bluuebunny/crossref_metadata_2025 huggingface dataset:
A Coupled Lagrangian-Earth System Model for Predicting Oil Photooxidation
Authors: Vaz Ana C. , Faillettaz Robin , Paris Claire B.
Published: February 2021

During the Deepwater Horizon (DWH) blowout, photooxidation of surface oil led to the formation of persistent photooxidized compounds, still found in shoreline sediments a decade later. Studies demonstrated that photooxidation modified both biodegradation rates of the surface oil and the effectiveness of aerial dispersant applications. Despite the significant consequences of this weathering pathway, the lack of measurements prevented photooxidation to be accounted for in the DWH oil budget calculations and in most predictive models. Here we develop a Lagrangian photooxidation module that estimates the dose of solar radiation individual oil droplets receive while moving in the ocean, quantifies the likelihood of photooxidative changes, and continues to track the transport of these persistent photooxidized compounds. We estimate and track the likelihood of photooxidation of Lagrangian oil droplets in the upper layers of the water column for the DWH case by coupling the net shortwave radiation from NOGAPS to the oil application of the Connectivity Modeling System (oil-CMS). The dose of solar radiation upon a droplet is computed with the intensity of the incoming irradiance at the ocean’s surface, the light attenuation coefficient, and the depth of the oil droplets. Considering a range of DWH empirical irradiance thresholds, we find that photooxidation can happen at short time scales of hours to days, in agreement with the new paradigm of oil photooxidation. Furthermore, the oxidized compounds are likely to form in a 110 km radius around the response site, suggesting that the oil reaching the coastline was already photooxidized. This new dynamic coupling provides a powerful tool to test oil weathering hypotheses, refine the oil budget during the DWH, and ultimately inform rapid response in future oil spills.
Environmental Awareness Gained During a Citizen Science Project in Touristic Resorts Is Maintained After 3 Years Since Participation
Authors: Meschini Marta , Prati Francesca , Simoncini Ginevra A. , Airi Valentina , Caroselli Erik , Prada Fiorella , Marchini Chiara , Machado Toffolo Mariana , Branchini Simone , Brambilla Viviana , Covi Claudia , Goffredo Stefano
Published: February 2021

Tourism is one of the largest economic sectors in the world. It has a positive effect on the economy of many countries, but it can also lead to negative impacts on local ecosystems. Informal environmental education through Citizen Science (CS) projects can be effective in increasing citizen environmental knowledge and awareness in the short-term. A change of awareness could bring to a behavioral change in the long-term, making tourism more sustainable. However, the long-term effects of participating in CS projects are still unknown. This is the first follow-up study concerning the effects of participating in a CS project on cognitive and psychological aspects at the basis of pro-environmental behavior. An environmental education program was developed, between 2012 and 2013, in a resort in Marsa Alam, Egypt. The study directly evaluated, through paper questionnaires, the short-term (after 1 week or 10 days) retention of knowledge and awareness of volunteers that had participated in the activities proposed by the program. After three years, participants were re-contacted via email to fill in the same questionnaire as in the short-term study, plus a new section with psychological variables. 40.5% of the re-contacted participants completed the follow-up questionnaires with a final sample size of fifty-five people for this study. Notwithstanding the limited sample size, positive trends in volunteer awareness, personal satisfaction regarding the CS project, and motivation to engage in pro-environmental behavior in the long-term were observed.
Patterns of Sediment Fungal Community Dependent on Farming Practices in Aquaculture Ponds
Authors: Zhang Zhimin , Deng Qinghui , Cao Xiuyun , Zhou Yiyong , Song Chunlei
Published: February 2021

Despite fungi playing an important role in nutrient decomposition in aquatic ecosystems and being considered as vital actors in the ecological processes, they received limited attention regarding the community in aquaculture pond sediments which are extremely important and typically disturbed habitats. Using an ITS1 region of fungal rDNA, this study aimed to investigate sediment fungal communities in fish, crab, and crayfish ponds for decades of farming practices at representative aquaculture regions in the middle Yangtze River basin, China. We then aimed to explore the community patterns associated with species-based farming practices in the ponds at 18 farms. The results showed that the pond sediments harbored more than 9,000 operational taxonomic units. The sediments had significantly higher alpha diversity in crab ponds compared to that in fish and crayfish ponds. The fungal phyla largely belonged to Ascomycota and Chytridiomycota, and the dominance of Rozellomycota over Basidiomycota and Aphelidiomycota was observed. The majority of sediment fungal members were ascribed to unclassified fungi, with higher proportions in fish ponds than crab and crayfish ponds. Further, the fungal communities were markedly distinct among the three types of ponds, suggesting divergent patterns of fungal community assemblages caused by farming practices in aquaculture ponds. The community diversity and structure were closely correlated to sediment properties, especially sediment carbon content and pH. Thus, the distribution and pattern of fungal communities in the sediments appear to primarily depend on species-based farming practices responsible for the resulting sediment carbon content and pH in aquaculture ponds. This study provides a detailed snapshot and extension of understanding fungal community structure and variability in pond ecosystems, highlighting the impacts of farming practices on the assembly and succession of sediment fungal communities in aquaculture ponds.
Exogenous Aspergillus aculeatus Enhances Drought and Heat Tolerance of Perennial Ryegrass
Authors: Li Xiaoning , Zhao Chuncheng , Zhang Ting , Wang Guangyang , Amombo Erick , Xie Yan , Fu Jinmin
Published: February 2021

