bluuebunny/crossref_metadata_2025 huggingface dataset:
Generative Model of Brain Microbleeds for MRI Detection of Vascular Marker of Neurodegenerative Diseases
Authors: Momeni Saba , Fazlollahi Amir , Lebrat Leo , Yates Paul , Rowe Christopher , Gao Yongsheng , Liew Alan Wee-Chung , Salvado Olivier
Published: December 2021

Cerebral microbleeds (CMB) are increasingly present with aging and can reveal vascular pathologies associated with neurodegeneration. Deep learning-based classifiers can detect and quantify CMB from MRI, such as susceptibility imaging, but are challenging to train because of the limited availability of ground truth and many confounding imaging features, such as vessels or infarcts. In this study, we present a novel generative adversarial network (GAN) that has been trained to generate three-dimensional lesions, conditioned by volume and location. This allows one to investigate CMB characteristics and create large training datasets for deep learning-based detectors. We demonstrate the benefit of this approach by achieving state-of-the-art CMB detection of real CMB using a convolutional neural network classifier trained on synthetic CMB. Moreover, we showed that our proposed 3D lesion GAN model can be applied on unseen dataset, with different MRI parameters and diseases, to generate synthetic lesions with high diversity and without needing laboriously marked ground truth.
A Computational Modeling Study to Investigate the Use of Epicranial Electrodes to Deliver Interferential Stimulation to Subcortical Regions
Authors: Khatoun Ahmad , Asamoah Boateng , Mc Laughlin Myles
Published: December 2021

Background: Epicranial cortical stimulation (ECS) is a minimally invasive neuromodulation technique that works by passing electric current between subcutaneous electrodes positioned on the skull. ECS causes a stronger and more focused electric field in the cortex compared to transcranial electric stimulation (TES) where the electrodes are placed on the scalp. However, it is unknown if ECS can target deeper regions where the electric fields become relatively weak and broad. Recently, interferential stimulation (IF) using scalp electrodes has been proposed as a novel technique to target subcortical regions. During IF, two high, but slightly different, frequencies are applied which sum to generate a low frequency field (i.e., 10 Hz) at a target subcortical region. We hypothesized that IF using ECS electrodes would cause stronger and more focused subcortical stimulation than that using TES electrodes.

Objective: Use computational modeling to determine if interferential stimulation-epicranial cortical stimulation (IF-ECS) can target subcortical regions. Then, compare the focality and field strength of IF-ECS to that of interferential Stimulation-transcranial electric stimulation (IF-TES) in the same subcortical region.

Methods: A human head computational model was developed with 19 TES and 19 ECS disk electrodes positioned on a 10–20 system. After tetrahedral mesh generation the model was imported to COMSOL where the electric field distribution was calculated for each electrode separately. Then in MATLAB, subcortical targets were defined and the optimal configurations were calculated for both the TES and ECS electrodes.

Results: Interferential stimulation using ECS electrodes can deliver stronger and more focused electric fields to subcortical regions than IF using TES electrodes.

Conclusion: Interferential stimulation combined with ECS is a promising approach for delivering subcortical stimulation without the need for a craniotomy.
Optogenetic Interrogation of Circuits Following Neurotrauma
Authors: Ceto Steven , Courtine Grégoire
Published: December 2021

Biological and engineering strategies for neural repair and recovery from neurotrauma continue to emerge at a rapid pace. Until recently, studies of the impact of neurotrauma and repair strategies on the reorganization of the central nervous system have focused on broadly defined circuits and pathways. Optogenetic modulation and recording methods now enable the interrogation of precisely defined neuronal populations in the brain and spinal cord, allowing unprecedented precision in electrophysiological and behavioral experiments. This mini-review summarizes the spectrum of light-based tools that are currently available to probe the properties and functions of well-defined neuronal subpopulations in the context of neurotrauma. In particular, we highlight the challenges to implement these tools in damaged and reorganizing tissues, and we discuss best practices to overcome these obstacles.
Effects of Dietary Protein Levels on Fecal Amino Acids Excretion and Apparent Digestibility, and Fecal and Ileal Microbial Amino Acids Composition in Weaned Piglets
Authors: Yang Zhenguo , Deng Huan , He Tianle , Sun Zhihong , Gifty Ziema Bumbie , Hu Ping , Rao Zebing , Tang Zhiru
Published: December 2021

Background and Aims: The purpose of this study was to determine the effects of low protein diets with the same Lys, Met + Cys, Thr, and Trp levels as in high protein diets on the fecal amino acid excretion and apparent digestibility, and ileal and fecal microbial amino acids composition in weaned piglets.

Methods: Fifty-four 21-day-old Duroc × Landrace × Yorkshire weaned piglets were randomly divided into three groups and fed with corn-soybean meal basal diets, in which the crude protein (CP) content was 20% (H-CP), 17% (M-CP), and 14% (L-CP), respectively. The experiment included a 7-day adaptation period and a 45-day trial period. Six piglets in each group were randomly slaughtered on days 10, 25, and 45 of the trial period, and the intestinal contents, intestinal mucosa, and feces were collected.

