bluuebunny/crossref_metadata_2025 huggingface dataset:
G6PD Polymorphisms and Hemolysis After Antimalarial Treatment With Low Single-Dose Primaquine: A Pooled Analysis of Six African Clinical Trials
Authors: Sepúlveda Nuno , Grignard Lynn , Curry Jonathan , Mahey Laleta , Bastiaens Guido J. H. , Tiono Alfred B. , Okebe Joseph , Coulibaly Sam A. , Gonçalves Bronner P. , Affara Muna , Ouédraogo Alphonse , Bougouma Edith C. , Sanou Guillaume S. , Nébié Issa , Lanke Kjerstin , Sirima Sodiomon B. , Dicko Alassane , d’Alessandro Umberto , Clark Taane G. , Campino Susana , Chen Ingrid , Eziefula Alice C. , Gosling Roly , Bousema Teun , Drakeley Chris
Published: April 2021

Primaquine (PQ) is an antimalarial drug with the potential to reduce malaria transmission due to its capacity to clear maturePlasmodium falciparumgametocytes in the human host. However, the large-scale roll-out of PQ has to be counterbalanced by the additional risk of drug-induced hemolysis in individuals suffering from Glucose-6-phospate dehydrogenase (G6PD) deficiency, a genetic condition determined by polymorphisms on the X-linkedG6PDgene. Most studies on G6PD deficiency and PQ-associated hemolysis focused on the G6PD A- variant, a combination of the two single nucleotide changes G202A (rs1050828) and A376G (rs1050829), although other polymorphisms may play a role. In this study, we tested the association of 20 G6PD single nucleotide polymorphisms (SNPs) with hemolysis measured seven days after low single dose of PQ given at the dose of 0.1 mg/kg to 0.75 mg/kg in 957 individuals from 6 previously published clinical trials investigating the safety and efficacy of this drug spanning five African countries. After adjusting for inter-study effects, age, gender, baseline hemoglobin level, PQ dose, and parasitemia at screening, our analysis showed putative association signals from the common G6PD mutation, A376G [−log10(p-value) = 2.44] and two less-known SNPs, rs2230037 [−log10(p-value] = 2.60), and rs28470352 [−log10(p-value) = 2.15]; A376G and rs2230037 were in very strong linkage disequilibrium with each other (R2= 0.978). However, when the effects of these SNPs were included in the same regression model, the subsequent associations were in the borderline of statistical significance. In conclusion, whilst a role for the A- variant is well established, we did not observe an important additional role for other G6PD polymorphisms in determining post-treatment hemolysis in individuals treated with low single-dose PQ.
PMDFI: Predicting miRNA–Disease Associations Based on High-Order Feature Interaction
Authors: Tang Mingyan , Liu Chenzhe , Liu Dayun , Liu Junyi , Liu Jiaqi , Deng Lei
Published: April 2021

MicroRNAs (miRNAs) are non-coding RNA molecules that make a significant contribution to diverse biological processes, and their mutations and dysregulations are closely related to the occurrence, development, and treatment of human diseases. Therefore, identification of potential miRNA–disease associations contributes to elucidating the pathogenesis of tumorigenesis and seeking the effective treatment method for diseases. Due to the expensive cost of traditional biological experiments of determining associations between miRNAs and diseases, increasing numbers of effective computational models are being used to compensate for this limitation. In this study, we propose a novel computational method, named PMDFI, which is an ensemble learning method to predict potential miRNA–disease associations based on high-order feature interactions. We initially use a stacked autoencoder to extract meaningful high-order features from the original similarity matrix, and then perform feature interactive learning, and finally utilize an integrated model composed of multiple random forests and logistic regression to make comprehensive predictions. The experimental results illustrate that PMDFI achieves excellent performance in predicting potential miRNA–disease associations, with the average area under the ROC curve scores of 0.9404 and 0.9415 in 5-fold and 10-fold cross-validation, respectively.
High Dose IFN-β Activates GAF to Enhance Expression of ISGF3 Target Genes in MLE12 Epithelial Cells
Authors: Kishimoto Kensei , Wilder Catera L. , Buchanan Justin , Nguyen Minh , Okeke Chidera , Hoffmann Alexander , Cheng Quen J.
Published: April 2021

Interferon β (IFN-β) signaling activates the transcription factor complex ISGF3 to induce gene expression programs critical for antiviral defense and host immune responses. It has also been observed that IFN-β activates a second transcription factor complex, γ-activated factor (GAF), but the significance of this coordinated activation is unclear. We report that in murine lung epithelial cells (MLE12) high doses of IFN-β indeed activate both ISGF3 and GAF, which bind to distinct genomic locations defined by their respective DNA sequence motifs. In contrast, low doses of IFN-β preferentially activate ISGF3 but not GAF. Surprisingly, in MLE12 cells GAF binding does not induce nearby gene expression even when strongly bound to the promoter. Yet expression of interferon stimulated genes is enhanced when GAF and ISGF3 are both active compared to ISGF3 alone. We propose that GAF may function as a dose-sensitive amplifier of ISG expression to enhance antiviral immunity and establish pro-inflammatory states.
PSMP Is Discriminative for Chronic Active Antibody-Mediated Rejection and Associate With Intimal Arteritis in Kidney Transplantation
Authors: Zhan Panpan , Li Haizheng , Han Mingzhe , Wang Zhen , Zhao Jie , Tu Jinpeng , Shi Xiaofeng , Fu Yingxin
Published: April 2021

