bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of biochar and organic-inorganic fertilizer on pomelo orchard soil properties, enzymes activities, and microbial community structure
Authors: Song Yang , Zhao Quan , Guo Xiuzhu , Ali Izhar , Li Fayong , Lin Shaosheng , Liu Dongfeng
Published: August 2022

Fertilizer management can influence soil microbes, soil properties, enzymatic activities, abundance and community structure. However, information on the effects of biochar in combination with organic-inorganic fertilizer after 3 years under pomelo orchard on soil bacterial abundance, soil properties and enzyme activities are not clear. Therefore, we conducted a field experiment with seven treatments, i.e., (1) Ck (control), (2) T1 (2 kg biochar plant–1), (3) T2 (4 kg biochar plant–1), (4) T3 (2 kg organic-inorganic mixed fertilizer plant–1), (5) T4 (4 kg biochar + 1.7 kg organic-inorganic mixed fertilizer plant–1), (6) T5 (4 kg biochar + 1.4 kg organic-inorganic mixed fertilizer plant–1), and (7) T6 (4 kg biochar + 1.1 kg organic-inorganic mixed fertilizer plant–1). The soil microbial communities were characterized using high-throughput sequencing of 16S and internal transcribed spacer (ITS) ribosomal RNA gene amplicons. The results showed that biochar combined with organic-organic fertilizer significantly improved soil properties (pH, alkali hydrolysable nitrogen, available phosphorus, available potassium, and available magnesium) and soil enzymatic activities [urease, dehydrogenase (DHO), invertase and nitrate reductase (NR) activities]. Furthermore, soil bacterial relative abundance was higher in biochar and organic-inorganic treatments as compared to control plots and the most abundant phyla were Acidobacteria (40%), Proteobacteria (21%), Chloroflexi (17%), Planctomycetes (8%), Bacteroidetes (4%), Verrucomicrobia (2%), and Gemmatimonadetes (1%) among others. Among the treatments, Acidothermus, Acidibacter, Candidatus Solibacter and F473 bacterial genera were highest in combined biochar and organic-inorganic treatments. The lowest bacterial abundance and bacterial compositions were recorded in control plots. The correlation analysis showed that soil attributes, including soil enzymes, were positively correlated with Chloroflexi, Planctomycetes, verrucomicrobia, GAL15 and WPS-2 bacterial abundance. This study demonstrated that biochar with organic-inorganic fertilizer improves soil nutrients, enzymatic activities and bacterial abundance.
Swimming and the human microbiome at the intersection of sports, clinical, and environmental sciences: A scoping review of the literature
Authors: Puce Luca , Hampton-Marcell Jarrad , Trabelsi Khaled , Ammar Achraf , Chtourou Hamdi , Boulares Ayoub , Marinelli Lucio , Mori Laura , Cotellessa Filippo , Currà Antonio , Trompetto Carlo , Bragazzi Nicola Luigi
Published: August 2022

The human microbiota is comprised of more than 10–100 trillion microbial taxa and symbiotic cells. Two major human sites that are host to microbial communities are the gut and the skin. Physical exercise has favorable effects on the structure of human microbiota and metabolite production in sedentary subjects. Recently, the concept of “athletic microbiome” has been introduced. To the best of our knowledge, there exists no review specifically addressing the potential role of microbiomics for swimmers, since each sports discipline requires a specific set of techniques, training protocols, and interactions with the athletic infrastructure/facility. Therefore, to fill in this gap, the present scoping review was undertaken. Four studies were included, three focusing on the gut microbiome, and one addressing the skin microbiome. It was found that several exercise-related variables, such as training volume/intensity, impact the athlete’s microbiome, and specifically the non-core/peripheral microbiome, in terms of its architecture/composition, richness, and diversity. Swimming-related power-/sprint- and endurance-oriented activities, acute bouts and chronic exercise, anaerobic/aerobic energy systems have a differential impact on the athlete’s microbiome. Therefore, their microbiome can be utilized for different purposes, including talent identification, monitoring the effects of training methodologies, and devising ad hoc conditioning protocols, including dietary supplementation. Microbiomics can be exploited also for clinical purposes, assessing the effects of exposure to swimming pools and developing potential pharmacological strategies to counteract the insurgence of skin infections/inflammation, including acne. In conclusion, microbiomics appears to be a promising tool, even though current research is still limited, warranting, as such, further studies.
Challenges in describing the conformation and dynamics of proteins with ambiguous behavior
Authors: Roca-Martinez Joel , Lazar Tamas , Gavalda-Garcia Jose , Bickel David , Pancsa Rita , Dixit Bhawna , Tzavella Konstantina , Ramasamy Pathmanaban , Sanchez-Fornaris Maite , Grau Isel , Vranken Wim F.
Published: August 2022

Traditionally, our understanding of how proteins operate and how evolution shapes them is based on two main data sources: the overall protein fold and the protein amino acid sequence. However, a significant part of the proteome shows highly dynamic and/or structurally ambiguous behavior, which cannot be correctly represented by the traditional fixed set of static coordinates. Representing such protein behaviors remains challenging and necessarily involves a complex interpretation of conformational states, including probabilistic descriptions. Relating protein dynamics and multiple conformations to their function as well as their physiological context (e.g., post-translational modifications and subcellular localization), therefore, remains elusive for much of the proteome, with studies to investigate the effect of protein dynamics relying heavily on computational models. We here investigate the possibility of delineating three classes of protein conformational behavior: order, disorder, and ambiguity. These definitions are explored based on three different datasets, using interpretable machine learning from a set of features, from AlphaFold2 to sequence-based predictions, to understand the overlap and differences between these datasets. This forms the basis for a discussion on the current limitations in describing the behavior of dynamic and ambiguous proteins.
SPD-CNN: A plain CNN-based model using the symmetric positive definite matrices for cross-subject EEG classification with meta-transfer-learning
Authors: Chen Lezhi , Yu Zhuliang , Yang Jian
Published: August 2022

