bluuebunny/crossref_metadata_2025 huggingface dataset:
Varicocele, wat moet je ermee? Een overzicht van evidence based informatie en controverse als basis voor een goed gesprek
Authors: Dinkelman-Smit Marij
Published: February 2022

Samenvatting

In dit overzichtsartikel wordt de relatie besproken tussen een varicocele, mannelijke subfertiliteit, kans op een kind met en zonder behandeling van de varicocele na natuurlijke conceptie of geassisteerde voortplanting. Er wordt kort ingegaan op de verschillende theorieën over de pathofysiologie van de varicocele. Daarnaast worden de klinische diagnose en de overwegingen besproken rond de selectie en indicatiestelling bij subfertiele mannen, kinderen en adolescenten met een varicocele, en bij mannen met klachten en hypogonadisme. Tot slot worden de verschillende behandeltypen, uitkomst, recidief en evaluatie van het effect van interventies doorgenomen.
Segment-Unit Reading Comprehension Training for Japanese Students with Autism Spectrum Disorder and Learning Disabilities
Authors: Omori Mikimasa , Yamamoto Junichi
Published: February 2022

Students with autism spectrum disorder (ASD) and learning disabilities (LDs) often experience reading difficulties. In particular, reading long passages can cause comprehension problems. We examined whether 8 Japanese students with ASD, 7 students with LDs, and 13 typically developing (TD) students improved their reading comprehension through two types of repeated reading training: whole-sentence-unit reading (WSUR) training and segment-unit reading (SUR) training. Participants undergoing WSUR training read whole sentences repeatedly. In SUR training, they repeatedly read a segment of a sentence in its correct spatial location. Results indicated that students with ASD and LDs showed greater improvement in reading comprehension after SUR training than after WSUR training, whereas both procedures were equally effective for TD students. Moreover, students with ASD showed only negligible reading comprehension improvements, whereas students with LDs showed intermediate improvements after WSUR training. These results suggest that sequentially presenting word segments can improve the reading comprehension of students with ASD and specific LDs.
Decision-making based on probabilistic linguistic term sets without loss of information
Authors: Yi Zhihong
Published: February 2022

Probabilistic linguistic term set (PLTS) provides a much more effective model to compute with words and to express the uncertainty in the pervasive natural language by probability information. In this paper, to avoid loss of information, we redefine the classical probabilistic linguistic term sets (PLTSs) by multiple probability distributions from an ambiguity perspective and present some basic operations using Archimedean t-(co)norms. Different from the classical PLTSs, the reformulated PLTSs are not necessarily normalized beforehand for further investigations. Moreover, the multiple probability distributions based PLTSs facilitate the incorporation of the different attitudes of the DMs in their score values and the deviation, and thus the comparisons. Then the Decision-Making Trial and Evaluation Laboratory (DEMATEL) method is extended to the reformulated PLTS frame by incorporating probability information. With these newly developed elements in the reformulated PLTSs, a DEMATEL based multiple attributes decision-making is proposed. The illustrative example and comparison analysis show that the method over the reformulated PLTSs is feasible and valid, and has the advantage in processing without any information loss (i.e., without normalization) and fully exploration of the DMs-preference and knowledge.
TAUNet: a triple-attention-based multi-modality MRI fusion U-Net for cardiac pathology segmentation
Authors: Li Dapeng , Peng Yanjun , Guo Yanfei , Sun Jindong
Published: February 2022

Automated segmentation of cardiac pathology in MRI plays a significant role for diagnosis and treatment of some cardiac disease. In clinical practice, multi-modality MRI is widely used to improve the cardiac pathology segmentation, because it can provide multiple or complementary information. Recently, deep learning methods have presented implausible performance in multi-modality medical image segmentation. However, how to fuse the underlying multi-modality information effectively to segment the pathology with irregular shapes and small region at random locations, is still a challenge task. In this paper, a triple-attention-based multi-modality MRI fusion U-Net was proposed to learn complex relationship between different modalities and pay more attention on shape information, thus to achieve improved pathology segmentation. First, three independent encoders and one fusion encoder were applied to extract specific and multiple modality features. Secondly, we concatenate the modality feature maps and use the channel attention to fuse specific modal information at every stage of the three dedicate independent encoders, then the three single modality feature maps and channel attention feature maps are together concatenated to the decoder path. Spatial attention was adopted in decoder path to capture the correlation of various positions. Once more, we employ shape attention to focus shape-dependent information. Lastly, the training approach is made efficient by introducing deep supervision mechanism with object contextual representations block to ensure precisely boundary prediction. Our proposed network was evaluated on the public MICCAI 2020 Myocardial pathology segmentation dataset which involves patients suffering from myocardial infarction. Experiments on the dataset with three modalities demonstrate the effectiveness of fusion mode of our model, and attention mechanism can integrate various modality information well. We demonstrated that such a deep learning approach could better fuse complementary information to improve the segmentation performance of cardiac pathology.
Critical Correlation of Predictors for an Efficient Risk Prediction Framework of ICU Patient Using Correlation and Transformation of MIMIC-III Dataset
Authors: Khope Sarika R. , Elias Susan
Published: February 2022

