bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative Study of the Molecular Characterization, Evolution, and Structure Modeling of Digestive Lipase Genes Reveals the Different Evolutionary Selection Between Mammals and Fishes
Authors: Tang Shu-Lin , Liang Xu-Fang , He Shan , Li Ling , Alam Muhammad Shoaib , Wu Jiaqi
Published: August 2022

Vertebrates need suitable lipases to digest lipids for the requirement of energy and essential nutrients; however, the main digestive lipase genes of fishes have certain controversies. In this study, two types of digestive lipase genes (pancreatic lipase (pl) and bile salt-activated lipase (bsal)) were identified in mammals and fishes. The neighborhood genes and key active sites of the two lipase genes were conserved in mammals and fishes. Three copies of PL genes were found in mammals, but only one copy of the pl gene was found in most of the fish species, and the pl gene was even completely absent in some fish species (e.g., zebrafish, medaka, and common carp). Additionally, the hydrophobic amino acid residues (Ile and Leu) which are important to pancreatic lipase activity were also absent in most of the fish species. The PL was the main digestive lipase gene in mammals, but the pl gene seemed not to be the main digestive lipase gene in fish due to the absence of the pl gene sequence and the important amino acid residues. In contrast, the bsal gene existed in all fish species, even two to five copies of bsal genes were found in most of the fishes, but only one copy of the BSAL gene was found in mammals. The amino acid residues of bile salt-binding sites and the three-dimensional (3D) structure modeling of Bsal proteins were conserved in most of the fish species, so bsal might be the main digestive lipase gene in fish. The phylogenetic analysis also indicated that pl or bsal showed an independent evolution between mammals and fishes. Therefore, we inferred that the evolutionary selection of the main digestive lipase genes diverged into two types between mammals and fishes. These findings will provide valuable evidence for the study of lipid digestion in fish.
A Joint Model Considering Measurement Errors for Optimally Identifying Tumor Mutation Burden Threshold
Authors: Wang Yixuan , Lai Xin , Wang Jiayin , Xu Ying , Zhang Xuanping , Zhu Xiaoyan , Liu Yuqian , Shao Yang , Zhang Li , Fang Wenfeng
Published: August 2022

Tumor mutation burden (TMB) is a recognized stratification biomarker for immunotherapy. Nevertheless, the general TMB-high threshold is unstandardized due to severe clinical controversies, with the underlying cause being inconsistency between multiple assessment criteria and imprecision of the TMB value. The existing methods for determining TMB thresholds all consider only a single dimension of clinical benefit and ignore the interference of the TMB error. Our research aims to determine the TMB threshold optimally based on multifaceted clinical efficacies accounting for measurement errors. We report a multi-endpoint joint model as a generalized method for inferring the TMB thresholds, facilitating consistent statistical inference using an iterative numerical estimation procedure considering mis-specified covariates. The model optimizes the division by combining objective response rate and time-to-event outcomes, which may be interrelated due to some shared traits. We augment previous works by enabling subject-specific random effects to govern the communication among distinct endpoints. Our simulations show that the proposed model has advantages over the standard model in terms of precision and stability in parameter estimation and threshold determination. To validate the feasibility of the proposed thresholds, we pool a cohort of 73 patients with non-small-cell lung cancer and 64 patients with nasopharyngeal carcinoma who underwent anti-PD-(L)1 treatment, as well as validation cohorts of 943 patients. Analyses revealed that our approach could grant clinicians a holistic efficacy assessment, culminating in a robust determination of the TMB screening threshold for superior patients. Our methodology has the potential to yield innovative insights into therapeutic selection and support precision immuno-oncology.
Effects of diet and temperature on the fatty acid composition of the gammarid Gammarus locusta fed alternative terrestrial feeds
Authors: Ribes-Navarro Alberto , Alberts-Hubatsch Hilke , Monroig Óscar , Hontoria Francisco , Navarro Juan C.
Published: August 2022

The fast and remarkable growth of global aquaculture in recent years has created new challenges, such as guaranteeing a sustainable supply of raw materials used for aquafeed formulation. Gammarids are low-trophic crustaceans with an increasing interest in aquaculture due to their high nutritional profiles and their capacity to grow under high-density conditions. Moreover, gammarids have the ability to thrive on a wide range of sidestreams while accumulating relatively high levels of long-chain (≥C20) polyunsaturated fatty acids (LC-PUFA). In the present study, juveniles of the marine gammarid Gammarus locusta were cultured at four different temperatures (5°C, 10°C, 15°C, and 20°C) for 21 days and fed three diets, including the seaweed Fucus sp. as control, and carrot leaves and coconut flesh representing two agri-food industry sidestreams. Our results indicate that both the survival and biomass of G. locusta were highly affected by diet, with coconut showing the lowest growth performance. The temperature had no effect on biomass, although high temperature (20°C) resulted in a decrease in survival. The effects of temperature on the gammarid fatty acids were not evident, with diet being the main modulator of the profiles. Furthermore, the results also reveal that the Fucus sp. diet was associated with relatively high percentages of n-3 and n-6 LC-PUFA. Interestingly, essential LC-PUFA such as eicosapentaenoic (20:5n-3, EPA) and docosahexaenoic (22:6n-3, DHA) acids were detected in gammarids fed on either Fucus sp. or any of the sidestreams irrespectively of their presence in the diets. These results suggest an ability of G. locusta for LC-PUFA biosynthesis (trophic upgrading) and/or retention, making this species a promising candidate for the production of high-value ingredients for aquafeeds.
Sorting strategy to retune the disordered periodic structures regarding vibration reduction in band gaps
Authors: Li Anlue , Wu Yaguang , Fan Yu , Li Lin
Published: August 2022

