Immune Infiltration
Authors: Qian Xiao-hang , Liu Xiao-li , Chen Sheng-di , Tang Hui-dong
Published: May 2022

Background

Alzheimer’s disease (AD) is the most common type of neurodegenerative disease. Tau pathology is one of the pathological features of AD, and its progression is closely related to the progress of AD. Immune system dysfunction is an important mediator of Tau pathological progression, but the specific molecular mechanism is still unclear. The purpose of this study is to determine the immune hub genes and peripheral immune cell infiltration associated with the Braak stages, and the molecular mechanisms between them.

Methods

In this study, 60 samples with different Braak stages in the GSE106241 dataset were used to screen Braak stages-related immune hub genes by using the WGCNA package in R and cytoHubba plugin. The temporal lobe expression data in the Alzdata database were used to verify the results. The correlation between the expression level of immune core genes and the pathological features of AD was analyzed to evaluate the abundance of peripheral immune cell infiltration and screened Braak stages-related cells. Finally, we used correlation analysis of immune hub genes and immune cells and Gene Set Enrichment Analysis (GSEA) of them.

Results

Seven genes (GRB2, HSP90AA1, HSPA4, IGF1, KRAS, PIK3R1, and PTPN11) were identified as immune core genes after the screening of the test datasets and validation of independent data. Among them, Kirsten rat sarcoma viral oncogene homolog (KRAS) and Phosphoinositide-3-Kinase Regulatory Subunit 1 (PIK3R1) were the most closely related to Tau and Aβ pathology in AD. In addition, the ImmuneScore increased gradually with the increase of Braak stages. Five types of immune cells (plasma cells, T follicular helper cells, M2 macrophage, activated NK cells, and eosinophils) were correlated with Braak stages. KRAS and PIK3R1 were the immune core genes most related to the abnormal infiltration of peripheral immune cells. They participated in the regulation of the pathological process of AD through axon guidance, long-term potentiation, cytokine–cytokine receptor interaction, RNA polymerase, etc.

Conclusion

The KRAS and PIK3R1 genes were identified as the immune hub genes most associated with Tau pathological progress in AD. The abnormal infiltration of peripheral immune cells mediated by these cells was involved in the Tau pathological process. This provides new insights for AD.
Goal Oriented Behavior With a Habit-Based Adaptive Sensorimotor Map Network
Authors: Woolford Felix M. G. , Egbert Matthew D.
Published: May 2022

We present a description of an ASM-network, a new habit-based robot controller model consisting of a network of adaptive sensorimotor maps. This model draws upon recent theoretical developments in enactive cognition concerning habit and agency at the sensorimotor level. It aims to provide a platform for experimental investigation into the relationship between networked organizations of habits and cognitive behavior. It does this by combining (1) a basic mechanism of generating continuous motor activity as a function of historical sensorimotor trajectories with (2) an evaluative mechanism which reinforces or weakens those historical trajectories as a function of their support of a higher-order structure of higher-order sensorimotor coordinations. After describing the model, we then present the results of applying this model in the context of a well-known minimal cognition task involving object discrimination. In our version of this experiment, an individual robot is able to learn the task through a combination of exploration through random movements and repetition of historic trajectories which support the structure of a pre-given network of sensorimotor coordinations. The experimental results illustrate how, utilizing enactive principles, a robot can display recognizable learning behavior without explicit representational mechanisms or extraneous fitness variables. Instead, our model's behavior adapts according to the internal requirements of the action-generating mechanism itself.
Epileptic Seizures and Right-Sided Hippocampal Swelling as Presenting Symptoms of Anti-IgLON5 Disease: A Case Report and Systematic Review of the Literature
Authors: Fu Yaoqi , Zou Xiangting , Liu Ling
Published: May 2022

Background and Objective

Anti-IgLON5 disease is an uncommon neurological disorder characterized by diverse clinical manifestations. Although many relevant cases have been reported, our understanding of this disorder is still quite restricted. We present a rare case of anti-IgLON5 disease and performed a comprehensive systematic review of all published cases to expand the clinical spectrum of this disorder.