Perennial ryegrass (Lolium perenne) is a cool-season grass whose growth and development are limited by drought and high temperature. Aspergillus aculeatus has been reported to promote plant growth and counteract the adverse effects of abiotic stresses. The objective of this study was to assess A. aculeatus-induced response mechanisms to drought and heat resistance in perennial ryegrass. We evaluated the physiological and biochemical markers of drought and heat stress based on the hormone homeostasis, photosynthesis, antioxidant enzymes activity, lipid peroxidation, and genes expression level. We found out that under drought and heat stress, A. aculeatus-inoculated leaves exhibited higher abscisic acid (ABA) and lower salicylic acid (SA) contents than non-inoculated regimes. In addition, under drought and heat stress, the fungus enhanced the photosynthetic performance, decreased the antioxidase activities, and mitigated membrane lipid peroxidation compared to non-inoculated regime. Furthermore, under drought stress, A. aculeatus induced a dramatic upregulation of sHSP17.8 and DREB1A and a downregulation of POD47, Cu/ZnSOD, and FeSOD genes. In addition, under heat stress, A. aculeatus-inoculated plants exhibited a higher expression level of HSP26.7a, sHSP17.8, and DREB1A while a lower expression level of POD47 and FeSOD than non-inoculated ones. Our results provide an evidence of the protective role of A. aculeatus in perennial ryegrass response to drought and heat stresses.
Prevalence and Genetic Characteristics of Staphylococcus aureus CC398 Isolates From Invasive Infections in Spanish Hospitals, Focusing on the Livestock-Independent CC398-MSSA Clade
Authors: Mama Olouwafemi Mistourath , Aspiroz Carmen , Ruiz-Ripa Laura , Ceballos Sara , Iñiguez-Barrio Maria , Cercenado Emilia , Azcona José Manuel , López-Cerero Lorena , Seral Cristina , López-Calleja Ana Isabel , Belles-Belles Alba , Berdonces Pilar , Siller María , Zarazaga Myriam , Torres Carmen ,   the Study Group of clinical S. aureus CC398
Published: February 2021

Background

Livestock-associated (LA)-CC398-MRSA is closely related to pigs, being unfrequently detected in human invasive infections. CC398-MSSA is emerging in human invasive infections in some countries, but genetic and epidemiological characteristics are still scarcely reported.

Objectives

To determine the prevalence of Staphylococcus aureus (SA) CC398, both MRSA and MSSA, among blood cultures SA isolates recovered in Spanish hospitals located in regions with different pig-farming densities (PD) and characterize the recovered isolates.

Methods

One thousand twenty-two SA isolates (761 MSSA, 261 MRSA) recovered from blood cultures during 6–12 months in 17 Spanish hospitals (2018–2019) were studied. CC398 lineage identification, detection of spa-types, and antibiotic resistance, virulence and human immune evasion cluster (IEC) genes were analyzed by PCR/sequencing.

Results

Forty-four CC398-MSSA isolates (4.3% of SA; 5.8% of MSSA) and 10 CC398-MRSA isolates (1% of SA; 3.8% of MRSA) were detected. Eleven spa-types were found among the CC398-MSSA isolates with t571 and t1451 the most frequent spa-types detected (75%). Most of CC398-MSSA isolates were Immune-Evasion-Cluster (IEC)-positive (88.6%), tetracycline-susceptible (95.5%) and erythromycin/clindamycin–inducible-resistant/erm(T)-positive (75%). No statistical significance was detected when the CC398-MSSA/MSSA rate was correlated to PD (pigs/km2) (p = 0.108). On the contrary, CC398-MRSA isolates were all IEC-negative, predominately spa-t011 (70%), and the CC398-MRSA/MRSA rate was significantly associated to PD (p < 0.005).

Conclusion

CC398-MSSA is an emerging clade in invasive infections in Spanish hospitals. CC398-MRSA (mostly t011) and CC398-MSSA (mostly t571 and t1451) show important differences, possibly suggesting divergent steps in host-adaptation evolutionary processes. While CC398-MRSA is livestock-associated (lacking IEC-system), CC398-MSSA seems to be mostly livestock-independent, carrying human-adaptation markers.
Gauging Working Memory Capacity From Differential Resting Brain Oscillations in Older Individuals With A Wearable Device
Authors: Borhani Soheil , Zhao Xiaopeng , Kelly Margaret R. , Gottschalk Karah E. , Yuan Fengpei , Jicha Gregory A. , Jiang Yang
Published: February 2021

