bluuebunny/crossref_metadata_2025 huggingface dataset:
Criticality in the Healthy Brain
Authors: Shi Jifan , Kirihara Kenji , Tada Mariko , Fujioka Mao , Usui Kaori , Koshiyama Daisuke , Araki Tsuyoshi , Chen Luonan , Kasai Kiyoto , Aihara Kazuyuki
Published: January 2022

The excellence of the brain is its robustness under various types of noise and its flexibility under various environments. However, how the brain works is still a mystery. The critical brain hypothesis proposes a possible mechanism and states that criticality plays an important role in the healthy brain. Herein, using an electroencephalography dataset obtained from patients with psychotic disorders (PDs), ultra-high risk (UHR) individuals and healthy controls (HCs), and its dynamical network analysis, we show that the brain of HCs remains around a critical state, whereas that of patients with PD falls into more stable states. Meanwhile, the brain of UHR individuals is similar to that of PD in terms of entropy but is analogous to that of HCs in causality patterns. These results not only provide evidence for the criticality of the normal brain but also highlight the practicability of using an analytic biophysical tool to study the dynamical properties of mental diseases.
Multidimensional Deep Learning Reduces False-Positives in the Automated Detection of Cerebral Aneurysms on Time-Of-Flight Magnetic Resonance Angiography: A Multi-Center Study
Authors: Terasaki Yuki , Yokota Hajime , Tashiro Kohei , Maejima Takuma , Takeuchi Takashi , Kurosawa Ryuna , Yamauchi Shoma , Takada Akiyo , Mukai Hiroki , Ohira Kenji , Ota Joji , Horikoshi Takuro , Mori Yasukuni , Uno Takashi , Suyari Hiroki
Published: January 2022

Current deep learning-based cerebral aneurysm detection demonstrates high sensitivity, but produces numerous false-positives (FPs), which hampers clinical application of automated detection systems for time-of-flight magnetic resonance angiography. To reduce FPs while maintaining high sensitivity, we developed a multidimensional convolutional neural network (MD-CNN) designed to unite planar and stereoscopic information about aneurysms. This retrospective study enrolled time-of-flight magnetic resonance angiography images of cerebral aneurysms from three institutions from June 2006 to April 2019. In the internal test, 80% of the entire data set was used for model training and 20% for the test, while for the external tests, data from different pairs of the three institutions were used for training and the remaining one for testing. Images containing aneurysms > 15 mm and images without aneurysms were excluded. Three deep learning models [planar information-only (2D-CNN), stereoscopic information-only (3D-CNN), and multidimensional information (MD-CNN)] were trained to classify whether the voxels contained aneurysms, and they were evaluated on each test. The performance of each model was assessed using free-response operating characteristic curves. In total, 732 aneurysms (5.9 ± 2.5 mm) of 559 cases (327, 120, and 112 from institutes A, B, and C; 469 and 263 for 1.5T and 3.0T MRI) were included in this study. In the internal test, the highest sensitivities were 80.4, 87.4, and 82.5%, and the FPs were 6.1, 7.1, and 5.0 FPs/case at a fixed sensitivity of 80% for the 2D-CNN, 3D-CNN, and MD-CNN, respectively. In the external test, the highest sensitivities were 82.1, 86.5, and 89.1%, and 5.9, 7.4, and 4.2 FPs/cases for them, respectively. MD-CNN was a new approach to maintain sensitivity and reduce the FPs simultaneously.
Pathophysiological Underpinnings of Extra-Motor Neurodegeneration in Amyotrophic Lateral Sclerosis: New Insights From Biomarker Studies
Authors: Reyes-Leiva David , Dols-Icardo Oriol , Sirisi Sonia , Cortés-Vicente Elena , Turon-Sans Janina , de Luna Noemi , Blesa Rafael , Belbin Olivia , Montal Victor , Alcolea Daniel , Fortea Juan , Lleó Alberto , Rojas-García Ricard , Illán-Gala Ignacio
Published: January 2022

Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) lie at opposing ends of a clinical, genetic, and neuropathological continuum. In the last decade, it has become clear that cognitive and behavioral changes in patients with ALS are more frequent than previously recognized. Significantly, these non-motor features can impact the diagnosis, prognosis, and management of ALS. Partially overlapping neuropathological staging systems have been proposed to describe the distribution of TAR DNA-binding protein 43 (TDP-43) aggregates outside the corticospinal tract. However, the relationship between TDP-43 inclusions and neurodegeneration is not absolute and other pathophysiological processes, such as neuroinflammation (with a prominent role of microglia), cortical hyperexcitability, and synaptic dysfunction also play a central role in ALS pathophysiology. In the last decade, imaging and biofluid biomarker studies have revealed important insights into the pathophysiological underpinnings of extra-motor neurodegeneration in the ALS-FTLD continuum. In this review, we first summarize the clinical and pathophysiological correlates of extra-motor neurodegeneration in ALS. Next, we discuss the diagnostic and prognostic value of biomarkers in ALS and their potential to characterize extra-motor neurodegeneration. Finally, we debate about how biomarkers could improve the diagnosis and classification of ALS. Emerging imaging biomarkers of extra-motor neurodegeneration that enable the monitoring of disease progression are particularly promising. In addition, a growing arsenal of biofluid biomarkers linked to neurodegeneration and neuroinflammation are improving the diagnostic accuracy and identification of patients with a faster progression rate. The development and validation of biomarkers that detect the pathological aggregates of TDP-43 in vivo are notably expected to further elucidate the pathophysiological underpinnings of extra-motor neurodegeneration in ALS. Novel biomarkers tracking the different aspects of ALS pathophysiology are paving the way to precision medicine approaches in the ALS-FTLD continuum. These are essential steps to improve the diagnosis and staging of ALS and the design of clinical trials testing novel disease-modifying treatments.
Sustaining Protein Nutrition Through Plant-Based Foods
Authors: Langyan Sapna , Yadava Pranjal , Khan Fatima Nazish , Dar Zahoor A. , Singh Renu , Kumar Ashok
Published: January 2022

