Miracle-dz/UniFAR-FTUs huggingface dataset:
Exaggerated hypoxic vascular breakdown in aged brain due to reduced microglial vasculo‐protection

In a recent study of young mice, we showed that chronic mild hypoxia (CMH, 8% O2) triggers transient blood–brain barrier (BBB) disruption, and that microglia play an important vasculo‐protective function in maintaining BBB integrity. As hypoxia is a common component of many age‐related diseases, here we extended these studies to aged mice and found that hypoxia‐induced vascular leak was greatly amplified (5‐fold to 10‐fold) in aged mice, being particularly high in the olfactory bulb and midbrain. While aged mice showed no obvious difference in the early stages of hypoxic angiogenic remodeling, the compensatory increase in vascularity and vessel maturation was significantly delayed. Compared with young brain, microglia in the normoxic aged brain were markedly activated, and this was further increased under hypoxic conditions, but paradoxically, this correlated with reduced vasculo‐protection. Microglial depletion studies showed that microglial still play an important vasculo‐protective role in aged brain, but interestingly, partial attenuation of microglial activation with minocycline resulted in fewer vascular leaks and reduced loss of endothelial tight junction proteins. Taken together, these findings suggest that increased BBB disruption in hypoxic aged mice can be explained both by a delayed vascular remodeling response and reduced microglial vasculo‐protection. Importantly, they show that overly activated microglia in the aged brain are less effective at maintaining vascular integrity, though this can be improved by reducing microglial activation with minocycline, suggesting therapeutic potential for enhancing BBB integrity in the hypoxia‐predisposed elderly population.
Valency Rearrangement Phenomena and Their Limitations with Polish ‘Clear’ Verbs

The paper is concerned with very basic questions concerning the nature of lexical representation of verbs which take part in valency rearrangement alternations and the contribution of grammar to the morpho-syntactic phenomena involved in this rearrangement. We analyze a group of such valency rearrangement verbs which are referred to as ‘clear’ verbs in Polish and compare their behaviour and properties with the corresponding material from English, Greek and Hebrew. In particular we try to establish which properties enable some verbs to undergo the alternation, while some others accept only one of the alternants. We propose lexical representations for alternating and non-alternating verbs and establish a connection between these representations and the alternating propensity of prefixed verbs in Polish.
CGDD: Multiview Graph Clustering via Cross-Graph Diversity Detection

Multiview graph clustering has emerged as an important yet challenging technique due to the difficulty of exploiting the similarity relationships among multiple views. Typically, the similarity graph for each view learned by these methods is easily corrupted because of the unavoidable noise or diversity among views. To recover a clean graph, existing methods mainly focus on the diverse part within each graph yet overlook the diversity across multiple graphs. In this article, instead of merely considering the sparsity of diversity within a graph as previous methods do, we incline to a more suitable consideration that the diversity should be sparse across graphs. It is intuitive that the divergent parts are supposed to be inconsistent with each other, otherwise it would contradict the definition of diversity. By simultaneously and explicitly detecting the multiview consistency and cross-graph diversity, a pure graph for each view can be expected. The multiple pure graphs are further fused to the structured consensus graph with exactly $r$ connected components where $r$ is the number of clusters. Once the consensus graph is obtained, the cluster label to each instance can be directly allocated as each connected component precisely corresponds to an individual cluster. An alternating iterative algorithm is designed to optimize the subtasks of learning the similarity graphs adaptively, detecting the consistency as well as cross-graph diversity, fusing the multiple pure graphs, and assigning cluster label to each instance in a mutual reinforcement manner. Extensive experimental results on several benchmark multiview datasets demonstrate the effectiveness of our model, in comparison to several state-of-the-art algorithms.
Plasma and muscle tissue disposition of enrofloxacin in Nile tilapia (Oreochromis niloticus) after intravascular, intraperitoneal, and oral administrations

