Miracle-dz/UniFAR-FTUs huggingface dataset:
Loss of PKD1/polycystin-1 impairs lysosomal activity in a CAPN (calpain)-dependent manner

ABSTRACT Mutations in the PKD1 gene result in autosomal dominant polycystic kidney disease (ADPKD), the most common monogenetic cause of end-stage renal disease (ESRD) in humans. Previous reports suggested that PKD1, together with PKD2/polycystin-2, may function as a receptor-cation channel complex at cilia and on intracellular membranes and participate in various signaling pathways to regulate cell survival, proliferation and macroautophagy/autophagy. However, the exact molecular function of PKD1 and PKD2 has remained enigmatic. Here we used Pkd1-deficient mouse inner medullary collecting duct cells (mIMCD3) genetically deleted for Pkd1, and tubular epithelial cells isolated from nephrons of doxycycline-inducible conditional pkd1fl/fl;Pax8rtTA;TetOCre+ knockout mice to show that the lack of Pkd1 caused diminished lysosomal acidification, LAMP degradation and reduced CTSB/cathepsin B processing and activity. This led to an impairment of autophagosomal-lysosomal fusion, a lower delivery of ubiquitinated cargo from multivesicular bodies (MVB)/exosomes to lysosomes and an enhanced secretion of unprocessed CTSB into the extracellular space. The TFEB-dependent lysosomal biogenesis pathway was however unaffected. Pkd1-deficient cells exhibited increased activity of the calcium-dependent CAPN (calpain) proteases, probably due to a higher calcium influx. Consistent with this notion CAPN inhibitors restored lysosomal function, CTSB processing/activity and autophagosomal-lysosomal fusion, and blocked CTSB secretion and LAMP degradation in pkd1 knockout cells. Our data reveal for the first time a lysosomal function of PKD1 which keeps CAPN activity in check and ensures lysosomal integrity and a correct autophagic flux. Abbreviations: acCal: acetyl-calpastatin peptide; ADPKD: autosomal dominant polycystic kidney disease; CI-1: calpain inhibitor-1; CQ: chloroquine; Dox: doxycycline; EV: extracellular vesicles; EXO: exosomes; LAMP1/2: lysosomal-associated membrane protein 1/2; LGALS1/GAL1/galectin-1: lectin, galactose binding, soluble 1; LMP: lysosomal membrane permeabilization; mIMCD3: mouse inner medullary collecting duct cells; MV: microvesicles; MVB: multivesicular bodies; PAX8: paired box 8; PKD1/polycystin-1: polycystin 1, transient receptor potential channel interacting; PKD2/polycystin-2: polycystin 2, transient receptor potential cation channel; Tet: tetracycline; TFEB: transcription factor EB; VFM: vesicle-free medium; WT: wild-type.
Utility of contrast-enhanced ultrasound in differential diagnosis of adrenal tumors in dogs

This prospective case study aimed to clarify the clinical significance of contrast-enhanced ultrasound (CEUS) for the differential diagnosis of canine adrenal tumors. Forty-three client-owned dogs with adrenal tumors were included. All dogs underwent CEUS, which was evaluated qualitatively and quantitatively. The peak signal intensity (PI), time to peak signal intensity (TPI), mean transit time (MTT), upslope, and downslope were calculated for each time-intensity curve. The histopathological diagnosis of each resected mass was compared with the CEUS findings and parameters. Enhancement distribution, vascularity, tortuous nourishing vessels, enhancement pattern, and late-phase enhancement did not differ significantly between adrenal cortical adenoma (CA), adenocarcinoma (CAC), and pheochromocytoma (PHEO) in qualitative assessment. In PHEO, the TPI was significantly more rapid compared with that in CA (P=0.0287) and CAC (P=0.0404). The MTT in PHEO was significantly shorter than that in CA (P=0.0016) and CAC (P=0.0003). Upslope in PHEO was larger than that in CAC (P=0.0406). Downslope in PHEO was significantly larger than that in CA (P=0.0048) and CAC (P=0.0018). A receiver operating characteristic curve analysis demonstrated that the area under the MTT curve yielded 0.91 for distinguishing PHEO from adrenocortical tumors in dogs; an MTT cut-off value less than 6,225 msec yielded a sensitivity of 69%, specificity of 94%, and likelihood ratio of 12.46. CEUS appears to be clinically applicable for the differential diagnosis between cortical and medullary origins of primary adrenal tumors in dogs.
Mental Component Score (MCS) from Health-Related Quality of Life Predicts Incidence of Dementia in U.S. Males