Chronic active antibody-mediated rejection (CAAMR) is an intermediate process that occurs during the development of chronic antibody-mediated rejection (CAMR), which is a key problem associated with the long-term kidney grafts survival. This study investigated the role played by PC3-secreted microprotein (PSMP) in the progression of CAAMR and CAMR. We showed that CAAMR and CAMR patients’ allografts dysfunction with declined survival rate, which suggested that earlier diagnosis and treatment of CAAMR might be important to prevent irreversible chronic injury of CAMR progression. We found PSMP was an important factor in the development of chronic antibody-mediated rejection. The PSMP expression increased significantly in CAAMR biopsy samples but not in CAMR and control patients, which distinguished CAAMR patients from CAMR and non-rejection patients. Moreover, our results showed that infiltration of CD68+ macrophages in CAAMR increased, and the correlation between CD68+ macrophages and PSMP expression in CAAMR patients was significant. Additionally, our data also revealed that intimal arteritis (v-lesion) accompanied by increased macrophage infiltration might have contributed to more graft loss in CAAMR, and PSMP expression was significantly associated with the v-lesion score. These results indicated that PSMP played an important role in the recruitment of macrophages and promote intimal arteritis inducing allograft lost in CAAMR progression. In future study PSMP could be a potential histopathological diagnostic biomarker and treatment target for CAAMR in kidney transplantation.
Refining Fisheries Advice With Stock-Specific Ecosystem Information
Authors: Bentley Jacob W. , Lundy Mathieu G. , Howell Daniel , Beggs Steven E. , Bundy Alida , de Castro Francisco , Fox Clive J. , Heymans Johanna J. , Lynam Christopher P. , Pedreschi Debbi , Schuchert Pia , Serpetti Natalia , Woodlock Johnny , Reid David G.
Published: April 2021

Although frequently suggested as a goal for ecosystem-based fisheries management, incorporating ecosystem information into fisheries stock assessments has proven challenging. The uncertainty of input data, coupled with the structural uncertainty of complex multi-species models, currently makes the use of absolute values from such models contentious for short-term single-species fisheries management advice. Here, we propose a different approach where the standard assessment methodologies can be enhanced using ecosystem model derived information. Using a case study of the Irish Sea, we illustrate how stock-specific ecosystem indicators can be used to set an ecosystem-based fishing mortality reference point (FECO) within the “Pretty Good Yield” ranges for fishing mortality which form the present precautionary approach adopted in Europe by the International Council for the Exploration of the Sea (ICES). We propose that this new target, FECO, can be used to scale fishing mortality down when the ecosystem conditions for the stock are poor and up when conditions are good. This approach provides a streamlined quantitative way of incorporating ecosystem information into catch advice and provides an opportunity to operationalize ecosystem models and empirical indicators, while retaining the integrity of current assessment models and the FMSY-based advice process.
Improvement of Solvent Exchange for Supercritical Dried Aerogels
Authors: Schwan Marina , Nefzger Sarah , Zoghi Behdad , Oligschleger Christina , Milow Barbara
Published: April 2021

The solvent exchange as one of the most important steps during the manufacturing process of organic aerogels was investigated. This step is crucial as a preparatory step for the supercritical drying, since the pore solvent must be soluble in supercritical carbon dioxide to enable solvent extraction. The development and subsequent optimization of a suitable system with a peristaltic pump for automatic solvent exchange proved to be a suitable approach. In addition, the influence of zeolites on the acceleration of the process was found to be beneficial. To investigate the process, the water content in acetone was determined at different times using Karl Fischer titration. The shrinkage, densities, as well as the surface areas of the aerogels were analyzed. Based on these, the influence of various process parameters on the final structure of the obtained aerogels was investigated and evaluated. Modeling on diffusion in porous materials completes this study.
Fostering Well-Being in the Elderly: Translating Theories on Positive Aging to Practical Approaches
Authors: Bar-Tur Liora
Published: April 2021

This article overviews positive aging concepts and strategies to enhance well-being in the elderly and then presents a translation of theories on positive aging to practical approaches for Positive Aging. Drawing upon positive psychology and positive aging research and tools, this program is designed to help older adults improve their well-being by acquiring skills and strategies to cope with present and future challenges. The Mental Fitness Program for Positive Aging (MFPPA) can enhance seniors' quality of life by increasing their vital involvement and active engagement in life. This model is most appropriate for community dwelling individuals. It can easily be conducted in wide range of adult education programs in community centers, sheltered homes, and primary care clinics. It can also be conducted through online psychoeducational training.
Bacterial Gamma-Glutamyl Transpeptidase, an Emerging Biocatalyst: Insights Into Structure–Function Relationship and Its Biotechnological Applications
Authors: Saini Meenu , Kashyap Amuliya , Bindal Shruti , Saini Kuldeep , Gupta Rani
Published: April 2021

Gamma-glutamyl transpeptidase (GGT) enzyme is ubiquitously present in all life forms and plays a variety of roles in diverse organisms. Higher eukaryotes mainly utilize GGT for glutathione degradation, and mammalian GGTs have implications in many physiological disorders also. GGTs from unicellular prokaryotes serve different physiological functions in Gram-positive and Gram-negative bacteria. In the present review, the physiological significance of bacterial GGTs has been discussed categorizing GGTs from Gram-negative bacteria like Escherichia coli as glutathione degraders and from pathogenic species like Helicobacter pylori as virulence factors. Gram-positive bacilli, however, are considered separately as poly-γ-glutamic acid (PGA) degraders. The structure–function relationship of the GGT is also discussed mainly focusing on the crystallization of bacterial GGTs along with functional characterization of conserved regions by site-directed mutagenesis that unravels molecular aspects of autoprocessing and catalysis. Only a few crystal structures have been deciphered so far. Further, different reports on heterologous expression of bacterial GGTs in E. coli and Bacillus subtilis as hosts have been presented in a table pointing toward the lack of fermentation studies for large-scale production. Physicochemical properties of bacterial GGTs have also been described, followed by a detailed discussion on various applications of bacterial GGTs in different biotechnological sectors. This review emphasizes the potential of bacterial GGTs as an industrial biocatalyst relevant to the current switch toward green chemistry.
A Novel Gene vp0610 Negatively Regulates Biofilm Formation in Vibrio parahaemolyticus
Authors: Jiang Fufeng , Lei Tao , Wang Zhi , He Min , Zhang Jumei , Wang Juan , Zeng Haiyan , Chen Moutong , Xue Liang , Ye Qinghua , Pang Rui , Wu Shi , Gu Qihui , Ding Yu , Wu Qingping
Published: April 2021