Abstract The aim of the study was to investigate the plasma and muscle pharmacokinetic of enrofloxacin (ENR) and its active metabolite ciprofloxacin (CIP) in Nile tilapia (Oreochromis niloticus) following single intravascular (IV), intraperitoneal (IP), or oral (PO) administration at 30 ± 1 °C. In this study, 234 healthy Nile tilapia (120–150 g) were used. The fish received a single IV, IP, or PO treatment of ENR at a dose of 10 mg/kg. The plasma and muscle tissue concentrations of ENR and CIP were measured using high–performance liquid chromatography with fluorescence detection and were evaluated using non–compartmental analysis. The elimination half–life, volume of distribution at steady state, and total body clearance of ENR were 21.7 h, 2.69 L/kg, and 0.09 L/h/kg, respectively. The peak plasma concentrations of ENR after IP or PO administration were 6.11 and 4.21 µg/mL at 0.25 and 2 h, respectively. The bioavailability of ENR for IP or PO routes was 78% and 86%, respectively. AUC(0–120)muscle/AUC(0–120)plasma ratios following the IV, IP, or PO administrations were 1.43, 1.49, and 1.07, respectively. CIP was detected after all routes, but the AUC0–last ratios of CIP to ENR were <1.0% for plasma and muscle. ENR was detected up to 120 h following the IV, IP, or PO administrations. The long residence time of ENR after single IV, IP, or PO administration ensured the plasma concentration was ≥1 × MIC for bacteria with threshold MIC values of 0.92, 0.72, and 0.80 μg/mL over the whole 120 h observed. However, further studies are necessary to determine the optimum pharmacokinetic/pharmacodynamics data of ENR for the treatment of infections caused by susceptible bacteria in tilapia.
Circ_0005615 contributes to the progression and Bortezomib resistance of multiple myeloma by sponging miR-185-5p and upregulating IRF4

Circular RNAs (circRNAs) have been shown to play critical regulatory roles in multiple myeloma progression. Here, we aimed to explore the biologic role of circ_0005615 in multiple myeloma progression and its associated mechanism. Cell counting kit-8 assay was conducted to analyze the bortezomib resistance and proliferation of multiple myeloma cells. Cell proliferation was also analyzed by 5-Ethynyl-2’-deoxyuridine incorporation and flow cytometry assays. Cell apoptosis was assessed by flow cytometry. The interaction between microRNA-185-5p (miR-185-5p) and circ_0005615 or interferon regulatory factor 4 (IRF4) was verified by the dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. A xenograft tumor model was established in non-obese diabetic/server combined immune-deficiency mice to analyze the roles of circ_0005615 in tumor growth and bortezomib resistance. Circ_0005615 was upregulated in multiple myeloma tissues and cell lines. Circ_0005615 knockdown restrained the bortezomib resistance and proliferation and induced the apoptosis of multiple myeloma cells. Circ_0005615 acted as a molecular sponge for miR-185-5p, and the antitumor effects mediated by circ_0005615 knockdown were reversed by silencing miR-185-5p. IRF4 was confirmed as a direct target of miR-185-5p, and miR-185-5p overexpression-induced antitumor influences could be counteracted by IRF4 overexpression. Circ_0005615 could positively regulate IRF4 expression by sponging miR-185-5p in multiple myeloma cells. Circ_0005615 knockdown suppressed the growth and bortezomib resistance of xenograft tumors in vivo. Circ_0005615 contributed to the malignant progression and bortezomib resistance of multiple myeloma through mediating miR-185-5p/IRF4 signaling.
-adic estimates for exponential sums and the theorem of

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Evaluation of SEAWAVE–QEX in a high agricultural intensity catchment in Belgium

Pesticide surface water monitoring data have rarely been used as the only quantitative measure of exposure because the available monitoring data for most pesticides has not been considered robust enough for direct use in pesticide exposure assessments due to infrequent sampling. The cost of daily sample collection and analysis prohibits frequent sampling for most monitoring programs. In this context, a common question raised in assessments is how likely peak concentrations (i.e., annual maxima) may be missed if sampling intervals are longer than daily. The US Geological Survey developed the statistical model “seasonal wave with streamflow adjustment and extended capability” (SEAWAVE–QEX) to address the need to estimate infrequently occurring pesticide concentrations, such as annual maximum daily concentrations, for sites with nondaily monitoring data. This study compares the results of two postprocessing methods and evaluates the capability of SEAWAVE–QEX to estimate annual maximum concentrations of three commonly used herbicides and one metabolite in a catchment in Belgium. The study concludes that the appropriateness of using SEAWAVE–QEX to estimate annual maximum concentrations depends on pesticide characteristics and use and that the model can be particularly sensitive to nonflow correlated exposure events (e.g., point source contributions or drift). Integr Environ Assess Manag 2023;19:513–526. © 2022 Stone Environmental and Bayer AG Crop Science Division. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).
Biallelic loss‐of‐function mutations in SEPTIN4 (C17ORF47), encoding a conserved annulus protein, cause thin midpiece spermatozoa and male infertility in humans

