bluuebunny/crossref_metadata_2025 huggingface dataset:
The Technological Advance and Application of Coprolite Analysis
Authors: Yang Liu , Zhang Xing , Zhao Xingbo , Xiang Hai
Published: January 2022

Coprolites (mummified or fossilized feces), belonging to the group of ichnofossils, are fossilized remains of feces produced by animals. Various types of data from coprolites provide detailed evidence of the producer’s condition, like diet, intestinal microbiome, virus infection and parasites diseases. In addition, the palaeoenvironment information relevant to producers’ ecological niche can be drawn from taphonomy details the coprolites mirrored. At present, the phylogenetic clues of the producer’s population can be determined by advanced molecular biotechnologies. With the integration of multiple methods and techniques, coprolite has been widely accepted as an ideal material to study the diet, evolution, and palaeoenvironment of producers. In this paper, we reviewed the history of coprolite research, enumerated and interpreted the data recovered from coprolites, and explained their research value to palaeocoprology and evolutionary biology. Finally, we summarized the current directions of coprolite research and looked into its future prospects.
SNP and Haplotype Regional Heritability Mapping (SNHap-RHM): Joint Mapping of Common and Rare Variation Affecting Complex Traits
Authors: Oppong Richard F. , Boutin Thibaud , Campbell Archie , McIntosh Andrew M. , Porteous David , Hayward Caroline , Haley Chris S. , Navarro Pau , Knott Sara
Published: January 2022

We describe a genome-wide analytical approach, SNP and Haplotype Regional Heritability Mapping (SNHap-RHM), that provides regional estimates of the heritability across locally defined regions in the genome. This approach utilises relationship matrices that are based on sharing of SNP and haplotype alleles at local haplotype blocks delimited by recombination boundaries in the genome. We implemented the approach on simulated data and show that the haplotype-based regional GRMs capture variation that is complementary to that captured by SNP-based regional GRMs, and thus justifying the fitting of the two GRMs jointly in a single analysis (SNHap-RHM). SNHap-RHM captures regions in the genome contributing to the phenotypic variation that existing genome-wide analysis methods may fail to capture. We further demonstrate that there are real benefits to be gained from this approach by applying it to real data from about 20,000 individuals from the Generation Scotland: Scottish Family Health Study. We analysed height and major depressive disorder (MDD). We identified seven genomic regions that are genome-wide significant for height, and three regions significant at a suggestive threshold (p-value < 1 × 10−5) for MDD. These significant regions have genes mapped to within 400 kb of them. The genes mapped for height have been reported to be associated with height in humans. Similarly, those mapped for MDD have been reported to be associated with major depressive disorder and other psychiatry phenotypes. The results show that SNHap-RHM presents an exciting new opportunity to analyse complex traits by allowing the joint mapping of novel genomic regions tagged by either SNPs or haplotypes, potentially leading to the recovery of some of the “missing” heritability.
Comprehensive Analysis of CD4+ T Cell Response Cross-Reactive to SARS-CoV-2 Antigens at the Single Allele Level of HLA Class II
Authors: Hyun You-Seok , Lee Yong-Hun , Jo Hyeong-A , Baek In-Cheol , Kim Sun-Mi , Sohn Hyun-Jung , Kim Tai-Gyu
Published: January 2022

Common human coronaviruses have been circulating undiagnosed worldwide. These common human coronaviruses share partial sequence homology with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); therefore, T cells specific to human coronaviruses are also cross-reactive with SARS-CoV-2 antigens. Herein, we defined CD4+ T cell responses that were cross-reactive with SARS-CoV-2 antigens in blood collected in 2016–2018 from healthy donors at the single allele level using artificial antigen-presenting cells (aAPC) expressing a single HLA class II allotype. We assessed the allotype-restricted responses in the 42 individuals using the aAPCs matched 22 HLA-DR alleles, 19 HLA-DQ alleles, and 13 HLA-DP alleles. The response restricted by the HLA-DR locus showed the highest magnitude, and that by HLA-DP locus was higher than that by HLA-DQ locus. Since two alleles of HLA-DR, -DQ, and -DP loci are expressed co-dominantly in an individual, six different HLA class II allotypes can be used to the cross-reactive T cell response. Of the 16 individuals who showed a dominant T cell response, five, one, and ten showed a dominant response by a single allotype of HLA-DR, -DQ, and -DP, respectively. The single allotype-restricted T cells responded to only one antigen in the five individuals and all the spike, membrane, and nucleocapsid proteins in the six individuals. In individuals heterozygous for the HLA-DPA and HLA-DPB loci, four combinations of HLA-DP can be expressed, but only one combination showed a dominant response. These findings demonstrate that cross-reactive T cells to SARS-CoV-2 respond with single-allotype dominance.
Co-Mutation of FAT3 and LRP1B in Lung Adenocarcinoma Defines a Unique Subset Correlated With the Efficacy of Immunotherapy
Authors: Zhu Mingyu , Zhang Lu , Cui Haiyan , Zhao Qiang , Wang Hao , Zhai Baochao , Jiang Richeng , Jiang Zhansheng
Published: January 2022

