bluuebunny/crossref_metadata_2025 huggingface dataset:
An EMT-Related Gene Signature for Predicting Response to Adjuvant Chemotherapy in Pancreatic Ductal Adenocarcinoma
Authors: Feng Zengyu , Li Kexian , Lou Jianyao , Wu Yulian , Peng Chenghong
Published: April 2021

Background

For pancreatic ductal adenocarcinoma (PDAC) patients, chemotherapy failure is the major reason for postoperative recurrence and poor outcomes. Establishment of novel biomarkers and models for predicting chemotherapeutic efficacy may provide survival benefits by tailoring treatments.

Methods

Univariate cox regression analysis was employed to identify EMT-related genes with prognostic potential for DFS. These genes were subsequently submitted to LASSO regression analysis and multivariate cox regression analysis to identify an optimal gene signature in TCGA training cohort. The predictive accuracy was assessed by Kaplan–Meier (K-M), receiver operating characteristic (ROC) and calibration curves and was validated in PACA-CA cohort and our local cohort. Pathway enrichment and function annotation analyses were conducted to illuminate the biological implication of this risk signature.

Results

LASSO and multivariate Cox regression analyses selected an 8-gene signature comprised DLX2, FGF9, IL6R, ITGB6, MYC, LGR5, S100A2, and TNFSF12. The signature had the capability to classify PDAC patients with different DFS, both in the training and validation cohorts. It provided improved DFS prediction compared with clinical indicators. This signature was associated with several cancer-related pathways. In addition, the signature could also predict the response to immune-checkpoint inhibitors (ICIs)-based immunotherapy.

Conclusion

We established a novel EMT-related gene signature that was capable of predicting therapeutic response to adjuvant chemotherapy and immunotherapy. This signature might facilitate individualized treatment and appropriate management of PDAC patients.
Modulating the Inflammatory Response to Wounds and Cancer Through Infection
Authors: López-Cuevas Paco , Cross Stephen J. , Martin Paul
Published: April 2021

The zebrafish (Danio rerio) has recently emerged as an excellent model to study cancer biology and the tumour microenvironment, including the early inflammatory response to both wounding and early cancer growth. Here, we use high-resolution confocal imaging of translucent zebrafish larvae, with novel automated tracking and cell:cell interaction software, to investigate how innate immune cells behave and interact with repairing wounds and early cancer (pre-neoplastic) cells expressing a mutant active human oncogene (HRASG12V). We show that bacterial infections, delivered either systemically or locally, induce a change in the number and behaviour of neutrophils and macrophages recruited to acute wounds and to pre-neoplastic cells, and that infection can modify cellular interactions in ways that lead to a significant delay in wound healing and a reduction in the number of pre-neoplastic cells. Besides offering insights as to how Coley’s toxins and other cancer bacteriotherapies may function to reduce cancer burden, our study also highlights novel software tools that can be easily adapted to investigate cellular behaviours and interactions in other zebrafish models.
Application of MALDI-TOF MS Profiling Coupled With Functionalized Magnetic Enrichment for Rapid Identification of Pathogens in a Patient With Open Fracture
Authors: Ying Jichong , Gao Wenjing , Huang Dichao , Ding Chuanfan , Ling Ling , Pan Tao , Yu Shaoning
Published: April 2021

Posttraumatic infections can occur in orthopedic trauma patients, especially in open fractures. Rapid and accurate identification of pathogens in orthopedic trauma is important for clinical diagnosis and antimicrobial treatment. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) has been successfully used for first-line identification of pathogens grown on culture plates. However, for direct analysis of liquid clinical specimens, pre-purification of the sample is necessary. Herein, we investigated the feasibility of coupling Fc-MBL@Fe3O4 enrichment with MALDI-TOF MS profiling in the identification of pathogens in liquid-cultured samples. This method is successfully used for the identification of pathogens in a patient with an open-leg fracture obtained at sea. Pathogens were enriched by Fc-MBL@Fe3O4 from briefly pre-cultured liquid media and identified by MALDI-TOF MS. We identified an opportunistic pathogen, Vibrio alginolyticus, which is uncommon in clinical orthopedic trauma infection but exists widely in the sea. Therefore, combining Fc-MBL@Fe3O4 enrichment and MALDI-TOF MS profiling has great potential for direct identification of microbes in clinical samples.
Protein-Inorganic Hybrid Nanoflowers as Efficient Biomimetic Antibiotics in the Treatment of Bacterial Infection
Authors: Zhou Ying , Li Ying , Fei Yunwei , Zhang Mingrui , Wang Shuang , Li Fuqiu , Bao Xingfu
Published: April 2021

Nanozymes have been developed as new generation of biomimetic antibiotics against wound infection. However, most of new-developed nanozymes based on inorganic particles or hybrid ones usually originate from incompatible raw materials or unwanted metal salts, highly limiting their further biomedical usages. To overcome above drawbacks, it is highly required to develop novel nanozymes with great antibacterial activity by using biocompatible reagents and endogenous metal species as raw materials. Here, we demonstrated that bovine serum albumin enwrapped copper phosphate-based protein-inorganic hybrid nanoflowers possessed intrinsic peroxidase-like activity, which could be used as efficient biomimetic antibiotics against bacterial infection via the nanozyme-mediated generation of high toxic reactive oxygen species (ROS). With the admirable peroxidase-like activity, our nanoflowers could efficiently kill drug-resistance bacteria under physiological conditions, improve the wound healing after pathogen-induced infection, as well as avoid the potential tissue injury in time. Comprehensive toxicity exploration of these nanoflowers indicated their high biocompatibility and excellent biosafety. Our current strategy toward the design of protein-inorganic hybrid nanozymes with high biosafety and few side effects could provide a new paradigm for the development of nanozyme-based antibacterial platform in future.
High-Throughput Absolute Quantification Sequencing Revealed Osteoporosis-Related Gut Microbiota Alterations in Han Chinese Elderly
Authors: Wei Muhong , Li Can , Dai Yu , Zhou Haolong , Cui Yuan , Zeng Yun , Huang Qin , Wang Qi
Published: April 2021

