bluuebunny/crossref_metadata_2025 huggingface dataset:
Preparing Distributed Computing Operations for the HL-LHC Era With Operational Intelligence
Authors: Di Girolamo Alessandro , Legger Federica , Paparrigopoulos Panos , Schovancová Jaroslava , Beermann Thomas , Boehler Michael , Bonacorsi Daniele , Clissa Luca , Decker de Sousa Leticia , Diotalevi Tommaso , Giommi Luca , Grigorieva Maria , Giordano Domenico , Hohn David , Javůrek Tomáš , Jezequel Stephane , Kuznetsov Valentin , Lassnig Mario , Mageirakos Vasilis , Olocco Micol , Padolski Siarhei , Paltenghi Matteo , Rinaldi Lorenzo , Sharma Mayank , Tisbeni Simone Rossi , Tuckus Nikodemas
Published: January 2022

As a joint effort from various communities involved in the Worldwide LHC Computing Grid, the Operational Intelligence project aims at increasing the level of automation in computing operations and reducing human interventions. The distributed computing systems currently deployed by the LHC experiments have proven to be mature and capable of meeting the experimental goals, by allowing timely delivery of scientific results. However, a substantial number of interventions from software developers, shifters, and operational teams is needed to efficiently manage such heterogenous infrastructures. Under the scope of the Operational Intelligence project, experts from several areas have gathered to propose and work on “smart” solutions. Machine learning, data mining, log analysis, and anomaly detection are only some of the tools we have evaluated for our use cases. In this community study contribution, we report on the development of a suite of operational intelligence services to cover various use cases: workload management, data management, and site operations.
Spatiotemporal Variations of Focal Mechanism Solutions and Stress Field of the 2019 Changning Ms 6.0 Earthquake Sequence
Authors: Zhang Zhiwei , Liang Chuntao , Long Feng , Zhao Min , Wang Di
Published: January 2022

The June 17, 2019, MS 6.0 Changning earthquake is the largest recorded event in the Sichuan basin, spatiotemporal variations of stress field may shed light on the seismogenic mechanism of the earthquake. We determined the focal mechanism solutions (FMSs) of 124 earthquakes with MS ≥ 3.0 occurring in the Changning area from April 1, 2007, to February 29, 2020, and analyzed changes of FMSs and stress field before and after Changning earthquake. The Changning aftershocks were predominantly thrust fault earthquakes, followed by strike slip. The P-axis azimuths of the aftershock FMSs were oriented predominantly in the NEE direction, notably differing from the NWW-oriented P-axis azimuths of pre-earthquake FMSs; it shows the rotation of local stress field before and after the Changning earthquake, it is speculated that the change of stress field in Changning area may be caused by long-term water injection and salt mining activities. From the southeast to the northwest of the aftershock zone, the azimuths of principal compressive stress (S1) change from NEE to near-EW in both horizontal and vertical planes. Significant changes occurred in the FMS types and stress field of the aftershock zone following the Changning earthquake, the FMSs became diverse, the S1 azimuth of the Changning area changed from NWW to NEE, and then EW, the plunge and stress tensor variances increased, it reflects that the stress field of the Changning area adjusts continually with time.
Changing Police Personal Safety Training Using Scenario-Based-Training: A Critical Analysis of the ‘Dilemmas of Practice’ Impacting Change
Authors: Cushion Christopher
Published: January 2022

This paper outlines an analysis of using Scenario-Based-Training (SBT) to change officer Personal Safety Training (PST) based on existing research evidence and reflections from supporting a National Police Agency attempting to change PST practice. SBT is interrogated in light of its underlying assumptions and situated within the ambiguities, tensions and compromises inherent within police training cultures. Using Windschitl’s framework of conceptual, pedagogical, cultural, and political dilemmas this paper analyses the forces impacting using SBT to change PST. An alternative agenda for change is presented to develop skilled officers and trainers equipped with innovative pedagogies to ‘re-culture’ PST.
Long-Term Exposure to Ambient PM2.5, Sunlight, and Obesity: A Nationwide Study in China
Authors: Chen Rui , Yang Chao , Li Pengfei , Wang Jinwei , Liang Ze , Wang Wanzhou , Wang Yueyao , Liang Chenyu , Meng Ruogu , Wang Huai-yu , Peng Suyuan , Sun Xiaoyu , Su Zaiming , Kong Guilan , Wang Yang , Zhang Luxia
Published: January 2022

Background

Accumulated researches revealed that both fine particulate matter (PM2.5) and sunlight exposure may be a risk factor for obesity, while researches regarding the potential effect modification by sunlight exposure on the relationship between PM2.5 and obesity are limited. We aim to investigate whether the effect of PM2.5 on obesity is affected by sunlight exposure among the general population in China.

Methods

A sample of 47,204 adults in China was included. Obesity and abdominal obesity were assessed based on body mass index, waist circumference and waist-to-hip ratio, respectively. The five-year exposure to PM2.5 and sunlight were accessed using the multi-source satellite products and a geochemical transport model. The relationship between PM2.5, sunshine duration, and the obesity or abdominal obesity risk was evaluated using the general additive model.

Results

The proportion of obesity and abdominal obesity was 12.6% and 26.8%, respectively. Levels of long-term PM2.5 ranged from 13.2 to 72.1 μg/m3 with the mean of 46.6 μg/m3. Each 10 μg/m3 rise in PM2.5 was related to a higher obesity risk [OR 1.12 (95% CI 1.09-1.14)] and abdominal obesity [OR 1.10 (95% CI 1.07-1.13)]. The association between PM2.5 and obesity varied according to sunshine duration, with the highest ORs of 1.56 (95% CI 1.28-1.91) for obesity and 1.66 (95% CI 1.34-2.07) for abdominal obesity in the bottom quartile of sunlight exposure (3.21-5.34 hours/day).

