Miracle-dz/UniFAR-FTUs huggingface dataset:
Experimental and Field Data Support Range Expansion in an Allopolyploid Arabidopsis Owing to Parental Legacy of Heavy Metal Hyperaccumulation

Empirical evidence is limited on whether allopolyploid species combine or merge parental adaptations to broaden habitats. The allopolyploid Arabidopsis kamchatica is a hybrid of the two diploid parents Arabidopsis halleri and Arabidopsis lyrata. A. halleri is a facultative heavy metal hyperaccumulator, and may be found in cadmium (Cd) and zinc (Zn) contaminated environments, as well as non-contaminated environments. A. lyrata is considered non-tolerant to these metals, but can be found in serpentine habitats. Therefore, the parents have adaptation to different environments. Here, we measured heavy metals in soils from native populations of A. kamchatica. We found that soil Zn concentration of nearly half of the sampled 40 sites was higher than the critical toxicity level. Many of the sites were near human construction, suggesting adaptation of A. kamchatica to artificially contaminated soils. Over half of the A. kamchatica populations had >1,000 μg g–1 Zn in leaf tissues. Using hydroponic treatments, most genotypes accumulated >3,000 μg g–1 Zn, with high variability among them, indicating substantial genetic variation in heavy metal accumulation. Genes involved in heavy metal hyperaccumulation showed an expression bias in the A. halleri-derived homeolog in widely distributed plant genotypes. We also found that two populations were found growing on serpentine soils. These data suggest that A. kamchatica can inhabit a range of both natural and artificial soil environments with high levels of ions that either of the parents specializes and that it can accumulate varying amount of heavy metals. Our field and experimental data provide a compelling example of combining genetic toolkits for soil adaptations to expand the habitat of an allopolyploid species.
Twenty-Four-Hour Ambulatory Blood Pressure Variability Associated With Cerebral Small Vessel Disease MRI Burden and Its Progression in Inpatients With Cerebrovascular Disease

Background: Lacunar infarcts, white matter lesions, cerebral microbleed, enlarged perivascular space and brain atrophy are regarded as magnetic resonance imaging (MRI) manifestations of cerebral small vessel disease (cSVD). 24-hour blood pressure variability (BPV) has been reported to relate with cerebral small vessel disease, but the impact of 24-h BPV on the total MRI cSVD burden and its progression in inpatients with cerebrovascular disease has not been investigated yet. Methods: We enrolled inpatients with cerebrovascular disease, who underwent the 24-h ambulatory blood pressure monitoring (ABPM) and the brain MRI scan at baseline and had the follow-up brain MRI images stored in the clinical information system of our hospital. BPV was quantified by the calculation of standard deviation (SD), coefficient of variation (CV), weighted standard deviation (wSD) of blood pressure record. We evaluated the total cSVD score on baseline MRI and the MRI followed-up to obtain the total burden of cSVD. The cSVD burden progression was estimated through the comparison of the total cSVD score on the two MRIs. Results: A total of 140 patients with an average age of 65.6 years were finally enrolled, 82.9% (116/140) of whom had one or more cSVD markers. After a median of 4.4 years follow-up, cSVD score progression were found in 50.7% (71/140) of the patients. Both SD and CV of SBP and DBP during 24-h and daytime as well as the SBP wSD differed significantly among different total cSVD score groups. The SBP SD and CV during 24-h and daytime, the SBP SD in nighttime, the DBP SD and CV during the daytime were significantly higher in the cSVD progression group than those in the cSVD no-progression group. The SBP wSD and the DBP wSD were significantly higher in the cSVD progression group than those in the cSVD no-progression group. Logistic regression analyses revealed that daytime SBP SD and SBP wSD were independent risk factors for total cSVD burden [daytime SBP SD: OR = 1.628, 95% CI = 1.105–2.398 (per 5 mmHg increase in SD), P = 0.014; SBP wSD: OR = 2.248, 95% CI = 1.564–3.230 (per 5 mmHg increase in wSD), P < 0.001)] and SBP wSD was a significant predictor for cSVD progression [OR = 2.990, 95% CI = 1.053–8.496 (per 5 mmHg increase in wSD), P = 0.040]. Conclusion: Higher BPV were significantly related with total cSVD burden in inpatients with cerebrovascular disease. SBP SD during daytime and SBP wSD were independent risk factor for total cSVD burden and SBP wSD was an predictive factor for cSVD progression.
Construction of Cognitive Maps to Improve Reading Performance by Text Signaling: Reading Text on Paper Compared to on Screen