Various predictive frameworks have evolved over the last decade to facilitate the efficient diagnosis of critical diseases in the healthcare sector. Some have been commercialized, while others are still in the research and development stage. An effective early predictive principle must provide more accurate outcomes in complex clinical data and various challenging environments. The open-source database system medical information mart for intensive care (MIMIC) simplifies all of the attributes required in predictive analysis in this regard. This database contains clinical and non-clinical information on a patient’s stay at a healthcare facility, gathered during their duration of stay. Regardless of the number of focused research attempts employing the MIMIC III database, a simplified and cost-effective computational technique for developing the early analysis of critical problems has not yet been found. As a result, the proposed study provides a novel and cost-effective machine learning framework that evolves into a novel feature engineering methodology using the MIMIC III dataset. The core idea is to forecast the risk associated with a patient’s clinical outcome. The proposed study focused on the diagnosis and clinical procedures and found distinct variants of independent predictors from the MIMIC III database and ICD-9 code. The proposed logic is scripted in Python, and the outcomes of three common machine learning schemes, namely Artificial Neural Networks, K-Nearest Neighbors, and Logistic Regression, have been evaluated. Artificial Neural Networks outperform alternative machine learning techniques when accuracy is taken into account as the primary performance parameter over the MIMIC III dataset.
Log-concavity and other concepts of bivariate increasing failure rate distributions
Authors: Gupta Ramesh C. , Kirmani S. N. U. A.
Published: February 2022

Log-concavity of a joint survival function is proposed as a model for bivariate increasing failure rate (BIFR) distributions. Its connections with or distinctness from other notions of BIFR are discussed. A necessary and sufficient condition for a bivariate survival function to be log-concave (BIFR-LCC) is given that elucidates the impact of dependence between lifetimes on ageing. Illustrative examples are provided to explain BIFR-LCC for both positive and negative dependence.
Science interrupted
Authors: Parma Valentina , Arceneaux Kevin
Published: February 2022

Abstract

Recent research contends that the behavioral immune system, operating largely outside conscious awareness, motivates individuals to exhibit higher levels of prejudice toward unfamiliar out-groups. This research finds that individual variance in disgust sensitivity correlates with support for political policies that facilitate the avoidance of out-groups. We were interested in developing less intrusive indicators of disgust sensitivity via olfactory measures (i.e., ratings of disgusting odors) and behavioral measures (e.g., willingness to touch disgusting objects) and studying the association between measures of disgust sensitivity and in-group bias among children and adults. We submitted a registered report to conduct this research and received an in-principle acceptance. Unfortunately, unforeseen events impaired our data collection, leaving us with a limited sample (nchildren = 32, nadults = 29) and reducing our ability to draw reliable conclusions from our results. In this essay, we describe our motivation and plan of research, the events that made completing the research impossible, and our preliminary results. In doing so, we hope to offer support for studying the effects of the behavioral immune system, even in ways that we did not originally plan. We conclude with a reflection on the value of registered reports for advancing science.
Challenging UN Security Council- and International Criminal Court-Requested Asset Freezes in Domestic Courts: Views from the United Kingdom and Italy
Authors: Birkett Daley J , Sejko Dini
Published: February 2022

This article analyses attempts by the Libyan Investment Authority (LIA), the sovereign wealth fund of Libya, to challenge the domestic implementation of asset-freezing measures requested by the United Nations Security Council (UNSC) and the International Criminal Court (ICC) in the United Kingdom (UK) and Italy. The UNSC requested that states freeze LIA assets in early 2011 before partially easing the restrictions imposed in September of the same year, while the ICC requested the freezing of assets belonging to the then Libyan leader, Muammar Gaddafi, and two further accused persons shortly thereafter. The article scrutinises how these measures were incorporated into the legal orders of the UK and Italy before analysing how the LIA has challenged these actions in the Italian courts and those of England and Wales. In so doing, it aims to demonstrate that domestic courts offer additional fora in which individuals (and entities) might seek to enforce the legal protection to which they are entitled when faced with their assets having been frozen by states at the request of the UNSC and/or the ICC.
Historical Diaglossia and the Selection of Multiple Norms:MijandMijnas 1st Person Singular Object Pronouns in 17th- and 18th-Century Dutch
Authors: Rutten Gijsbert
Published: February 2022

This paper argues that the Dutch sociolinguistic situation in the 17th and 18th centuries should be analyzed as diaglossic, that is, involving a wide spectrum of variation in between localized spoken dialects and the supposed written standard. In fact, multiple instances of norm selection for writing render this diaglossic situation even more complex. The paper shows that multiple norm selection even occurred in cases when a strict and simple norm was selected early on, that is, in the late 16th–early 17th century. The case study is based on the Letters as Loot Corpus comprising private letters from the 1660s–1670s and the 1770s–1780s and focuses on the object form of the 1st person singular personal pronoun, namely,mijormijn. Despite the early selection ofmij, some language users in the late 17th and 18th century adoptedmijnin writing. The analysis shows a normative split in written Dutch of the time, with most language users either converging to or diverging from the supposed standard formmij.*
“A kaleidoscope of relationships” — cervical cancer survivors’ perspectives on their intimate relationships: A qualitative study
Authors: Levkovich Inbar , Hamama-Raz Yaira , Shinan-Altman Shiri
Published: February 2022

Objective

Cervical cancer is known to affect survivors’ intimate relationships, as well as their communication and coping. Yet little is known about the perspectives of these survivors on their intimate relationships in the context of their needs during and after medical treatment. Additionally, only a few studies have focused on survivors’ perceived needs or on existing psychosexual support. Understanding these perceptions can help provide a tailored response and improve dyadic interventions. The aim of this study was to examine cervical cancer survivors’ perspectives on their intimate relationships during and after their treatment.