Immunotherapy based on immune checkpoint inhibitors (ICIs) have demonstrated remarkable survival benefits and gained regulatory approval in non-small cell lung cancer (NSCLC) patients without an actionable driver mutation, but currently there is no well-established standard for how to screen the most suitable population for ICIs treatment. Here, we conducted a comprehensive analysis of the somatic mutation landscape of lung adenocarcinoma (LUAD) samples. After the stepwise screening of high-frequency mutated genes, two genes with prominent significance, FAT3 and LRP1B, were finally screened out. Through further analysis, we discovered that the co-mutation of FAT3 and LRP1B was associated with an earlier age of onset and occurred more frequently in Black/African American. Furthermore, co-mutation defines a unique subgroup of lung adenocarcinoma that can increase tumor mutational burden (TMB), boost cytotoxicity and tumor immunogenicity, and facilitate lymphocyte infiltration. The results of gene set enrichment analysis (GSEA) indicated that co-mutation can influence tumorigenesis through a variety of mechanisms. More strikingly, the subset of LUAD with co-mutation of FAT3 and LRP1B exhibited significantly prolonged immunotherapy progression free survival (PFS). In summary, co-mutation of FAT3 and LRP1B is a promising useful biomarker for predicting the efficacy of immunotherapy, which can improve the clinical efficiency of practicing precision medicine in lung adenocarcinoma patients.
Coupling Relationship of Human Activity and Geographical Environment in Stage-Specific Development of Urban Coastal Zone: A Case Study of Quanzhou Bay, China (1954–2020)
Authors: Xiao Xianbiao , Li Yunhai , Shu Fangfang , Wang Liang , He Jia , Zou Xiaochun , Chi Wenqi , Lin Yuting , Zheng Binxin
Published: January 2022

Owing to the development of the social economy, the geographical environment and ocean utilization patterns of urban coastal zones have changed. This change, in turn, has influenced the socio-economic development of urban coastal zones. Based on the Geographic Information System technology, the area, coastline length, and shoreland use function of reclamation areas were obtained from the geographic charts (1954–2020) and remote sensing data (1988–2017) of Quanzhou Bay. In this study, we analyzed the geomorphologic change process and the relationship between land use patterns and economic development in Quanzhou Bay from the perspectives of hydrodynamics, sediments, and human activity. Our results indicated that over the past 70 years, the bay area has reduced by 21.5%. The length of the coastline decreased from 208.36 km in 1959 to 149.11 km in 1988, whereas the shape index of the bay (SIB) decreased from 3.09 to 2.41 during the same period. Between 1988 and 2017, the coastline increased to 162.91 km, causing the SIB to increase to 2.72. The artificial index of the bay increased from 0.28 in 1959 to 0.90 in 2017. The intensity of bay the development (IBD) first increased from 0.27 in 1959 to 0.77 in 2006. During the transition to a more modern society (2006 to present), the IBD slightly decreased to 0.73 in 2017. Affected by human activity, the transformation of the reclaimed land in Quanzhou Bay can be divided into four stages that are closely linked to the economic development in the region. In the early industrialization period, reclaimed land in the region was used for agricultural production, whereas in the mid-industrialization period, it was gradually transformed into a combination of industrial (29.8%) and agricultural (56.1%) lands. In the later period of industrialization, the reclaimed land was gradually converted into urban industrial and port lands. Finally, with further refinement and upgrading of economic and industrial structures, the socio-economic and environmental benefits from coastal reclamation projects have been increasing, whereas the proportion of economic benefits (in the total benefits) has been decreasing. The results of this study can provide decision-making references for the optimization of utilization patterns and the economic development of reclamation lands in coastal areas.
Deep Learning for Photonic Design and Analysis: Principles and Applications
Authors: Duan Bing , Wu Bei , Chen Jin-hui , Chen Huanyang , Yang Da-Quan
Published: January 2022

Innovative techniques play important roles in photonic structure design and complex optical data analysis. As a branch of machine learning, deep learning can automatically reveal the inherent connections behind the data by using hierarchically structured layers, which has found broad applications in photonics. In this paper, we review the recent advances of deep learning for the photonic structure design and optical data analysis, which is based on the two major learning paradigms of supervised learning and unsupervised learning. In addition, the optical neural networks with high parallelism and low energy consuming are also highlighted as novel computing architectures. The challenges and perspectives of this flourishing research field are discussed.
Acute Vertigo After COVID-19 Vaccination: Case Series and Literature Review
Authors: Di Mauro Paola , La Mantia Ignazio , Cocuzza Salvatore , Sciancalepore Pasqua Irene , Rasà Deborak , Maniaci Antonino , Ferlito Salvatore , Tundo Isabella , Anzivino Roberta
Published: January 2022

Objective: The aim of this study was to present some cases of acute vertigo potentially related to the coronavirus disease 2019 (COVID-19) vaccine and review the available literature about cochleovestibular dysfunction after the COVID-19 vaccination.

Methods: In the period from May to July 2021, we evaluated 33 patients (mean age 54.3 ± 14.1) with “acute vertigo” post COVID-19 vaccination. A detailed medical history was taken on comorbidities, types of vaccines received, and symptoms associated. All patients underwent otoneurological evaluation, such as head impulse test, nystagmus evaluation, test of skew (HINTS) examination. Head shaking test-induced nystagmus, hyperventilation-induced nystagmus, and parossistic positional nystagmus were studied to search for vestibular impairment.

Results: Symptoms included 16 patients (48.5%) with objective vertigo, 14 patients (42.4%) with subjective vertigo, and 3 patients (9.1%) with dizziness. Of the associated ear, nose, and throat (ENT) symptoms, the most expressed was tinnitus (18.2%). Bedside examination showed absent nystagmus in 7 patients (21.2%), 9 patients (27.3%) had horizontal or rotatory nystagmus, 17 patients (51.5%) had a vertical or oblique nystagmus, negative HST, or “central HINTS.”