Objective

Accumulative evidence suggests that gut microbiota play an important role in bone remodeling and hence bone health maintenance. This study aimed to explore the association of gut microbiota with the risk of osteoporosis and to identify potential disease-related taxa, which may be promising targets in osteoporosis prevention and treatment in the future.

Methods

Absolute quantification 16S ribosomal RNA gene sequencing was used to detect absolute and relative abundances of gut microbiota in 44 patients with osteoporosis and 64 controls. In combination with one of our previous studies, a total of 175 samples were involved in the relative abundance analysis.

Results

Compared with the controls, the patients with osteoporosis had higher absolute and relative abundances of Bacteroidetes phylum, and Bacteroides and Eisenbergiella genera. The absolute abundances of Clostridium_XlVa, Coprococcus, Lactobacillus, and Eggerthella genera increased, and that of the Veillonella genus decreased in the osteoporosis group. As for relative abundance, that of the Parabacteroides and Flavonifractor genera increased, whereas that of the Raoultella genus decreased in the osteoporosis group. Controlling for potential confounders, the associations of Clostridium_XlVa, Coprococcus, and Veillonella genera with the risk of osteoporosis did not maintain significance. Ridge regression analysis suggested that Bacteroides is associated with reduced bone mineral density (BMD) and T-score at lumbar spines, and Anaerovorax is associated with increased BMD at the femoral neck. Functional predictions revealed that 10 Kyoto Encyclopedia of Genes and Genomes pathways were enriched in the osteoporosis group.

Conclusions

Gut microbiota compositions may contribute to the risk of osteoporosis. Several specific taxa and functional pathways are identified to associate with reduced bone density, thus providing epidemiologic evidence for the potential role of aberrant gut microbiota in osteoporosis pathogenesis.
Detection and Numerical Simulation of Potential Hazard in Oil Pipeline Areas Based on UAV Surveys
Authors: Yan Yan , Ma Shuyue , Yin Shuyao , Hu Sheng , Long Yongqing , Xie Cheng , Jiang Hongtao
Published: April 2021

Western China is rich in oil and gas resources, and many oil and gas pipelines are under construction or have been completed. However, many water-related natural hazards, such as landslides, collapses, rockfalls, and debris flows, have developed in the areas passed through by oil and gas pipelines and seriously threaten the operational safety of these pipelines. Therefore, it is urgent to carry out large-scale identification and assessment of pipeline geological hazards. At present, conventional on-site investigation, evaluation, monitoring, and early warning methods are difficult to apply for rapid identification and evaluation of pipeline geological hazards across large-scale areas. Based on this, this study takes the pipeline of Sinopec Marketing South China Branch in Yunnan Province as the research area. In this research, unmanned aerial vehicle (UAV) and photogrammetry technology were used to quickly and accurately obtain multi-phase images of an oil pipeline passing through the study area, and the images were post-processed to obtain multi-phase high-resolution, high-precision digital orthophoto maps and digital terrain models (DTMs) to identify landform changes and deformation. The focus of this research is to propose a set of technical methods for UAV point cloud filtering. The DTMs obtained based on this method can effectively identify unstable areas of oil pipelines. In addition, we have carried out numerical simulations under different motion scenarios in unstable regions, providing scientific support for future geological hazard prevention and mitigation and engineering practices in oil pipeline areas.
IgG4-Related Inflammatory Pseudotumor Involving the Clivus: A Case Report and Literature Review
Authors: Liu Xiaohai , Wang Renzhi , Li Mingchu , Chen Ge
Published: April 2021

IgG4-related inflammatory pseudotumors are very uncommon and are characterized histologically by the presence of inflammatory swellings with increasing IgG4-positive plasma cells and lymphocytes infiltrating the tissues. As reports of intracranial IgG4-related pseudotumors are very rare, we report a case of an IgG4-related inflammatory pseudotumor involving the clivus mimicking meningioma. A 46-year-old male presented with intermittent headache for 2 years and a sudden onset of dysphagia and dysphonia of 7 days’ duration along with lower limb weakness. Enhanced magnetic resonance imaging (MRI) of the skull base revealed an isointense signal on T1- and T2-weighted images from an enhanced mass located at the middle of the upper clivus region, for which a meningioma was highly suspected. Then, an endoscopic transsphenoidal approach was adopted and the lesion was partially resected, as the subdural extra-axial lesion was found to be very tough and firm, exhibiting fibrous scarring attaching to the brain stem and basal artery. After the surgery, brain stem and posterior cranial nerve decompression was achieved, and the patient’s symptoms, such as dysphagia, dysphonia and lower limb weakness, improved. Pathological findings showed many IgG4-positive plasma cells and lymphocytes surrounded by collagen-rich fibers. The patient was sent to the rheumatology department for further glucocorticoids after the diagnosis of an IgG4-related inflammatory pseudotumor was made. This case highlights the importance of considering IgG4-related inflammatory pseudotumors as a differential diagnosis in patients with lesions involving the clivus presenting with a sudden onset of symptoms of dysphagia and dysphonia along with lower limb weakness when other more threatening causes have been excluded. IgG4-related inflammatory pseudotumors are etiologically enigmatic and unpredictable, and total resection might not be warranted. Glucocorticoids are usually the first line of treatment after diagnosis.
Does Anti-corruption Policy Influence Energy Efficiency in China?
Authors: Liu Jie , Guo Jianming , Liu Xiangfeng , Bai Xiao , Taghizadeh-Hesary Farhad
Published: April 2021