Working memory is a core cognitive function and its deficits is one of the most common cognitive impairments. Reduced working memory capacity manifests as reduced accuracy in memory recall and prolonged speed of memory retrieval in older adults. Currently, the relationship between healthy older individuals’ age-related changes in resting brain oscillations and their working memory capacity is not clear. Eyes-closed resting electroencephalogram (rEEG) is gaining momentum as a potential neuromarker of mild cognitive impairments. Wearable and wireless EEG headset measuring key electrophysiological brain signals during rest and a working memory task was utilized. This research’s central hypothesis is that rEEG (e.g., eyes closed for 90 s) frequency and network features are surrogate markers for working memory capacity in healthy older adults. Forty-three older adults’ memory performance (accuracy and reaction times), brain oscillations during rest, and inter-channel magnitude-squared coherence during rest were analyzed. We report that individuals with a lower memory retrieval accuracy showed significantly increased alpha and beta oscillations over the right parietal site. Yet, faster working memory retrieval was significantly correlated with increased delta and theta band powers over the left parietal sites. In addition, significantly increased coherence between the left parietal site and the right frontal area is correlated with the faster speed in memory retrieval. The frontal and parietal dynamics of resting EEG is associated with the “accuracy and speed trade-off” during working memory in healthy older adults. Our results suggest that rEEG brain oscillations at local and distant neural circuits are surrogates of working memory retrieval’s accuracy and processing speed. Our current findings further indicate that rEEG frequency and coherence features recorded by wearable headsets and a brief resting and task protocol are potential biomarkers for working memory capacity. Additionally, wearable headsets are useful for fast screening of cognitive impairment risk.
Plasma Neurofilament Light Chain as a Predictive Biomarker for Post-stroke Cognitive Impairment: A Prospective Cohort Study
Authors: Wang Zhiqiang , Wang Rongyu , Li Yuxia , Li Mao , Zhang Yaodan , Jiang Lianyan , Fan Jin , Wang Qingsong , Yang Dongdong
Published: February 2021

Background

Plasma neurofilaments light chain (pNfL) is a marker of axonal injury. The purpose of this study was to examine the role of pNfL as a predictive biomarker for post-stroke cognitive impairment (PSCI).

Methods

A prospective single-center observational cohort study was conducted at the General Hospital of Western Theater Command between July 1, 2017 and December 31, 2019. Consecutive patients ≥18 years with first-ever acute ischemic stroke (AIS) of anterior circulation within 24 h of symptom onset were included. PSCI was defined by the Montreal Cognitive Assessment (MOCA) (MOCA < 26) at 90 days after stroke onset.

Results

A total of 1,694 patients [male, 893 (52.70%); median age, 64 (16) years] were enrolled in the cohort analysis, and 1,029 (60.70%) were diagnosed with PSCI. Patients with PSCI had significantly higher pNfL [median (IQR), 55.96 (36.13) vs. 35.73 (17.57) pg/ml; P < 0.001] than Non-PSCI. pNfL was valuable for the prediction of PSCI (OR 1.044, 95% CI 1.038–1.049, P < 0.001) after a logistic regression analysis, even after adjusting for conventional risk factors including age, sex, education level, NIHSS, TOAST classification, and infarction volume (OR 1.041, 95% CI 1.034–1.047, P < 0.001). The optimal cutoff value of the pNfL concentration was 46.12 pg/ml, which yielded a sensitivity of 71.0% and a specificity of 81.5%, with the area under the curve (AUC) at 0.785 (95% CI 0.762–0.808, P < 0.001).

Conclusion

This prospective cohort study showed that the pNfL concentration within 48 h of onset was an independent risk factor for PSCI 90 days after an anterior circulation stroke, even after being adjusted for potential influencing factors regarded as clinically relevant.

Clinical Trial Registration

www.chictr.org.cn, identifier ChiCTR1800020330.
Indolaminergic System in Adult Rat Testes: Evidence for a Local Serotonin System
Authors: Jiménez-Trejo Francisco , Coronado-Mares Isabel , Arriaga-Canon Cristian , Herrera Luis A. , Roque-Ramírez Bladimir , Chávez-Saldaña Margarita , Rojas-Castañeda Julio , Cerbón Marco , Vigueras-Villaseñor Rosa M.
Published: February 2021

Serotonin (5-HT) is member of a family of indolamine molecules that participate in a wide variety of biological processes. Despite its important role in the regulation of local blood systems, little is known about the physiological function of 5-HT in reproductive organs, its functional implications, and its role in the reproduction of mammals. In the present work, we evaluated the localization and distribution of 5-HT (using histochemical analysis of indolamines) and different components of the serotoninergic system in rat testes. We detected local synthesis and degradation through immunofluorescence and western blot analyses against the TPH1, MAOA, 5-HTT, and VMAT1 serotonin transporters. We also identified the localization and distribution of the 5-HT1B, 5-HT2A, and 5-HT3Areceptors. RT-PCR results showed the presence of the Tph1, Maoa, Slc6a4, and Htr3a genes in testes and in the brain stem (Tph1 was used as a negative control). High-performance liquid chromatography was used to determine the presence of 5-HT and the activity of tryptophan hydroxylase in testes homogenatesin vitro. Our observations suggest that TPH1 activity and local 5-HT synthesis befall in rat testes. We propose that 5-HT could participate in the regulation of testosterone synthesis and in the spermatogenesis process via local serotoninergic system. However, more studies are needed before concluding that rat testes, or those of other mammals, contain an active form of tryptophan hydroxylase and produce 5-HT.
Automatic Detection of Focal Cortical Dysplasia Type II in MRI: Is the Application of Surface-Based Morphometry and Machine Learning Promising?
Authors: Ganji Zohreh , Hakak Mohsen Aghaee , Zamanpour Seyed Amir , Zare Hoda
Published: February 2021

Background and Objectives

Focal cortical dysplasia (FCD) is a type of malformations of cortical development and one of the leading causes of drug-resistant epilepsy. Postoperative results improve the diagnosis of lesions on structural MRIs. Advances in quantitative algorithms have increased the identification of FCD lesions. However, due to significant differences in size, shape, and location of the lesion in different patients and a big deal of time for the objective diagnosis of lesion as well as the dependence of individual interpretation, sensitive approaches are required to address the challenge of lesion diagnosis. In this research, a FCD computer-aided diagnostic system to improve existing methods is presented.