The electroencephalography (EEG) signals are easily contaminated by various artifacts and noise, which induces a domain shift in each subject and significant pattern variability among different subjects. Therefore, it hinders the improvement of EEG classification accuracy in the cross-subject learning scenario. Convolutional neural networks (CNNs) have been extensively applied to EEG-based Brain-Computer Interfaces (BCIs) by virtue of the capability of performing automatic feature extraction and classification. However, they have been mainly applied to the within-subject classification which would consume lots of time for training and calibration. Thus, it limits the further applications of CNNs in BCIs. In order to build a robust classification algorithm for a calibration-less BCI system, we propose an end-to-end model that transforms the EEG signals into symmetric positive definite (SPD) matrices and captures the features of SPD matrices by using a CNN. To avoid the time-consuming calibration and ensure the application of the proposed model, we use the meta-transfer-learning (MTL) method to learn the essential features from different subjects. We validate our model by making extensive experiments on three public motor-imagery datasets. The experimental results demonstrate the effectiveness of our proposed method in the cross-subject learning scenario.
Suppression of the necroptotic cell death pathways improves survival in Smn2B/− mice
Authors: Chehade Lucia , Deguise Marc-Olivier , De Repentigny Yves , Yaworski Rebecca , Beauvais Ariane , Gagnon Sabrina , Hensel Niko , Kothary Rashmi
Published: August 2022

Spinal muscular atrophy (SMA) is a monogenic neuromuscular disease caused by low levels of the Survival Motor Neuron (SMN) protein. Motor neuron degeneration is the central hallmark of the disease. However, the SMN protein is ubiquitously expressed and depletion of the protein in peripheral tissues results in intrinsic disease manifestations, including muscle defects, independent of neurodegeneration. The approved SMN-restoring therapies have led to remarkable clinical improvements in SMA patients. Yet, the presence of a significant number of non-responders stresses the need for complementary therapeutic strategies targeting processes which do not rely solely on restoring SMN. Dysregulated cell death pathways are candidates for SMN-independent pathomechanisms in SMA. Receptor-interacting protein kinase 1 (RIPK1) and RIPK3 have been widely recognized as critical therapeutic targets of necroptosis, an important form of programmed cell death. In addition, Caspase-1 plays a fundamental role in inflammation and cell death. In this study, we evaluate the role of necroptosis, particularly RIPK3 and Caspase-1, in the Smn2B/− mouse model of SMA. We have generated a triple mutant (TKO), the Smn2B/−; Ripk3−/−; Casp1−/− mouse. TKO mice displayed a robust increase in survival and improved motor function compared to Smn2B/− mice. While there was no protection against motor neuron loss or neuromuscular junction pathology, larger muscle fibers were observed in TKO mice compared to Smn2B/− mice. Our study shows that necroptosis modulates survival, motor behavior and muscle fiber size independent of SMN levels and independent of neurodegeneration. Thus, small-molecule inhibitors of necroptosis as a combinatorial approach together with SMN-restoring drugs could be a future strategy for the treatment of SMA.
Nonlinear optimal control of a mean-field model of neural population dynamics
Authors: Salfenmoser Lena , Obermayer Klaus
Published: August 2022

We apply the framework of nonlinear optimal control to a biophysically realistic neural mass model, which consists of two mutually coupled populations of deterministic excitatory and inhibitory neurons. External control signals are realized by time-dependent inputs to both populations. Optimality is defined by two alternative cost functions that trade the deviation of the controlled variable from its target value against the “strength” of the control, which is quantified by the integrated 1- and 2-norms of the control signal. We focus on a bistable region in state space where one low- (“down state”) and one high-activity (“up state”) stable fixed points coexist. With methods of nonlinear optimal control, we search for the most cost-efficient control function to switch between both activity states. For a broad range of parameters, we find that cost-efficient control strategies consist of a pulse of finite duration to push the state variables only minimally into the basin of attraction of the target state. This strategy only breaks down once we impose time constraints that force the system to switch on a time scale comparable to the duration of the control pulse. Penalizing control strength via the integrated 1-norm (2-norm) yields control inputs targeting one or both populations. However, whether control inputs to the excitatory or the inhibitory population dominate, depends on the location in state space relative to the bifurcation lines. Our study highlights the applicability of nonlinear optimal control to understand neuronal processing under constraints better.
Centromedian thalamic neuromodulation for the treatment of idiopathic generalized epilepsy
Authors: Zillgitt Andrew J. , Haykal M. Ayman , Chehab Ahmad , Staudt Michael D.
Published: August 2022