The Chinese government has stepped up its anti-corruption efforts since 2013; the National Energy Administration (NEA), an energy regulatory agency, has been hard hit by corruption. This paper analyzes the impact of government corruption on energy efficiency (EE) from a perspective of energy regulations and also a mechanism of the impact of corruption on EE, and then adopts statistical methods to estimate the impact of corruption on EE in China. The results show that government corruption generally has a negative effect on EE in China. The establishment of dispatched energy regulatory agencies in eastern China can significantly reduce the adverse effects of corruption on EE. Furthermore, a single threshold effect was found between corruption and EE. Finally, based on the results of an empirical analysis, suggestions for a constructive policy are put forward.
Carbon Emission and Endogenous Growth Between Two Economic Systems
Authors: Sun Peng , Li Shijie , Zhou Kechong
Published: April 2021

In recent years, many scholars have shown an increasing interest in the problem of pollution (carbon emission) in the endogenous growth but less concern about the interactions of polluting activities between two economy systems. This study explains the effects of carbon emission on the optimal balanced growth path by establishing an endogenous growth model involving exhaustible resources, human capital, physical capital, and labor time under one economy and a similar system involving two economic systems. The second system is used to analyze the interactions of polluting activities across the two economic systems that it covers. The results show that the negative externality (carbon emission) caused by one economy will bring remarkable adverse impacts on the optimal resource extraction and growth rates of other economies. If the people in one economy pay greater attention to the environmental problem (carbon emission), its own resource input will be lowered to reduce carbon emissions, but carbon emissions of another economy will be increased simultaneously to accelerate the economic growth. That is why carbon emission is one of the most challenging issues in global governance. Therefore, the global environmental pollution control needs the help of the cross-regional governance mechanism.
Retrieval of Dust Properties From Spectral Snow Reflectance Measurements
Authors: Kokhanovsky Alexander , Di Mauro Biagio , Garzonio Roberto , Colombo Roberto
Published: April 2021

In this paper, we present a simplified algorithm to retrieve snow grain size, dust mass absorption coefficient and dust mass concentration from spectral diffuse reflectance measurements at three wavelengths located in the visible and near infrared. The theoretical model is then compared with field spectroscopy data collected in different days from an automated spectrometer in the Alps.
Development and First Tests of a Lab-Scale Electric Field for Investigating Potential Effects of Electric Barriers on Aquatic Invasive Invertebrates
Authors: Egly Rachel M. , Polak Robert D. , Cook Zalia A. , Moy Harrison D. , Staunton Jonathon T. , Keller Reuben P.
Published: April 2021

Canals and other connected waterway systems, including the Chicago Area Waterway System (CAWS), have often facilitated the spread of non-native species. Electric barriers have recently emerged as a method for preventing this spread and protecting uninvaded ecosystems from new invaders. The largest system of electric barriers in the world is in the CAWS and is operated primarily to prevent the spread of invasive Asian carp. It is not known whether these barriers are effective for other species, particularly invasive invertebrates. Here, we provide data regarding the efficacy of an electric field that operates at the same parameters as the electric barrier in the CAWS in affecting behaviors of two invertebrate species, the red swamp crayfish Procambarus clarkii and the amphipod Hyalella azteca. We constructed an electric field within a tank that operates at the same parameters as the existing CAWS barriers and determined the effects of the electric field on our test species. At the electric field parameters of the CAWS barriers, the vast majority of P. clarkii individuals showed altered movement with maintained equilibrium. For H. azteca, behavioral responses were less extreme than for P. clarkii, with a majority of individuals experiencing altered movement. By measuring the orientation of organisms to the electric field, we determined that the test organisms are affected by the electric field, especially at lower field strengths where they exhibited no or little other behavioral response. At lower field strengths, P. clarkii exhibited changes in orientation, but at higher field strengths, individuals were less able to orient themselves. H. azteca exhibited changes in orientation to the electric field at all field strengths. The results of this study suggest that the existing electric barriers may not slow or prevent spread of invasive invertebrates—including amphipods and crayfish—through passive movement attached boats/barges or through downstream drift, but that the barriers may prevent spread by active upstream movement. Overall, our work gives new data regarding the efficacy of electric fields in preventing the spread of invasive invertebrates and can inform management decisions regarding current and future electric barriers in the CAWS.
Feeding Ecology of Elusive Caribbean Killer Whales Inferred From Bayesian Stable Isotope Mixing Models and Whalers’ Ecological Knowledge
Authors: Kiszka Jeremy J. , Caputo Michelle , Méndez-Fernandez Paula , Fielding Russell
Published: April 2021

