bluuebunny/crossref_metadata_2025 huggingface dataset:
Porcine Respiratory Coronavirus as a Model for Acute Respiratory Coronavirus Disease
Authors: Keep Sarah , Carr Brigid Veronica , Lean Fabian Z. X. , Fones Albert , Newman Joseph , Dowgier Giulia , Freimanis Graham , Vatzia Eleni , Polo Noemi , Everest Holly , Webb Isobel , Mcnee Adam , Paudyal Basu , Thakur Nazia , Nunez Alejandro , MacLoughlin Ronan , Maier Helena , Hammond John , Bailey Dalan , Waters Ryan , Charleston Bryan , Tuthill Toby , Britton Paul , Bickerton Erica , Tchilian Elma
Published: March 2022

In the light of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, we have developed a porcine respiratory coronavirus (PRCV) model for in depth mechanistic evaluation of the pathogenesis, virology and immune responses of this important family of viruses. Pigs are a large animal with similar physiology and immunology to humans and are a natural host for PRCV. Four PRCV strains were investigated and shown to induce different degrees of lung pathology. Importantly, although all four strains replicated equally well in porcine cell linesin vitroand in the upper respiratory tractin vivo, PRCV strains causing more severe lung pathology were also able to replicate inex vivotracheal organ cultures as well asin vivoin the trachea and lung. The time course of infection of PRCV 135, which caused the most severe pulmonary pathology, was investigated. Virus was shed from the upper respiratory tract until day 10 post infection, with infection of the respiratory mucosa, as well as olfactory and sustentacular cells, providing an excellent model to study upper respiratory tract disease in addition to the commonly known lower respiratory tract disease from PRCV. Infected animals made antibody and T cell responses that cross reacted with the four PRCV strains and Transmissible Gastroenteritis Virus. The antibody response was reproducedin vitroin organ cultures. Comparison of mechanisms of infection and immune control in pigs infected with PRCVs of differing pathogenicity with human data from SARS-CoV-2 infection and from ourin vitroorgan cultures, will enable key events in coronavirus infection and disease pathogenesis to be identified.
Female Genital Schistosomiasis Lesions Explored Using Circulating Anodic Antigen as an Indicator for Live Schistosoma Worms
Authors: Nemungadi Takalani Girly , Kleppa Elisabeth , van Dam Govert J. , Corstjens Paul L. A. M. , Galappaththi-Arachchige Hashini Nilushika , Pillay Pavitra , Gundersen Svein Gunnar , Vennervald Birgitte J. , Ndhlovu Patricia , Taylor Myra , Naidoo Saloshni , Kjetland Eyrun F.
Published: March 2022

Background

In areas where reinfection with schistosomiasis is rampant, it is not known if the lesions of Female Genital Schistosomaisis are a consequence of live worms, or caused by dead ova. Live schistosome worms regurgitate Circulating Anodic Antigen (CAA). We sought to explore the association between the different lesions of FGS (grainy sandy patches, homogenous yellow patches, rubbery papules and abnormal blood vessels) and the presence of live worms as indicated by S. haematobium-derived CAA in blood.

Materials and Methods

In this cross-sectional study, rural high schools were randomly selected from Ilembe, uThungulu and Ugu Districts on the East Coast of South Africa, KwaZulu-Natal Province. Serum samples for CAA analysis were collected from 246 female learners aged 16 - 23 years. Uncorrected chi-square and odds ratio with 95% confidence interval (CI) were used to evaluate the null hypothesis.

Results

CAA was positive in 82/246 (33%) of the participants. Sandy patches were found in 123 (50%) of the study population. Grainy sandy patches were significantly associated with CAA even after controlling for age (Adjusted Odds Ratio (AOR) 4.2, 95% CI 2.3 - 7.9, p < 0.001). Likewise, abnormal blood vessels were associated with CAA (AOR 3.0, 95% CI 1.5-4.5, p = 0.001) whereas homogenous yellow patches were not associated with CAA (p = 0.57). Rubbery papules were not found in this study population.

Conclusion

Grainy sandy patches and abnormal blood vessels are found more commonly in women who harbour live Schistosoma haematobium worms whilst homogenous yellow patches may indicate chronic tissue damage due to dead ova.
Screening of Surface-Exposed Lipoproteins of Leptospira Involved in Modulation of Host Innate Immune Response
Authors: Kumar Ajay , Varma Vivek P. , Faisal Syed M.
Published: March 2022