Vibrio parahaemolyticus is an important foodborne pathogen and its biofilm formation ability facilitates its colonization and persistence in foods by protecting it from stresses including environmental variation and antibiotic exposure. Several important proteins are involved in biofilm formation; however, the identity and function of many remain unknown. In this study, we discovered a hypothetical protein, VP0610 that negatively regulates biofilm formation in Vibrio parahaemolyticus, and we found that the loss of vp0610 typically results in pleiotropic phenotypes that contribute toward promoting biofilm formation, including significantly increased insoluble exopolysaccharide production and swimming motility, decreased soluble exopolysaccharide production, and decreased bis-(3′-5′)-cyclic dimeric guanosine monophosphate production. Pull-down assays revealed that VP0610 can interact with 180 proteins, some of which (Hfq, VP0710, VP0793, and CyaA) participate in biofilm formation. Moreover, deleting vp0610 enhanced the expression of genes responsible for biofilm component (flaE), the sugar phosphotransferase system (PTS) EIIA component (vp0710 and vp0793), and a high-density regulator of quorum sensing (opaR), while reducing the expression of the bis-(3′-5′)-cyclic dimeric guanosine monophosphate degradation protein (CdgC), resulting in faster biofilm formation. Taken together, our results indicate that vp0610 is an integral member of the key biofilm regulatory network of V. parahaemolyticus that functions as a repressor of biofilm formation.
Multi-Replicated Enrichment Communities as a Model System in Microbial Ecology
Authors: Estrela Sylvie , Sánchez Álvaro , Rebolleda-Gómez María
Published: April 2021

Recent advances in robotics and affordable genomic sequencing technologies have made it possible to establish and quantitatively track the assembly of enrichment communities in high-throughput. By conducting community assembly experiments in up to thousands of synthetic habitats, where the extrinsic sources of variation among replicates can be controlled, we can now study the reproducibility and predictability of microbial community assembly at different levels of organization, and its relationship with nutrient composition and other ecological drivers. Through a dialog with mathematical models, high-throughput enrichment communities are bringing us closer to the goal of developing a quantitative predictive theory of microbial community assembly. In this short review, we present an overview of recent research on this growing field, highlighting the connection between theory and experiments and suggesting directions for future work.
Machine Learning for Predicting Mycotoxin Occurrence in Maize
Authors: Camardo Leggieri Marco , Mazzoni Marco , Battilani Paola
Published: April 2021

Meteorological conditions are the main driving variables for mycotoxin-producing fungi and the resulting contamination in maize grain, but the cropping system used can mitigate this weather impact considerably. Several researchers have investigated cropping operations’ role in mycotoxin contamination, but these findings were inconclusive, precluding their use in predictive modeling. In this study a machine learning (ML) approach was considered, which included weather-based mechanistic model predictions for AFLA-maize and FER-maize [predicting aflatoxin B1(AFB1) and fumonisins (FBs), respectively], and cropping system factors as the input variables. The occurrence of AFB1and FBs in maize fields was recorded, and their corresponding cropping system data collected, over the years 2005–2018 in northern Italy. Two deep neural network (DNN) models were trained to predict, at harvest, which maize fields were contaminated beyond the legal limit with AFB1and FBs. Both models reached an accuracy >75% demonstrating the ML approach added value with respect to classical statistical approaches (i.e., simple or multiple linear regression models). The improved predictive performance compared with that obtained for AFLA-maize and FER-maize was clearly demonstrated. This coupled to the large data set used, comprising a 13-year time series, and the good results for the statistical scores applied, together confirmed the robustness of the models developed here.
Biosynthesis of Commodity Chemicals From Oil Palm Empty Fruit Bunch Lignin
Authors: Lo Tat-Ming , Hwang In Young , Cho Han-Saem , Fedora Raissa Eka , Chng Si Hui , Choi Won Jae , Chang Matthew Wook
Published: April 2021

Lignin is one of the most abundant natural resources that can be exploited for the bioproduction of value-added commodity chemicals. Oil palm empty fruit bunches (OPEFBs), byproducts of palm oil production, are abundant lignocellulosic biomass but largely used for energy and regarded as waste. Pretreatment of OPEFB lignin can yield a mixture of aromatic compounds that can potentially serve as substrates to produce commercially important chemicals. However, separation of the mixture into desired individual substrates is required, which involves expensive steps that undermine the utility of OPEFB lignin. Here, we report successful engineering of microbial hosts that can directly utilize heterogeneous mixtures derived from OPEFB lignin to produce commodity chemicals, adipic acid and levulinic acid. Furthermore, the corresponding bioconversion pathway was placed under a genetic controller to autonomously activate the conversion process as the cells are fed with a depolymerized OPEFB lignin mixture. This study demonstrates a simple, one-pot biosynthesis approach that directly utilizes derivatives of agricultural waste to produce commodity chemicals.
Understanding the Holobiont: Crosstalk Between Gut Microbiota and Mitochondria During Long Exercise in Horse
Authors: Mach Núria , Moroldo Marco , Rau Andrea , Lecardonnel Jérôme , Le Moyec Laurence , Robert Céline , Barrey Eric
Published: April 2021