Methods

Magnetic resonance imaging (MRI) data were collected from 58 participants (30 with histologically confirmed FCD type II and 28 without a record of any neurological prognosis). Morphological and intensity-based features were calculated for each cortical surface and inserted into an artificial neural network. Statistical examinations evaluated classifier efficiency.

Results

Neural network evaluation metrics—sensitivity, specificity, and accuracy—were 96.7, 100, and 98.6%, respectively. Furthermore, the accuracy of the classifier for the detection of the lobe and hemisphere of the brain, where the FCD lesion is located, was 84.2 and 77.3%, respectively.

Conclusion

Analyzing surface-based features by automated machine learning can give a quantitative and objective diagnosis of FCD lesions in presurgical assessment and improve postsurgical outcomes.
Efficient Spike-Driven Learning With Dendritic Event-Based Processing
Authors: Yang Shuangming , Gao Tian , Wang Jiang , Deng Bin , Lansdell Benjamin , Linares-Barranco Bernabe
Published: February 2021

A critical challenge in neuromorphic computing is to present computationally efficient algorithms of learning. When implementing gradient-based learning, error information must be routed through the network, such that each neuron knows its contribution to output, and thus how to adjust its weight. This is known as the credit assignment problem. Exactly implementing a solution like backpropagation involves weight sharing, which requires additional bandwidth and computations in a neuromorphic system. Instead, models of learning from neuroscience can provide inspiration for how to communicate error information efficiently, without weight sharing. Here we present a novel dendritic event-based processing (DEP) algorithm, using a two-compartment leaky integrate-and-fire neuron with partially segregated dendrites that effectively solves the credit assignment problem. In order to optimize the proposed algorithm, a dynamic fixed-point representation method and piecewise linear approximation approach are presented, while the synaptic events are binarized during learning. The presented optimization makes the proposed DEP algorithm very suitable for implementation in digital or mixed-signal neuromorphic hardware. The experimental results show that spiking representations can rapidly learn, achieving high performance by using the proposed DEP algorithm. We find the learning capability is affected by the degree of dendritic segregation, and the form of synaptic feedback connections. This study provides a bridge between the biological learning and neuromorphic learning, and is meaningful for the real-time applications in the field of artificial intelligence.
The Pathology of Morphine-Inhibited Nerve Repair and Morphine-Induced Nerve Damage Is Mediated via Endoplasmic Reticulum Stress
Authors: Liu Jie , Yi Shanyong , Shi Weibo , Zhang Guozhong , Wang Songjun , Qi Qian , Cong Bin , Li Yingmin
Published: February 2021

Objective

The aim of the present study was to observe the pathological damage in the cerebral cortex of rats under acute morphine exposure (AME) and different durations of morphine dependence (MD), explore whether endoplasmic reticulum stress (ERS) is involved in the damage process, and assess the effect of morphine exposure on the proliferation and differentiation of newborn neurons.

Methods

Rat models of AME and different durations of MD were established. Pathological changes in cortical neurons were assessed by hematoxylin and eosin (H&E) and thionine staining. The expression of nuclear receptor-related factor 1 (NURR1) and that of the ERS-related proteins glucose-regulated protein 78 (GRP78), p-eIF2α, activating transcription factor 6 (ATF6), and CHOP in cortical neurons was assessed by immunohistochemistry. Double immunofluorescence labeling was used to observe the expression of Ki-67.

Results

H&E and thionine staining revealed that AME resulted in pyknotic changes in cortical neurons. With prolonged morphine exposure, the number of pyknotic neurons was significantly increased, the protein expression of Ki-67 and NURR1 was significantly decreased, and the protein levels of GRP78, p-eIF2α, ATF6, and CHOP showed marked dynamic changes.

Conclusion

AME and different durations of MD caused varying degrees of pathological changes in the cortex. Furthermore, the dynamic changes observed in ERS-related protein expression suggested that ERS may be associated with cortical injury. Different durations of MD inhibited the proliferation, differentiation, and migration of newborn neurons, which may affect the nerve repair process after injury.
Circadian Chimeric Mice Reveal an Interplay Between the Suprachiasmatic Nucleus and Local Brain Clocks in the Control of Sleep and Memory
Authors: Maywood Elizabeth Susan , Chesham Johanna Elizabeth , Winsky-Sommerer Raphaelle , Smyllie Nicola Jane , Hastings Michael Harvey
Published: February 2021