Discussion and Conclusions: The 9 patients had an evoked nystagmus pathognomonic for benign paroxysmal positional vertigo; in the remaining 17 cases, peripheral vestibular dysfunction could be excluded and central disorder may be suggested. Due to the prevalence of nystagmus of non-peripheral origin, a central nervous system involvement could not be excluded. However, due to the small sample size, a definite cause–effect relationship between vaccination and vertigo cannot be inferred. In light of expected third dose, large-scale and well-designed studies are needed to better define possible adverse reactions of the COVID-19 vaccine.
Complete Genome Sequencing and Comparative Genomics of Three Potential Probiotic Strains, Lacticaseibacillus casei FBL6, Lacticaseibacillus chiayiensis FBL7, and Lacticaseibacillus zeae FBL8
Authors: Kim Eiseul , Yang Seung-Min , Kim Dayoung , Kim Hae-Yeong
Published: January 2022

Lacticaseibacillus casei, Lacticaseibacillus chiayiensis, and Lacticaseibacillus zeae are very closely related Lacticaseibacillus species. L. casei has long been proposed as a probiotic, whereas studies on functional characterization for L. chiayiensis and L. zeae are some compared to L. casei. In this study, L. casei FBL6, L. chiayiensis FBL7, and L. zeae FBL8 were isolated from raw milk, and their probiotic properties were investigated. Genomic analysis demonstrated the role of L. chiayiensis and L. zeae as probiotic candidates. The three strains were tolerant to acid and bile salt, with inhibitory action against pathogenic bacterial strains and capacity of antioxidants. Complete genome sequences of the three strains were analyzed to highlight the probiotic properties at the genetic level, which results in the discovery of genes corresponding to phenotypic characterization. Moreover, genes known to confer probiotic characteristics were identified, including genes related to biosynthesis, defense machinery, adhesion, and stress adaptation. The comparative genomic analysis with other available genomes revealed 256, 214, and 32 unique genes for FBL6, FBL7, and FBL8, respectively. These genomes contained individual genes encoding proteins that are putatively involved in carbohydrate transport and metabolism, prokaryotic immune system for antiviral defense, and physiological control processes. In particular, L. casei FBL6 had a bacteriocin gene cluster that was not present in other genomes of L. casei, resulting in this strain may exhibit a wide range of antimicrobial activity compared to other L. casei strains. Our data can help us understand the probiotic functionalities of the three strains and suggest that L. chiayiensis and L. zeae species, which are closely related to L. casei, can also be considered as novel potential probiotic candidate strains.
A Recombinase Polymerase Amplification-Coupled Cas12a Mutant-Based Module for Efficient Detection of Streptomycin-Resistant Mutations in Mycobacterium tuberculosis
Authors: Liu Peng , Wang Xinjie , Liang Juan , Dong Qian , Zhang Jinping , Liu Dongxin , Wang Shuai , Bi Jing , Liu Wenqi , Wang Zhaoqin , Chen Liang , Liu Lei , Huang Xingxu , Zhang Guoliang
Published: January 2022

Drug-resistant tuberculosis (TB) is a serious public health problem and threat to global TB prevention and control. Streptomycin (STR) is the earliest and classical anti-TB drug, and it is the earliest drug that generated resistance to anti-TB treatment, which limits its use in treating TB and impedes TB control efforts. The rapid, economical, and highly sensitive detection of STR-resistant TB may help reduce disease transmission and morbimortality. CRISPR/CRISPR-associated protein (Cas) is a new-generation pathogen detection method that can detect single-nucleotide polymorphisms with high sensitivity and good specificity. In this study, a Cas12a RR detection system that can recognize more non-traditional protospacer-adjacent motif-targeting sequences was developed based on Cas12a combined with recombinase polymerase amplification technology. This system detects 0.1% of the target substance, and the entire detection process can be completed within 60 min. Its sensitivity and specificity for detecting clinical STR-resistant Mycobacterium tuberculosis were both 100%. Overall, the Cas12 RR detection system provides a novel alternative for the rapid, simple, sensitive, and specific detection of STR-resistant TB, which may contribute to the prompt treatment and prevention of disease transmission in STR-resistant TB.
Diabetes Treatment Is Associated With Better Cognitive Function: The Age Disparity
Authors: Wu Keyi , Liu Huamin , Zheng Jiazhen , Zou Lianwu , Gu Shanyuan , Zhou Rui , Yuan Zelin , Huang Zhiwei , Wu Xianbo
Published: January 2022

Background: Diabetes mellitus (DM) is a recognised risk factor for cognitive dysfunction. The purpose of this study was to explore the relationship between active treatment for DM and cognitive function in middle-aged (< 60 years) and older adults (≥60 years), respectively.

Methods: A total of 13,691 participants (58.55 ± 9.64 years, 47.40% of men) from the Chinese Health and Retirement Longitudinal Study (CHARLS) were included. The participants were classified into three groups according to whether or not they have diabetes and to their diabetes treatment status: diabetes-free, treated-diabetes and untreated-diabetes, in which the diabetes-free group was regarded as reference specially. Cognitive function was assessed by two interview-based measurements for mental intactness and episodic memory.

Results: Compared with the participants in the diabetes-free group, the older participants in the treated-diabetes group had better performance in terms of mental intactness (β = 0.37, 95% CI = 0.04–0.70). No significant association was observed in the middle-aged participants. In the subgroup analyses, the lower cognitive score was only observed in people without depression, who had never smoked and drunk, and with a normal weight (body mass index: 18.5–23.9 kg/m2).