Method

The present study adopted a qualitative-phenomenological approach. In-depth, semi-structured interviews were conducted with 15 survivors of cervical cancer between the ages of 38 and 44 who were diagnosed at stages I–II and were treated with radiotherapy or chemo-radiotherapy and surgery. Data collection continued until saturation of concepts was reached. The results underwent thematic analysis.

Results

Analysis of the findings revealed two key themes: (1) Together and apart in the shadow of cervical cancer. This theme focuses on the recovery period as a potential opportunity for changing and improving the couple relationship, such that men no longer withdraw but rather provide their partners with needed support and encouragement. (2) Changes in sexual life and couple intimacy. This theme focuses on changes in sexual relations, which have become a burden, painful, and something to avoid.

Significance of results

The study provides a comprehensive picture of intimate relationships during and after cervical cancer treatment and highlights the women's needs and desires for support from their intimate partners. The discussion notes that oncology providers can better facilitate supportiveness on the part of cervical cancer partners by offering better couple-oriented education and interventions to promote couple communication.
An act of love
Authors: Gambril John Alan
Published: February 2022

End-of-life conversations are a difficult part of medicine. The COVID-19 pandemic has made them simultaneously more necessary and more difficult. Encouraging patients to have these conversations with their own providers and loved ones can help ensure, when the unfortunate time comes, their end-of-life wishes are carried out. This honors the patient and limits burden on others. Here, I reflect on how my personal experience as both a grieving grandson and as a resident physician has emphasized the importance of end-of-life conversations.
Strong ULVZ and Slab Interaction at the Northeastern Edge of the Pacific LLSVP Favors Plume Generation
Authors: Lai Voon Hui , Helmberger Don V. , Dobrosavljevic Vasilije V. , Wu Wenbo , Sun Daoyuan , Jackson Jennifer M. , Gurnis Michael
Published: February 2022

Strong waveform complexities, including multipathing of the S diffracted phase and rapid changes in differential ScS‐S times, are observed for multiple deep Fiji earthquakes recorded at the USArray. The complexities occur at the northeastern edge of the Pacific Large Low Shear Velocity Province (LLSVP), about 12 degrees southeast of present‐day Hawaiʻi. Waveform modeling of the multipathing provides good constraints on an ultra‐low velocity zone (ULVZ) with a width of 5 degree located near the inner edge of the LLSVP. Based on the mineralogical‐modeling of the ULVZ as a solid iron‐rich magnesiowüstite‐bearing assemblage with compatible morphology predicted from geodynamical simulations, a ULVZ model with a thickness of 30 km and a shear wave velocity reduction of 18% is preferred. The rapid change in differential ScS‐S travel time is best explained by having both the aforementioned ULVZ and an adjacent high velocity structure near the LLSVP. Furthermore, a low‐velocity plume‐like structure could potentially explain the observed S travel time delay independent of ScS. These seismic features are proposed to be a ULVZ driven toward the edge of the LLSVP while potentially pushed by a subducted slab. This configuration may trigger plume generation due to strong thermal instabilities and is in the same vicinity where mantle flow models place the present‐day Hawaiian plume source. Multiple ScS can potentially be used to verify vertical plume structure in tomographic models but the accuracy of upper mantle structure, which is a key reflection point, needs to be considered.
Wintertime Brine Discharge at the Surface of a Cold Polar Glacier and the Unexpected Absence of Associated Seismicity
Authors: Carr C. G. , Carmichael J. D. , Pettit E. C.
Published: February 2022

A subglacial groundwater system beneath Taylor Glacier, Antarctica, discharges hypersaline, iron‐rich brine episodically at the glacier surface to create Blood Falls. However, the triggering mechanism for these brine release events is not yet understood. Identifying which fracture processes are observed seismically can help us better characterize the hydrological system at Taylor Glacier, and more generally, provide us with a broader understanding of englacial hydrologic activity in cold glaciers. We document wintertime brine discharge using time‐lapse photography. Subfreezing air temperatures during the brine discharge indicate that surface melt‐induced hydrofracture is an unlikely trigger for brine release. Further, we analyze local seismic data to test a hypothesis that fracturing generates elevated surface wave energy preceding and/or coinciding with brine release events. Our results show no discernible elevated Rayleigh wave activity prior to or during Blood Falls brine release. Instead, we find a pattern of seismic events dominated by a seasonal signal, with more Rayleigh events occurring in the summer than the winter from the Blood Falls source area. We calculate that the volumetric opening of cracks that would generate Rayleigh waves at our detection limits are of similar size to myriad cracks in glacier ice, lake ice, and frozen sediment in the terminus area. We therefore propose that any fracturing coincident with brine release activity likely consists of a series of smaller opening events that are masked by other seismicity in the local environment.
Molecular regulations of circadian rhythm and implications for physiology and diseases
Authors: Fagiani Francesca , Di Marino Daniele , Romagnoli Alice , Travelli Cristina , Voltan Davide , Di Cesare Mannelli Lorenzo , Racchi Marco , Govoni Stefano , Lanni Cristina
Published: February 2022