Sleep is regulated by circadian and homeostatic processes. Whereas the suprachiasmatic nucleus (SCN) is viewed as the principal mediator of circadian control, the contributions of sub-ordinate local circadian clocks distributed across the brain are unknown. To test whether the SCN and local brain clocks interact to regulate sleep, we used intersectional genetics to create temporally chimeric CK1ε Tau mice, in which dopamine 1a receptor (Drd1a)-expressing cells, a powerful pacemaking sub-population of the SCN, had a cell-autonomous circadian period of 24 h whereas the rest of the SCN and the brain had intrinsic periods of 20 h. We compared these mice with non-chimeric 24 h wild-types (WT) and 20 h CK1ε Tau mutants. The periods of the SCN ex vivo and the in vivo circadian behavior of chimeric mice were 24 h, as with WT, whereas other tissues in the chimeras had ex vivo periods of 20 h, as did all tissues from Tau mice. Nevertheless, the chimeric SCN imposed its 24 h period on the circadian patterning of sleep. When compared to 24 h WT and 20 h Tau mice, however, the sleep/wake cycle of chimeric mice under free-running conditions was disrupted, with more fragmented sleep and an increased number of short NREMS and REMS episodes. Even though the chimeras could entrain to 20 h light:dark cycles, the onset of activity and wakefulness was delayed, suggesting that SCN Drd1a-Cre cells regulate the sleep/wake transition. Chimeric mice also displayed a blunted homeostatic response to 6 h sleep deprivation (SD) with an impaired ability to recover lost sleep. Furthermore, sleep-dependent memory was compromised in chimeras, which performed significantly worse than 24 h WT and 20 h Tau mice. These results demonstrate a central role for the circadian clocks of SCN Drd1a cells in circadian sleep regulation, but they also indicate a role for extra-SCN clocks. In circumstances where the SCN and sub-ordinate local clocks are temporally mis-aligned, the SCN can maintain overall circadian control, but sleep consolidation and recovery from SD are compromised. The importance of temporal alignment between SCN and extra-SCN clocks for maintaining vigilance state, restorative sleep and memory may have relevance to circadian misalignment in humans, with environmental (e.g., shift work) causes.
DNA Damage Repair Gene Mutations Are Indicative of a Favorable Prognosis in Colorectal Cancer Treated With Immune Checkpoint Inhibitors
Authors: Song Yipeng , Huang Jian , Liang Dandan , Hu Ying , Mao Beibei , Li Qiujing , Sun Huaibo , Yang Ying , Zhang Jiao , Zhang Henghui , Chen Huan , Liu Hao , Zhang Shukun
Published: February 2021

Background

DNA damage repair (DDR) genes were recently implicated in the anti-tumor immune response. Therefore, it is worthwhile to unravel the implications of DDR pathways in the shaping of immune responsiveness in colorectal cancer (CRC) patients receiving immune checkpoint inhibitors (ICI).

Methods

We analyzed publicly available genomic data from a cohort treated with ICI from Memorial Sloan Kettering Cancer Center (MSK ICI cohort). To characterize the impact of the DDR mutation, the genomic data of The Cancer Genome Atlas (TCGA) colorectal adenocarcinoma (COADREAD) dataset was explored. We also analyzed the incidence of DDR mutation and microsatellite instability-high (MSI-H) in a Chinese CRC cohort using panel sequencing.

Results

The DDR pathway was commonly mutated (21.8%) in the multicancer MSK ICI cohort, with the highest frequency of 36.4% in CRCs. Survival analysis showed that DDR mutation correlated with an improved overall survival (OS) in CRCs and pan-cancer in the MSK ICI cohort. However, no significant associations were identified in the TCGA COADREAD and MSK non-ICI CRCs. DDR mutation was associated with higher tumor mutational burden (TMB) levels and increased immune cell infiltration and immune checkpoint molecule expression in the TCGA COADREAD dataset. Last, we investigated the DDR mutational pattern and its associations with MSI-H and other genomic features in a Chinese CRC cohort. Notably, MSI-H and DDR mutation was present in 5.7% and 13.4% of cases, respectively, which suggests that DDR identifies a higher proportion of potential responders than MSI-H.

Conclusion

Our data suggest that DDR mutation as an indication of enhanced cancer immunity, and it may function as a biomarker for patients with CRCs receiving ICI treatment. The high incidence of DDR mutation in the Chinese CRC cohort emphasizes the future utility of panel-based DDR evaluation in guiding ICI treatment.
Prognostic Signatures Based on Thirteen Immune-Related Genes in Colorectal Cancer
Authors: Ma Xiao-Bo , Xu Yuan-Yuan , Zhu Meng-Xuan , Wang Lu
Published: February 2021

Background

The immunosuppressive microenvironment is closely related to tumorigenesis and cancer development, including colorectal cancer (CRC). The aim of the current study was to identify new immune biomarkers for the diagnosis and treatment of CRC.

Materials and Methods

CRC data were downloaded from the Gene Expression Omnibus and The Cancer Genome Atlas databases. Sequences of immune-related genes (IRGs) were obtained from the ImmPort and InnateDB databases. Gene set enrichment analysis (GSEA) and transcription factor regulation analysis were used to explore potential mechanisms. An immune-related classifier for CRC prognosis was conducted using weighted gene co-expression network analysis (WGCNA), Cox regression analysis, and least absolute shrinkage and selection operator (LASSO) analysis. ESTIMATE and CIBERSORT algorithms were used to explore the tumor microenvironment and immune infiltration in the high-risk CRC group and the low-risk CRC group.

Results

By analyzing the IRGs that were significantly associated with CRC in the module, a set of 13 genes (CXCL1, F2RL1, LTB4R, GPR44, ANGPTL5, BMP5, RETNLB, MC1R, PPARGC1A, PRKDC, CEBPB, SYP, and GAB1) related to the prognosis of CRC were identified. An IRG-based prognostic signature that can be used as an independent potentially prognostic indicator was generated. The ROC curve analysis showed acceptable discrimination with AUCs of 0.68, 0.68, and 0.74 at 1-, 3-, and 5- year follow-up respectively. The predictive performance was validated in the train set. The potential mechanisms and functions of prognostic IRGs were analyzed, i.e., NOD-like receptor signaling, and transforming growth factor beta (TGFβ) signaling. Besides, the stromal score and immune score were significantly different in high-risk group and low-risk group (p=4.6982e-07, p=0.0107). Besides, the proportions of resting memory CD4+ T cells was significantly higher in the high-risk groups.

