bluuebunny/crossref_metadata_2025 huggingface dataset:
Size-Fractionated PM10 and Bioaerosol Indicator Development by Different Methods in Composting Plants for Risk Assessment
Authors: Pascale Erica , Franchitti Elena , Zanchi Noemi , Anedda Elisa , Bonetta Sara , Traversi Deborah
Published: February 2022

Rapid population growth and urbanization have led to increased waste generation rates. Avoiding, reducing and reusing waste is imperative in the international approach to avoid impacting disposals. Composting plants are crucial for better organic waste management, although one of their environmental impacts is bioaerosol production, which can lead to adverse health effects. This work analyzed bioaerosol contamination in composting plants through multiple analytic methods, including culture-based techniques and qPCR, subfractionated PM10, and PM4.5 sampling. The aim was to identify indicators useful for assessing the human health risk associated with bioaerosol exposure during organic waste treatment. Two composting plants and four different areas (reception/selection, methanization, composting and refinement) were selected for sampling. The analysis revealed high contamination levels and large microbial heterogeneity both for PM (until to 3 times above the guideline value) and bioaerosol samples (until to 3 magnitude orders above the proposed reference value). Bacillus spp., Saccharopolyspora, and Thermomyces always showed detectable but highly variable concentrations (ranging from 2.12 to 4.86, from 3.65 to 7.30 and from 3.45 to 6.94 Log gene copies/m3 respectively). They correlated positively and significantly with other measured microbial parameters, suggesting their potential use as indicators of biological contamination in composting plants. Moreover, the integration of culture indipendent methods can increase the monitoring sensitivity and improve the bioaerosol risk assessment. The reduction of bioaerosol exposure levels in composting plants remains a primary goal but it requires in-depth characterization of the complex bioaerosol composition, its airborne dispersion, and its association with specific adverse health outcomes.
Biodiversity and Ecosystem Functions Across an Afro-Tropical Forest Biodiversity Hotspot
Authors: Seifert Tobias , Teucher Mike , Ulrich Werner , Mwania Felistas , Gona Francis , Habel Jan Christian
Published: February 2022

Ecosystem functions are important for the resilience of ecosystems and for human livelihood quality. Intact habitats and heterogeneous environments are known to provide a large variety of ecosystem functions. Natural and near natural ecosystems surrounding agroecosystems may positively support crop growing conditions and thus facilitate crop yields. In contrast, monocultures of crops and trees as well as degraded landscapes are known to provide less ecosystem functions. The Taita Hills in southern Kenya are part of the Eastern Afromontane biodiversity hotspot, and represent a habitat mosaic consisting of largely intact cloud forests, agroecosystems and plantations of exotic trees. In this region, subsistence farmers rely on ecosystem functions provided by natural ecosystems. In this study, we analyze three proxies of biodiversity and ecosystem functions, namely pollination activity, predation rates, and arthropod diversity in tree canopies. We set study plots along forest-agroecosystem-gradients, covering cloud forest, forest edge and agricultural fields, as well as plantations of exotic trees. We assessed environmental conditions, to evaluate the extent to which local environmental factors influence ecosystem functions. Based on these data we investigate potential spill over of ecosystem functions from forest into adjoining agroecosystems. For predation rates we found trends of spill over effects from forest interior into the agroecosystem. The expression of ecosystem functions differed among habitat types, with comparatively high predation rates in the forest, high pollinator activity in the open agricultural areas, and highest arthropod diversity along the forest edge. Eucalyptus plantations showed reduced ecosystem functions and lowest arthropod diversity. Local factors such as vegetation cover and flower supply positively influence pollinator activity. Our study show that natural ecosystems may positively contribute ecosystem functions such as predation, while the homogenization of biota through planting of invasive exotic tree species significantly reduce biodiversity and ecosystem functions. Transition habitats such as forest margins, and small-scale ecological enhancement positively influences biodiversity and ecosystem functions.
Identification and Quantification of Necroptosis Landscape on Therapy and Prognosis in Kidney Renal Clear Cell Carcinoma
Authors: Xin Sheng , Mao Jiaquan , Duan Chen , Wang Jiaxin , Lu Yuchao , Yang Jun , Hu Jia , Liu Xiaming , Guan Wei , Wang Tao , Wang Shaogang , Liu Jihong , Song Wen , Song Xiaodong
Published: February 2022

Kidney renal clear cell carcinoma (KIRC) has high morbidity and gradually increased in recent years, and the rate of progression once relapsed is high. At present, owing to lack of effective prognosis predicted markers and post-recurrence drug selection guidelines, the prognosis of KIRC patients is greatly affected. Necroptosis is a regulated form of cell necrosis in a way that is independent of caspase. Induced necroptosis is considered an effective strategy in chemotherapy and targeted drugs, and it can also be used to improve the efficacy of immunotherapy. Herein, we quantified the necroptosis landscape of KIRC patients from The Cancer Genome Atlas (TCGA) database and divided them into two distinct necroptosis-related patterns (C1 and C2) through the non-negative matrix factorization (NMF) algorithm. Multi-analysis revealed the differences in clinicopathological characteristics and tumor immune microenvironment (TIME). Then, we constructed the NRG prognosis signature (NRGscore), which contained 10 NRGs (PLK1, APP, TNFRSF21, CXCL8, MYCN, TNFRSF1A, TRAF2, HSP90AA1, STUB1, and FLT3). We confirmed that NRGscore could be used as an independent prognostic marker for KIRC patients and performed excellent stability and accuracy. A nomogram model was also established to provide a more beneficial prognostic indicator for the clinic. We found that NRGscore was significantly correlated with clinicopathological characteristics, TIME, and tumor mutation burden (TMB) of KIRC patients. Moreover, NRGscore had effective guiding significance for immunotherapy, chemotherapy, and targeted drugs.
SARS-CoV-2 Immunization Orchestrates the Amplification of IFNγ-Producing T Cell and NK Cell Persistence
Authors: La Sala Lucia , Gandini Sara , Bruno Antonino , Allevi Raffaele , Gallazzi Matteo , Senesi Pamela , Palano Maria Teresa , Meregalli Paola , Longhi Ermanno , Sommese Carmen , Luzi Livio , Trabucchi Emilio
Published: February 2022

