Miracle-dz/UniFAR-FTUs huggingface dataset:
Genetic variation in BnGRP1 contributes to low phosphorus tolerance in Brassica napus

The lack of phosphorus (P) is a major environmental factor affecting rapeseed root growth and development. For breeding purposes, it is crucial to identify the molecular mechanisms of root system architecture (RSA) traits underlying low P tolerance in rapeseed. Using genome-wide association study (GWAS), transcriptome and re-sequencing analyses were done on 400 rapeseed cultivars, the natural variations of glycine-rich protein gene, BnGRP1, in response to low P tolerance. Based on 11 SNP mutations in the BnGRP1 sequence, ten types of haplotypes (Hap) were formed. Compared with the other types, the cultivar of the BnGRP1Hap1 type in the panel demonstrated the longest root length and heaviest root weight. Over-expression of BnGRP1Hap1 in rapeseed depicted the ability to enhance the resistance of rapeseed in its response to low P tolerance. CRISPR/Cas9-derived BnGRP1Hap1 knockout mutations in rapeseed could lead to sensitivity to low P stress. Furthermore, BnGRP1Hap1 influenced the expression of phosphate transporter 1 (PHT1) genes associated with P absorption. Overall, the findings of this study highlight the new mechanisms of GRP1 genes in enhancing the low P tolerance in rapeseed.
A PAK kinase family member and the Hippo/Yorkie pathway modulate WNT signaling to functionally integrate body axes during regeneration

Successful regeneration of missing tissues requires seamless integration of positional information along the body axes. Planarians, which regenerate from almost any injury, use conserved, developmentally important signaling pathways to pattern the body axes. However, the molecular mechanisms which facilitate crosstalk between these signaling pathways to integrate positional information remain poorly understood. Here, we report a p21-activated kinase (smed-pak1) which functionally integrates the anterior-posterior (AP) and the medio-lateral (ML) axes. pak1 inhibits WNT/β-catenin signaling along the AP axis and, functions synergistically with the β-catenin-independent WNT signaling of the ML axis. Furthermore, this functional integration is dependent on warts and merlin - the components of the Hippo/Yorkie (YKI) pathway. Hippo/YKI pathway is a critical regulator of body size in flies and mice, but our data suggest the pathway is required to pattern body axes in planarians. Our study provides a signaling network integrating positional information which can mediate coordinated growth and patterning during planarian regeneration.
The Ketogenic Diet for Refractory Mental Illness: A Retrospective Analysis of 31 Inpatients

Background and Hypothesis The robust evidence base supporting the therapeutic benefit of ketogenic diets in epilepsy and other neurological conditions suggests this same metabolic approach may also benefit psychiatric conditions. Study Design In this retrospective analysis of clinical care, 31 adults with severe, persistent mental illness (major depressive disorder, bipolar disorder, and schizoaffective disorder) whose symptoms were poorly controlled despite intensive psychiatric management were admitted to a psychiatric hospital and placed on a ketogenic diet restricted to a maximum of 20 grams of carbohydrate per day as an adjunct to conventional inpatient care. The duration of the intervention ranged from 6 to 248 days. Study Results Three patients were unable to adhere to the diet for >14 days and were excluded from the final analysis. Among included participants, means and standard deviations (SDs) improved for the Hamilton Depression Rating Scale scores from 25.4 (6.3) to 7.7 (4.2), P < 0.001 and the Montgomery-Åsberg Depression Rating Scale from 29.6 (7.8) to 10.1 (6.5), P < 0.001. Among the 10 patients with schizoaffective illness, mean (SD) of the Positive and Negative Syndrome Scale (PANSS) scores improved from 91.4 (15.3) to 49.3 (6.9), P < 0.001. Significant improvements were also observed in metabolic health measures including weight, blood pressure, blood glucose, and triglycerides. Conclusions The administration of a ketogenic diet in this semi-controlled setting to patients with treatment-refractory mental illness was feasible, well-tolerated, and associated with significant and substantial improvements in depression and psychosis symptoms and multiple markers of metabolic health.
Support Pressure Acting on the Epicardial Surface of a Rat Left Ventricle—A Computational Study