Results: The results showed that the interaction between feeding time and dietary CP levels was reflected in the apparent digestibility of dietary CP and amino acid (AA) (p < 0.01). With the increase of age, the apparent digestibility of CP and AA were increased (p < 0.01). With the increase of CP levels, the excretion of nitrogen (N) was decreased (p < 0.01), whereas the flow of microbial AA in the ileum and feces were increased (p < 0.01). The interaction between feeding time and dietary CP levels was also reflected in the composition of AA in the ileum and stool of piglets (p < 0.01). The proportion of His, Lyr, Met, Cys, and Ser was lower than the average, whereas the proportion of Phe, Leu, Pro, Ala, Glu, and Asp was higher than the average. With the increase of age, the AA content of microorganisms increased (p < 0.01).

Conclusion: All in all, this work revealed the changes of N, CP, and AA excretion and digestibility of feces and microorganisms of piglets under the combined action of different dietary protein levels and different feeding times, and also the changes of AA composition of intestinal microorganisms and AA composition of microorganisms.
Glutamine Supplementation Enhances the Effects of a Low FODMAP Diet in Irritable Bowel Syndrome Management
Authors: Rastgoo Samira , Ebrahimi-Daryani Nasser , Agah Shahram , Karimi Sara , Taher Mohammad , Rashidkhani Bahram , Hejazi Ehsan , Mohseni Fatemeh , Ahmadzadeh Mina , Sadeghi Amir , Hekmatdoost Azita
Published: December 2021

Background and Aims: Although irritable bowel syndrome is one of the most common gastrointestinal disorders presented to gastroenterologists, therapeutic strategies are not yet well-established. Accordingly, we conducted a randomized, double-blind, placebo-controlled, clinical trial to evaluate the possible superiority of adding glutamine supplement to low fermentable oligo- di- monosaccharides and polyols (FODMAP) diet in patients with irritable bowel syndrome (IBS).

Methods: Eligible adults were randomized to receive a low FODMAP diet either with glutamine (15 g/day) or a placebo for 6 weeks. The primary endpoint was a significant reduction in IBS-symptom severity score (IBS-SSS). Secondary endpoints were changes in IBS symptoms, stool frequency, consistency, and quality of life.

Results: The study group enrolled 50 patients, among which 22 participants from each group completed the study protocol. The glutamine group had significant changes in total IBS-severity score, dissatisfaction of bowel habit and interference with community function (58% reduction; P < 0.001, 57% reduction; P < 0.001, 51% reduction; P = 0.043, respectively). Improvement in IBS-severity score of more than 45% was observed in 22 of 25 participants (88%) in the glutamine group, while it was only 15 of 25 participants (60%) in the control group (p = 0.015). No serious adverse events were observed.

Conclusions: Our findings indicated the superiority of adding glutamine supplementation to a low FODMAP diet in amelioration of IBS symptoms while confirming the beneficial effects of a low FODMAP diet in IBS management.
Communicating Food Risk-Benefit Assessments: Edible Insects as Red Meat Replacers
Authors: Boehm Emilia , Borzekowski Dan , Ververis Ermolaos , Lohmann Mark , Böl Gaby-Fleur
Published: December 2021

Risk-benefit Assessment (RBA) is an emerging methodology in the area of Food and Nutrition that offers a simultaneous evaluation of both risks and benefits linked to dietary choices. Communication of such research to consumers may present a challenge due to the dual nature of RBA. We present a case study of a communication strategy developed for the NovRBA-project. The NovRBA-project (Novel foods as red meat replacers—an insight using Risk Benefit Assessment methods) performed a risk-benefit assessment to evaluate the overall health impact of substituting red meat (beef) by a novel food (house cricket), considering the microbial, toxicological and nutritional characteristics of the respective dietary choices. A literature review of risk perceptions and acceptance of beef and insects as food formed the basis of the communication strategy for the study's results, drawing on environmental and emotional as well as health-related motivations to consume or avoid either food and considering the sociodemographic characteristics of likely consumers. Challenges and future directions for consumer protection organizations communicating findings of risk-benefit analyses on food safety are discussed.
Chemical, Manufacturing, and Standardization Controls of Grape Polyphenol Dietary Supplements in Support of a Clinical Study: Mass Uniformity, Polyphenol Dosage, and Profiles
Authors: Lyu Weiting , Rodriguez David , Ferruzzi Mario G. , Pasinetti Giulio M. , Murrough James W. , Simon James E. , Wu Qingli
Published: December 2021

Bioactive dietary polyphenols in grape (Vitis vinifera) have been used in Dietary Supplements (DSs) with the aim to prevent numerous diseases, including cardiovascular and neurodegenerative diseases, and to reduce depression and anxiety. Given prior recognition that DSs can be quality challenged from the purity, authentication, adulteration, and actual concentration of targeted bioactives, to ensure consumer health protection as well as the quality and safety of grape polyphenol-based DSs, the present investigation was aimed at establishing a comprehensive quality control (QC) approach for grape polyphenol-based DSs in support of a human clinical study. In this study, the manufactured grape seed polyphenol extract (GSPE) and trans-resveratrol (RSV) capsules and Concord Grape Juice (CGJ) along with the corresponding original drug materials were analyzed using the developed different liquid chromatography/UV-visible spectroscopy/mass spectrometry (LC/UV-Vis/MS) methods. The weight variation of GSPE and RSV capsules was also evaluated according to the US Pharmacopeia (USP) tests. The results indicate that the total identified polyphenol content in each grape seed extract (GSE) capsule/CGJ is very similar and all GSE/RSV capsules pass the content/weight uniformity test. Given the complexity of these and many botanical products from the issues of purity, quality, adulteration, consistency, and their coupling to the complex chemistry in each grape-derived botanical, quality assurance and the steps needed to ensure grape-derived DSs being well homogeneous and stable and containing the known and expected bioactives at specific concentration ranges are fundamental to any research study and in particular to a clinical trial. Each of these issues is essential to provide a solid foundation upon which clinical trials with botanicals can be conducted with the goal of realizing measurable mental health outcomes such as reducing depression and anxiety as well as understanding of their underlying biological mechanisms.
Exploring Psychosocial Determinants of Eating Behavior: Fruit and Vegetable Intake Among Brazilian Adolescents
Authors: Moraes César Henrique de Carvalho , Alvarenga Marle dos Santos , Moraes Jéssica Maria Muniz , Cyrillo Denise Cavallini
Published: December 2021