A successful vaccination would represent the most efficient means to control the pandemic of Coronavirus Disease-19 (COVID-19) that led to millions of deaths worldwide. Novel mRNA-based vaccines confer protective immunity against SARS-CoV-2, but whether immunity is immediately effective and how long it will remain in recipients are uncertain. We sought to assess the effectiveness of a two-dose regimen since the boosts are often delayed concerning the recommended intervals.

Methods

A longitudinal cohort of healthcare workers (HCW, N = 46; 30.4% men; 69.6% women; mean age 36.05 ± 2.2 years) with no SARS-CoV-2 infection as documented by negative polymerase chain reaction was immunophenotyped in PBMC once a week for 4 weeks from the prime immunization (Pfizer mRNA BNT162b2) and had received 2 doses, to study the kinetic response.

Results

We identified three risk groups to develop SARS-CoV-2 infection IgG+-based (late responders, R-; early responders, R+; pauci responders, PR). In all receipts, amplification of B cells and NK cells, including IL4-producing B cells and IL4-producing CD8+ T cells, is early stimulated by the vaccine. After the boost, we observed a growing increase of NK cells but a resistance of T cells, IFNγ-producing CD4+T cells, and IFNγ-producing NK cells. Also, hematologic parameters decline until the boost. The positive association of IFNγ-producing NK with IFNγ-producing CD4+T cells by the multiple mixed-effect model, adjusted for confounders (p = 0.036) as well as the correlation matrix (r = 0.6, p < 0.01), suggests a relationship between these two subsets of lymphocytes.

Conclusions

These findings introduce several concerns about policy delay in vaccination: based on immunological protection, B cells and the persistent increase of NK cells during 2 doses of the mRNA-based vaccine could provide further immune protection against the virus, while CD8+ T cells increased slightly only in the R+ and PR groups.
Adenosine A2A Receptor Suppressed Astrocyte-Mediated Inflammation Through the Inhibition of STAT3/YKL-40 Axis in Mice With Chronic Cerebral Hypoperfusion-induced White Matter Lesions
Authors: Yuan Jichao , Chen Lin , Wang Jie , Xia Simin , Huang Jialu , Zhou Linke , Feng Chengjian , Hu Xiaofei , Zhou Zhenhua , Ran Hong
Published: February 2022

White matter lesions are an important pathological manifestation of cerebral small vessel disease, with inflammation playing a pivotal role in their development. The adenosine A2a receptor (ADORA2A) is known to inhibit the inflammation mediated by microglia, but its effect on astrocytes is unknown. Additionally, although the level of YKL-40 (expressed mainly in astrocytes) has been shown to be elevated in the model of white matter lesions induced by chronic cerebral hypoperfusion, the specific regulatory mechanism involved is not clear. In this study, we established in vivo and in vitro chronic cerebral hypoperfusion models to explore whether the ADORA2A regulated astrocyte-mediated inflammation through STAT3/YKL-40 axis and using immunohistochemical, western blotting, ELISA, PCR, and other techniques to verify the effect of astrocytes ADORA2A on the white matter injury. The in vivo experiments showed that activation of the ADORA2A decreased the expression of both STAT3 and YKL-40 in the astrocytes and alleviated the white matter injury, whereas its inhibition had the opposite effects. Similarly, ADORA2A inhibition significantly increased the expression of STAT3 and YKL-40 in astrocytes in vitro, with more proinflammatory cytokines being released by astrocytes. STAT3 inhibition enhanced the inhibitory effect of ADORA2A on YKL-40 synthesis, whereas its activation reversed the phenomenon. These results suggest that the activation of ADORA2A in astrocytes can inhibit the inflammation mediated by the STAT3/YKL-40 axis and thereby reduce white matter injury in cerebral small vessel disease.
Declining Pre-bloom Calanus finmarchicus Egg Production Adjacent to Two Major Overwintering Regions in the Northeastern Atlantic
Authors: Jacobsen Sólvá , Gaard Eilif , Hátún Hjálmar
Published: February 2022

Calanus finmarchicusis a key secondary producer in the North Atlantic. Shortly prior to the spring bloom the animals ascend from diapause at depth to surface waters, where the females spawn partly, based on winter lipid reserves.C. finmarchicuseggs are an important prey of first feeding fish larvae inhabiting North Atlantic shelves during early spring and are thus essential for larval survival. Comprehensive late April surveys have been carried out on and around the Faroe shelf, which is located between the Northeast Atlantic and the Nordic Seas, for more than two decades. One aim is to investigate the critical match-mismatch between the spring bloom development, zooplankton reproduction and occurrence of first feeding fish larvae. In this study, we examine spatial and temporal changes in pre-bloom reproductive activity ofC. finmarchicuson and around the shelf using a unique dataset of more than 8,000 examined females sampled during the period 1997–2020. Enhanced productivity was observed on the north-western side of the shelf, where the main flow of oceanic water to the inner permanently well mixed shelf takes place. We attribute this increased productivity to enhanced food (phytoplankton) availability in the seasonally stratified outer shelf, slightly upstream of the main egg production area. Both individual egg production rates and the fraction of spawning females declined throughout the Faroe shelf during the examined period. This decline could not be explained by the employed environmental parameters. The declining pre-bloom egg production may have consequences for first feeding fish larvae.
Efficient Exploration of Microstructure-Property Spaces via Active Learning
Authors: Morand Lukas , Link Norbert , Iraki Tarek , Dornheim Johannes , Helm Dirk
Published: February 2022