Reading text from a screen has been shown to be less effective compared with reading text from paper. Various signals may provide both background information and navigational cues, and may promote the construction of cognitive maps during on-screen reading, thus improving reading performance. This study randomly divided 75 college students into a paper reading group and an on-screen reading group. Both groups were tested for navigation and reading comprehension in response to three different forms of signaling (plain text, physical signaling, and verbal signaling). The results showed that when plain text was presented, the navigation and comprehension scores of the paper reading group were significantly higher than those of the on-screen reading group. However, no significant difference was found between both groups under signaling conditions. The navigation and comprehension scores of both groups were significantly higher under signaling conditions than under plain text. Moreover, the comprehension score of the on-screen reading group under physical signaling was significantly higher than that under verbal signaling. This research suggested that signals help to construct cognitive maps and effectively improve reading performance. Besides, physical signaling, such as underlining and bold formatting, is more effective for on-screen reading. The present study provides a practical and effective approach for improving on-screen reading based on cognitive map theory.
Virtual Reality Meets Non-invasive Brain Stimulation: Integrating Two Methods for Cognitive Rehabilitation of Mild Cognitive Impairment

Mild cognitive impairment (MCI) refers to a subtle, general cognitive decline with a detrimental impact on elderlies' independent living and quality of life. Without a timely diagnosis, this condition can evolve into dementia over time, hence the crucial need for early detection, prevention, and rehabilitation. For this purpose, current neuropsychological interventions have been integrated with (i) virtual reality, which immerses the user in a controlled, ecological, and safe environment (so far, both virtual reality-based cognitive and motor rehabilitation have revealed promising positive outcomes); and (ii) non-invasive brain stimulation, i.e., transcranial magnetic or electric brain stimulation, which has emerged as a promising cognitive treatment for MCI and Alzheimer's dementia. To date, these two methods have been employed separately; only a few studies (limited to motor rehabilitation) have suggested their integration. The present paper suggests to extend this integration to cognitive rehabilitation as well as to provide a multimodal stimulation that could enhance cognitive training, resulting in a more efficient rehabilitation.
Subsets of CD1c+ DCs: Dendritic Cell Versus Monocyte Lineage

Currently three bona fide dendritic cell (DC) types are distinguished in human blood. Herein we focus on type 2 DCs (DC2s) and compare the three defining markers CD1c, CD172, and CD301. When using CD1c to define DC2s, a CD14+ and a CD14− subset can be detected. The CD14+ subset shares features with monocytes, and this includes substantially higher expression levels for CD64, CD115, CD163, and S100A8/9. We review the current knowledge of these CD1c+CD14+ cells as compared to the CD1c+CD14− cells with respect to phenotype, function, transcriptomics, and ontogeny. Here, we discuss informative mutations, which suggest that two populations have different developmental requirements. In addition, we cover subsets of CD11c+CD8− DC2s in the mouse, where CLEC12A+ESAMlow cells, as compared to the CLEC12A−ESAMhigh subset, also express higher levels of monocyte-associated markers CD14, CD3, and CD115. Finally, we summarize, for both man and mouse, the data on lower antigen presentation and higher cytokine production in the monocyte-marker expressing DC2 subset, which demonstrate that the DC2 subsets are also functionally distinct.
A 10-Week Block of Combined High-Intensity Endurance and Strength Training Produced Similar Changes in Dynamic Strength, Body Composition, and Serum Hormones in Women and Men