In most Western countries, children and adolescents do not eat the recommended amount of fruits and vegetables (FVs). Theoretical frameworks on social psychology of eating, such as the Reason Action Approach, Social Cognitive Theory, and Theory of Normal Conduct have been applied to understand how psychosocial variables can explain FV intake. However, considering those predictors is still rare on the understanding of FV intake among adolescents (particularly in Brazil) despite its importance within eating behavior. Therefore, this study explored important psychosocial determinants of weekly frequency of FV intake among Brazilian adolescents in a model testing socioeconomic status (SES) and body mass index (BMI). A cross-sectional design was performed with 429 students (58% female), mean age 14.45 (SD 1.86). Key variables of theoretical framework on social psychology of food were investigated by structural equation modeling. The model included self-efficacy, attitudes, and social norms (with its subcomponents descriptive and injunctive) as psychosocial predictors of weekly frequency of FV intake along with SES and BMI. An instrument developed for Brazilian Portuguese was used to collect psychosocial variables as well as to verify FV reported intake. The total model explained 45.5% of weekly frequency of FV intake, and self-efficacy was the only significant psychosocial determinant (λ = 0.51, p = 0.001). SES also showed an important effect on the model (λ = 0.21, p = 0.001), while for BMI no significance was observed. In conclusion, the model was adequate to understand psychosocial determinants of weekly frequency of FV intake for Brazilian adolescents, with self-efficacy and SES as the major determinants of this eating behavior.
The Formation of Antibiotic Resistance Genes in Bacterial Communities During Garlic Powder Processing
Authors: Liu Yanxia , Gao Peng , Wu Yuhao , Wang Xiaorui , Lu Xiaoming , Liu Chao , Li Ningyang , Sun Jinyue , Xiao Jianbo , Jesus Simal-Gandara
Published: December 2021

Chinese garlic powder (GP) is exported to all countries in the world, but the excess of microorganisms is a serious problem that affects export. The number of microorganisms has a serious impact on the pricing of GP. It is very important to detect and control the microorganism in GP. The purpose of this study was to investigate the contamination and drug resistance of microorganisms during the processing of GP. We used metagenomics and Illumina sequencing to study the composition and dynamic distribution of antibiotic resistance genes (ARGs), but also the microbial community in three kinds of garlic products from factory processing. The results showed that a total of 126 ARG genes were detected in all the samples, which belonged to 11 ARG species. With the processing of GP, the expression of ARGs showed a trend to increase at first and then to decrease. Network analysis was used to study the co-occurrence patterns among ARG subtypes and bacterial communities and ARGs.
Development and Validation of an Immune-Related Signature for the Prediction of Recurrence Risk of Patients With Laryngeal Cancer
Authors: Zhang Hang , Zhao Xudong , Wang Jin , Ji Wenyue
Published: December 2021

Objective

Our purpose was to develop and verify an immune-related signature for predicting recurrence risk of patients with laryngeal cancer.

Methods

RNA-seq data of 51 recurrence and 81 non-recurrence laryngeal cancer samples were downloaded from TCGA database, as the training set. Microarray data of 34 recurrence and 75 non-recurrence cancer samples were obtained from GEO dataset, as the validation set. Single factor cox regression was utilized to screen prognosis-related immune genes. After LASSO regression analysis, an immune-related signature was constructed. Recurrence free survival (RFS) between high- and low- recurrence risk patients was presented, followed by ROC. We also evaluated the correlation between immune infiltration and the signature using the CIBERSORT algorithm. The genes in the signature were validated in laryngeal cancer tissues by western blot or RT-qPCR. After RCN1 knockdown, migration and invasion of laryngeal cancer cells were investigated.

Results

Totally, 43 prognosis-related immune genes were identified for laryngeal cancer. Among them, eight genes were used for constructing a prognostic signature. High risk group exhibited a higher recurrence risk than low risk group. The AUC for 1-year was separately 0.803 and 0.715 in the training and verification sets, suggesting its well efficacy for predicting the recurrence. Furthermore, this signature was closely related to distinct immune cell infiltration. RCN1, DNAJA2, LASP1 and IBSP were up-regulated in laryngeal cancer. RCN1 knockdown restrained migrated and invasive abilities of laryngeal cancer cells.

Conclusion

Our findings identify a reliable immune-related signature that can predict the recurrence risk of patients with laryngeal cancer.
Prognostic Efficacy of Tumor-Stroma Ratio in Women With Breast Cancer: A Meta-Analysis of Cohort Studies
Authors: Jiang Pengli , Chen Yulong , Liu Bin
Published: December 2021

Background

Tumor-stroma ratio (TSR) has been suggested as an emerging prognostic predictor in women with breast cancer. However, previous studies evaluating the association between TSR and survival in women with breast cancer showed inconsistent results. We performed a meta-analysis to systematically evaluate the possible prognostic role of TSR in breast cancer.