Periodic structures exhibit frequency band gaps, in which the propagation of certain waves is attenuated. A periodic structure can be designed such that its band gaps cover the excitation frequencies and its vibration can be reduced. However, perfectly periodic structures do not exist in reality due to inevitable deviations in the material and geometric properties. The vibration reduction performance can be significantly altered by the disorder, as reported by various authors. Therefore, it is favorable to find approaches that can retune disordered structures to the best possible state. In this way, robust vibration reduction performance can be achieved. In this study, a sorting strategy is proposed to rearrange the disordered unit cells. The aim is to reduce the performance change of vibration reduction. Specifically, a diatomic lumped-mass model has been used, where one mass coefficient in each unit cell is subject to random error. The forced response is computed, and the frequency-averaged spatially maximum amplitude is used as the indicator to quantify the influence of the disorder. Then, we reveal the importance of the deviation at different unit cells by a global sensitivity analysis. A variance-based approach termed Sobol’s sensitivity analysis is used. The results show that the deviation in the unit cell nearest to the excitation source is of the greatest importance. A theoretical interpretation from the perspective of wave propagation is given. Eventually, a simple sorting strategy is proposed, and the rule is to ensure that the unit cell in the first position has the smallest deviation. This strategy can significantly improve the similarity of the dynamic characteristics between the nominal and disordered structures. Overall, the conducted work provides a reference to the manufacture and assembly of periodic structures and a further understanding of the vibration reduction in band gaps.
The commercialization of biospecimens from Indigenous Peoples: A scoping review of benefit-sharing
Authors: Tone-Pah-Hote Tarlynn , Redvers Nicole
Published: August 2022

Background

There is ongoing and increasing interest in the commercialization of biospecimen-derived products from Indigenous Peoples. Discourse on benefit-sharing specifically in the context of the commercialization of Indigenous Peoples biospecimens are currently lacking. A better understanding of the potential ethical imperatives is in need of exploration on this emerging topic. This review sought to elucidate through categorization the current discourse in the peer-reviewed literature on the commercialization of Indigenous Peoples' biospecimens from a benefit-sharing perspective.

Methods

A scoping review methodology was utilized to perform a search of PubMed, CINAHL, Embase and Google Scholar. A two-stage screening process was used to assess the relevance of any included articles with subsequent manual open coding of articles. Content analysis was applied to identify the main categories and sub-categories within the article data.

Results

Thirty-three articles met the inclusion criteria for analysis. Four overarching categories from the included articles were identified regarding the most common discourse on the commercialization of Indigenous Peoples' biospecimens from a benefit-sharing perspective, including: exploitation through biocolonialism, sovereignty and Indigenous rights, ethical considerations for benefit-sharing, and guidelines and standards concerns.

Conclusion

This scoping review highlighted the crucial need to keep Indigenous communities at the center of research projects, ensuring any benefits, advancement, and potential commercial profits are returned to communities through clear and ethical agreements. We encourage all research institutions and institutional ethical review bodies to better clarify the collective needs and interests of Indigenous communities while centering their sovereignty and rights within the research process as it pertains to potential biospecimen product commercialization.
Encapsulation of Salmonella phage SL01 in alginate/carrageenan microcapsules as a delivery system and its application in vitro
Authors: Zhou Yuqiao , Xu Dingting , Yu Haijie , Han Jianzhong , Liu Weilin , Qu Daofeng
Published: August 2022

Phages can be used successfully to treat pathogenic bacteria including zoonotic pathogens that colonize the intestines of animals and humans. However, low pH and digestive enzyme activity under harsh gastric conditions affect phage viability, thereby reducing their effectiveness. In this study, alginate (ALG)/κ-carrageenan (CG) microcapsules were developed to encapsulate and release phage under simulated gastrointestinal conditions. The effects of ALG and CG concentrations on the encapsulation and loading efficiency of microcapsules, as well as the release behavior and antibacterial effects of microcapsules in simulating human intestinal pH and temperature, were investigated. Based on various indicators, when the concentration of ALG and CG were 2.0 and 0.3%, respectively, the obtained microcapsules have high encapsulation efficiency, strong protection, and high release efficiency in simulated intestinal fluid. This effect is attributed to the formation of a more tightly packed biopolymer network within the composite microcapsules based on the measurements of their microstructure properties. Bead-encapsulation is a promising, reliable, and cost-effective method for the functional delivery of phage targeting intestinal bacteria.
The impact of PrsA over-expression on the Bacillus subtilis transcriptome during fed-batch fermentation of alpha-amylase production
Authors: Geissler Adrian S. , Poulsen Line D. , Doncheva Nadezhda T. , Anthon Christian , Seemann Stefan E. , González-Tortuero Enrique , Breüner Anne , Jensen Lars J. , Hjort Carsten , Vinther Jeppe , Gorodkin Jan
Published: August 2022

