bluuebunny/crossref_metadata_2025 huggingface dataset:
Artificial Insemination and Parthenogenesis in the Zebra Shark Stegostoma tigrinum
Authors: Adams Lance , Lyons Kady , Larkin Elizabeth , Leier Nicole , Monday Janet , Plante Chris , Dubach Jean , Wyffels Jennifer
Published: June 2022

Maintaining self-sustaining populations of zoo and aquarium collections can be challenged when natural reproduction fails within mixed-sex populations; however, reproductive success can sometimes be restored with the application of reproductive technologies. Among a population of three female and one male Zebra Sharks (Stegostoma tigrinum), production of young failed despite constant male presence with two of the females. To determine if assisted techniques could be used to rescue sexual reproduction, artificial insemination was performed in a singleton female twice over a three-year period using freshly collected semen. Hatching success for eggs laid by all three females was monitored to compare natural and artificial insemination modes. After the first insemination (December 15th, 2011), 143 yolked eggs resulted in no sexually produced offspring and four genetically-confirmed, parthenogenetic offspring. After the second insemination (September 24th, 2013), 62 yolked eggs resulted in two sexually produced offspring, 18 and 33 days after insemination, and three parthenogenetic offspring > 213 days post-insemination. For the two females housed with the male, no sexual offspring resulted. All females produced at least one hatched parthenote. This study successfully employed artificial insemination to circumvent barriers to natural reproduction in Zebra Sharks. With further development, artificial insemination represents a powerful tool that could be used for maintaining genetic diversity for animals housed in aquaria and conservation-based breeding programs for elasmobranchs.
Some Distinct Features of Transformative High Entropy Alloys for Metal Additive Manufacturing
Authors: Nene S.S.
Published: June 2022

Sudden damage in engineering materials during service was always a challenge, and a lot of efforts have been put forward by materials scientists to resolve this issue. This motivated the design of a variety of classes of alloys such as stainless steel, deformed and partitioned steels, metastable Ti alloys, and recently developed high entropy alloys (HEA). A continuous evolving journey from single-phase to multi-phase HEAs showed exceptional work hardenability in them, which is required for improved failure resistance in metallic systems. In line with that, recently developed transformative high entropy alloys (T-HEAs) displayed interesting outcomes in terms of improved damage tolerance (σUTS ∼1.2 GPa and ductility ∼20% with 1.5% defect density) after conventional processing, severe deformation, and laser-assisted 3D printing. These outcomes were attributed to the localized WH activity within the stress concentration regions due to the activation of transformation induced plasticity (TRIP) effect near the defects. As a result, defects present in these T-HEAs act as sites for delaying the damage by showing a pronounced transformation induced crack retardation (TRICR) effect, thereby improving failure resistance during service.
Influence of Ammonia on the Corrosion Behavior of a Zr–Sn–Nb Alloy in High Temperature Water
Authors: Chen Zirui , Zhao Yongfu , Tang Min , Yin Zhaohui , Gong Bin , Wu Zongpei
Published: June 2022

Corrosion behaviors, microstructures of oxide films, and hydrogen absorptions of a Chinese domestic Zr alloy in 6.7 × 10−3 mol/L ammonia solution and 2.9 × 10−4 mol/L LiOH+9.3 × 10−2 mol/L H3BO3 solution at 360 °C, 18.6 MPa were studied. Weight gains, oxide film thicknesses, and hydrogen absorptions showed that the corrosion rate in the ammonia solution is a little higher than that in the boron–lithium solution. There is no significant difference in the microstructure and crystalline structure between the oxide films formed in the two types of solutions. The element distributions along the depth direction of the oxide films showed the existence of nitrogen in the oxide film formed in ammonia solution. Moreover, nitrogen was found to be segregated in local areas in a range of about 2 μm from the oxide/metal interface. The corrosion behavior of the Chinese domestic Zr alloy in 360 °C aqueous solution shows no difference with other Zr alloys.
Sugar Shock: Probing Streptococcus pyogenes Metabolism Through Bioluminescence Imaging
Authors: Davis Richard W. , Muse Charlotte G. , Eggleston Heather , Hill Micaila , Panizzi Peter
Published: June 2022

Streptococcus pyogenes (S. pyogenes) can thrive in its host during an infection, and, as a result, it must be able to respond to external stimuli and available carbon sources. The preclinical use of engineered pathogens capable of constitutive light production may provide real-time information on microbial-specific metabolic processes. In this study, we mapped the central metabolism of a luxABCDE-modified S. pyogenes Xen20 (Strep. Xen20) to its de novo synthesis of luciferase substrates as assessed by the rate of light production in response to different environmental triggers. Previous characterization predicted that the lux operon was under the myo-inositol iolE promotor. In this study, we revealed that supplementation with myo-inositol generated increased Strep. Xen20 luminescence. Surprisingly, when supplemented with infection-relevant carbon sources, such as glucose or glycine, light production was diminished. This was presumably due to the scavenging of pyruvate by L-lactate dehydrogenase (LDH). Inhibition of LDH by its inhibitor, oxamate, partially restored luminescent signal in the presence of glucose, presumably by allowing the resulting pyruvate to proceed to acetyl-coenzyme A (CoA). This phenomenon appeared specific to the lactic acid bacterial metabolism as glucose or glycine did not reduce signal in an analogous luxABCDE-modified Gram-positive pathogen, Staph. Xen29. The Strep. Xen20 cells produced light in a concentration-dependent manner, inversely related to the amount of glucose present. Taken together, our measures of microbial response could provide new information regarding the responsiveness of S. pyogenes metabolism to acute changes in its local environments and cellular health.
Impact of Modified Atmospheres on Growth and Metabolism of Meat-Spoilage Relevant Photobacterium spp. as Predicted by Comparative Proteomics
Authors: Fuertes-Perez Sandra , Abele Miriam , Ludwig Christina , Vogel Rudi F. , Hilgarth Maik
Published: June 2022