In materials design, supervised learning plays an important role for optimization and inverse modeling of microstructure-property relations. To successfully apply supervised learning models, it is essential to train them on suitable data. Here, suitable means that the data covers the microstructure and property space sufficiently and, especially for optimization and inverse modeling, that the property space is explored broadly. For virtual materials design, typically data is generated by numerical simulations, which implies that data pairs can be sampled on demand at arbitrary locations in microstructure space. However, exploring the space of properties remains challenging. To tackle this problem, interactive learning techniques known as active learning can be applied. The present work is the first that investigates the applicability of the active learning strategy query-by-committee for an efficient property space exploration. Furthermore, an extension to active learning strategies is described, which prevents from exploring regions with properties out of scope (i.e., properties that are physically not meaningful or not reachable by manufacturing processes).
Probing the Damage Recovery Mechanism in Irradiated Stainless Steels Using In-Situ Microcantilever Bending Test
Authors: Mao Keyou S. , Wang Hao , Qu Haozheng J. , Yano Kayla H. , Edmondson Philip D. , Sun Cheng , Wharry Janelle P.
Published: February 2022

Single crystalline microcantilevers are fabricated from the base metal and heat-affected zone (HAZ) of a laser welded, neutron irradiated austenitic stainless steel, for scanning electron microscope (SEM) in-situ bending. In the HAZ, cantilevers exhibit higher yield point and lower crack tip blunting displacement than in the base metal and unirradiated archive specimen. These results suggest that radiation-induced defects harden the base metal, whereas the HAZ exhibits annealing of defects leading to mechanical softening. Dislocation nucleation ahead of the crack tip is responsible for ductile blunting behavior and provides a pathway to mitigating helium-induced cracking during weld repairs of irradiated materials.
Dynamic Response Analysis and Vibration Reduction of Steel Truss Corridor Pedestrian Bridge Under Pedestrian Load
Authors: Chen Zhou , Chen Zehong , Li Guangjun , Zhang Weixiong , Zhang Xiaoqing , Huang Shiping , Chen Zepeng
Published: February 2022

With the advancement in civil engineering, the applications of lightweight and high-strength materials, and large-span, low-damping structural systems, are increasing. One important structural system for such applications is the corridor pedestrian bridge structure. The vibration frequency of the corridor pedestrian bridge structure is often in the same range as the step frequency of pedestrians, and it is easy to cause the appearance of the corridor structure. The vibration frequency of the corridor pedestrian bridge structure is often in the same range as the step frequency of pedestrians, and it is easy to cause the appearance of the corridor structure. Vibration comfort issues even affect the safe use of the corridor. Vibration comfort issues even affect the safe use of the corridor. Regarding the vertical vibration caused by pedestrians on the steel structure corridor footbridge, using a tuned mass damper (TMD) system can reduce the vibration effect. After the TMD vibration reduction test of the steel structure corridor footbridge, it can be found that the vibration reduction rate of the footbridge has reached 62.56%. The results show that vibration reduction by TMD system is a safe and effective method for pedestrian bridge vibration reduction, improving the structural performance and pedestrian comfort of the structural corridor pedestrian bridge.
Challenges in Implementing Cardiovascular Risk Scores for Assessment of Young People With Childhood-Onset Autoimmune Rheumatic Conditions
Authors: Ciurtin Coziana , Robinson George A. , Pineda-Torra Ines , Jury Elizabeth C.
Published: February 2022

Cardio-vascular risk (CVR) stratification tools have been implemented in clinical practice to guide management decision for primary prevention of cardiovascular disease. Less is known about how we can optimally estimate the CVR in children and adolescents or about the reliability of the risk stratification tools validated in adult populations. Chronic inflammation associated with autoimmune rheumatic disease (ARD) drives an increased risk for accelerated atherosclerosis in patients of all ages. Although the research is less advanced than in adult populations, it is recognized that young people with ARDs with childhood-onset have increased CVR compared to age-matched healthy controls, as supported by studies investigating lipid biomarker profile and markers of endothelial dysfunction. Further research is needed to address the unmet need for adequate CVR identification and management strategies in young people in general, and in those with underlying chronic inflammation in particular. This perspective paper explores various challenges in adequately identifying and managing CVR in younger populations and potential directions for future research.
A Novel System for Measuring Pterygium's Progress Using Deep Learning
Authors: Wan Cheng , Shao Yiwei , Wang Chenghu , Jing Jiaona , Yang Weihua
Published: February 2022