The production of the alpha-amylase (AMY) enzyme in Bacillus subtilis at a high rate leads to the accumulation of unfolded AMY, which causes secretion stress. The over-expression of the PrsA chaperone aids enzyme folding and reduces stress. To identify affected pathways and potential mechanisms involved in the reduced growth, we analyzed the transcriptomic differences during fed-batch fermentation between a PrsA over-expressing strain and control in a time-series RNA-seq experiment. We observe transcription in 542 unannotated regions, of which 234 had significant changes in expression levels between the samples. Moreover, 1,791 protein-coding sequences, 80 non-coding genes, and 20 riboswitches overlapping UTR regions of coding genes had significant changes in expression. We identified putatively regulated biological processes via gene-set over-representation analysis of the differentially expressed genes; overall, the analysis suggests that the PrsA over-expression affects ATP biosynthesis activity, amino acid metabolism, and cell wall stability. The investigation of the protein interaction network points to a potential impact on cell motility signaling. We discuss the impact of these highlighted mechanisms for reducing secretion stress or detrimental aspects of PrsA over-expression during AMY production.
A strategic model of a host–microbe–microbe system reveals the importance of a joint host–microbe immune response to combat stress-induced gut dysbiosis
Authors: Scheuring István , Rasmussen Jacob A. , Bozzi Davide , Limborg Morten T.
Published: August 2022

Microbiomes provide key ecological functions to their host; however, most host-associated microbiomes are too complicated to allow a model of essential host–microbe–microbe interactions. The intestinal microbiota of salmonids may offer a solution since few dominating species often characterize it. Healthy fish coexist with a mutualistic Mycoplasma sp. species, while stress allows the spread of pathogenic strains, such as Aliivibrio sp. Even after a skin infection, the Mycoplasma does not recover; Aliivibrio sp. often remains the dominant species, or Mycoplasma–Aliivibrio coexistence was occasionally observed. We devised a model involving interactions among the host immune system, Mycoplasma sp. plus a toxin-producing pathogen. Our model embraces a complete microbiota community and is in harmony with experimental results that host–Mycoplasma mutualism prevents the spread of pathogens. Contrary, stress suppresses the host immune system allowing dominance of pathogens, and Mycoplasma does not recover after stress disappears.
Single-cell Raman spectroscopy identifies Escherichia coli persisters and reveals their enhanced metabolic activities
Authors: Wang Chuan , Chen Rongze , Xu Jian , Jin Lijian
Published: August 2022

Microbial persisters are the featured tiny sub-population of microorganisms that are highly tolerant to multiple antimicrobials. Currently, studies on persisters remain a considerable challenge owing to technical limitations. Here, we explored the application of single-cell Raman spectroscopy (SCRS) in the investigation of persisters. Escherichia coli (ATCC 25922) cells were treated with a lethal dosage of ampicillin (100 μg/mL, 32 × MIC, 4 h) for the formation of persisters. The biochemical characters of E. coli and its persisters were assessed by SCRS, and their metabolic activities were labeled and measured with D2O-based single-cell Raman spectroscopy (D2O-Ramanometry). Notable differences in the intensity of Raman bands related to major cellular components and metabolites were observed between E. coli and its ampicillin-treated persisters. Based on their distinct Raman spectra, E. coli and its persister cells were classified into different projective zones through the principal component analysis and t-distributed stochastic neighbor embedding. According to the D2O absorption rate, E. coli persisters exhibited higher metabolic activities than those of untreated E. coli. Importantly, after the termination of ampicillin exposure, these persister cells showed a temporal pattern of D2O intake that was distinct from non-persister cells. To our knowledge, this is the first report on identifying E. coli persisters and assessing their metabolic activities through the integrated SCRS and D2O-Ramanometry approach. These novel findings enhance our understanding of the phenotypes and functionalities of microbial persister cells. Further investigations could be extended to other pathogens by disclosing microbial pathogenicity mechanisms for developing novel therapeutic strategies and approaches.
MicroRNA-451a and Th1/Th2 ratio inform inflammation, septic organ injury, and mortality risk in sepsis patients
Authors: Geng Feng , Liu Wei , Yu Li
Published: August 2022

Aims

MicroRNA-451a (miR-451a) regulates Th1/Th2 cell differentiation, inflammation, and septic organ injury in several experiments. Therefore, the present study aimed to explore the inter-correlation of miR-451a with the Th1/Th2 ratio, and their association with inflammation, septic organ injury, and mortality risk in patients with sepsis.

Methods

Consecutively, 117 patients with sepsis and 50 healthy controls (HCs) were enrolled. Peripheral blood mononuclear cell samples were collected to detect miR-451a expression and the Th1/Th2 ratio in all subjects.