Idiopathic generalized epilepsy (IGE) is a common type of epilepsy and despite an increase in the number of available anti-seizure medications, approximately 20–30% of people with IGE continue to experience seizures despite adequate medication trials. Unlike focal epilepsy, resective surgery is not a viable treatment option for IGE; however, neuromodulation may be an effective surgical treatment for people with IGE. Thalamic stimulation through deep brain stimulation (DBS) and responsive neurostimulation (RNS) have been explored for the treatment of generalized and focal epilepsies. Although the data regarding DBS and RNS in IGE is limited to case reports and case series, the results of the published studies have been promising. The current manuscript will review the published literature of DBS and RNS within the centromedian nucleus of the thalamus for the treatment of IGE, as well as highlight an illustrative case.
Association between tennis training experience and executive function in children aged 8–12
Authors: Xu Yue , Zhang Wanxia , Zhang Hanfeng , Wang Lijuan , Luo Yanlin , Ni Guoxin
Published: August 2022

Cognitively engaging activities have been shown to facilitate the improvement of executive functions in children. However, a limited number of studies have investigated whether the relationship between dose parameters of physical activities and executive functions, and heterogeneity exists. In the present study, we aim to explore the association between tennis training experience and executive functions in children. Sixty children between the ages of 8 and 12 were recruited in this study and were allocated to the short-term (ST) group (<12 months, n = 30) and the long-term (LT) group (more than 12 months, n = 30). The abilities of inhibitory control, cognitive flexibility, and working memory were measured by the Stop-signal task, Switching task, and N-back task, respectively. There was no significant group difference in either the accuracy or reaction time of the Stop-signal task. No significant difference between the groups' accuracy in the Switching task was observed. However, the LT group presented a shorter reaction time than the ST group (731.69 ± 149.23 ms vs. 857.15 ± 157.99 ms, P < 0.01) in the Switching task. Additionally, training experience was positively associated with the reaction time of the Switching task. As for the N-back task, in comparison with the LT group, the ST group showed a longer reaction time (711.37 ± 168.14 ms vs. 164.75 ± 635.88 ms, P < 0.05). Moreover, training experience was also positively associated with the reaction time of the N-back task. But there was no significant group difference in the accuracy of the N-back task. In conclusion, children trained for over 1 year have better performance in cognitive flexibility and working memory than those trained in <1 year; thus, tennis experience is positively associated with executive functions.
PELP: Accounting for Missing Data in Neural Time Series by Periodic Estimation of Lost Packets
Authors: Dastin-van Rijn Evan M. , Provenza Nicole R. , Vogt Gregory S. , Avendano-Ortega Michelle , Sheth Sameer A. , Goodman Wayne K. , Harrison Matthew T. , Borton David A.
Published: August 2022

Recent advances in wireless data transmission technology have the potential to revolutionize clinical neuroscience. Today sensing-capable electrical stimulators, known as “bidirectional devices”, are used to acquire chronic brain activity from humans in natural environments. However, with wireless transmission come potential failures in data transmission, and not all available devices correctly account for missing data or provide precise timing for when data losses occur. Our inability to precisely reconstruct time-domain neural signals makes it difficult to apply subsequent neural signal processing techniques and analyses. Here, our goal was to accurately reconstruct time-domain neural signals impacted by data loss during wireless transmission. Towards this end, we developed a method termed Periodic Estimation of Lost Packets (PELP). PELP leverages the highly periodic nature of stimulation artifacts to precisely determine when data losses occur. Using simulated stimulation waveforms added to human EEG data, we show that PELP is robust to a range of stimulation waveforms and noise characteristics. Then, we applied PELP to local field potential (LFP) recordings collected using an implantable, bidirectional DBS platform operating at various telemetry bandwidths. By effectively accounting for the timing of missing data, PELP enables the analysis of neural time series data collected via wireless transmission—a prerequisite for better understanding the brain-behavior relationships underlying neurological and psychiatric disorders.
A deep learning approach with subregion partition in MRI image analysis for metastatic brain tumor
Authors: Shi Jiaxin , Zhao Zilong , Jiang Tao , Ai Hua , Liu Jiani , Chen Xinpu , Luo Yahong , Fan Huijie , Jiang Xiran
Published: August 2022

Purpose

To propose a deep learning network with subregion partition for predicting metastatic origins and EGFR/HER2 status in patients with brain metastasis.

Methods

We retrospectively enrolled 140 patients with clinico-pathologically confirmed brain metastasis originated from primary NSCLC (n = 60), breast cancer (BC, n = 60) and other tumor types (n = 20). All patients underwent contrast-enhanced brain MRI scans. The brain metastasis was subdivided into phenotypically consistent subregions using patient-level and population-level clustering. A residual network with a global average pooling layer (RN-GAP) was proposed to calculate deep learning-based features. Features from each subregion were selected with least absolute shrinkage and selection operator (LASSO) to build logistic regression models (LRs) for predicting primary tumor types (LR-NSCLC for the NSCLC origin and LR-BC for the BC origin), EGFR mutation status (LR-EGFR) and HER2 status (LR-HER2).

Results

The brain metastasis can be partitioned into a marginal subregion (S1) and an inner subregion (S2) in the MRI image. The developed models showed good predictive performance in the training (AUCs, LR-NSCLC vs. LR-BC vs. LR-EGFR vs. LR-HER2, 0.860 vs. 0.909 vs. 0.850 vs. 0.900) and validation (AUCs, LR-NSCLC vs. LR-BC vs. LR-EGFR vs. LR-HER2, 0.819 vs. 0.872 vs. 0.750 vs. 0.830) set.