Methods

We report a 61-year-old woman with an atypical presentation of epileptic seizures with abnormal signals in her right hippocampus on brain magnetic resonance imaging (MRI). A systematic review was performed of electronic databases, including PubMed, EMBASE, China National Knowledge Infrastructure (CNKI), WanFang and VIP China Science.

Results

We identified 161 cases from 65 publications. With heterogeneous clinical manifestations, we found that bulbar dysfunction, sleep apnea, gait instability and neurocognitive and behavioral symptoms are the most common symptoms of anti-IgLON5 disease. Anti-IgLON5 antibodies presented a higher positive rate and titer in the serum than in the cerebrospinal fluid (CSF). Haplotype DRB1*10:01-DQB1*05:01 is highly correlated with anti-IgLON5 disease. Only 38 patients have presented distinctive MRI alterations (26.2%). Approximately half of the cases are responsive to immunosuppressive or immunomodulatory treatment.

Conclusion

Anti-IgLON5 disease is characterized by various clinical manifestations and laboratory findings. Immunotherapy may be effective in treating anti-IgLON5 disease, but the results are far from satisfactory. Studies with larger sample sizes are required to improve the current understanding of this disorder.
Combined Intrinsic Local Functional Connectivity With Multivariate Pattern Analysis to Identify Depressed Essential Tremor
Authors: Zhang Xueyan , Tao Li , Chen Huiyue , Zhang Xiaoyu , Wang Hansheng , He Wanlin , Li Qin , Lv Fajin , Luo Tianyou , Luo Jin , Man Yun , Xiao Zheng , Cao Jun , Fang Weidong
Published: May 2022

Background

Although depression is one of the most common neuropsychiatric symptoms in essential tremor (ET), the diagnosis biomarker and intrinsic brain activity remain unclear. We aimed to combine multivariate pattern analysis (MVPA) with local brain functional connectivity to identify depressed ET.

Methods

Based on individual voxel-level local brain functional connectivity (regional homogeneity, ReHo) mapping from 41 depressed ET, 43 non-depressed ET, and 45 healthy controls (HCs), the binary support vector machine (BSVM) and multiclass Gaussian Process Classification (MGPC) algorithms were used to identify depressed ET patients from non-depressed ET and HCs, the accuracy and permutations test were used to assess the classification performance.

Results

The MGPC algorithm was able to classify the three groups (depressed ET, non-depressed ET, and HCs) with a total accuracy of 84.5%. The BSVM algorithm achieved a better classification performance with total accuracy of 90.7, 88.64, and 90.48% for depressed ET vs. HCs, non-depressed ET vs. HCs, and depressed ET vs. non-depressed ET, and the sensitivity for them at 80.49, 76.64, and 80.49%, respectively. The significant discriminative features of depressed ET vs. HCs were primarily located in the cerebellar-motor-prefrontal gyrus-anterior cingulate cortex pathway, and for depressed ET vs. non-depressed ET located in the cerebellar-prefrontal gyrus-anterior cingulate cortex circuits. The partial correlation showed that the ReHo values in the bilateral middle prefrontal gyrus (positive) and the bilateral cerebellum XI (negative) were significantly correlated with clinical depression severity.

Conclusion

Our findings suggested that combined individual ReHo maps with MVPA not only could be used to identify depressed ET but also help to reveal the intrinsic brain activity changes and further act as the potential diagnosis biomarker in depressed ET patients.
Increased Carotid Siphon Tortuosity Is a Risk Factor for Paraclinoid Aneurysms
Authors: Liu Shilin , Jin Yu , Wang Xukou , Zhang Yang , Jiang Luwei , Li Guanqing , Zhao Xi , Jiang Tao
Published: May 2022

Background

Geometrical factors associated with the surrounding vasculature can affect the risk of aneurysm formation. The aim of this study was to determine the association between carotid siphon curvature and the formation and development of paraclinoid aneurysms of the internal carotid artery.