Results

MiR-451a (p < 0.001), Th1 cells (p = 0.014), and the Th1/Th2 ratio (p < 0.001) increased, while Th2 cells (p < 0.001) declined in patients with sepsis compared with HCs. It was of note that miR-451a was positively correlated with Th1 cells (p = 0.002) and the Th1/Th2 ratio (p = 0.001), while it was negatively related to Th2 cells (p = 0.005) in patients with sepsis. Meanwhile, miR-451a and the Th1/Th2 ratio correlated with most of the following indexes: TNF-α, IL-1β, IL-6, C-reactive protein, sequential organ failure assessment (SOFA) score, or Acute Physiology and Chronic Health Evaluation II (APACHE II) score (most p < 0.05). Moreover, miR-451a (p < 0.001) and the Th1/Th2 ratio (p = 0.001) increased in deaths compared to survivors of sepsis; further ROC curve showed both miR-451a and the Th1/Th2 ratio possessed a certain value to predict mortality of patients with sepsis. Additionally, the Th1/Th2 ratio [odds ratio (OR): 2.052, p = 0.005] was independently related to 28-day mortality risk from multivariate logistic regression.

Conclusion

MiR-451a correlates with the Th1/Th2 ratio, and they both relate to inflammation, septic organ injury, and mortality risk in patients with sepsis.
An in vitro study on the degradation of multispecies biofilm of periodontitis-related microorganisms by bovine trypsin
Authors: Zhou Jing , Meng Xinhui , Han Qunchao , Huang Yinxue , Huo Lijun , Lei Yayan
Published: August 2022

To investigate the degradation effect of bovine trypsin on multispecies biofilm of periodontitis-related bacteria and to provide an experimental reference for exploring new methods for controlling biofilms of periodontitis-related microorganisms, the multispecies biofilm of periodontitis-related microorganisms was established. Standard strains of Porphyromonas gingivalis, Fusobacterium nucleatum subsp. polymorpha, Actinomyces viscosus, and Aggregatibacter actinomycetemcomitans were co-cultured to form the biofilm. The experimental groups were treated with bovine trypsin, distilled water was applied as the blank control group, and phosphate saline buffer (pH = 7.4) as the negative control group. Morphological observation and quantitative analysis of extracellular polymeric substances (EPS), live bacteria, and dead bacteria were conducted using a laser confocal microscope. The morphological changes of EPS and bacteria were also observed using a scanning electron microscope. The results of morphological observations of modeling were as follows. EPS aggregated as agglomerates, and bacteria flora were wrapped by them, showing a three-dimensional network structure, and channel-like structures were inside the biofilm. Live bacteria were distributed on the surface of the EPS or embedded in them, dead bacteria aggregated between live flora and the bottom layer of biofilms. After being treated with bovine trypsin, the three-dimensional network structure and the channel-like structure disappeared, and the EPS and live and dead bacteria decreased. Quantitative analysis results are as follows. When biofilm was treated for 30 s, 1 min, and 3 min, the minimum effective concentrations of bovine trypsin to reduce EPS were 2 mg/ml (P < 0.05), 0.5 mg/ml (P < 0.05), and 0.25 mg/ml (P < 0.05), respectively. The minimum effective concentrations of bovine trypsin to reduce the live or dead bacteria were 2 mg/ml (P < 0.05), 0.5 mg/ml (P < 0.05), and 0.5 mg/ml (P < 0.05), respectively. There was no significant difference in the ratio of live/dead bacteria after the biofilm was treated for 30 s with bovine trypsin at the concentration of 0.25, 0.5, 1, and 2 mg/ml (P > 0.05), and the minimum effective concentration to reduce the ratio of live bacteria/dead bacteria was 0.25 mg/ml (P < 0.05) after treatment for 1 min and 3 min. Therefore, bovine trypsin can destroy biofilm structure, disperse biofilm and bacteria flora, and reduce the EPS and bacterial biomass, which are positively correlated with the application time and concentration.
Overfertilization reduces tomato yield under long-term continuous cropping system via regulation of soil microbial community composition
Authors: Song Qiaobo , Fu Hongdan , Shi Qingwen , Shan Xuan , Wang Zhen , Sun Zhouping , Li Tianlai
Published: August 2022

Long-term monoculture cropping and overfertilization degrade soil fertility, which reduces crop growth and promotes the development of soil-borne diseases. However, it remains unclear what the temporal effects of the above factors are on the tomato yield and microbial community structure. Thus, a greenhouse experiment with different amounts of fertilization [2,196 kg ha−1 (control) and 6,588 kg ha−1 (overfertilization) of inorganic fertilizers (NPK)] was carried out with the soils used previously for 1, 2, and 12 years under monoculture of tomato. A 12-year overfertilization decreased soil pH by 1.37 units. Soil electrical conductivity (EC) and concentrations of soil nutrients are enhanced with the increase in tomato cropping duration. Higher content of soil nutrients was found under overfertilization compared to the control in the 12-year soil. Overfertilization decreased the activity of β-1,4-glucosidase (BG) and oxidase compared to the control in the 12-year soil. Bacterial diversity and richness decreased by 6 and 31%, respectively, under overfertilization in 12-year soil compared to the control. The relative abundance of Gemmatimonas and Gp6 in 12-year soil under overfertilization was 17 and 78%, respectively, lower than in control soil. Soil pH and total carbon (TC) were the major factors explaining changes in microbial composition. A 38% decrease in yield was caused by overfertilization in 12-year soil compared to the control. Microbial community composition was the main factor that moderated tomato yield. In addition, fertilization rather than cropping duration had a greater impact on tomato yield. Therefore, our results suggest that long-term overfertilization influenced soil pH, soil TC, and soil microbial community composition to regulate tomato yield.
Specialized acyl carrier protein used by serine palmitoyltransferase to synthesize sphingolipids in Rhodobacteria
Authors: Padilla-Gómez Jonathan , Olea-Ozuna Roberto Jhonatan , Contreras-Martínez Sandra , Morales-Tarré Orlando , García-Soriano Daniela A. , Sahonero-Canavesi Diana X. , Poggio Sebastian , Encarnación-Guevara Sergio , López-Lara Isabel M. , Geiger Otto
Published: August 2022