Asthenoteratozoospermia is the primary cause of infertility in humans. However, the genetic etiology remains largely unknown for those suffering from severe asthenoteratozoospermia caused by thin midpiece defects. In this study, we identified two biallelic loss‐of‐function variants of SEPTIN4 (previously SEPT4) (Patient 1: c.A721T, p.R241* and Patient 2: c.C205T, p.R69*) in two unrelated individuals from two consanguineous Chinese families. SEPT4 is a conserved annulus protein that is critical for male fertility and the structural integrity of the sperm midpiece in mice. SEPT4 mutations disrupted the formation of SEPT‐based annulus and localization of SEPTIN subunits in sperms from patients. The ultrastructural analysis demonstrated striking thin midpiece spermatozoa defects owing to annulus loss and disorganized mitochondrial sheath. Immunofluorescence and immunoblotting analyses of the mitochondrial sheath proteins TOMM20 and HSP60 further indicated that the distribution and abundance of mitochondria were impaired in men harboring biallelic SEPT4 variants. Additionally, we found that the precise localization of SLC26A8, a testis‐specific anion transporter that colocalizes with SEPT4 at the sperm annulus, was missing without SEPT4. Moreover, the patient achieved a good pregnancy outcome following intracytoplasmic sperm injection. Overall, our study demonstrated for the first time that SEPT4 variants that induced thin midpiece spermatozoa defects were directly associated with human asthenoteratozoospermia.
Association of omega-3 and omega-6 fatty acid intake with leukocyte telomere length in US males.

BACKGROUND Omega-3 (n-3) and omega-6 (n-6) fatty acids may contribute to oxidative stress and inflammation, which are related to telomere shortening. Evidence supporting an association between intake of n-3 or n-6 fatty acids and leukocyte telomere length (LTL) in males has been limited. OBJECTIVE We conducted a cross-sectional study to examine the associations of total or individual n-3 or total n-6 fatty acid intake with LTL in US males. METHODS We included 2,494 US males with LTL measurement from 4 nested case-control studies within the Health Professionals Follow-up Study. Individuals with previous histories of cancers, diabetes, and cardiovascular diseases at or prior to blood collection were excluded. Blood collection was performed between 1993 and 1995, and relevant information including n-3 and n-6 intake was collected in 1994 by questionnaire. The LTL was log-transformed and Z scores of the LTL were calculated for statistical analyses by standardizing the LTL in comparison with the mean within each selected nested case-control study. RESULTS We found that consumption of docosahexaenoic acid (DHA) was positively associated with LTL. In the multivariable-adjusted model, compared to individuals who had the lowest intake of DHA (i.e., first quartile group), the percentage differences [95% confidence intervals (CIs)] of LTL were -3.7 (-13.7, 7.5), 7.0 (-4.3, 19.7), and 8.2 (-3.5, 21.3) for individuals in the second, third, and fourth quartiles of consumption, respectively (P for trend = 0.0498). We did not find significant associations between total n-3 or total n-6 fatty acid intakes and LTL. Additionally, we found that males who consumed canned tuna had longer LTL than those who did not; in the multivariable-adjusted model, the percentage difference (95% CI) of LTL was 10.5 (1.3, 20.4) (P value = 0.02). CONCLUSIONS Our results suggest that higher intakes of DHA and canned tuna consumption are associated with longer LTL.
Clusters of Rapid HIV Transmission Among Gay, Bisexual, and Other Men Who Have Sex with Men — United States, 2018–2021