Methods

Digital subtraction angiography (DSA) data from 42 patients with paraclinoid aneurysms (31 with non-aneurysmal contralateral sides) and 42 age- and gender-matched healthy controls were analyzed, retrospectively. Morphological characteristics of the carotid siphon [the posterior angle (α), anterior angle (β), and Clinoid@Ophthalmic angle (γ)] were explored via three-dimensional rotational angiography (3D RA) multiplanar reconstruction. The association between carotid siphon morphology and the formation of paraclinoid aneurysms was assessed through univariate analysis. After this, logistic regression analysis was performed to identify independent risk factors for aneurysms.

Results

Significantly smaller α, β, and γ angles were reported in the aneurysmal carotid siphon group when compared with the non-aneurysmal contralateral healthy controls. The β angle was best for discriminating between aneurysmal and non-aneurysmal carotid siphons, with an optimal threshold of 18.25°. By adjusting for hypertension, smoking habit, hyperlipidemia, and diabetes mellitus, logistic regression analysis demonstrated an independent association between the carotid siphons angles α [odds ratio (OR) 0.953; P < 0.05], β (OR 0.690; P < 0.001), and γ (OR 0.958; P < 0.01) with the risk of paraclinoid aneurysms.

Conclusions

The present findings provide evidence for the importance of morphological carotid siphon variations and the likelihood of paraclinoid aneurysms. These practical morphological parameters specific to paraclinoid aneurysms are easy to assess and may aid in risk assessment in these patients.
Adult Female Sleep During Hypoxic Bed Rest
Authors: Van Cutsem Jeroen , Pattyn Nathalie , Mairesse Olivier , Delwiche Bérénice , Fernandez Tellez Helio , Van Puyvelde Martine , Lacroix Emilie , McDonnell Adam C. , Eiken Ola , Mekjavic Igor B.
Published: May 2022

Purpose

Hypobaric hypoxic habitats are currently being touted as a potential solution to minimise decompression procedures in preparation for extra vehicular activities during future space missions. Since astronauts will live in hypoxic environments for the duration of such missions, the present study sought to elucidate the separate and combined effects of inactivity [simulated with the experimental bed rest (BR) model] and hypoxia on sleep characteristics in women.

Methods

Twelve women (Age = 27 ± 3 year) took part in three 10-day interventions, in a repeated measures cross-over counterbalanced design: (1) normobaric normoxic BR (NBR), (2) normobaric hypoxic BR (HBR; simulated altitude of 4,000 m), and (3) normobaric hypoxic ambulatory (HAMB; 4,000 m) confinement, during which sleep was assessed on night 1 and night 10 with polysomnography. In addition, one baseline sleep assessment was performed. This baseline assessment, although lacking a confinement aspect, was included statistically as a fourth comparison (i.e., pseudo normobaric normoxic ambulatory; pNAMB) in the present study.

Results

Hypoxia decreased sleep efficiency (p = 0.019), increased N1% sleep (p = 0.030), decreased N3 sleep duration (p = 0.003), and increased apnea hypopnea index (p < 0.001). BR impaired sleep maintenance, efficiency, and architecture [e.g., N2% sleep increased (p = 0.033)]. Specifically, for N3% sleep, the effects of partial pressure of oxygen and activity interacted. Hypoxia decreased N3% sleep both when active (pNAMB vs HAMB; p < 0.001) and inactive (NBR vs HBR; p = 0.021), however, this decrease was attenuated in the inactive state (–3.8%) compared to the active state (–10.2%).