Serine palmitoyltransferase (SPT) catalyzes the first and committed step in sphingolipid biosynthesis condensating L-serine and acyl-CoA to form 3-oxo-sphinganine. Whenever the structural gene for SPT is present in genomes of Rhodobacteria (α-, β-, and γ-Proteobacteria), it co-occurs with genes coding for a putative acyl carrier protein (ACP) and a putative acyl-CoA synthetase (ACS). In the α-proteobacterium Caulobacter crescentus, CC_1162 encodes an SPT, whereas CC_1163 and CC_1165 encode the putative ACP and ACS, respectively, and all three genes are known to be required for the formation of the sphingolipid intermediate 3-oxo-sphinganine. Here we show that the putative ACP possesses a 4'-phosphopantetheine prosthetic group, is selectively acylated by the putative ACS and therefore is a specialized ACP (AcpR) required for sphingolipid biosynthesis in Rhodobacteria. The putative ACS is unable to acylate coenzyme A or housekeeping ACPs, but acylates specifically AcpR. Therefore, it is a specialized acyl-ACP synthetase (AasR). SPTs from C. crescentus, Escherichia coli B, or Sphingomonas wittichii use preferentially acyl-AcpR as thioester substrate for 3-oxo-sphinganine synthesis. Whereas acyl-AcpR from C. crescentus is a good substrate for SPTs from distinct Rhodobacteria, acylation of a specific AcpR is achieved by the cognate AasR from the same bacterium. Rhodobacteria might use this more complex way of 3-oxo-sphinganine formation in order to direct free fatty acids toward sphingolipid biosynthesis.
Alphaherpesvirus glycoprotein E: A review of its interactions with other proteins of the virus and its application in vaccinology
Authors: Ning Yaru , Huang Yalin , Wang Mingshu , Cheng Anchun , Yang Qiao , Wu Ying , Tian Bin , Ou Xumin , Huang Juan , Mao Sai , Sun Di , Zhao Xinxin , Zhang Shaqiu , Gao Qun , Chen Shun , Liu Mafeng , Zhu Dekang , Jia Renyong
Published: August 2022

The viral envelope glycoprotein E (gE) is required for cell-to-cell transmission, anterograde and retrograde neurotransmission, and immune evasion of alphaherpesviruses. gE can also interact with other proteins of the virus and perform various functions in the virus life cycle. In addition, the gE gene is often the target gene for the construction of gene-deleted attenuated marker vaccines. In recent years, new progress has been made in the research and vaccine application of gE with other proteins of the virus. This article reviews the structure of gE, the relationship between gE and other proteins of the virus, and the application of gE in vaccinology, which provides useful information for further research on gE.
Ribosome profiling enhances understanding of mycobacterial translation
Authors: Sawyer Elizabeth B. , Cortes Teresa
Published: August 2022

A recent addition to the -omics toolkit, ribosome profiling, enables researchers to gain insight into the process and regulation of translation by mapping fragments of mRNA protected from nuclease digestion by ribosome binding. In this review, we discuss how ribosome profiling applied to mycobacteria has led to discoveries about translational regulation. Using case studies, we show that the traditional view of “canonical” translation mechanisms needs expanding to encompass features of mycobacterial translation that are more widespread than previously recognized. We also discuss the limitations of the method and potential future developments that could yield further insight into the fundamental biology of this important human pathogen.
Embodiment of a virtual prosthesis through training using an EMG-based human-machine interface: Case series
Authors: Rodrigues Karina Aparecida , Moreira João Vitor da Silva , Pinheiro Daniel José Lins Leal , Dantas Rodrigo Lantyer Marques , Santos Thaís Cardoso , Nepomuceno João Luiz Vieira , Nogueira Maria Angélica Ratier Jajah , Cavalheiro Esper Abrão , Faber Jean
Published: August 2022