Conclusion

Our proposed deep learning network with subregion partitions can accurately predict metastatic origins and EGFR/HER2 status of brain metastasis, and hence may have the potential to be non-invasive and preoperative new markers for guiding personalized treatment plans in patients with brain metastasis.
Benign regulation of the gut microbiota: The possible mechanism through which the beneficial effects of manual acupuncture on cognitive ability and intestinal mucosal barrier function occur in APP/PS1 mice
Authors: Hao Xin , Ding Ning , Zhang Yue , Yang Yichen , Zhao Yali , Zhao Jun , Li Yiran , Li Zhigang
Published: August 2022

Background

Gut microbiota dysbiosis and intestinal barrier injury play vital roles in Alzheimer’s disease (AD) onset and development. Our previous studies have demonstrated that manual acupuncture (MA) could improve the cognitive abilities of APP/PS1 mice. However, the effect of MA on the intestinal mucosal barrier and the gut microbiota mechanism through which this effect occurs remain to be clarified.

Methods

In the APP/PS1 manual acupuncture (Am) group, MA was applied in Baihui (GV20), Yintang (GV29), and Zusanli (ST36). Mice in the APP/PS1 antibiotic + manual acupuncture (Aa) group were treated with an antibiotic mixture and MA at the same time. Probiotics were delivered to the APP/PS1 probiotics (Ap) group. Alterations in spatial learning and memory, the gut microbiota, the intestinal barrier function, and the expression of glial fibrillary acidic protein (GFAP), lipopolysaccharide (LPS), and TNF-α were evaluated in each group.

Results

Compared with the C57BL/6 control (Cc) group, cognitive ability was significantly decreased, the gut microbiota structure was obviously disrupted, intestinal barrier integrity was drastically impaired, and the intestinal inflammatory response was enhanced in the APP/PS1 control (Ac) group (P < 0.01). These changes were reversed by MA and probiotics (P < 0.01 or P < 0.05), whereas antibiotics inhibited the benign regulation by MA (P < 0.01 or P < 0.05).

Conclusion

Manual acupuncture can benignly modulate gut microbiota dysbiosis, significantly reduce intestinal inflammation, and effectively alleviate the destruction of the intestinal mucosal barrier in APP/PS1 mice, and the effects are comparable to those of probiotics. The gut microbiota may play an important role in the improvement of the cognitive function and intestinal barrier function by MA.
Habenula bibliometrics: Thematic development and research fronts of a resurgent field
Authors: Chen Sifan , Sun Xiaoyu , Zhang Yizhe , Mu Yu , Su Diansan
Published: August 2022

The habenula (Hb) is a small structure of the posterior diencephalon that is highly conserved across vertebrates but nonetheless has attracted relatively little research attention until the past two decades. The resurgent interest is motivated by neurobehavioral studies demonstrating critical functions in a broad spectrum of motivational and cognitive processes, including functions relevant to psychiatric diseases. The Hb is widely conceived as an “anti-reward” center that acts by regulating brain monoaminergic systems. However, there is still no general conceptual framework for habenula research, and no study has focused on uncovering potentially significant but overlooked topics that may advance our understanding of physiological functions or suggest potential clinical applications of Hb-targeted interventions. Using science mapping tools, we quantitatively and qualitatively analyzed the relevant publications retrieved from the Web of Science Core Collection (WoSCC) database from 2002 to 2021. Herein we present an overview of habenula-related publications, reveal primary research trends, and prioritize some key research fronts by complementary bibliometric analysis. High-priority research fronts include Ventral Pallidum, Nucleus Accumbens, Nicotine and MHb, GLT-1, Zebrafish, and GCaMP, Ketamine, Deep Brain Stimulation, and GPR139. The high intrinsic heterogeneity of the Hb, extensive connectivity with both hindbrain and forebrain structures, and emerging associations with all three dimensions of mental disorders (internalizing, externalizing, and psychosis) suggest that the Hb may be the neuronal substrate for a common psychopathology factor shared by all mental illnesses termed the p factor. A future challenge is to explore the therapeutic potential of habenular modulation at circuit, cellular, and molecular levels.
Neuronopathic Gaucher disease: Beyond lysosomal dysfunction
Authors: Arévalo Nohela B. , Lamaizon Cristian M. , Cavieres Viviana A. , Burgos Patricia V. , Álvarez Alejandra R. , Yañez María J. , Zanlungo Silvana
Published: August 2022

Gaucher disease (GD) is an inherited disorder caused by recessive mutations in the GBA1 gene that encodes the lysosomal enzyme β-glucocerebrosidase (β-GC). β-GC hydrolyzes glucosylceramide (GluCer) into glucose and ceramide in the lysosome, and the loss of its activity leads to GluCer accumulation in different tissues. In severe cases, enzymatic deficiency triggers inflammation, organomegaly, bone disease, and neurodegeneration. Neuronopathic Gaucher disease (nGD) encompasses two different forms of the disease, characterized by chronic or acute damage to the central nervous system (CNS). The cellular and molecular studies that uncover the pathological mechanisms of nGD mainly focus on lysosomal dysfunction since the lysosome is the key organelle affected in GD. However, new studies show alterations in other organelles that contribute to nGD pathology. For instance, abnormal accumulation of GluCer in lysosomes due to the loss of β-GC activity leads to excessive calcium release from the endoplasmic reticulum (ER), activating the ER-associated degradation pathway and the unfolded protein response. Recent evidence indicates mitophagy is altered in nGD, resulting in the accumulation of dysfunctional mitochondria, a critical factor in disease progression. Additionally, nGD patients present alterations in mitochondrial morphology, membrane potential, ATP production, and increased reactive oxygen species (ROS) levels. Little is known about potential dysfunction in other organelles of the secretory pathway, such as the Golgi apparatus and exosomes. This review focuses on collecting evidence regarding organelle dysfunction beyond lysosomes in nGD. We briefly describe cellular and animal models and signaling pathways relevant to uncovering the pathological mechanisms and new therapeutic targets in GD.
Pitavastatin protects against neomycin-induced ototoxicity through inhibition of endoplasmic reticulum stress
Authors: Wu Yunhao , Meng Wei , Guan Ming , Zhao Xiaolong , Zhang Chen , Fang Qiaojun , Zhang Yuhua , Sun Zihui , Cai Mingjing , Huang Dongdong , Yang Xuechun , Yu Yafeng , Cui Yong , He Shuangba , Chai Renjie
Published: August 2022