Conclusion: The cognitive function of actively treated diabetic patients was better than that of patients without diabetes, but the improvement was significant only in elderly people. Depression, smoking, drinking, and an abnormal weight may attenuate this effect.
Disturbed Balance of Inhibitory Signaling Links Hearing Loss and Cognition
Authors: Knipper Marlies , Singer Wibke , Schwabe Kerstin , Hagberg Gisela E. , Li Hegner Yiwen , Rüttiger Lukas , Braun Christoph , Land Rüdiger
Published: January 2022

Neuronal hyperexcitability in the central auditory pathway linked to reduced inhibitory activity is associated with numerous forms of hearing loss, including noise damage, age-dependent hearing loss, and deafness, as well as tinnitus or auditory processing deficits in autism spectrum disorder (ASD). In most cases, the reduced central inhibitory activity and the accompanying hyperexcitability are interpreted as an active compensatory response to the absence of synaptic activity, linked to increased central neural gain control (increased output activity relative to reduced input). We here suggest that hyperexcitability also could be related to an immaturity or impairment of tonic inhibitory strength that typically develops in an activity-dependent process in the ascending auditory pathway with auditory experience. In these cases, high-SR auditory nerve fibers, which are critical for the shortest latencies and lowest sound thresholds, may have either not matured (possibly in congenital deafness or autism) or are dysfunctional (possibly after sudden, stressful auditory trauma or age-dependent hearing loss linked with cognitive decline). Fast auditory processing deficits can occur despite maintained basal hearing. In that case, tonic inhibitory strength is reduced in ascending auditory nuclei, and fast inhibitory parvalbumin positive interneuron (PV-IN) dendrites are diminished in auditory and frontal brain regions. This leads to deficits in central neural gain control linked to hippocampal LTP/LTD deficiencies, cognitive deficits, and unbalanced extra-hypothalamic stress control. Under these conditions, a diminished inhibitory strength may weaken local neuronal coupling to homeostatic vascular responses required for the metabolic support of auditory adjustment processes. We emphasize the need to distinguish these two states of excitatory/inhibitory imbalance in hearing disorders: (i) Under conditions of preserved fast auditory processing and sustained tonic inhibitory strength, an excitatory/inhibitory imbalance following auditory deprivation can maintain precise hearing through a memory linked, transient disinhibition that leads to enhanced spiking fidelity (central neural gain⇑) (ii) Under conditions of critically diminished fast auditory processing and reduced tonic inhibitory strength, hyperexcitability can be part of an increased synchronization over a broader frequency range, linked to reduced spiking reliability (central neural gain⇓). This latter stage mutually reinforces diminished metabolic support for auditory adjustment processes, increasing the risks for canonical dementia syndromes.
Prediction and Modeling of Neuropsychological Scores in Alzheimer’s Disease Using Multimodal Neuroimaging Data and Artificial Neural Networks
Authors: Hojjati Seyed Hani , Babajani-Feremi Abbas ,   the Alzheimer’s Disease Neuroimaging Initiative
Published: January 2022

Background: In recent years, predicting and modeling the progression of Alzheimer’s disease (AD) based on neuropsychological tests has become increasingly appealing in AD research.

Objective: In this study, we aimed to predict the neuropsychological scores and investigate the non-linear progression trend of the cognitive declines based on multimodal neuroimaging data.

Methods: We utilized unimodal/bimodal neuroimaging measures and a non-linear regression method (based on artificial neural networks) to predict the neuropsychological scores in a large number of subjects (n = 1143), including healthy controls (HC) and patients with mild cognitive impairment non-converter (MCI-NC), mild cognitive impairment converter (MCI-C), and AD. We predicted two neuropsychological scores, i.e., the clinical dementia rating sum of boxes (CDRSB) and Alzheimer’s disease assessment scale cognitive 13 (ADAS13), based on structural magnetic resonance imaging (sMRI) and positron emission tomography (PET) biomarkers.

Results: Our results revealed that volumes of the entorhinal cortex and hippocampus and the average fluorodeoxyglucose (FDG)-PET of the angular gyrus, temporal gyrus, and posterior cingulate outperform other neuroimaging features in predicting ADAS13 and CDRSB scores. Compared to a unimodal approach, our results showed that a bimodal approach of integrating the top two neuroimaging features (i.e., the entorhinal volume and the average FDG of the angular gyrus, temporal gyrus, and posterior cingulate) increased the prediction performance of ADAS13 and CDRSB scores in the converting and stable stages of MCI and AD. Finally, a non-linear AD progression trend was modeled to describe the cognitive decline based on neuroimaging biomarkers in different stages of AD.

Conclusion: Findings in this study show an association between neuropsychological scores and sMRI and FDG-PET biomarkers from normal aging to severe AD.
“Emergency Room Evaluation and Recommendations” (ER2) Tool for the Screening of Older Emergency Department Visitors With Major Neurocognitive Disorders: Results From the ER2 Database
Authors: Beauchet Olivier , Cooper-Brown Liam A. , Lubov Joshua , Allali Gilles , Afilalo Marc , Launay Cyrille P.
Published: January 2022

Purpose: The Emergency Room Evaluation and Recommendation (ER2) is an application in the electronic medical file of patients visiting the Emergency Department (ED) of the Jewish General Hospital (JGH; Montreal, Quebec, Canada). It screens for older ED visitors at high risk of undesirable events. The aim of this study is to examine the performance criteria (i.e., sensitivity, specificity, positive predictive value [PPV], negative predictive value [NPV], positive likelihood ratio [LR+], negative likelihood ratio [LR-] and area under the receiver operating characteristic curve [AUROC]) of the ER2 high-risk level and its “temporal disorientation” item alone to screen for major neurocognitive disorders in older ED visitors at the JGH.