Therapeutic strategies capable of inducing and enhancing prosthesis embodiment are a key point for better adaptation to and acceptance of prosthetic limbs. In this study, we developed a training protocol using an EMG-based human-machine interface (HMI) that was applied in the preprosthetic rehabilitation phase of people with amputation. This is a case series with the objective of evaluating the induction and enhancement of the embodiment of a virtual prosthesis. Six men and a woman with unilateral transfemoral traumatic amputation without previous use of prostheses participated in the study. Participants performed a training protocol with the EMG-based HMI, composed of six sessions held twice a week, each lasting 30 mins. This system consisted of myoelectric control of the movements of a virtual prosthesis immersed in a 3D virtual environment. Additionally, vibrotactile stimuli were provided on the participant’s back corresponding to the movements performed. Embodiment was investigated from the following set of measurements: skin conductance response (affective measurement), crossmodal congruency effect (spatial perception measurement), ability to control the virtual prosthesis (motor measurement), and reports before and after the training. The increase in the skin conductance response in conditions where the virtual prosthesis was threatened, recalibration of the peripersonal space perception identified by the crossmodal congruency effect, ability to control the virtual prosthesis, and participant reports consistently showed the induction and enhancement of virtual prosthesis embodiment. Therefore, this protocol using EMG-based HMI was shown to be a viable option to achieve and enhance the embodiment of a virtual prosthetic limb.
Intramuscular coherence during challenging walking in incomplete spinal cord injury: Reduced high-frequency coherence reflects impaired supra-spinal control
Authors: Zipser-Mohammadzada Freschta , Conway Bernard A. , Halliday David M. , Zipser Carl Moritz , Easthope Chris A. , Curt Armin , Schubert Martin
Published: August 2022

Individuals regaining reliable day-to-day walking function after incomplete spinal cord injury (iSCI) report persisting unsteadiness when confronted with walking challenges. However, quantifiable measures of walking capacity lack the sensitivity to reveal underlying impairments of supra-spinal locomotor control. This study investigates the relationship between intramuscular coherence and corticospinal dynamic balance control during a visually guided Target walking treadmill task. In thirteen individuals with iSCI and 24 controls, intramuscular coherence and cumulant densities were estimated from pairs of Tibialis anterior surface EMG recordings during normal treadmill walking and a Target walking task. The approximate center of mass was calculated from pelvis markers. Spearman rank correlations were performed to evaluate the relationship between intramuscular coherence, clinical parameters, and center of mass parameters. In controls, we found that the Target walking task results in increased high-frequency (21–44 Hz) intramuscular coherence, which negatively related to changes in the center of mass movement, whereas this modulation was largely reduced in individuals with iSCI. The impaired modulation of high-frequency intramuscular coherence during the Target walking task correlated with neurophysiological and functional readouts, such as motor-evoked potential amplitude and outdoor mobility score, as well as center of mass trajectory length. The Target walking effect, the difference between Target and Normal walking intramuscular coherence, was significantly higher in controls than in individuals with iSCI [F(1.0,35.0) = 13.042, p < 0.001]. Intramuscular coherence obtained during challenging walking in individuals with iSCI may provide information on corticospinal gait control. The relationships between biomechanics, clinical scores, and neurophysiology suggest that intramuscular coherence assessed during challenging tasks may be meaningful for understanding impaired supra-spinal control in individuals with iSCI.
Resting and TMS-EEG markers of treatment response in major depressive disorder: A systematic review
Authors: Strafella Rebecca , Chen Robert , Rajji Tarek K. , Blumberger Daniel M. , Voineskos Daphne
Published: August 2022

Electroencephalography (EEG) is a non-invasive method to identify markers of treatment response in major depressive disorder (MDD). In this review, existing literature was assessed to determine how EEG markers change with different modalities of MDD treatments, and to synthesize the breadth of EEG markers used in conjunction with MDD treatments. PubMed and EMBASE were searched from 2000 to 2021 for studies reporting resting EEG (rEEG) and transcranial magnetic stimulation combined with EEG (TMS-EEG) measures in patients undergoing MDD treatments. The search yielded 966 articles, 204 underwent full-text screening, and 51 studies were included for a narrative synthesis of findings along with confidence in the evidence. In rEEG studies, non-linear quantitative algorithms such as theta cordance and theta current density show higher predictive value than traditional linear metrics. Although less abundant, TMS-EEG measures show promise for predictive markers of brain stimulation treatment response. Future focus on TMS-EEG measures may prove fruitful, given its ability to target cortical regions of interest related to MDD.
Overdose, opioid treatment admissions and prescription opioid pain reliever relationships: United States, 2010–2019
Authors: Aubry Larry , Carr B. Thomas
Published: August 2022

Background

“As part of the U.S. government's urgent response to the epidemic of overdose deaths (1)” the United States Centers for Disease Control and Prevention (CDC) issued the “CDC Guideline for Prescribing Opioids for Chronic Pain-United States, 2016 (2)” (guideline) followed by the “CDC Clinical Practice Guideline for Prescribing Opioids–United States, 2022 (3) (guideline update). ” The guideline and guideline update cite a direct correlation between prescription opioids sales (POS) and opioid treatment admissions (OTA) and prescription opioid deaths (POD), which was based on data from 1999 to 2010. This paper updates those relationships and includes the correlations between prescription opioid sales (POS) and any opioid deaths (AOD) and total overdose deaths (TOD) from 2010 to 2019.

Methods

Linear regression models were fit to each response separately. Opioid sales (measured as MME (morphine milligram equivalent) per capita) was the independent variable. Total overdose deaths (TOD), any opioid overdose deaths (AOD), prescription opioid overdose deaths (POD) and opioid treatment admissions (OTA) were the dependent, response variables. The models were assessed using three criteria: the statistical significance of the model (Overall P-Value), the quality of the fit (R2), and the sign of the slope coefficient (positive or negative).