Methods

Relevant cohort studies were obtained via search of PubMed, Embase, and Web of Science databases. A random-effects model, which incorporated the potential heterogeneity, was used to pool the results.

Results

Twelve cohort studies with 6175 patients were included. Nine of the 12 studies used 50% as the cutoff to divide the patients into those with stroma-rich (low TSR) and stroma-poor (high TSR) tumors. Pooled results showed that compared women with stroma-poor tumor, those with stroma-rich tumor were associated with worse survival outcomes (disease-free survival [DFS]: hazard ratio [HR] = 1.56, 95% confidence interval [CI]: 1.32 to 1.85, P < 0.001; overall survival [OS]: HR = 1.67, 95% CI: 1.46 to 1.91, P < 0.001; and cancer-specific survival [CSS]: HR = 1.75, 95% CI: 1.40 to 2.20, P < 0.001). Analysis limited to women with triple-negative breast cancer (TNBC) showed consistent results (DFS: HR: 2.07, 95% CI: 1.59 to 2.71, P < 0.001; OS: HR: 2.04, 95% CI: 1.52 to 2.73, P < 0.001; and CSS: HR: 2.40, 95% CI: 1.52 to 3.78, P < 0.001).

Conclusions

Current evidence from retrospective studies supports that tumor TSR is a prognostic predictor or poor survival in women with breast cancer.
Case Report: Identification of Multiple TERT and FGFR2 Gene Fusions in a Pineal Region Glioblastoma Case
Authors: Guo Xing , Chen Teng , Chen Shiming , Song Chao , Shan Dezhi , Xu Shujun , Xu Shuo
Published: December 2021

As an oncogenic somatic variant, telomerase reverse transcriptase promoter (TERTp) mutations are frequently observed in adult glioblastoma (GBM). Alternatively, we report the first case of glioblastoma with TERT amplification accompanied by multiple TERT and FGFR2 gene fusions instead of TERTp mutation. A 55-year-old woman presented with dizziness, headache, and diplopia for three weeks. Magnetic resonance imaging (MRI) demonstrated a heterogeneously enhancing lobulated mass centered in the pineal region. Partial tumor resection and ventriculoperitoneal shunt were achieved, and the residual tumor was then treated with standard radiation. The tumor was diagnosed as GBM, IDH-wild type, WHO grade IV, and the Ki67 proliferation index was high (30–40%). Intriguingly, TERT amplification without TERTp mutation was identified via next generation sequencing (NGS). Further analysis revealed multiple TERT (TERT–NUBPL, MARCH6–TERT, and CJD4–TERT) and FGFR2 (CXCL17–FGFR2, SIPA1L3–FGFR2, FGFR2–SIPA1L3, and FGFR2–CEACAM1) gene fusions. After the surgery, the patient’s condition deteriorated rapidly due to the malignant nature of the tumor and she died with an overall survival of 3 months. Our report provides the molecular clue for a novel telomerase activation and maintenance mechanism in GBM.
Comparison of Two Circular-Stapled Techniques for Esophageal Cancer: A Propensity-Matched Analysis
Authors: Lin Hang , Liang Ge’ao , Chai Huiping , Liao Yongde , Zhang Chunfang , Cheng Yuanda
Published: December 2021

Objective

The optimal technique for the thoracoscopic construction of an intrathoracic esophagogastric anastomosis continues to be a subject of controversy. The aim of this study was to compare the perioperative outcomes of circular-stapled anastomosis using a transorally inserted anvil (Orvil™) with those of circular-stapled anastomosis using a transthoracically placed anvil (non-Orvil™) in totally minimally invasive Ivor Lewis esophagectomy (Ivor Lewis TMIE).

Methods

The data of 272 patients who underwent Ivor Lewis TMIE for esophageal cancer at multiple centers were collected from January 1, 2014 to December 31, 2017. After propensity score matching (1:1) for patient baseline characteristics, 65 paired cases were selected for statistical analysis. Logistic regression analysis was performed to investigate the significant factors of anastomotic leakage.

Results

In the propensity score-matched analysis, compared with the non-Orvil™ group, the Orvil™ group was associated with a significantly shorter operation time (p=0.031), less intraoperative hemorrhage (p<0.001), lower need for intraoperative transfusions (p=0.009), earlier postoperative oral feeding time (p=0.010), longer chest tube duration (p<0.001), shorter postoperative hospital stays (p=0.001), lower total hospitalization costs (p<0.001) and a lower postoperative anastomotic leakage rate (p=0.033). Multivariate logistic regression analysis showed that anastomotic technique and pulmonary infection were independent factors for the development of postoperative anastomotic leakage (p< 0.05).