Investigating the feeding ecology of marine predators is critical for understanding their roles and functional importance in ecosystems. However, assessing the diet of large and wide-ranging predators can be challenging, particularly in the case of rare and elusive species. Killer whales (Orcinus orca) are large apex predators in global oceans, but very little is known about their feeding ecology in tropical ecosystems, particularly in the Caribbean Sea. Killer whales are distributed throughout the Caribbean, and are a regular target of artisanal whalers in St. Vincent and the Grenadines (West Indies). Here we investigate the feeding ecology of Caribbean killer whales using a combination of stable isotope analysis (δ15N, δ13C) and traditional ecological knowledge (TEK) data from whalers operating from St. Vincent. Potential prey data from the Caribbean region included large pelagic teleosts, sea turtles, oceanic sharks, cetaceans, and oceanic cephalopods. Mixing models suggest that the contribution of odontocete cetaceans to the diet of killer whales is the most important (overall mean contribution: 60.4%), particularly mesopelagic delphinids (Lagenodelphis hosei; 26.4%, SD = 0.14), large teuthophageous odontocetes (Physeter macrocephalus,Globicephala macrorhynchus; 20.0%, SD = 0.14), and epipelagic delphinids (Stenella attenuata; 14%, SD = 0.14). Oceanic sharks (Carcharhinus longimanus) had a contribution of 17.0% of the diet of killer whales (SD = 0.13), and other potential prey had a relatively marginal contribution. TEK data suggest that whalers believe killer whales feed almost exclusively on cetaceans, particularly odontocete species that they hunt (e.g.,G. macrorhynchus). Stable isotope and TEK data were consistent to some extent, although TEK data are qualitative and based on a limited number of observations. Despite some limitations (including sample size for both methods), this study highlights the value of combining independent data sources and methodologies to investigate the ecological roles of marine predators in data-poor regions.
Modeling the Exposure of the Macaronesia Islands (NE Atlantic) to Marine Plastic Pollution
Authors: Cardoso Cláudio , Caldeira Rui M. A.
Published: April 2021

The constant increase of marine plastic pollution poses an unprecedented risk to oceanic islands, which become increasingly exposed to a hazard of which they have very little control. Located in the Northeast Atlantic Ocean, the Macaronesia is comprised by the Azores, Madeira, Canary Islands, and Cabo Verde. Although past studies suggest that most plastic items collected on these islands are from offshore regions, their actual sources remain unclear to present date. As such, we focus on the characterization of the potential sources and pathways of plastic particles reaching the Macaronesia archipelagos. This is achieved by combining modeled datasets for ocean currents, winds and waves with a Lagrangian tool used to track virtual particles released around the archipelagos for a 10-year period, making a distinction between surface and submerged particles. Global drifter trajectories are also assessed, selecting those that intercept the archipelagos. Our results demonstrate that the North Atlantic subtropical gyre is the most conspicuous feature in particles and drifter trajectories. The Gulf Stream acts as the main pathway for all archipelagos at a regional scale, though with less significance to Cabo Verde. Surface particles are connected to regional sources in a shorter timescale than mixed particles, mainly because of the wind. Intercepting high-windage particle trajectories are dominant at the center of the North Atlantic subtropical gyre, demonstrating that particles originating from the North Atlantic “garbage patch” are most likely to intercept the archipelagos if considerably exposed to the wind. Regarding the connectivity to sources, all archipelagos are significantly exposed to areas of intensive fishing activity, mainly those located in the Gulf Stream (Azores), in international waters off the Portuguese coast (Madeira and Canary Islands) and along the Northwestern African coast (Cabo Verde). The east coasts of Central and North America are the main sources of land-based particles reaching the Azores, Madeira, and Canary Islands, whereas the Northwestern African coast is the main source for land-based particles reaching Cabo Verde. Our results demonstrate how vulnerable the Macaronesian archipelagos are to marine plastic pollution, highlighting the urgency for international cooperation to mitigate the exposure of oceanic islands to marine plastic pollution.
Near-Infrared Spectroscopy Assessment of Tissue Oxygenation During Selective Cerebral Perfusion for Neonatal Aortic Arch Reconstruction
Authors: Huang Chi-Hsiang , Wang Yi-Chia , Chou Hen-Wen , Huang Shu-Chien
Published: April 2021

Objective: Optimal selective cerebral perfusion (SCP) management for neonatal aortic arch surgery has not been extensively studied. We induced mild hypothermia during SCP and used the tissue oxygenation monitor to ensure adequate perfusion during the cardiopulmonary bypass (CPB).

Methods: Eight cases were recruited from September 2018 to April 2020. SCP was maintained at 30°C, and CPB was adjusted to achieve a mean right radial artery pressure of 30 mmHg. The near-infrared tissue saturation (NIRS) monitor was applied to assess the right and left brain, flank, and lower extremity during the surgery.

Results: During surgery, the mean age was 4.75 days, the mean body weight was 2.92 kg, the CPB duration was 86.5 ±18.7 min, the aortic cross-clamp time was 46.1 ± 12.7 min, and the SCP duration was 14.6±3.4 min. The brain NIRS before, during, and after SCP was 64.2, 67.2, and 71.5 on the left side and 67.9, 66.2, and 70.1 on the right side (p = NS), respectively. However, renal and lower extremity tissue oxygenation, respectively decreased from 61.6 and 62.4 before SCP to 37.7 and 39.9 after SCP (p < 0.05) and then increased to 70.1 and 90.4 after full body flow resumed. No stroke was reported postoperatively.

