Miracle-dz/UniFAR-FTUs huggingface dataset:
Diet Quality, Saturated Fat and Metabolic Syndrome

Indices reflecting overall diet quality are used globally in research to predict the risk of various diseases and metabolic disorders such as metabolic syndrome (MetS). Such indices are built to measure adherence to current dietary guidelines or to best assess the diet–disease relationship. Although mostly food-based, dietary guidelines often include recommendations to limit saturated fatty acid (SFA) intake in order to prevent cardiovascular diseases. However, not all diet quality indices consider SFA in their definition of diet quality. Additionally, the relationship between SFA consumption and the development of MetS remains unclear. The purpose of this short review was to explore the association between MetS and various diet quality indices and dietary patterns, with a focus on how SFA contributes to these associations.
Robust estimation in the nested case‐control design under a misspecified covariate functional form

The Cox proportional hazards model is typically used to analyze time‐to‐event data. If the event of interest is rare and covariates are difficult or expensive to collect, the nested case‐control (NCC) design provides consistent estimates at reduced costs with minimal impact on precision if the model is specified correctly. If our scientific goal is to conduct inference regarding an association of interest, it is essential that we specify the model a priori to avoid multiple testing bias. We cannot, however, be certain that all assumptions will be satisfied so it is important to consider robustness of the NCC design under model misspecification. In this manuscript, we show that in finite sample settings where the functional form of a covariate of interest is misspecified, the estimates resulting from the partial likelihood estimator under the NCC design depend on the number of controls sampled at each event time. To account for this dependency, we propose an estimator that recovers the results obtained using using the full cohort, where full covariate information is available for all study participants. We present the utility of our estimator using simulation studies and show the theoretical properties. We end by applying our estimator to motivating data from the Alzheimer's Disease Neuroimaging Initiative.
Markers of acute toxicity of DDT exposure in pancreatic beta-cells determined by a proteomic approach

Many compounds have the potential to harm pancreatic beta-cells; organochlorine pollutants belong to those compounds. In this work, we aimed to find markers of acute toxicity of p,p‘-DDT exposure among proteins expressed in NES2Y human pancreatic beta-cells employing 2-D electrophoresis. We exposed NES2Y cells to a high concentration (150 μM, LC96 after 72 hours) of p,p‘-DDT for 24 and 30 hours and determined proteins with changed expression using 2-D electrophoresis. We have found 22 proteins that changed their expression. They included proteins involved in ER stress (GRP78, and endoplasmin), mitochondrial proteins (GRP75, ECHM, IDH3A, NDUS1, and NDUS3), proteins involved in the maintenance of the cell morphology (EFHD2, TCPA, NDRG1, and ezrin), and some other proteins (HNRPF, HNRH1, K2C8, vimentin, PBDC1, EF2, PCNA, biliverdin reductase, G3BP1, FRIL, and HSP27). The proteins we have identified may serve as indicators of p,p‘-DDT toxicity in beta-cells in future studies, including long-term exposure to environmentally relevant concentrations.
Antibiotics in hives and their effects on honey bee physiology and behavioral development

ABSTRACT Recurrent honeybee losses make it critical to understand the impact of human interventions, such as antibiotic use in apiculture. Antibiotics are used to prevent or treat bacterial infections in colonies. However, little is known about their effects on honeybee development. We studied the effect of two commercial beekeeping antibiotics on the bee physiology and behavior throughout development. Our results show that antibiotic treatments have an effect on amount of lipids and rate of behavioral development. Lipid amount in treated bees was higher than those not treated. Also, the timing of antibiotic treatment had distinct effects for the age of onset of behaviors, starting with cleaning, then nursing and lastly foraging. Bees treated during larva-pupa stages demonstrated an accelerated behavioral development and loss of lipids, while bees treated from larva to adulthood had a delay in behavioral development and loss of lipids. The effects were shared across the two antibiotics tested, TerramycinR (oxytetracycline) and TylanR (tylosin tartrate). These effects of antibiotic treatments suggest a role of microbiota in the interaction between the fat body and brain that is important for honeybee behavioral development. This paper has an associated First Person interview with the first author of the article. Summary: Antibiotic treatments in bee colonies cause an increase or decrease in rate of behavioral development and lipid stores of workers, affecting fat body–interaction, likely through effects on microbiota.
Genetic population structure of the blue sea star Linckia laevigata in the Visayas (Philippines)