Conclusions

Orvil™ anastomosis exhibited better perioperative effects than non-Orvil™ anastomosis after the propensity score-matched analysis. Remarkably, the Orvil™ technique contributed to a lower postoperative anastomotic leakage rate than the non-Orvil™ technique.
Can Acute Postoperative Pain Management After Tumour Resection Surgery Modulate Risk of Later Recurrence or Metastasis?
Authors: Moorthy Aneurin , Eochagáin Aisling Ní , Buggy Donal J.
Published: December 2021

Background

Cancer is a leading cause of mortality worldwide, but death is rarely from the primary tumour: Rather it is multi-organ dysfunction from metastatic disease that is responsible for up to 90% of cancer-related deaths. Surgical resection of the primary tumour is indicated in 70% of cases. The perioperative stress response, tissue hypoxia at the site of surgery, and acute pain contribute to immunosuppression and neo-angiogenesis, potentially promoting tumour survival, proliferation, and metastasis. Poorly controlled acute postoperative pain decreases Natural Killer (NK) immune cell activity, which could potentially facilitate circulating tumour cells from evading immune detection. This consequently promotes tumour growth and distal metastasis.

Methods

We conducted a comprehensive literature search for links between acute pain and cancer outcomes using multiple online databases. Relevant articles from January 1st, 2010 to September 1st, 2021 were analysed and appraised on whether postoperative pain control can modulate the risk of recurrence, metastasis, and overall cancer survival.

Results

Although experimental and retrospective clinical data suggest a plausible role for regional anaesthesia in cancer outcome modulation, this has not been supported by the single, largest prospective trial to date concerning breast cancer. While there are mixed results on anaesthesiology drug-related interventions, the most plausible data relates to total intravenous anaesthesia with propofol, and to systemic administration of lidocaine.

Conclusion

The hypothesis that anaesthetic and analgesic technique during cancer surgery could influence risk of subsequent recurrence or metastasis has been prevalent for >15 years. The first, large-scale definitive trial among women with breast cancer found robust equivalent findings between volatile anaesthesia with opioid analgesia and regional anaesthesia. Therefore, while regional anaesthesia during tumour resection does not seem to have any effect on cancer outcomes, it remains plausible that other anaesthetic techniques (e.g. total intravenous anaesthesia and systemic lidocaine infusion) might influence oncologic outcome in other major tumour resection surgery (e.g. colorectal and lung). Therefore, another large trial is needed to definitively answer these specific research questions. Until such evidence is available, perioperative analgesia for cancer surgery of curative intent should be based on patient co-morbidity and non-cancer endpoints, such as optimising analgesia and minimising postoperative complications.
Case Report: Glaucoma in an Infant With Retinopathy of Prematurity
Authors: Lenis Tamara Lee , Ledesma Vicioso Nahomy , Reddy Varun , Kovacs Kyle D , Van Tassel Sarah H , Orlin Anton
Published: December 2021

Retinopathy of prematurity (ROP) is a leading cause of childhood blindness that occurs due to incomplete development of retinal blood vessels in preterm infants. Glaucoma is an ocular comorbidity in some patients with ROP, and it may be associated with immature anterior chamber development, ROP itself, or the treatment for ROP. There have been a few reports of narrow-angle glaucoma after laser treatment for ROP. In this case report, we describe the course of a female infant born at 24 weeks and 5 days of gestational age with treatment-requiring ROP treated with laser photocoagulation who subsequently developed very elevated intraocular pressure and shallow anterior chambers without pupillary block. The patient required bilateral ab externo trabeculotomy for elevated intraocular pressure, which normalized after the procedure. The patient has remained stable at the last follow-up at 51 weeks postmenstrual age. Differing from previous glaucoma presentations in this setting, we illustrate a case of elevated intraocular pressure and anterior chamber narrowing after laser therapy without pupillary block or synechiae. The possible multifactorial etiology of glaucoma in this patient, including incomplete angle development, ischemia, and laser treatment, highlight the need for glaucoma screening in patients with ROP, both in the short and long term.
Cross-Talk Between Large Artery Stiffness and Retinal Microvasculature in Children: The ExAMIN Youth SA Study
Authors: Breet Yolandi , Craig Ashleigh , Smith Wayne , Botha-Le Roux Shani , Gafane-Matemane Lebo F. , Brits Sanette , Rooyen Johannes M. van , Hanssen Henner , Kruger Ruan
Published: December 2021

Background: Cross-talk between the macro-and microvasculature is considered an important contributor to target organ damage. Previous findings were predominantly in adult populations and investigation into this mechanism in children may provide insight into the development of early adverse vascular changes. Whether any ethnic differences in cross-talk is evident, also remains to be determined.

Objective: To determine whether retinal microvascular diameters are associated with large artery stiffness in young children and whether ethnic differences are evident.

Materials and Methods: In this cross-sectional study, 730 black (n = 437) and white (n = 293) school children aged 5-9 years were included. Pulse wave velocity (PWV) was measured and the central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE) diameters were calculated from fundus images. The arterio-venous ratio (AVR) was subsequently calculated.

Results: Pulse wave velocity was lower (p ≤ 0.001) in the black group when compared to the white group. The black group had a narrower CRAE, wider CRVE and lower AVR (all p < 0.001). Pulse wave velocity associated negatively with CRAE (r = –0.141, p = 0.003) and AVR (r = –0.185, p ≤ 0.001) in the black group only. A positive association between PWV and CRVE was seen in the black (r = 0.174, p ≤ 0.001) and white (r = 0.119, p = 0.043) group.