Irreversible injury to inner ear hair cells induced by aminoglycoside antibiotics contributes to the formation of sensorineural hearing loss. Pitavastatin (PTV), a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, has been reported to exert neuroprotective effects. However, its role in aminoglycoside-induced hearing loss remains unknown. The objectives of this study were to investigate the beneficial effects, as well as the mechanism of action of PTV against neomycin-induced ototoxicity. We found that PTV remarkably reduced hair cell loss in mouse cochlear explants and promoted auditory HEI-OC1 cells survival after neomycin stimulation. We also observed that the auditory brainstem response threshold that was increased by neomycin was significantly reduced by pretreatment with PTV in mice. Furthermore, neomycin-induced endoplasmic reticulum stress in hair cells was attenuated by PTV treatment through inhibition of PERK/eIF2α/ATF4 signaling. Additionally, we found that PTV suppressed the RhoA/ROCK/JNK signal pathway, which was activated by neomycin stimulation in HEI-OC1 cells. Collectively, our results showed that PTV might serve as a promising therapeutic agent against aminoglycoside-induced ototoxicity.
Neural signals implicated in the processing of appetitive and aversive events in social and non-social contexts
Authors: Vázquez Daniela , Schneider Kevin N. , Roesch Matthew R.
Published: August 2022

In 2014, we participated in a special issue of Frontiers examining the neural processing of appetitive and aversive events. Specifically, we reviewed brain areas that contribute to the encoding of prediction errors and value versus salience, attention and motivation. Further, we described how we disambiguated these cognitive processes and their neural substrates by using paradigms that incorporate both appetitive and aversive stimuli. We described a circuit in which the orbitofrontal cortex (OFC) signals expected value and the basolateral amygdala (BLA) encodes the salience and valence of both appetitive and aversive events. This information is integrated by the nucleus accumbens (NAc) and dopaminergic (DA) signaling in order to generate prediction and prediction error signals, which guide decision-making and learning via the dorsal striatum (DS). Lastly, the anterior cingulate cortex (ACC) is monitoring actions and outcomes, and signals the need to engage attentional control in order to optimize behavioral output. Here, we expand upon this framework, and review our recent work in which within-task manipulations of both appetitive and aversive stimuli allow us to uncover the neural processes that contribute to the detection of outcomes delivered to a conspecific and behaviors in social contexts. Specifically, we discuss the involvement of single-unit firing in the ACC and DA signals in the NAc during the processing of appetitive and aversive events in both social and non-social contexts.
Anti-Migratory Effect of Dipotassium Glycyrrhizinate on Glioblastoma Cell Lines: Microarray Data for the Identification of Key MicroRNA Signatures
Authors: Bonafé Gabriel Alves , dos Santos Jéssica Silva , Fernandes Anna Maria Alves de Piloto , Ziegler Jussara Vaz , Marson Fernando Augusto Lima , Rocha Thalita , Carvalho Patricia de Oliveira , Ortega Manoela Marques
Published: August 2022

The nuclear factor kappa B (NF-κB) pathway has been reported to be responsible for the aggressive disease phenomenon observed in glioblastoma (GBM). Dipotassium glycyrrhizinate (DPG), a dipotassium salt of glycyrrhizic acid isolated from licorice, has recently demonstrated an anti-tumoral effect on GBM cell lines U87MG and T98G through NF-κB suppression by IRAK2- and TRAF6-mediating microRNA (miR)-16 and miR-146a, respectively. Thus, the present study aimed to evaluate the expression profiles of miRNAs related to NF-κB suppression in T98G GBM cell line after DPG exposure using miRNA microarray (Affymetrix Human miRNA 4.0A), considering only predicted miRNAs as NF-κB regulator genes. Additional assays using U251 and U138MG cells were performed to validate the array results. DPG cytotoxicity was determined by (4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, and cellular apoptosis was quantified by DNA fragmentation and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay. The anti-proliferative effect was observed by cell proliferation and wound-healing assays, and the sphere formation assay examined whether DPG reduced stem cell subpopulation formation. The most over-expressed miRNAs were miR-4443 and miR-3620. The cytotoxic effect of DPG in U251 and U138MG was observed with an IC50 of 32 and 20 mM for 48 h, respectively. The IC50 of each cell line was used in all further assays. DPG treatment-induced apoptosis is observed by DNA fragmentation and increased TUNEL-positive cells. Cell proliferation and wound-healing assays showed an anti-proliferative and anti-migratory effect by DPG on the evaluated cell lines. In addition, DPG treatment led to a 100% reduction in sphere formation. The qPCR results in U251 and U138MG cells showed that DPG increased miR-4443 (2.44 vs. 1.11, p-value = 0.11; 8.27 vs. 1.25, p-value = 0.04) and miR-3620 expression (1.66 vs. 1.00, p-value = 0.03; 8.47 vs. 1.01, p-value = 0.03) and decreased CD209 (0.44 vs. 1.10, p-value = 0.03; 0.49 vs. 1.07, p-value = 0.04) and TNC (0.20 vs. 1.03, p-value = 0.001; 0.39 vs. 1.06, p-value = 0.01) mRNA levels compared to controls. Our results suggest that DPG inhibits cell viability by activating apoptosis and inhibiting cell proliferation and stem cell subpopulation formation through miR-4443 and miR-3620 upregulation. Both miRNAs are responsible for the post-transcriptional inhibition of NF-κB by CD209 and TNC modulation.
Hyperprogressive disease in patients suffering from solid malignancies treated by immune checkpoint inhibitors: A systematic review and meta-analysis
Authors: Zhao Zijun , Bian Jin , Zhang Junwei , Zhang Ting , Lu Xin
Published: August 2022