Proteins are essential components of the human diet. Dietary proteins could be derived from animals and plants. Animal protein, although higher in demand, is generally considered less environmentally sustainable. Therefore, a gradual transition from animal- to plant-based protein food may be desirable to maintain environmental stability, ethical reasons, food affordability, greater food safety, fulfilling higher consumer demand, and combating of protein-energy malnutrition. Due to these reasons, plant-based proteins are steadily gaining popularity, and this upward trend is expected to continue for the next few decades. Plant proteins are a good source of many essential amino acids, vital macronutrients, and are sufficient to achieve complete protein nutrition. The main goal of this review is to provide an overview of plant-based protein that helps sustain a better life for humans and the nutritional quality of plant proteins. Therefore, the present review comprehensively explores the nutritional quality of the plant proteins, their cost-effective extraction and processing technologies, impacts on nutrition, different food wastes as an alternative source of plant protein, and their environmental impact. Furthermore, it focuses on the emerging technologies for improving plant proteins' bioavailability, digestibility, and organoleptic properties, and highlights the aforementioned technological challenges for future research work.
Hunger, Obesity, Public Policies, and Food-Based Dietary Guidelines: A Reflection Considering the Socio-Environmental World Context
Authors: Amorim Alessandra , Barbosa Ana de Holanda , Sobral Paulo José do Amaral
Published: January 2022

Nowadays, the world has been characterized by hunger, obesity, and food loss and waste (FLW). With the COVID-19 pandemic, the food issue became more intense, serious, and evident. Hunger demands urgent actions. Obesity levels have been raised and are removing health and quality of life from the population. Production planting practices and the food supply chain are not necessarily ecologically friendly. Sustainability issues greatly intensify social problems. As well as food loss (FL), food waste (FW), and sustainability concerns, obesity, and malnutrition are enhanced due to the lack of knowledge by the population. Processed food (PF), packaging, and additives, despite still needing improvement, are essential to food security control. Nowadays, hunger is not due to insufficient agricultural practices but rather to inequality and absence of adequate public policies. In the context of a certain abundance of food production and processing, the hunger scenario in contrast to FLW is an ethical, social, moral, and sustainable issue. In this context, a Food-Based Dietary Guideline (FBDG) can be an important public policy tool from the health, nutrition, environmental, and educational points of view. Despite the effort, the literature shows that FBDGs can be better used to fulfill healthiness and sustainability purposes. In this scenario, the elaboration/revision of the FBDG, adopting a clearer, simpler, and a better-suited communication strategy is essential. In this way, this article discusses the importance of the FBDG as a public policy tool, not only regarding health issues but also communication strategies, production sustainability, and humanitarian ones, which are crucial to FBDG's efficiency.
Altering Dietary Soluble Protein Levels With Decreasing Crude Protein May Be a Potential Strategy to Improve Nitrogen Efficiency in Hu Sheep Based on Rumen Microbiome and Metabolomics
Authors: Zhang Zhenbin , Shahzad Khuram , Shen Sijun , Dai Rong , Lu Yue , Lu Zhiqi , Li Chuang , Chen Yifei , Qi Ruxin , Gao Pengfei , Yang Qingyong , Wang Mengzhi
Published: January 2022

Ruminants account for a relatively large share of global nitrogen (N) emissions. It has been reported that nutrition control and precise feeding can improve the N efficiency of ruminants. The objective of the study was to determine the effects of soluble protein (SP) levels in low-protein diets on growth performance, nutrient digestibility, rumen microbiota, and metabolites, as well as their associations of N metabolism in fatteningHusheep. Approximately 6-month-old, 32 healthy fattening maleHusheep with similar genetic merit and an initial body weight of 40.37 ± 1.18 kg were selected, and divided into four groups (n= 8) using the following completely randomized design: the control diet (CON) with a 16.7% crude protein (CP) content was prepared to meet the nutritional requirements of fattening sheep [body weight (BW): 40 kg, average daily gain (ADG): 200–250 g/d] according to the NRC recommendations; other three include low protein diets (LPA, LPB, and LPC) of CP decreased by ~10%, with SP proportion (%CP) of 21.2, 25.9, and 29.4 respectively. The feeding trial lasted for 5 weeks including the first week of adaptation. The results showed no difference in the growth performance (P> 0.05); DM and CP digestibility were higher in LPB and LPC, with maximum organic matter digestibility in LPB (P< 0.05). Low-protein diets decreased serum urea-N whereas urinary urea-N was lower in LPB and LPC (P< 0.05), while N retention and the biological value of N were higher in LPB and LPC (P< 0.05). Ruminal NH3-N concentration in LPA and LPB was low than CON (P< 0.05), while total volatile fatty acid (TVFA), acetate, propionate, and butanoate were all lowest in LPA (P< 0.05). In the rumen microbiome, LPB increased the community richness in Prevotellaceae andPrevotella_1(P< 0.05); Metabolomics analysis revealed low-protein diets downregulated the amino acid metabolism pathways, while the biosynthesis of unsaturated fatty acids along with vitamin B6 metabolism were upregulated with increased SP. These findings could help us understand the role of different SP levels in the regulation of rumen microbial metabolism and N efficiency. Overall, low-protein diets (CP decreased by ~10%) can reduce serum urea-N and ruminal NH3-N without affecting the growth performance of fatteningHusheep. Additionally higher N efficiency was obtained with an SP proportion of ~25–30%.
m6A Methyltransferase METTL3 Promotes the Progression of Primary Acral Melanoma via Mediating TXNDC5 Methylation
Authors: Yue Zhanghui , Cao Meng , Hong Anlan , Zhang Qian , Zhang Guoqiang , Jin Zhibin , Zhao Liang , Wang Qiang , Fang Fang , Wang Yan , Sun Jianfang
Published: January 2022