Leptospira, a zoonotic pathogen, is capable of causing both chronic and acute infection in a susceptible host. Surface-exposed lipoproteins play a major role in modulating the host immune response by activating the innate cells like macrophages and dendritic cells or evading complement attack and killing by phagocytes like neutrophils to favor pathogenesis and establish infection. In this study, we screened some surface-exposed lipoproteins known to be involved in pathogenesis to assess their possible role in immune modulation (innate immune activation or evasion). Surface proteins of the Len family (LenB, LenD, and LenE), Lsa30, Loa22, and Lipl21 were purified in recombinant form and then tested for their ability to activate macrophages of the different host (mouse, human, and bovine). These proteins were tested for binding with complement regulators like Factor H (FH), C4 Binding Protein (C4BP), and host protease Plasminogen (PLG) and also as nucleases to access their possible role in innate immune evasion. Our results show that, of various proteins tested, Loa22 induced strong innate activation and Lsa30 was least stimulatory, as evident from the production of pro-inflammatory cytokines (interleukin-6 and tumor necrosis factor–α) and expression of surface markers [CD80, CD86, and major histocompatibility complex class II (MHCII)]. All the tested proteins were able to bind to FH, C4BP, and PLG; however, Loa22 showed strong binding to PLG correlating to plasmin activity. All the proteins except Loa22 showed nuclease activity, albeit with a requirement of different metal ions. The nuclease activity of these proteins correlated toin vitrodegradation of neutrophil extracellular trap (NET). In conclusion, our results indicate that these surface proteins are involved in innate immune modulation and may play a critical role in assisting the bacteria in invading and colonizing the host tissue for persistent infection.
Application of MinION Amplicon Sequencing to Buccal Swab Samples for Improving Resolution and Throughput of Rumen Microbiota Analysis
Authors: Miura Hiroto , Takeda Masayuki , Yamaguchi Megumi , Ohtani Yoshihisa , Endo Go , Masuda Yasuhisa , Ito Kaede , Nagura Yoshio , Iwashita Kunihiro , Mitani Tomohiro , Suzuki Yutaka , Kobayashi Yasuo , Koike Satoshi
Published: March 2022

The Illumina MiSeq platform has been widely used as a standard method for studying the rumen microbiota. However, the low resolution of taxonomic identification is the only disadvantage of MiSeq amplicon sequencing, as it targets a part of the 16S rRNA gene. In the present study, we performed three experiments to establish a high-resolution and high-throughput rumen microbial profiling approach using a combination of MinION platform and buccal swab sample, which is a proxy for rumen contents. In experiment 1, rumen contents and buccal swab samples were collected simultaneously from cannulated cattle (n = 6) and used for microbiota analysis using three different analytical workflows: amplicon sequencing of the V3–V4 region of the 16S rRNA gene using MiSeq and amplicon sequencing of near full-length 16S rRNA gene using MinION or PacBio Sequel II. All reads derived from the MinION and PacBio platforms were classified at the species-level. In experiment 2, rumen fluid samples were collected from beef cattle (n = 28) and used for 16S rRNA gene amplicon sequencing using the MinION platform to evaluate this sequencing platform for rumen microbiota analysis. We confirmed that the MinION platform allowed species-level taxa assignment for the predominant bacterial groups, which were previously identified at the family- and genus-level using the MiSeq platform. In experiment 3, buccal swab samples were collected from beef cattle (n = 30) and used for 16S rRNA gene amplicon sequencing using the MinION platform to validate the applicability of a combination of the MinION platform and buccal swab samples for rumen microbiota analysis. The distribution of predominant bacterial taxa in the buccal swab samples was similar to that in the rumen samples observed in experiment 2. Based on these results, we concluded that the combination of the MinION platform and buccal swab samples may be potentially applied for rumen microbial analysis in large-scale studies.
Human Alphacoronavirus Universal Primers for Genome Amplification and Sequencing
Authors: Choi Sungmi , Kim Kwan Woo , Ku Keun Bon , Kim Seong-Jun , Park Changwoo , Park Dongju , Kim Seil , Yi Hana
Published: March 2022

Rapid and accurate sequencing covering the entire genome is essential to identify genetic variations of viral pathogens. However, due to the low viral titers in clinical samples, certain amplification steps are required for viral genome sequencing. At present, there are no universal primers available for alphacoronaviruses and that, since these viruses have diverse strains, new primers specific to the target strain must be continuously developed for sequencing. Thus, in this study, we aimed to develop a universal primer set valid for all human alphacoronaviruses and applicable to samples containing trace amounts of the virus. To this aim, we designed overlapping primer pairs capable of amplifying the entire genome of all known human alphacoronaviruses. The selected primers, named the AC primer set, were composed of 10 primer pairs stretching over the entire genome of alphacoronaviruses, and produced PCR products of the expected size (3–5 kb) from both the HCoV-229E and HCoV-NL63 strains. After genome amplification, an evaluation using various sequencing platforms was carried out. The amplicon library sequencing data were assembled into complete genome sequences in all sequencing strategies examined in this study. The sequencing accuracy varied depending on the sequencing technology, but all sequencing methods showed a sequencing error of less than 0.01%. In the mock clinical specimen, the detection limit was 10−3 PFU/ml (102 copies/ml). The AC primer set and experimental procedure optimized in this study may enable the fast diagnosis of mutant alphacoronaviruses in future epidemics.
Sodium Humate Alleviates Enterotoxigenic Escherichia coli-Induced Intestinal Dysfunction via Alteration of Intestinal Microbiota and Metabolites in Mice
Authors: Wang Dong , He Yanjun , Liu Kexin , Deng Shouxiang , Fan Yuying , Liu Yun
Published: March 2022