The present computational study investigates the effects of an epicardial support pressure mimicking a heart support system without direct blood contact. We chose restrictive cardiomyopathy as a model for a diseased heart. By changing one parameter representing the amount of fibrosis, this model allows us to investigate the impairment in a diseased left ventricle, both during diastole and systole. The aim of the study is to determine the temporal course and value of the support pressure that leads to a normalization of the cardiac parameters in diseased hearts. These are quantified via the end-diastolic pressure, end-diastolic volume, end-systolic volume, and ejection fraction. First, the amount of fibrosis is increased to model diseased hearts at different stages. Second, we determine the difference in the left ventricular pressure between a healthy and diseased heart during a cardiac cycle and apply for the epicardial support as the respective pressure difference. Third, an epicardial support pressure is applied in form of a piecewise constant step function. The support is provided only during diastole, only during systole, or during both phases. Finally, the support pressure is adjusted to reach the corresponding parameters in a healthy rat. Parameter normalization is not possible to achieve with solely diastolic or solely systolic support; for the modeled case with 50% fibrosis, the ejection fraction can be increased by 5% with purely diastolic support and 14% with purely systolic support. However, the ejection fraction reaches the value of the modeled healthy left ventricle (65.6%) using a combination of diastolic and systolic support. The end-diastolic pressure of 13.5 mmHg cannot be decreased with purely systolic support. However, the end-diastolic pressure reaches the value of the modeled healthy left ventricle (7.5 mmHg) with diastolic support as well as with the combination of the diastolic and systolic support. The resulting negative diastolic support pressure is −4.5 mmHg, and the positive systolic support pressure is 90 mmHg. We, thereby, conclude that ventricular support during both diastole and systole is beneficial for normalizing the left ventricular ejection fraction and the end-diastolic pressure, and thus it is a potentially interesting therapy for cardiac insufficiency.
Nanobodies: COVID-19 and Future Perspectives

The COVID-19 pandemic has driven biotechnological developments to provide new and more effective tools for prophylaxis, diagnosis, and therapy. Historically, monoclonal antibodies have been valuable tools; however, the pandemic has shown some weaknesses, such as production limitations at a global scale. An alternative to conventional monoclonal antibodies are nanobodies, recombinant fragments of the variable region of single-domain antibodies derived mainly from the Camelidae family. Nanobodies have multiple characteristic benefits: they are small (15 KDa) and have remarkable refolding capability and unlimited possibilities for modifications due to their recombinant nature. Here, we review the application of nanobodies in diagnosis and treatment of SARS-CoV-2 infection.
Evidence of Two Novel LAMA2 Variants in a Patient With Muscular Dystrophy: Facing the Challenges of a Certain Diagnosis

Background Benefits and challenges resulting from advances in genetic diagnostics are two sides of the same coin. Facilitation of a correct and timely diagnosis is paralleled by challenges in interpretation of variants of unknown significance (VUS). Focusing on an individual VUS-re-classification pipeline, this study offers a diagnostic approach for clinically suspected hereditary muscular dystrophy by combining the expertise of an interdisciplinary team. Methods In a multi-step approach, a thorough phenotype assessment including clinical examination, laboratory work, muscle MRI and histopathological evaluation of muscle was performed in combination with advanced Next Generation Sequencing (NGS). Different in-silico tools and prediction programs like Alamut, SIFT, Polyphen, MutationTaster and M-Cap as well as 3D- modeling of protein structure and RNA-sequencing were employed to determine clinical significance of the LAMA2 variants. Results Two previously unknown sequence alterations in LAMA2 were detected, a missense variant was classified initially according to ACMG guidelines as a VUS (class 3) whereas a second splice site variant was deemed as likely pathogenic (class 4). Pathogenicity of the splice site variant was confirmed by mRNA sequencing and nonsense mediated decay (NMD) was detected. Combination of the detected variants could be associated to the LGMDR23-phenotype based on the MRI matching and literature research. Discussion Two novel variants in LAMA2 associated with LGMDR23-phenotype are described. This study illustrates challenges of the genetic findings due to their VUS classification and elucidates how individualized diagnostic procedure has contributed to the accurate diagnosis in the spectrum of LGMD.
Restructuration of architectural practice in integrated project delivery (IPD): two case studies