Pterygium is a common ocular surface disease. When pterygium significantly invades the cornea, it limits eye movement and impairs vision, which requires surgery to remove. It is medically recognized that when the width of the pterygium that invades the cornea is >3 mm, the patient can be treated with surgical resection. Owing to this, this study proposes a system for diagnosing and measuring the pathological progress of pterygium using deep learning methods, which aims to assist doctors in designing pterygium surgical treatment strategies. The proposed system only needs to input the anterior segment images of patients to automatically and efficiently measure the width of the pterygium that invades the cornea, and the patient's pterygium symptom status can be obtained. The system consists of three modules, including cornea segmentation module, pterygium segmentation module, and measurement module. Both segmentation modules use convolutional neural networks. In the pterygium segmentation module, to adapt the diversity of the pterygium's shape and size, an improved U-Net++ model by adding an Attention gate before each up-sampling layer is proposed. The Attention gates extract information related to the target, so that the model can pay more attention to the shape and size of the pterygium. The measurement module realizes the measurement of the width and area of the pterygium that invades the cornea and the classification of pterygium symptom status. In this study, the effectiveness of the proposed system is verified using datasets collected from the ocular surface diseases center at the Affiliated Eye Hospital of Nanjing Medical University. The results obtained show that the Dice coefficient of the cornea segmentation module and the pterygium segmentation module are 0.9620 and 0.9020, respectively. The Kappa consistency coefficient between the final measurement results of the system and the doctor's visual inspection results is 0.918, which proves that the system has practical application significance.
The Importance of Being “That” Colorectal pT1: A Combined Clinico-Pathological Predictive Score to Improve Nodal Risk Stratification
Authors: Gambella Alessandro , Falco Enrico Costantino , Benazzo Giacomo , Osella-Abate Simona , Senetta Rebecca , Castellano Isabella , Bertero Luca , Cassoni Paola
Published: February 2022

The management of endoscopically resected pT1 colorectal cancer (CRC) relies on nodal metastasis risk estimation based on the assessment of specific histopathological features. Avoiding the overtreatment of metastasis-free patients represents a crucial unmet clinical need. By analyzing a consecutive series of 207 pT1 CRCs treated with colectomy and lymphadenectomy, this study aimed to develop a novel clinicopathological score to improve pT1 CRC metastasis prediction. First, we established the clinicopathological profile of metastatic cases: lymphovascular invasion (OR: 23.8; CI: 5.12–110.9) and high-grade tumor budding (OR: 5.21; CI: 1.60–16.8) correlated with an increased risk of nodal metastasis, while age at diagnosis >65 years (OR: 0.26; CI: 0.09–0.71) and high tumor-infiltrating lymphocytes (OR: 0.19; CI: 0.06–0.59) showed a protective effect. Combining these features, we built a five-tier risk score that, applied to our series, identified cases with a higher risk (score ≥ 2) of nodal metastasis (OR: 7.7; CI: 2.4–24.4). Notably, a score of 0 was only assigned to cases with no metastases (13/13 cases) and all the score 4 samples (2/2 cases) showed nodal metastases. In conclusion, we developed an effectively combined score to assess pT1 CRC nodal metastasis risk. We believe that its adoption within a multidisciplinary pT1 unit could improve patients' clinical management and limit surgical overtreatment.
Development and Validation of a Multidimensional Population-Based Healthy Aging Scale: Results From the China Health and Retirement Longitudinal Study
Authors: Gao Junling , Xu Jixiang , Chen Yingwei , Wang Yujie , Ye Bo , Fu Hua
Published: February 2022

Background

The World Health Organization proposed a multidimensional concept of healthy aging in 2015; there was limited evidence about how the concept was constructed and measured. The current study aims to develop a health aging scale (HAS) following the WHO framework and validate it using data from the China Health and Retirement Longitudinal Study (CHARLS).

Methods

A total of 13,233 adults aged ≥ 45 years old from the CHARLS included in current study. Based on the WHO framework, 37 self-reported indicators were used to determine healthy aging. Exploratory factor analysis and second-order and bi-factor modeling, as well as psychometric coefficients, were used to examine the structure of healthy aging. To assess concurrent validity of the HAS, regression analyses were used to examine the associations of HAS and its subscales with sociodemographic characteristics, health conditions, healthcare utilization and life satisfaction in Wave 1. The predictive validity of HAS and subscales was assessed by their associations with mortality in Wave 2 follow-up using Cox regressions.

Results

The general HAS and its five subscales were generated according to bi-factor modeling [CFI = 0.949; TLI = 0.942; SRMSR = 0.030; and RMSEA = 0.033 (95% CI, 0.032–0.034)] and psychometric coefficients (ω = 0.903; ωH = 0.692; ECV = 0.459). The general HAS presented solid evidence of concurrent validity with various sociodemographic characteristics, health conditions, healthcare utilization and life satisfaction; and predictive validity with mortality.

Conclusions

The population-based multidimensional healthy aging scale and its subscales can be used to monitor the trajectories of general healthy aging and its subdomains to support the development of healthy aging policies and interventions.
Contribution of Heterotrophic Diazotrophs to N2 Fixation in a Eutrophic River: Free-Living vs. Aggregate-Associated
Authors: Geisler Eyal , Rahav Eyal , Bar-Zeev Edo
Published: February 2022