Conclusions

The IRG-based classifier exhibited strong predictive capacity with regard to CRC. The survival difference between the high-risk and low-risk groups was associated with tumor microenvironment and immune infiltration of CRC. Innovative biomarkers for the prediction of CRC prognosis and response to immunological therapy were identified in the present study.
Metastases to the Kidney: An Analysis of 35 Cases and a Review of Literature
Authors: Chen Jinchao , Qi Nienie , Zhu Shaoxing
Published: February 2021

Introduction

In addition to being rare, metastases to the kidney present clinicians with issues regarding their treatment.

Materials and Methods

We retrospectively analyzed 35 cases of diagnosed renal metastases. The clinical characteristics, imaging features, pathological features, diagnosis, and treatment were analyzed, and Kaplan-Meier methods and Cox regression analysis were used to calculate overall survival (OS) and influencing factors.

Results

The average age of the patients was 62 years, and 40% presented with symptoms. The most common primary tumor was lung cancer (60%), and two patients had renal metastases coexisting with renal cell carcinoma. The average interval from primary tumor to renal metastasis was 29.4 months. Only 45.5% of the patients who underwent enhanced computerized tomography were diagnosed with renal metastases. Renal biopsy was performed in 16 patients (45.7%), leading to a diagnosis in 15 (93.8%). Twenty-one patients (60%) received surgical treatment, and median recurrence free survival of these patients was 7 months (95% CI, 5 to 12). Overall, the median OS was 44 months for patients who underwent renal surgery, and 52 months for patients who did not (P = 0.672). However, for patients without metastases at other sites, surgery could significantly prolong OS (P = 0.001).

Conclusion

Although rare, the possibility of renal metastasis should be considered after finding renal tumors in patients with primary tumors in other organs, and can be diagnosed by imaging examination and puncture biopsy. For patients without other metastases, surgical intervention can be considered for the renal lesions.
The Role of Real-Time Contrast-Enhanced Ultrasound in Guiding Radiofrequency Ablation of Reninoma: Case Report and Literature Review
Authors: Zhang Rui , Xu Ming , Xie Xiao-yan
Published: February 2021

Background

Reninoma is a rare renal endocrine tumor that can cause secondary hypertension, characterized by hypertension, hypokalemia, high renin and aldosterone with normal aldosterone renin ratio (ARR), and occurs more in young female. Mainstream treatment option is surgery, but is less suitable for small or deep lesions, which makes ablation a promising alternative.

Case presentation

Two young female with typical manifestations of reninoma, including hypertension, hypokalemia, high renin, high aldosterone and normal ARR, were treated successfully with real-time contrast-enhanced ultrasound guided radiofrequency ablation, and contrast-enhanced ultrasound was also performed before and after treatment for diagnosis and postoperative assessment. Afterward, their blood pressure and laboratory tests became normal and remained steady during the follow-up of 32 and 6 months, respectively.

Conclusion

Contrast-enhanced ultrasound guided radiofrequency ablations is a promising alternative for reninoma treatment with comparable safety and efficacy with surgery, and has advantages especially in small or deep lesions.
Genetic Testing in Neurodevelopmental Disorders
Authors: Savatt Juliann M. , Myers Scott M.
Published: February 2021

Neurodevelopmental disorders are the most prevalent chronic medical conditions encountered in pediatric primary care. In addition to identifying appropriate descriptive diagnoses and guiding families to evidence-based treatments and supports, comprehensive care for individuals with neurodevelopmental disorders includes a search for an underlying etiologic diagnosis, primarily through a genetic evaluation. Identification of an underlying genetic etiology can inform prognosis, clarify recurrence risk, shape clinical management, and direct patients and families to condition-specific resources and supports. Here we review the utility of genetic testing in patients with neurodevelopmental disorders and describe the three major testing modalities and their yields – chromosomal microarray, exome sequencing (with/without copy number variant calling), and FMR1 CGG repeat analysis for fragile X syndrome. Given the diagnostic yield of genetic testing and the potential for clinical and personal utility, there is consensus that genetic testing should be offered to all patients with global developmental delay, intellectual disability, and/or autism spectrum disorder. Despite this recommendation, data suggest that a minority of children with autism spectrum disorder and intellectual disability have undergone genetic testing. To address this gap in care, we describe a structured but flexible approach to facilitate integration of genetic testing into clinical practice across pediatric specialties and discuss future considerations for genetic testing in neurodevelopmental disorders to prepare pediatric providers to care for patients with such diagnoses today and tomorrow.
Pan-Cancer Analysis and Drug Formulation for GPR139 and GPR142
Authors: Kaushik Aman Chandra , Mehmood Aamir , Dai Xiaofeng , Wei Dong-Qing
Published: February 2021