Enterotoxigenic Escherichia coli (ETEC) can damage intestinal epithelial barrier function and lead to serious intestinal diarrhea in newborns and young animals. Sodium humate (HNa) is natural organic bioactive compound possessing antibacterial, anti-inflammatory, and anti-diarrheal properties. This study investigated the alleviative potential of HNa on the impaired intestinal barrier and intestinal inflammation, and regulatory effects on gut microbiota and metabolites in ETEC K88 infected mice. A total of 30 female mice were randomly assigned into three groups. The mice in the control and ETEC groups were gavaged with 0.2 mL of sterile saline, while the mice in the ETEC + HNa group were gavaged with 0.2 mL of 5% HNa, daily. On day 8, the mice in ETEC and ETEC + HNa group were challenged with ETEC K88. The trial lasted for 12 days. HNa administration elevated ETEC K88-induced body weight loss and ameliorated jejunum and colon pathological injury. HNa also reduced the levels of pro-inflammatory cytokines in the serum, jejunum, and colon. Additionally, HNa reduced intestinal barrier damage by up-regulating the expression of tight junction proteins (TJPs) and mucosal repair factors. 16s rDNA gene sequencing results showed that HNa increased the abundance of beneficial bacteria Lactobacillus, Prevotella_9, and Odoribacter but decreased the abundance of pathogenic bacteria Escherichia and Gastranaerophilales in the feces of mice. Moreover, metabolomic analysis revealed that the concentrations of 15 metabolites, the pathways of protein digestion and absorption, and propanoic acid metabolism were changed by HNa administration. In conclusion, HNa could alleviate ETEC K88-induced intestinal dysfunction through restoring intestinal barrier integrity, modulating gut microbiota, and metabolites.
Bt GS57 Interaction With Gut Microbiota Accelerates Spodoptera exigua Mortality
Authors: Li Yazi , Zhao Dan , Wu Han , Ji Yujie , Liu Zhaorui , Guo Xiaochang , Guo Wei , Bi Yang
Published: March 2022

The Beet armyworm Spodoptera exigua (Lepidoptera: Noctuidae, Spodoptera) is an important global polyphagous pest. Pathogen infection could destroy the intestinal microbial homeostasis of insects, leading to the death of the host. However, the effect of the host intestinal microbial community on the insecticidal effect of Bacillus thuringiensis is rarely studied. In this study, the genome characteristics of Bt GS57 and the diversity and functions of the gut bacteria in S. exigua are investigated using crystal morphology, biological activity, and Illumina HiSeq high-throughput sequencing. The total size of the Bt GS57 genome is 6.17 Mbp with an average G + C content of 35.66%. Furthermore, the Bt GS57 genome contains six cry genes: cry1Ca, cry1Da, cry2Ab, cry9Ea, cry1Ia, and cry1Aa, and a vegetative insecticidal protein gene vip3Aa. The Bt GS57 strain can produce biconical crystals, mainly expressing 70 kDa and 130 kDa crystal proteins. The LC50 value of the Bt GS57 strain against the S. exigua larvae was 0.339 mg mL–1. Physiological and biochemical reactions showed that Bt GS57 belongs to B.t. var. thuringiensis. In addition, we found that B. thuringiensis can cause a dynamic change in the gut microbiota of S. exigua, with a significant reduction in bacterial diversity and a substantial increase in bacterial load. In turn, loss of gut microbiota significantly decreased the B. thuringiensis susceptibility of S. exigua larvae. Our findings reveal the vital contribution of the gut microbiota in B. thuringiensis-killing activity, providing new insights into the mechanisms of B. thuringiensis pathogenesis in insects.
Pangenome Analysis of the Soilborne Fungal Phytopathogen Rhizoctonia solani and Development of a Comprehensive Web Resource: RsolaniDB
Authors: Kaushik Abhinav , Roberts Daniel P. , Ramaprasad Abhinay , Mfarrej Sara , Nair Mridul , Lakshman Dilip K. , Pain Arnab
Published: March 2022

Rhizoctonia solani is a collective group of genetically and pathologically diverse basidiomycetous fungi that damage economically important crops. Its isolates are classified into 13 Anastomosis Groups (AGs) and subgroups having distinctive morphology and host ranges. The genetic factors driving the unique features of R. solani pathology are not well characterized due to the limited availability of its annotated genomes. Therefore, we performed genome sequencing, assembly, annotation and functional analysis of 12 R. solani isolates covering 7 AGs and select subgroups (AG1-IA; AG1-IB; AG1-IC; AG2-2IIIB; AG3-PT, isolates Rhs 1AP and the hypovirulent Rhs1A1; AG3-TB; AG4-HG-I, isolates Rs23 and R118-11; AG5; AG6; and AG8), in which six genomes are reported for the first time. Using a pangenome comparative analysis of 12 R. solani isolates and 15 other Basidiomycetes, we defined the unique and shared secretomes, CAZymes, and effectors across the AGs. We have also elucidated the R. solani-derived factors potentially involved in determining AG-specific host preference, and the attributes distinguishing them from other Basidiomycetes. Finally, we present the largest repertoire of R. solani genomes and their annotated components as a comprehensive database, viz. RsolaniDB, with tools for large-scale data mining, functional enrichment and sequence analysis not available with other state-of-the-art platforms.
Optimization of Early Antimicrobial Strategies for Lung Transplant Recipients Based on Metagenomic Next-Generation Sequencing
Authors: Zhang Xiao-qin , Lei Yu , Tan Xiao-li , Guo Lu , Huang Xiao-bo , Yang Fu-xun , Yu Hua , Liu Xiao-shu , Wang Yi-ping , Lu Sen , Pan Ling-ai
Published: March 2022