m6A modification is one of the most important post-transcriptional modifications in RNA and plays an important role in promoting translation or decay of RNAs. The role of m6A modifications has been highlighted by increasing evidence in various cancers, which, however, is rarely explored in acral melanoma. Here, we demonstrated that m6A level was highly elevated in acral melanoma tissues, along with the expression of METTL3, one of the most important m6A methyltransferase. Besides, higher expression of METTL3 messenger RNA (mRNA) correlated with a higher stage in primary acral melanoma patients. Knockdown of METTL3 decreased global m6A level in melanoma cells. Furthermore, METTL3 knockdown suppressed the proliferation, migration, and invasion of melanoma cells. In METTL3 knockdown xenograft mouse models, we observed decreased volumes and weights of melanoma tissues. Mechanistically, we found that METTL3 regulates certain m6A-methylated transcripts, thioredoxin domain containing protein 5 (TXNDC5), with the confirmation of RNA-seq, MeRIP-seq, and Western blot. These data suggest that METTL3 may play a key role in the progression of acral melanoma, and targeting the m6A dependent-METTL3 signaling pathway may serve as a promising therapeutic strategy for management of patients of acral melanomas.
A Nomogram for Predicting the Risk of Radiotherapy-Related Esophageal Fistula in Esophageal Cancer Patients
Authors: Gui Zhongxuan , Liu Huiquan , Shi Weijiong , Xu Yuechen , Qian Han , Wang Fan
Published: January 2022

Background

To construct and validate a nomogram for predicting the risk of esophageal fistula in esophageal cancer patients receiving radiotherapy.

Methods

A retrospective nested case–control study was performed, in which a total of 81 esophageal fistula patients and 243 controls from 2014 to 2020 in the First Affiliated Hospital of Anhui Medical University were enrolled. Factors included in the nomogram were determined by univariate and multiple logistic regression analysis. The following methods including ROC curve, C-index, calibration curves, Brier score, and decision curve analysis (DCA) were adopted to evaluate this nomogram.

Results

Multivariate logistic regression analysis showed that T4 stage, level 4 stenosis, ulcerative esophageal cancer, prealbumin, and maximum diameters of GTV and NLR were the independent risk factors of esophageal fistula. Accordingly, a nomogram incorporating the aforementioned six parameters was constructed. The AUC was 0.848 (95% CI 0.901–0.895), indicating a high prediction accuracy of this nomogram. Further evaluation of this model showed that the C-index was 0.847, while the bias-corrected C-index after internal validation was 0.833. The Brier score was 0.127. The calibration curves presented good concordance, and the DCA revealed promising clinical application.

Conclusions

The nomogram presents accurate and applicable prediction for the esophageal fistula risk in esophageal cancer patients receiving radiotherapy.
The Prognostic Impact of Combined Tumor-Infiltrating Lymphocytes and Pretreatment Blood Lymphocyte Percentage in Locally Advanced Nasopharyngeal Carcinoma
Authors: Cai Zhuochen , Jiang Jiali , Huang Laiji , Yuan Yawei , Zheng Ronghui , Zhang Jiangyu , Qiu Wenze
Published: January 2022

Purpose

To explore the prognostic impact of combined tumor-infiltrating lymphocytes (TILs) and pretreatment peripheral lymphocyte percentage (LYM%) among patients with locally advanced nasopharyngeal carcinoma (LA-NPC).

Patients and Methods

TILs and pretreatment LYM% were retrospectively assessed in 253 LA-NPC patients who underwent chemoradiation therapy between January 2012 and December 2017. According to TILs and LYM% status, the patients were divided into three groups: high-risk group (HRG) (TILs–LYM% score = 0), middle-risk group (MRG) (TILs–LYM% score = 1), and low-risk group (LRG) (TILs–LYM% score = 2). The relationship between TILs level and LYM%, and also the associations of TILs–LYM% status with clinicopathological factors and survival, were evaluated.

Results

As a continuous variable, LYM% was significantly higher in TILs-high group. High TILs or high LYM% alone was significantly related to better 3-year disease-free survival (DFS), overall survival (OS), distant metastasis-free survival (DMFS) and locoregional relapse-free survival (LRRFS), respectively. Kaplan–Meier analysis and log-rank tests also revealed significant decreases in DFS, OS, DMFS, and LRRFS among LA-NPC patients with TILs–LYM% score of 0, 1, and 2 (all P <0.05). Further multivariate analyses showed that TILs–LYM% score was an independent factor affecting survival of the patients, and HRG (TILs–LYM% score = 0) had increased hazard ratios (HRs) for disease (HR = 6.89, P <0.001), death (HR = 8.08, P = 0.008), distant metastasis (HR = 7.66, P = 0.001), and local relapse (HR = 5.18, P = 0.013) compared with LRG (TILs–LYM% score = 2). In receiver operating characteristics (ROC) analyses, TILs–LYM% score had a higher area under the ROC curve (AUC) for the prediction of DFS than did TILs or LYM% alone.