Methods: Based on a cross-sectional design, 999 older adults (age 84.9 ± 5.6, 65.1% female) visiting the ED of the JGH were selected from the ER2 database. ER2 was completed upon the patients' arrival at the ED. The outcomes were ER2's high-risk level, the answer to ER2's temporal disorientation item (present vs. absent), and the diagnosis of major neurocognitive disorders (yes vs. no) which was confirmed when it was present in a letter or other files signed by a physician.

Results: The sensitivities of both ER2's high-risk level and temporal disorientation item were high (≥0.91). Specificity, the PPV, LR+, and AROC were higher for the temporal disorientation item compared to ER2's high-risk level, whereas a highest sensitivity, LR-, and NPV were obtained with the ER2 high-risk level. Both area under the receiver operating characteristic curves were high (0.71 for ER2's high-risk level and 0.82 for ER2 temporal disorientation item). The odds ratios (OR) of ER2's high-risk level and of temporal disorientation item for the diagnosis of major neurocognitive disorders were positive and significant with all OR above 18, the highest OR being reported for the temporal disorientation item in the unadjusted model [OR = 26.4 with 95% confidence interval (CI) = 17.7–39.3].

Conclusion: Our results suggest that ER2 and especially its temporal disorientation item may be used to screen for major neurocognitive disorders in older ED users.
Indirect Flow Diversion for Off-Centered Bifurcation Aneurysms and Distant Small-Vessel Aneurysms, a Retrospective Proof of Concept Study From Five Neurovascular Centers
Authors: Schob Stefan , Brill Richard , Siebert Eberhard , Sponza Massimo , Schüngel Marie-Sophie , Wohlgemuth Walter Alexander , Götz Nico , Mucha Dirk , Gopinathan Anil , Scheer Maximilian , Prell Julian , Bohner Georg , Gavrilovic Vladimir , Skalej Martin
Published: January 2022

Background: Treatment of cerebral aneurysms using hemodynamic implants such as endosaccular flow disruptors and endoluminal flow diverters has gained significant momentum during recent years. The intended target zone of those devices is the immediate interface between aneurysm and parent vessel. The therapeutic success is based on the reduction of aneurysmal perfusion and the subsequent formation of a neointima along the surface of the implant. However, a subset of aneurysms–off-centered bifurcation aneurysms involving the origin of efferent branches and aneurysms arising from peripheral segments of small cerebral vessels–oftentimes cannot be treated via coiling or implanting a hemodynamic implant at the neck level for technical reasons. In those cases, indirect flow diversion–a flow diverter deployed in the main artery proximal to the parent vessel of the aneurysm–can be a viable treatment strategy, but clinical evidence is lacking in this regard.

Materials and Methods: Five neurovascular centers contributed to this retrospective analysis of patients who were treated with indirect flow diversion. Clinical data, aneurysm characteristics, anti-platelet medication, and follow-up results, including procedural and post-procedural complications, were recorded.

Results: Seventeen patients (mean age: 60.5 years, range: 35–77 years) with 17 target aneurysms (vertebrobasilar: n = 9) were treated with indirect flow diversion. The average distance between the flow-diverting stent and the aneurysm was 1.65 mm (range: 0.4–2.4 mm). In 15/17 patients (88.2%), perfusion of the aneurysm was reduced immediately after implantation. Follow-ups were available for 12 cases. Delayed opacification (OKM A3: 11.8%), reduction in size (OKM B1-3: 29.4%) and occlusion (D1: 47.1%) were observable at the latest investigation. Clinically relevant procedural complications and adverse events in the early phase and in the late subacute phase were not observed in any case.

Conclusion: Our preliminary data suggest that indirect flow diversion is a safe, feasible, and effective approach to off-centered bifurcation aneurysms and distant small-vessel aneurysms. However, validation with larger studies, including long-term outcomes and optimized imaging, is warranted.
Neural Suppression Elicited During Motor Imagery Following the Observation of Biological Motion From Point-Light Walker Stimuli
Authors: Grazia Alice , Wimmer Michael , Müller-Putz Gernot R. , Wriessnegger Selina C.
Published: January 2022

Introduction: Advantageous effects of biological motion (BM) detection, a low-perceptual mechanism that allows the rapid recognition and understanding of spatiotemporal characteristics of movement via salient kinematics information, can be amplified when combined with motor imagery (MI), i.e., the mental simulation of motor acts. According to Jeannerod’s neurostimulation theory, asynchronous firing and reduction of mu and beta rhythm oscillations, referred to as suppression over the sensorimotor area, are sensitive to both MI and action observation (AO) of BM. Yet, not many studies investigated the use of BM stimuli using combined AO-MI tasks. In this study, we assessed the neural response in the form of event-related synchronization and desynchronization (ERD/S) patterns following the observation of point-light-walkers and concordant MI, as compared to MI alone.

Methods: Twenty right-handed healthy participants accomplished the experimental task by observing BM stimuli and subsequently performing the same movement using kinesthetic MI (walking, cycling, and jumping conditions). We recorded an electroencephalogram (EEG) with 32 channels and performed time-frequency analysis on alpha (8–13 Hz) and beta (18–24 Hz) frequency bands during the MI task. A two-way repeated-measures ANOVA was performed to test statistical significance among conditions and electrodes of interest.