Gay, bisexual, and other men who have sex with men (MSM) accounted for 68% of new HIV diagnoses in the United States in 2020* (1). Despite advances in treatment and prevention, HIV transmission among MSM continues, in part because of stigma and barriers to accessing prevention and treatment services (2). HIV cluster detection and response, a core strategy of the Ending the HIV Epidemic in the United States initiative,† is an important tool for early identification and response to rapid HIV transmission, including among MSM. To better understand rapid HIV transmission among this population, CDC characterized large HIV molecular clusters detected using analysis of HIV-1 nucleotide sequence data from the National HIV Surveillance System (NHSS). § Among 38 such clusters first detected during 2018-2019 that had grown to include more than 25 persons by December 2021, 29 occurred primarily among MSM. Clusters primarily among MSM occurred in all geographic regions, and 97% involved multiple states. Clusters were heterogeneous in age, gender identity, and race and ethnicity and had rapid growth rates (median = nine persons added per year). The overall transmission rate at cluster detection was 22 transmission events per 100 person-years, more than six times that of previously estimated national transmission rates (3). Most clusters of rapid HIV transmission occur among MSM. Swift response to reach diverse persons and communities with early, tailored, and focused interventions is essential to reducing HIV transmission (4).
Comprehensive review on natural pharmacophore tethered 1,2,3‐triazoles as active pharmaceuticals

The privileged 1,2,3‐triazole scaffold is drawing researcher's attention due to its widespread applications in diverse fields such as drug discovery (e.g., carboxyamidotriazole), organic synthesis (click‐reaction template), polymeric materials (e.g., triazolamer), supramolecular receptors (e.g., triazolophane), fluorescent materials (e.g., metal–organic frameworks), and agricultural sectors (e.g., fungicides). Various 1,2,3‐triazole persuasion modules are also currently available in the market that have multiple assets such as active pharmaceuticals and agricultural purposes. Owed to the highly consistent and firmest synthesis approach, that is, click reaction of various azides and acetylene derivatives by copper (I)‐catalyzed 1,3‐dipolar cycloaddition (CuAAC), highly functionalized 1,2,3‐triazoles are prepared in scalar yields for drug discovery. Given the importance of 1,2,3‐triazole chemistry, the present review focuses specifically on the synthesis of structurally diverse 1,2,3‐triazoles linked to natural pharmacophores and their biological importance. Furthermore, the dual/multi‐pharmacophores assimilated 1,2,3‐triazoles have listed interesting biological activities that could be valuable as future drug leads. In addition, this comprehensive review can serve as a template for the development of new diverse scaffolds that will ensure for new therapeutic approaches for the existing myriad diseases and disorders.
Efficacy of Oral Psyllium in Pediatric Irritable Bowel Syndrome: A Double-Blind Randomized Control Trial

Objective: Pediatric irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder with variable response to various therapeutic agents. Psyllium has been proven to be effective in adults; however, there is no study in children. The objective of this study is to evaluate the efficacy of psyllium husk as compared to placebo in pediatric IBS patients. Methods: In this double-blind randomized controlled trial, 43 children were assigned to psyllium arm (Group A) and 38 into placebo arm (Group B). Severity is assessed at baseline and after 4 weeks of treatment using IBS severity scoring scale (IBS-SSS) and classified into mild, moderate, and severe categories. Categorical data was compared with chi-square test and paired categorical variable was compared with McNemer test. Results: Mean ages (±SD; in years) of Groups A and B were 9.87 (2.7) and 9.82 (3.17), respectively, with median duration of illness of 12 months. At baseline, type, severity, and parameters (IBS-SSS) of IBS were equally distributed in 2 groups. There was a significant reduction in median interquartile range (IQR) of total IBS-SSS in psyllium versus placebo [75 (42.5–140) vs 225 (185–270); P < 0.001] at 4 weeks. Similarly 43.9% in Group A versus 9.7% in Group B attained remission [IBS-SSS < 75 (P < 0.0001)]. The mean difference in IBS-SSS between Group A and Group B was −122.85 with risk ratio of 0.64 (95% CI; 0.42–0.83; P= 0.001) and absolute risk reduction of 32% (NNT = 3). Conclusions: Psyllium husk is effective for the therapy of pediatric IBS when compared with placebo in short term.
Community Assembly of Fungi and Bacteria along Soil-Plant Continuum Differs in a Zoige Wetland