GPR (G protein receptor) 139 and 142 are novel foundling GPCRs (G protein-coupled receptors) in the class “A” of the GPCRs family and are suitable targets for various biological conditions. To engage these targets, validated pharmacophores and 3D QSAR (Quantitative structure-activity relationship) models are widely used because of their direct fingerprinting capability of the target and an overall accuracy. The current work initially analyzes GPR139 and GPR142 for its genomic alteration via tumor samples. Next to that, the pharmacophore is developed to scan the 3D database for such compounds that can lead to potential agonists. As a result, several compounds have been considered, showing satisfactory performance and a strong association with the target. Additionally, it is gripping to know that the obtained compounds were observed to be responsible for triggering pan-cancer. This suggests the possible role of novel GPR139 and GPR142 as the substances for initiating a physiological response to handle the condition incurred as a result of cancer.
Insulin Fused to Apolipoprotein A-I Reduces Body Weight and Steatosis in DB/DB Mice
Authors: Ardaiz Nuria , Gomar Celia , Vasquez Marcos , Tenesaca Shirley , Fernandez-Sendin Myriam , Di Trani Claudia Augusta , Belsué Virginia , Escalada Javier , Werner Ulrich , Tennagels Norbert , Berraondo Pedro
Published: February 2021

Background: Targeting long-lasting insulins to the liver may improve metabolic alterations that are not corrected with current insulin replacement therapies. However, insulin is only able to promote lipogenesis but not to block gluconeogenesis in the insulin-resistant liver, exacerbating liver steatosis associated with diabetes.

Methods: In order to overcome this limitation, we fused a single-chain insulin to apolipoprotein A-I, and we evaluated the pharmacokinetics and pharmacodynamics of this novel fusion protein in wild type mice and in db/db mice using both recombinant proteins and recombinant adenoassociated virus (AAV).

Results: Here, we report that the fusion protein between single-chain insulin and apolipoprotein A-I prolonged the insulin half-life in circulation, and accumulated in the liver. We analyzed the long-term effect of these insulin fused to apolipoprotein A-I or insulin fused to albumin using AAVs in the db/db mouse model of diabetes, obesity, and liver steatosis. While AAV encoding insulin fused to albumin exacerbated liver steatosis in several mice, AAV encoding insulin fused to apolipoprotein A-I reduced liver steatosis. These results were confirmed upon daily subcutaneous administration of the recombinant insulin-apolipoprotein A-I fusion protein for six weeks. The reduced liver steatosis was associated with reduced body weight in mice treated with insulin fused to apolipoprotein A-I. Recombinant apolipoprotein A-I alone significantly reduces body weight and liver weight, indicating that the apolipoprotein A-I moiety is the main driver of these effects.

Conclusion: The fusion protein of insulin and apolipoprotein A-I could be a promising insulin derivative for the treatment of diabetic patients with associated fatty liver disease.
Evaluation of the Quality of Antibiotic Prescribing in Primary Care: A Multicenter Longitudinal Study From Shenzhen, China
Authors: Gong Yanhong , Li Hui , Yang Heping , Tan Kun , Liu Wei , Li Xiaotong , Wu Jianxiong , Zhang Guopeng , Yin Xiaoxv
Published: February 2021

Background: Currently, there is no comprehensive evaluation of the quality of antibiotic prescribing in China’s primary care facilities based on longitudinal data.

Methods: We randomly selected 11 community health centers in Shenzhen, China, and collected all outpatient prescriptions of these centers from 2010 to 2015. To evaluate the quality of antibiotic prescribing, we used six quality indicators for analysis, including number of antibiotics per 100 consultations, ratio between broad-spectrum and narrow-spectrum antibiotics (B/N ratio), percentage of first-line antibiotics recommended by guidelines, percentage of oral antibiotics with a duration exceeding the guideline recommendation, and new pediatric-specific indicators such as percentage of antibiotics with amoxicillin (A index) and ratio between amoxicillin and broad-spectrum antibiotics (A/B ratio).

Results: During the study period, 571,362 outpatient consultations resulted in antibiotic prescriptions, which contained 706,411 antibiotics. The overall number of antibiotics per 100 consultations decreased significantly from 93.50 in 2010 to 19.98 in 2015 (p = 0.004), but the B/N ratio showed an upward trend over time (p = 0.009). In different populations and different common infections, the number of antibiotics used decreased to varying degrees, while the B/N ratio increased to varying degrees, with the most obvious change in children <5 years. The percentage of first-line antibiotics for common infections was not high, ranging from 3.45 to 44.25% during 2014–2015. The percentage of oral antibiotics with an exceeded duration ranged from 0.70 to 19.39%. Moreover, the A index and A/B ratio in children remained low for a long time, which was 0.76% and 0.01 in 2015.

Conclusion: A review of antibiotic prescribing in Shenzhen, China, showed a substantial reduction in antibiotic use in primary care. However, problems such as widespread use of broad-spectrum antibiotics, insufficient use of first-line antibiotics and low use of amoxicillin were prevalent. Improving and optimizing the quality of antibiotic prescribing, particularly in children prescriptions, will be the focus of future antibiotic stewardship in China.
Overexpression of Activating Transcription Factor 3 Alleviates Cardiac Microvascular Ischemia/Reperfusion Injury in Rats
Authors: Liu Yi , Hu Yisen , Xiong Jingjie , Zeng Xiaocong
Published: February 2021