Coral reef associated marine invertebrates, such as the blue sea star Linckia laevigata, have a life history with two phases: sedentary adults and planktonic larvae. On the one hand it is hypothesised that the long pelagic larval duration facilitates large distance dispersal. On the other hand, complex oceanographic and geographic characteristics of the Visayan seascape could cause isolation of populations. The study aims to investigate the genetic diversity, genetic population structure and gene flow in L. laevigata to reveal connectivity among populations in the Visayas. The analysis is based on partial sequences (626 bp in length) of the mitochondrial cytochrome oxidase I gene (COI) from 124 individuals collected from five localities in the Visayas. A comparative analysis of these populations with populations from the Indo-Malay Archipelago (IMA) published previously is also presented. Genetic diversity was high (h = 0.98, π = 1.6%) and comparable with preceding studies. Analyses of molecular variance (AMOVA) revealed a lack of spatial population differentiation among sample sites in the Visayas (ΦST-value = 0.009; P > 0.05). The lack of genetic population structure indicates high gene flow among populations of L. laevigata in the Visayas. Comparative analysis with data from the previous study indicates high connectivity of the Visayas with the central part of the IMA.
Plasma Metabolome and Circulating Vitamins Stratified Onset Age of an Initial Islet Autoantibody and Progression to Type 1 Diabetes: the TEDDY Study.

Children's plasma metabolome, especially lipidome reflects gene regulation and dietary exposures, heralding the development of islet autoantibodies (IA) and type 1 diabetes (T1D). The TEDDY study enrolled 8676 newborns by screening HLA-DR-DQ genotypes at six clinical centers in four countries; profiled metabolome and measured concentrations of ascorbic acid, 25-hydroxyvitamin D (25(OH)D), erythrocyte membrane fatty acids following birth until IA seroconversion under nested case-control design. We grouped children having an initial autoantibody only against insulin (IAA-first) or glutamic acid decarboxylase (GADA-first) by unsupervised clustering of temporal lipidome, identifying a subgroup of children having early onset of each initial autoantibody, i.e., IAA-first by 12 months and GADA-first by 21 months, consistent with population-wide early seroconversion age. Differential analysis showed that infants having reduced plasma ascorbic acid and cholesterol experienced IAA-first earlier, while early onset of GADA-first was preceded by reduced sphingomyelins at infancy. Plasma 25(OH)D prior to either autoantibody was lower in T1D progressors compared to non-progressors, with simultaneous lower diglycerides, lysophosphatidylcholines, triglycerides, alanine before GADA-first. Plasma ascorbic acid and 25(OH)D at infancy were lower in HLA-DR3/DR4 children among IA cases but not in matched controls, implying gene expression dysregulation of circulating vitamins as latent signals for IA or T1D progression.
Suppressing competitive dominants and community restoration with native parasitic plants using the hemiparasitic Rhinanthus alectorolophus and the dominant grass Calamagrostis epigejos