Elucidating the community microbiome assemblage alone the soil-plant continuum will help to better understand the biodiversity maintenance and ecosystem functioning. Here, we examined the fungal and bacterial communities in rhizosphere soil, roots, and leaves of two dominant AM plants and a non-AM plant in Zoige Wetland. ABSTRACT Distinct plant associated microbiomes live in rhizosphere soil, roots, and leaves. However, the differences in community assembly of fungi and bacteria along soil-plant continuum are less documented in ecosystems. We examined fungal and bacterial communities associated with leaves, roots, and rhizosphere soil of the dominant arbuscular mycorrhizal (AM) plants Taraxacum mongolicum and Elymus nutans and non-AM plant Carex enervis in the Zoige Wetland by using high throughput sequencing techniques. The operational taxonomic unit (OTU) richness of fungi and bacteria was significantly higher in rhizosphere soil than in roots and leaves, and their community compositions were significantly different in the rhizosphere soil, roots, and leaves in each plant species. The co-occurrence network analysis revealed that the sensitive fungal and bacterial OTUs with various taxonomic positions were mainly clustered into different modules according to rhizosphere soil, roots, and leaves in each plant species. Along the soil-plant continuum, the rhizosphere soil pool contributed more source on bacterial than on fungal communities in roots and leaves of the three plant species, and more source on bacterial and fungal communities in leaves of T. mongolicum and E. nutans compared with C. enervis. Furthermore, the root pool contributed more source on bacterial than on fungal communities in leaves of T. mongolicum and E. nutans but not that of C. enervis. This study highlights that the host plant selection intensity is higher in fungal than in bacterial communities in roots and leaves from rhizosphere soil in each plant species, and differs in fungal and bacterial communities along the soil-plant continuum in AM plants T. mongolicum and E. nutans and non-AM plant C. enervis in the Zoige Wetland. IMPORTANCE Elucidating the community microbiome assemblage alone the soil-plant continuum will help to better understand the biodiversity maintenance and ecosystem functioning. Here, we examined the fungal and bacterial communities in rhizosphere soil, roots, and leaves of two dominant AM plants and a non-AM plant in Zoige Wetland. We found that along the soil – plant continuum, host plant selection intensity is higher in fungal than in bacterial communities in roots and leaves from rhizosphere soil in each plant species, and differs in fungal and bacterial communities in the AM- and non-AM plants. This is the first report provides evidence of different assembly patterns of fungal and bacterial communities along the soil-plant continuum in the AM- and non-AM plants in the Zoige Wetland.
Is Corneal Subbasal Nerve Loss Associated With Meibomian Gland Loss in Inactive Mild and Moderate-to-Severe Graves’ Ophthalmopathy?

Purpose: To evaluate meibomian gland and subbasal nerve plexus parameters in Graves’ Ophthalmopathy (GO) and association of meibomian gland loss with corneal subbasal nerve plexus loss. Methods: Fifty-two eyes of 52 mild and moderate-to-severe GO patients and 32 eyes of 32 healthy controls were enrolled. The meibomian gland dropout area (MGDA) and meibography scores were evaluated using noncontact meibography. In vivo confocal microscopy of corneal subbasal nerve plexus were conducted. ACCMetrics was used to obtain corneal parameters. Results: Compared with healthy subjects, GO patients had worse upper and lower eyelid MGDA (p < 0.001, for all) and upper, lower and total meibography scores (p < 0.001, p = 0.001, and p < 0.001, respectively). Eyelid margin scores were worse in the GO group (p < 0.001) and showed correlation with all noncontact meibography parameters (p < 0.001 for all). All corneal subbasal nerve parameters were significantly lower in the GO group compared with the controls (p < 0.05 for all). Subbasal nerve parameters of GO patients did not reveal a correlation with MGDA and meibography scores but showed correlations with ocular surface disease index score and Schirmer I test (r = –0.304; p = 0.042 and r = 0.336; p = 0.021, respectively). Conclusion: Meibomian gland and corneal nerve loss could be observed even in the inactive phase and mild GO. The lack of a correlation between meibomian gland loss and subbasal nerve loss suggests that meibomian gland loss is not a significant additional component in the pathogenesis of subbasal nerve damage in GO. Furthermore, our study revealed new evidence regarding the use of eyelid margin score to represent meibomian gland loss in GO. MG and subbasal nerve loss could be observed even in the inactive and mild GO. MG loss did not appear to correlate with nerve loss, postulating against MG loss as a significant additional factor in the pathogenesis of nerve damage in GO.