Conclusion

Long-term PM2.5 effect on obesity risk among the general Chinese population are influenced by sunlight exposure. More attention might be paid to reduce the adverse impacts of exposure to air pollution under short sunshine duration conditions.
Microbial Diversity of Reconstituted, Degraded, and Agricultural Soils Assessed by 16S rDNA Multi-Amplicon Sequencing
Authors: Maretto Laura , Deb Saptarathi , Ravi Samathmika , Chiodi Claudia , Manfredi Paolo , Squartini Andrea , Concheri Giuseppe , Renella Giancarlo , Stevanato Piergiorgio
Published: January 2022

The microbial diversity is, among soil key factors, responsible for soil fertility and nutrient biogeochemical cycles, and can be modified upon changes in main soil physicochemical properties and soil pollution. Over the years, many restoration techniques have been applied to restore degraded soils. However, the effect of these approaches on soil microbial diversity is less understood and thus requires more investigation. In this study, we analyzed the impact, on soil microbial diversity of a patented novel technology, used to restore degraded soils. Soil samples were collected from three nearby sites located in Borgotrebbia, Piacenza, Italy, and categorized as reconstituted, degraded, and agricultural soils. After total soil DNA extraction, 16S rDNA multi-amplicon sequencing was carried out using an Ion GeneStudio S5 System to compare soils’ bacterial community profiles. Sequenced reads were processed to assign taxonomy and then key microbial community differences were identified across the sampling sites. Species diversity featured significant abatement at all rank levels in the degraded soil when compared to the agricultural control. The 5 year restoration technique showed full recovery of this index at the genus level but not at the phylum level, displaying a rank-dependent gradient of restored richness. In parallel, the abundance of genes involved in the nitrogen (N) biogeochemical cycle was assessed using quantitative Real-Time PCR (qPCR). Total DNA content was significantly higher (p < 0.05) in degraded (μ = 12.69 ± 2.58 μg g−1) and reconstituted (μ = 11.73 ± 1.65 μg g−1) soil samples when compared to the agricultural soil samples (μ = 2.39 ± 0.50 μg g−1). The taxonomic diversity of each soil site was significantly different, with some instances unique of the agricultural soil even at the phylum level. The analysis of N functional genes showed that the relative abundance of bacterial amoA (p < 0.05) and nosZ (p < 0.01) genes were significantly lower in the agricultural than in the reconstituted and degraded soils. We concluded that the application of the soil reconstitution technique appears to enhance the active microbial community, with distinct diversity and functionality towards genes involved in N biogeochemical cycle, as compared to both the degraded and the agricultural soil.
Comprehensive Analysis of Pyroptosis-Associated in Molecular Classification, Immunity and Prognostic of Glioma
Authors: Chen Peng , Li Yanyan , Li Na , Shen Liangfang , Li Zhanzhan
Published: January 2022

Integrative analysis was performed in the Chinese Glioma Genome Atlas and The Cancer Genome Atlas to describe the pyroptosis-associated molecular classification and prognostic signature in glioma. Pyroptosis-related genes were used for consensus clustering and to develop a prognostic signature. The immune statuses, molecular alterations, and clinical features of differentially expressed genes were analyzed among different subclasses and risk groups. A lncRNA-miRNA-mRNA network was built, and drug sensitivity analysis was used to identify small molecular drugs for the identified genes. Glioma can be divided into two subclasses using 30 pyroptosis-related genes. Cluster 1 displayed high immune signatures and poor prognosis as well as high immune-related function scores. A prognostic signature based on 15 pyroptosis-related genes of the CGGA cohort can predict the overall survival of glioma and was well validated in the TCGA cohort. Cluster 1 had higher risk scores. The high-risk group had high immune cell and function scores and low DNA methylation of pyroptosis-related genes. The differences in pyroptosis-related gene mutations and somatic copy numbers were significant between the high-risk and low-risk groups. The ceRNA regulatory network uncovered the regulatory patterns of different risk groups in glioma. Nine pairs of target genes and drugs were identified. In vitro, CASP8 promotes the progression of glioma cells. Pyroptosis-related genes can reflect the molecular biological and clinical features of glioma subclasses. The established prognostic signature can predict prognosis and distinguish molecular alterations in glioma patients. Our comprehensive analyses provide valuable guidelines for improving glioma patient management and individualized therapy.
GMQN: A Reference-Based Method for Correcting Batch Effects and Probe Bias in HumanMethylation BeadChip
Authors: Xiong Zhuang , Li Mengwei , Ma Yingke , Li Rujiao , Bao Yiming
Published: January 2022

The Illumina HumanMethylation BeadChip is one of the most cost-effective methods to quantify DNA methylation levels at single-base resolution across the human genome, which makes it a routine platform for epigenome-wide association studies. It has accumulated tens of thousands of DNA methylation array samples in public databases, providing great support for data integration and further analysis. However, the majority of public DNA methylation data are deposited as processed data without background probes which are widely used in data normalization. Here, we present Gaussian mixture quantile normalization (GMQN), a reference based method for correcting batch effects as well as probe bias in the HumanMethylation BeadChip. Availability and implementation: https://github.com/MengweiLi-project/gmqn.
“Worn-out but happy”: Postpartum Women's Mental Health and Well-Being During COVID-19 Restrictions in Australia
Authors: Christie Hannah E. , Beetham Kassia , Stratton Elizabeth , Francois Monique E.
Published: January 2022

Background: From late 2019, COVID-19 disease has infiltrated the global population causing widespread challenges to public health. One cohort that has received less attention, but who may be more vulnerable to the mental and physical health related impacts of COVID-19 restrictions are postpartum mothers. The aim of this study was to explore the mental health, well-being, and health behaviours of mothers up to 12 months postpartum whilst living in Australia under COVID-19 level 3 and 4 restrictions.

