Miracle-dz/UniFAR-FTUs huggingface dataset:
Peripheral Inflammation and Cognitive Performance in Middle-Aged Adults With and Without Type 2 Diabetes: Results From the ENBIND Study

Midlife Type 2 Diabetes Mellitus (T2DM) is associated with a greater risk of dementia in later life. Peripheral inflammation and its impact on cognition is proposed as one of the pathological mechanisms mediating this link. However, studies have primarily focused on older individuals with established cognitive impairment and a long duration of T2DM. Importantly, knowledge of which individuals with midlife T2DM who are at greatest risk of later cognitive decline is lacking. We examined the cross-sectional relationship between serum levels of 8 pro-inflammatory markers (IL-1β, IL-6, TNF-α, IL-8, MCP-1, CXCL10, IL-12p70, CRP) and performance on a detailed neuropsychological assessment battery in middle-aged adults with uncomplicated T2DM (N = 89; 52 ± 8.1 years, 47% female) and matched healthy controls (N = 50; 52 ± 8.3 years, 59% female). Linear regression was used to analyze associations between serum markers and cognitive performance in the overall cohort, followed by a T2DM∗protein concentration interaction analysis to identify any T2DM-specific effects. We observed a significant T2DM-specific association between serum TNF-α levels and scores on the Paired Associates Learning (PAL) task (β: −3.16, SE: 1.32, p = 0.01, Std. Beta: −0.94), a task with significant working memory demands previously implicated in T2DM-related cognitive dysfunction. However, this did not persist on controlling for multiple testing. We provide exploratory evidence for a significant T2DM-specific relationship between serum TNF-α and memory performance. These findings require further replication and longitudinal analysis with the aim of selecting-out individuals with midlife T2DM at risk of future cognitive decline for potential preventative interventions.
Cardiac Ambulatory Monitoring: New Wireless Device Validated Against Conventional Holter Monitoring in a Case Series

Background: Cardiac arrhythmias are very common but underdiagnosed due to their transient and asymptomatic nature. An optimization of arrhythmia detection would permit to better treat patients and could substantially reduce morbidity and mortality. The SmartCardia ScaAI wireless patch is a novel CE IIa approved, single-lead electrocardiographic (ECG) ambulatory monitor designed for cardiac arrhythmias detection. Hypothesis: The accuracy of the new SmartCardia wireless patch to detect arrhythmias is comparable to the conventional Holter monitoring. Methods: Patients referred for a suspicion of arrhythmia between February and March 2020 were included in the trial. Simultaneous ambulatory ECG were recorded using a conventional 24-h Holter and the SmartCardia. The primary endpoint was the detection of cardiac arrhythmias over the total wear time of the devices, defined as premature atrial contraction (PAC), supraventricular tachycardia ≥3 beats, premature ventricular contraction (PVC), and ventricular tachycardia ≥3 beats. Conduction abnormalities, pause ≥2 s and atrioventricular block (AVB), were also tracked. McNemar's test was used to compare the matched pairs of data from both devices. Results: A total of 40 patients were included in the trial. Over the total wear time, there was no significant difference between the devices for ventricular and supraventricular arrhythmias detection. Pauses and AVB were equally identified by the two devices in three patients. Conclusion: Over the total wear time, the SmartCardia device showed an accuracy to detect arrhythmia similar to the 24-h Holter monitoring: single-lead, adhesive-patch monitoring might become an interesting alternative to the conventional Holter monitoring.
Pharmacological Programming of Endosomal Signaling Activated by Small Molecule Ligands of the Follicle Stimulating Hormone Receptor