Results

The analyses revealed that the direct correlations (i.e., significant, positive slopes) reported by the CDC based on data from 1999 to 2010 no longer exist. Based on data from 2010 to 2019, the relationships either have reversed (i.e., significant, negative slopes) or are non-existent (i.e., no significant model).

Conclusions

The guideline, guideline update, CDC's public, medical profession, and intergovernmental communications should be corrected/updated to state no direct correlation has existed between POS to OTA, POD, AOD, and TOD since 2010. Individualized patient care and public health policy should be amended accordingly.
Functional status of pediatric patients after extracorporeal membrane oxygenation: A five-year single-center study
Authors: Yuhang Yang , Ni Yang , Tiening Zhang , Lijie Wang , Wei Xu , Chunfeng Liu
Published: August 2022

Objective

Extracorporeal membrane oxygenation (ECMO) is a widely used treatment for circulatory and pulmonary support in newborns and young children. Over the past decade, the number of children successfully treated with ECMO has gradually increased. However, despite an increasing number of survivors, new morbidity and long-term health issues are becoming more prevalent. A better understanding of the pediatric ECMO prognosis contributes to improved treatment and care programs and minimizes the risk of sequelae and dysfunctions. We aimed to determine the incidence of new morbidity, prognoses, and follow-up data of survivors treated with ECMO in pediatric intensive care units (PICU) using the Functional Status Scale (FSS).

Methods

We retrospectively collected and analyzed clinical data of patients in the PICU who received ECMO from January 2016 to January 2020. Clinical and functional outcomes were assessed at admission and discharge using the FSS. Twenty-seven patients aged between 1 month and 14 years who received ECMO in the PICU were included. Fifty-two percent were male, and the median age was 36 months (interquartile range, 21–114 months). The patients were admitted for fulminant myocarditis (n = 13), acute respiratory distress syndrome (ARDS) (n = 11), and septic shock (n = 3).

Results

This study reviewed a single-center experience using the FSS for ECMO treatment in a PICU. The patients' original conditions included fulminant myocarditis, ARDS, and septic shock. Of the 27 patients who received ECMO, 9 (33%) died, 12 (67%) showed improved condition, and 6 (33%) discontinued treatment and left the hospital. Furthermore, the following adverse events were observed in the survivors who were discharged: nine (50%) cases of lower extremity deep vein thrombosis, seven (39%) jugular vein thrombosis, six (33%) acute kidney injury, five (27%) intracranial hemorrhage and cerebral infarction, and one each of (6% each) pulmonary embolism and peripheral nerve injury. Of the 12 patients who survived through 1 year after discharge, five (42%) recovered completely, whereas seven (58%) showed mild to moderate communication and motor dysfunction. The short-term survival rate and 1-year survival rate of ECMO patients were 67% (18/27) and 44% (12/27), respectively. Additionally, approximately one-third of the patients developed a new morbidity after ECMO treatment (6/18).

Conclusions

High mortality and new morbidity were common in patients who received ECMO treatment. New morbidity increased the risk of death and exacerbated the functional state. Follow-up and rehabilitation after discharge are essential to achieve positive outcomes.
Case report: Bilateral pleural effusion secondary to late migration of a tunneled central venous catheter in a patient affected by high risk neuroblastoma
Authors: D'Angelo Tommaso Domenico , Persano Giorgio , Crocoli Alessandro , Martucci Cristina , Parapatt George Koshy , Natali Gian Luigi , Inserra Alessandro
Published: August 2022

The insertion of long-term central venous catheters is a standard of care for children affected by malignancies, although it can be associated with life-threatening complications. The present paper reports an unusual mechanical complication related to the use of a long term tunneled central venous catheter in a pediatric oncologic patient. An 18 months old child, diagnosed with stage M high-risk retroperitoneal neuroblastoma, underwent ultrasound-guided placement of a 6 Fr bilumen long-term tunneled central venous catheter in the right internal jugular vein prior to the beginning of induction chemotherapy. The correct position of the distal tip of the catheter was confirmed by fluoroscopy. After 4 months of regular use of the device, the patient experienced neck swelling during high-dose chemotherapy infusion. A chest x-ray showed a dislocated catheter and bilateral pleural effusion. CT scan demonstrated the tip of the catheter rupturing the medial wall of the right jugular vein and entering the mediastinum; furthermore, pneumomediastinum, subcutaneous neck emphysema and bilateral pleural effusion were noticed and a thrombus was evident in the right jugular vein at the insertion in the brachiocephalic vein. The patient was then transferred to the Intensive Care Unit and bilateral thoracostomy tubes were placed urgently (500 mL of clear fluid were evacuated from pleural spaces). The dislocated catheter was removed electively on the following day under fluoroscopy. Despite ultrasound-guided placement and long-term uneventful use of the catheter, life-threatening central venous catheter-related mechanical complications can occur; the current case report emphasizes the importance of careful monitoring of patients with central venous catheters in order to quickly diagnose and treat potentially lethal complications.
Nutritional status at age 1 year in patients born with esophageal atresia: A population-based, prospective cohort study
Authors: Depoortere Suzanne , Lapillonne Alexandre , Sfeir Rony , Bonnard Arnaud , Gelas Thomas , Panait Nicoleta , Rabattu Pierre-Yves , Guignot Audrey , Lamireau Thierry , Irtan Sabine , Habonimana Edouard , Breton Anne , Fouquet Virginie , Allal Hossein , Elbaz Frédéric , Talon Isabelle , Ranke Aline , Abely Michel , Michel Jean-Luc , Lirussi Borgnon Joséphine , Buisson Philippe , Schmitt Françoise , Lardy Hubert , Petit Thierry , Chaussy Yann , Borderon Corinne , Levard Guillaume , Cremillieux Clara , Tolg Cécilia , Breaud Jean , Jaby Olivier , Grossos Céline , De Vries Philine , Arnould Myriam , Pelatan Cécile , Geiss Stephan , Laplace Christophe , Kyheng Maéva , Nicolas Audrey , Aumar Madeleine , Gottrand Frédéric
Published: August 2022