Modified atmosphere packaging (MAP) is a common strategy to selectively prevent the growth of certain species of meat spoiling bacteria. This study aimed to determine the impact of high oxygen MAP (70% O2, 30% CO2, red and white meats) and oxygen-free MAP (70% N2, 30% CO2, also white meat and seafood) on preventing the growth of spoiling photobacteria on meat. Growth ofPhotobacterium carnosumandP. phosphoreumwas monitored in a meat simulation media under different gas mixtures of nitrogen, oxygen, and carbon dioxide, and samples were taken during exponential growth for a comparative proteomic analysis. Growth under air atmosphere appears optimal, particularly forP. carnosum. Enhanced protein accumulation affected energy metabolism, respiration, oxygen consuming reactions, and lipid usage. However, all the other atmospheres show some degree of growth reduction. An increase in oxygen concentration leads to an increase in enzymes counteracting oxidative stress for both species and enhancement of heme utilization and iron-sulfur cluster assembly proteins forP. phosphoreum. Absence of oxygen appears to switch the metabolism toward fermentative pathways where either ribose (P. phosphoreum)or glycogen (P. carnosum)appear to be the preferred substrates. Additionally, it promotes the use of alternative electron donors/acceptors, mainly formate and nitrate/nitrite. Stress response is manifested as an enhanced accumulation of enzymes that is able to produce ammonia (e.g., carbonic anhydrase, hydroxylamine reductase) and regulate osmotic stress. Our results suggest that photobacteria do not sense the environmental levels of carbon dioxide, but rather adapt to their own anaerobic metabolism. The regulation in presence of carbon dioxide is limited and strain-specific under anaerobic conditions. However, when oxygen at air-like concentration (21%) is present together with carbon dioxide (30%), the oxidative stress appears enhanced compared to air conditions (very low carbon dioxide), as explained if both gases have a synergistic effect. This is further supported by the increase in oxygen concentration in the presence of carbon dioxide. The atmosphere is able to fully inhibitP. carnosum, heavily reduceP. phosphoreumgrowthin vitro, and trigger diversification of energy production with higher energetic cost, highlighting the importance of concomitant bacteria for their growth on raw meat under said atmosphere.
Strawberry Vein Banding Virus Movement Protein P1 Interacts With Light-Harvesting Complex II Type 1 Like of Fragaria vesca to Promote Viral Infection
Authors: Xu Shiqiang , Zhang Xiangxiang , Xu Kai , Wang Zhanqi , Zhou Xueping , Jiang Lei , Jiang Tong
Published: June 2022

Chlorophyll a/b-binding protein of light-harvesting complex II type 1 like (LHC II-1L) is an essential component of photosynthesis, which mainly maintains the stability of the electron transport chain. However, how the LHC II-1L protein of Fragaria vesca (FvLHC II-1L) affects viral infection remains unclear. In this study, we demonstrated that the movement protein P1 of strawberry vein banding virus (SVBV P1) interacted with FvLHC II-1L in vivo and in vitro by bimolecular fluorescence complementation and pull-down assays. SVBV P1 was co-localized with FvLHC II-1L at the edge of epidermal cells of Nicotiana benthamiana leaves, and FvLHC II-1L protein expression was upregulated in SVBV-infected F. vesca. We also found that FvLHC II-1L effectively promoted SVBV P1 to compensate for the intercellular movement of movement-deficient potato virus X (PVXΔP25) and the systemic movement of movement-deficient cucumber mosaic virus (CMVΔMP). Transient overexpression of FvLHC II-1L and inoculation of an infectious clone of SVBV showed that the course of SVBV infection in F. vesca was accelerated. Collectively, the results showed that SVBV P1 protein can interact with FvLHC II-1L protein, which in turn promotes F. vesca infection by SVBV.
Feasibility of Hepatitis C Elimination in China: From Epidemiology, Natural History, and Intervention Perspectives
Authors: Zhao Zeyu , Chu Meijie , Guo Yichao , Yang Shiting , Abudurusuli Guzainuer , Frutos Roger , Chen Tianmu
Published: June 2022