The management of perioperative antibiotic options after lung transplantation varies widely around the world, but there is a common trend to limit antibiotic use duration. Metagenomic next-generation sequencing (mNGS) has become a hot spot in clinical pathogen detection due to its precise, rapid, and wide detection spectrum of pathogens. Thus, we defined a new antibiotic regimen adjustment strategy in the very early stage (within 7 days) after lung transplantation mainly depending on mNGS reports combined with clinical conditions to reduce the use of antibiotics. To verify the clinical effect of the strategy, we carried out this research. Thirty patients who underwent lung transplantation were finally included, whose information including etiology, antibiotic adjustment, and the effect of our strategy was recorded. Lung transplant recipients in this study were prescribed with initial antibiotic regimen immediately after surgery; their antibiotic regimens were adjusted according to the strategy. According to our study, the entire effectiveness of the strategy was 90.0% (27/30). Besides, a total of 86 samples containing donor lung tissue, recipient lung tissue, and bronchoalveolar lavage fluid (BALF) were obtained in this study; they were all sent to mNGS test, while BALF was also sent to pathogen culture. Their results showed that the positive rate of BALF samples was higher (86.67%) than that of donor’s lung tissue (20.0%) or recipient’s lung tissue (13.33%) by mNGS test, indicating BALF samples are more valuable than other clinical samples from early postoperative period to guide the early adjustment of antibiotics after lung transplantation. It is effective for mNGS combined with traditional methods and clinical situations to optimize antibiotic regimens in lung transplantation recipients within 7 days after surgery.
Phage-Derived Depolymerase as an Antibiotic Adjuvant Against Multidrug-Resistant Acinetobacter baumannii
Authors: Chen Xi , Liu Miao , Zhang Pengfei , Xu Miao , Yuan Weihao , Bian Liming , Liu Yannan , Xia Jiang , Leung Sharon S. Y.
Published: March 2022

Bacteriophage-encoded depolymerases are responsible for degrading capsular polysaccharides (CPS), lipopolysaccharides (LPS), and exopolysaccharides (EPS) of the host bacteria during phage invasion. They have been considered as promising antivirulence agents in controlling bacterial infections, including those caused by multidrug-resistant (MDR) bacteria. This feature inspires hope of utilizing these enzymes to disarm the polysaccharide capsules of the bacterial cells, which then strengthens the action of antibiotics. Here we have identified, cloned, and expressed a depolymerase Dpo71 from a bacteriophage specific for the gram-negative bacterium Acinetobacter baumannii in a heterologous host Escherichia coli. Dpo71 sensitizes the MDR A. baumannii to the host immune attack, and also acts as an adjuvant to assist or boost the action of antibiotics, for example colistin. Specifically, Dpo71 at 10 μg/ml enables a complete bacterial eradication by human serum at 50% volume ratio. A mechanistic study shows that the enhanced bactericidal effect of colistin is attributed to the improved outer membrane destabilization capacity and binding rate to bacteria after stripping off the bacterial capsule by Dpo71. Dpo71 inhibits biofilm formation and disrupts the pre-formed biofilm. Combination of Dpo71 could significantly enhance the antibiofilm activity of colistin and improve the survival rate of A. baumannii infected Galleria mellonella. Dpo71 retains the strain-specificity of the parent phage from which Dpo71 is derived: the phage-sensitive A. baumannii strains respond to Dpo71 treatment, whereas the phage-insensitive strains do not. In summary, our work demonstrates the feasibility of using recombinant depolymerases as an antibiotic adjuvant to supplement the development of new antibacterials and to battle against MDR pathogens.
Continuous Semi-autonomous Prosthesis Control Using a Depth Sensor on the Hand
Authors: Castro Miguel Nobre , Dosen Strahinja
Published: March 2022

Modern myoelectric prostheses can perform multiple functions (e.g., several grasp types and wrist rotation) but their intuitive control by the user is still an open challenge. It has been recently demonstrated that semi-autonomous control can allow the subjects to operate complex prostheses effectively; however, this approach often requires placing sensors on the user. The present study proposes a system for semi-autonomous control of a myoelectric prosthesis that requires a single depth sensor placed on the dorsal side of the hand. The system automatically pre-shapes the hand (grasp type, size, and wrist rotation) and allows the user to grasp objects of different shapes, sizes and orientations, placed individually or within cluttered scenes. The system “reacts” to the side from which the object is approached, and enables the user to target not only the whole object but also an object part. Another unique aspect of the system is that it relies on online interaction between the user and the prosthesis; the system reacts continuously on the targets that are in its focus, while the user interprets the movement of the prosthesis to adjust aiming. Experimental assessment was conducted in ten able-bodied participants to evaluate the feasibility and the impact of training on prosthesis-user interaction. The subjects used the system to grasp a set of objects individually (Phase I) and in cluttered scenarios (Phase II), while the time to accomplish the task (TAT) was used as the performance metric. In both phases, the TAT improved significantly across blocks. Some targets (objects and/or their parts) were more challenging, requiring thus significantly more time to handle, but all objects and scenes were successfully accomplished by all subjects. The assessment therefore demonstrated that the system is indeed robust and effective, and that the subjects could successfully learn how to aim with the system after a brief training. This is an important step toward the development of a self-contained semi-autonomous system convenient for clinical applications.
Emergent Diversity and Persistent Turnover in Evolving Microbial Cross-Feeding Networks
Authors: Lücken Leonhard , Lennartz Sinikka T. , Froehlich Jule , Blasius Bernd
Published: March 2022