Follicle-stimulating hormone receptor (FSHR) is a G protein-coupled receptor (GPCR) with pivotal roles in reproduction. One key mechanism dictating the signal activity of GPCRs is membrane trafficking. After binding its hormone FSH, FSHR undergoes internalization to very early endosomes (VEEs) for its acute signaling and sorting to a rapid recycling pathway. The VEE is a heterogeneous compartment containing the Adaptor Protein Phosphotyrosine Interacting with Pleckstrin homology Domain and Leucine Zipper 1 (APPL1) with distinct functions in regulating endosomal Gαs/cAMP signaling and rapid recycling. Low molecular weight (LMW) allosteric FSHR ligands were developed for use in assisted reproductive technology yet could also provide novel pharmacological tools to study FSHR. Given the critical nature of receptor internalization and endosomal signaling for FSHR activity, we assessed whether these compounds exhibit differential abilities to alter receptor endosomal trafficking and signaling within the VEE. Two chemically distinct LMW agonists (benzamide, termed B3 and thiazolidinone, termed T1) were employed. T1 was able to induce a greater level of cAMP than FSH and B3. As cAMP signaling drives gonadotrophin hormone receptor recycling, rapid exocytic events were evaluated at single event resolution. Strikingly, T1 was able to induce a 3-fold increase in recycling events compared to FSH and two-fold more compared to B3. As T1-induced internalization was only marginally greater, the dramatic increase in recycling and cAMP signaling may be due to additional mechanisms. All compounds exhibited a similar requirement for receptor internalization to increase cAMP and proportion of FSHR endosomes with active Gαs, suggesting regulation of cAMP signaling induced by T1 may be altered. APPL1 plays a central role for GPCRs targeted to the VEE, and indeed, loss of APPL1 inhibited FSH-induced recycling and increased endosomal cAMP signaling. While T1-induced FSHR recycling was APPL1-dependent, its elevated cAMP signaling was only partially increased following APPL1 knockdown. Unexpectedly, B3 altered the dependence of FSHR to APPL1 in an opposing manner, whereby its endosomal signaling was negatively regulated by APPL1, while B3-induced FSHR recycling was APPL1-independent. Overall, FSHR allosteric compounds have the potential to re-program FSHR activity via altering engagement with VEE machinery and also suggests that these two distinct functions of APPL1 can potentially be selected pharmacologically.
Roles of Endovascular Calyx Related Enzymes in Endothelial Dysfunction and Diabetic Vascular Complications

In recent years, the number of diabetic patients has rapidly increased. Diabetic vascular complications seriously affect people’s quality of life. Studies found that endothelial dysfunction precedes the vascular complications of diabetes. Endothelial dysfunction is related to glycocalyx degradation on the surface of blood vessels. Heparanase (HPSE), matrix metalloproteinase (MMP), hyaluronidase (HYAL), hyaluronic acid synthase (HAS), and neuraminidase (NEU) are related to glycocalyx degradation. Therefore, we reviewed the relationship between endothelial dysfunction and the vascular complications of diabetes from the perspective of enzymes.
Comparison Between Blood-Brain Barrier Water Exchange Rate and Permeability to Gadolinium-Based Contrast Agent in an Elderly Cohort

Background: Dynamic contrast-enhanced (DCE) MRI using intravenous injection of gadolinium-based contrast agents (GBCAs) is commonly used for imaging blood-brain barrier (BBB) permeability. Water is an alternative endogenous tracer with limited exchange rate across the BBB. A direct comparison between BBB water exchange rate and BBB permeability to GBCA is missing. The purpose of this study was to directly compare BBB permeability to GBCA (Ktrans and kGad = Ktrans/Vp) and water exchange rate (kw) in a cohort of elderly subjects at risk of cerebral small vessel disease (cSVD). Methods: Ktrans/kGad and kw were measured by DCE-MRI and diffusion prepared pseudo-continuous arterial spin labeling (DP-pCASL), respectively, at 3 Tesla in 16 elderly subjects (3 male, age = 67.9 ± 3.0 yrs) at risk of cSVD. The test-retest reproducibility of kw measurements was evaluated with repeated scans ~6 weeks apart. Mixed effects linear regression was performed in the whole brain, gray matter (GM), white matter (WM), and 6 subcortical brain regions to investigate associations between Ktrans/kGad and test-retest kw. In addition, kw and Ktrans/kGad were compared in normal appearing white matter (NAWM), white matter hyperintensity (WMH) lesions and penumbra. Results: Significant correlation was found between kw and Ktrans only in WM (β = 6.7 × 104, P = 0.036), caudate (β = 8.6 × 104, P = 0.029), and middle cerebral artery (MCA) perforator territory (β = 6.9 × 104, P = 0.009), but not in the whole brain, GM or rest 5 brain regions. Significant correlation was found between kw and kGad in MCA perforator territory (β = 1.5 × 103, P = 0.049), medial-temporal lobe (β = 3.5 × 103, P = 0.032), and hippocampus (β = 3.4 × 103, P = 0.038), but not in the rest brain regions. Good reproducibility of kw measurements (ICC=0.75) was achieved. Ktrans was significantly lower inside WMH than WMH penumbra (16.2%, P = 0.026), and kGad was significantly lower in NAWM than in the WMH penumbra (20.8%, P < 0.001). Conclusion: kw provides a measure of water exchange rate across the BBB with good test-retest reproducibility. The BBB mechanism underlying kw and Ktrans/kGad is likely to be different, as manifested by correlations in only three brain regions for each pair of comparison between kw and Ktrans or kGad.
Genetic Diversity of Phyllanthus emblica From Two Different Climate Type Areas