Conclusions

A positive correlation was found between TILs level and pretreatment blood lymphocyte percentage. Moreover, TILs–LYM% score can be considered as a novel independent prognostic indicator of survival outcome among patients with LA-NPC.
Genomic Feature of a Rare Case of Mix Small-Cell and Large-Cell Neuroendocrine Lung Carcinoma: A Case Report
Authors: Zhu Youcai , Zhang Feng , Yu Dong , Wang Fang , Yin Manxiang , Chen Liangye , Xiao Chun , Huang Yueyan , Ding Feng
Published: January 2022

Background

Cases of both of small- (SCLC) and large-cell neuroendocrine lung carcinoma (LCNEC) were rarely reported. Although typical cases are morphologically distinct, the distinction between LCNEC and SCLC is still controversial, with some LCNECs showing close morphologies with SCLC. Here, we reported on a patient who had tumor with a mix of SCLC and LCNEC and uncovered these components’ histological and genomic features.

Case Presentation

A 59-year-old man was diagnosed with lung cancer and had resection surgery in our hospital. The H&E and immunohistochemistry staining revealed that the tumor had 30%–35% LCNEC and 65%–70% SCLC cells. The whole-exome sequencing (WES) identified no potentially actionable alteration in the tumor sample but found five alterations all with allele frequency over 90%, including TP53 p.R273H, MYH8 p.Q1814K, SLC17A6 p.W505L, PTPN5 p.M40I, and RB1 p.L267X. The genomic results supported that these two different components shared a similar dominant clonal origin. Furthermore, fluorescence in situ hybridization analysis revealed that the LCNECs have a higher copy number of MET than the SCLC component while without notable difference in the copy number of HER2 and TP53. Chemotherapy with pemetrexed and carboplatin was administrated for two cycles after the surgery. Although the chest CT showed remission in the lung, he was diagnosed with bone metastasis in 1 year later. Then, he received chemotherapy with etoposide and carboplatin but had severe side effect, leading to the discontinuation of the regime. Unfortunately, he returned to the local hospital with supportive care and died shortly after.

Conclusion

Based on these observations, we proposed that LCNEC and SCLC components in this patient may have a common clonal origin with dual mutations in TP53 and RB1, while the chromosome instability may cause multiple independent conversion that leads to LCNEC or SCLC morphologies.
Advantages of Widefield Optical Coherence Tomography in the Diagnosis of Retinopathy of Prematurity
Authors: Nguyen Thanh-Tin P. , Ni Shuibin , Khan Shanjida , Wei Xiang , Ostmo Susan , Chiang Michael F. , Jia Yali , Huang David , Jian Yifan , Campbell J. Peter
Published: January 2022

Recent advances in portable optical coherence tomography (OCT) and OCT angiography (OCTA) have resulted in wider fields of view (FOV) and shorter capture times, further expanding the potential clinical role of OCT technology in the diagnosis and management of retinopathy of prematurity (ROP). Using a prototype, handheld OCT device, retinal imaging was obtained in non-sedated infants in the neonatal intensive care unit (NICU) as well as sedated infants in the operating room of Oregon Health & Science University (OHSU) Hospital. In this observational study, we provide an overview of potential advantages of OCT-based disease assessment in ROP. We observed that next-generation OCT imaging (a) may be sufficient for objective diagnosis and zone/stage/plus disease categorization, (b) allows for minimally-invasive longitudinal monitoring of disease progression and post-treatment course, (c) provides three-dimensional mapping of the vitreoretinal interface, and (d) with OCTA, enables dye-free visualization of normal and pathologic vascular development.
Substrate Reduction Therapy for Krabbe Disease: Exploring the Repurposing of the Antibiotic D-Cycloserine
Authors: LeVine Steven M. , Tsau Sheila
Published: January 2022

Krabbe disease is a lysosomal storage disease that is caused by a deficiency in galactosylceramidase. Infantile onset disease is the most common presentation, which includes progressive neurological deterioration with corresponding demyelination, development of globoid cells, astrocyte gliosis, etc. Hemopoietic stem cell transplantation (HSCT) is a disease modifying therapy, but this intervention is insufficient with many patients still experiencing developmental delays and progressive deterioration. Preclinical studies have used animal models, e.g., twitcher mice, to test different experimental therapies resulting in developments that have led to progressive improvements in the therapeutic impact. Some recent advances have been in the areas of gene therapy and substrate reduction therapy (SRT), as well as using these in combination with HSCT. Unfortunately, new experimental approaches have encountered obstacles which have impeded the translation of novel therapies to human patients. In an effort to identify a safe adjunct therapy, D-cycloserine was tested in preliminary studies in twitcher mice. When administered as a standalone therapy, D-cycloserine was shown to lengthen the lifespan of twitcher mice in a small but significant manner. D-Cycloserine is an FDA approved antibiotic used for drug resistant tuberculosis. It also acts as a partial agonist of the NMDA receptor, which has led to numerous human studies for a range of neuropsychiatric and neurological conditions. In addition, D-cycloserine may inhibit serine palmitoyltransferase (SPT), which catalyzes the rate-limiting step in sphingolipid production. The enantiomer, L-cycloserine, is a much more potent inhibitor of SPT than D-cycloserine. Previously, L-cycloserine was found to act as an effective SRT agent in twitcher mice as both a standalone therapy and as part of combination therapies. L-Cycloserine is not approved for human use, and its potent inhibitory properties may limit its ability to maintain a level of partial inactivation of SPT that is also safe. In theory, D-cycloserine would encompass a much broader dosage range to achieve a safe degree of partial inhibition of SPT, which increases the likelihood it could advance to human studies in patients with Krabbe disease. Furthermore, additional properties of D-cycloserine raise the possibility of other therapeutic mechanisms that could be exploited for the treatment of this disease.
DBP rs7041 and DHCR7 rs3829251 are Linked to CD4+ Recovery in HIV Patients on Antiretroviral Therapy
Authors: Resino Salvador , Jiménez-Sousa María Ángeles , Blanco Julià , Pacheco Yolanda M. , del Romero Jorge , Peraire Joaquim , Virseda-Berdices Ana , Muñoz-Gómez María José , Galera-Peñaranda Carlos , García-Fraile Lucio Jesus , Benito José M. , Rallón Norma
Published: January 2022