The term “circadian rhythms” describes endogenous oscillations with ca. 24-h period associated with the earth’s daily rotation and light/dark cycle. Such rhythms reflect the existence of an intrinsic circadian clock that temporally orchestrates physiological processes to adapt the internal environment with the external cues. At the molecular level, the circadian clock consists of multiple sets of transcription factors resulting in autoregulatory transcription-translation feedback loops. Notably, in addition to their primary role as generator of circadian rhythm, the biological clock plays a key role in controlling physiological functions of almost all tissues and organs. It regulates several intracellular signaling pathways, ranging from cell proliferation, DNA damage repair and response, angiogenesis, metabolic and redox homeostasis, to inflammatory and immune response. In this review, we summarize findings showing the crosstalk between the circadian molecular clock and some key intracellular pathways, describing a scenario wherein their reciprocal regulation impinges upon several aspects of mammalian physiology. Moreover, based on evidence indicating that circadian rhythms can be challenged by environmental factors, social behaviors, as well as pre-existing pathological conditions, we discuss implications of circadian misalignment in human pathologies, such as cancer and inflammatory diseases. Accordingly, disruption of circadian rhythm has been reported to affect several physiological processes that are relevant to human diseases. Expanding our understanding of this field represents an intriguing and transversal medicine challenge in order to establish a circadian precision medicine.
Parallel profiling of antigenicity alteration and immune escape of SARS-CoV-2 Omicron and other variants
Authors: Sun Cong , Kang Yin-Feng , Liu Yuan-Tao , Kong Xiang-Wei , Xu Hui-Qin , Xiong Dan , Xie Chu , Liu Yi-Hao , Peng Sui , Feng Guo-Kai , Liu Zheng , Zeng Mu-Sheng
Published: February 2022

SARS-CoV-2 variants have evolved a variety of critical mutations, leading to antigenicity changes and immune escape. The recent emerging SARS-CoV-2 Omicron variant attracted global attention due to its significant resistance to current antibody therapies and vaccines. Here, we profiled the mutations of Omicron and other various circulating SARS-CoV-2 variants in parallel by computational interface analysis and in vitro experimental assays. We identified critical mutations that lead to antigenicity changes and diminished neutralization efficiency of a panel of 14 antibodies due to diverse molecular mechanisms influencing the antigen-antibody interaction. Our study identified that Omicron exhibited extraordinary potency in immune escape compared to the other variants of concern, and explores the application of computational interface analysis in SARS-CoV-2 mutation surveillance and demonstrates its potential for the early identification of concerning variants, providing preliminary guidance for neutralizing antibody therapy.
Inhibition of mitoNEET attenuates LPS-induced inflammation and oxidative stress
Authors: Lee Seunghee , Seok Byeong Geun , Lee Seon-Jin , Chung Su Wol
Published: February 2022

MitoNEET (mitochondrial protein containing Asn–Glu–Glu–Thr (NEET) sequence) is a 2Fe–2S cluster-containing integral membrane protein that resides in the mitochondrial outer membrane and participates in a redox-sensitive signaling and Fe–S cluster transfer. Thus, mitoNEET is a key regulator of mitochondrial oxidative capacity and iron homeostasis. Moreover, mitochondrial dysfunction and oxidative stress play critical roles in inflammatory diseases such as sepsis. Increased iron levels mediated by mitochondrial dysfunction lead to oxidative damage and generation of reactive oxygen species (ROS). Increasing evidence suggests that targeting mitoNEET to reverse mitochondrial dysfunction deserves further investigation. However, the role of mitoNEET in inflammatory diseases is unknown. Here, we investigated the mechanism of action and function of mitoNEET during lipopolysaccharide (LPS)-induced inflammatory responses in vitro and in vivo. Levels of mitoNEET protein increased during microbial or LPS-induced sepsis. Pharmacological inhibition of mitoNEET using mitoNEET ligand-1 (NL-1) decreased the levels of pro-inflammatory cytokines such as IL-1β, IL-6, and TNF-α in animal models of sepsis, as well as LPS-induced inflammatory responses by macrophages in vitro. Inhibition of mitoNEET using NL-1 or mitoNEET shRNA abrogated LPS-induced ROS formation and mitochondrial dysfunction. Furthermore, mitochondrial iron accumulation led to generation of LPS-induced ROS, a process blocked by NL-1 or shRNA. Taken together, these data suggest that mitoNEET could be a key therapeutic molecule that targets mitochondrial dysfunction during inflammatory diseases and sepsis.
Role of mTORC1 activity during early retinal development and lamination in human-induced pluripotent stem cell‐derived retinal organoids
Authors: Lee Si Hyung , Han Jung Woo , Yang Jin Young , Jun Hyoung Oh , Bang Ji Hong , Shin Heejeong , Choi Ji Hye , Lee Jongwoo , Madrakhimov Sanjar Batirovich , Chung Kyung Hwun , Chang Hun Soo , Lyu Jungmook , Park Tae Kwann
Published: February 2022

Retinal organoids derived from human-induced pluripotent stem cells (hiPSC) are powerful tools for studying retinal development as they model spatial and temporal differentiation of retinal cell types. Vertebrate retinal development involves a delicate and coordinated process of retinal progenitor cell (RPC) differentiation, and the mammalian target of rapamycin complex 1 (mTORC1) has been reported to play a significant role in this complex process. Herein, using hiPSC-derived retinal organoids, we identify the time-dependent role of mTORC1 in retinal development, specifically in retinal ganglion cell (RGC) differentiation and the retinal lamination process, during the early stages of retinal organoid (RO) development. mTORC1 activity in ROs was the highest at 40 days of differentiation. MHY1485-induced hyperactivation of mTORC1 during this period resulted in a significant increase in the overall size of ROs compared to the untreated controls and rapamycin-treated Ros; there was also a marked increase in proliferative activity within the inner and outer layers of ROs. Moreover, the MHY1485-treated ROs showed a significant increase in the number of ectopic RGCs in the outer layers (indicating disruption of retinal laminar structure), with robust expression of HuC/D-binding proteins in the inner layers. These results demonstrate that mTORC1 plays a critical role in the development of hiPSC-derived ROs, especially during the early stages of differentiation.
ECM1 modified HF-MSCs targeting HSC attenuate liver cirrhosis by inhibiting the TGF-β/Smad signaling pathway
Authors: Liu Qi , Lv Chengqian , Huang Qianqian , Zhao Lei , Sun Xiaoli , Ning Dandan , Liu Jingyang , Jiang Yanan , Jin Shizhu
Published: February 2022