Phyllanthus emblica L. is a well-known medicinal and edible plant species. Various medicinal compounds in the fruit make it an important medicinal and promising economic material. The plant is widely distributed in Southwestern and Southern China. However, due to massive deforestation and land reclamation as well as deterioration of its natural habitat in recent years, the wild resources of this species have been sharply reduced, and it is rare to see large-scale wild P. emblica forests so far. In order to effectively protect and rationally utilize this species, we investigated the genetic diversity, genetic structure, and population dynamics of 260 individuals from 10 populations of P. emblica sampled from the dry climate area in Yunnan and wet climate area in Guangxi using 20 polymorphic EST-SSR markers. We found high genetic diversity at the species level (He = 0.796) and within populations (He = 0.792), but low genetic differentiation among populations (FST = 0.084). In addition, most genetic variation existed within populations (92.44%) compared with variation among the populations (7.56%). Meanwhile, the NJ tree, STRUCTURE, and hierarchical analysis suggested that the sampled individuals were clustered into two distinct genetic groups. In contrast, the genetic diversity of the dry climate group (He = 0.786, Na = 11.790, I = 1.962) was higher than that of the wet climate group (He = 0.673, Na = 9.060, I = 1.555), which might be attributed to the combined effects of altitude, precipitation, and geographic distance. Interestingly, only altitude and precipitation had significant pure effects on the genetic diversity, and the former was slightly stronger. In addition, DIYABC analysis suggested the effective population size of P. emblica might have contracted in the beginning of the Last Glacial Maximum. These genetic features provided vital information for the conservation and sustainable development of genetic resources of P. emblica, and they also provided new insights and guidelines for ecological restoration and economic development in dry-hot valleys of Yunnan and karst areas in Guangxi.
Impact of Chromosomal Rearrangements on the Interpretation of Lupin Karyotype Evolution

Plant genome evolution can be very complex and challenging to describe, even within a genus. Mechanisms that underlie genome variation are complex and can include whole-genome duplications, gene duplication and/or loss, and, importantly, multiple chromosomal rearrangements. Lupins (Lupinus) diverged from other legumes approximately 60 mya. In contrast to New World lupins, Old World lupins show high variability not only for chromosome numbers (2n = 32–52), but also for the basic chromosome number (x = 5–9, 13) and genome size. The evolutionary basis that underlies the karyotype evolution in lupins remains unknown, as it has so far been impossible to identify individual chromosomes. To shed light on chromosome changes and evolution, we used comparative chromosome mapping among 11 Old World lupins, with Lupinus angustifolius as the reference species. We applied set of L. angustifolius-derived bacterial artificial chromosome clones for fluorescence in situ hybridization. We demonstrate that chromosome variations in the species analyzed might have arisen from multiple changes in chromosome structure and number. We hypothesize about lupin karyotype evolution through polyploidy and subsequent aneuploidy. Additionally, we have established a cytogenomic map of L. angustifolius along with chromosome markers that can be used for related species to further improve comparative studies of crops and wild lupins.
Greenhouse Gas Emissions Dynamics in Restored Fens After In-Situ Oil Sands Well Pad Disturbances of Canadian Boreal Peatlands