Hepatitis C imposes a heavy burden on many countries, including China, where the number of reported cases and the incidence of hepatitis C virus (HCV) increased yearly from 2005 to 2012, with a stable trend after 2012. The geographical distribution of HCV infections varies widely in China, with the northwest and southwest regions and the Henan Province showing a high disease burden. Elderly, men, sexually active people, drug users, migrants, blood transfusion recipients, and renal dialysis patients have become the target populations for hepatitis C prevention and control. It is important to improve the diagnosis rate in high-risk groups and asymptomatic people. Identifying secondary HCV infections, especially in HCV patients co-infected with the human immunodeficiency virus (HIV) is a priority of hepatitis C prevention and control. Enhancing universal access to direct antiviral agents (DAAs) treatment regimens is an effective way to improve the cure rate of HCV infection. For China to contribute to the WHO 2030 global HCV elimination plan, strategic surveillance, management, and treatment program for HCV are needed.
Patterns of Microbiome Composition Vary Across Spatial Scales in a Specialist Insect
Authors: Paddock Kyle J. , Finke Deborah L. , Kim Kyung Seok , Sappington Thomas W. , Hibbard Bruce E.
Published: June 2022

Microbial communities associated with animals vary based on both intrinsic and extrinsic factors. Of many possible determinants affecting microbiome composition, host phylogeny, host diet, and local environment are the most important. How these factors interact across spatial scales is not well understood. Here, we seek to identify the main influences on microbiome composition in a specialist insect, the western corn rootworm (WCR; Diabrotica virgifera virgifera), by analyzing the bacterial communities of adults collected from their obligate host plant, corn (Zea mays), across several geographic locations and comparing the patterns in communities to its congeneric species, the northern corn rootworm (NCR; Diabrotica barberi). We found that bacterial communities of WCR and NCR shared a portion of their bacterial communities even when collected from disparate locations. However, within each species, the location of collection significantly influenced the composition of their microbiome. Correlations of geographic distance between sites with WCR bacterial community composition revealed different patterns at different spatial scales. Community similarity decreased with increased geographic distance at smaller spatial scales (~25 km between the nearest sites). At broad spatial scales (>200 km), community composition was not correlated with distances between sites, but instead reflected the historical invasion path of WCR across the United States. These results suggest bacterial communities are structured directly by dispersal dynamics at small, regional spatial scales, while landscape-level genetic or environmental differences may drive community composition across broad spatial scales in this specialist insect.
Molecular Tools for Typing Mycoplasma pneumoniae and Mycoplasma genitalium
Authors: Dumke Roger
Published: June 2022

Mycoplasma pneumoniae and Mycoplasma genitalium are cell wall-less bacteria with strongly reduced genome content and close phylogenetic relatedness. In humans, the only known natural host, the microorganisms colonize the respiratory or genitourinary mucosa and may cause a broad range of clinical presentations. Besides fundamental differences in their tissue specificity, transmission route, and ability to cause prevalence peaks, both species share similarities such as the occurrence of asymptomatic carriers, preferred populations for infection, and problems with high rates of antimicrobial resistance. To further understand the epidemiology of these practically challenging bacteria, typing of strains is necessary. Since the cultivation of both pathogens is difficult and not performed outside of specialized laboratories, molecular typing methods with adequate discriminatory power, stability, and reproducibility have been developed. These include the characterization of genes containing repetitive sequences, of variable genome regions without the presence of repetitive sequences, determination of single and multi-locus variable-number tandem repeats, and detection of single nucleotide polymorphisms in different genes, respectively. The current repertoire of procedures allows reliable differentiation of strains circulating in different populations and in different time periods as well as comparison of strains occurring subsequently in individual patients. In this review, the methods for typing M. pneumoniae and M. genitalium, including the results of their application in different studies, are summarized and current knowledge regarding the association of typing data with the clinical characteristics of infections is presented.
Rare c-KIT c.1926delA and c.1936T>G Mutations in Exon 13 Define Imatinib Resistance in Gastrointestinal Stromal Tumors and Melanoma Patients: Case Reports and Cell Experiments
Authors: Yan Chi , Zhao Chengzhi , Yang Ke , Zhou Hongyan , Jing Limin , Zhao Weixing , Dou Wenguang , Xia Qingxin , Ma Jie , Wei Bing , Guo Yongjun
Published: June 2022

Background: Target therapies play more and more important roles in gastrointestinal stromal tumors (GISTs) and melanoma with the advancement of clinical drugs that overcome the resistance caused by gene mutations. c-KIT gene mutations account for a large portion of GIST patients, which are known to be sensitive or resistant to tyrosine kinase inhibitors. However, the role rare mutations play in drug efficacy and progression-free duration remains elusive.

Methods: Two rare mutations were identified using Sanger sequencing from the GIST and melanoma cases. Cell experiments were further carried out to demonstrate their role in the imatinib resistance.

Results:c-KIT c.1926delA p.K642S*FS mutation in primary and recurrent GIST patients and c-KIT c.1936T>G p.Y646D point mutation in melanoma patients in exon 13 were first demonstrated to be novel targets resistant to imatinib agent.