Recent studies have indicated that heterotrophic diazotrophs are highly diverse and fix N2 in aquatic environments with potentially adverse conditions for diazotrophy, such as oxic and rich in total nitrogen. In this study, we compared the activity and diversity of heterotrophic diazotrophs associated with aggregates (>12 μm) to free-living cells in the eutrophic Qishon River during the winter and summer seasons. Overall, measured heterotrophic N2 fixation rates in the Qishon River ranged between 2.6–3.5 nmol N L–1 d–1. Heterotrophic N2 fixation was mainly associated with aggregates in the summer samples (74 ± 24%), whereas during the winter the bulk diazotrophic activity was mostly ascribed to the free-living fraction (90 ± 6%). In addition, immunolabeled micrographs indicated the presence of aggregate-associated heterotrophic diazotrophs in both seasons, while phototrophic diazotrophs were also captured during the winter. The richness of free-living and aggregate-associated heterotrophic diazotrophs were overall similar, yet the evenness of the later was significantly smaller, suggesting that few of the species gained advantage from particle lifestyle. The differences in the activity, micro-localization and diversity of the diazotrophic community were mostly attributed to spatiotemporal changes in the ambient C:N ratios (total organic carbon, TOC: total nitrogen) and the TOC concentrations. Taken together, our results shed new light on the contribution of heterotrophic diazotroph associated with aggregates to total heterotrophic N2 fixation in oxic, highly eutrophic aquatic environments.
Differential Expression of Serum TUG1, LINC00657, miR-9, and miR-106a in Diabetic Patients With and Without Ischemic Stroke
Authors: Abdelaleem Omayma O , Shaker Olfat G. , Mohamed Mohamed M. , Ahmed Tarek I. , Elkhateeb Ahmed F. , Abdelghaffar Noha K. , Ahmed Naglaa A. , Khalefa Abeer A. , Hemeda Nada F. , Mahmoud Rania H.
Published: February 2022

Background: Ischemic stroke is one of the serious complications of diabetes. Non-coding RNAs are established as promising biomarkers for diabetes and its complications. The present research investigated the expression profiles of serum TUG1, LINC00657, miR-9, and miR-106a in diabetic patients with and without stroke.

Methods: A total of 75 diabetic patients without stroke, 77 patients with stroke, and 71 healthy controls were recruited in the current study. The serum expression levels of TUG1, LINC00657, miR-9, and miR-106a were assessed using quantitative real-time polymerase chain reaction assays.

Results: We observed significant high expression levels of LINC00657 and miR-9 in the serum of diabetic patients without stroke compared to control participants. At the same time, we found marked increases of serum TUG1, LINC00657, and miR-9 and a marked decrease of serum miR-106a in diabetic patients who had stroke relative to those without stroke. Also, we revealed positive correlations between each of TUG1, LINC00657, and miR-9 and the National Institutes of Health Stroke Scale (NIHSS). However, there was a negative correlation between miR-106a and NIHSS. Finally, we demonstrated a negative correlation between LINC00657 and miR-106a in diabetic patients with stroke.

Conclusion: Serum non-coding RNAs, TUG1, LINC00657, miR-9, and miR-106a displayed potential as novel molecular biomarkers for diabetes complicated with stroke, suggesting that they might be new therapeutic targets for the treatment of diabetic patients with stroke.
Selection and Modelling of a New Single-Domain Intrabody Against TDP-43
Authors: Gilodi Martina , Lisi Simonetta , F. Dudás Erika , Fantini Marco , Puglisi Rita , Louka Alexandra , Marcatili Paolo , Cattaneo Antonino , Pastore Annalisa
Published: February 2022

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder associated to deteriorating motor and cognitive functions, and short survival. The disease is caused by neuronal death which results in progressive muscle wasting and weakness, ultimately leading to lethal respiratory failure. The misbehaviour of a specific protein, TDP-43, which aggregates and becomes toxic in ALS patient’s neurons, is supposed to be one of the causes. TDP-43 is a DNA/RNA-binding protein involved in several functions related to nucleic acid metabolism. Sequestration of TDP-43 aggregates is a possible therapeutic strategy that could alleviate or block pathology. Here, we describe the selection and characterization of a new intracellular antibody (intrabody) against TDP-43 from a llama nanobody library. The structure of the selected intrabody was predicted in silico and the model was used to suggest mutations that enabled to improve its expression yield, facilitating its experimental validation. We showed how coupling experimental methodologies with in silico design may allow us to obtain an antibody able to recognize the RNA binding regions of TDP-43. Our findings illustrate a strategy for the mitigation of TDP-43 proteinopathy in ALS and provide a potential new tool for diagnostics.
Identification and Validation of a Novel Three Hub Long Noncoding RNAs With m6A Modification Signature in Low-Grade Gliomas
Authors: Nguyen Quang-Huy , Nguyen Tin , Le Duc-Hau
Published: February 2022

It has been evident that N6-methyladenosine (m6A)-modified long noncoding RNAs (m6A-lncRNAs) involves regulating tumorigenesis, invasion, and metastasis for various cancer types. In this study, we sought to pick computationally up a set of 13 hub m6A-lncRNAs in light of three state-of-the-art tools WGCNA, iWGCNA, and oCEM, and interrogated their prognostic values in brain low-grade gliomas (LGG). Of the 13 hub m6A-lncRNAs, we further detected three hub m6A-lncRNAs as independent prognostic risk factors, including HOXB-AS1, ELOA-AS1, and FLG-AS1. Then, the m6ALncSig model was built based on these three hub m6A-lncRNAs. Patients with LGG next were divided into two groups, high- and low-risk, based on the median m6ALncSig score. As predicted, the high-risk group was more significantly related to mortality. The prognostic signature of m6ALncSig was validated using internal and external cohorts. In summary, our work introduces a high-confidence prognostic prediction signature and paves the way for using m6A-lncRNAs in the signature as new targets for treatment of LGG.
Comprehensive Analysis of Necroptosis-Related Long Noncoding RNA Immune Infiltration and Prediction of Prognosis in Patients With Colon Cancer
Authors: Liu Li , Huang Liu , Chen Wenzheng , Zhang Guoyang , Li Yebei , Wu Yukang , Xiong Jianbo , Jie Zhigang
Published: February 2022