Purpose: To examine the potential sex differences in adaptations to combined endurance and strength training in recreationally endurance trained (eumenorrheic) women (n = 9) and men (n = 10). Methods: Isometric (ISOMmax) and dynamic bilateral leg press (1RM), countermovement jump (CMJ), running performance (3,000 m time trial), lean mass and body fat % (LEAN and FAT% determined by dual X-ray absorptiometry) as well as serum testosterone and cortisol (TES and COR, respectively, measured using hormone-specific immunoassay kits) were examined before a control period and pre, mid, and post a supervised 10-week combined high-intensity interval endurance training (4 × 4 min intervals and 3 × 3 × 100 m repeated sprints) and mixed maximal and explosive strength training. No more than 2 weeks separated training and testing for either women or men and all women were tested in the early follicular phase of the menstrual cycle to minimize the possible influence of menstrual cycle phase on performance measures. Results: Absolute and relative changes in 1RM, CMJ, 3,000 m, LEAN, and FAT% were similar between groups. The only statistically significant differences observed between groups were observed at post and included a larger Δ% increase in ISOMmax force in men and a relatively greater Δ% decrease in serum TES in women. Conclusion: Women and men can achieve similar relative adaptations in dynamic maximal strength and CMJ as well as endurance performance gains and body composition over the same high-intensity 10-week combined program, although relative adaptations in TES may differ.
Short-Term Effects of Single-Session Split-Belt Treadmill Training on Dual-Task Performance in Parkinson's Disease and Healthy Elderly

Background: Dual-tasking is challenging for people with Parkinson's disease and freezing of gait (PD+FOG) and can exacerbate freezing episodes and falls. Split-belt treadmill training (SBT) is a novel tool to train complex gait and may improve dual-task (DT) walking and turning. Objective: To investigate the single-session effects of SBT on DT walking and DT turning performance in PD+FOG and older adults (OA), compared to regular treadmill training. Methods: Forty-five PD+FOG and 36 OA participated in a single training session (30 min). They were randomized into one of four training groups: (A) SB75—steady belt speed ratio 0.75:1; (B) SB50—steady belt speed ratio 0.5:1; (C) SBCR—changing belt speed ratios between 0.75:1 and 0.5:1; and (D) Tied-Belt (TBT). Over-ground straight-line gait and an alternating turning in place task combined with a cognitive dual-task (DT) (auditory Stroop) were assessed pre- and post-training, and the following day (retention). Constrained longitudinal data analysis was used to investigate the training effects for all participants and for PD+FOG alone. Results: DT gait speed improved at post-training for all groups (p < 0.001). However, SBT (SB50 and SBCR) led to larger post-training improvements compared to TBT, which were still visible at retention (SB50). For mean DT turning speed and Stroop response time while walking, only SBT groups showed significant improvements at post-training or retention. DT stride length, peak DT turning speed, and Stroop performance index while walking also showed larger gains in SBT compared to TBT. Results for PD+FOG alone showed similar effects although with smaller effect sizes. Conclusions: A single session of SBT in PD+FOG and OA showed larger short-term effects on DT walking and turning compared to TBT. Cognitive DT performance was also improved in SBT, likely due to reduced cortical control of gait. These results illustrate the potential for SBT to improve DT during complex gait and possibly reduce fall risk in clinical and healthy populations.
The Role of Type I Interferons in the Pathogenesis and Treatment of COVID-19

Type I interferons (IFN-I) were first discovered over 60 years ago in a classical experiment by Isaacs and Lindenman, who showed that IFN-Is possess antiviral activity. Later, it became one of the first approved protein drugs using heterologous protein expression systems, which allowed its large-scale production. It has been approved, and widely used in a pleiotropy of diseases, including multiple-sclerosis, hepatitis B and C, and some forms of cancer. Preliminary clinical data has supported its effectiveness against potential pandemic pathogens such as Ebola and SARS. Still, more efficient and specific drugs have taken its place in treating such diseases. The COVID-19 global pandemic has again lifted the status of IFN-Is to become one of the more promising drug candidates, with initial clinical trials showing promising results in reducing the severity and duration of the disease. Although SARS-CoV-2 inhibits the production of IFNβ and thus obstructs the innate immune response to this virus, it is sensitive to the antiviral activity of externally administrated IFN-Is. In this review I discuss the diverse modes of biological actions of IFN-Is and how these are related to biophysical parameters of IFN-I–receptor interaction and cell-type specificity in light of the large variety of binding affinities of the different IFN-I subtypes towards the common interferon receptor. Furthermore, I discuss how these may guide the optimized use IFN-Is in combatting COVID-19.
Individual and combined effects of fine sediment and glyphosate herbicide on invertebrate drift and insect emergence: a stream mesocosm experiment