Summary Dominance of native or alien competitive plants causes competitive exclusion of subordinate species and represents a major mechanism reducing biodiversity following land-use changes. The successful competitive strategies may, however, be interfered with by parasitic plants, which withdraw resources from other plants' vasculature. Parasitism may strongly reduce the growth of the dominants, which may facilitate regeneration of other species and consequently trigger restoration of natural communities of high diversity. Here, we aim to provide robust empirical evidence demonstrating this restoration potential of parasitic plants. We present a case study testing suppressive effects of hemiparasitic Rhinanthus alectorolophus on competitive grass Calamagrostis epigejos. In recent decades, C. epigejos has invaded many high-nature-value semi-natural grasslands of Central Europe, which is one of the prominent factors causing their biodiversity decline. We conducted three manipulative field experiments testing the effect of sowing of R. alectorolophus in different vegetation types infested by C. epigejos. Rhinanthus sowing was compared to different mowing treatments recommended as the ‘best practice’ management at respective sites. Rhinanthus alectorolophus established itself in most C. epigejos-dominated plots where sown. Calamagrostis epigejos was virtually exterminated in 2 years in two of the experiments (dry meadow and industrial area). In the wet-meadow experiment, the suppressive effect was variable as a result of uneven establishment success of Rhinanthus. In this experiment increased mowing intensity had an additional suppressive effect on C. epigejos. Rhinanthus also increased regeneration potential of other species by a temporary reduction of vegetation density. Restoration of target vegetation composition was, however, dependent on community context. Synthesis and applications. We demonstrated that hemiparasitic Rhinanthus alectorolophus is an accessible and efficient tool for targeted biological control of Calamagrostis epigejos, with a great potential to restore infested grassland vegetation. The strong effect of Rhinanthus is caused by interference with the underground storage and clonal growth strategy of Calamagrostis epigejos, which are both traits that underlie its competitive ability. The potential of native parasitic plants should be considered in restoration management of sites infested by competitive dominants, either alien or native.
Effects of Acute Aerobic Exercise Combined with Resistance Exercise on Neurocognitive Performance in Obese Women

To the best of the author’s knowledge, there have been no previous studies conducted on the effects of a combination of acute aerobic and resistance exercise on deficit of inhibitory control in obese individuals. The aim of this study was, thus, to examine the effect of a single bout of such an exercise mode on behavioral and cognitive electrophysiological performance involving cognitive interference inhibition in obese women. After the estimated VO2max and percentage fat (measured with dual-energy X-ray absorptiometry (Hologic, Bedford, MA, USA) were assessed, 32 sedentary obese female adults were randomly assigned to an exercise group (EG) and a control group (CG), with their behavioral performance being recorded with concomitant electrophysiological signals when performing a Stroop task. Then, the EG engaged in 30 min of moderate-intensity aerobic exercise combined with resistance exercise, and the CG rested for a similar duration of time without engaging in any type of exercise. After the interventions, the neurocognitive performance was measured again in the two groups. The results revealed that although acute exercise did not enhance the behavioral indices (e.g., accuracy rates (ARs) and reaction times (RTs)), cognitive electrophysiological signals were improved (e.g., shorter N2 and P3 latencies, smaller N2 amplitudes, and greater P3 amplitudes) in the Stroop task after the exercise intervention in the EG. The findings indicated that a combination of acute moderate-intensity aerobic and resistance exercise may improve the neurophysiological inhibitory control performance of obese women.
Repetitive Transcranial Magnetic Stimulation With and Without Internet-Delivered Cognitive-Behavioral Therapy for the Treatment of Resistant Depression: Protocol for Patient-Centered Randomized Controlled Pilot Trial

Background Major depression is a severe, disabling, and potentially lethal clinical disorder. Only about half of patients respond to an initial course of antidepressant pharmacotherapy. At least 15% of all patients with major depressive disorder (MDD) remain refractory to any treatment intervention. By the time that a patient has experienced 3 definitive treatment failures, the likelihood of achieving remission with the fourth treatment option offered is below 10%. Repetitive transcranial magnetic stimulation (rTMS) is considered a treatment option for patients with MDD who are refractory to antidepressant treatment. It is not currently known if the addition of internet-delivered cognitive-behavioral therapy (iCBT) enhances patients’ responses to rTMS treatments. Objective This study will evaluate the initial comparative clinical effectiveness of rTMS with and without iCBT as an innovative patient-centered intervention for the treatment of participants diagnosed with treatment-resistant depression (TRD). Methods This study is a prospective, two-arm randomized controlled trial. In total, 100 participants diagnosed with resistant depression at a psychiatric care clinic in Edmonton, Alberta, Canada, will be randomized to one of two conditions: (1) enrolment in rTMS sessions alone and (2) enrolment in the rTMS sessions plus iCBT. Participants in each group will complete evaluation measures (eg, recovery, general symptomatology, and functional outcomes) at baseline, 1 month, 3 months, and 6 months. The primary outcome measure will be the mean change to scores on the Hamilton Depression Rating Scale. Patient service utilization data and clinician-rated measures will also be used to gauge patient progress. Patient data will be analyzed with descriptive statistics, repeated measures, and correlational analyses. Results We expect the results of the study to be available in 24 months. We hypothesize that participants enrolled in the study who receive rTMS plus iCBT will achieve superior outcomes in comparison to participants who receive rTMS alone. Conclusions The concomitant application of psychotherapy with rTMS has not been investigated previously. We hope that this project will provide us with a concrete base of data to evaluate the practical application and efficacy of using a novel combination of these two treatment modalities (rTMS plus iCBT). Trial Registration ClinicalTrials.gov NCT0423965; https://clinicaltrials.gov/ct2/show/NCT04239651 International Registered Report Identifier (IRRID) PRR1-10.2196/18843
Association of Dilated Perivascular Spaces and Disease Severity in Patients With Huntington Disease