Conclusion: Large artery stiffness is associated with retinal arterial narrowing and venular widening in children, suggesting cross-talk between the macro-and microvasculature. Ethnic differences in these associations are also evident. Our findings warrant further investigation into environmental and sociocultural risk factors contributing to premature cardiovascular disease development.
Centella asiatica Alters Metabolic Pathways Associated With Alzheimer’s Disease in the 5xFAD Mouse Model of ß-Amyloid Accumulation
Authors: Speers Alex B. , García-Jaramillo Manuel , Feryn Alicia , Matthews Donald G. , Lichtenberg Talia , Caruso Maya , Wright Kirsten M. , Quinn Joseph F. , Stevens Jan F. , Maier Claudia S. , Soumyanath Amala , Gray Nora E.
Published: December 2021

Centella asiatica is an herb used in Ayurvedic and traditional Chinese medicine for its beneficial effects on brain health and cognition. Our group has previously shown that a water extract of Centella asiatica (CAW) elicits cognitive-enhancing effects in animal models of aging and Alzheimer’s disease, including a dose-related effect of CAW on memory in the 5xFAD mouse model of ß-amyloid accumulation. Here, we endeavor to elucidate the mechanisms underlying the effects of CAW in the brain by conducting a metabolomic analysis of cortical tissue from 5xFAD mice treated with increasing concentrations of CAW. Tissue was collected from 8-month-old male and female 5xFAD mice and their wild-type littermates treated with CAW (0, 200, 500, or 1,000 mg/kg/d) dissolved in their drinking water for 5 weeks. High-performance liquid chromatography coupled to high-resolution mass spectrometry analysis was performed and relative levels of 120 annotated metabolites were assessed in the treatment groups. Metabolomic analysis revealed sex differences in the effect of the 5xFAD genotype on metabolite levels compared to wild-type mice, and variations in the metabolomic response to CAW depending on sex, genotype, and CAW dose. In at least three of the four treated groups (5xFAD or wild-type, male or female), CAW (500 mg/kg/d) significantly altered metabolic pathways related to purine metabolism, nicotinate and nicotinamide metabolism, and glycerophospholipid metabolism. The results are in line with some of our previous findings regarding specific mechanisms of action of CAW (e.g., improving mitochondrial function, reducing oxidative stress, and increasing synaptic density). Furthermore, these findings provide new information about additional, potential mechanisms for the cognitive-enhancing effect of CAW, including upregulation of nicotinamide adenine dinucleotide in the brain and modulation of brain-derived neurotrophic factor. These metabolic pathways have been implicated in the pathophysiology of Alzheimer’s disease, highlighting the therapeutic potential of CAW in this neurodegenerative disease.
Emerging Roles of Myeloid-Derived Suppressor Cells in Diabetes
Authors: Wang Shiqi , Tan Qian , Hou Yayi , Dou Huan
Published: December 2021

Diabetes is a syndrome characterized by hyperglycemia with or without insulin resistance. Its etiology is attributed to the combined action of genes, environment and immune cells. Myeloid-derived suppressor cell (MDSC) is a heterogeneous population of immature cells with immunosuppressive ability. In recent years, different studies have debated the quantity, activity changes and roles of MDSC in the diabetic microenvironment. However, the emerging roles of MDSC have not been fully documented with regard to their interactions with diabetes. Here, the manifestations of MDSC and their subsets are reviewed with regard to the incidence of diabetes and diabetic complications. The possible drugs targeting MDSC are discussed with regard to their potential of treating diabetes. We believe that understanding MDSC will offer opportunities to explain pathological characteristics of different diabetes. MDSC also will be used for personalized immunotherapy of diabetes.
Dynamic Surface Tension Enhances the Stability of Nanobubbles in Xylem Sap
Authors: Ingram Stephen , Salmon Yann , Lintunen Anna , Hölttä Teemu , Vesala Timo , Vehkamäki Hanna
Published: December 2021

Air seeded nanobubbles have recently been observed within tree sap under negative pressure. They are stabilized by an as yet unidentified process, although some embolize their vessels in extreme circumstances. Current literature suggests that a varying surface tension helps bubbles survive, but few direct measurements of this quantity have been made. Here, we present calculations of dynamic surface tension for two biologically relevant lipids using molecular dynamics simulations. We find that glycolipid monolayers resist expansion proportionally to the rate of expansion. Their surface tension increases with the tension applied, in a similar way to the viscosity of a non-Newtonian fluid. In contrast, a prototypical phospholipid was equally resistant to all applied tensions, suggesting that the fate of a given nanobubble is dependent on its surface composition. By incorporating our results into a Classical Nucleation Theory (CNT) framework, we predict nanobubble stability with respect to embolism. We find that the metastable radius of glycolipid coated nanobubbles is approximately 35 nm, and that embolism is in this case unlikely when the external pressure is less negative than –1.5 MPa.
Quantitative Trait Loci and Transcriptome Analysis Reveal Genetic Basis of Fiber Quality Traits in CCRI70 RIL Population of Gossypium hirsutum
Authors: Jiang Xiao , Gong Juwu , Zhang Jianhong , Zhang Zhen , Shi Yuzhen , Li Junwen , Liu Aiying , Gong Wankui , Ge Qun , Deng Xiaoying , Fan Senmiao , Chen Haodong , Kuang Zhengcheng , Pan Jingtao , Che Jincan , Zhang Shuya , Jia Tingting , Wei Renhui , Chen Quanjia , Wei Shoujun , Shang Haihong , Yuan Youlu
Published: December 2021