Hair follicle-derived mesenchymal stem cells (HF-MSCs) show considerable therapeutic potential for liver cirrhosis (LC). To improve the effectiveness of naïve HF-MSC treatments on LC, we used bioinformatic tools to identify an exogenous gene targeting HSCs among the differentially expressed genes (DEGs) in LC to modify HF-MSCs. Extracellular matrix protein 1 (ECM1) was identified as a DEG that was significantly downregulated in the cirrhotic liver. Then, ECM1-overexpressing HF-MSCs (ECM1-HF-MSCs) were transplanted into mice with LC to explore the effectiveness and correlated mechanism of gene-overexpressing HF-MSCs on LC. The results showed that ECM1-HF-MSCs significantly improved liver function and liver pathological injury in LC after cell therapy relative to the other treatment groups. Moreover, we found that ECM1-HF-MSCs homed to the injured liver and expressed the hepatocyte-specific surface markers ALB, CK18, and AFP. In addition, hepatic stellate cell (HSC) activation was significantly inhibited in the cell treatment groups in vivo and in vitro, especially in the ECM1-HF-MSC group. Additionally, TGF-β/Smad signal inhibition was the most significant in the ECM1-HF-MSC group in vivo and in vitro. The findings indicate that the genetic modification of HF-MSCs with bioinformatic tools may provide a broad perspective for precision treatment of LC.
Therapeutic effects of eperisone on pulmonary fibrosis via preferential suppression of fibroblast activity
Authors: Tanaka Ken-ichiro , Shimoda Mikako , Sugizaki Toshifumi , Ikeda Maki , Takafuji Ayaka , Kawahara Masahiro , Yamakawa Naoki , Mizushima Tohru
Published: February 2022

Although the exact pathogenesis of idiopathic pulmonary fibrosis (IPF) is still unknown, the transdifferentiation of fibroblasts into myofibroblasts and the production of extracellular matrix components such as collagen, triggered by alveolar epithelial cell injury, are important mechanisms of IPF development. In the lungs of IPF patients, apoptosis is less likely to be induced in fibroblasts than in alveolar epithelial cells, and this process is involved in the pathogenesis of IPF. We used a library containing approved drugs to screen for drugs that preferentially reduce cell viability in LL29 cells (lung fibroblasts from an IPF patient) compared with A549 cells (human alveolar epithelial cell line). After screening, we selected eperisone, a central muscle relaxant used in clinical practice. Eperisone showed little toxicity in A549 cells and preferentially reduced the percentage of viable LL29 cells, while pirfenidone and nintedanib did not have this effect. Eperisone also significantly inhibited transforming growth factor-β1-dependent transdifferentiation of LL29 cells into myofibroblasts. In an in vivo study using ICR mice, eperisone inhibited bleomycin (BLM)-induced pulmonary fibrosis, respiratory dysfunction, and fibroblast activation. In contrast, pirfenidone and nintedanib were less effective than eperisone in inhibiting BLM-induced pulmonary fibrosis under this experimental condition. Finally, we showed that eperisone did not induce adverse effects in the liver and gastrointestinal tract in the BLM-induced pulmonary fibrosis model. Considering these results, we propose that eperisone may be safer and more therapeutically beneficial for IPF patients than current therapies.
Hsa_circ_0134111 promotes intervertebral disc degeneration via sponging miR-578
Authors: Yan Peng , Sun Chong , Luan Liangrui , Han Jialuo , Qu Yang , Zhou Chuanli , Xu Derong
Published: February 2022

Intervertebral disc degeneration (IDD) is a chronic degenerative and age-dependent process characterized by aberrant apoptosis, proliferation, synthesis, and catabolism of the extracellular matrix of the nucleus pulposus (NP) cells. Recently, studies showed that circular RNAs play important roles in the development of many diseases. However, the role of circRNAs in IDD development remains unknown. We showed that circ_0134111 level was overexpressed in IDD tissue samples as compar-ed to control tissues. The upregulation of circ_0134111 was more drastic in the moderate and severe IDD cases than in those with mild IDD. In addition, we showed that interleukin-1β and tumor necrosis factor-α exposure significantly enhanced circ_0134111 expression in NP cells. Furthermore, ectopic expression of circ_0134111 induced proliferation, pro-inflammatory cytokine secretion, and ECM degradation in the NP cells. We also showed that circ_0134111 directly interacted with microRNA (miR)-578 in NP cells where elevated expression of circ_0134111 enhanced the ADAMTS-5 and MMP-9 expression. Moreover, miR-578 expression was significantly decreased in IDD patients and the miR-578 expression was negatively correlated with circ_0134111 expression in the IDD samples. Interleukin-1β and tumor necrosis factor-α exposure significantly decreased miR-578 levels in NP cells, in which ectopic miR-578 expression inhibited cell growth, pro-inflammatory cytokine expression, and ECM degradation. Finally, we showed that circ_0134111 overexpression induced the IDD-related phenotypic changes through inhibiting miR-578. These data suggested that circ_0134111 could promote the progression of IDD through enhancing aberrant NP cell growth, inflammation, and ECM degradation partly via regulating miR-578.
Alternative splicing in seasonal plasticity and the potential for adaptation to environmental change
Authors: Steward Rachel A. , de Jong Maaike A. , Oostra Vicencio , Wheat Christopher W.
Published: February 2022