A distinguishing feature of many ecological networks in the microbial realm is the diversity of substrates that could potentially serve as energy sources for microbial consumers. The microorganisms are themselves the agents of compound diversification via metabolite excretion or overflow metabolism. It has been suggested that the emerging richness of different substrates is an important condition for the immense biological diversity in microbial ecosystems. In this work, we study how complex cross-feeding networks (CFN) of microbial species may develop from a simple initial community given some elemental evolutionary mechanisms of resource-dependent speciation and extinctions using a network flow model. We report results of several numerical experiments and report an in-depth analysis of the evolutionary dynamics. We find that even in stable environments, the system is subject to persisting turnover, indicating an ongoing co-evolution. Further, we compare the impact of different parameters, such as the ratio of mineralization, as well as the metabolic versatility and variability on the evolving community structure. The results imply that high microbial and molecular diversity is an emergent property of evolution in cross-feeding networks, which affects transformation and accumulation of substrates in natural systems, such as soils and oceans, with potential relevance to biotechnological applications.
Body Weight Control Is a Key Element of Motor Control for Toddlers’ Walking
Authors: Kerkman Jennifer N. , Zandvoort Coen S. , Daffertshofer Andreas , Dominici Nadia
Published: March 2022

New-borns can step when supported for about 70–80% of their own body weight. Gravity-related sensorimotor information might be an important factor in developing the ability to walk independently. We explored how body weight support alters motor control in toddlers during the first independent steps and in toddlers with about half a year of walking experience. Sixteen different typically developing children were assessed during (un)supported walking on a running treadmill. Electromyography of 18–24 bilateral leg and back muscles and vertical ground reaction forces were recorded. Strides were grouped into four levels of body weight support ranging from no (<10%), low (10–35%), medium (35–55%), and high (55–95%) support. We constructed muscle synergies and muscle networks and assessed differences between levels of support and between groups. In both groups, muscle activities could be described by four synergies. As expected, the mean activity decreased with body weight support around foot strikes. The younger first-steps group showed changes in the temporal pattern of the synergies when supported for more than 35% of their body weight. In this group, the muscle network was dense with several interlimb connections. Apparently, the ability to process gravity-related information is not fully developed at the onset of independent walking causing motor control to be fairly disperse. Synergy-specific sensitivity for unloading implies distinct neural mechanisms underlying (the emergence of) these synergies.
Fully Automatic Classification of Brain Atrophy on NCCT Images in Cerebral Small Vessel Disease: A Pilot Study Using Deep Learning Models
Authors: Wang Jincheng , Chen Sijie , Liang Hui , Zhao Yilei , Xu Ziqi , Xiao Wenbo , Zhang Tingting , Ji Renjie , Chen Tao , Xiong Bing , Chen Feng , Yang Jun , Lou Haiyan
Published: March 2022

Objective

Brain atrophy is an important imaging characteristic of cerebral small vascular disease (CSVD). Our study explores the linear measurement application on CT images of CSVD patients and develops a fully automatic brain atrophy classification model. The second aim was to compare it with the end-to-end Convolutional Neural Networks (CNNs) model.

Methods

A total of 385 subjects such as 107 no-atrophy brain, 185 mild atrophy, and 93 severe atrophy were collected and randomly separated into training set (n = 308) and test set (n = 77). Key slices for linear measurement were manually identified and used to annotate nine linear measurements and a binary classification of cerebral sulci widening. A linear-measurement-based pipeline (2D model) was constructed for two-types (existence/non-existence brain atrophy) or three-types classification (no/mild atrophy/severe atrophy). For comparison, an end-to-end CNN model (3D-deep learning model) for brain atrophy classification was also developed. Furthermore, age and gender were integrated to the 2D and 3D models. The sensitivity, specificity, accuracy, average F1 score, receiver operating characteristics (ROC) curves for two-type classification and weighed kappa for three-type classification of the two models were compared.

Results

Automated measurement of linear measurements and cerebral sulci widening achieved moderate to almost perfect agreement with manual annotation. In two-type atrophy classification, area under the curves (AUCs) of the 2D model and 3D model were 0.953 and 0.941 with no significant difference (p = 0.250). The Weighted kappa of the 2D model and 3D model were 0.727 and 0.607 according to standard classification they displayed, mild atrophy and severe atrophy, respectively. Applying patient age and gender information improved classification performances of both 2D and 3D models in two-type and three-type classification of brain atrophy.