In-situ oil extraction activities impact the vast mosaic of boreal wetlands and uplands. Peatland restoration in these regions aims at reestablishing crucial peatland functions, such as peat accumulation and carbon (C) sequestration. In order to assess the success of fen restoration, we evaluated the biogeochemical conditions, the seasonal carbon balances via carbon dioxide (CO2) fluxes and methane (CH4) emissions, and addressed the global warming potential following different restoration techniques at two restored in-situ oil sands well pads, during two consecutive growing seasons. Restoration work involved: 1) the partial or complete removal of introduced well pad construction materials, and spontaneous revegetation, or 2) the partial removal of foreign clay, in addition to reintroduction of typical fen plant species such as Larix laricina, Salix lutea and Carex aquatilis. Comparisons were done with regional reference ecosystems (REF) consisting of three peatlands: a wooded bog, a wooded rich fen and a wooded extreme-rich fen. While the average electric conductivity of restored sectors (946 μS cm−1) was higher compared to REF (360 μS cm−1), the pH was quite similar (pH 5.8 REF, pH 6 restored). Dissolved organic carbon concentration was lower in all restored sectors (5–11 mg L-1 restored sectors, 15–35 mg L-1 REF), presumably due to the still incomplete recovery of vegetation and lower organic matter content associated with remnant well pad material. Re-establishment of shrub and brown moss species improved significantly the C uptake. However, the active introduction of plant species was no crucial restoration step, in order to return species beneficial for C uptake. Restoration treatments that were leveled closest to the surrounding REF showed the most similar seasonal C balance to REF. In shallow open water areas resulting from the complete removal of all construction materials, we measured the highest methane emissions making these flooded sites net C sources to the atmosphere with elevated global warming potential. The partial removal of the well pad’s mineral soil to near the water table level and the surface elevation of the surrounding ecosystem seems to be the most effective site management method to sequester carbon efficiently. However, further research is needed to evaluate the suitability of this restoration method for the recovery of biodiversity and possible impacts of residual foreign materials on fen ecosystems.
Disentangling the Properties of Human Evaluation Methods: A Classification System to Support Comparability, Meta-Evaluation and Reproducibility Testing

Current standards for designing and reporting human evaluations in NLP mean it is generally unclear which evaluations are comparable and can be expected to yield similar results when applied to the same system outputs. This has serious implications for reproducibility testing and meta-evaluation, in particular given that human evaluation is considered the gold standard against which the trustworthiness of automatic metrics is gauged. %and merging others, as well as deciding which evaluations should be able to reproduce each other’s results. Using examples from NLG, we propose a classification system for evaluations based on disentangling (i) what is being evaluated (which aspect of quality), and (ii) how it is evaluated in specific (a) evaluation modes and (b) experimental designs. We show that this approach provides a basis for determining comparability, hence for comparison of evaluations across papers, meta-evaluation experiments, reproducibility testing.
Comparative Genome Analyses of 18 Verticillium dahliae Tomato Isolates Reveals Phylogenetic and Race Specific Signatures

Host resistance is one of the few strategies available to combat the soil borne pathogenic fungus Verticillium dahliae. Understanding pathogen diversity in populations is key to successfully deploying host resistance. In this study the genomes of 18 V. dahliae isolates of races 1 (n = 2), 2 (n = 4), and 3 (n = 12) from Japan, California, and North Carolina were sequenced and mapped to the reference genome of JR2 (from tomato). The genomes were analyzed for phylogenetic and pathogen specific signatures to classify specific strains or genes for future research. Four highly clonal lineages/groups were discovered, including a lineage unique to North Carolina isolates, which had the rare MAT1-1 mating type. No evidence for recombination between isolates of different mating types was observed, even in isolates of different mating types discovered in the same field. By mapping these 18 isolates genomes to the JR2 reference genome, 193 unique candidate effectors were found using SignalP and EffectorP. Within these effectors, 144 highly conserved effectors, 42 mutable effectors (truncated or present in some isolates but absent in others), and 7 effectors present in highly variable regions of the chromosomes were discovered. Of the 144 core effectors, 21 were highly conserved in V. alfalfae and V. longisporum, 7 of which have no known function. Within the non-core effectors 30 contained large numbers of non-synonymous mutations, while 15 of them contained indels, frameshift mutations, or were present on highly variable regions of the chromosome. Two of these highly variable region effectors (HVREs) were only present in race 2 isolates, but not in race 3 isolates. The race 1 effector Ave1 was also present in a highly variable region. These data may suggest that these highly variable regions are enriched in race determinant genes, consistent with the two-speed genome hypothesis.
IGLR-2, a Leucine-Rich Repeat Domain Containing Protein, Is Required for the Host Defense in Caenorhabditis elegans