Conclusion:c-KIT mutations c.1926delA and c.1936T>G in exon 13 are clinically significant targets that exhibit resistance to imatinib. This study provides guidance to GIST and melanoma treatments.
Identifying Topics and Evolutionary Trends of Literature on Brain Metastases Using Latent Dirichlet Allocation
Authors: Chen Jiarong , Williams Matt , Huang Yanming , Si Shijing
Published: June 2022

Research on brain metastases kept innovating. We aimed to illustrate what topics the research focused on and how it varied in different periods of all the studies on brain metastases with topic modelling. We used the latent Dirichlet allocation model to analyse the titles and abstracts of 50,176 articles on brain metastases retrieved from Web of Science, Embase and MEDLINE. We further stratified the articles to find out the topic trends of different periods. Our study identified that a rising number of studies on brain metastases were published in recent decades at a higher rate than all cancer articles. Overall, the major themes focused on treatment and histopathology. Radiotherapy took over the first and third places in the top 20 topics. Since the 2010’s, increasing attention concerned about gene mutations. Targeted therapy was a popular topic of brain metastases research after 2020.
Reorganization of the Brain Structural Covariance Network in Ischemic Moyamoya Disease Revealed by Graph Theoretical Analysis
Authors: Wang Peijing , Li Wenjie , Zhu Huan , Liu Xingju , Yu Tao , Zhang Dong , Zhang Yan
Published: June 2022

Objective

Ischemic moyamoya (MMD) disease could alter the cerebral structure, but little is known about the topological organization of the structural covariance network (SCN). This study employed structural magnetic resonance imaging and graph theory to evaluate SCN reorganization in ischemic MMD patients.

Method

Forty-nine stroke-free ischemic MMD patients and 49 well-matched healthy controls (HCs) were examined by T1-MPRAGE imaging. Structural images were pre-processed using the Computational Anatomy Toolbox 12 (CAT 12) based on the diffeomorphic anatomical registration through exponentiated lie (DARTEL) algorithm and both the global and regional SCN parameters were calculated and compared using the Graph Analysis Toolbox (GAT).

Results

Most of the important metrics of global network organization, including characteristic path length (Lp), clustering coefficient (Cp), assortativity, local efficiency, and transitivity, were significantly reduced in MMD patients compared with HCs. In addition, the regional betweenness centrality (BC) values of the bilateral medial orbitofrontal cortices were significantly lower in MMD patients than in HCs after false discovery rate (FDR) correction for multiple comparisons. The BC was also reduced in the left medial superior frontal gyrus and hippocampus, and increased in the bilateral middle cingulate gyri of patients, but these differences were not significant after FDR correlation. No differences in network resilience were detected by targeted attack analysis or random failure analysis.

Conclusions

Both global and regional properties of the SCN are altered in MMD, even in the absence of major stroke or hemorrhagic damage. Patients exhibit a less optimal and more randomized SCN than HCs, and the nodal BC of the bilateral medial orbitofrontal cortices is severely reduced. These changes may account for the cognitive impairments in MMD patients.
Growth Differentiation Factor 15 Protects SH-SY5Y Cells From Rotenone-Induced Toxicity by Suppressing Mitochondrial Apoptosis
Authors: Li Peizheng , Lv Hongbo , Zhang Bohan , Duan Ruonan , Zhang Xiufang , Lin Pengfei , Song Chengyuan , Liu Yiming
Published: June 2022

Objective

Parkinson’s disease (PD) is the second most common neurodegenerative disorder worldwide. Mitochondrial dysfunction is suspected as one of the pathogenic mechanisms of PD. Growth/differentiation Factor-15 (GDF15) has been reported to affect mitochondrial function in PD. However, the relationship between mitochondrial function and GDF15 induction has not been explained well. Hence, we aimed to reveal the effect of GDF15 induction on SH-SY5Y cells with rotenone toxicity, a cell model of PD.

Methods

SH-SY5Y cells were exposed to 1 μM rotenone as a PD model. Cells were transfected with a GDF15-overexpression plasmid and empty vector. We then analyzed the expression level of GDF15, BCL-2/BAX, P53, PGC1-α, α-syn, and TH in GDF15-overexpressing cells by western blotting, enzyme-linked immunosorbent assay, and quantitative real-time polymerase chain reaction. The cytotoxicity of rotenone was measured by CCK-8 assays. Cell apoptosis was detected by flow cytometric and TUNEL assays. The effect of GDF15 on oxidative stress and mitochondrial function was revealed using DCFH-DA, mito-SOX, and JC-10 assays and a Seahorse XF Cell Mito Stress Test.

Results

GDF15 protected rotenone-treated SH-SY5Y cells from toxicity by preserving mitochondrial function and decreasing apoptosis, during which GDF15 might function by influencing PGC1α through the regulation of p53. In addition, GDF15 overexpression could improve Akt and mTOR phosphorylation, leading to PI3K/Akt/mTOR pathway activation. However, these protective effects were eliminated when cells were treated with the PI3K/Akt specific inhibitor LY294002.