Objective

Despite recent progress in caring for patients born with esophageal atresia (EA), undernutrition and stunting remain common. Our study objective was to assess nutritional status in the first year after birth with EA and to identify factors associated with growth failure.

Study design

We conducted a population-based study of all infants born in France with EA between 2010 and 2016. Through the national EA register, we collected prenatal to 1 year follow-up data. We used body mass index and length-for-age ratio Z scores to define patients who were undernourished and stunted, respectively. Factors with P < 0.20 in univariate analyses were retained in a logistic regression model.

Results

Among 1,154 patients born with EA, body mass index and length-for-age ratio Z scores at 1 year were available for about 61%. Among these, 15.2% were undernourished and 19% were stunted at the age of 1 year. There was no significant catch-up between ages 6 months and 1 year. Patients born preterm (41%), small for gestational age (17%), or with associated abnormalities (55%) were at higher risk of undernutrition and stunting at age 1 year (P < 0.05). Neither EA type nor surgical treatment was associated with growth failure.

Conclusion

Undernutrition and stunting are common during the first year after birth in patients born with EA. These outcomes are significantly influenced by early factors, regardless of EA type or surgical management. Identifying high-risk patient groups with EA (i.e., those born preterm, small for gestational age, and/or with associated abnormalities) may guide early nutritional support strategies.
What a Difference an Amino Acid Makes: An All-Atom Simulation Study of Nonameric Peptides in Inhibitory HLA-E/NKG2A/CD94 Immune Complexes
Authors: Prašnikar Eva , Perdih Andrej , Borišek Jure
Published: August 2022

MHC class I antigen E (HLA-E), a ligand for the inhibitory NKG2A/CD94 receptor of the immune system, is responsible for evading the immune surveillance in several settings, including senescent cell accumulation and tumor persistence. The formation of this ligand-receptor interaction promotes the inhibition of the cytolytic action of immune system natural killer (NK) cells and CD8+T-cells expressing this receptor. The final outcome of the HLA-E/NKG2A/CD94 interaction on target cells is also highly dependent on the identity of the nonameric peptide incorporated into the HLA-E ligand. To better understand the role played by a nonameric peptide in these immune complexes, we performed a series of multi-microsecond all-atom molecular dynamics simulations. We generated natural and alternative variants of the nonameric peptide bound to the HLA-E ligand alone or in the HLA-E/NKG2A/CD94 complexes. A systematic study of molecular recognition between HLA-E and peptides led to the development of new variants that differ at the strategic 6th position (P6) of the peptide and have favorablein silicoproperties comparable to those of natural binding peptides. Further examination of a selected subset of peptides in full complexes revealed a new variant that, according to our previously derived atomistic model, can interfere with the signal transductionviaHLA-E/NKG2A/CD94 and thus prevent the target cell from evading immune clearance by NK and CD8+T-cells. These simulations provide an atomistic picture of how a small change in amino acid sequence can lead to a profound effect on binding and molecular recognition. Furthermore, our study also provides new data on the peptide interaction motifs as well as the energetic and conformational properties of the binding interface, laying the structure-based foundation for future development of potential therapeutic peptides, peptidomimetics, or even small molecules that would bind to the HLA-E ligand and abrogate NKG2A/CD94 recognition. Such external intervention would be useful in the emerging field of targeting senescent cells in a variety of age-related diseases, as well as in novel cancer immunotherapies.
Disruption of cancer cell functions by task-specific drug perturbations
Authors: Ahmed Mahmoud , Kim Deok Ryong
Published: August 2022

Cancer expands clonally, capitalizing on the variations between growing cells. Cancer cells specialize in one or more functions to gain an advantage. This study examined the prediction that cells would be vulnerable to drugs that perturb their specific tasks. We analyzed the correlation between gene expression and the response to drug perturbations in different cancer cells. Next, we assigned every cancer cell to an archetype based on gene expression. Finally, we calculated the enrichment of the cancer hallmark gene sets in each cell, archetypes, and response to drug treatment. We found that the extremes of gene expression were susceptible to change in response to perturbations. This correlation predicted the growth rate inhibition of breast cancer cells. Cancer hallmarks were enriched differently in the archetypes, and this enrichment predicted the cell’s response to perturbations. We present evidence that specialized cancer cells are sensitive to compounds that perturb their tasks.