Conclusion

A 10-day exposure to hypoxia and BR negatively impacted sleep on multiple levels as in macrostructure, microstructure and respiratory functioning. Interestingly, hypoxia appeared to have less adverse effects on sleep macrostructure while the participants were inactive (bed ridden) compared to when ambulatory. Data were missing to some extent (i.e., 20.8%). Therefore, multiple imputation was used, and our results should be considered as exploratory.
Parallelization of Neural Processing on Neuromorphic Hardware
Authors: Peres Luca , Rhodes Oliver
Published: May 2022

Learning and development in real brains typically happens over long timescales, making long-term exploration of these features a significant research challenge. One way to address this problem is to use computational models to explore the brain, with Spiking Neural Networks a popular choice to capture neuron and synapse dynamics. However, researchers require simulation tools and platforms to execute simulations in real- or sub-realtime, to enable exploration of features such as long-term learning and neural pathologies over meaningful periods. This article presents novel multicore processing strategies on the SpiNNaker Neuromorphic hardware, addressing parallelization of Spiking Neural Network operations through allocation of dedicated computational units to specific tasks (such as neural and synaptic processing) to optimize performance. The work advances previous real-time simulations of a cortical microcircuit model, parameterizing load balancing between computational units in order to explore trade-offs between computational complexity and speed, to provide the best fit for a given application. By exploiting the flexibility of the SpiNNaker Neuromorphic platform, up to 9× throughput of neural operations is demonstrated when running biologically representative Spiking Neural Networks.
Comprehensive Volumetric Analysis of Mecp2-Null Mouse Model for Rett Syndrome by T2-Weighted 3D Magnetic Resonance Imaging
Authors: Akaba Yuichi , Shiohama Tadashi , Komaki Yuji , Seki Fumiko , Ortug Alpen , Sawada Daisuke , Uchida Wataru , Kamagata Koji , Shimoji Keigo , Aoki Shigeki , Takahashi Satoru , Suzuki Takeshi , Natsume Jun , Takahashi Emi , Tsujimura Keita
Published: May 2022

Rett syndrome (RTT) is a severe progressive neurodevelopmental disorder characterized by various neurological symptoms. Almost all RTT cases are caused by mutations in the X-linked methyl-CpG-binding protein 2 (MeCP2) gene, and several mouse models have been established to understand the disease. However, the neuroanatomical abnormalities in each brain region of RTT mouse models have not been fully understood. Here, we investigated the global and local neuroanatomy of the Mecp2 gene-deleted RTT model (Mecp2-KO) mouse brain using T2-weighted 3D magnetic resonance imaging with different morphometry to clarify the brain structural abnormalities that are involved in the pathophysiology of RTT. We found a significant reduction in global and almost all local volumes in the brain of Mecp2-KO mice. In addition, a detailed comparative analysis identified specific volume reductions in several brain regions in the Mecp2-deficient brain. Our analysis also revealed that the Mecp2-deficient brain shows changes in hemispheric asymmetry in several brain regions. These findings suggest that MeCP2 affects not only the whole-brain volume but also the region-specific brain structure. Our study provides a framework for neuroanatomical studies of a mouse model of RTT.
Squaric Acid Bisphposphonates for Theranostics of Bone Metastasis – the Easy DOTA-Zoledronate
Authors: Greifenstein Lukas , Engelbogen Nils , Máthé Domokos , Grus Tilmann , Rösch Frank , Bergmann Ralf
Published: May 2022

Bisphosponates are an interesting molecular class and in recent years their application has found its way into radiopharmaceutical research and thus into molecular imaging. In addition to great imaging of bone metastases, bisphospnate-based tracers for imaging also have some significant drawbacks. For example, their synthesis is often difficult. Additionally, this can lead to complex and almost impossible purification and quality control. This has limited the production and labeling of suitable molecular and their widespread use to a few facilities. Our squaric acid-based approach provides a way to overcome these problems and makes the synthesis as well as the purification of the compounds much easier. In addition, we were able to demonstrate that labeling with 68Ga is possible under the typical conditions.
Determinants of Exclusive Breastfeeding and Mixed Feeding Among Mothers of Infants in Dubai and Sharjah, United Arab Emirates
Authors: Al Sabbah Haleama , Assaf Enas A. , Taha Zainab , Qasrawi Radwan , Radwan Hadia
Published: May 2022

Background

Breastfeeding (BF) is considered the ultimate method of infant feeding for at least the first 6 months of life. Exclusive breastfeeding (EBF) is one of the most effective interventions to improve child survival. The main objective of this study was to assess the prevalence and duration of exclusive breastfeeding and the associated factors among women in Dubai and Sharjah, UAE.