Conclusion

We provide a model composed of different modules that can classify CSVD-related brain atrophy on CT images automatically, using linear measurement. It has similar performance and better interpretability than the end-to-end CNNs model and may prove advantageous in the clinical setting.
Evaluation of the Effectiveness of the Tap Test by Combining the Use of Functional Gait Assessment and Global Rating of Change
Authors: Kameda Masahiro , Kajimoto Yoshinaga , Nikaido Yasutaka , Kambara Akihiro , Tsujino Kohei , Yamada Hironori , Takagi Fugen , Fukuo Yusuke , Kosaka Takuya , Kanemitsu Takuya , Katayama Yoshihide , Tsuji Yuichiro , Yagi Ryokichi , Hiramatsu Ryo , Ikeda Naokado , Nonoguchi Naosuke , Furuse Motomasa , Kawabata Shinji , Takami Toshihiro , Wanibuchi Masahiko
Published: March 2022

Background

Although the tap test for patients with suspected idiopathic normal pressure hydrocephalus (iNPH) is still often performed as part of the preoperative evaluation, it is true that some studies have reported the limitations of the tap test, claiming that it does not provide the additional information for appropriate patient selection for surgery. We aimed to determine whether a better method of pre- and post-tap test assessment could lead to appropriate patient selection for shunting.

Methods

We performed the tap test as part of the preoperative evaluation in all 40 patients who underwent lumboperitoneal shunt surgery for iNPH from April 2021 to September 2021. We retrospectively analyzed the patient data. We examined whether a comprehensive evaluation of the effect of the tap test using the Functional Gait Assessment (FGA) and Global Rating of Change (GRC) scales would identify a wider range of patients who would benefit from shunt surgery than the 3-m Timed Up and Go test (TUG) alone.

Results

Assuming a prevalence of 1% for iNPH, the TUG had a sensitivity of 0.23, specificity of 0.71, positive likelihood ratio of 0.79, and negative likelihood ratio of 1.09. When improvement in either the FGA or the GRC was used as a criterion for the validity of the tap test, the sensitivity was 0.88, specificity was 0.17, positive likelihood ratio was 1.06, and negative likelihood ratio was 0.71.

Conclusion

Improvement in either the FGA or the GRC is a more sensitive criterion for the effectiveness of the tap test for the gait aspect than the TUG. Since the negative likelihood ratio is lower than that for the TUG alone, it is more appropriate to exclude patients with neither FGA nor GRC improvement from surgical indications than to exclude surgical indications based on a negative TUG.
The Role of Predictions, Their Confirmation, and Reward in Maintaining the Self-Concept
Authors: Mokady Aviv , Reggev Niv
Published: March 2022

The predictive processing framework posits that people continuously use predictive principles when interacting with, learning from, and interpreting their surroundings. Here, we suggest that the same framework may help explain how people process self-relevant knowledge and maintain a stable and positive self-concept. Specifically, we recast two prominent self-relevant motivations, self-verification and self-enhancement, in predictive processing (PP) terms. We suggest that these self-relevant motivations interact with the self-concept (i.e., priors) to create strong predictions. These predictions, in turn, influence how people interpret information about themselves. In particular, we argue that these strong self-relevant predictions dictate how prediction error, the deviation from the original prediction, is processed. In contrast to many implementations of the PP framework, we suggest that predictions and priors emanating from stable constructs (such as the self-concept) cultivate belief-maintaining, rather than belief-updating, dynamics. Based on recent findings, we also postulate that evidence supporting a predicted model of the self (or interpreted as such) triggers subjective reward responses, potentially reinforcing existing beliefs. Characterizing the role of rewards in self-belief maintenance and reframing self-relevant motivations and rewards in predictive processing terms offers novel insights into how the self is maintained in neurotypical adults, as well as in pathological populations, potentially pointing to therapeutic implications.
Motor Learning in Response to Different Experimental Pain Models Among Healthy Individuals: A Systematic Review
Authors: Izadi Mohammad , Franklin Sae , Bellafiore Marianna , Franklin David W.
Published: March 2022

Learning new movement patterns is a normal part of daily life, but of critical importance in both sport and rehabilitation. A major question is how different sensory signals are integrated together to give rise to motor adaptation and learning. More specifically, there is growing evidence that pain can give rise to alterations in the learning process. Despite a number of studies investigating the role of pain on the learning process, there is still no systematic review to summarize and critically assess investigations regarding this topic in the literature. Here in this systematic review, we summarize and critically evaluate studies that examined the influence of experimental pain on motor learning. Seventeen studies that exclusively assessed the effect of experimental pain models on motor learning among healthy human individuals were included for this systematic review, carried out based on the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement. The results of the review revealed there is no consensus regarding the effect of pain on the skill learning acquisition and retention. However, several studies demonstrated that participants who experienced pain continued to express a changed motor strategy to perform a motor task even 1 week after training under the pain condition. The results highlight a need for further studies in this area of research, and specifically to investigate whether pain has different effects on motor learning depending on the type of motor task.
Impaired Local and Long-Range Brain Connectivity and Visual Response in a Genetic Rat Model of Hyperactivity Revealed by Functional Ultrasound
Authors: Droguerre Marine , Vidal Benjamin , Valdebenito Marco , Mouthon Franck , Zimmer Luc , Charvériat Mathieu
Published: March 2022