Endurance exercise has a dramatic impact on the functionality of mitochondria and on the composition of the intestinal microbiome, but the mechanisms regulating the crosstalk between these two components are still largely unknown. Here, we sampled 20 elite horses before and after an endurance race and used blood transcriptome, blood metabolome and fecal microbiome to describe the gut-mitochondria crosstalk. A subset of mitochondria-related differentially expressed genes involved in pathways such as energy metabolism, oxidative stress and inflammation was discovered and then shown to be associated with butyrate-producing bacteria of the Lachnospiraceae family, especially Eubacterium. The mechanisms involved were not fully understood, but through the action of their metabolites likely acted on PPARγ, the FRX-CREB axis and their downstream targets to delay the onset of hypoglycemia, inflammation and extend running time. Our results also suggested that circulating free fatty acids may act not merely as fuel but drive mitochondrial inflammatory responses triggered by the translocation of gut bacterial polysaccharides following endurance. Targeting the gut-mitochondria axis therefore appears to be a potential strategy to enhance athletic performance.
Predictive Coding Over the Lifespan: Increased Reliance on Perceptual Priors in Older Adults—A Magnetoencephalography and Dynamic Causal Modeling Study
Authors: Chan Jason S. , Wibral Michael , Stawowsky Cerisa , Brandl Mareike , Helbling Saskia , Naumer Marcus J. , Kaiser Jochen , Wollstadt Patricia
Published: April 2021

Aging is accompanied by unisensory decline. To compensate for this, two complementary strategies are potentially relied upon increasingly: first, older adults integrate more information from different sensory organs. Second, according to the predictive coding (PC) model, we form “templates” (internal models or “priors”) of the environment through our experiences. It is through increased life experience that older adults may rely more on these templates compared to younger adults. Multisensory integration and predictive coding would be effective strategies for the perception of near-threshold stimuli, which may however come at the cost of integrating irrelevant information. Both strategies can be studied in multisensory illusions because these require the integration of different sensory information, as well as an internal model of the world that can take precedence over sensory input. Here, we elicited a classic multisensory illusion, the sound-induced flash illusion, in younger (mean: 27 years, N = 25) and older (mean: 67 years, N = 28) adult participants while recording the magnetoencephalogram. Older adults perceived more illusions than younger adults. Older adults had increased pre-stimulus beta-band activity compared to younger adults as predicted by microcircuit theories of predictive coding, which suggest priors and predictions are linked to beta-band activity. Transfer entropy analysis and dynamic causal modeling of pre-stimulus magnetoencephalography data revealed a stronger illusion-related modulation of cross-modal connectivity from auditory to visual cortices in older compared to younger adults. We interpret this as the neural correlate of increased reliance on a cross-modal predictive template in older adults leading to the illusory percept.
Embodied Cooperation to Promote Forgiving Interactions With Autonomous Machines
Authors: Schofield Jonathon S. , Battraw Marcus A. , Parker Adam S. R. , Pilarski Patrick M. , Sensinger Jonathon W. , Marasco Paul D.
Published: April 2021

During every waking moment, we must engage with our environments, the people around us, the tools we use, and even our own bodies to perform actions and achieve our intentions. There is a spectrum of control that we have over our surroundings that spans the extremes from full to negligible. When the outcomes of our actions do not align with our goals, we have a tremendous capacity to displace blame and frustration on external factors while forgiving ourselves. This is especially true when we cooperate with machines; they are rarely afforded the level of forgiveness we provide our bodies and often bear much of our blame. Yet, our brain readily engages with autonomous processes in controlling our bodies to coordinate complex patterns of muscle contractions, make postural adjustments, adapt to external perturbations, among many others. This acceptance of biological autonomy may provide avenues to promote more forgiving human-machine partnerships. In this perspectives paper, we argue that striving for machine embodiment is a pathway to achieving effective and forgiving human-machine relationships. We discuss the mechanisms that help us identify ourselves and our bodies as separate from our environments and we describe their roles in achieving embodied cooperation. Using a representative selection of examples in neurally interfaced prosthetic limbs and intelligent mechatronics, we describe techniques to engage these same mechanisms when designing autonomous systems and their potential bidirectional interfaces.
Preliminary Evidence of Orthostatic Intolerance and Altered Cerebral Vascular Control Following Sport-Related Concussion
Authors: Worley Morgan L. , O'Leary Morgan C. , Sackett James R. , Schlader Zachary J. , Willer Barry , Leddy John J. , Johnson Blair D.
Published: April 2021