Conclusion

Our findings suggest that GDF15 can protect mitochondrial function and inhibit apoptosis in SH-SY5Y cells after exposure to rotenone by upregulating PGC1α via p53. These properties might comprise its anti-apoptotic effects, mediated by the PI3K/Akt/mTOR signaling pathway.
Are the Anterior and Mid-Cingulate Cortices Distinct in Rodents?
Authors: Francis-Oliveira Jose , Leitzel Owen , Niwa Minae
Published: June 2022

The prefrontal cortex (PFC) is involved in cognitive control, emotional regulation, and motivation. In this Perspective article, we discuss the nomenclature of the subdivisions of the medial prefrontal cortex (mPFC), since the anatomical definitions of the PFC subregions have been confusing. Although the mid-cingulate cortex (MCC) and anterior cingulate cortex (ACC) have distinct features in humans and non-human primates, it is unclear whether these regions serve different functions in rodents. Accurate mapping of the cingulate cortex in rodents is important to allow comparisons between species. A proposed change in the nomenclature of the rodent cingulate cortex to anterior cingulate cortex (aCg) and mid-cingulate cortex (mCg) is presented based on our data. We show evidence for distinct cortico-cortical projections from the aCg and mCg to the PrL. The aCg→PrL neurons were abundant in layer VI, while the mCg→PrL neurons were mainly distributed in layer V. In addition, a sex difference was detected in the aCg, with males having a higher proportion of layer V neurons projecting to the PrL than females. Based on this laminar distribution and considering that layer V and VI send efferent projections to different brain areas such as the brain stem, amygdala, and thalamus, we propose that aCg and mCg need to be considered separate entities for future rodent studies. This new definition will put into perspective the role of rodent cingulate cortex in diverse aspects of cognition and facilitate interspecies comparisons in cingulate cortex research.
The Effect of Empowering Education Combined With Mindfulness Meditation Training on Negative Emotion and Quality of Life in Patients With Inflammatory Bowel Disease
Authors: Xi Wei-Zhen , Xu Chong-Wu , Wang Ling-Ling
Published: June 2022

Objective

To investigate the effect of empowerment education combined with mindfulness meditation training on negative emotions and quality of life in patients with inflammatory bowel disease (IBD).

Methods

A total of 40 patients with IBD were selected and divided into experimental group and control group according to the random number table method, 20 cases in each group. The patients in the control group were treated with conventional nursing methods. The patients in the experimental group used empowerment education combined with mindfulness meditation training. Changes in mood and quality of life were compared between the two groups at admission and 3 months after discharge.

Results

There was no significant difference in SAS score and quality of life score between the two groups. After authorization education combined with mindfulness meditation training, the SAS score of the experimental group was significantly lower than that of the control group (P < 0.01). The score of quality of life in the experimental group was significantly higher than that in the control group (P < 0.01).

Conclusion

Empowerment education combined with mindfulness meditation can effectively improve the negative emotions and quality of life of patients with inflammatory bowel disease, and benefit the patients in many aspects.
Reinforcement Learning Model With Dynamic State Space Tested on Target Search Tasks for Monkeys: Extension to Learning Task Events
Authors: Sakamoto Kazuhiro , Yamada Hinata , Kawaguchi Norihiko , Furusawa Yoshito , Saito Naohiro , Mushiake Hajime
Published: June 2022

Learning is a crucial basis for biological systems to adapt to environments. Environments include various states or episodes, and episode-dependent learning is essential in adaptation to such complex situations. Here, we developed a model for learning a two-target search task used in primate physiological experiments. In the task, the agent is required to gaze one of the four presented light spots. Two neighboring spots are served as the correct target alternately, and the correct target pair is switched after a certain number of consecutive successes. In order for the agent to obtain rewards with a high probability, it is necessary to make decisions based on the actions and results of the previous two trials. Our previous work achieved this by using a dynamic state space. However, to learn a task that includes events such as fixation to the initial central spot, the model framework should be extended. For this purpose, here we propose a “history-in-episode architecture.” Specifically, we divide states into episodes and histories, and actions are selected based on the histories within each episode. When we compared the proposed model including the dynamic state space with the conventional SARSA method in the two-target search task, the former performed close to the theoretical optimum, while the latter never achieved target-pair switch because it had to re-learn each correct target each time. The reinforcement learning model including the proposed history-in-episode architecture and dynamic state scape enables episode-dependent learning and provides a basis for highly adaptable learning systems to complex environments.
Identifying the Conditions for Cost-Effective Minimally Invasive Neurosurgery in Spontaneous Supratentorial Intracerebral Hemorrhage
Authors: Schreuder Floris H. B. M. , Scholte Mirre , Ulehake Marike J. , Sondag Lotte , Rovers Maroeska M. , Dammers Ruben , Klijn Catharina J. M. , Grutters Janneke P. C.
Published: June 2022

Background

In patients with spontaneous supratentorial intracerebral hemorrhage (ICH), open craniotomy has failed to improve a functional outcome. Innovative minimally invasive neurosurgery (MIS) may improve a health outcome and reduce healthcare costs.

Aims

Before starting phase-III trials, we aim to assess conditions that need to be met to reach the potential cost-effectiveness of MIS compared to usual care in patients with spontaneous supratentorial ICH.

Methods

We used a state-transition model to determine at what effectiveness and cost MIS would become cost-effective compared to usual care in terms of quality-adjusted life-years (QALYs) and direct healthcare costs. Threshold and two-way sensitivity analyses were used to determine the minimal effectiveness and maximal costs of MIS, and the most cost-effective strategy for each combination of cost and effectiveness. Scenario and probabilistic sensitivity analyses addressed model uncertainty.