Methods

A cross-sectional study was conducted in four hospitals and four healthcare centers in Dubai and Sharjah between September 2017 and December 2017. Hospitals and centers are governmental and provide maternal and child health services. A convenience sample of 858 Arab and Emirati mothers with children under the age of 2 years participated in the study. Face-to-face interviews were conducted by using structured questionnaires. The study was approved by the University Ethical Committee and the UAE Ministry of Health before data collection. Descriptive statistics were computed to describe all the questionnaire items. The chi-square test was used to compare the study's categorical variables. A binary logistic regression analysis was used to predict the relationship between BF and its associated factors. Statistical tests with P-values < 0.05 were considered statistically significant.

Results

The mean age of the participating mothers was 30.6 (SD 5.5) years. Results showed that the prevalence of exclusive breastfeeding among the study participants was 24.4% (31.1% in Sharjah and 22% in Dubai; P = 0.003). The binary logistic regression reported that mother's and father's education, skin-to-skin period, number of children, mothers' health, and place of living were significantly associated with exclusive breastfeeding (P < 0.05). The results reported a significant association between EB and duration of breastfeeding (OR = 6.9, P = 0.002), husband education (OR = 2.1, P = 0.015), mother education (OR = 1.3, P = 0.027), number of children (OR = 7.9, P = 0.045), having any health problem (OR = 1.2, P = 0.045), and living place (OR = 1.4, P = 0.033), and a non-significant positive effect of family size and family income. Furthermore, the result reported a significant association between mixed breastfeeding and duration of breastfeeding (OR = 0.1, P = 0.000), skin-to-skin period (OR = 0.3, P = 0.002), underweight (OR = 4.7, P = 0.034), last infant's sex (OR = 1.6, P = 0.010), having maid at home (OR = 2.1, P = 0.000), number of children (OR = 0.2, P = 0.013), and living place (OR =1.1, P = 0.014), and a non-significant association with family size and family income.

Conclusions

Therefore, a health promotion program for exclusive breastfeeding during antenatal health visits, together with initiating health policies in maternal hospitals to encourage the initiation of breastfeeding during the first hour of birth and the introduction of skin-to-skin contact during the first 5 min of birth are highly recommended.
Production of Prebiotic Xylooligosaccharides via Dilute Maleic Acid-Mediated Xylan Hydrolysis Using an RSM-Model-Based Optimization Strategy
Authors: Jiang Kankan , Fu Xiaoliang , Huang Rong , Fan Xingli , Ji Lei , Cai Damin , Liu Xiaoxiang , Fu Yixiu , Sun Aihua , Feng Chenzhuo
Published: May 2022

Xylooligosaccharides (XOS) are functional feed additives that are attracting growing commercial interest owing to their excellent ability to modulate the composition of the gut microbiota. The acid hydrolysis-based processing of xylan-containing materials has been proposed to represent a cost-effective approach to XOS preparation, with organic acids being preferable in this context. As such, in the present study, maleic acid was selected as a mild, edible organic acid for use in the hydrolysis of xylan to produce XOS. A response surface methodology (RSM) approach with a central composite design was employed to optimize maleic acid-mediated XOS production, resulting in a yield of 50.3% following a 15 min treatment with 0.08% maleic acid at 168°C. Under these conditions, the desired XOS degree of polymerization (2-3) was successfully achieved, demonstrating the viability of this using a low acid dose and a high reaction temperature to expedite the production of desired functional products. Moreover, as maleic acid is a relatively stable carboxylic acid, it has the potential to be recycled. These results suggest that dilute maleic acid-based thermal treatment of corncob-derived xylan can achieve satisfactory XOS yields, highlighting a promising and cost-effective approach to XOS production.
Hippocampal Metastasis Rate Based on Non-Small Lung Cancer TNM Stage and Molecular Markers
Authors: Ahn Sung Jun , Kwon Hyeokjin , Kim Jun Won , Park Goeun , Park Mina , Joo Bio , Suh Sang Hyun , Chang Yoon Soo , Lee Jong-Min
Published: May 2022