Colon cancer (CC) is one of the most frequent malignancies in the world, with a high rate of morbidity and death. In CC, necroptosis and long noncoding RNA (lncRNAs) are crucial, but the mechanism is not completely clear. The goal of this study was to create a new signature that might predict patient survival and tumor immunity in patients with CC. Expression profiles of necroptosis-related lncRNAs in 473 patients with CC were retrieved from the TCGA database. A consensus clustering analysis based on differentially expressed (DE) genes and a prognostic model based on least absolute shrinkage and selection operator (LASSO) regression analysis were conducted. Clinicopathological correlation analysis, expression difference analysis, PCA, TMB, GO analysis, KEGG enrichment analysis, survival analysis, immune correlation analysis, prediction of clinical therapeutic compounds, and qRT–PCR were also conducted. Fifty-six necroptosis-related lncRNAs were found to be linked to the prognosis, and consensus clustering analysis was performed. There were substantial variations in survival, immune checkpoint expression, clinicopathological correlations, and tumor immunity among the different subgroups. Six lncRNAs were discovered, and patients were split into high-risk and low-risk groups based on a risk score generated using these six lncRNAs. The survival time of low-risk patients was considerably longer than that of high-risk patients, indicating that these lncRNAs are directly associated with survival. The risk score was associated with the tumor stage, infiltration depth, lymph node metastasis, and distant metastasis. After univariate and multivariate Cox regression analysis, the risk score and tumor stage remained significant. Cancer- and metabolism-related pathways were enriched by KEGG analyses. Immune infiltration was shown to differ significantly between high- and low-risk patients in a tumor immunoassay. Eight compounds were screened out, and qRT–PCR confirmed the differential expression of the six lncRNAs. Overall, in CC, necroptosis-related lncRNAs have an important function, and the prognosis of patients with CC can be predicted by these six necroptosis-related lncRNAs. They may be useful in the future for customized cancer therapy.
Mitochondrial ATP Synthase is a Target of Oxidative Stress in Neurodegenerative Diseases
Authors: Ebanks Brad , Chakrabarti Lisa
Published: February 2022

The mitochondrial ATP synthase is responsible for the production of cellular ATP, and it does so by harnessing the membrane potential of the mitochondria that is produced by the sequential oxidation of select cellular metabolites. Since the structural features of ATP synthase were first resolved nearly three decades ago, significant progress has been made in understanding its role in health and disease. Mitochondrial dysfunction is common to neurodegeneration, with elevated oxidative stress a hallmark of this dysfunction. The patterns of this oxidative stress, including molecular targets and the form of oxidative modification, can vary widely. In this mini review we discuss the oxidative modifications of ATP synthase that have been observed in Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease. Oxidative modifications of ATP synthase in Alzheimer’s disease are well-documented, and there is a growing body of knowledge on the subject in Parkinson’s disease. The consideration of ATP synthase as a pharmacological target in a variety of diseases underlines the importance of understanding these modifications, both as a potential target, and also as inhibitors of any pharmacological intervention.
Altered Intra- and Inter-Network Connectivity in Drug-Naïve Patients With Early Parkinson’s Disease
Authors: Zeng Weiqi , Fan Wenliang , Kong Xiangchuang , Liu Xiaoming , Liu Ling , Cao Ziqin , Zhang Xiaoqian , Yang Xiaoman , Cheng Chi , Wu Yi , Xu Yu , Cao Xuebing , Xu Yan
Published: February 2022

The aim of our study was to investigate differences in whole brain connectivity at different levels between drug-naïve individuals with early Parkinson’s disease (PD) and healthy controls (HCs). Resting-state functional magnetic resonance imaging data were collected from 47 patients with early-stage, drug-naïve PD and 50 HCs. Functional brain connectivity was analyzed at the integrity, network, and edge levels; UPDRS-III, MMSE, MOCA, HAMA, and HAMD scores, reflecting the symptoms of PD, were collected for further regression analysis. Compared with age-matched HCs, reduced functional connectivity were mainly observed in the visual (VSN), somatomotor (SMN), limbic (LBN), and deep gray matter networks (DGN) at integrity level [p < 0.05, false discovery rate (FDR) corrected]. Intra-network analysis indicated decreased functional connectivity in DGN, SMN, LBN, and ventral attention networks (VAN). Inter-network analysis indicated reduced functional connectivity in nine pairs of resting-state networks. At the edge level, the LBN was the center of abnormal functional connectivity (p < 0.05, FDR corrected). MOCA score was associated with the intra-network functional connectivity strength (FC) of the DGN, and inter-network FC of the DGN-VAN. HAMA and HAMD scores were associated with the FC of the SMN and DGN, and either the LBN or VAN, respectively. We demonstrated variations in whole brain connections of drug-naïve patients with early PD. Major changes involved the SMN, DGN, LBN, and VSN, which may be relevant to symptoms of early PD. Additionally, our results support PD as a disconnection syndrome.
Sex Differences in Ischemic Stroke Within the Younger Age Group: A Register-Based Study
Authors: Norman Kristina , Eriksson Marie , von Euler Mia
Published: February 2022

Background

Stroke incidence is decreasing in most developing countries. However, worrisome trends of an increase in the younger population have been described.

Aim

To investigate sex differences and longitudinal changes in ischemic stroke regarding incidence, cardiovascular risk factors, and outcome, in the young.