Seasonal plasticity is accomplished via tightly regulated developmental cascades that translate environmental cues into trait changes. Little is known about how alternative splicing and other posttranscriptional molecular mechanisms contribute to plasticity or how these mechanisms impact how plasticity evolves. Here, we use transcriptomic and genomic data from the butterfly Bicyclus anynana, a model system for seasonal plasticity, to compare the extent of differential expression and splicing and test how these axes of transcriptional plasticity differ in their potential for evolutionary change. Between seasonal morphs, we find that differential splicing affects a smaller but functionally unique set of genes compared to differential expression. Further, we find strong support for the novel hypothesis that spliced genes are more susceptible than differentially expressed genes to erosion of genetic variation due to selection on seasonal plasticity. Our results suggest that splicing plasticity is especially likely to experience genetic constraints that could affect the potential of wild populations to respond to rapidly changing environments.
Structural and biochemical rationale for enhanced spike protein fitness in delta and kappa SARS-CoV-2 variants
Authors: Saville James W. , Mannar Dhiraj , Zhu Xing , Srivastava Shanti S. , Berezuk Alison M. , Demers Jean-Philippe , Zhou Steven , Tuttle Katharine S. , Sekirov Inna , Kim Andrew , Li Wei , Dimitrov Dimiter S. , Subramaniam Sriram
Published: February 2022

The Delta and Kappa variants of SARS-CoV-2 co-emerged in India in late 2020, with the Delta variant underlying the resurgence of COVID-19, even in countries with high vaccination rates. In this study, we assess structural and biochemical aspects of viral fitness for these two variants using cryo-electron microscopy (cryo-EM), ACE2-binding and antibody neutralization analyses. Both variants demonstrate escape of antibodies targeting the N-terminal domain, an important immune hotspot for neutralizing epitopes. Compared to wild-type and Kappa lineages, Delta variant spike proteins show modest increase in ACE2 affinity, likely due to enhanced electrostatic complementarity at the RBD-ACE2 interface, which we characterize by cryo-EM. Unexpectedly, Kappa variant spike trimers form a structural head-to-head dimer-of-trimers assembly, which we demonstrate is a result of the E484Q mutation and with unknown biological implications. The combination of increased antibody escape and enhanced ACE2 binding provides an explanation, in part, for the rapid global dominance of the Delta variant.
Few-layer bismuth selenide cathode for low-temperature quasi-solid-state aqueous zinc metal batteries
Authors: Zhao Yuwei , Lu Yue , Li Huiping , Zhu Yongbin , Meng You , Li Na , Wang Donghong , Jiang Feng , Mo Funian , Long Changbai , Guo Ying , Li Xinliang , Huang Zhaodong , Li Qing , Ho Johnny C. , Fan Jun , Sui Manling , Chen Furong , Zhu Wenguang , Liu Weishu , Zhi Chunyi
Published: February 2022

The performances of rechargeable batteries are strongly affected by the operating environmental temperature. In particular, low temperatures (e.g., ≤0 °C) are detrimental to efficient cell cycling. To circumvent this issue, we propose a few-layer Bi2Se3 (a topological insulator) as cathode material for Zn metal batteries. When the few-layer Bi2Se3 is used in combination with an anti-freeze hydrogel electrolyte, the capacity delivered by the cell at −20 °C and 1 A g−1 is 1.3 larger than the capacity at 25 °C for the same specific current. Also, at 0 °C the Zn | |few-layer Bi2Se3 cell shows capacity retention of 94.6% after 2000 cycles at 1 A g−1. This behaviour is related to the fact that the Zn-ion uptake in the few-layer Bi2Se3 is higher at low temperatures, e.g., almost four Zn2+ at 25 °C and six Zn2+ at −20 °C. We demonstrate that the unusual performance improvements at low temperatures are only achievable with the few-layer Bi2Se3 rather than bulk Bi2Se3. We also show that the favourable low-temperature conductivity and ion diffusion capability of few-layer Bi2Se3 are linked with the presence of topological surface states and weaker lattice vibrations, respectively.
Physics-informed deep learning for solving phonon Boltzmann transport equation with large temperature non-equilibrium
Authors: Li Ruiyang , Wang Jian-Xun , Lee Eungkyu , Luo Tengfei
Published: February 2022

Phonon Boltzmann transport equation (BTE) is a key tool for modeling multiscale phonon transport, which is critical to the thermal management of miniaturized integrated circuits, but assumptions about the system temperatures (i.e., small temperature gradients) are usually made to ensure that it is computationally tractable. To include the effects of large temperature non-equilibrium, we demonstrate a data-free deep learning scheme, physics-informed neural network (PINN), for solving stationary, mode-resolved phonon BTE with arbitrary temperature gradients. This scheme uses the temperature-dependent phonon relaxation times and learns the solutions in parameterized spaces with both length scale and temperature gradient treated as input variables. Numerical experiments suggest that the proposed PINN can accurately predict phonon transport (from 1D to 3D) under arbitrary temperature gradients. Moreover, the proposed scheme shows great promise in simulating device-level phonon heat conduction efficiently and can be potentially used for thermal design.
High-throughput SNPs dataset reveal restricted population connectivity of marine gastropod within the narrow distribution range of peripheral oceanic islands
Authors: Yamazaki Daishi , Ito Shun , Miura Osamu , Sasaki Tetsuro , Chiba Satoshi
Published: February 2022