Background: The lack of the recovery of CD4+ T-cells (CD4+ recovery) among immunodeficiency virus (HIV)-infected patients on antiretroviral therapy (ART) is not well known. We aimed to analyze the association between single nucleotide polymorphisms (SNPs) underlying vitamin D metabolism and the CD4+ recovery in naïve HIV-infected patients who started ART with low baseline CD4+.

Methods: We conducted a retrospective study in 411 naïve individuals with plasma HIV load >200 copies/mL and CD4+ <200 cells/mm3. During 24 months of follow-up, all patients had plasma HIV load <50 copies/mL. DNA genotyping was performed using the Sequenom MassARRAY platform. The outcome variable was the change in CD4+ during the study.

Results: CD4+ recovery was higher in patients carrying DBP rs7041 AA genotype (AA versus CC/AC) and DHCR7 rs3829251 AA genotype (AA versus GG/AG) (p-value < 0.05). DBP rs7041 AA genotype was linked to increase in CD4+ (adjusted arithmetic mean ratio (aAMR) = 1.22; q-value = 0.011), increase in CD4+ ≥P75th [adjusted odds ratio (aOR) = 2.31; q-value = 0.005], slope of CD4+ recovery (aAMR = 1.25; q-value = 0.008), slope of CD4+ recovery ≥ P75th (aOR = 2.55; q-value = 0.005) and achievement of CD4+ ≥500 cells/mm3 (aOR = 1.89; q-value = 0.023). Besides, DHCR7 rs3829251 AA genotype was related to increase in CD4+ (aAMR = 1.43; q-value = 0.031), increase in CD4+ ≥P75th (aOR = 3.92; q-value = 0.030), slope of CD4+ recovery (aAMR = 1.40; q-value = 0.036), slope of CD4+ recovery ≥ P75th (aOR = 3.42; q-value = 0.031) and achievement of CD4+ ≥500 cells/mm3 (aOR = 5.68; q-value = 0.015).

Conclusion: In summary, DHCR7 rs3829251 and DBP rs7041 polymorphisms were associated with CD4+ recovery in HIV-infected patients who started cART with low CD4+ T-cell counts.
Mechanism of Dihydromyricetin on Inflammatory Diseases
Authors: Sun Yang , Liu Shasha , Yang Songwei , Chen Chen , Yang Yantao , Lin Meiyu , Liu Chao , Wang Wenmao , Zhou Xudong , Ai Qidi , Wang Wei , Chen Naihong
Published: January 2022

Inflammation plays a crucial role in a variety of diseases, including diabetes, arthritis, asthma, Alzheimer’s disease (AD), acute cerebral stroke, cancer, hypertension, and myocardial ischemia. Therefore, we need to solve the problem urgently for the study of inflammation-related diseases. Dihydromyricetin (DHM) is a flavonoid mainly derived from Nekemias grossedentata (Hand.-Mazz.) J.Wen and Z.L.Nie (N.grossedentata). DHM possesses many pharmacological effects, including anti-inflammatory (NLRP-3, NF-κB, cytokines, and neuroinflammation), antioxidant, improving mitochondrial dysfunction, and regulating autophagy and so on. In this review, we consulted the studies in the recent 20 years and summarized the mechanism of DHM in inflammation-related diseases. In addition, we also introduced the source, chemical structure, chemical properties, and toxicity of DHM in this review. We aim to deepen our understanding of DHM on inflammation-related diseases, clarify the relevant molecular mechanisms, and find out the problems and solutions that need to be solved urgently. Providing new ideas for DHM drug research and development, as well as broaden the horizons of clinical treatment of inflammation-related diseases in this review. Moreover, the failure of clinical transformation of DHM poses a great challenge for DHM as an inflammation related disease.
An Application of Quantum Annealing Computing to Seismic Inversion
Authors: Souza Alexandre M. , Martins Eldues O. , Roditi Itzhak , Sá Nahum , Sarthour Roberto S. , Oliveira Ivan S.
Published: January 2022

Quantum computing, along with quantum metrology and quantum communication, are disruptive technologies that promise, in the near future, to impact different sectors of academic research and industry. Among the computational challenges with great interest in science and industry are the inversion problems. These kinds of numerical procedures can be described as the process of determining the cause of an event from measurements of its effects. In this paper, we apply a recursive quantum algorithm to a D-Wave quantum annealer to solve a small scale seismic inversions problem. We compare the obtained results from the quantum computer to those derived from a classical algorithm. The accuracy achieved by the quantum computer is at least as good as that of the classical computer.
Aerobic Exercise Improves Pulmonary Fibrosis by Improving Insulin Resistance and Inflammation in Obese Mice
Authors: Wang Xishuai , Yi Xuejie , Tang Donghui
Published: January 2022

Background

Previous studies have demonstrated that obesity is associated with pulmonary fibrosis. We attempted to identify whether regular aerobic exercise (AE) can protect against high-fat diet (HFD)-associated pulmonary fibrosis.