Methods: 351 women in their first year postpartum residing in Australia whilst under level 3/4 social distancing restrictions (during April 13 and June 11, 2020) were recruited to participate in an online questionnaire. The survey measured symptoms of depression, anxiety, and stress (DASS), wellness (SF-36), physical activity (Godin-Shephard score), perceived value of health outcomes, diet, and sleep. Descriptive statistics and linear regressions were performed.

Results: Data was analysed for 139 eligible women. Of these women, 74% scored “normal” for depression, 84% for anxiety, and 72% for stress. Over half (58%) of women reported being worn out all, most, or a good bit of the time and 77% reported being a happy person all, most, or a good bit of the time. Analysis of the perceived values of health outcome revealed women had high value for “getting out of the house,” “achieving a better overall mood,” and “to feel better physically.” Women were considered physically active according to the Godin Leisure score, however only 41% of women met the current Australian national physical activity guidelines of 150 min.week−1.

Conclusions: Overall the majority of postpartum mums that were surveyed, have normal mental health symptoms, and despite being worn out most are happy at least a good bit of the time. This study highlights the importance of health values in maintaining leisure physical activity and mental health. In addition it appears women may benefit from virtual group exercise and community programs to encourage being physically active and socialising with friends simultaneously.
Therapeutic Implications of Tumor Microenvironment in Lung Cancer: Focus on Immune Checkpoint Blockade
Authors: Genova Carlo , Dellepiane Chiara , Carrega Paolo , Sommariva Sara , Ferlazzo Guido , Pronzato Paolo , Gangemi Rosaria , Filaci Gilberto , Coco Simona , Croce Michela
Published: January 2022

In the last decade, the treatment of non-small cell lung cancer (NSCLC) has been revolutionized by the introduction of immune checkpoint inhibitors (ICI) directed against programmed death protein 1 (PD-1) and its ligand (PD-L1), or cytotoxic T lymphocyte antigen 4 (CTLA-4). In spite of these improvements, some patients do not achieve any benefit from ICI, and inevitably develop resistance to therapy over time. Tumor microenvironment (TME) might influence response to immunotherapy due to its prominent role in the multiple interactions between neoplastic cells and the immune system. Studies investigating lung cancer from the perspective of TME pointed out a complex scenario where tumor angiogenesis, soluble factors, immune suppressive/regulatory elements and cells composing TME itself participate to tumor growth. In this review, we point out the current state of knowledge involving the relationship between tumor cells and the components of TME in NSCLC as well as their interactions with immunotherapy providing an update on novel predictors of benefit from currently employed ICI or new therapeutic targets of investigational agents. In first place, increasing evidence suggests that TME might represent a promising biomarker of sensitivity to ICI, based on the presence of immune-modulating cells, such as Treg, myeloid derived suppressor cells, and tumor associated macrophages, which are known to induce an immunosuppressive environment, poorly responsive to ICI. Consequently, multiple clinical studies have been designed to influence TME towards a pro-immunogenic state and subsequently improve the activity of ICI. Currently, the mostly employed approach relies on the association of “classic” ICI targeting PD-1/PD-L1 and novel agents directed on molecules, such as LAG-3 and TIM-3. To date, some trials have already shown promising results, while a multitude of prospective studies are ongoing, and their results might significantly influence the future approach to cancer immunotherapy.
Potential Role of the Gut Microbiome In Colorectal Cancer Progression
Authors: Kim Jaeho , Lee Heung Kyu
Published: January 2022

An increasing number of studies have revealed that the progression of colorectal cancer (CRC) is related to gut microbiome composition. Under normal conditions, the gut microbiome acts as a barrier to other pathogens or infections in the intestine and modulates inflammation by affecting the host immune system. These gut microbiota are not only related to the intestinal inflammation associated with tumorigenesis but also modulation of the anti-cancer immune response. Thus, they are associated with tumor progression and anti-cancer treatment efficacy. Studies have shown that the gut microbiota can be used as biomarkers to predict the effect of immunotherapy and improve the efficacy of immunotherapy in treating CRC through modulation. In this review, we discuss the role of the gut microbiome as revealed by recent studies of the growth and progression of CRC along with its synergistic effect with anti-cancer treatment modalities.
Myeloid Diagnostic and Prognostic Markers of Immune Suppression in the Blood of Glioma Patients
Authors: Del Bianco Paola , Pinton Laura , Magri Sara , Canè Stefania , Masetto Elena , Basso Daniela , Padovan Marta , Volpin Francesco , d’Avella Domenico , Lombardi Giuseppe , Zagonel Vittorina , Bronte Vincenzo , Della Puppa Alessandro , Mandruzzato Susanna
Published: January 2022

Background

Although gliomas are confined to the central nervous system, their negative influence over the immune system extends to peripheral circulation. The immune suppression exerted by myeloid cells can affect both response to therapy and disease outcome. We analyzed the expansion of several myeloid parameters in the blood of low- and high-grade gliomas and assessed their relevance as biomarkers of disease and clinical outcome.