Concussions have been shown to result in autonomic dysfunction and altered cerebral vascular function. We tested the hypothesis that concussed athletes (CA) would have altered cerebral vascular function during acute decreases and increases in blood pressure compared to healthy controls (HC). Ten CA (age: 20 ± 2 y, 7 females) and 10 HC (age: 21 ± 2 y, 6 females) completed 5 min of lower body negative pressure (LBNP; −40 mmHg) and 5 min of lower body positive pressure (LBPP; 20 mmHg). Protocols were randomized and separated by 10 min. Mean arterial pressure (MAP) and middle cerebral artery blood velocity (MCAv) were continuously recorded. Cerebral vascular resistance (CVR) was calculated as MAP/MCAv. Values are reported as change from baseline to the last minute achieved (LBNP) or 5 min (LBPP). There were no differences in baseline values between groups. During LBNP, there were no differences in the change for MAP (CA: −23 ± 18 vs. HC: −21 ± 17 cm/s;P= 0.80) or MCAv (CA: −13 ± 8 vs. HC: −18 ± 9 cm/s;P= 0.19). The change in CVR was different between groups (CA: −0.08 ± 0.26 vs. HC: 0.18 ± 0.24 mmHg/cm/s;P= 0.04). Total LBNP time was lower for CA (204 ± 92 s) vs. HC (297 ± 64 s;P= 0.04). During LBPP, the change in MAP was not different between groups (CA: 13 ± 6 vs. HC: 10 ± 7 mmHg;P= 0.32). The change in MCAv (CA: 7 ± 6 vs. HC: −4 ± 13 cm/s;P= 0.04) and CVR (CA: −0.06 ± 0.27 vs. HC: 0.38 ± 0.41 mmHg/cm/s;P= 0.03) were different between groups. CA exhibited impaired tolerance to LBNP and had a different cerebral vascular response to LBPP compared to HC.
A Dynamic Systems Framework for Gender/Sex Development: From Sensory Input in Infancy to Subjective Certainty in Toddlerhood
Authors: Fausto-Sterling Anne
Published: April 2021

From birth to 15 months infants and caregivers form a fundamentally intersubjective, dyadic unit within which the infant’s ability to recognize gender/sex in the world develops. Between about 18 and 36 months the infant accumulates an increasingly clear and subjective sense of self as female or male. We know little about how the precursors to gender/sex identity form during the intersubjective period, nor how they transform into an independent sense of self by 3 years of age. In this Theory and Hypothesis article I offer a general framework for thinking about this problem. I propose that through repetition and patterning, the dyadic interactions in which infants and caregivers engage imbue the infant with an embodied, i.e., sensori-motor understanding of gender/sex. During this developmental period (which I label Phase 1) gender/sex is primarily an intersubjective project. From 15 to 18 months (which I label Phase 2) there are few reports of newly appearing gender/sex behavioral differences, and I hypothesize that this absence reflects a period of developmental instability during which there is a transition from gender/sex as primarily inter-subjective to gender/sex as primarily subjective. Beginning at 18 months (i.e., the start of Phase 3), a toddler’s subjective sense of self as having a gender/sex emerges, and it solidifies by 3 years of age. I propose a dynamic systems perspective to track how infants first assimilate gender/sex information during the intersubjective period (birth to 15 months); then explore what changes might occur during a hypothesized phase transition (15 to 18 months), and finally, review the emergence and initial stabilization of individual subjectivity-the period from 18 to 36 months. The critical questions explored focus on how to model and translate data from very different experimental disciplines, especially neuroscience, physiology, developmental psychology and cognitive development. I close by proposing the formation of a research consortium on gender/sex development during the first 3 years after birth.
Optogenetic Neuronal Stimulation Promotes Functional Recovery After Spinal Cord Injury
Authors: Deng Wei-wei , Wu Guang-yan , Min Ling-xia , Feng Zhou , Chen Hui , Tan Ming-liang , Sui Jian-feng , Liu Hong-liang , Hou Jing-ming
Published: April 2021

Although spinal cord injury (SCI) is the main cause of disability worldwide, there is still no definite and effective treatment method for this condition. Our previous clinical trials confirmed that the increased excitability of the motor cortex was related to the functional prognosis of patients with SCI. However, it remains unclear which cell types in the motor cortex lead to the later functional recovery. Herein, we applied optogenetic technology to selectively activate glutamate neurons in the primary motor cortex and explore whether activation of glutamate neurons in the primary motor cortex can promote functional recovery after SCI in rats and the preliminary neural mechanisms involved. Our results showed that the activation of glutamate neurons in the motor cortex could significantly improve the motor function scores in rats, effectively shorten the incubation period of motor evoked potentials and increase motor potentials’ amplitude. In addition, hematoxylin-eosin staining and nerve fiber staining at the injured site showed that accurate activation of the primary motor cortex could effectively promote tissue recovery and neurofilament growth (GAP-43, NF) at the injured site of the spinal cord, while the content of some growth-related proteins (BDNF, NGF) at the injured site increased. These results suggested that selective activation of glutamate neurons in the primary motor cortex can promote functional recovery after SCI and may be of great significance for understanding the neural cell mechanism underlying functional recovery induced by motor cortex stimulation.
Current Landscape of Nutrition Within Prehabilitation Oncology Research: A Scoping Review
Authors: Gillis Chelsia , Davies Sarah J. , Carli Francesco , Wischmeyer Paul E. , Wootton Stephen A. , Jackson Alan A. , Riedel Bernhard , Marino Luise V. , Levett Denny Z. H. , West Malcolm A.
Published: April 2021

Background: Prehabilitation aims to improve functional capacity prior to cancer treatment to achieve better psychosocial and clinical outcomes. Prehabilitation interventions vary considerably in design and delivery. In order to identify gaps in knowledge and facilitate the design of future studies, we undertook a scoping review of prehabilitation studies to map the range of work on prehabilitation being carried out in any cancer type and with a particular focus on diet or nutrition interventions.

Objectives: Firstly, to describe the type of prehabilitation programs currently being conducted. Secondly, to describe the extent to which prehabilitation studies involved aspects of nutrition, including assessment, interventions, implementation, and outcomes.

Eligibility Criteria: Any study of quantitative or qualitative design that employed a formal prehabilitation program before cancer treatment (“prehabilitation” listed in keywords, title, or abstract).