Hippocampal-avoidance whole-brain radiation therapy (HA-WBRT) is justified because of low hippocampal brain metastases (BM) rate and its prevention of cognitive decline. However, we hypothesize that the risk of developing BM in the hippocampal-avoidance region (HAR) may differ depending on the lung-cancer stage and molecular status. We retrospectively reviewed 123 patients with non-small cell lung cancer (NSCLC) at the initial diagnosis of BM. The number of BMs within the HAR (5 mm expansion) was counted. The cohort was divided into patients with and without BMs in the HAR, and their clinical variables, TNM stage, and epidermal growth factor receptor (EGFR) status were compared. The most influential variable predicting BMs in the HAR was determined using multi-variable logistic regression, classification and regression tree (CART) analyses, and gradient boosting method (GBM). The feasibility of HAR expansion was tested using generalized estimating equation marginal model. Patients with BMs in the HAR were more frequently non-smokers, and more likely to have extra-cranial metastases and EGFR mutations (p<0.05). Multi-variable analysis revealed that extra-cranial metastases were independently associated with the presence of BM in the HAR (odds ratio=8.75, p=0.04). CART analysis and GBM revealed that the existence of extra-cranial metastasis was the most influential variable predicting BM occurrence in the HAR (variable importance: 23% and relative influence: 37.38). The estmated BM incidence of patients without extra-cranial metastases in th extended HAR (7.5-mm and 10-mm expansion) did not differ significantly from that in the conventional HAR. In conclusion, NSCLC patients with extra-cranial metastases were more likely to have BMs in the HAR than those without extra-cranial metastases.
New Advances in Nano-Drug Delivery Systems: Helicobacter pylori and Gastric Cancer
Authors: Zhu Xiang , Su Tingting , Wang Shouhua , Zhou Huiqing , Shi Weibin
Published: May 2022

With the development of materials science and biomedicine, the application of nanomaterials in the medical field is further promoted. In the process of the diagnosis and treatment of diseases, a variety of drugs need to be used. It is an ideal state to make these drugs arrive at a specific location at a specific time and release at a specific speed, which can improve the bioavailability of drugs and reduce the adverse effects of drugs on normal tissues. Traditional drug delivery methods such as tablets, capsules, syrups, and ointments have certain limitations. The emergence of a new nano-drug delivery system further improves the accuracy of drug delivery and the efficacy of drugs. It is well known that the development of the cancer of the stomach is the most serious consequence for the infection of Helicobacter pylori. For the patients who are suffering from gastric cancer, the treatments are mainly surgery, chemotherapy, targeted and immune therapy, and other comprehensive treatments. Although great progress has been made, the diagnosis and prognosis of gastric cancer are still poor with patients usually diagnosed with cancer at an advanced stage. Current treatments are of limited benefits for patients, resulting in a poor 5-year survival rate. Nanomaterials may play a critical role in early diagnosis. A nano-drug delivery system can significantly improve the chemotherapy, targeted therapy, and immunotherapy of advanced gastric cancer, reduce the side effects of the original treatment plan and provide patients with better benefits. It is a promising treatment for gastric cancer. This article introduces the application of nanomaterials in the diagnosis and treatment of H. pylori and gastric cancer.
Pre-Treatment Computed Tomography Radiomics for Predicting the Response to Neoadjuvant Chemoradiation in Locally Advanced Rectal Cancer: A Retrospective Study
Authors: Mao Yitao , Pei Qian , Fu Yan , Liu Haipeng , Chen Changyong , Li Haiping , Gong Guanghui , Yin Hongling , Pang Peipei , Lin Huashan , Xu Biaoxiang , Zai Hongyan , Yi Xiaoping , Chen Bihong T.
Published: May 2022