Conclusion: SCP under mild hypothermia can aid in efficient maintenance of brain perfusion during neonatal arch reconstruction. The clinical outcome of this strategy was favorable for up to 20 min, but the safety duration of lower body ischemia warrants further analysis.
Recent Updates on the Involvement of PI3K/AKT/mTOR Molecular Cascade in the Pathogenesis of Hyperproliferative Skin Disorders
Authors: Mercurio Laura , Albanesi Cristina , Madonna Stefania
Published: April 2021

PhosphoInositide-3 Kinase (PI3K) represents a family of different classes of kinases which control multiple biological processes in mammalian cells, such as cell growth, proliferation, and survival. Class IA PI3Ks, the main regulators of proliferative signals, consists of a catalytic subunit (α, β, δ) that binds p85 regulatory subunit and mediates activation of AKT and mammalian Target Of Rapamycin (mTOR) pathways and regulation of downstream effectors. Dysregulation of PI3K/AKT/mTOR pathway in skin contributes to several pathological conditions characterized by uncontrolled proliferation, including skin cancers, psoriasis, and atopic dermatitis (AD). Among cutaneous cancers, basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC) display PI3K/AKT/mTOR signaling hyperactivation, implicated in hyperproliferation, and tumorigenesis, as well as in resistance to apoptosis. Upregulation of mTOR signaling proteins has also been reported in psoriasis, in association with enhanced proliferation, defective keratinocyte differentiation, senescence-like growth arrest, and resistance to apoptosis, accounting for major parts of the overall disease phenotypes. On the contrary, PI3K/AKT/mTOR role in AD is less characterized, even though recent evidence demonstrates the relevant function for mTOR pathway in the regulation of epidermal barrier formation and stratification. In this review, we provide the most recent updates on the role and function of PI3K/AKT/mTOR molecular axis in the pathogenesis of different hyperproliferative skin disorders, and highlights on the current status of preclinical and clinical studies on PI3K-targeted therapies.
A Single Mutation in the Outer Lipid-Facing Helix of a Pentameric Ligand-Gated Ion Channel Affects Channel Function Through a Radially-Propagating Mechanism
Authors: Crnjar Alessandro , Mesoy Susanne M. , Lummis Sarah C. R. , Molteni Carla
Published: April 2021

Pentameric ligand-gated ion channels (pLGICs) mediate fast synaptic transmission and are crucial drug targets. Their gating mechanism is triggered by ligand binding in the extracellular domain that culminates in the opening of a hydrophobic gate in the transmembrane domain. This domain is made of four α-helices (M1 to M4). Recently the outer lipid-facing helix (M4) has been shown to be key to receptor function, however its role in channel opening is still poorly understood. It could act through its neighboring helices (M1/M3), or via the M4 tip interacting with the pivotal Cys-loop in the extracellular domain. Mutation of a single M4 tyrosine (Y441) to alanine renders one pLGIC—the 5-HT3A receptor—unable to function despite robust ligand binding. Using Y441A as a proxy for M4 function, we here predict likely paths of Y441 action using molecular dynamics, and test these predictions with functional assays of mutant receptors in HEK cells and Xenopus oocytes using fluorescent membrane potential sensitive dye and two-electrode voltage clamp respectively. We show that Y441 does not act via the M4 tip or Cys-loop, but instead connects radially through M1 to a residue near the ion channel hydrophobic gate on the pore-lining helix M2. This demonstrates the active role of the M4 helix in channel opening.
LINC02257, an Enhancer RNA of Prognostic Value in Colon Adenocarcinoma, Correlates With Multi-Omics Immunotherapy-Related Analysis in 33 Cancers
Authors: Xiao Junbo , Liu Yajun , Yi Jun , Liu Xiaowei
Published: April 2021

Accumulated evidence supports that long non-coding RNAs (lncRNAs) are involved significantly in the development of human cancers. Enhancer RNAs (eRNAs), a subtype of lncRNAs, have recently attracted much attention about their roles in carcinogenesis. Colon adenocarcinoma is one of the most commonly diagnosed tumors with unfavorable prognosis. It highlights the great significance of screening and identifying novel biomarkers. More importantly, it remains to be elucidated with respect to the function of eRNAs in colon adenocarcinoma, as is in pan-cancers. The expression of LINC02257 was determined based on the data obtained from The Cancer Genome Atlas (TCGA). Further evaluation was performed on the basis of the following analyses: clinicopathology and survival analysis, gene ontology (GO) terms, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, as well as multi-omics immunotherapy-related analysis and co-expression analysis. The statistical analysis was conducted in R software, and immune cell infiltration of LINC02257 expression in cancers was investigated by using the CIBERSORT algorithm. By large-scale data mining, our study highlighted that a total of 39 eRNA genes were associated with colon adenocarcinoma prognosis, among which 25 eRNAs showed significant associations with their predicted target genes. LINC02257 was identified as the most significant survival-associated eRNA, with DUSP10 as its target gene. Besides, the high expression of LINC02257 in colon adenocarcinoma was more vulnerable to unfavorable prognosis and correlated with various clinical characteristics. GO and KEGG analyses revealed that LINC02257 was closely correlated with extracellular matrix organization via the PI3K-Akt signaling pathway. Besides, LINC02257 expression correlated with a multi-omics analysis of 33 cancer types, such as survival analysis [overall survival (OS), disease-specific survival (DSS), disease-free interval (DFI), and progression-free interval (PFI)] and immunotherapy-related analysis [tumor microenvironment (TME), tumor mutational burden (TMB), and microsatellite instability (MSI)]. Finally, we investigated the co-expression genes of LINC02257 and its potential signaling pathways across different cancer types. LINC02257 is screened and can function as an independent prognostic biomarker through the PI3K-Akt signaling pathway for colon adenocarcinoma. Simultaneously, LINC02257 may be a multifaceted and significant immunotherapy-related eRNA in different cancers.
Delirium: A Marker of Vulnerability in Older People
Authors: Bellelli Giuseppe , Brathwaite Justin S. , Mazzola Paolo
Published: April 2021