Results

Given €10,000 of surgical costs, MIS would become cost-effective when at least 0.7–1.3% of patients improve to a modified Rankin Scale (mRS) score of 0–3 compared to usual care. When 11% of patients improve to mRS 0–3, surgical costs may be up to €83,301–€164,382, depending on the population studied. The cost-effectiveness of MIS was mainly determined by its effectiveness. In lower mRS states, MIS needs to be more effective to be cost-effective compared to higher mRS states.

Conclusion

MIS has the potential to be cost-effective in patients with spontaneous supratentorial ICH, even with relatively low effectiveness. These results support phase-III trials to investigate the effectiveness of MIS.
Criteria for Treatment Response in Myasthenia Gravis: Comparison Between Absolute Change and Improvement Percentage in Severity Scores
Authors: Li Hong-Yan , Jiang Ping , Xie Yanchen , Liang Bing , Li Ling , Zhao Cuiping , Yue Yao-Xian , Li Hai-Feng
Published: June 2022

Background

The absolute change in the severity score between the baseline and pre-specified time frame (absolute criterion) was recommended as a criterion for myasthenia gravis (MG) treatment response. But heterogeneity of disease severity might dilute major changes in individual patients. The rationality of relative criterion (improvement percentage) had not been evaluated in treatment response in patients with MG.

Objectives

To investigate the consistency between an absolute criterion and a relative criterion in the evaluation of treatment response in patients with MG.

Methods

We retrospectively analyzed the treatment response to a 3-month standardized treatment protocol with only glucocorticoid in 257 MG patients native to immunological treatments. With the commonly used absolute criterion, cut-offs of relative criteria were generated with the receiver operating characteristic (ROC) curve in the whole cohort and in patients with different degrees of baseline severity stratified by pre-treatment quantitative myasthenia gravis score (QMGS). The consistency between absolute and relative criteria was examined with Cohen's Kappa test and Venn diagrams.

Results

The absolute and relative criteria had an overall substantial consistency (Kappa value, 0.639, p < 0.001) in the cohort. The Kappa values were substantial to almost perfect in mild and moderate groups and moderate in severe groups between the absolute and relative criteria (all p ≤ 0.001). More patients were classified as responsive with an absolute criterion while as unresponsive with a relative criterion in the moderate and severe groups.

Conclusions

The overall consistency between absolute and relative criteria was substantial in the whole cohort. The inconsistency between the two criteria was mainly from the moderate or severe patients at the baseline.
Social Action Effects: Representing Predicted Partner Responses in Social Interactions
Authors: Neszmélyi Bence , Weller Lisa , Kunde Wilfried , Pfister Roland
Published: June 2022

The sociomotor framework outlines a possible role of social action effects on human action control, suggesting that anticipated partner reactions are a major cue to represent, select, and initiate own body movements. Here, we review studies that elucidate the actual content of social action representations and that explore factors that can distinguish action control processes involving social and inanimate action effects. Specifically, we address two hypotheses on how the social context can influence effect-based action control: first, by providing unique social features such as body-related, anatomical codes, and second, by orienting attention towards any relevant feature dimensions of the action effects. The reviewed empirical work presents a surprisingly mixed picture: while there is indirect evidence for both accounts, previous studies that directly addressed the anatomical account showed no signs of the involvement of genuinely social features in sociomotor action control. Furthermore, several studies show evidence against the differentiation of social and non-social action effect processing, portraying sociomotor action representations as remarkably non-social. A focus on enhancing the social experience in future studies should, therefore, complement the current database to establish whether such settings give rise to the hypothesized influence of social context.
Skin and Mechanoreceptor Contribution to Tactile Input for Perception: A Review of Simulation Models
Authors: Deflorio Davide , Di Luca Massimiliano , Wing Alan M.
Published: June 2022

We review four current computational models that simulate the response of mechanoreceptors in the glabrous skin to tactile stimulation. The aim is to inform researchers in psychology, sensorimotor science and robotics who may want to implement this type of quantitative model in their research. This approach proves relevant to understanding of the interaction between skin response and neural activity as it avoids some of the limitations of traditional measurement methods of tribology, for the skin, and neurophysiology, for tactile neurons. The main advantage is to afford new ways of looking at the combined effects of skin properties on the activity of a population of tactile neurons, and to examine different forms of coding by tactile neurons. Here, we provide an overview of selected models from stimulus application to neuronal spiking response, including their evaluation in terms of existing data, and their applicability in relation to human tactile perception.
Dynamic Inter-Brain Networks Correspond With Specific Communication Behaviors: Using Functional Near-Infrared Spectroscopy Hyperscanning During Creative and Non-creative Communication
Authors: Wang Xinyue , Zhang Yu , He Yingyao , Lu Kelong , Hao Ning
Published: June 2022

Social interaction is a dynamic and variable process. However, most hyperscanning studies implicitly assume that inter-brain synchrony (IBS) is constant and rarely investigate the temporal variability of the multi-brain networks. In this study, we used sliding windows and k-mean clustering to obtain a set of representative inter-brain network states during different group communication tasks. By calculating the network parameters and temporal occurrence of the inter-brain states, we found that dense efficient interbrain states and sparse inefficient interbrain states appeared alternately and periodically, and the occurrence of efficient interbrain states was positively correlated with collaborative behaviors and group performance. Moreover, compared to common communication, the occurrence of efficient interbrain states and state transitions were significantly higher during creative communication, indicating a more active and intertwined neural network. These findings may indicate that there is a close correspondence between inter-brain network states and social behaviors, contributing to the flourishing literature on group communication.
Altered Homotopic Connectivity in the Cerebellum Predicts Stereopsis Dysfunction in Patients With Comitant Exotropia
Authors: Chen Fei , Hu Zhirou , Liu Hui , Zhen Fangyuan , Liu Chenlu , Li Qiuming
Published: June 2022