Pesticides and deposited fine sediment have been associated independently with changes in relative abundance and number of sensitive species in aquatic ecosystems, but the interplay between these stressors in agricultural streams is poorly understood. We used a 28-d experiment in outdoor streamside mesocosms to examine the effects of varying levels of fine sediment and a glyphosate-based herbicide on 2 important aspects of macroinvertebrate community dynamics, invertebrate drift and adult insect emergence. We applied 4 levels of each stressor in a full factorial, repeated-measures design (4 glyphosate × 4 sediment levels × 2 replicates of each treatment combination). We focused on the propensities of the invertebrates to drift or emerge (number drifting per mesocosm/benthic individuals per m2). Sediment addition affected drift propensities of 4 of the 10 most common invertebrate taxa, community-level measures of drift (total taxon and Ephemeroptera, Plecoptera, Trichoptera [EPT] richness) and adult emergence (total propensity and taxon richness), whereas glyphosate addition affected drift propensity of only 1 taxon. These results suggest that glyphosate entering streams during terrestrial herbicide operations may be less problematic for aquatic invertebrate community dynamics than fine sediment from catchment erosion. No significant sediment × glyphosate interaction was detected for any individual taxon drift propensity or community-level drift or emergence measure, indicating that the 2 stressors acted additively, rather than synergistically or antagonistically. The dynamic measures (invertebrate drift and adult insect emergence propensities) often showed the opposite pattern compared to benthic invertebrate densities in the same experiment, a result highlighting the value of using dynamic aspects of stream invertebrate communities to identify mechanisms underlying stressor effects on benthic standing stocks.
Image-Guided Treatment of Primary Liver Cancer in Mice Leads to Vascular Disruption and Increased Drug Penetration

Despite advances in interventional procedures and chemotherapeutic drug development, hepatocellular carcinoma (HCC) is still the fourth leading cause of cancer-related deaths worldwide with a <30% 5-year survival rate. This poor prognosis can be attributed to the fact that HCC most commonly occurs in patients with pre-existing liver conditions, rendering many treatment options too aggressive. Patient survival rates could be improved by a more targeted approach. Ultrasound-induced cavitation can provide a means for overcoming traditional barriers defining drug uptake. The goal of this work was to evaluate preclinical efficacy of image-guided, cavitation-enabled drug delivery with a clinical ultrasound scanner. To this end, ultrasound conditions (unique from those used in imaging) were designed and implemented on a Philips EPIQ and S5-1 phased array probe to produced focused ultrasound for cavitation treatment. Sonovue® microbubbles which are clinically approved as an ultrasound contrast agent were used for both imaging and cavitation treatment. A genetically engineered mouse model was bred and used as a physiologically relevant preclinical analog to human HCC. It was observed that image-guided and targeted microbubble cavitation resulted in selective disruption of the tumor blood flow and enhanced doxorubicin uptake and penetration. Histology results indicate that no gross morphological damage occurred as a result of this process. The combination of these effects may be exploited to treat HCC and other challenging malignancies and could be implemented with currently available ultrasound scanners and reagents.
Helper Innate Lymphoid Cells in Allogenic Hematopoietic Stem Cell Transplantation and Graft Versus Host Disease

Helper Innate Lymphoid Cells (hILCs), including ILC1s, ILC2s, and ILC3s, are mainly localized at the mucosal barriers where they play an important role in tissue regeneration and homeostasis through the secretion of specific sets of cytokines. The recent identification of a circulating ILC precursor able to generate all ILC mature subsets in physiological conditions, suggests that “ILC-poiesis” may be important in the context of hematopoietic stem cell transplantation (HSCT). Indeed, in HSCT the conditioning regimen (chemotherapy and radiotherapy) and Graft vs Host Disease (GvHD) may cause severe damages to mucosal tissues. Therefore, it is conceivable that rapid reconstitution of the hILC compartment may be beneficial in HSCT, by promoting mucosal tissue repair/regeneration and providing protection from opportunistic infections. In this review, we will summarize the evidence for a role of hILCs in allogenic HSCT for the treatment of hematological malignancies in all its steps, from the preparative regimen to the immune reconstitution in the recipient. The protective properties of hILCs at the mucosal barrier interfaces make them an attractive target to exploit in future cellular therapies aimed at improving allogenic HSCT outcome.
Changes in Brain Function Networks in Patients With Amnestic Mild Cognitive Impairment: A Resting-State fMRI Study