Enterohemorrhagic Escherichia coli (EHEC), a human pathogen, also infects Caenorhabditis elegans. We demonstrated previously that C. elegans activates the p38 MAPK innate immune pathway to defend against EHEC infection. However, whether a C. elegans pattern recognition receptor (PRR) exists to regulate the immune pathway remains unknown. PRRs identified in other metazoans contain several conserved domains, including the leucine-rich repeat (LRR). By screening a focused RNAi library, we identified the IGLR-2, a transmembrane protein containing the LRR domain, as a potential immune regulator in C. elegans. Our data showed that iglr-2 regulates the host susceptibility to EHEC infection. Moreover, iglr-2 is required for pathogen avoidance to EHEC. The iglr-2 overexpressed strain, which was more resistant to EHEC originally, showed hypersusceptibility to EHEC upon knockdown of the p38 MAPK pathway. Together, our data suggested that iglr-2 plays an important role in C. elegans to defend EHEC by regulating pathogen-avoidance behavior and the p38 MAPK pathway.
Evaluation of Airway Measurements in Class II Patients Following Functional Treatment.

Objective This study aimed to evaluate the effect of fixed and removable functional treatment on pharyngeal airway measurements in class II patients. Methods In this study, patients treated with fixed (Forsus Fatigue Resistant Device-FRD) and removable (twin-block-TWB) appliances were included (n=15, eight females, seven males in each group). These groups were compared with untreated individuals as the control group (n=10). The mean age of individuals was 13.22±2.39 years. Initial and post-treatment cephalometric radiographs were digitized, and the sagittal pharyngeal airway changes were evaluated. The pharyngeal airway was divided into the nasopharynx, oropharynx, and hypopharynx. The one-way ANOVA, Kruskal-Wallis test, and paired samples t-test were used for statistical analyses. Results At the initial values, no statistically significant difference was observed between the groups. Only the ANB values differed between the groups (p<0.05). Although the skeletal effects of removable and fixed treatment were not exactly the same, the changes of the airway dimensions were similar. Conclusion The TWB and FRD appliances lead to an increase in nasopharynx, oropharynx, and hypopharynx sagittal dimensions. However, in terms of the effect on airway sagittal dimensions, there was no significant difference between treatment groups and the control group.
Lessons Learned Comparing Immune System Alterations of Bacterial Sepsis and SARS-CoV-2 Sepsis

Background Bacterial sepsis has been used as a prototype to understand the pathogenesis of severe coronavirus disease 2019 (COVID-19). In addition, some management programs for critically ill COVID-19 patients are also based on experience with bacterial sepsis. However, some differences may exist between these two types of sepsis. Methods This retrospective study investigated whether there are differences in the immune system status of these two types of sepsis. A total of 64 bacterial sepsis patients and 43 patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sepsis were included in this study. Demographic data were obtained from medical records. Laboratory results within 24 h after the diagnosis of sepsis were provided by the clinical laboratory. Results The results of blood routine (neutrophil, lymphocyte, and monocyte counts), infection biomarkers (C-reactive protein, ferritin, and procalcitonin levels), lymphocyte subset counts (total T lymphocyte, CD4+ T cell, CD8+ T cell, B cell, and NK cell counts), and lymphocyte subset functions (the proportions of PMA/ionomycin-stimulated IFN-γ positive cells in CD4+, CD8+ T cells, and NK cells) were similar in bacterial sepsis patients and SARS-CoV-2 sepsis patients. Cytokine storm was milder, and immunoglobulin and complement protein levels were higher in SARS-CoV-2 sepsis patients. Conclusions There are both similarities and differences in the immune system status of bacterial sepsis and SARS-CoV-2 sepsis. Our findings do not support blocking the cytokine storm or supplementing immunoglobulins in SARS-CoV-2 sepsis, at least in the early stages of the disease. Treatments for overactivation of the complement system and lymphocyte depletion may be worth exploring further.