Activating transcription factor 3 (ATF3) has been confirmed to be responsive to oxidative stress and to negatively regulate the activity of Toll-like receptor 4 (TLR4). However, the effect of ATF3 on cardiac microvascular ischemia/reperfusion (I/R) injury remains unknown. The GEO2R online tool was employed to obtain differentially expressed genes GSE4105 and GSE122020, in two rat I/R injury microarray datasets. We established a rat myocardial I/R model in vivo, and also generated an in vitro hypoxia/reoxygenation (H/R) model of cardiomyoblast H9c2 cells. Overexpression of ATF3 was achieved by adenoviral-mediated gene transfer (Ad-ATF3). Rats were randomly divided into four groups: sham, I/R, I/R + Ad-Lacz (as a control), and I/R + Ad-ATF3. ELISA, CCK-8, DCFH-DA probe, qRT-PCR and Western blotting were used to determine the expression of ATF3, oxidative indices, cellular injury and TLR4/NF-κB pathway-associated proteins. Transmission electron microscopy, immunohistochemistry and immunofluorescence were used to detect the leukocyte infiltration and the alteration of microvascular morphology and function in vivo. Echocardiographic and hemodynamic data were also obtained. Bioinformatics analysis revealed that ATF3 was upregulated in I/R myocardia in two independent rat myocardial I/R models. Cardiac microvascular I/R injury included leukocyte infiltration, microvascular integrity disruption, and microvascular perfusion defect, which eventually resulted in the deterioration of hemodynamic parameters and heart function. Ad-ATF3 significantly restored microvascular function, increased cardiac microvascular perfusion, and improved hemodynamic parameters and heart function. Mechanistically, Ad-ATF3 ameliorated oxidative stress, inhibited TLR4/NF-κB pathway activation and down-regulated the expression of downstream proinflammatory cytokines in I/R myocardium in vivo and in H/R H9c2 cells in vitro. ATF3 overexpression protects against cardiac microvascular I/R injury in part by inhibiting the TLR4/NF-κB pathway and oxidative stress.
Blood microRNA Signatures Serve as Potential Diagnostic Biomarkers for Hepatic Sinusoidal Obstruction Syndrome Caused by Gynura japonica Containing Pyrrolizidine Alkaloids
Authors: Wang Xunjiang , Zhang Wei , Yang Yongfeng , Chen Yiran , Zhuge Yuzheng , Xiong Aizhen , Yang Li , Wang Zhengtao
Published: February 2021

Background and Aims: The Gynura japonica-induced hepatic sinusoidal obstruction syndrome (HSOS) is closely related to pyrrolizidine alkaloids (PAs), and its prevalence has been increasing worldwide in recent years. However, no effective therapy for PA-induced HSOS in clinics is available, partially due to the failure of quick diagnosis. This study aims to identify blood microRNA (miRNA) signatures as potential biomarkers for PA-induced HSOS in clinics.

Methods: The microarray-based miRNA profiling was performed on blood samples of the discovery cohort, which consisted of nine patients with HSOS and nine healthy donors. Differentially expressed miRNAs were further confirmed using a validation cohort, which consisted of 20 independent patients with HSOS. In addition, the rat model was established through the oral administration of the total alkaloid extract from G. japonica to investigate the association of miRNA biomarkers with the progression of HSOS. Bioinformatic analyses, including GO and KEGG enrichment, receiver operating characteristics curve, and correlation analyses were conducted to evaluate the accuracy of the potential miRNA biomarkers.

Results: Three miRNAs, namely miR-148a-3p, miR-362-5p, and miR-194-5p, were overexpressed in patients and rats with PA-induced HSOS. These miRNAs were positively related to the severity of liver injury and displayed considerable diagnostic accuracy for patients with HSOS with areas under the curve over 0.87.

Conclusion: In summary, this study demonstrated that three miRNAs, hsa-miR-148a-3p, hsa-miR-362-5p, and hsa-miR-194-5p, might serve as potential biomarkers for PA-induced HSOS in clinics.
Copper and Cobalt Ions Released from Metal Oxide Nanoparticles Trigger Skin Sensitization
Authors: Kim Sung-Hyun , Lee Jin Hee , Jung Kikyung , Yang Jun-Young , Shin Hyo-Sook , Lee Jeong Pyo , Jeong Jayoung , Oh Jae-Ho , Lee Jong Kwon
Published: February 2021

Human skins are exposed to nanomaterials in everyday life from various sources such as nanomaterial-containing cosmetics, air pollutions, and industrial nanomaterials. Nanomaterials comprising metal haptens raises concerns about the skin sensitization to nanomaterials. In this study, we evaluated the skin sensitization of nanomaterials comparing metal haptens in vivo and in vitro. We selected five metal oxide NPs, containing copper oxide, cobalt monoxide, cobalt oxide, nickel oxide, or titanium oxide, and two types of metal chlorides (CoCl2 and CuCl2), to compare the skin sensitization abilities between NPs and the constituent metals. The materials were applied to KeratinoSensTM cells for imitated skin-environment setting, and luciferase induction and cytotoxicity were evaluated at 48 h post-incubation. In addition, the response of metal oxide NPs was confirmed in lymph node of BALB/C mice via an in vivo method. The results showed that CuO and CoO NPs induce a similar pattern of positive luciferase induction and cytotoxicity compared to the respective metal chlorides; Co3O4, NiO, and TiO2 induced no such response. Collectively, the results implied fast-dissolving metal oxide (CuO and CoO) NPs release their metal ion, inducing skin sensitization. However, further investigations are required to elucidate the mechanism underlying NP-induced skin sensitization. Based on ion chelation data, metal ion release was confirmed as the major “factor” for skin sensitization.