Methods

Forty-eight C57BL/6 mice were randomly assigned to four groups: chow group (Ch), chow plus exercise group (CE), obesity group (Ob), and obesity plus exercise group (OE). The mice were fed either an HFD or a chow diet for 16 weeks, and low-intensity aerobic exercise (AE) was performed in the last 8 weeks. We measured the degree of pulmonary fibrosis; pulmonary inflammation; oxidative stress parameters; insulin resistance-related indicators; the number of inflammatory cells in bronchoalveolar lavage fluid (BALF); the mRNA expression levels of IL-10, IL-1β, TGF-β, TNF-α, CXCL-1, IL-17, MMP-9, MPO, NE, and sirt-1; and the BALF levels of CXCL-1, IL-17, TGF-β, IL-10, IL-1β, and TNF-α in lung tissue.

Results

AE in obese mice protected against obesity-associated pulmonary fibrosis, chronic inflammation, pro-oxidative/antioxidative imbalance, and insulin resistance. AE ameliorated the HFD-induced inflammatory response and neutrophil infiltration in the lung. AE downregulated BALF levels of CXCL-1, IL-1β, TNF-α IL-17, and TGF-β but upregulated BALF levels of IL-10. AE decreased IL-1β, TGF-β, TNF-α, CXCL-1, IL-17, MMP-9, MPO, and NE mRNA expression levels but upregulated IL-10 and sirt-1 mRNA expression levels in the lung.

Conclusions

AE protects against HFD-induced pulmonary fibrosis by improving obesity-associated insulin resistance, chronic low-grade inflammation, and pro-oxidative/antioxidative imbalance. AE improved HFD-induced pulmonary fibrosis by suppressing IL-17, TGF-β, NE, and MMP-9 expression and activating IL-10 and sirt-1 expression.
Design Study of a Novel Positron Emission Tomography System for Plant Imaging
Authors: Antonecchia Emanuele , Bäcker Markus , Cafolla Daniele , Ciardiello Mariachiara , Kühl Charlotte , Pagnani Giancarlo , Wang Jiale , Wang Shuai , Zhou Feng , D'Ascenzo Nicola , Gialanella Lucio , Pisante Michele , Rose Georg , Xie Qingguo
Published: January 2022

Positron Emission Tomography is a non-disruptive and high-sensitive digital imaging technique which allows to measure in-vivo and non invasively the changes of metabolic and transport mechanisms in plants. When it comes to the early assessment of stress-induced alterations of plant functions, plant PET has the potential of a major breakthrough. The development of dedicated plant PET systems faces a series of technological and experimental difficulties, which make conventional clinical and preclinical PET systems not fully suitable to agronomy. First, the functional and metabolic mechanisms of plants depend on environmental conditions, which can be controlled during the experiment if the scanner is transported into the growing chamber. Second, plants need to be imaged vertically, thus requiring a proper Field Of View. Third, the transverse Field of View needs to adapt to the different plant shapes, according to the species and the experimental protocols. In this paper, we perform a simulation study, proposing a novel design of dedicated plant PET scanners specifically conceived to address these agronomic issues. We estimate their expected sensitivity, count rate performance and spatial resolution, and we identify these specific features, which need to be investigated when realizing a plant PET scanner. Finally, we propose a novel approach to the measurement and verification of the performance of plant PET systems, including the design of dedicated plant phantoms, in order to provide a standard evaluation procedure for this emerging digital imaging agronomic technology.
New Insights Into the Evolution of C4 Photosynthesis Offered by the Tarenaya Cluster of Cleomaceae
Authors: Parma Daniele F. , Vaz Marcelo G. M. V. , Falquetto Priscilla , Silva Jéssica C. , Clarindo Wellington R. , Westhoff Philipp , van Velzen Robin , Schlüter Urte , Araújo Wagner L. , Schranz M. Eric , Weber Andreas P. M. , Nunes-Nesi Adriano
Published: January 2022

Cleomaceae is closely related to Brassicaceae and includes C3, C3–C4, and C4 species. Thus, this family represents an interesting system for studying the evolution of the carbon concentrating mechanism. However, inadequate genetic information on Cleomaceae limits their research applications. Here, we characterized 22 Cleomaceae accessions [3 genera (Cleoserrata, Gynandropsis, and Tarenaya) and 11 species] in terms of genome size; molecular phylogeny; as well as anatomical, biochemical, and photosynthetic traits. We clustered the species into seven groups based on genome size. Interestingly, despite clear differences in genome size (2C, ranging from 0.55 to 1.3 pg) in Tarenaya spp., this variation was not consistent with phylogenetic grouping based on the internal transcribed spacer (ITS) marker, suggesting the occurrence of multiple polyploidy events within this genus. Moreover, only G. gynandra, which possesses a large nuclear genome, exhibited the C4 metabolism. Among the C3-like species, we observed intra- and interspecific variation in nuclear genome size as well as in biochemical, physiological, and anatomical traits. Furthermore, the C3-like species had increased venation density and bundle sheath cell size, compared to C4 species, which likely predisposed the former lineages to C4 photosynthesis. Accordingly, our findings demonstrate the potential of Cleomaceae, mainly members of Tarenaya, in offering novel insights into the evolution of C4 photosynthesis.
Reciprocal Field Transplant Experiment and Comparative Transcriptome Analysis Provide Insights Into Differences in Seed Germination Time of Two Populations From Different Geographic Regions of Zostera marina L.
Authors: Zhang Yu , Xu Shaochun , Yue Shidong , Zhang Xiaomei , Qiao Yongliang , Liu Mingjie , Zhou Yi
Published: January 2022