Introduction

Hyperprogressive disease (HPD) is a paradoxically rapid disease progression during or shortly after antitumor treatment, especially immune checkpoint inhibitors (ICIs). Various diagnosis criteria of HPD cause heterogeneous incidence rates in different clinical research, and there is no consensus on potential risk factors associated with HPD occurrence. Hence, we aimed to summarize incidence of HPD in ICI treatment for solid tumors. Clinicopathological factors associated with HPD are also analyzed.

Methods

Clinical studies about HPD during/after ICI treatment of solid malignancies are included. Pubmed, Embase, and Cochrane library were searched for eligible studies published before October 7. The Newcastle–Ottawa scale was used to assess the quality of the included studies. Random effect and fixed effect models were, respectively, used for pooling incidence of HPD and analysis of risk factors for HPD. Heterogeneity, subgroup analysis, and publication bias were also analyzed. All meta-analysis was performed via R software (y -40v4.0.2).

Results

Forty-one studies with 6009 patients were included. The pooled incidence of HPD was 13.2% (95% CI, 11.2%–15.4%). Head and neck cancer (HNC) had the highest incidence of HPD (18.06%), and melanoma had the lowest (9.9%). Tumor types (P = .0248) and gender ratio (P = .0116) are sources of heterogeneity of pooled incidence of HPD. For five clinicopathological factors associated with HPD, only programmed cell death protein 1 ligand 1 (PD-L1) positivity was a preventive factor (odds ratio = 0.61, P <.05). High lactate dehydrogenase (LDH) level (OR = 1.51, P = .01), metastatic sites >2 (OR = 2.38, P <.0001), Eastern Cooperative Oncology Group Performance Score ≥2 (OR = 1.47, P = .02), and liver metastasis (OR = 3.06, P <.0001) indicate higher risk of HPD.

Conclusions

The pooled incidence of HPD was less than 15%, and HNC had the highest incidence of HPD. LDH and PD-L1 are remarkable biomarkers for prediction of HPD in future medical practice.
Hepatobiliary Phase Features of Preoperative Gadobenate-Enhanced MR can Predict Early Recurrence of Hepatocellular Carcinoma in Patients Who Underwent Anatomical Hepatectomy
Authors: Liu Wanmin , Song Kairong , Zheng Wei , Huo Lei , Zhang Sisi , Xu Xiaowen , Wang Peijun , Jia Ningyang
Published: August 2022

Purpose

The purpose of this study was to establish a model for predicting early recurrence (≤2 years) of hepatocellular carcinoma (HCC) after anatomical hepatectomy based on the hepatobiliary phase (HBP) imaging characteristics of gadobenate-enhanced MRI.

Methods

A total of 155 patients who underwent anatomical hepatectomy HCC therapy and gadobenate-enhanced MRI were included retrospectively. The patients were divided into the early recurrence-free group (n = 103) and the early recurrence group (n = 52). Univariate and multivariate Cox regression analysis was used to determine the independent risk factors related to early recurrence, and four models were established. The preoperative model with/without HBP imaging features (HBP-pre/No HBP-pre model) and the postoperative model with/without HBP imaging features (HBP-post/No HBP-post model). Bootstrap resampling 1,000 times was used to verify the model and displayed by nomograms. The performance of nomograms was evaluated by discrimination, calibration, and clinical utility. Net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were used to evaluate the differences between models and to select the optimal model.

Results

Shape, arterial peritumoral enhancement, AFP-L3, and peritumoral hypointensity on HBP were identified as independent risk factors. Prothrombin time (PT) and r-glutamyltransferase (GGT) were selected by multivariate Cox regression. These six factors construct the HBP-pre model. Removing peritumoral hypointensity on HBP was the No HBP-pre model. Adding microvascular invasion (MVI) and microscopic capsule factors were the HBP-post and No HBP-post model. The C-index was 0.766, 0.738, 0.770, and 0.742, respectively. The NRI and IDI of the HBP-pre vs. the No HBP-pre model and the HBP-post vs. the No HBP-post model significantly increased 0.258, 0.092, 0.280, and 0.086, respectively. The calibration curve and decision curve analysis (DCA) had good consistency and clinical utility. However, the NRI and IDI of the No HBP-post vs. the No HBP-pre model and the HBP-post vs. the HBP-pre model did not increase significantly.