Sources of Evidence: Search was conducted in July 2020 using MEDLINE, PubMed, EMBASE, EMCARE, CINAHL, and AMED.

Charting Methods: Quantitative data were reported as frequencies. Qualitative nutrition data were charted using a framework analysis that reflects the Nutrition Care Process Model: assessment, intervention, and monitoring/evaluation of the nutrition intervention.

Results: Five hundred fifty unique articles were identified: 110 studies met inclusion criteria of a formal prehabilitation study in oncology. prehabilitation studies were mostly cohort studies (41%) or randomized-controlled trials (38%) of multimodal (49%), or exercise-only (44%) interventions that were applied before surgery (94%). Nutrition assessment was inconsistently applied across these studies, and often conducted without validated tools (46%). Of the 110 studies, 37 (34%) included a nutrition treatment component. Half of these studies provided the goal for the nutrition component of their prehabilitation program; of these goals, less than half referenced accepted nutrition guidelines in surgery or oncology. Nutrition interventions largely consisted of counseling with dietary supplementation. The nutrition intervention was indiscernible in 24% of studies. Two-thirds of studies did not monitor the nutrition intervention nor evaluate nutrition outcomes.

Conclusion: Prehabilitation literature lacks standardized and validated nutritional assessment, is frequently conducted without evidence-based nutrition interventions, and is typically implemented without monitoring the nutrition intervention or evaluating the intervention's contribution to outcomes. We suggest that the development of a core outcome set could improve the quality of the studies, enable pooling of evidence, and address some of the research gaps identified.
De Novo Versus Secondary Metastatic EGFR-Mutated Non-Small-Cell Lung Cancer
Authors: Bozorgmehr Farastuk , Kazdal Daniel , Chung Inn , Kirchner Martina , Magios Nikolaus , Kriegsmann Mark , Allgäuer Michael , Klotz Laura V. , Muley Thomas , El Shafie Rami A. , Fischer Jürgen R. , Faehling Martin , Stenzinger Albrecht , Thomas Michael , Christopoulos Petros
Published: April 2021

Background

Metastatic epidermal growth factor receptor-mutated (EGFR+) non-small-cell lung cancer (NSCLC) can present de novo or following previous nonmetastatic disease (secondary). Potential differences between these two patient subsets are unclear at present.

Methods

We retrospectively analyzed characteristics of tyrosine kinase inhibitor (TKI)-treated patients with de novo vs. secondary metastatic EGFR+ NSCLC until December 2019 (n = 401).

Results

De novo metastatic disease was 4× more frequent than secondary (n = 83/401), but no significant differences were noted regarding age (median 66 vs. 70 years), sex (65% vs. 65% females), smoking history (67% vs. 62% never/light-smokers), and histology (both >95% adenocarcinoma). Patients with secondary metastatic disease showed a better ECOG performance status (PS 0–1 67%–32% vs. 46%–52%, p = 0.003), fewer metastatic sites (mean 1.3 vs. 2.0, p < 0.001), and less frequent brain involvement (16% vs. 28%, p = 0.022) at the time of stage IV diagnosis. Progression-free survival (PFS) under TKI (median 17 for secondary vs. 12 months for de novo, p = 0.26) and overall survival (OS, 29 vs. 25 months, respectively, p = 0.47) were comparable. EGFR alterations (55% vs. 60% exon 19 deletions), TP53 mutation rate at baseline (47% vs. 43%, n = 262), and T790M positivity at the time of TKI failure (51% vs. 56%, n = 193) were also similar. OS according to differing characteristics, e.g., presence or absence of brain metastases (19–20 or 30–31 months, respectively, p = 0.001), and ECOG PS 0 or 1 or 2 (32–34 or 20–23 or 5–7 months, respectively, p < 0.001), were almost identical for de novo and secondary metastatic disease.

Conclusions

Despite the survival advantage reported in the pre-TKI era for relapsed NSCLC, molecular features and outcome of TKI-treated metastatic EGFR+ tumors are currently independent of preceding nonmetastatic disease. This simplifies design of outcome studies and can assist prognostic considerations in everyday management of patients with secondary metastatic EGFR+ tumors.
Modulatory Effect of Intermittent Fasting on Adipose Tissue Inflammation: Amelioration of Cardiovascular Dysfunction in Early Metabolic Impairment
Authors: Dwaib Haneen S. , AlZaim Ibrahim , Eid Ali H. , Obeid Omar , El-Yazbi Ahmed F.
Published: April 2021

Cardiometabolic syndrome (CMS) is a cluster of maladaptive cardiovascular, renal, thrombotic, inflammatory, and metabolic disorders. It confers a high risk of cardiovascular mortality and morbidity. CMS is triggered by major shifts in lifestyle and dietary habits with increased consumption of refined, calorie-dense diets. Evidence indicates that diet-induced CMS is linked to Adipose tissue (AT) inflammation. This led to the proposal that adipose inflammation may be involved in metabolic derangements, such as insulin resistance and poor glycemic control, as well as the contribution to the inflammatory process predisposing patients to increased cardiovascular risk. Therefore, in the absence of direct pharmacological interventions for the subclinical phase of CMS, time restricted feeding regimens were anticipated to alleviate early metabolic damage and subsequent comorbidities. These regimens, referred to as intermittent fasting (IF), showed a strong positive impact on the metabolic state of obese and non-obese human subjects and animal models, positive AT remodeling in face of overnutrition and high fat diet (HFD) consumption, and improved CV outcomes. Here, we summarize the available evidence on the role of adipose inflammation in triggering cardiovascular impairment in the context of diet induced CMS with an emphasis on the involvement of perivascular adipose tissue. As well, we propose some possible molecular pathways linking intermittent fasting to the ameliorative effect on adipose inflammation and cardiovascular dysfunction under such circumstances. We highlight a number of targets, whose function changes in perivascular adipose tissue inflammation and could be modified by intermittent fasting acting as a novel approach to ameliorate the inflammatory status.
Combined Cornus Officinalis and Paeonia Lactiflora Pall Therapy Alleviates Rheumatoid Arthritis by Regulating Synovial Apoptosis via AMPK-Mediated Mitochondrial Fission
Authors: Huang Lichuang , Hu Shaoqi , Shao Meiyu , Wu Xin , Zhang Jida , Cao Gang
Published: April 2021