Results: The results revealed significant ERD/S patterns in the alpha frequency band between conditions and electrode positions. Post hoc comparisons showed significant differences between condition 1 (walking) and condition 3 (jumping) over the left primary motor cortex. For the beta band, a significantly less difference in ERD patterns (p < 0.01) was detected only between condition 3 (jumping) and condition 4 (reference).

Discussion: Our results confirmed that the observation of BM combined with MI elicits a neural suppression, although just in the case of jumping. This is in line with previous findings of AO and MI (AOMI) eliciting a neural suppression for simulated whole-body movements. In the last years, increasing evidence started to support the integration of AOMI training as an adjuvant neurorehabilitation tool in Parkinson’s disease (PD).

Conclusion: We concluded that using BM stimuli in AOMI training could be promising, as it promotes attention to kinematic features and imitative motor learning.
Preferences for Renal Cell Carcinoma Pharmacological Treatment: A Discrete Choice Experiment in Patients and Oncologists
Authors: Fernández Ovidio , Lázaro-Quintela Martín , Crespo Guillermo , Soto de Prado Diego , Pinto Álvaro , Basterretxea Laura , Gómez de Liaño Alfonso , Etxaniz Olatz , Blasco Sara , Gabás-Rivera Clara , Aceituno Susana , Palomar Virginia , Polanco-Sánchez Carlos
Published: January 2022

Introduction

The purpose of this investigation was to explore patients’ and oncologists’ preferences for the characteristics of a pharmacological regimen for patients with advanced renal cell carcinoma (aRCC).

Material and Methods

Cross-sectional observational study based on a discrete choice experiment (DCE) conducted in Spain. A literature review, a focus group with oncologists and interviews with patients informed the DCE design. Five attributes were included: progression survival gain, risk of serious adverse events (SAEs), health-related quality of life (HRQoL), administration mode, and treatment cost. Preferences were analyzed using a mixed-logit model to estimate relative importance (RI) of attributes (importance of an attribute in relation to all others), which was compared between aRCC patients and oncologists treating aRCC. Willingness to pay (WTP, payer: health system) for a benefit in survival or in risk reduction and maximum acceptable risk (MAR) in SAEs for improving survival were estimated from the DCE. Subgroup analyses were performed to identify factors that influence preference.

Results

A total of 105 patients with aRCC (77.1% male, mean age 65.9 years [SD: 10.4], mean time since RCC diagnosis 6.3 years [SD: 6.1]) and 67 oncologists (52.2% male, mean age 41.9 years [SD: 8.4], mean duration of experience in RCC 10.2 years [SD: 7.5]) participated in the study. The most important attribute for patients and oncologists was survival gain (RI: 43.6% vs. 54.7% respectively, p<0.05), followed by HRQoL (RI: 35.5% vs. 18.0%, respectively, p<0.05). MAR for SAEs was higher among oncologists than patients, while WTP (for the health system) was higher for patients. Differences in preferences were found according to time since diagnosis and education level (patients) or length of professional experience (oncologists).

Conclusion

Patients’ and oncologists’ preferences for aRCC treatment are determined mainly by the efficacy (survival gain) but also by the HRQoL provided. The results of the study can help to inform decision-making in the selection of appropriate aRCC treatment.
An 11-Gene Signature Based on Treatment Responsiveness Predicts Radiation Therapy Survival Benefit Among Breast Cancer Patients
Authors: Shen Junjie , Yan Derui , Bai Lu , Geng Ruirui , Zhao Xulun , Li Huijun , Dong Yongfei , Cao Jianping , Tang Zaixiang , Liu Song-bai
Published: January 2022

Purpose

We developed a strategy of building prognosis gene signature based on clinical treatment responsiveness to predict radiotherapy survival benefit in breast cancer patients.

Methods and Materials

Analyzed data came from the public database. PFS was used as an indicator of clinical treatment responsiveness. WGCNA was used to identify the most relevant modules to radiotherapy response. Based on the module genes, Cox regression model was used to build survival prognosis signature to distinguish the benefit group of radiotherapy. An external validation was also performed.

Results

In the developed dataset, MEbrown module with 534 genes was identified by WGCNA, which was most correlated to the radiotherapy response of patients. A number of 11 hub genes were selected to build the survival prognosis signature. Patients that were divided into radio-sensitivity group and radio-resistant group based on the signature risk score had varied survival benefit. In developed dataset, the 3-, 5-, and 10-year AUC of the signature were 0.814 (CI95%: 0.742–0.905), 0.781 (CI95%: 0.682–0.880), and 0.762 (CI95%: 0.626–0.897), respectively. In validation dataset, the 3- and 5-year AUC of the signature were 0.706 (CI95%: 0.523–0.889) and 0.743 (CI95%: 0.595–0.891). The signature had higher predictive power than clinical factors alone and had more clinical prognosis efficiency. Functional enrichment analysis revealed that the identified genes were mainly enriched in immune-related processes. Further immune estimated analysis showed the difference in distribution of immune micro-environment between radio-sensitivity group and radio-resistant group.

Conclusions

The 11-gene signature may reflect differences in tumor immune micro-environment that underlie the differential response to radiation therapy and could guide clinical-decision making related to radiation in breast cancer patients.
Neonates in the Intensive Care Unit: Maternal Health-Related Quality of Life and Depression After Term and Preterm Births
Authors: Mautner Eva , Stern Christina , Avian Alexander , Deutsch Maria , Schöll Wolfgang , Greimel Elfriede
Published: January 2022

Background/Objective: To examine maternal physical and mental health-related quality of life (HRQoL) and depression after early and late preterm and term births in the early postpartum period.