Purpose The purpose of this paper is to clarify that while integrated project delivery (IPD) methods can be momenta for restructuring architectural practice, they do not predetermine specific patterns of restructuration for the roles, responsibilities and services of architects. Design/methodology/approach This paper is based on a multiple case study design; two IPD projects were theoretically sampled and studied. The data collection methods included semi-structured interviews and observations. An inductive data analysis approach was applied to frame the phenomena, conduct cross-case comparisons and develop propositions. Findings While IPD implementations set expectations for new structures for practices, it is the project participants’ situated decisions that lead to the restructuration of some dimensions of architectural practice. The dimensions in this study included team formation, design leadership and collaboration and architectural services. IPD project participants locally changed and redefined conventional roles, responsibilities and project artifacts (e.g. drawings and models) that concerned design development and coordination. Practical implications IPD context, by itself, does not predetermine a fixed pattern of change in establishing designers’ roles, responsibilities and services because restructuration is highly negotiated amongst the IPD parties and can lead to different responses to this contractual setting. Contracts set expectations for collaborative behavior, but the fulfillment of these expectations is situated and emerging as project participants negotiate to develop practices. Originality/value While IPD research and guidelines aim to provide recipes for IPD implementation, this study contributes to the body of knowledge by clarifying that IPD is a context in which unprecedented ways of practice restructuration could emerge.
Mismatches in scale between highly mobile marine megafauna and marine protected areas

Marine protected areas (MPAs), particularly large MPAs, are increasing in number and size around the globe in part to facilitate the conservation of marine megafauna under the assumption that large-scale MPAs better align with vagile life histories; however, this alignment is not well established. Using a global tracking dataset from 36 species across five taxa, chosen to reflect the span of home range size in highly mobile marine megafauna, we show most MPAs are too small to encompass complete home ranges of most species. Based on size alone, 40% of existing MPAs could encompass the home ranges of the smallest ranged species, while only < 1% of existing MPAs could encompass those of the largest ranged species. Further, where home ranges and MPAs overlapped in real geographic space, MPAs encompassed < 5% of core areas used by all species. Despite most home ranges of mobile marine megafauna being much larger than existing MPAs, we demonstrate how benefits from MPAs are still likely to accrue by targeting seasonal aggregations and critical life history stages and through other management techniques.
Using Glycated Albumin and Stimulated C-Peptide to Define Partial Remission in Type 1 Diabetes

Objective To propose a new definition of partial remission (PR) for patients with type 1 diabetes (T1D) of all-ages using insulin dose and glycated albumin (GA), and find the optimal cut-off values for stimulated C-peptide to diagnose PR in different age-groups. Research Design and Methods Patients with newly diagnosed T1D (n=301) were included. GA/insulin dose was used to diagnose PR, and insulin dose-adjusted glycated albumin (IDAGA) was proposed to facilitate clinical application. The optimal diagnostic levels of IDAGA and stimulated C-peptide were determined in different age-groups (≤ 12y, 12-18y and ≥ 18y). Furthermore, the diagnostic consistency between different PR definitions was studied. Results GA≤ 23%/insulin dose ≤ 0.5u/kg/day was used to define PR, and IDAGA (GA (%) + 40 * insulin dose(u/kg/day)) ≤ 40 was feasible in all age-groups. Whereas, the optimal diagnostic level showed difference for stimulated C-peptide (265.5, 449.3 and 241.1 pmol/L for the ≤ 12y, 12-18y and ≥ 18y age-group, respectively). About 40% of patients met the PR definition by stimulated C-peptide but not GA/insulin dose or IDAGA, who showed dyslipidemia and higher insulin resistance. Conclusions A new definition of the PR phase is proposed using GA/insulin dose, and the calculated IDAGA≤ 40 applies to all age-groups. The stimulated C-peptide to diagnose PR is the highest in the 12-18y age-group, which reflects the effect of puberty on metabolism. For patients with insulin resistance, it is not recommended to use stimulated C-peptide alone to diagnose PR.
Major areas of interest of artificial intelligence research applied to health care administrative data: a scoping review