Molecular studies based on the high resolution genetic markers help us to grasp the factor shaping the genetic structure of marine organisms. Ecological factors linking to life history traits have often explained the process of genetic structuring in open and connectable oceanic environments. Besides, population genetic divergence can be affected by fragmented habitat, oceanic current, and past geographical events. In the present study, we demonstrated the genetic differentiation of marine gastropod Monodonta sp. within a narrow range of peripheral oceanic islands, the Ogasawara Islands. Genetic analyses were performed not only with a mitochondrial DNA marker but also with a high-throughput SNPs dataset obtained by ddRAD-seq. The results of the mtDNA analyses did not show genetic divergence among populations, while the SNPs dataset detected population genetic differentiation. Population demographic analyses and gene flow estimation suggested that the genetic structure was formed by sea level fluctuation associated with the past climatic change and regulated by temporal oceanographic conditions. These findings provide important insights into population genetic patterns in open and connectable environments.
Droplet digital PCR assay provides intrahepatic HBV cccDNA quantification tool for clinical application
Authors: Hayashi Sanae , Isogawa Masanori , Kawashima Keigo , Ito Kyoko , Chuaypen Natthaya , Morine Yuji , Shimada Mitsuo , Higashi-Kuwata Nobuyo , Watanabe Takehisa , Tangkijvanich Pisit , Mitsuya Hiroaki , Tanaka Yasuhito
Published: February 2022

The persistence of covalently closed circular DNA (cccDNA) poses a major obstacle to curing chronic hepatitis B (CHB). Here, we used droplet digital PCR (ddPCR) for cccDNA quantitation. The cccDNA-specific ddPCR showed high accuracy with the dynamic range of cccDNA detection from 101 to 105 copies/assay. The ddPCR had higher sensitivity, specificity and precisely than qPCR. The results of ddPCR correlated closely with serum HB core-related antigen and HB surface antigen (HBsAg) in 24 HBV-infected human-liver-chimeric mice (PXB-mice). We demonstrated that in 2 PXB-mice after entecavir treatment, the total cccDNA content did not change during liver repopulation, although the cccDNA content per hepatocyte was reduced after the treatment. In the 6 patients with HBV-related hepatocellular carcinoma, ddPCR detected cccDNA in both tumor and non-tumor tissues. In 13 HBeAg-negative CHB patients with pegylated interferon alpha-2a, cccDNA contents from paired biopsies were more significantly reduced in virological response (VR) than in non-VR at week 48 (p = 0.0051). Interestingly, cccDNA levels were the lowest in VR with HBsAg clearance but remained detectable after the treatment. Collectively, ddPCR revealed that cccDNA content is stable during hepatocyte proliferation and persists at quantifiable levels, even after serum HBsAg clearance.
A deep learning algorithm to identify cervical ossification of posterior longitudinal ligaments on radiography
Authors: Tamai Koji , Terai Hidetomi , Hoshino Masatoshi , Yabu Akito , Tabuchi Hitoshi , Sasaki Ryo , Nakamura Hiroaki
Published: February 2022

The cervical ossification of the posterior longitudinal ligament (cOPLL) is sometimes misdiagnosed or overlooked on radiography. Thus, this study aimed to validate the diagnostic yield of our deep learning algorithm which diagnose the presence/absence of cOPLL on cervical radiography and highlighted areas of ossification in positive cases and compare its diagnostic accuracy with that of experienced spine physicians. Firstly, the radiographic data of 486 patients (243 patients with cOPLL and 243 age and sex matched controls) who received cervical radiography and a computer tomography were used to create the deep learning algorithm. The diagnostic accuracy of our algorithm was 0.88 (area under curve, 0.94). Secondly, the numbers of correct diagnoses were compared between the algorithm and consensus of four spine physicians using 50 independent samples. The algorithm had significantly more correct diagnoses than spine physicians (47/50 versus 39/50, respectively; p = 0.041). In conclusion, the accuracy of our deep learning algorithm for cOPLL diagnosis was significantly higher than that of experienced spine physicians. We believe our algorithm, which uses different diagnostic criteria than humans, can significantly improve the diagnostic accuracy of cOPLL when radiography is used.
Aggregation-induced emission monomer-based fluorescent molecularly imprinted poly(ionic liquid) synthesized by a one-pot method for sensitively detecting 4-nitrophenol
Authors: Yang Hanxing , Ji Zhongguang , Zeng Yanbo , Zhang Jian , Chen Lifen , Wang Hailong , Yang Yiwen , Guo Longhua , Li Lei
Published: February 2022

An aggregation-induced emission monomer-based fluorescent molecularly imprinted poly(ionic liquid) (AIE-FMIPIL) was synthesized for the sensitive and selective fluorescent detection of 4-nitrophenol based on fluorescence quenching.
Inhibitory effects of phenolic glycosides from Trollius chinensis Bunge on α-glucosidase: inhibition kinetics and mechanisms
Authors: Feng Jie , He Fengming , Huang Yuhui , Zhou Mi , Liu Xiangzhong , Ye Xiansheng , Yang Renjing , Tian Wenjing , Chen Haifeng
Published: February 2022