Delirium is an acute neuropsychiatric syndrome and one of the most common presenting symptoms of acute medical illnesses in older people. Delirium can be triggered by a single cause, but in most cases, it is multifactorial as it depends on the interaction between predisposing and precipitating factors. Delirium is highly prevalent in older patients across various settings of care and correlates with an increased risk of adverse clinical outcomes. Several pathophysiological mechanisms may contribute to its onset, including neurotransmitter imbalance, neuroinflammation, altered brain metabolism, and impaired neuronal network connectivity. Several screening and diagnostic tools for delirium exist, but they are unfortunately underutilized. Additionally, the diagnosis of delirium superimposed on dementia poses a formidable challenge – especially if dementia is severe. Non-pharmacological approaches for the prevention and multidomain interventions for the treatment of delirium are recommended, given that there is currently no robust evidence of drugs that can prevent or resolve delirium. This article aims to review the current understanding about delirium in older people. To achieve this goal, we will describe the epidemiology and outcomes of the syndrome, the pathophysiological mechanisms that are supposed to be involved, the most commonly used tools for screening and diagnosis, and prevention strategies and treatments recommended. This review is intended as a brief guide for clinicians in hospital wards to improve their knowledge and practice. At the end of the article, we propose an approach to improve the quality of care provided to older patients throughout a systematic detection of delirium.
Case Report: Behavioral Unresponsiveness in Acute COVID-19 Patients: The Utility of the Motor Behavior Tool-Revised and 18F-FDG PET/CT
Authors: Vijiala Sergiu , Epiney Jean-Benoît , Jöhr Jane , Pincherle Alessandro , Meyer Marie M. , Du Pasquier Renaud , Prior John O. , Diserens Karin
Published: April 2021

Along with the propagation of COVID-19, emerging evidence reveals significant neurological manifestations in severely infected COVID-19 patients. Among these patients admitted to the intensive care unit (ICU), behavioral unresponsiveness may occur frequently, yet, there are still only a few cases reported and with rare descriptions of their motor behavior after pathological awakening. Several hypotheses regarding central lesions in these patients are conceivable. Here, we describe two acute SARS-CoV-2- infected patients who developed neurological symptoms evoking the condition of clinical cognitive motor dissociation (CMD). This diagnosis could be confirmed first by clinical observation of a dissociation between preserved cognitive abilities and lack of initial motor interaction and second, by performing 18F- FDG PET imaging. Accurate diagnosis led to an appropriate neuro-rehabilitation regimen with long-term neuro-rehabilitation leading to an improved outcome for both patients.
Integrating Histologic and Genomic Characteristics to Predict Tumor Mutation Burden of Early-Stage Non-Small-Cell Lung Cancer
Authors: Qiu Yuan , Liu Liping , Yang Haihong , Chen Hanzhang , Deng Qiuhua , Xiao Dakai , Lin Yongping , Zhu Changbin , Li Weiwei , Shao Di , Jiang Wenxi , Wu Kui , He Jianxing
Published: April 2021

Tumor mutation burden (TMB) serves as an effective biomarker predicting efficacy of mono-immunotherapy for non-small cell lung cancer (NSCLC). Establishing a precise TMB predicting model is essential to select which populations are likely to respond to immunotherapy or prognosis and to maximize the benefits of treatment. In this study, available Formalin-fixed paraffin embedded tumor tissues were collected from 499 patients with NSCLC. Targeted sequencing of 636 cancer related genes was performed, and TMB was calculated. Distribution of TMB was significantly (p < 0.001) correlated with sex, clinical features (pathological/histological subtype, pathological stage, lymph node metastasis, and lympho-vascular invasion). It was also significantly (p < 0.001) associated with mutations in genes like TP53, EGFR, PIK3CA, KRAS, EPHA3, TSHZ3, FAT3, NAV3, KEAP1, NFE2L2, PTPRD, LRRK2, STK11, NF1, KMT2D, and GRIN2A. No significant correlations were found between TMB and age, neuro-invasion (p = 0.125), and tumor location (p = 0.696). Patients with KRAS p.G12 mutations and FAT3 missense mutations were associated (p < 0.001) with TMB. TP53 mutations also influence TMB distribution (P < 0.001). TMB was reversely related to EGFR mutations (P < 0.001) but did not differ by mutation types. According to multivariate logistic regression model, genomic parameters could effectively construct model predicting TMB, which may be improved by introducing clinical information. Our study demonstrates that genomic together with clinical features yielded a better reliable model predicting TMB-high status. A simplified model consisting of less than 20 genes and couples of clinical parameters were sought to be useful to provide TMB status with less cost and waiting time.
Practical Strategies Using Medical Cannabis to Reduce Harms Associated With Long Term Opioid Use in Chronic Pain
Authors: MacCallum Caroline A. , Eadie Lauren , Barr Alasdair M. , Boivin Michael , Lu Shaohua
Published: April 2021

Background:Chronic non-cancer pain (CNCP) is estimated to affect 20% of the adult population. Current United States and Canadian Chronic non-cancer pain guidelines recommend careful reassessment of the risk-benefit ratio for doses greater than 90 mg morphine equivalent dose (MED), due to low evidence for improved pain efficacy at higher morphine equivalent dose and a significant increase in morbidity and mortality. There are a number of human studies demonstrating cannabis opioid synergy. This preliminary evidence suggests a potential role of cannabis as an adjunctive therapy with or without opioids to optimize pain control.