Seagrasses are the only submerged marine higher plants, which can colonize the sea through sexual (via seeds) reproduction. The transition between seed dormancy and germination is an important ecological trait and a key stage in the life cycle of higher plants. According to our observations, the seeds of Zostera marina L. (eelgrass) in Swan Lake (SL) and Qingdao Bay (QB) in northern China have the same maturation time (summer) but different germination time. To investigate this phenomenon, we further carried out reciprocal transplantation experiment and transcriptome analysis. Results revealed that differences in the seed germination time between the two sites do exist and are determined by internal molecular mechanisms as opposed to environmental factors. Furthermore, we conducted comparative transcriptome analysis of seeds at the mature and early germination stages in both locations. The results that the number of genes related to energy, hormone and cell changes was higher in SL than in QB, could account for that the dormancy depth of seeds in SL was deeper than that in QB; consequently, the seeds in SL needed to mobilize more related genes to break dormancy and start germination. The results could have important practical implications for seagrass meadow restoration via seeds and provide in-depth and comprehensive data for understanding the molecular mechanisms related to seagrass seed germination.
RNA-Seq Transcriptome Analysis Provides Candidate Genes for Resistance to Tomato Leaf Curl New Delhi Virus in Melon
Authors: Sáez Cristina , Flores-León Alejandro , Montero-Pau Javier , Sifres Alicia , Dhillon Narinder P. S. , López Carmelo , Picó Belén
Published: January 2022

Tomato leaf curl New Delhi virus (ToLCNDV) emerged in the Mediterranean Basin in 2012 as the first DNA bipartite begomovirus (Geminiviridae family), causing severe yield and economic losses in cucurbit crops. A major resistance locus was identified in the wild melon accession WM-7 (Cucumis melo kachri group), but the mechanisms involved in the resistant response remained unknown. In this work, we used RNA-sequencing to identify disease-associated genes that are differentially expressed in the course of ToLCNDV infection and could contribute to resistance. Transcriptomes of the resistant WM-7 genotype and the susceptible cultivar Piñonet Piel de Sapo (PS) (C. melo ibericus group) in ToLCNDV and mock inoculated plants were compared at four time points during infection (0, 3, 6, and 12 days post inoculation). Different gene expression patterns were observed over time in the resistant and susceptible genotypes in comparison to their respective controls. Differentially expressed genes (DEGs) in ToLCNDV-infected plants were classified using gene ontology (GO) terms, and genes of the categories transcription, DNA replication, and helicase activity were downregulated in WM-7 but upregulated in PS, suggesting that reduced activity of these functions reduces ToLCNDV replication and intercellular spread and thereby contributes to resistance. DEGs involved in the jasmonic acid signaling pathway, photosynthesis, RNA silencing, transmembrane, and sugar transporters entail adverse consequences for systemic infection in the resistant genotype, and lead to susceptibility in PS. The expression levels of selected candidate genes were validated by qRT-PCR to corroborate their differential expression upon ToLCNDV infection in resistant and susceptible melon. Furthermore, single nucleotide polymorphism (SNPs) with an effect on structural functionality of DEGs linked to the main QTLs for ToLCNDV resistance have been identified. The obtained results pinpoint cellular functions and candidate genes that are differentially expressed in a resistant and susceptible melon line in response to ToLCNDV, an information of great relevance for breeding ToLCNDV-resistant melon cultivars.
Anxiety, Depression, and Satisfaction With Life Among College Students in China: Nine Months After Initiation of the Outbreak of COVID-19
Authors: Xiao Pei , Chen Liang , Dong Xiaoqin , Zhao Zhiya , Yu Jincong , Wang Dongming , Li Wenzhen
Published: January 2022

Background/Objective

Mental health problems are common among college students. This study sought to assess the prevalence and risk factors of depressive and anxiety symptoms and well-being among Chinese college students 9 months after initiation of the outbreak of COVID-19.

Method

A cross-sectional study (N = 3,951, mean age = 19.58) was conducted from October to December 2020. An online survey was used to collect socio-demographic data, and the symptoms of depression and anxiety and satisfaction with life using Disorder 7-Item Scale (GAD-7), the Patient Health Questionnaire 9-Item Scale (PHQ-9), and the 5-items Satisfaction with Life Scale (SWLS).

Results

The prevalence of depressive and anxiety symptoms was 59.35 and 54.34%, respectively, and the score of satisfaction with life was 20.51 ± 6.42 among Chinese college students during the pandemic. After controlling for covariates, students in urban areas (AOR = 0.73, 95% CI = 0.61–0.87), with good family economic levels (AOR = 0.77, 95% CI = 0.66–0.91), and having psychological counseling (AOR = 0.55, 95% CI = 0.42–0.73) were positively associated with depression symptoms; meanwhile, higher anxiety symptoms were observed among medical students (AOR = 0.81, 95% CI = 0.69–0.95). Besides, healthy lifestyle such as regular physical activity and diet was associated with depression and anxiety symptoms. Multiple linear models revealed that medical students (β = 0.479, P = 0.031), those with good family economic level by self-evaluation (β = 1.283, P < 0.001 for good; β = 3.013, P < 0.001 for general), good academic performance by self-evaluation (β = 1.786, P < 0.001 for good; β = 3.386, P < 0.001 for general), learning burden (β = 1.607, P < 0.001 for general; β = 2.117, P < 0.001 for light), regular physical activity (β = 0.859, P < 0.001), daily routine (β = 1.289, P < 0.001), diet (β = 1.714, P < 0.001), and sufficient sleep (β = 1.408, P < 0.001) had more score of SWLS (all β > 0, P < 0.05), while senior students (β = −1.053, P=0.009), students having psychological counseling (β = −1.753, P < 0.001), and drinking (β = −0.743, P = 0.012) had lower satisfaction with life.