Method: In a prospective pilot study, three groups of women whose newborns had to be treated in the neonatal ward during the immediate postpartum period were established and compared with each other: 20 women with extremely to very preterm birth, 20 with moderate to late preterm birth and 20 women with term birth. All participants completed the Short Form-12 Health Survey (SF-12) to measure HRQoL, and the Edinburgh Postnatal Depression Scale (EPDS) to detect depressive symptoms combined with independently developed questions to evaluate anxiety and psychological distress.

Results: Maternal psychological HRQoL was significantly worse in the very preterm birth group compared to moderate to late preterm birth (p < 0.001) and full-term birth groups (p = 0.004). There were no differences between the birth groups in depressive symptoms (p = 0.083), anxiety (p = 0.238), perceived stress (p = 0.340) and the general psychological distress values (p = 0.755). In the EPDS, the depression screening instrument 30 to 65% were beyond the cut-off-value to detect major depression.

Conclusions: During the early postpartum period, an extensive medical care focussing on acute stress, HRQoL parameters and depression may be a good step to improving maternal well-being.
Arsenic-Related Health Risk Assessment of Realgar-Containing NiuHuangJieDu Tablets in Healthy Volunteers Po Administration
Authors: Wu Xiao , Yan Ruoning , Guan Rong , Du Yi , Liu Yuexin , Wu Shanhu , Zhu Song , Song Min , Hang Taijun
Published: January 2022

Realgar, an arsenic-containing traditional Chinese medicine of As2S2, has significant therapeutic effects for hundreds of years. NiuHuangJieDu tablets (NHJDT) is one of the most commonly prescribed realgar-containing preparations for the treatment of sore throat, swelling, and aching of gums. However, realgar-containing TCMs raise great safety concerns due to the adverse effects reported by arsenic poisoning. In this study, the arsenic-related health risk assessment of NHJDT was conducted in healthy volunteers after single and multiple doses oral administration. Blood, plasma, and urine samples were collected after dosing at predetermined time points or periods. Simple, rapid, and sensitive methods were established for the quantification of total arsenic and arsenic speciation in biological samples. The total arsenic and arsenic speciation were determined by hydride generation-atomic fluorescence spectrometry (HG-AFS) and high-performance liquid chromatography–hydride generation–atomic fluorescence spectrometry (HPLC-HG-AFS), respectively. No significant fluctuation of total arsenic was observed in human blood, and no traces of arsenic speciation were found in human plasma. Dimethylarsenic acid was detected as the predominated arsenic species in human urine after dosing. Therapeutic dose administration of NHJDT was relatively safe in single dose for the limited blood arsenic exposure, but long-term medication may still pose health risks due to the accumulation of arsenics in blood and its extremely slow excretion rate. Therefore, arsenic exposure should be carefully monitored during realgar-containing TCM medication, especially for long-term regimen. The results obtained in this study will provide scientific references for the clinical application of realgar and its-containing TCMs.
Association Between Nonselective Beta-Blocker Use and Hepatocellular Carcinoma in Patients With Chronic Hepatitis B Without Cirrhosis and Decompensation
Authors: Cheng He-Yun , Lin Hsiu C. , Lin Hsiu L. , Uang Yow S. , Keller Joseph J. , Wang Li H.
Published: January 2022

Background: Nonselective beta-blockers (NSBBs) can reduce the incidence or mortality of certain types of cancers, and NSBBs exert a protective effect on hepatocellular carcinoma (HCC) in patients with cirrhosis. However, the potential preventive effect of NSBBs has not yet been investigated in patients with chronic hepatitis B (CHB) who have a high HCC risk regardless of the presence of underlying cirrhosis.

Aim: This study evaluated the association between NSBB use and HCC incidence in patients with CHB without cirrhosis and decompensation.

Methods: From the 2000 Longitudinal Generation Tracking Database, we enrolled patients who were newly diagnosed as having CHB from January 2001 to December 2011 and then followed them up for at least 5 years. To estimate the causal effect of NSBBs on the time-to-event outcomes of HCC, a marginal Cox proportional hazards model was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs).

Results: After adjustment, no significant benefit of HCC risk reduction was observed between the NSBB users and nonusers (adjusted HR, 0.82; 95% CI, 0.52–1.31). The cumulative defined daily dose (cDDD) analysis revealed no significant dose correlation among the three groups [adjusted HR (95% CI): 1.08, (0.56–2.05), 0.54 (0.17–1.77), and 0.76 (0.40–1.42) in the <90 cDDD, 90 to <180 cDDD, and ≥180 cDDD groups, respectively]. Duration-dependent associations were not observed. Multivariable stratified analysis results demonstrated that HCC risk markedly decreased in the patients aged >55 years (adjusted HR, 0.49; 95% CI, 0.25–0.96; p = 0.04).

Conclusion: NSBB did not significantly prevent HCC in the patients with CHB infection without cirrhosis and decompensation. This study provided one of valuable results that it is not clinically required to use NSBBs as recommended chemoprevention for HCC in high-risk patients who have CHB.
Genetic Blockade of NAAA Cell-specifically Regulates Fatty Acid Ethanolamides (FAEs) Metabolism and Inflammatory Responses
Authors: Xie Xiaohua , Li Yitian , Xu Sennan , Zhou Pan , Yang Longhe , Xu Yaping , Qiu Yan , Yang Yungang , Li Yuhang
Published: January 2022