Patients with amnestic mild cognitive impairment (aMCI) are at high risk of developing dementia. This study used resting-state functional magnetic resonance imaging (rs-fMRI) and an independent component analysis (ICA) approach to explore changes in functional connectivity (FC) in the default mode network (DMN), executive control network (ECN), and salience network (SN). Thirty patients with aMCI and 30 healthy controls (HCs) were enrolled. All the participants underwent an rs-fMRI scan. The brain FC in DMN, ECN, and SN was calculated using the ICA approach. We found that the FC of brain regions in DMN decreased significantly and that of brain regions in ECN increased, which was in accordance with the findings of previous studies on Alzheimer's disease (AD) and aMCI. We also found that the FC of brain regions in SN increased, which was different from the findings of previous studies on AD. The increase in FC in brain regions in SN might result from different pathophysiological states in AD and aMCI, indicating that a decrease in FC in SN does not occur in a person with aMCI. These results are consistent with those of previous studies using the voxel-mirrored homotopic connectivity approach and seed-based correlation analysis. We therefore considered that the decrease in FC in DMN and the increase in FC in ECN and SN might be peculiar patterns observed on the rs-fMRI of a person with aMCI. These findings may contribute to the development of imaging biomarkers for the diagnosis of aMCI.
Clinical Outcomes for PD-1 Inhibitor Plus Chemotherapy as Second-Line or Later Therapy Compared to PD-1/PD-L1 Inhibitor Alone in Advanced Non-small-cell Lung Cancer

Background Programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitor monotherapy has been approved as second-line or later therapy in advanced non-small-cell lung cancer (NSCLC). The study aimed to compare the clinical outcomes of PD-1 inhibitor plus chemotherapy with PD-1/PD-L1 inhibitor monotherapy as second-line or later therapy in advanced NSCLC. Methods The clinical data of patients with advanced NSCLC who received PD-1/PD-L1 inhibitors as second-line or later line therapy was retrospectively collected. Patients were assigned to one of the two groups according to the therapeutic modality used: PD-1/PD-L1 inhibitor monotherapy group or PD-1 inhibitor plus chemotherapy combination therapy group. Disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) were evaluated between the two groups. The prognostic effect of the derived neutrophil-to-lymphocyte ratio (dNLR) and lactate dehydrogenase (LDH) on the outcomes was also evaluated. Results From April 2017 to October 2019, a total of 84 patients were enrolled in the current study. Twenty-six patients (PD-1 inhibitor, n = 25; PD-L1 inhibitor, n = 1) received PD-1/PD-L1 inhibitor monotherapy, and fifty-eight patients received PD-1 inhibitor plus chemotherapy. The chemotherapy regimens used were as follows: liposome paclitaxel (n = 15); nab-paclitaxel (n = 12); docetaxel (n = 9); pemetrexed (n = 6); and others (n = 16). The DCR and OS were not significantly different between the two groups. The PFS of the monotherapy group was longer than that of the combination therapy group (mPFS: 9.6 vs. 4.6 months, P = 0.01). Univariate and multivariate analyses suggested that LDH and sex were independent prognostic factors of PFS. In the second-line therapy subgroup of 38 patients, OS and PFS were not significantly different between the two groups. In the subgroup of 46 patients treated beyond the 2nd line, the monotherapy group had a longer PFS (mPFS: 9.6 vs. 4.2 months, P = 0.01). The incidence of any-grade adverse events was not significantly different between the monotherapy group and the combination therapy group (19.2 vs. 18.9%, P = 1.000). One patient in the PD-1 inhibitor plus chemotherapy group died of immune-related pneumonitis. Conclusion The clinical outcomes of PD-1 inhibitor plus chemotherapy as second-line or later therapy were similar to those of PD-1/PD-L1 inhibitor alone in advanced NSCLC.