Methods

Peripheral blood was obtained from 134 low- and high-grade glioma patients. CD14+, CD14+/p-STAT3+, CD14+/PD-L1+, CD15+ cells and four myeloid-derived suppressor cell (MDSC) subsets, were evaluated by flow cytometry. Arginase-1 (ARG1) quantity and activity was determined in the plasma. Multivariable logistic regression model was used to obtain a diagnostic score to discriminate glioma patients from healthy controls and between each glioma grade. A glioblastoma prognostic model was determined by multiple Cox regression using clinical and myeloid parameters.

Results

Changes in myeloid parameters associated with immune suppression allowed to define a diagnostic score calculating the risk of being a glioma patient. The same parameters, together with age, permit to calculate the risk score in differentiating each glioma grade. A prognostic model for glioblastoma patients stemmed out from a Cox multiple analysis, highlighting the role of MDSC, p-STAT3, and ARG1 activity together with clinical parameters in predicting patient’s outcome.

Conclusions

This work emphasizes the role of systemic immune suppression carried out by myeloid cells in gliomas. The identification of biomarkers associated with immune landscape, diagnosis, and outcome of glioblastoma patients lays the ground for their clinical use.
Red Blood Cell Distribution Width in Hospitalized COVID-19 Patients
Authors: Ramachandran Preethi , Gajendran Mahesh , Perisetti Abhilash , Elkholy Karim Osama , Chakraborti Abhishek , Lippi Giuseppe , Goyal Hemant
Published: January 2022

Introduction: Coronavirus disease-2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is causing dramatic morbidity and mortality worldwide. The Red Blood Cell Distribution Width (RDW) has been strongly associated with increased morbidity and mortality in multiple diseases.

Objective: To assess if elevated RDW is associated with unfavorable outcomes in hospitalized COVID-19.

Methods: We retrospectively studied clinical outcomes of hospitalized COVID-19 patients for their RDW values. In-hospital mortality was defined as primary outcome, while septic shock, need for mechanical ventilation, and length of stay (LOS) were secondary outcomes.

Results: A total of 294 COVID-19 patients were finally studied. Overall prevalence of increased RDW was 49.7% (146/294). RDW was associated with increased risk of in-hospital mortality (aOR, 4.6; 95%CI, 1.5-14.6) and septic shock (aOR, 4.6; 95%CI, 1.4-15.1) after adjusting for anemia, ferritin, lactate, and absolute lymphocyte count. The association remained unchanged even after adjusting for other clinical confounders such as age, sex, body mass index, coronary artery disease, hypertension, diabetes mellitus, and chronic obstructive pulmonary disease. No association was found instead with mechanical ventilation and median LOS.

Conclusion: Elevated RDW in hospitalized COVID-19 patients is associated with a significantly increased risk of mortality and septic shock.
Small-Molecule Compound SYG-180-2-2 to Effectively Prevent the Biofilm Formation of Methicillin-Resistant Staphylococcus aureus
Authors: Rao Lulin , Sheng Yaoguang , Zhang Jiao , Xu Yanlei , Yu Jingyi , Wang Bingjie , Zhao Huilin , Wang Xinyi , Guo Yinjuan , Wu Xiaocui , Song Zengqiang , Yu Fangyou , Zhan Lingling
Published: January 2022

The resistance of methicillin-resistant Staphylococcus aureus (MRSA) has augmented due to the abuse of antibiotics, bringing about difficulties in the treatment of infection especially with the formation of biofilm. Thus, it is essential to develop antimicrobials. Here we synthesized a novel small-molecule compound, which we termed SYG-180-2-2 (C21H16N2OSe), that had antibiofilm activity. The aim of this study was to demonstrate the antibiofilm effect of SYG-180-2-2 against clinical MRSA isolates at a subinhibitory concentration (4 μg/ml). In this study, it was showed that significant suppression in biofilm formation occurred with SYG-180-2-2 treatment, the inhibition ranged between 65.0 and 85.2%. Subsequently, confocal laser scanning microscopy and a bacterial biofilm metabolism activity assay further demonstrated that SYG-180-2-2 could suppress biofilm. Additionally, SYG-180-2-2 reduced bacterial adhesion and polysaccharide intercellular adhesin (PIA) production. It was found that the expression of icaA and other biofilm-related genes were downregulated as evaluated by RT-qPCR. At the same time, icaR and codY were upregulated when biofilms were treated with SYG-180-2-2. Based on the above results, we speculate that SYG-180-2-2 inhibits the formation of biofilm by affecting cell adhesion and the expression of genes related to PIA production. Above all, SYG-180-2-2 had no toxic effects on human normal alveolar epithelial cells BEAS-2B. Collectively, the small-molecule compound SYG-180-2-2 is a safe and effective antibacterial agent for inhibiting MRSA biofilm.
Molecular Network Analysis Reveals Transmission of HIV-1 Drug-Resistant Strains Among Newly Diagnosed HIV-1 Infections in a Moderately HIV Endemic City in China
Authors: Zhao Bin , Song Wei , Kang Mingming , Dong Xue , Li Xin , Wang Lu , Liu Jianmin , Ding Haibo , Chu Zhenxing , Wang Lin , Qiu Yu , Shang Hong , Han Xiaoxu
Published: January 2022