N-Acylethanolamine acid amidase (NAAA) is a lysosomal enzyme responsible for the hydrolysis of fatty acid ethanolamides (FAEs). However, the role of NAAA in FAEs metabolism and regulation of pain and inflammation remains mostly unknown. Here, we generated NAAA-deficient (NAAA-/-) mice using CRISPR-Cas9 technique, and found that deletion of NAAA increased PEA and AEA levels in bone marrow (BM) and macrophages, and elevated AEA levels in lungs. Unexpectedly, genetic blockade of NAAA caused moderately effective anti-inflammatory effects in lipopolysaccharides (LPS)-induced acute lung injury (ALI), and poor analgesic effects in carrageenan-induced hyperalgesia and sciatic nerve injury (SNI)-induced mechanical allodynia. These data contrasted with acute (single dose) or chronic NAAA inhibition by F96, which produced marked anti-inflammation and analgesia in these models. BM chimera experiments indicated that these phenotypes were associated with the absence of NAAA in non-BM cells, whereas deletion of NAAA in BM or BM-derived cells in rodent models resulted in potent analgesic and anti-inflammatory phenotypes. When combined, current study suggested that genetic blockade of NAAA regulated FAEs metabolism and inflammatory responses in a cell-specifical manner.
Cementation of Sand With Enzyme-Induced Carbonate Precipitation (EICP) Using Concrete-Extracted Calcium
Authors: He Jia , Mao Xunyu , Zhou Yundong , Tang Qiang
Published: January 2022

Calcium carbonate precipitation and crystallization induced by urease enzyme to solidify soil is known as biocement technology. The uses of waste and cheap materials can make this technology more cost-effective and practical for applications. In this study, calcium ions were obtained by dissolving waste concretes in acidic liquid. Sand columns were treated by enzyme-induced carbonate precipitation (EICP) with either concrete-extracted calcium or reagent calcium for comparison. Compressive strengths, calcium carbonate contents, and microscopic analysis on the treated sand were carried out. It was found that the compressive strength of the former could reach 833 kPa in the dry state and 204 kPa in the wet state after 5 times of EICP treatment, both of which were higher than that of the latter. The calcium carbonate contents could reach 2–3% after 3–5 times of treatment. Based on the scanning electron microscope (SEM) and X-ray diffractometer (XRD) analyses, the crystal type of calcium carbonate produced in sand was calcite. The comparative results showed that the treatment effect using concrete-extracted calcium was similar or better than that using reagent calcium.
How to Tackle Phylogenetic Discordance in Recent and Rapidly Radiating Groups? Developing a Workflow Using Loricaria (Asteraceae) as an Example
Authors: Kandziora Martha , Sklenář Petr , Kolář Filip , Schmickl Roswitha
Published: January 2022

A major challenge in phylogenetics and -genomics is to resolve young rapidly radiating groups. The fast succession of species increases the probability of incomplete lineage sorting (ILS), and different topologies of the gene trees are expected, leading to gene tree discordance, i.e., not all gene trees represent the species tree. Phylogenetic discordance is common in phylogenomic datasets, and apart from ILS, additional sources include hybridization, whole-genome duplication, and methodological artifacts. Despite a high degree of gene tree discordance, species trees are often well supported and the sources of discordance are not further addressed in phylogenomic studies, which can eventually lead to incorrect phylogenetic hypotheses, especially in rapidly radiating groups. We chose the high-Andean Asteraceae genusLoricariato shed light on the potential sources of phylogenetic discordance and generated a phylogenetic hypothesis. By accounting for paralogy during gene tree inference, we generated a species tree based on hundreds of nuclear loci, using Hyb-Seq, and a plastome phylogeny obtained from off-target reads during target enrichment. We observed a high degree of gene tree discordance, which we found implausible at first sight, because the genus did not show evidence of hybridization in previous studies. We used various phylogenomic analyses (trees and networks) as well as the D-statistics to test for ILS and hybridization, which we developed into a workflow on how to tackle phylogenetic discordance in recent radiations. We found strong evidence for ILS and hybridization within the genusLoricaria. Low genetic differentiation was evident between species located in different Andean cordilleras, which could be indicative of substantial introgression between populations, promoted during Pleistocene glaciations, when alpine habitats shifted creating opportunities for secondary contact and hybridization.
EARLY FLOWERING 3 and Photoperiod Sensing in Brachypodium distachyon
Authors: Bouché Frédéric , Woods Daniel P. , Linden Julie , Li Weiya , Mayer Kevin S. , Amasino Richard M. , Périlleux Claire
Published: January 2022

The proper timing of flowering, which is key to maximize reproductive success and yield, relies in many plant species on the coordination between environmental cues and endogenous developmental programs. The perception of changes in day length is one of the most reliable cues of seasonal change, and this involves the interplay between the sensing of light signals and the circadian clock. Here, we describe a Brachypodium distachyon mutant allele of the evening complex protein EARLY FLOWERING 3 (ELF3). We show that the elf3 mutant flowers more rapidly than wild type plants in short days as well as under longer photoperiods but, in very long (20 h) days, flowering is equally rapid in elf3 and wild type. Furthermore, flowering in the elf3 mutant is still sensitive to vernalization, but not to ambient temperature changes. Molecular analyses revealed that the expression of a short-day marker gene is suppressed in elf3 grown in short days, and the expression patterns of clock genes and flowering time regulators are altered. We also explored the mechanisms of photoperiodic perception in temperate grasses by exposing B. distachyon plants grown under a 12 h photoperiod to a daily night break consisting of a mixture of red and far-red light. We showed that 2 h breaks are sufficient to accelerate flowering in B. distachyon under non-inductive photoperiods and that this acceleration of flowering is mediated by red light. Finally, we discuss advances and perspectives for research on the perception of photoperiod in temperate grasses.