Conclusions

Preoperative gadobenate-enhanced MR HBP imaging features significantly improve the model performance while the postoperative pathological factors do not. Therefore, the HBP-pre model is selected as the optimal model. The strong performance of this model may help hepatologists to assess the risk of recurrence in order to guide the selection of treatment options.
Associations of clinical and circulating metabolic biomarkers with low physical fitness and function in adults with chronic lymphocytic leukemia
Authors: Sitlinger Andrea , Deal Michael A. , Garcia Erwin , Connelly Margery , Thompson Dana , Stewart Tiffany , Macdonald Grace , Hanson Erik D. , Neely Megan , Neely Ben , Artese Ashley , Weinberg J. Brice , Brander Danielle , Bartlett David B.
Published: August 2022

Many patients with chronic lymphocytic leukemia (CLL) experience physical dysfunction and low overall fitness. It remains unknown what factors drive CLL physical dysfunction. We assessed physical function and metabolic lipoprotein panels in 106 patients with CLL. In univariate analyses of clinical factors, a longer time since diagnosis was associated with a higher likelihood of dysfunctional aerobic fitness (OR = 3.56, 95% CI: 1.37–9.22; p = 0.002) and physical performance (SPPB: OR = 2.03, 95% CI: 1.20–3.44; p = 0.004). Having received treatment was associated with a higher likelihood of dysfunctional aerobic fitness (OR = 1.57, 95% CI: 1.02–2.40; p = 0.036), SPPB (OR = 1.85, 95% CI: 1.13–3.03; p = 0.011) and grip strength (OR = 1.67, 95% CI: 1.10–2.55; p = 0.015). We found that several small HDL particle parameters, higher levels of citrate (OR = 2.01, 95% CI: 1.22–3.31; p = 0.030), and lower levels of hemoglobin (OR = 0.50, 95% CI: 0.31–0.82; p = 0.030) were associated with a higher likelihood of dysfunctional aerobic fitness. Multivariable least absolute shrinkage and selection operator (LASSO)-penalized regression analyses using variable importance measures (VIM) showed that 7.8-nm HDL particles (VIM = 1.000) and total HDL particle levels (VIM = 1.000) were more informative than clinical measures for the odds of dysfunctional aerobic fitness and 6-min walk functional fitness, respectively, while 10.3-nm HDL particles (VIM = 0.383) were more informative for grip strength. Time since diagnosis (VIM = 0.680) and having received treatment (VIM = 0.490) were more informative than lipoprotein measures for the odds of having dysfunctional SPPB. Taken together, we establish significant relationships between clinical and metabolic factors and physical characteristics that might prompt early use of ancillary support services.
Case Report: Upper limb dysfunction may be caused by chest wall mass excision: An enlightenment from a special case
Authors: Wu Ping-Shang , Yuan Ling , Xiong Dan , Gao Yan-Hong , Xiang Luan
Published: August 2022

Of all the thoracic surgical procedures, chest wall surgery is probably the lowest-risk type. In fact, it is not so. Clinical work also often has the trap of chest wall surgery. An operation to remove a mass in the axilla may result in upper limb disability on the affected side. Here, we report the case of a 47-year-old female patient with a left chest wall adjacent axillary mass, which was considered an abnormal structural lymph node on color ultrasound examination and chest CT. Otherwise, she felt no discomfort. The left upper limb moved freely without being affected by the mass. A routine resection of the tumor was performed after the preoperative examination was completed. After the operation, the incision recovered well. However, the day after the surgery, she developed numbness and pain in her left little finger and ring finger, pain that often kept her from sleeping. The mass was confirmed to be a schwannoma with cystic degeneration by pathology slicing after the operation. By this time, doctors were alerted to the fact that the removal of the chest wall mass had nearly disabled the left upper limb of the patient, which was a great warning to the thoracic surgeon. In this case report, we hope that all surgeons will be cautious and careful and will not trust the imaging diagnosis too much. It is also hoped that the patient understands that some procedures may lead to unexpected complications.
Molecular and cellular mechanisms underlying postoperative paralytic ileus by various immune cell types
Authors: Sui Chao , Tao Liang , Bai Chunhua , Shao Lihua , Miao Ji , Chen Kai , Wang Meng , Hu Qiongyuan , Wang Feng
Published: August 2022

Postoperative ileus (POI) is a well-known complication following gut manipulation or surgical trauma, leading to an impaired gut motility and prolonged postoperative recovery time. Few current therapeutic strategies can prevent POI, and this disorder remains to be a major clinical challenge for patients undergoing surgery. Comprehensive understanding of cellular and molecular mechanisms related to the pathogenesis of POI stimulates the discovery of more promising targets for treatment. POI is closely associated with a series of inflammatory events within the bowel wall, and as key components of inflammatory mechanisms, different types of immune cells, including macrophages, dendritic cells, and T lymphocytes, play significant roles during the development of POI. A variety of immune cells are recruited into the manipulation sites after surgery, contributing to early inflammatory events or impaired gut motility. Our review intends to summarize the specific relationship between different immune cells and POI, mainly focusing on the relevant mechanisms underlying this disorder.
Inferring Insulin Secretion Rate from Sparse Patient Glucose and Insulin Measures
Authors: Abohtyra Rammah M. , Chan Christine L. , Albers David J. , Gluckman Bruce J.
Published: August 2022

The insulin secretion rate (ISR) contains information that can provide a personal, quantitative understanding of endocrine function. If the ISR can be reliably inferred from measurements, it could be used for understanding and clinically diagnosing problems with the glucose regulation system.