Since the implementation of the “treat all” policy in China in 2016, there have been few data on the prevalence of transmitted drug resistance (TDR) in China. In this study, we describe TDR in patients newly diagnosed with human immunodeficiency virus (HIV) infection between 2016 and 2019 in Shenyang city, China. Demographic information and plasma samples from all newly reported HIV-infected individuals in Shenyang from 2016 to 2019 were collected. The HIVpolgene was amplified and sequenced for subtyping and TDR. The spread of TDR was analyzed by inferring an HIV molecular network based on pairwise genetic distance. In total, 2,882 sequences including CRF01_AE (2019/2,882, 70.0%), CRF07_BC (526/2,882, 18.3%), subtype B (132/2,882, 4.6%), and other subtypes (205/2,882, 7.1%) were obtained. The overall prevalence of TDR was 9.1% [95% confidence interval (CI): 8.1–10.2%]; the prevalence of TDR in each subtype in descending order was CRF07_BC [14.6% (95% CI: 11.7–18.0%)], subtype B [9.1% (95% CI: 4.8–15.3%)], CRF01_AE [7.9% (95% CI: 6.7–9.1%)], and other sequences [7.3% (95% CI: 4.2–11.8%)]. TDR mutations detected in more than 10 cases were Q58E (n= 51), M46ILV (n= 46), K103N (n= 26), E138AGKQ (n= 25), K103R/V179D (n= 20), and A98G (n= 12). Molecular network analysis revealed three CRF07_BC clusters with TDR [two with Q58E (29/29) and one with K103N (10/19)]; and five CRF01_AE clusters with TDR [two with M46L (6/6), one with A98G (4/4), one with E138A (3/3), and one with K103R/V179D (3/3)]. In the TDR clusters, 96.4% (53/55) of individuals were men who have sex with men (MSM). These results indicate that TDR is moderately prevalent in Shenyang (5–15%) and that TDR strains are mainly transmitted among MSM, providing precise targets for interventions in China.
Real-Time Monitoring of the Yeast Intracellular State During Bioprocesses With a Toolbox of Biosensors
Authors: Torello Pianale Luca , Rugbjerg Peter , Olsson Lisbeth
Published: January 2022

Industrial fermentation processes strive for high robustness to ensure optimal and consistent performance. Medium components, fermentation products, and physical perturbations may cause stress and lower performance. Cellular stress elicits a range of responses, whose extracellular manifestations have been extensively studied; whereas intracellular aspects remain poorly known due to lack of tools for real-time monitoring. Genetically encoded biosensors have emerged as promising tools and have been used to improve microbial productivity and tolerance toward industrially relevant stresses. Here, fluorescent biosensors able to sense the yeast intracellular environment (pH, ATP levels, oxidative stress, glycolytic flux, and ribosome production) were implemented into a versatile and easy-to-use toolbox. Marker-free and efficient genome integration at a conserved site on chromosome X of Saccharomyces cerevisiae strains and a commercial Saccharomyces boulardii strain was developed. Moreover, multiple biosensors were used to simultaneously monitor different intracellular parameters in a single cell. Even when combined together, the biosensors did not significantly affect key physiological parameters, such as specific growth rate and product yields. Activation and response of each biosensor and their interconnection were assessed using an advanced micro-cultivation system. Finally, the toolbox was used to screen cell behavior in a synthetic lignocellulosic hydrolysate that mimicked harsh industrial substrates, revealing differences in the oxidative stress response between laboratory (CEN.PK113-7D) and industrial (Ethanol Red) S. cerevisiae strains. In summary, the toolbox will allow both the exploration of yeast diversity and physiological responses in natural and complex industrial conditions, as well as the possibility to monitor production processes.
Volatile Organic Compound Profiles From Wheat Diseases Are Pathogen-Specific and Can Be Exploited for Disease Classification
Authors: Ficke Andrea , Asalf Belachew , Norli Hans Ragnar
Published: January 2022

Plants and fungi emit volatile organic compounds (VOCs) that are either constitutively produced or are produced in response to changes in their physico-chemical status. We hypothesized that these chemical signals could be utilized as diagnostic tools for plant diseases. VOCs from several common wheat pathogens in pure culture (Fusarium graminearum, Fusarium culmorum, Fusarium avenaceum, Fusarium poae, and Parastagonospora nodorum) were collected and compared among isolates of the same fungus, between pathogens from different species, and between pathogens causing different disease groups [Fusarium head blight (FHB) and Septoria nodorum blotch (SNB)]. In addition, we inoculated two wheat varieties with either F. graminearum or P. nodorum, while one variety was also inoculated with Blumeria graminis f.sp. tritici (powdery mildew, PM). VOCs were collected 7, 14, and 21 days after inoculation. Each fungal species in pure culture emitted a different VOC blend, and each isolate could be classified into its respective disease group based on VOCs with an accuracy of 71.4 and 84.2% for FHB and SNB, respectively. When all collection times were combined, the classification of the tested diseases was correct in 84 and 86% of all cases evaluated. Germacrene D and sativene, which were associated with FHB infection, and mellein and heptadecanone, which were associated with SNB infection, were consistently emitted by both wheat varieties. Wheat plants infected with PM emitted significant amounts of 1-octen-3-ol and 3,5,5-trimethyl-2-hexene. Our study suggests that VOC blends could be used to classify wheat diseases. This is the first step toward a real-time disease detection in the field based on chemical signatures of wheat diseases.
Seeing What I Did (Not): Cerebral and Behavioral Effects of Agency and Perspective on Episodic Memory Re-activation
Authors: Jainta Benjamin , Siestrup Sophie , El-Sourani Nadiya , Trempler Ima , Wurm Moritz F. , Werning Markus , Cheng Sen , Schubotz Ricarda I.
Published: January 2022