Attention-Deficit hyperactivity disorder (ADHD) is a central nervous system (CNS) disorder frequently associated with other psychiatric disorders. Pathophysiology processes at stake in ADHD are still under investigation and interestingly neuroimaging data points to modulated brain connectivity in patients. The genetic spontaneously hypertensive rat (SHR) model has been widely used to study pathophysiological underpinnings of ADHD and resting-state brain connectivity using functional magnetic resonance imaging. Here, functional ultrasound imaging, a new technique enabling fast measurement of cerebral blood volume (CBV), was used to further characterize resting-state functional connectivity – at both local and long-range – and visual response in SHR. We demonstrated that response to visual stimulation was increased in SHR in the visual cortex and the superior colliculus. They displayed altered long-range functional connectivity between spatially distinct regions. SHR also displayed modulated local connectivity, with strong increases of regional homogeneity in parts of the motor and visual cortex, along with decreases in the secondary cingulate cortex, the superior colliculus and the pretectal area. As CBV is intricately coupled to cerebral activity, these results suggest an abnormal neural activity in the SHR animal model, consistent with previous clinical studies and demonstrate the potential of functional ultrasound imaging as a translational tool in ADHD.
Extraction, Structural Characterization, and Immunomodulatory Activity of a High Molecular Weight Polysaccharide From Ganoderma lucidum
Authors: Liu Guo , Zhang Jun , Kan Qixin , Song Mingyue , Hou Tao , An Siyu , Lin Hongyu , Chen Hongzhang , Hu Liuyun , Xiao Jie , Chen Yunjiao , Cao Yong
Published: March 2022

Ganoderma lucidum polysaccharides (GLP) exhibited excellent immunomodulatory activity. Unfortunately, the structure and immunomodulatory activity of GLP are still unclear. GLP was separated into two fractions [high Mw Restriction Fragment Length Polymorphism (RGLP) and low Mw EGLP] using 10 kDa cut-off ultrafiltration membrane. Although the RGLP content was low in GLP, the immunomodulatory activity in RGLP was significantly higher than that of EGLP. Moreover, RGLP was further separated via the Sephacryl column to obtain RGLP-1 showed the best immunomodulatory activity in the macrophage RAW264.7 model. Structural analysis revealed that RGLP-1 was 3,978 kDa and mainly consisted of glucose. Periodate oxidation, Smith degradation, and methylation results indicated that RGLP-1 is a β-pyran polysaccharide mainly with 1→3, 1→4, 1→6, and 1→3, 6 glycosyl bonds at a molar ratio of 40.08: 8.11: 5.62: 17.81. Scanning electron microscopy, atomic force microscopy, and Congo red experiments revealed that RGLP-1 intertwined with each other to form circular aggregates and might possess a globular structure with triple-helix conformation in water. Overall, these results provide RGLP-1 as a potential functional food ingredient or pharmaceutical for immunomodulatory.
A Data-Driven Fragmentation Model for Carbon Therapy GPU-Accelerated Monte-Carlo Dose Recalculation
Authors: De Simoni Micol , Battistoni Giuseppe , De Gregorio Angelica , De Maria Patrizia , Fischetti Marta , Franciosini Gaia , Marafini Michela , Patera Vincenzo , Sarti Alessio , Toppi Marco , Traini Giacomo , Trigilio Antonio , Schiavi Angelo
Published: March 2022

The advent of Graphics Processing Units (GPU) has prompted the development of Monte Carlo (MC) algorithms that can significantly reduce the simulation time with respect to standard MC algorithms based on Central Processing Unit (CPU) hardware. The possibility to evaluate a complete treatment plan within minutes, instead of hours, paves the way for many clinical applications where the time-factor is important. FRED (Fast paRticle thErapy Dose evaluator) is a software that exploits the GPU power to recalculate and optimise ion beam treatment plans. The main goal when developing the FRED physics model was to balance accuracy, calculation time and GPU execution guidelines. Nowadays, FRED is already used as a quality assurance tool in Maastricht and Krakow proton clinical centers and as a research tool in several clinical and research centers across Europe. Lately the core software has been updated including a model of carbon ions interactions with matter. The implementation is phenomenological and based on carbon fragmentation data currently available. The model has been tested against the MC FLUKA software, commonly used in particle therapy, and a good agreement was found. In this paper, the new FRED data-driven model for carbon ion fragmentation will be presented together with the validation tests against the FLUKA MC software. The results will be discussed in the context of FRED clinical applications to 12C ions treatment planning.
Network Pharmacologic Analysis of Dendrobium officinale Extract Inhibiting the Proliferation of Gastric Cancer Cells
Authors: Wei Lianping , Dong Wenhao , Han Zhen , Chen Chen , Jin Qing , He Jinling , Cai Yongping
Published: March 2022