Purpose

Comitant exotropia (CE) is a common eye disorder characterized by impaired stereoscopic vision and eye deviation. Previous neuroimaging studies demonstrated that patients with CE were accompanied by specific functional and structural abnormalities of the brain. However, the effect of impaired stereoscopic vision and eye deviation on interhemispheric homotopic connectivity remains unknown.

Methods

A total of thirty-six patients with CE (25 males and 11 females) and 36 well-matched healthy controls underwent magnetic resonance imaging scanning. The voxel-mirrored homotopic connectivity (VMHC) method was applied to assess the interhemispheric homotopic connectivity changes in patients with CE. Furthermore, the support vector machine method was applied to assess to differentiate patients with CE from healthy controls (HCs) with the VMHC maps as a feature.

Results

Compared with HCs, patients with CE showed significantly increased VMHC values in the bilateral cerebelum_ 8 and cerebelum_4_5. Moreover, we found that the VMHC maps showed an accuracy of 81.94% and an area under the curve of 0.87 for distinguishing the patients with CE from HCs.

Conclusion

Our study demonstrates that patients with CE showed interhemispheric homotopic connectivity changes in the cerebellum, which might reflect the neurological mechanisms of impaired stereoscopic vision and eye deviation in patients with CE.
Gut Bacteria Regulate the Pathogenesis of Huntington’s Disease in Drosophila Model
Authors: Chongtham Anjalika , Yoo Jung Hyun , Chin Theodore M. , Akingbesote Ngozi D. , Huda Ainul , Marsh J. Lawrence , Khoshnan Ali
Published: June 2022

Changes in the composition of gut microbiota are implicated in the pathogenesis of several neurodegenerative disorders. Here, we investigated whether gut bacteria affect the progression of Huntington’s disease (HD) in transgenic Drosophila melanogaster (fruit fly) models expressing full-length or N-terminal fragments of human mutant huntingtin (HTT) protein. We find that elimination of commensal gut bacteria by antibiotics reduces the aggregation of amyloidogenic N-terminal fragments of HTT and delays the development of motor defects. Conversely, colonization of HD flies with Escherichia coli (E. coli), a known pathobiont of human gut with links to neurodegeneration and other morbidities, accelerates HTT aggregation, aggravates immobility, and shortens lifespan. Similar to antibiotics, treatment of HD flies with small compounds such as luteolin, a flavone, or crocin a beta-carotenoid, ameliorates disease phenotypes, and promotes survival. Crocin prevents colonization of E. coli in the gut and alters the levels of commensal bacteria, which may be linked to its protective effects. The opposing effects of E. coli and crocin on HTT aggregation, motor defects, and survival in transgenic Drosophila models support the involvement of gut-brain networks in the pathogenesis of HD.
Ca2+ Regulates Dimerization of the BAR Domain Protein PICK1 and Consequent Membrane Curvature
Authors: Stan Georgiana F. , Shoemark Deborah K. , Alibhai Dominic , Hanley Jonathan G.
Published: June 2022

Bin-Amphiphysin-Rvs (BAR) domain proteins are critical regulators of membrane geometry. They induce and stabilize membrane curvature for processes, such as clathrin-coated pit formation and endosomal membrane tubulation. BAR domains form their characteristic crescent-shaped structure in the dimeric form, indicating that the formation of the dimer is critical to their function of inducing membrane curvature and suggesting that a dynamic monomer–dimer equilibrium regulated by cellular signaling would be a powerful mechanism for controlling BAR domain protein function. However, to the best of our knowledge, cellular mechanisms for regulating BAR domain dimerization remain unexplored. PICK1 is a Ca2+-binding BAR domain protein involved in the endocytosis and endosomal recycling of neuronal AMPA receptors and other transmembrane proteins. In this study, we demonstrated that PICK1 dimerization is regulated by a direct effect of Ca2+ ions via acidic regions in the BAR domain and at the N-terminus. While the cellular membrane tubulating activity of PICK1 is absent under basal conditions, Ca2+ influx causes the generation of membrane tubules that originate from the cell surface. Furthermore, in neurons, PICK1 dimerization increases transiently following NMDA receptor stimulation. We believe that this novel mechanism for regulating BAR domain dimerization and function represents a significant conceptual advance in our knowledge about the regulation of cellular membrane curvature.
Clinical and Biological Significance of a Necroptosis-Related Gene Signature in Glioma
Authors: Zhou Zunjie , Xu Jing , Huang Ning , Tang Jun , Ma Ping , Cheng Yuan
Published: June 2022

Background

As a novel form of programmed cell death, necroptosis is related to multiple tumor types and their immune microenvironments. However, its association with glioma has not been clarified.