Rheumatoid arthritis (RA) is a chronic autoimmune disease that leads to cartilage destruction and bone erosion. In-depth exploration of the pathogenesis of RA and the development of effective therapeutic drugs are of important clinical and social value. Herein, we explored the medicinal value of Cornus officinalis Sieb. and Paeonia lactiflora Pall. in RA treatment using a rat model of collagen-induced arthritis (CIA). We compared the therapeutic effect of Cornus officinalis and Paeonia lactiflora with that of their main active compounds, ursolic acid and paeoniflorin, respectively. We demonstrated that the combination of Cornus officinalis and Paeonia lactiflora effectively inhibited the release of factors associated with oxidative stress and inflammation during RA, therein ameliorating the symptoms and suppressing the progression of RA. We further showed that the underlying mechanisms may be related to the regulation of apoptosis in synovial tissues, and we investigated the potential involvement of AMPK-mediated mitochondrial dynamics in the therapeutic action of the two drugs and their active components.
Sirt2 in the Spinal Cord Regulates Chronic Neuropathic Pain Through Nrf2-Mediated Oxidative Stress Pathway in Rats
Authors: Zhao Mengnan , Zhang Xiaojiao , Tao Xueshu , Zhang Bohan , Sun Cong , Wang Pinying , Song Tao
Published: April 2021

Reduction in Nrf2-mediated antioxidant response in the central nervous system plays an important role in the development and maintenance of neuropathic pain (NP). However, the mechanisms regulating Nrf2 activity in NP remain unclear. A recent in vitro study revealed that Sirt2, a member of the sirtuin family of proteins, affects antioxidant capacity by modulating Nrf2 activity. Here we examined whether central Sirt2 regulates NP through Nrf2-mediated oxidative stress pathway. In a rat model of spared nerve injury (SNI)-induced NP, mechanical allodynia and thermal hyperalgesia were observed on day 1 and up to day 14 post-SNI. The expression of Sirt2, Nrf2 and its target gene NQO1 in the spinal cord in SNI rats, compared with sham rats, was significantly decreased from day 7 and remained lower until the end of the experiment (day 14). The mechanical allodynia and thermal hyperalgesia in SNI rats were ameliorated by intrathecal injection of Nrf2 agonist tBHQ, which normalized expression of Nrf2 and NQO1 and reversed SNI-induced decrease in antioxidant enzyme superoxide dismutase (SOD) and increase in oxidative stress marker 8-hydroxy-2′-deoxyguanosine (8-OHdG) in the spinal cord. Moreover, intrathecal injection of a recombinant adenovirus expressing Sirt2 (Ad-Sirt2) that upregulated expression of Sirt2, restored expression of Nrf2 and NQO1 and attenuated oxidative stress in the spinal cord, leading to improvement of thermal hyperalgesia and mechanical allodynia in SNI rats. These findings suggest that peripheral nerve injury downregulates Sirt2 expression in the spinal cord, which inhibits Nrf2 activity, leading to increased oxidative stress and the development of chronic NP.
Ig Glycosylation in Ulcerative Colitis: It’s Time for New Biomarkers
Authors: Capecchi Riccardo , Migliorini Paola , Zanzi Federico , Maltinti Simona , Puxeddu Ilaria , de Bortoli Nicola , Bellini Massimo , Costa Francesco , Marchi Santino , Bertani Lorenzo
Published: April 2021

Background:Ulcerative colitis (UC) is a chronic relapsing disease, which needs a continue monitoring, especially during biological therapies. An increasing number of patients is treated with anti-Tumor Necrosis factor (TNF) drugs, and current research is focalized to identify biomarkers able to monitor the disease and to predict therapeutic outcome.

Methods:We enrolled consecutive UC patients treated with anti-TNF, naïve to biologic drugs. Therapeutic outcome was evaluated after 54 weeks of treatment in terms of clinical remission (Partial Mayo Score -PMS- <2) and mucosal healing (Mayo Endoscopic Score <2). On serum samples collected at baseline and after 54 weeks of treatment, a Lectin-based ELISA assay was performed, and specific glycosylation patterns were evaluated by biotin-labelled lectins. We have also collected 21 healthy controls (NHS) samples, age and sex-matched.

Results:Out of 44 UC patients enrolled, 22 achieved clinical remission and mucosal healing after 54 weeks. At baseline, when Protein A was used as coating, UC patients non-responders showed a reduced reactivity to Jacalin (JAC) in comparison with NHS (p= 0.04). After one year of treatment, a decrease in JAC binding was seen only in responders, in comparison with baseline (p= 0.04). When JAC binding was tested selecting IgG by means of Fab anti-IgG Fab, UC patients displayed an increased reactivity after anti-TNF therapy (p< 0,0001 vs controls). At baseline, PMS inversely correlates with JAC binding when Fab anti-IgG Fab was used in solid phase (r2= 0,2211;p= 0,0033). Patients with higher PMS at baseline (PMS ≥5) presented lower binding capacity for JAC in comparison with NHS and with lower PMS patients (p= 0,0135 andp= 0,0089, respectively).