Globally, gastric cancer (GC) is one of the three most deadly cancers. Dendrobium officinale (D. officinale) is a traditional Chinese medicine (TCM), and its extract can significantly inhibit the proliferation of gastric cancer cells. However, there are no unified conclusions on its potential active components and possible mechanisms of action. This paper aims at exploring the potential active components, targets, and cell pathways of D. officinale extract in inhibiting the proliferation of gastric cancer cells by using network pharmacology and cytology experiments. In this paper, UPLC-MS/MS was used to identify the main chemical components in the extracts of D. officinale, and the an ADME model was used to screen the potential active components. Network pharmacology methods such as target prediction, pathway identification, and network construction were used to determine the mechanism through which the D. officinale extract inhibited gastric cancer cell proliferation. MTT assays, fluorescence confocal microscopy, clone formation, and flow cytometry were used to verify the inhibitory activity of the D. officinale extract on gastric cancer cell proliferation in vitro. The UPLC-MS/MS analysis identified 178 chemical components from the D. officinale extract. Network pharmacology analysis showed that 13 chemical components had the potential to inhibit the proliferation of gastric cancer cells, with the possible involvement of 119 targets and 20 potential signaling pathways. In vitro experiments confirmed that the D. officinale extract could significantly inhibit the proliferation of gastric cancer cells. Therefore, we believe that the D. officinale extract can inhibit the proliferation of gastric cancer cells through effects on multiple components, multiple targets, and multiple pathways.
Large-Scale Black Silicon Induced by Femtosecond Laser Assisted With Laser Cleaning
Authors: Wen Zhidong , Shi Haiyan , Yue Song , Li Man , Zhang Zhe , Wang Ran , Song Qi , Xu Ziye , Zhang Zichen , Hou Yu
Published: March 2022

Black silicon is a promising and effective candidate in the field of photoelectric devices due to the high absorptance and broad-spectrum absorption property. The deposition around the processing area induced by the pressure of SF6, gravity, and the block of the processing chamber interferes the adjacent laser ablation and hampers uniform large-scale black silicon fabrication. To solve the problem, femtosecond laser- induced black silicon assisted with laser plasma shockwave cleaning is creatively proposed in our study. The results showed that higher, denser, and more uniform microstructures can be obtained than the conventional laser-induced method without laser cleaning. The average absorptance is 99.15% in the wavelength range of 0.3–2.5 µm, while it is more than 90% in the range of 2.5–20 µm. In addition, the scanning pitch dependence of surface morphology is discussed, and the better result is obtained in the range of 25–35 µm with 40-µm laser spot. Finally, a large-scale 50-mm × 50-mm black silicon with uniform microstructures was prepared by our method. It has been demonstrated that the deposition is effectively eliminated via our method, and the optical absorption is also enhanced significantly. It is of great significance for realizing large-scale preparation of photoelectric devices based on black silicon and lays the foundation for the development of laser-inducing equipment and industrial application.
The Physiological and Evolutionary Ecology of Sperm Thermal Performance
Authors: Wang Wayne Wen-Yeu , Gunderson Alex R.
Published: March 2022

Ongoing anthropogenic climate change has increased attention on the ecological and evolutionary consequences of thermal variation. Most research in this field has focused on the physiology and behavior of diploid whole organisms. The thermal performance of haploid gamete stages directly tied to reproductive success has received comparatively little attention, especially in the context of the evolutionary ecology of wild (i.e., not domesticated) organisms. Here, we review evidence for the effects of temperature on sperm phenotypes, emphasizing data from wild organisms whenever possible. We find that temperature effects on sperm are pervasive, and that above normal temperatures in particular are detrimental. That said, there is evidence that sperm traits can evolve adaptively in response to temperature change, and that adaptive phenotypic plasticity in sperm traits is also possible. We place results in the context of thermal performance curves, and encourage this framework to be used as a guide for experimental design to maximize ecological relevance as well as the comparability of results across studies. We also highlight gaps in our understanding of sperm thermal performance that require attention to more fully understand thermal adaptation and the consequences of global change.
Role of Scar and Border Zone Geometry on the Genesis and Maintenance of Re-Entrant Ventricular Tachycardia in Patients With Previous Myocardial Infarction
Authors: Gionti Vincenzo , Scacchi Simone , Colli Franzone Piero , Pavarino Luca F. , Dore Roberto , Storti Cesare
Published: March 2022

In patients with healed myocardial infarction, the left ventricular ejection fraction is characterized by low sensitivity and specificity in the prediction of future malignant arrhythmias. Thus, there is the need for new parameters in daily practice to perform arrhythmic risk stratification. The aim of this study is to identify some features of proarrhythmic geometric configurations of scars and border zones (BZ), by means of numerical simulations based on left ventricular models derived from post myocardial infarction patients. Two patients with similar clinical characteristics were included in this study. Both patients exhibited left ventricular scars characterized by subendo- and subepicardial BZ and a transmural BZ isthmus. The scar of patient #1 was significantly larger than that of patient #2, whereas the transmural BZ isthmus and the subdendo- and subepicardial BZs of patient #2 were thicker than those of patient #1. Patient #1 was positive at electrophysiologic testing, whereas patient #2 was negative. Based on the cardiac magnetic resonance (CMR) data, we developed a geometric model of the left ventricles of the two patients, taking into account the position, extent, and topological features of scars and BZ. The numerical simulations were based on the anisotropic monodomain model of electrocardiology. In the model of patient #1, sustained ventricular tachycardia (VT) was inducible by an S2 stimulus delivered at any of the six stimulation sites considered, while in the model of patient #2 we were not able to induce sustained VT. In the model of patient #1, making the subendo- and subepicardial BZs as thick as those of patient #2 did not affect the inducibility and maintenance of VT. On the other hand, in the model of patient #2, making the subendo- and subepicardial BZs as thin as those of patient #1 yielded sustained VT. In conclusion, the results show that the numerical simulations have an effective predictive capability in discriminating patients at high arrhythmic risk. The extent of the infarct scar and the presence of transmural BZ isthmuses and thin subendo- and subepicardial BZs promote sustained VT.