Intuitively, we assume that we remember episodes better when we actively participated in them and were not mere observers. Independently of this, we can recall episodes from either the first-person perspective (1pp) or the third-person perspective (3pp). In this functional magnetic resonance imaging (fMRI) study, we tested whether agency and perspective modulate neural activity during memory retrieval and subsequently enhance memory performance. Subjects encoded a set of different episodes by either imitating or only observing videos that showed short toy stories. A week later, we conducted fMRI and cued episodic retrieval by presenting the original videos, or slightly modified versions thereof, from 1pp or from 3pp. The hippocampal formation was sensitive to self-performed vs. only observed actions only when there was an episodic mismatch. In a post-fMRI memory test a history of self-performance did not improve behavioral memory performance. However, modified videos were often (falsely) accepted as showing truly experienced episodes when: (i) they were already presented in this modified version during fMRI or (ii) they were presented in their original form during fMRI but from 3pp. While the overall effect of modification was strong, the effects of perspective and agency were more subtle. Together, our findings demonstrate that self-performance and self-perspective modulate the strength of a memory trace in different ways. Even when memory performance remains the same for different agentive states, the brain is capable of detecting mismatching information. Re-experiencing the latter impairs memory performance as well as retrieving encoded episodes from 3pp.
Amygdala Underlies the Environment Dependency of Defense Responses Induced via Superior Colliculus
Authors: Isa Kaoru , Tokuoka Kota , Ikeda Sakura , Karimi Sara , Kobayashi Kenta , Sooksawate Thongchai , Isa Tadashi
Published: January 2022

In our previous study, we showed that the defense responses induced by the selective optogenetic activation of the uncrossed output pathway from the deeper layer of the superior colliculus were environment dependent in the mouse. In a small closed box, the stimulus frequently induced flight (fast forward run away) responses, while in a large open field, the stimulus tended to induce backward retreat responses. We tested a hypothesis that the amygdala is involved in such environment dependency of the innate defense responses. For this purpose, we made a bilateral lesion of the amygdala induced by the ibotenic acid injections in male mice. As a result, in the mice with lesions of substantial portions of the basolateral and basomedial complex, the flight responses in the closed box disappeared and retreat responses were mainly induced. The retreat responses on the open platform were unchanged. Classically, the amygdala has been considered to be involved in the memory-dependent contextual modulation of the fear responses. In contrast, the present results suggest a novel view on the role of the amygdala in which the amygdala plays a key role in sensing the current environmental setting for making a quick decision of action upon emergency, which is critical for survival in the natural environment.
Late-Onset Ictal Asystole and Falls Related to Severe Coronary Artery Stenosis: A Case Report
Authors: Fortunato Francesco , Labate Angelo , Trimboli Michele , Spaccarotella Carmen , Indolfi Ciro , Gambardella Antonio
Published: January 2022

Introduction: Ictal asystole (IA) is a rare, underestimated, and life-threatening cause of transient loss of consciousness and fall. Current treatment options for seizures associated with IA usually include cardiac pacemaker implantation. We report, for the first time, a case of IA that is related to coronary stenosis, which was resolved after coronary angioplasty.

Case Presentation: A 73-year-old man had a 2-year history of focal seizures with impaired awareness. Three months before our observation, he started to have sudden falls resulting in injury on several occasions. General and neurological examinations, as well as brain MRI, were unremarkable. Interictal electroencephalography (EEG) showed bitemporal spiking. Ictal video-polygraphy revealed a diffuse electrodecrement, followed by a buildup of rhythmic 4–6 Hz sharp activity, which was more evident in the left temporal region. After the seizure onset, the ECG showed sinus bradycardia, followed by sinus arrest that was associated with the patient's fall from the standing position. Afterwards, sinus rhythm returned spontaneously. A diagnosis of IA was made. A comprehensive cardiologic evaluation revealed a sub-occlusive stenosis of the left anterior descending artery. Successful coronary angioplasty resolved IA, levetiracetam was added, and no seizure or fall has occurred in the following 20 months. Moreover, he underwent a 7-day Holter ECG monitoring, and no asystole was depicted.

Conclusion: The present case was unique as it shows the potential association between IA and coronary stenosis, also suggesting a possible therapeutic role for coronary angioplasty. It also highlights the importance of carefully investigating epilepsy patients with falls, especially in the elderly, since IA-related falls can be easily misdiagnosed in older age. Thus, if IA is identified, a deeper cardiac evaluation should be considered. As seen in our patient, non-invasive diagnostic examination including routine, prolonged, and exercise ECG, as well as echocardiogram, were readily available and were informative in diagnosing cardiac abnormalities that are amenable to specific treatment.
Associated Factors and Prognostic Implications of Non-convulsive Status Epilepticus in Ischemic Stroke Patients With Impaired Consciousness
Authors: Zhang Liren , Zheng Wensi , Chen Feng , Bai Xiaolin , Xue Lixia , Liang Mengke , Geng Zhi
Published: January 2022

Background and Purpose: Non-convulsive status epilepticus (NCSE) is common in patients with disorders of consciousness and can cause secondary brain injury. Our study aimed to explore the determinants and prognostic significance of NCSE in stroke patients with impaired consciousness.

Method: Consecutive ischemic stroke patients with impaired consciousness who were admitted to a neuro intensive care unit were enrolled for this study. Univariate and multivariable logistic regression were used to identify factors associated with NCSE and their correlation with prognosis.