Upland cotton (Gossypium hirsutum) is widely planted around the world for its natural fiber, and producing high-quality fiber is essential for the textile industry. CCRI70 is a hybrid cotton plant harboring superior yield and fiber quality, whose recombinant inbred line (RIL) population was developed from two upland cotton varieties (sGK156 and 901-001) and were used here to investigate the source of high-quality related alleles. Based on the material of the whole population, a high-density genetic map was constructed using specific locus-amplified fragment sequencing (SLAF-seq). It contained 24,425 single nucleotide polymorphism (SNP) markers, spanning a distance of 4,850.47 centimorgans (cM) over 26 chromosomes with an average marker interval of 0.20 cM. In evaluating three fiber quality traits in nine environments to detect multiple environments stable quantitative trait loci (QTLs), we found 289 QTLs, of which 36 of them were stable QTLs and 18 were novel. Based on the transcriptome analysis for two parents and two RILs, 24,941 unique differentially expressed genes (DEGs) were identified, 473 of which were promising genes. For the fiber strength (FS) QTLs, 320 DEGs were identified, suggesting that pectin synthesis, phenylpropanoid biosynthesis, and plant hormone signaling pathways could influence FS, and several transcription factors may regulate fiber development, such asGAE6,C4H,OMT1,AFR18,EIN3,bZIP44, andGAI. Notably, the marker D13_56413025 inqFS-chr18-4provides a potential basis for enhancing fiber quality of upland cottonviamarker-assisted breeding and gene cloning of important fiber quality traits.
GPTransformer: A Transformer-Based Deep Learning Method for Predicting Fusarium Related Traits in Barley
Authors: Jubair Sheikh , Tucker James R. , Henderson Nathan , Hiebert Colin W. , Badea Ana , Domaratzki Michael , Fernando W. G. Dilantha
Published: December 2021

Fusarium head blight (FHB) incited by Fusarium graminearum Schwabe is a devastating disease of barley and other cereal crops worldwide. Fusarium head blight is associated with trichothecene mycotoxins such as deoxynivalenol (DON), which contaminates grains, making them unfit for malting or animal feed industries. While genetically resistant cultivars offer the best economic and environmentally responsible means to mitigate disease, parent lines with adequate resistance are limited in barley. Resistance breeding based upon quantitative genetic gains has been slow to date, due to intensive labor requirements of disease nurseries. The production of a high-throughput genome-wide molecular marker assembly for barley permits use in development of genomic prediction models for traits of economic importance to this crop. A diverse panel consisting of 400 two-row spring barley lines was assembled to focus on Canadian barley breeding programs. The panel was evaluated for FHB and DON content in three environments and over 2 years. Moreover, it was genotyped using an Illumina Infinium High-Throughput Screening (HTS) iSelect custom beadchip array of single nucleotide polymorphic molecular markers (50 K SNP), where over 23 K molecular markers were polymorphic. Genomic prediction has been demonstrated to successfully reduce FHB and DON content in cereals using various statistical models. Herein, we have studied an alternative method based on machine learning and compare it with a statistical approach. The bi-allelic SNPs represented pairs of alleles and were encoded in two ways: as categorical (–1, 0, 1) or using Hardy-Weinberg probability frequencies. This was followed by selecting essential genomic markers for phenotype prediction. Subsequently, a Transformer-based deep learning algorithm was applied to predict FHB and DON. Apart from the Transformer method, a Residual Fully Connected Neural Network (RFCNN) was also applied. Pearson correlation coefficients were calculated to compare true vs. predicted outputs. Models which included all markers generally showed marginal improvement in prediction. Hardy-Weinberg encoding generally improved correlation for FHB (6.9%) and DON (9.6%) for the Transformer network. This study suggests the potential of the Transformer based method as an alternative to the popular BLUP model for genomic prediction of complex traits such as FHB or DON, having performed equally or better than existing machine learning and statistical methods.
Is It Possible to Produce Certified Hazelnut Plant Material in Sicily? Identification and Recovery of Nebrodi Genetic Resources, in vitro Establishment, and Innovative Sanitation Technique From Apple Mosaic Virus
Authors: Yahyaoui Emna , Marinoni Daniela Torello , Botta Roberto , Ruffa Paola , Germanà Maria Antonietta
Published: December 2021

Eight Sicilian cultivars of hazelnut (Corylus avellanaL.), namely-Curcia, Nociara Collica, Panottara Collica, Panottara Galati Grande, Parrinara, Panottara Baratta Piccola, Enzo, and Rossa Galvagno, registered into the Italian Cultivar Register of fruit tree species in 2017 were selected from Nebrodi area and establishedin vitro. The aim of the work was to carry out the sanitation of the cultivars and get virus-free plants from the most important viral pathogen threat, theapple mosaic virus. Virus-free plant material is essential for the production of certified plants from Sicilian hazelnut cultivars, complying the CE (cat. CAC) quality and the technical standards established in 2017 for voluntary certification by the Italian Ministry of Agricultural, Food and Forestry Policies (MIPAAF). In this study, we investigated the possibility of establishingin vitrotrue-to-type and virus-free hazelnut plantletsviathe encapsulation technology of apexes. Thein vitroshoot proliferation rates were assessed for the different cultivars, sampling periods, temperature treatments, and type of explant used for culture initiation. Viability, regrowth, and conversion rates of both conventional meristem tip culture (MTC) and not conventional (MTC combined with the encapsulation technology) sanitation techniques were evaluated.
Hairiness Gene Regulated Multicellular, Non-Glandular Trichome Formation in Pepper Species
Authors: Liu Jinqiu , Wang Haoran , Liu Mengmeng , Liu Jinkui , Liu Sujun , Cheng Qing , Shen Huolin
Published: December 2021