Methods

This is an observational study based on the data from the Swedish national stroke registry, Riksstroke. Patients, 18–54 years of age, having ischemic stroke between 2005 and 2018 were included, resulting in a study population of 16,210 patients.

Results

The incidence was higher in men than in women (30.6 vs. 19.1 per 100,000, P < 0.001). After an initial increase, the incidence stabilized and then decreased, resulting in a similar level in 2018 as in 2005. Atrial fibrillation, diabetes, and usage of anti-hypertensives at stroke onset were more common among men and did not change over time. Smoking was common and slightly more so in women, but with a reduced prevalence in both men and women during the study period. Dependency in Activities of Daily Living (ADL) and case fatality showed no clear trends or sex differences.

Conclusions

The results show that there are sex differences in ischemic stroke in the younger age group regarding incidence and vascular risk factors, particularly smoking. Temporal trends in stroke incidence are difficult to interpret as fluctuations are substantial, largely due to stroke being quite uncommon in the younger population.
Combining Neural and Behavioral Measures Enhances Adaptive Training
Authors: Rahman Md Lutfor , Files Benjamin T. , Oiknine Ashley H. , Pollard Kimberly A. , Khooshabeh Peter , Song Chengyu , Passaro Antony D.
Published: February 2022

Adaptive training adjusts a training task with the goal of improving learning outcomes. Adaptive training has been shown to improve human performance in attention, working memory capacity, and motor control tasks. Additionally, correlations have been observed between neural EEG spectral features (4–13 Hz) and the performance of some cognitive tasks. This relationship suggests some EEG features may be useful in adaptive training regimens. Here, we anticipated that adding a neural measure into a behavioral-based adaptive training system would improve human performance on a subsequent transfer task. We designed, developed, and conducted a between-subjects study of 44 participants comparing three training regimens: Single Item Fixed Difficulty (SIFD), Behaviorally Adaptive Training (BAT), and Combined Adaptive Training (CAT) using both behavioral and EEG measures. Results showed a statistically significant transfer task performance advantage of the CAT-based system relative to SIFD and BAT systems of 6 and 9 percentage points, respectively. Our research shows a promising pathway for designing closed-loop BCI systems based on both users' behavioral performance and neural signals for augmenting human performance.
14-3-3 Dysfunction in Dorsal Hippocampus CA1 (dCA1) Induces Psychomotor Behavior via a dCA1-Lateral Septum-Ventral Tegmental Area Pathway
Authors: Zhang Jiajing , Navarrete Meaghan , Wu Yuying , Zhou Yi
Published: February 2022

While hippocampal hyperactivity is implicated in psychosis by both human and animal studies, whether it induces a hyperdopaminergic state and the underlying neural circuitry remains elusive. Previous studies established that region-specific inhibition of 14-3-3 proteins in the dorsal hippocampus CA1 (dCA1) induces schizophrenia-like behaviors in mice, including a novelty-induced locomotor hyperactivity. In this study, we showed that 14-3-3 dysfunction in the dCA1 over-activates ventral tegmental area (VTA) dopaminergic neurons, and such over-activation is necessary for eliciting psychomotor behavior in mice. We demonstrated that such hippocampal dysregulation of the VTA during psychomotor behavior is dependent on an over-activation of the lateral septum (LS), given that inhibition of the LS attenuates over-activation of dopaminergic neurons and psychomotor behavior induced by 14-3-3 inhibition in the dCA1. Moreover, 14-3-3 inhibition-induced neuronal activations within the dCA1-LS-VTA pathway and psychomotor behavior can be reproduced by direct chemogenetic activation of LS-projecting dCA1 neurons. Collectively, these results suggest that 14-3-3 dysfunction in the dCA1 results in hippocampal hyperactivation which leads to psychomotor behavior via a dCA1-LS-VTA pathway.
The Effects of GABA-Rich Adzuki Beans on Glycolipid Metabolism, as Well as Intestinal Flora, in Type 2 Diabetic Mice
Authors: Zhang Aiwu , Jiang Xiujie , Ge Yunfei , Xu Qingpeng , Li Zhijiang , Tang Huacheng , Cao Dongmei , Zhang Dongjie
Published: February 2022

Objectives

In this study, the effects of γ-aminobutyric acid (GABA)-rich sprouted adzuki beans on the glycolipid metabolism and gastrointestinal health were investigated in mice with type 2 diabetes mellitus (T2DM).

Methods

Mice with T2DM were subjected to dietary intervention with different doses of GABA-rich sprouted adzuki beans for 6 consecutive weeks, during which growth indicators, glycolipid metabolism, and the composition and diversity of the gut microbiota changes were observed.

Results

A high dietary intake of GABA-rich sprouted adzuki beans had a preventive effect against weight gain, significantly reduced serum levels of FBG, TG, and TC. Additionally, high dietary intake of GABA-rich sprouted adzuki beans increased the abundances of Firmicutes, Bacteroidetes, Verrucomicrobia, and Akkermansia, leading to a shift in the structure of the gut microbiota toward the dominance of probiotics with regulatory effects on glycolipid metabolism.

Conclusions

GABA-rich sprouted adzuki beans can effectively control the bodyweight of mice with T2DM, maintain a balanced blood glucose level, improve glycolipid metabolism and the changes in the microbiota may mediate the anti-diabetic effect of sprouted adzuki beans.
A Deep Learning Image Data Augmentation Method for Single Tumor Segmentation
Authors: Zhang Chunling , Bao Nan , Sun Hang , Li Hong , Li Jing , Qian Wei , Zhou Shi
Published: February 2022

Purpose

Medical imaging examination is the primary method of diagnosis, treatment, and prevention of cancer. However, the amount of medical image data is often not enough to meet deep learning needs. This article aims to expand the small data set in tumor segmentation based on the deep learning method.