Results: Among the 80 patients studied, 20 (25%) died during hospitalization, and 51 (63.75%) had unfavorable outcomes at the 3-month follow-up. A total of 31 patients (38.75%) developed NCSE during 24-h electroencephalogram (EEG) monitoring. Logistic regression revealed that NCSE was significantly associated with an increased risk of death during hospital stay and adverse outcomes at the 3-month follow-up. Patients with stroke involving the cerebral cortex or those who had a severely depressed level of consciousness were more prone to epileptogenesis after stroke.

Conclusion: Our results suggest that NCSE is a common complication of ischemic stroke, and is associated with both in-hospital mortality and dependency at the 3-month follow-up. Long-term video EEG monitoring of stroke patients is, therefore required, especially for those with severe consciousness disorders (stupor or coma) or cortical injury.
Are Brain–Computer Interfaces Feasible With Integrated Photonic Chips?
Authors: Salari Vahid , Rodrigues Serafim , Saglamyurek Erhan , Simon Christoph , Oblak Daniel
Published: January 2022

The present paper examines the viability of a radically novel idea for brain–computer interface (BCI), which could lead to novel technological, experimental, and clinical applications. BCIs are computer-based systems that enable either one-way or two-way communication between a living brain and an external machine. BCIs read-out brain signals and transduce them into task commands, which are performed by a machine. In closed loop, the machine can stimulate the brain with appropriate signals. In recent years, it has been shown that there is some ultraweak light emission from neurons within or close to the visible and near-infrared parts of the optical spectrum. Such ultraweak photon emission (UPE) reflects the cellular (and body) oxidative status, and compelling pieces of evidence are beginning to emerge that UPE may well play an informational role in neuronal functions. In fact, several experiments point to a direct correlation between UPE intensity and neural activity, oxidative reactions, EEG activity, cerebral blood flow, cerebral energy metabolism, and release of glutamate. Therefore, we propose a novel skull implant BCI that uses UPE. We suggest that a photonic integrated chip installed on the interior surface of the skull may enable a new form of extraction of the relevant features from the UPE signals. In the current technology landscape, photonic technologies are advancing rapidly and poised to overtake many electrical technologies, due to their unique advantages, such as miniaturization, high speed, low thermal effects, and large integration capacity that allow for high yield, volume manufacturing, and lower cost. For our proposed BCI, we are making some very major conjectures, which need to be experimentally verified, and therefore we discuss the controversial parts, feasibility of technology and limitations, and potential impact of this envisaged technology if successfully implemented in the future.
Clinical and Genetic Characteristics of Thymoma Patients With Autoimmune Hepatitis and Myocarditis
Authors: Yu Xin-tao , Yu Lei , Du Xin , Yu Zhen , Yang Xing-guo , Jiang Yu-xuan
Published: January 2022

Background

Our study investigated a special series of thymoma with autoimmune hepatitis and myocarditis and tried to reveal the gene expression profiles of this series of thymoma.

Methods

From 2011 to 2019, a total of 13 special thymoma patients presented with autoimmune hepatitis and myocarditis, accounting for about 1.26% of thymoma patients undergoing surgery in Beijing TongRen Hospital. Clinical data were retrospectively collected. All samples were harvested during surgical procedures, and analyzed to identify changes in gene expression using the CapitalBio mRNA microarray analysis, the Whole exome sequencing analysis (WES), qPCR and immunohistochemistry (IHC) tools.

Results

After surgery, patient symptoms were relieved gradually. Levels of lactate dehydrogenase (LDH), creatine kinase MB (CK-MB), aspartate transaminase (AST), and alanine amiotransferase (ALT) increased to some extent within 1 to 3 months after surgery, and fluctuated, and then, gradually decreased close to normal within 6 months after surgery. Enrichment analysis of Kyoto Genome and Genome Encyclopedia (KEGG) pathway was performed and enrichment results were visualized. It indicated that gene expression of 5 signaling pathways, including cell cycle and p53 signaling pathway, were generally abnormal. P53 expression was up-regulated in all tumor tissues. However, IHC and qPCR analysis showed that there was no significant difference in p21 expression between normal and tumor tissue. Results of WES showed that only one driver gene-MDM4 amplified 4 fold in 53.2% thymoma cells. Further qPCR and IHC analysis confirmed the up-regulation of the expression of p53 and mdm4 in 13 thymoma patients with autoimmune hepatitis and myocarditis.

Conclusion

Our study reveals the clinical and genetic characteristics of thymoma patients with autoimmune hepatitis and myocarditis. For this special category of thymoma, the up-regulation of p53 and mdm4 plays an important role in the occurrence of thymoma and autoimmune hepatitis/myocarditis.
Case Report: Significant Clinical Benefit From Pemetrexed-Based Therapy in ROS1- and ALK-rearranged Lung Cancer With Adenosquamous Histology
Authors: Patil Tejas , Nie Yunan , Aisner Dara L. , Camidge David Ross
Published: January 2022