Methods:In 2017, the Canadian Opioid Guidelines Clinical Tool was created to encourage judicious opioid prescribing for CNCP patients and to reevaluate those who have been chronically using high MED. Mirroring this approach, we draw on our clinical experiences and available evidence to create a clinical tool to serve as a foundational clinical guideline for the initiation of medical cannabis in the management of CNCP patients using chronic opioid therapy.

Findings:Following principles of harm reduction and risk minimization, we suggest cannabis be introduced in appropriately selected CNCP patients, using a stepwise approach, with the intent of pain management optimization. We use a structured approach to focus on low dose cannabis (namely, THC) initiation, slow titration, dose optimization and frequent monitoring.

Conclusion:When low dose THC is introduced as an adjunctive therapy, we observe better pain control clinically with lower doses of opioids, improved pain related outcomes and reduced opioid related harm.
Global Analysis the Potential Medicinal Substances of Shuangxia Decoction and the Process In Vivo via Mass Spectrometry Technology
Authors: Zhang Chenning , Liu Chuanxin , Wu Hao , Wang Jiaqi , Sun Yu , Liu Runhua , Li Tianyi , Yu Xue , Geng Di , Sun Yi-Kun
Published: April 2021

Shuangxia decoction is an effective traditional Chinese medicine formula for treating insomnia. Up to now, there has not been any report about the effective substances. An omics data processing method based on mass spectrometry technology is used to explore the chemical composition changes of Shuangxia decoction, the components absorbed into the blood and brain, and to explore the anti-insomnia mechanism based on molecular docking technology. Forty-nine chemical components in Shuangxia decoction have been identified, and 51 new components generated by co-decoction have been discovered. It was found that 7,404 compounds of Shuangxia decoction were absorbed into the blood. Forty kinds of known compounds were quickly identified, and 15 new compounds generated by co-decoction were also found to be absorbed into the blood. By using UPLC-MS/MS method, it was confirmed that 10 compounds were absorbed into the blood and 9 compounds were absorbed into the brain. Furthermore, it is found that rosmarinic acid is mainly distributed in the hypothalamus and striatum, and caffeic acid is mainly distributed in the hypothalamus, striatum, and hippocampus. Molecular docking results showed rosmarinic acid, danshensu, and HMLA with GABAA receptor have excellent binding characteristics, even surpassing the proligand. Danshensu and HMLA with dopamine D2 receptor also showed good binding energy. Our findings will help to further confirm the mechanism of Shuangxia decoction for relieving insomnia, and we also establish a novel data processing method for supplementing the mechanism of the efficacy of other traditional Chinese medicine formula.
Evaluation of Aqueous Flare Intensity in Eyes Undergoing Intravitreal Bevacizumab Therapy to Treat Neovascular Age-Related Macular Degeneration
Authors: Dolar-Szczasny Joanna , Bucolo Claudio , Zweifel Sandrine , Carnevali Adriano , Rejdak Robert , Załuska Wojciech , Czarnek-Chudzik Aleksandra , Toro Mario Damiano
Published: April 2021

Purpose: To evaluate the effect of repeated intravitreal bevacizumab injections on blood-aqueous barrier permeability in eyes with neovascular age-related macular degeneration (AMD).

Patients and Methods: Forty-eight consecutive patients with neovascular AMD received 3 intravitreal bevacizumab injections (1 mg) every 30–40 days. Subjects were followed for a period of 4 months and were examined at baseline, 1 day and 1 month after each injection. A control group comprised of 19 neovascular AMD patients waiting to begin anti-vascular endothelial growth factor (VEGF) therapy. Anterior chamber (AC) inflammation was evaluated with biomicroscopy and laser flare photometry.

Results: None of the subjects treated with bevacizumab had detectable ocular inflammation during follow-up. An analysis for variance (ANOVA) of the mixed-effects model has shown neither an effect between treatment and control group (p = 0.921), nor over the time course of the follow-up (p = 0.773). Before treatment, median AC inflammation was 6.7 photons/ms (range: 3.5–18.2 photons/ms). One month after the first, second, and third injections, median laser flare was 6.4, 6.8, and 6.6 photons/ms, respectively, none of which were significantly different from baseline (all p > 0.05). Blood-aqueous barrier permeability did not change between injections and was not different from the control group.