Introduction: The ongoing collection of large medical data has created conditions for application of artificial intelligence (AI) in research. This scoping review aimed to identify major areas of interest of AI applied to health care administrative data. Methods: The search was performed in seven databases: Medline, Embase, CINAHL, Web of science, IEEE, ICM digital library, and Compendex. We included articles published between January 2001 and March 2021, that described research with AI applied to medical diagnostics, pharmacotherapy, and health outcomes data. We screened the full text content and used natural language processing to automatically extract health areas of interest, principal AI methods, and names of medications. Results: Out of 14,864 articles, 343 were included. We determined ten areas of interest, the most common being health diagnostic or treatment outcome prediction (32%); representation of medical data, clinical pathways, and data temporality (i.e., transformation of raw medical data into compact and analysis-friendly format) (22%); and adverse drug effects, drug-drug interactions, and medication cascades (15%). Less attention has been devoted to areas such as health effects of polypharmacy (1%); and reinforcement learning (1%). The most common AI methods were decision trees, cluster analysis, random forests, and support vector machines. Most frequently mentioned medications included insulin, metformin, vitamins, acetaminophen, and heparin. Conclusions: The scoping review revealed the potential of AI application to health-related studies. However, several areas of interest in pharmacoepidemiology are sparsely reported, and the lack of details in studies related to pharmacotherapy suggests that AI could be used more optimally in pharmacoepidemiologic research.
A Bayesian Modeling Approach to Examine the Role of Testosterone Administration on the Endowment Effect and Risk-Taking

Financial risk-taking and loss aversion are multifaceted phenomena that are the focus of neuroscience, psychology, and economics research. A growing number of studies highlighted the role of hormones (particularly of testosterone) on socio-economic decision-making. However, the effects of testosterone on risk-taking under framing and consumer-based choices and preferences are inconclusive. We investigated the effects of 100 mg testosterone administration on aspects of decision-making within the Prospect Theory framework which is the most used descriptive model of decision-making under risk. We assessed risk-taking under framing and the endowment effect (effect of possession) using Bayesian modeling. Forty men participated in this double-blind placebo-controlled fully-randomized cross-over experiment and performed two tasks. One was a risk-taking task with binary choices under positive and negative framing associated with different probabilities. In the second task participants had to bid money for hedonic and utilitarian items. We observed a significant increase in serum testosterone concentrations after transdermal application. Compared to placebo, testosterone administration increased risk-taking under the positive framing (very large effect size) and decreased under the negative framing (moderate to small). The sensitivity to gain was positive in each framing. Our model showed that decision-making is jointly influenced by testosterone and the trade-off between gains and losses. However, while the endowment effect was more pronounced for hedonic than for utilitarian items, the effect was independent of testosterone. The findings provide novel information on the complex modulatory role of testosterone on risk-taking within the framework of prospect theory and shed light on mechanisms of behavioral economic biases. The proposed models of effects of individual differences in testosterone on risk-taking could be used as predictive models for reference-depended behavior under positive and negative framing with low and high probabilities.
Convolutional Recurrent Neural Network for Dynamic Functional MRI Analysis and Brain Disease Identification

Dynamic functional connectivity (dFC) networks derived from resting-state functional magnetic resonance imaging (rs-fMRI) help us understand fundamental dynamic characteristics of human brains, thereby providing an efficient solution for automated identification of brain diseases, such as Alzheimer's disease (AD) and its prodromal stage. Existing studies have applied deep learning methods to dFC network analysis and achieved good performance compared with traditional machine learning methods. However, they seldom take advantage of sequential information conveyed in dFC networks that could be informative to improve the diagnosis performance. In this paper, we propose a convolutional recurrent neural network (CRNN) for automated brain disease classification with rs-fMRI data. Specifically, we first construct dFC networks from rs-fMRI data using a sliding window strategy. Then, we employ three convolutional layers and long short-term memory (LSTM) layer to extract high-level features of dFC networks and also preserve the sequential information of extracted features, followed by three fully connected layers for brain disease classification. Experimental results on 174 subjects with 563 rs-fMRI scans from the Alzheimer's Disease Neuroimaging Initiative (ADNI) demonstrate the effectiveness of our proposed method in binary and multi-category classification tasks.
Development of High Fat Diet-Induced Hyperinsulinemia in Mice Is Enhanced by Co-treatment With a TLR7 Agonist