Conclusion:Ig glycosylation was correlated with clinical and endoscopic activity in patients with UC. JAC protein A-selected Ig showed a possible role in predicting therapeutic effectiveness. If these data would be confirmed, Ig glycosylation could be used as biomarker in UC.
Maximal Fat Oxidation During Exercise Is Already Impaired in Pre-pubescent Children With Type 1 Diabetes Mellitus
Authors: Fel Solenne , Rochette Emmanuelle , Walther Guillaume , Echaubard Stéphane , Pereira Bruno , Merlin Etienne , Terral Daniel , Duché Pascale
Published: April 2021

Objective: We evaluated substrate utilization during submaximal exercise, together with glycemic responses and hormonal counter-regulation to exercise, in children with type 1 diabetes mellitus (T1DM).

Methods: Twelve pre-pubescent children with T1DM and 12 healthy children were matched by sex and age. Participants completed a submaximal incremental exercise test to determine their fat and carbohydrate oxidation rates by indirect calorimetry. Levels of glycemia, glucagon, cortisol, growth hormone, noradrenaline, adrenaline, and insulin were monitored until 120 min post-exercise.

Results: Absolute peak oxygen uptake (VO2 peak) was significantly lower in the children with T1DM than in the healthy controls (1131.4 ± 102.5 vs. 1383.0 ± 316.6 ml.min−1, p = 0.03). Overall carbohydrate and lipid oxidation rates were the same in the two groups, but for exercise intensities, higher than 50% of VO2 peak, fat oxidation rate was significantly lower in the children with T1DM. The absolute maximal lipid oxidation rate was significantly lower in the T1DM children (158.1 ± 31.6 vs. 205.4 ± 42.1 mg.min−1, p = 0.005), and they reached a significantly lower exercise power than the healthy controls (26.4 ± 1.2 vs. 35.4 ± 3.3 W, p = 0.03). Blood glucose responses to exercise were negatively correlated with pre-exercise blood glucose concentrations (r = −0.67; p = 0.03).

Conclusion: Metabolic and hormonal responses during sub-maximal exercise are impaired in young children with T1DM.
Applications of UAS in Crop Biomass Monitoring: A Review
Authors: Wang Tianhai , Liu Yadong , Wang Minghui , Fan Qing , Tian Hongkun , Qiao Xi , Li Yanzhou
Published: April 2021

Biomass is an important indicator for evaluating crops. The rapid, accurate and nondestructive monitoring of biomass is the key to smart agriculture and precision agriculture. Traditional detection methods are based on destructive measurements. Although satellite remote sensing, manned airborne equipment, and vehicle-mounted equipment can nondestructively collect measurements, they are limited by low accuracy, poor flexibility, and high cost. As nondestructive remote sensing equipment with high precision, high flexibility, and low-cost, unmanned aerial systems (UAS) have been widely used to monitor crop biomass. In this review, UAS platforms and sensors, biomass indices, and data analysis methods are presented. The improvements of UAS in monitoring crop biomass in recent years are introduced, and multisensor fusion, multi-index fusion, the consideration of features not directly related to monitoring biomass, the adoption of advanced algorithms and the use of low-cost sensors are reviewed to highlight the potential for monitoring crop biomass with UAS. Considering the progress made to solve this type of problem, we also suggest some directions for future research. Furthermore, it is expected that the challenge of UAS promotion will be overcome in the future, which is conducive to the realization of smart agriculture and precision agriculture.
Water Use by Chinese Pine Is Less Conservative but More Closely Regulated Than in Mongolian Scots Pine in a Plantation Forest, on Sandy Soil, in a Semi-Arid Climate
Authors: Dang Hongzhong , Zhang Xueli , Han Hui , Chen Shuai , Li Mingyang
Published: April 2021

The diversity of plant water use patterns among species and ecosystems is a matter of widespread debate. In this study, Chinese pine (Pinus tabuliformis, CP) and Mongolian Scots pine (Pinus sylvestris var. mongolica, MP), which is co-exist in the shelterbelt plantations in the Horqin Sandyland in northern China, were chosen for comparison of water use traits by monitoring xylem sap flow alongside recordings of the associated environmental factors over four growing seasons. Continuous sap flux density measurements were converted into crown projected area transpiration intensity (Tr) and canopy stomatal conductance (Gs). The results indicated that MP showed a higher canopy transpiration intensity than in CP, with Tr daily means (±standard deviation) of 0.84 ± 0.36 and 0.79 ± 0.43 mm⋅d–1, respectively (p = 0.07). However, the inter-annual variability of daily Tr in MP was not significant, varying only approximately a 1.1-fold (p = 0.29), while inter-annual variation was significant for CP, with 1.24-fold variation (p < 0.01). In particular, the daily mean Tr value for CP was approximately 1.7-times higher than that of MP under favorable soil moisture conditions, with values for relative extractable soil water within the 0–1.0 m soil layer (REW) being above 0.4. However, as the soil dried out, the value of Tr for CP decreased more sharply, falling to only approximately 0.5-times the value for MP when REW fell to < 0.2. The stronger sensitivity of Tr and/or Gs to REW, together with the more sensitive response of Gs to VPD in CP, confirms that CP exhibits less conservation of soil water utilization but features a stronger ability to regulate water use. Compared with MP, CP can better adapt to the dry conditions associated with climate change.