Inhibitory effects of phenolic glycosides from the functional tea Trollius chinensis Bunge on α-glucosidase: inhibition kinetics and mechanisms.
Effects of alkaloid-rich extracts obtained from Grifola frondosa on gut microbiota and glucose homeostasis in rats
Authors: Li Na , Gao Xiaoxiang , Pan Yuyang , Liu Bin , Pang Jie , Zhao Chao , Zeng Feng
Published: February 2022

Grifola frondosa (GF), also known as maitake (a type of mushroom), has been widely used as a food item and it exhibits various health-beneficial hypoglycemic activities.
Ca2+ accelerates peptide fibrillogenesis via a heterogeneous secondary nucleation pathway
Authors: Zhang Kuo , Gao Yong-Hong , Zhong Wei-Shen , Cao Hui , Yue Kai , Wang Lei , Wang Hao
Published: February 2022

Heterogeneous secondary nucleation accelerates binding-induced fibrillogenesis of peptide in solution.
Coordination framework materials fabricated by the self-assembly of Sn(iv) porphyrins with Ag(i) ions for the photocatalytic degradation of organic dyes in wastewater
Authors: Shee Nirmal Kumar , Jo Hwa Jin , Kim Hee-Joon
Published: February 2022

Two coordination framework materials were fabricated by the self-assembly of Sn(iv) porphyrins with Ag(i) ions, and their performances for the photocatalytic degradation of organic dyes were investigated.
Ferroelastic phase transition with large spontaneous strain caused by freezing the conformational dynamics of ammonium
Authors: Li Li-Ting , Ji Cui-Xian , Sun Ying-Xi , Jin Ya-Wei , Ni Guo-Hao , Sun Jia-Yue , Han Rui-Rui , Zhao Jiong-Peng , Liu Fu-Chen
Published: February 2022

Through the structural regulation of long chain organic ammonium in a confined space, a ferroelastic phase transition with large spontaneous strain is realized.
Acid-mediated decarboxylative C–H coupling between arenes and O-allyl carbamates
Authors: Loro Camilla , Oble Julie , Foschi Francesca , Papis Marta , Beccalli Egle M. , Giofrè Sabrina , Poli Giovanni , Broggini Gianluigi
Published: February 2022

Treatment of O-allyl N-tosyl carbamates with arenes in the presence of Cu(OTf)2 or TMSOTf as promoters affords N-substituted 1-arylpropan-2-amines, 1,2-diarylpropanes, 1,1-diarylpropanes, or indanes, depending on the nature of the promoter.
Unsupervised anomaly detection via dual transformation‐aware embeddings
Authors: Wang Zhipeng , Hou Chunping , Ge Bangbang , Liu Yang , Dong Zhicheng , Wu Zhiqiang
Published: February 2022

Unsupervised anomaly detection refers to the discovery of unconventional images that are globally or locally different from the training set. Recently, reconstruction‐based anomaly detection methods have made great progress. However, most of the existing methods take reconstructing the original image as the goal of latent feature learning. Due to lack of effective semantic guidance, latent features have intrinsic characteristics which retain redundant details of spatial structure. Such information is too general and cause over‐expression problem. To solve this problem, in this paper, dual transformation‐aware embeddings are coined which aims to achieve a stable model to learn high‐level latent features in a self‐supervised manner. To be more specific, the authors try to extract transformation‐detectable feature embeddings for both structure and content views which explore the regular pattern under different transformations in normal situations. In addition, the relationship between the original feature and the transformed feature is established. Based on such relationship, the latent feature of generated image to predict transformation parameter is extracted. Then, a transformation‐consistency regularization is proposed to constrain decoder to generate high‐quality image with high‐level consistency and achieve a more stable model. Experiments on MVTec‐AD and CIFAR10 datasets prove the effectiveness and robustness of the proposed method.
Evaluating the added value of blockchains to local energy markets—Comparing the performance of blockchain‐based and centralised implementations
Authors: Zade Michel , Feroce Marcello , Guridi Arturo , Lumpp Sebastian Dirk , Tzscheutschler Peter
Published: February 2022

The continuous decentralisation of the energy system due to the expansion of renewable energies requires new coordination mechanisms such as Local Energy Markets (LEMs) that are capable of integrating millions of prosumers as active participants. Since the end of the 2010s, the blockchain technology has been discussed as a potential infrastructure for LEMs and as a potential game‐changer in the energy industry. In this work, the authors introduce LEM specific technology‐independent infrastructure requirements, present a Solidity and Python toolbox that allows to compute a comparative performance analysis between a blockchain‐based and a central LEM and evaluate the added value of a blockchain‐based implementation compared to a conventional reference implementation. Simulations of a LEM with a periodic double auction and settlement showed that a blockchain‐based LEM operation requires more than 140 times the computation time compared to a centralised implementation and cannot fulfil data security requirements. Thus, the authors find that blockchain technology in its current state of development does not add significant value to LEMs. All implemented programmes are published in the open‐source project lemlab as part of the research project RegHEE.
Epilepsie im Jugend- und jungen Erwachsenenalter bewältigen
Authors: Ott-Ordelheide Petra , Ritze Michaela
Published: February 2022

Einmal erkannt, lässt sich Epilepsie medikamentös gut behandeln. Gerade in der Pubertät und beim Übergang in das Erwachsenenalter ist die Erkrankung mit ihren Anforderungen – beispielsweise an die Disziplin der betroffenen Jugendlichen – allerdings eine zusätzliche Belastung, die es zu bewältigen gilt. Pflegerische Fachberatung ist in dieser Phase wichtig.