Conclusions

These findings suggest that more attention should be paid to psychological health among college students, especially during and after the COVID-19 outbreak. Policy makers and educators should help college students develop a healthy lifestyle with regular diet and exercise to promote the psychological health of college students.
Prevalence and Developmental Profiles of Autism Spectrum Disorders in Children With Global Developmental Delay
Authors: Shan Ling , Feng Jun-Yan , Wang Tian-Tian , Xu Zhi-Da , Jia Fei-Yong
Published: January 2022

Background

Previous studies have mostly explored the comorbidities of Global developmental delay (GDD) in children with Autism Spectrum Disorders (ASD) from the perspective of ASD. The study focus on the perspective of GDD to investigate the prevalence and developmental profiles of ASD in GDD and to explore the correlation between the developmental level and symptoms of autism.

Methods

Clinical data of 521 children with GDD aged from 24 to 60 months were retrospectively analyzed. Analyses were performed first for the whole sample and then subdivided into two subgroups (GDD+ASD−, GDD+ASD+) according to whether had ASD. Symptoms of autism were evaluated by the Autism Behavior Checklist and the Childhood Autism Rating Scale. The Chinese version of the Gesell Developmental Schedules was used to evaluate the level of children's mental development.

Result

The prevalence of ASD in children with GDD was 62.3%. The total average developmental quotient (DQ) of GDD was mildly deficient and was negatively correlated with symptoms of autism (p < 0.05); language ability was severe and extremely severe deficient (P < 0.05). GDD+ASD− group and GDD+ASD+ group have some common points as well as differences in the developmental features. The language delay of children in both subgroups was the most obviously defected, thereafter followed by the item of personal social activity. In the GDD+ASD+ group, the DQ of gross motor skills>fine motor skills>adaptability (p < 0.05). There were no significant differences among the DQ of gross motor skills, fine motor skills and adaptability in GDD+ASD− group (p > 0.05). The GDD+ASD−group had better adaptability, fine motor skills, language ability, personal social activity than that of the GDD+ASD+ group, but the gross motor skills in GDD+ASD− group were worse (p < 0.05).

Conclusion

GDD children have a high proportion of comorbid ASD, and GDD children with poorer developmental levels are more likely to have ASD symptoms. Development profiles in both GDD+ASD− children and GDD+ASD+ children have common features but there are also differences. GDD+ASD+ group is worse than GDD+ASD− group in terms of the overall development level.
People Who Die by Suicide Without Receiving Mental Health Services: A Systematic Review
Authors: Tang Samantha , Reily Natalie M. , Arena Andrew F. , Batterham Philip J. , Calear Alison L. , Carter Gregory L. , Mackinnon Andrew J. , Christensen Helen
Published: January 2022

Introduction

The majority of people who die by suicide have never seen a mental health professional or been diagnosed with a mental illness. To date, this majority group has largely been ignored, with most existing research focusing on predictors of suicide such as past suicide attempts. Identifying the characteristics of people who die by suicide without receiving services, often with a fatal first attempt, is crucial to reduce suicide rates through guiding improvements to service pathways and “just in time” interventions.

Methods

In this systematic review, PsycInfo, PubMed, CINAHL, and Web of Science were searched for peer-reviewed articles published from 1980 to 1st March 2021. Included studies examined predictors of non-receipt of formal mental health services among people who died by suicide. Data were extracted from published reports and the quality of included studies was assessed using a modified version of the Joanna Briggs Institute Checklist for Analytical Cross Sectional Studies. This review was registered with PROSPERO, CRD 42021226543.

Results

Sixty-seven studies met inclusion criteria, with sample sizes ranging from 39 to 193,152 individuals. Male sex, younger or older age, and rural location were consistently associated with non-receipt of mental health services. People not receiving mental health services were also less likely to have a psychiatric diagnosis, past suicidal behavior or contact with general health services, and more likely to use violent means of suicide. There was some evidence that minority ethnicity and psychosocial stressors were associated with service non-receipt.

Conclusion

People who die by suicide without receiving mental health services are likely to have diverse profiles, indicating the need for multifaceted approaches to effectively support people at risk of suicide. Identifying the needs and preferences of individuals who are at risk of suicide is crucial in developing new support pathways and services, and improving the quality of existing services.

Systematic Review Registration

http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42021226543.
Social Media Use and Its Associations With Mental Health 9 Months After the COVID-19 Outbreak: A Cross-National Study
Authors: Thygesen Hilde , Bonsaksen Tore , Schoultz Mariyana , Ruffolo Mary , Leung Janni , Price Daicia , Geirdal Amy Østertun
Published: January 2022

Background

The covid-19 pandemic has impacted the health and well-being of millions across the globe. Strict social distancing policies and periodic lockdowns has led to an increased reliance on alternative online means of communication, including social media.

Objectives

to examine (i) social media use and mental health in the general population 9 months after the COVID-19 pandemic outbreak and (ii) mental health in relation to motives for and extent of social media use, while adjusting for sociodemographic variables.

Methods

A cross-national online survey was conducted in Norway, UK, USA and Australia. Participants (n= 3,474) reported extent of and motives for social media use and completed the 12-item General Health Questionnaire. The data were analyzed by chi-square tests, one-way analyses of variance, and multiple linear regression analysis.

Results

Poorer mental health was associated with using social media to decrease loneliness and for entertainment motives, while better mental health was associated with using social media for personal contact and maintaining relationships. Overall increased daily time on social media was associated with poorer mental health. The social media use variables were responsible for a substantial proportion of the outcome variance explained. These findings were consistent across the four countries, with only minor variations.

Conclusions

Motives for using, and time spent using, social media were associated with the participants' mental health. Guidance and recommendations for social media usage to the general public for prevention and intervention for behavioral health may be beneficial.