Metabolic syndrome (MetS) is common in Systemic Lupus Erythematosus (SLE) patients and is associated with increased cardio-renal risk. Toll-like receptor 7 (TLR7) stimulation promotes the development of SLE through mechanisms including activating type I Interferon (IFN) and autoreactive B cells. The current study tested whether combined TLR7 agonist treatment and exposure to a high fat, high sucrose “Western diet” intervention affects the early-stage development of SLE or MetS features. Female C57BL/6 mice were untreated or treated with the TLR7 agonist imiquimod (IMQ) and fed a high-fat diet (HFD; fat 42% kcal, sucrose 34% kcal) or control diet (fat 12.6% kcal, sucrose 34% kcal) for 6 weeks. Supporting early-stage induction of autoimmunity, spleen weights were significantly increased and anti-nuclear antibody (ANA) positivity was detected in IMQ-treated mice. Increased body weight, gonadal fat pad mass, and plasma leptin levels were observed between HFD and control animals for both IMQ and untreated mice. However, the increase in these parameters with HFD was slightly but significantly diminished in IMQ-treated mice. Both the HFD and IMQ treatments significantly increased fasting blood glucose levels. Notably, IMQ treatment affected fasting insulin concentrations in a diet-dependent manner, with hyperinsulinemia observed in IMQ-HFD treated mice. Together, this indicates that the IMQ model of SLE is associated with metabolic alterations, impaired glycemic control, and hyperinsulinemia under HFD conditions. This model may be helpful in further investigating the relationship between MetS and SLE, and supports a role of TLR7 signaling in promoting or accelerating the development of dysglycemia and hyperinsulinemia.
Investigating Affective Responses to Remotely Delivered “At Home” Low Volume High Intensity Interval Exercise: A Non-Randomized Parallel Group Feasibility Study

Background Low volume-high intensity interval exercise (LV-HIIE) has gained interest, due to its efficiency in invoking health and fitness benefits. However, little research has studied “at home” feasibility or effects of LV-HIIE. This study aimed to demonstrate that remote “at-home” LV-HIIE research is possible and to investigate if affective responses to the LV-HIIE protocol, subsequent intentions, and self-efficacy to repeat were related to self-reported tolerance of the intensity of exercise. Methods Using self-reported tolerance of the intensity of exercise, 41 healthy, physically active participants (25 female and 16 male; age 21.3 ± 1.0 years, body mass index 23.0 ± 2.9 kg.m2) were divided into low tolerance (LT, n = 14), middle tolerance (MT, n = 15), and high tolerance (HT, n = 12) groups. Participants completed a 20-min LV-HIIE circuit training video [2 × (10 ×30 s work, 15 s rest)] at home. Participants reported ratings of perceived exertion, affective valence, and perceived activation at baseline, during the protocol, immediately post-protocol, and during the cool down. 20-min after completion, respondents answered questions on exercise task self-efficacy and intentions to repeat LV-HIIE. Results The study recruited n = 65 individuals, of whom n = 50 passed screening. Ultimately n = 41 (82%) completed the exercise protocol and data collection. Ratings of perceived exertion were not significantly different between groups (p = 0.56), indicating similar perceptions of task difficulty. There was no significant effect of tolerance on affective valence (p = 0.36) or felt arousal (p = 0.06). There was evidence of high individual variability in affective responses within and between participants. Subsequent intentions and self-efficacy to repeat the exercise protocol did not seem to be related to affective valence during or after the protocol. Discussion Recruitment and data collection indicated that research into “at home” LV-HIIE is possible. High individual differences in affective responses suggest that LV-HEII may be appropriate for some but not all as an exercise option. Assessing self-reported tolerance of intensity of exercise may not appropriately identify whether or not LV-HIIE will be suitable for an individual.