Objective: This study aims to develop a model-based method for inferring a parametrization of the ISR and related physiological information among people with different glycemic conditions in a robust manner. The developed algorithm is applicable for both dense or sparsely sampled plasma glucose/insulin measurements, where sparseness is defined in terms of sampling time with respect to the fastest time scale of the dynamics.

Methods:An algorithm for parametrizing and validating a functional form of the ISR for different compartmental models with unknown but estimable ISR function and absorption/decay rates describing the dynamics of insulin accumulation was developed. The method and modeling applies equally to c-peptide secretion rate (CSR) when c-peptide is measured. Accuracy of fit is reliant on reconstruction error of the measured trajectories, and when c-peptide is measured the relationship between CSR and ISR. The algorithm was applied to data from 17 subjects with normal glucose regulatory systems and 9 subjects with cystic fibrosis related diabetes (CFRD) in which glucose, insulin and c-peptide were measured in course of oral glucose tolerance tests (OGTT).

Results:This model-based algorithm inferred parametrization of the ISR and CSR functional with relatively low reconstruction error for 12 of 17 control and 7 of 9 CFRD subjects. We demonstrate that when there are suspect measurements points, the validity of excluding them may be interrogated with this method.

Significance:A new estimation method is available to infer the ISR and CSR functional profile along with plasma insulin and c-peptide absorption rates from sparse measurements of insulin, c-peptide, and plasma glucose concentrations. We propose a method to interrogate and exclude potentially erroneous OGTT measurement points based on reconstruction errors.
Genome wide identification of lncRNAs and circRNAs having regulatory role in fruit shelf life in health crop cucumber (Cucumis sativus L.)
Authors: Dey Shyam S. , Sharma Parva Kumar , Munshi A. D. , Jaiswal Sarika , Behera T. K. , Kumari Khushboo , G. Boopalakrishnan , Iquebal Mir Asif , Bhattacharya R. C. , Rai Anil , Kumar Dinesh
Published: August 2022

Cucumber is an extremely perishable vegetable; however, under room conditions, the fruits become unfit for consumption 2–3 days after harvesting. One natural variant, DC-48 with an extended shelf-life was identified, fruits of which can be stored up to 10–15 days under room temperature. The genes involved in this economically important trait are regulated by non-coding RNAs. The study aims to identify the long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) by taking two contrasting genotypes, DC-48 and DC-83, at two different fruit developmental stages. The upper epidermis of the fruits was collected at 5 days and 10 days after pollination (DAP) for high throughput RNA sequencing. The differential expression analysis was performed to identify differentially expressed (DE) lncRNAs and circRNAs along with the network analysis of lncRNA, miRNA, circRNA, and mRNA interactions. A total of 97 DElncRNAs were identified where 18 were common under both the developmental stages (8 down regulated and 10 upregulated). Based on the back-spliced reads, 238 circRNAs were found to be distributed uniformly throughout the cucumber genomes with the highest numbers (71) in chromosome 4. The majority of the circRNAs (49%) were exonic in origin followed by inter-genic (47%) and intronic (4%) origin. The genes related to fruit firmness, namely, polygalacturonase, expansin, pectate lyase, and xyloglucan glycosyltransferase were present in the target sites and co-localized networks indicating the role of the lncRNA and circRNAs in their regulation. Genes related to fruit ripening, namely, trehalose-6-phosphate synthase, squamosa promoter binding protein, WRKY domain transcription factors, MADS box proteins, abscisic stress ripening inhibitors, and different classes of heat shock proteins (HSPs) were also found to be regulated by the identified lncRNA and circRNAs. Besides, ethylene biosynthesis and chlorophyll metabolisms were also found to be regulated by DElncRNAs and circRNAs. A total of 17 transcripts were also successfully validated through RT PCR data. These results would help the breeders to identify the complex molecular network and regulatory role of the lncRNAs and circRNAs in determining the shelf-life of cucumbers.
Estimation of amino acid contents in maize leaves based on hyperspectral imaging
Authors: Shu Meiyan , Zhou Long , Chen Haochong , Wang Xiqing , Meng Lei , Ma Yuntao
Published: August 2022

Estimation of the amino acid content in maize leaves is helpful for improving maize yield estimation and nitrogen use efficiency. Hyperspectral imaging can be used to obtain the physiological and biochemical parameters of maize leaves with the advantages of being rapid, non-destructive, and high throughput. This study aims to estimate the multiple amino acid contents in maize leaves using hyperspectral imaging data. Two nitrogen (N) fertilizer experiments were carried out to obtain the hyperspectral images of fresh maize leaves. The partial least squares regression (PLSR) method was used to build the estimation models of various amino acid contents by using the reflectance of all bands, sensitive band range, and sensitive bands. The models were then validated with the independent dataset. The results showed that (1) the spectral reflectance of most amino acids was more sensitive in the range of 400–717.08 nm than other bands. The estimation accuracy was better by using the reflectance of the sensitive band range than that of all bands; (2) the sensitive bands of most amino acids were in the ranges of 505.39–605 nm and 651–714 nm; and (3) among the 24 amino acids, the estimation models of the β-aminobutyric acid, ornithine, citrulline, methionine, and histidine achieved higher accuracy than those of other amino acids, with the R2, relative root mean square error (RE), and relative percent deviation (RPD) of the measured and estimated value of testing samples in the range of 0.84–0.96, 8.79%–19.77%, and 2.58–5.18, respectively. This study can provide a non-destructive and rapid diagnostic method for genetic sensitive analysis and variety improvement of maize.