Methods

This method includes three main parts: image cutting and mirroring augmentation, segmentation of augmented images, and boundary reconstruction. Firstly, the image is divided into four parts horizontally & vertically, and diagonally along the tumor’s approximate center. Then each part is mirrored to get a new image and hence a four times data set. Next, the deep learning network trains the augmented data and gets the corresponding segmentation model. Finally, the segmentation boundary of the original tumor is obtained by boundary compensation and reconstruction.

Results

Combined with Mask-RCNN and U-Net, this study carried out experiments on a public breast ultrasound data set. The results show that the dice similarity coefficient (DSC) value obtained by horizontal and vertical cutting and mirroring augmentation and boundary reconstruction improved by 9.66% and 12.43% compared with no data augmentation. Moreover, the DSC obtained by diagonal cutting and mirroring augmentation and boundary reconstruction method improved by 9.46% and 13.74% compared with no data augmentation. Compared with data augmentation methods (cropping, rotating, and mirroring), this method’s DSC improved by 4.92% and 12.23% on Mask-RCNN and U-Net.

Conclusion

Compared with the traditional methods, the proposed data augmentation method has better performance in single tumor segmentation.
Establishment and Validation of Pre-Therapy Cervical Vertebrae Muscle Quantification as a Prognostic Marker of Sarcopenia in Patients With Head and Neck Cancer
Authors: Olson Brennan , Edwards Jared , Degnin Catherine , Santucci Nicole , Buncke Michelle , Hu Jeffrey , Chen Yiyi , Fuller Clifton D. , Geltzeiler Mathew , Grossberg Aaron J. , Clayburgh Daniel
Published: February 2022

Background

Sarcopenia is prognostic for survival in patients with head and neck cancer (HNC). However, identification of this high-risk feature remains challenging without computed tomography (CT) imaging of the abdomen or thorax. Herein, we establish sarcopenia thresholds at the C3 level and determine if C3 sarcopenia is associated with survival in patients with HNC.

Methods

This retrospective cohort study was conducted in consecutive patients with a squamous cell carcinoma of the head and neck with cross-sectional abdominal or neck imaging within 60 days prior to treatment. Measurement of cross-sectional muscle area at L3 and C3 levels was performed from CT imaging. Primary study outcome was overall survival.

Results

Skeletal muscle area at C3 was strongly correlated with the L3 level in both men (n = 188; r = 0.77; p < 0.001) and women (n = 65; r = 0.80; p < 0.001), and C3 sarcopenia thresholds of 14.0 cm2/m2 (men) and 11.1 cm2/m2 (women) were best predictive of L3 sarcopenia thresholds. Applying these C3 thresholds to a cohort of patients with neck imaging alone revealed that C3 sarcopenia was independently associated with reduced overall survival in men (HR = 2.63; 95% CI, 1.79, 3.85) but not women (HR = 1.18, 95% CI, 0.76, 1.85).

Conclusions

This study identifies sarcopenia thresholds at the C3 level that best predict L3 sarcopenia in men and women. In HNC, C3-defined sarcopenia is associated with poor survival outcomes in men, but not women, suggesting sarcopenia may differentially affect men and women with HNC.
Association Between Neuroticism and Risk of Lung Cancer: Results From Observational and Mendelian Randomization Analyses
Authors: Wei Xiaoxia , Jiang Xiangxiang , Zhang Xu , Fan Xikang , Ji Mengmeng , Huang Yanqian , Xu Jing , Yin Rong , Wang Yuzhuo , Zhu Meng , Du Lingbin , Dai Juncheng , Jin Guangfu , Xu Lin , Hu Zhibin , Hang Dong , Ma Hongxia
Published: February 2022

Background

It remains undetermined whether neuroticism affects the risk of lung cancer. Therefore, we performed complementary observational and Mendelian randomization (MR) analyses to investigate the association between neuroticism and lung cancer risk.

Methods

We included 364,451 UK Biobank participants free of cancer at baseline. Neuroticism was ascertained using the 12-item of Eysenck Personality Inventory Neuroticism Scale. Multivariable Cox regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Two-sample MR analysis was carried out with summary genetic data from UK Biobank (374,323 individuals) and International Lung Cancer Consortium (29,266 lung cancer cases and 56,450 controls). Furthermore, we calculated a polygenic risk score of lung cancer, and examined the joint-effect and interaction between neuroticism and genetic susceptibility on lung cancer risk.

Results

During a median follow-up of 7.13 years, 1573 lung cancer cases were documented. After adjusting for smoking and other confounders, higher neuroticism was associated with an increased risk of lung cancer (HR per 1 SD=1.07, 95% CI: 1.02-1.12). Consistently, MR analysis suggested a causal effect of neuroticism on lung cancer risk (OR IVW=1.10, 95% CI: 1.03-1.17). Compared to individuals with low neuroticism and low PRS, those with both high neuroticism and high PRS had the greatest risk of lung cancer (HR=1.82, 95%CI: 1.51-2.20). Furthermore, there was a positive additive but no multiplicative interaction between neuroticism and genetic risk.

Conclusions

Our findings suggest that neuroticism is associated with an elevated risk of incident lung cancer, which is strengthened by the genetic susceptibility to lung cancer. Further studies are necessary to elucidate underlying mechanisms.