Objective To quantify the percent volume of dilated perivascular space (PVS) in the subcortical forebrain in patients with early Huntington disease (HD) and to explore the relationship between PVS and disease severity. Methods MRI scans were performed on 25 patients with HD and 23 healthy age-matched controls at Massachusetts General Hospital. The imaging data were analyzed with a novel algorithm to determine regional PVS volume. A fractional logistic regression analysis was used to quantify the association between regional percent PVS volume and (1) disease designation (HD or control) and (2) disease severity as assessed by normalized caudate volume. Results Patients with HD had the greatest percent volume of dilated PVS in the putamen (left putamen: odds ratio 2.06 [95% confidence interval (CI) 1.62–2.62], HD 3.27% [95% CI 2.83–3.78] vs controls 1.62% [95% CI 1.32–1.97], pfdr < 0.001; right putamen: odds ratio 1.66 [95% CI 1.33–2.08], HD 3.43% [95% CI 2.94–4.01] vs controls 2.09% [95% CI 1.79–2.45], pfdr < 0.001) and several subcortical white matter regions compared to controls. Dilated PVS increased with disease severity. Conclusions The objective quantification of dilated PVS suggests that PVS burden is high, is associated with disease severity, and may affect the distribution and success of treatments administered either intrathecally such as antisense oligonucleotides or by intraparenchymal administration such as cell and gene therapies. Classification of Evidence This study provides Class II evidence that increased dilated PVS is associated with worse HD severity. The study is rated Class II because of the cross-sectional design.
Discovery of Novel 3-Cyanopyridines as Survivin Modulators and Apoptosis Inducers

The overexpression of survivin is usually accompanied by an increased resistance of cancer cells to chemotherapeutic agents in addition to cancer aggressiveness. Consequently, survivin is considered as an attractive target to develop new promising anticancer candidates. A series of novel 3-cyanopyridine derivatives was synthesized and assessed for their cytotoxic activity against three human cancer cell lines: prostate carcinoma (PC-3), breast cancer (MDA-MB-231) and hepatocellular carcinoma (HepG2). In addition, their activities were evaluated in comparison with a standard anticancer drug 5-FU. Compounds 5c and 5e both exhibited promising cytotoxicity against all the tested cell lines; especially, 5e showed better cytotoxic effect than the reference drug 5-FU. In order to evaluate the safety of these compounds, they were tested on the normal cell line WI-38, revealing their toxic selectivity toward cancer cells over normal ones. Further studies were performed in order to understand their mechanism of action; we examined the ability of our promising compounds 5c and 5e to induce cell cycle arrest. Both resulted in a notable induction of cell cycle arrest at the G2/M phase, along with an increase in the DNA content in the pre-G1 phase, giving us an indication of the incidence of apoptosis. 5c and 5e were further subjected to additional study using Annexin V-FITC assay in order to evaluate their ability to induce apoptosis. The results showed a marked increase in the early and late apoptotic cells, as well as an increase in the percentage of necrosis. Furthermore, Western blotting assay was accomplished using different concentrations of 5c and 5e. The results revealed a striking reduction in survivin expression through proteasome-dependent survivin degradation in addition to a decrease in the expression of some other inhibitor of apoptosis proteins (IAP) family proteins: Livin, XIAP, and C-IAP1 in a concentration-dependent manner. A docking study of 5c and 5e compounds in the dimerization site of survivin was also performed, showing agreement with the in vitro anti-survivin activity.
Age-related adverse events of disease-modifying treatments for multiple sclerosis: A meta-regression