Pemetrexed (used as a platinum doublet or as a maintenance regimen) is an established therapy for patients with advanced non-squamous non-small-cell lung cancer (NSCLC). In addition, certain gene rearrangements (e.g., ALK, ROS1, RET) appear to especially benefit from the use of pemetrexed. Inferior outcomes with pemetrexed compared to other chemotherapies in patients with NSCLC demonstrating squamous histology removed these patients from the labeled indication for the drug. While most squamous cases do not harbor driver oncogenes, rare exceptions exist. Whether the poor outcomes with pemetrexed extend to NSCLC with squamous component harboring driver oncogenes remains unexplored. In this case series, we describe two patients with adenosquamous histology harboring an ROS1 and ALK gene arrangement, respectively, who derived significant benefit from pemetrexed-based therapy. These cases suggest that the value of pemetrexed may need to be re-explored in adenosquamous NSCLC harboring such alterations.
Significance of Lymph Node Metastasis in the Treatment of Gastric Cancer and Current Challenges in Determining the Extent of Metastasis
Authors: Kinami Shinichi , Saito Hitoshi , Takamura Hiroyuki
Published: January 2022

The stomach exhibits abundant lymphatic flow, and metastasis to lymph nodes is common. In the case of gastric cancer, there is a regularity to the spread of lymph node metastasis, and it does not easily metastasize outside the regional nodes. Furthermore, when its extent is limited, nodal metastasis of gastric cancer can be cured by appropriate lymph node dissection. Therefore, identifying and determining the extent of lymph node metastasis is important for ensuring accurate diagnosis and appropriate surgical treatment in patients with gastric cancer. However, precise detection of lymph node metastasis remains difficult. Most nodal metastases in gastric cancer are microscopic metastases, which often occur in small-sized lymph nodes, and are thus difficult to diagnose both preoperatively and intraoperatively. Preoperative nodal diagnoses are mainly made using computed tomography, although the specificity of this method is low because it is mainly based on the size of the lymph node. Furthermore, peripheral nodal metastases cannot be palpated intraoperatively, nodal harvesting of resected specimens remains difficult, and the number of lymph nodes detected vary greatly depending on the skill of the technician. Based on these findings, gastrectomy with prophylactic lymph node dissection is considered the standard surgical procedure for gastric cancer. In contrast, several groups have examined the value of sentinel node biopsy for accurately evaluating nodal metastasis in patients with early gastric cancer, reporting high sensitivity and accuracy. Sentinel node biopsy is also important for individualizing and optimizing the extent of uniform prophylactic lymph node dissection and determining whether patients are indicated for function-preserving curative gastrectomy, which is superior in preventing post-gastrectomy symptoms and maintaining dietary habits. Notably, advancements in surgical treatment for early gastric cancer are expected to result in individualized surgical strategies with sentinel node biopsy. Chemotherapy for advanced gastric cancer has also progressed, and conversion gastrectomy can now be performed after downstaging, even in cases previously regarded as inoperable. In this review, we discuss the importance of determining lymph node metastasis in the treatment of gastric cancer, the associated difficulties, and the need to investigate strategies that can improve the diagnosis of lymph node metastasis.
Comparison and Analysis of Gut Microbiota in Children With IgA Vasculitis With Different Clinical Symptoms
Authors: Li Meng , Wang Xiaoming , Lin Xingjie , Bian Xiuju , Jing Rui , Frelinger Andrew , Zhang Aijun
Published: January 2022

Background: Henoch-Schönlein purpura, now called immunoglobulin A (IgA) vasculitis, is a common autoimmune disease in children, its association with gut microbiota composition remains unknown.

Methods: The collected cases were divided into three groups: G1 group of simple skin type, G2 group with no digestive tract expression, G3 group of mixed digestive tract, and C group of healthy children. The fecal samples of each group of children were collected and the sequencing data was processed and analyzed. The dilution curve reflected the reasonableness of the amount of sequencing data.

Results: The number of species composition sequences in the G1, G2 and G3 groups was lower than that in the C group, especially for the G2 and G3 groups. The four most abundant bacteria were Bacteroidetes, Firmicutes, Proteobacteria and Actinobacteria. The relative abundance of Proteobacteria in the G2 and G3 groups was significantly higher than that in the G1 and C groups, while the relative abundance of Actinobacteria was significantly reduced, and the relative abundance of Actinobacteria in the G1 group was lower than that in the C group. Principal component analysis of the UPGMA clustering tree and each group of samples showed that the microbial community composition of the same group of samples was similar.

Conclusions: The abundance of intestinal microbes in children with IgA vasculitis is lower than in normal children. Bacteroidetes, Firmicutes, Proteobacteria and Actinobacteria are the four most abundant bacteria in the intestinal flora of children. Proteobacteria and Actinobacteria are associated with organ involvement in IgA vasculitis.
Effect of Space Fractional Parameter on Nonlinear Ion Acoustic Shock Wave Excitation in an Unmagnetized Relativistic Plasma
Authors: Uddin M.F. , Hafez M.G. , Hwang Inho , Park Choonkil
Published: January 2022

In this work, the model equation with space fractional-order (FO) is used to investigate the nonlinear ion acoustic shock wave excitations (NIASWEs) in an unmagnetized collisionless weakly relativistic plasma having inertial relativistic ions fluid with viscous effects, inertial-less non-thermal electrons and inertial-less Boltzmann positrons. To do it, the Korteweg-de Vries Burgers equation (KdVBE) is derived from the considered fluid model equations by implementing the standard reductive perturbation method. Accordingly, such equation is converted to space fractional KdVBE via Agrawal’s variational principle with the help of the beta fractional derivative and its properties. The exact analytical solutions of KdVBE with space FO are determined via the modified Kudryashov method. The influence of space fractional and other related plasma parameters on NIASWEs are investigated. The outcomes would be useful to understand the nature of shocks with the presence of non-local or local space in many astrophysical and space environments (especially in the relativistic wind of pulsar magnetosphere, polar regions of neutron stars, etc.) and further laboratory verification.