Conclusion: Inflammation induced by intravitreal bevacizumab was not detected by examination or flare photometry. This suggests that monthly bevacizumab dosing seems to be safe. The absence of AC inflammation could also reflect the known anti-inflammatory properties of anti-VEGF agents.
Clinical Strains of Helicobacter pylori With Strong Cell Invasiveness and the Protective Effect of Patchouli Alcohol by Improving miR-30b/C Mediated Xenophagy
Authors: Xu Yifei , Deng Qiuhua , Zhong Yuanzun , Jing Li , Li Haiwen , Li Jingwei , Yu Huimin , Pan Huafeng , Guo Shaoju , Cao Hongying , Huang Ping , Huang Bin
Published: April 2021

Helicobacter pylori was classified by the World Health Organization as a class 1 carcinogen. The development of drug-resistant strains of this pathogen poses a serious threat to human health worldwide. The cell invasion of H. pylori activates xenophagy in gastric epithelial cells by mediating miR-30b/c, and the emergence of autophagosomes provides a niche that enables the survival of intracellular H. pylori and promotes its drug resistance. This study revealed that some clinical drug-resistant H. pylori strains present much stronger invasive ability than standard strains. Patchouli alcohol (PA), a tricyclic sesquiterpene from Pogostemon cablin (Blanco) Benth (Labiatae), showed reliable activity against intracellular H. pylori. The mechanisms appeared to involve the downregulation of miR-30c-3p/5p and miR-30b-5p, thereby upregulating xenophagy-related gene expression (ULK1, ATG5, ATG12, and ATG14) and enhancing xenophagy. PA also inhibited the nuclear transfection of miR-30b-5p induced by H. pylori, thereby enhancing transcription factor EB function and increasing lysosome activity. The finding of strongly invasive intracellular H. pylori has great implications for clinical treatment, and PA can act against invasive H. pylori based on the improvement of miR-30b/c mediated xenophagy. Taken together, the results demonstrate that PA have potential use as a candidate medication for intracellular drug-resistant H. pylori.
Tracking Animal-Dispersed Seedlings Using 15N Xylem Injection Method
Authors: Wang Minghui , Yi Sijie , Ju Mengyao , Yi Xianfeng
Published: April 2021

Although various seed-marking methods have been developed for seed dispersal, it remains difficult to track the actual patterns of seed dispersal and seedling recruitment. Thus, new labeling methods that accurately track seedling establishment along with seed movement would help us better understand seed dispersal. Here, we developed a new nondestructive method using15N xylem injection to track seed dispersal and seedling recruitment based on the enriched isotopic signals in the mature seeds. Our results first showed that xylem injection of15N successfully enriched15N both in the acorns and seedlings ofQuercus variabilis. By marking acorns and seedlings with15N stable isotopes, we successfully tracked seedlings established from acorns dispersed by seed-eating animals in the field. Our xylem15N injection caused little alteration to seeds and showed no significant effects on seed selection by seed-eating animals as well as seed germination and seedling establishment, verifying the validity of the15N xylem injection method to track seedling establishment. Our xylem15N injection method is expected to be a powerful tool for tracking seed dispersal and seedling recruitment mediated by seed-eating animals in seed dispersal ecology.
Breeding for Climate Change Resilience: A Case Study of Loblolly Pine (Pinus taeda L.) in North America
Authors: Matallana-Ramirez Lilian P. , Whetten Ross W. , Sanchez Georgina M. , Payn Kitt G.
Published: April 2021

Earth’s atmosphere is warming and the effects of climate change are becoming evident. A key observation is that both the average levels and the variability of temperature and precipitation are changing. Information and data from new technologies are developing in parallel to provide multidisciplinary opportunities to address and overcome the consequences of these changes in forest ecosystems. Changes in temperature and water availability impose multidimensional environmental constraints that trigger changes from the molecular to the forest stand level. These can represent a threat for the normal development of the tree from early seedling recruitment to adulthood both through direct mortality, and by increasing susceptibility to pathogens, insect attack, and fire damage. This review summarizes the strengths and shortcomings of previous work in the areas of genetic variation related to cold and drought stress in forest species with particular emphasis on loblolly pine (Pinus taedaL.), the most-planted tree species in North America. We describe and discuss the implementation of management and breeding strategies to increase resilience and adaptation, and discuss how new technologies in the areas of engineering and genomics are shaping the future of phenotype-genotype studies. Lessons learned from the study of species important in intensively-managed forest ecosystems may also prove to be of value in helping less-intensively managed forest ecosystems adapt to climate change, thereby increasing the sustainability and resilience of forestlands for the future.
Hyperspectral Imaging for Identification of an Invasive Plant Mikania micrantha Kunth
Authors: Huang Yiqi , Li Jie , Yang Rui , Wang Fukuan , Li Yanzhou , Zhang Shuo , Wan Fanghao , Qiao Xi , Qian Wanqiang
Published: April 2021

Mile-a-minute weed (Mikania micrantha Kunth) is considered as one of top 100 most dangerous invasive species in the world. A fast and accurate detection technology will be needed to identify M. micrantha. It will help to mitigate the extensive ecologic and economic damage on our ecosystems caused by this alien plant. Hyperspectral technology fulfills the above requirement. However, when working with hyperspectral images, preprocessing, dimension reduction, and classifier are fundamental to achieving reliable recognition accuracy and efficiency. The spectral data of M. micrantha were collected using hyperspectral imaging in the spectral range of 450–998 nm. A different combination of preprocessing methods, principal component analysis (for dimension reduction), and three classifiers were used to analyze the collected hyperspectral images. The results showed that a combination of Savitzky-Golay (SG) smoothing, principal component analysis (PCA), and random forest (RF) achieved an accuracy (A) of 88.71%, an average accuracy (AA) of 88.68%, and a Kappa of 0.7740 with an execution time of 9.647 ms. In contrast, the combination of SG, PCA and a support vector machine (SVM) resulted in a weaker performance in terms of A (84.68%), AA(84.66%), and Kappa (0.6934), but with less execution time (1.318 ms). According to the requirements for specific identification accuracy and time cost, SG-PCA-RF and SG-PCA-SVM might represent two promising methods for recognizing M. micrantha in the wild.