Trichomes are unicellular or multicellular epidermal structures that play a defensive role against environmental stresses. Although unicellular trichomes have been extensively studied as a mechanistic model, the genes involved in multicellular trichome formation are not well understood. In this study, we first classified the trichome morphology structures in Capsicum species using 280 diverse peppers. We cloned a key gene (Hairiness) on chromosome 10, which mainly controlled the formation of multicellular non-glandular trichomes (types II, III, and V). Hairiness encodes a Cys2-His2 zinc-finger protein, and virus-induced gene silencing of the gene resulted in a hairless phenotype. Differential expression of Hairiness between the hairiness and hairless lines was due to variations in promoter sequences. Transgenic experiments verified the hypothesis that the promoter of Hairiness in the hairless line had extremely low activity causing a hairless phenotype. Hair controlled the formation of type I glandular trichomes in tomatoes, which was due to nucleotide differences. Taken together, our findings suggest that the regulation of multicellular trichome formation might have similar pathways, but the gene could perform slightly different functions in crops.
An Encounter With the Other: A Thematic and Content Analysis of DMT Experiences From a Naturalistic Field Study
Authors: Michael Pascal , Luke David , Robinson Oliver
Published: December 2021

Introduction:N,N-dimethyltryptamine(DMT) is an endogenous serotonergic psychedelic capable of producing radical shifts in conscious experience. Increasing trends in its use, as well as new trials administering DMT to patients, indicate the growing importance of a thorough elucidation of the qualitative content, over and above structure, which the drug occasions. This is particularly in light of the hyper-real, otherworldly, and often ontologically challenging yet potentially transformative, nature of the experience, not least encounters with apparently non-self social agents. Laboratory studies have been limited by clinical setting and lacking qualitative analyses of experiential content, while online surveys’ limitations lie in retrospective design, uncontrolled use, and both of which not guaranteeing ‘breakthrough’ experiences, i.e., producing very strong psychoactive effects.

Methods:We report on the first naturalistic field study of DMT use including its qualitative analysis. Screened, healthy, anonymised and experienced DMT users were observed during their non-clinical use of the drug at home (40–75 mg inhaled). In-depth semi-structured interviews (inspired by the micro-phenomenological technique) were employed immediately after their experience. This paper reports on the thematic analysis of one major domain of the breakthrough experiences elicited, the ‘other’. Thirty-six post-DMT experience interviews with mostly Caucasian (83%) males (eight female) of average 37 years were predominantly inductively coded.

Results:Invariably, profound and highly intense experiences occurred. The first overarching category comprised the encounter with other ‘beings’ (94% of reports), encompassing super-ordinate themes including the entities’ role, appearance, demeanour, communication and interaction; while the second overarching category comprised experiences of emerging into other ‘worlds’ (100% of reports), encompassing super-ordinate themes of the scene, the contents and quality of the immersive spaces. Many further mid-level themes and subthemes also illuminate the rich content of the DMT experience.

Discussion:The present study provides a systematic and in-depth analysis of the nuanced content of the otherworldly encounter within the breakthrough DMT experience, as well as elaborating on the resonances both with previous DMT studies focusing on entity encounters and other types of extraordinary experiences entailing such encounters. These include the alien abduction, folkloric, shamanic and near-death experience. Putative neural mechanisms of these features of the DMT experience and its promise as a psychotherapeutic agent are discussed in light of such findings.
The Impact of Entrepreneurship Education of Entrepreneurs on the Entrepreneurial Psychology of Sports Majors From the Perspective of Pedagogy
Authors: Liu Taofeng , Lipowski Mariusz , Xue Yingying , Xiao Tao , Liu Hongzhen , Xu Ruilin , Liu Kunpeng , Zhao Zijian
Published: December 2021

In recent years, with the continuous reform and innovation of the sports industry, the national training of sports talents has gradually developed into the training mode of skilled sports talents and professional talents in the field of sports. Therefore, the research on the influence of entrepreneurship education on the entrepreneurial psychology of sports majors has become the inevitable requirement of the development of the sports industry. The purposes are to understand the entrepreneurial psychology and its influencing factors of the students in sports majors after graduation and promote more suitable college students to start businesses and realize self-value. With the students in sports majors in four colleges of Y province as the research object, the typical model in psychology, planning behavior model, is taken as the basic theoretical basis. The questionnaire method combined with the data mining technology based on the decision tree model is adopted to study the influencing factors of entrepreneurial psychology of sports majors. It focuses on the influencing factors and mechanisms of the entrepreneurial drive of sports students. The results show that the three factors, namely, entrepreneurial behavior attitude, entrepreneurial subjective norms, and entrepreneurial perceptual behavior control, are different and interrelated. They are inseparable and can be transformed into each other under certain conditions. Three factors jointly drive the entrepreneurial behavior of students in sports majors. The entrepreneurial drive of students in sports majors in Y province is a dynamic system mechanism, which is analyzed using data mining technology. The entrepreneurial perceptual behavior control is the core factor affecting the entrepreneurial drive of students in sports majors. However, the success rate of entrepreneurs will be higher when the three elements play a reasonable role. The subjective factors driving their entrepreneurship will be reduced in direct proportion when entrepreneurs are deficient in one aspect.