Methods

Necroptosis genes were obtained from the Gene Set Enrichment Analysis (GSEA) database. RNA-seq and clinical data were downloaded from TCGA and CGGA databases. A necroptosis gene signature was constructed based on univariate and multivariate Cox regression analyses. Next, survival analysis, independent prognostic analysis, and nomogram were performed to assess and verify the model. Subsequently, we analyzed the tumor microenvironment (TME) and immune cell infiltration via ESTIMATE and CIBERSORTx algorithms. Finally, the response of glioma patients in the TCGA database to immune checkpoint inhibitor (ICI) therapy was predicted using the Tumor Immune Dysfunction and Exclusion (TIDE) database.

Results

Of the seven prognostic necroptosis genes, RIPK1, RIPK3, FAS, and FADD were used to construct the risk signature that accurately predicts the prognosis of glioma patients. Functional enrichment results suggest that necroptosis is correlated with immune response and angiogenesis. Immune analysis revealed that necroptosis can boost inflammatory activity and attract immunosuppressive cell infiltration to form a chronic inflammatory microenvironment, promoting glioma growth. Additionally, glioma patients in the TCGA cohort with high necroptosis gene expression exhibited a better response to ICI therapy predicted by the TIDE algorithm.

Conclusion

We constructed a necroptosis gene signature, which has the potential for use as a biomarker for predicting glioma patients’ prognosis, revealing the association between necroptosis and the immune microenvironment, and serving as a reference for immune therapy.
Identification and Verification of Immune Subtype-Related lncRNAs in Clear Cell Renal Cell Carcinoma
Authors: Wang Zhifeng , Chen Zihao , Guo Tengyun , Hou Menglin , Wang Junpeng , Guo Yanping , Du Tao , Zhang Xiaoli , Wang Ning , Ding Degang , Li Xiqing
Published: June 2022

Background

According to clinical study results, immune checkpoint blockade (ICB) treatment enhances the survival outcome of patients with clear cell renal cell carcinoma (ccRCC). Previous research has divided ccRCC patients into immune subtypes with distinct ICB response rates. However, the study on the association between lncRNAs and ccRCC immune subtypes is lacking.

Methods

Differentially expressed lncRNAs/mRNAs between two major immune subgroups were calculated. A weighted gene co-expression network analysis (WGCNA) was conducted to establish the lncRNA-mRNA co-expression network and select the key lncRNAs. Then, prognostic lncRNAs were selected from the network by the bioinformatics method. Next, the risk-score was estimated by lncRNA expression and their coefficients. Finally, a nomogram based on lncRNAs and clinical parameters was created to predict the prognosis of ccRCC.

Results

LncRNAs and mRNAs associated with ccRCC immune subtypes were identified. The lncRNAs and mRNAs from a gene module closely linked to the immune subtype were used to construct a network. The KEGG pathways enriched in the network were related to immune system activation processes. These 8 lncRNAs (AL365361.1, LINC01934, AC090152.1, PCED1B-AS1, LINC00426, AC007728.2, AC243829.4, and LINC00158) were found to be positively correlated with immune cells of the tumor microenvironment. The C-index of the nomogram was 0.777, and the calibration curve data suggests that the nomogram has a high degree of discriminating capacity.

Conclusion

In summary, we discovered core lncRNAs linked with immune subtypes and created corresponding lncRNA–mRNA networks. These lncRNAs are anticipated to have predictive significance for ccRCC and may provide insight into novel biomarkers for the disease.
Development of the Practice of Pharmaceutical Care for Cancer Pain Management in Outpatient Clinics Using the Delphi Method
Authors: Zhang Lu , Ren Xia-Yang , Huang Hang-Xing , Huang Ya-Min , Huang Ling , Chen Xiao-Ping , Chen Yao , Wang Chen , Xiao Jian
Published: June 2022

Background: There exists no broad agreement of experts on the practice of pharmaceutical care for cancer pain management in outpatient clinics.

Objectives: This study aimed to use the Delphi consensus process to provide expert recommendations on the practice of cancer pain management in outpatient clinics from the point of view of pharmaceutical care in clinical practice and future clinical trials.

Methods: A comprehensive literature review was conducted to draft the initial practice. In this process, 30–40 senior experts from various provinces in China were invited to rank the items of practice during the two Delphi consultations. The definitions of consensus included a combination with an average score of ≥4, the percentage of experts rating the scores at >4 points, and the coefficient of variation of the scores.

Results: The expert panel comprised 18 pharmacists, 3 anesthesiologists, 6 oncologists, and 9 nurses. As a result of a comprehensive review, 33 items were initially formed. Among them, the consensus was reached for 27 items after the first Delphi round. The other six items and a total of five items for supplementation entered the second round, among which consensus was reached for eight items and three items were excluded. Expert consensus was achieved on 35 items after two rounds of consultation, which involved the collection of patient basic information, comprehensive pain assessment, breakthrough or neuropathic pain assessment, analgesic treatment evaluation, out-of-hospital follow-up, medical records, and evidence-based documents for reference.

Conclusion: The final list of 35 items could be used to develop the practice of pharmaceutical care for cancer pain management in outpatient clinics in China. The practice may aid in the standardization of pharmaceutical care for pain, relieve pain to the greatest extent possible, and enhance the level of pain management in China.