Background and Purpose

Computerized tomography (CT) scans are commonly performed to assist in diagnosis and treatment of locally advanced rectal cancer (LARC). This study assessed the usefulness of pretreatment CT-based radiomics for predicting pathological complete response (pCR) of LARC to neoadjuvant chemoradiotherapy (nCRT).

Materials and Methods

Patients with LARC who underwent nCRT followed by total mesorectal excision surgery from July 2010 to December 2018 were enrolled in this retrospective study. A total of 340 radiomic features were extracted from pretreatment contrast-enhanced CT images. The most relevant features to pCR were selected using the least absolute shrinkage and selection operator (LASSO) method and a radiomic signature was generated. Predictive models were built with radiomic features and clinico-pathological variables. Model performance was assessed with decision curve analysis and was validated in an independent cohort.

Results

The pCR was achieved in 44 of the 216 consecutive patients (20.4%) in this study. The model with the best performance used both radiomics and clinical variables including radiomic signatures, distance to anal verge, lymphocyte-to-monocyte ratio, and carcinoembryonic antigen. This combined model discriminated between patients with and without pCR with an area under the curve of 0.926 and 0.872 in the training and the validation cohorts, respectively. The combined model also showed better performance than models built with radiomic or clinical variables alone.

Conclusion

Our combined predictive model was robust in differentiating patients with and without response to nCRT.
All-Oral Low-Dose Chemotherapy TEPIP is Effective and Well-Tolerated in Relapsed/Refractory Patients With Aggressive B-Cell Lymphoma
Authors: Fante Matthias A. , Felsenstein Mona , Mayer Stephanie , Gerken Michael , Klinkhammer-Schalke Monika , Herr Wolfgang , Vogelhuber Martin , Reichle Albrecht , Heudobler Daniel
Published: May 2022

Purpose

Treatment options in patients (pts.) with advanced relapsed and refractory aggressive B-cell lymphoma are limited. Palliative all-oral chemotherapy regimens reduce in-patient visits and contribute to quality of life. The all-oral low-dose chemotherapy regimen TEPIP comprises the conventional chemotherapy agents trofosfamide, etoposide, procarbazine, idarubicin and prednisolone.

Methods

Safety and efficacy of TEPIP was evaluated in an observational retrospective, single-center study at the University Medical Center Regensburg between 2010 and 2020. Treatment with TEPIP was applied for 7 or 10 days during a 28-days period. In a subgroup of fit and therapy-motivated pts. rituximab was added. End points were overall survival (OS) and progression free survival (PFS). Adverse events ≥ CTCAE grade III were reported.

Results

35 highly pre-treated pts. with aggressive B-cell lymphoma were enrolled. Median age at TEPIP start was 67 years and 85% of pts. received TEPIP as ≥ third treatment line. Overall response rate (ORR) was 23% (CR 17%). Pts. benefited from additional rituximab administration (ORR 67%) and a lower number of pre-treatments (ORR 41%). The OS was 3.3 months (m) with a 1y-OS of 25.7% and the PFS amounted to 1.3 m with a 1y-PFS of 8.8%. OS and PFS were significantly prolonged in pts. that responded to treatment or additionally received rituximab. Adverse events were mainly hematological and occurred in 49% of pts.

Conclusion

TEPIP was well-tolerated and induced respectable response in a difficult-to-treat patient cohort. In particular, the all-oral administration enables out-patient use with palliative intent.