Objective: To verify the hypothesis of an age-dependent increase of infections and neoplasms in patients with multiple sclerosis (MS) under disease-modifying treatments (DMTs) with different mechanisms of action. Methods: We extracted relevant data from 45 randomized clinical trials (RCTs) on currently licensed DMTs. We fitted inverse-variance weighted meta-regressions with random-effects models to estimate whether age and/or mechanism of action (immunomodulatory, sequestrating, and depletive) of currently licensed DMTs influenced the difference between experimental arm and control arm in the incidence of specific adverse events, namely, overall infections, opportunistic infections, and neoplasms. Results: A higher incidence of overall infections was observed in RCTs with depletive DMTs (event-rate ratio = 1.25, p < 0.001). Herpetic infections were more frequently observed in RCTs with both depletive (event-rate ratio = 3.51, p < 0.001) and, to a lesser extent, sequestrating DMTs (event-rate ratio = 1.52, p = 0.078). The interaction of age with depletive DMTs was associated with higher incidence of neoplasms (p = 0.017), especially above 45 years of age. Discussion: Our study supports a detrimental effect of age on the safety profile of depletive DMTs, with an increased incidence of neoplasms especially over 45 years of age. We failed to demonstrate an age-related increased incidence of infections, possibly due to latency in their occurrence.
Biodiversity and distribution patterns of Triplophysa species in the northeastern margin of the Tibetan Plateau

: The northeastern region of the Tibetan Plateau is a region with high genetic diversity for endemic species. To comprehensively document the patterns of diversity and the distribution of Triplophysa species in this area, we probed the allocation of Triplophysa species using field surveys from 2012 to 2015. We found that areal shrinkage and fragmentation had occurred in some species. Species richness in this area was une-ven. But the middle to upper reaches of the Heihe River, Datong River and Taohe River were uncommon ar-eas with high species-richness and high biodiversity. Along altitudinal gradients, species richness presented a unimodal pattern and peaked at mid-elevations (2,200–2,400 m), which was the transition area between two community zones with high species richness. The unimodal pattern fit Lomolino’s prediction regarding species density and altitude. Biodiversity indices displayed uniform patterns with species richness and elevation. Consistent with most studies, the unimodal shape may be the universal pattern of biodiversity distribution along elevational gradients in the Tibetan Plateau and its adjacent highlands. The intermediate elevational re-•研究报告• conservation priorities.
A Legume Lotus japonicus Genome Annotation

Comparative genomics is a promising approach to study genetic systems which are both unique and common to individual living organisms. The information on the entire genome and deduced gene structures of Arabidopsis thaliana, together with information of gene function accumulated in this plant, will be used as a standard for the comparative studies in higher plants. After contributing to the international Arabidopsis genome sequencing project [6], we are now in the process of genome sequence analysis of a leguminous plant Lotus japonicus to understand the genetic system of legume species and to facilitate isolation and characterization of genes responsible for legume-specific phenomena, including plant-microbe interactions and symbiotic nitrogen fixation. Together with this, we have determined the complete genome of the nitrogen fixing symbiont of L. japonicus, Mesorhizobium loti MAFF303099 [3]. M. loti is a member of rhizobia which is able to form determinant-type globular nodules and to perform nitrogen-fixation on several Lotus species. L. japonicus is a typical model plant with the following characteristics: short regeneration time (2-3 months), diploidy (n = 6) and small genome size (ca. 470 Mb). A large number of expressed sequence tags have been accumulated [1] and high-density linkage maps of all six chromosomes have been generated [2].