The Medical Outcomes Study Questionnaire Short Form 36 health survey (SF-36) measures health-related quality of life (HRQoL) from the individual’s point of view and is an indicator of overall health status. To examine whether HRQoL shows differential changes over time prior to dementia onset and investigate whether HRQoL predicts incidence of dementia. Prevention of Alzheimer’s Disease (AD) by Vitamin E and Selenium (PREADViSE) trial, which recruited 7,547 non-demented men between 2002 and 2009. A subset of 2,746 PREADViSE participants who completed up to five SF-36 assessments at annual visits was included in the current analysis. Secondary data analysis of PREADViSE data. A subset of 2,746 PREADViSE participants who completed up to five SF-36 assessments at annual visits was included in the current analysis. Two summary T scores were generated for analysis: physical component score (PCS) and mental component score (MCS), each with a mean of 50 (standard deviation of 10); higher scores are better. Linear mixed models (LMM) were applied to determine if mean component scores varied over time or by eventual dementia status. Cox proportional hazards regression was used to determine if the baseline component scores were associated with dementia incidence, adjusting for baseline age, race, APOE-4 carrier status, sleep apnea, and self-reported memory complaint at baseline. The mean baseline MCS score for participants who later developed dementia (mean+ SD: 53.9±9.5) was significantly lower than for those participants who did not develop dementia during the study (mean±SD: 56.4±6.5; p = 0.005). Mean PCS scores at baseline (dementia: 49.3±7.9 vs. non-dementia: 49.8±7.8) were not significantly different (p = 0.5) but LMM analysis showed a significant time effect. For MCS, the indicator for eventual dementia diagnosis was significantly associated with poorer scores after adjusting for baseline age, race, and memory complaint. Adjusted for other baseline risk factors, the Cox model showed that a 10-unit increase in MCS was associated with a 44% decrease in the hazard of a future dementia diagnosis (95% CI: 32%-55%). The SF-36 MCS summary score may serve as a predictor for future dementia and could be prognostic in longitudinal dementia research.
Forests of the Harvey N. Ott Preserve

Quantitative data for trees, saplings, tree seedlings, shrubs, herbs, and environmental characteristics were collected in seven forest stands in the Harvey N. Ott Preserve. , Calhoun Co., Michigan. Two lowland stands were sampled utilizing standing dead elms and live trees only to assess the impact of Dutch elm disease. Surveyors' records were examined to reconstruct the presettlement vegetation. A two- dimensional ordination, based on the densities and basal area per acre of 13 tree species, was used to illustrate canopy structure, and frequency values for 12 shrub species and 29 herb species were used to demonstrate subcanopy structure. The presettlement upland vegetation was oak savanna whereas the present upland vegetation is second-growth oak forests. The effect of past and recent fires, soil water retaining capacity, and pH on forest development is discussed. Larix laricina had a broader range in the lowland vegetation during presettlement times than at present. Ulmus americana is now rapidly disappearing due to Dutch elm disease. Changes in the lowland vegetation are correlated with changes in drain- age patterns, depth to water table, and disease.
Applicability of capillary electrophoresis-frontal analysis for displacement studies: effect of several drugs on L-tryptophan and lidocaine binding to human serum albumin.

The effective concentration of a drug in the blood, i.e. the concentration of a free drug in the blood, is influenced by the strength of drug binding onto plasma proteins. Besides its efficacy, these interactions subsequently influence the liberation, absorption, distribution, metabolism, excretion and toxicological properties of the drug. It is important to not only determine the binding strength and stoichiometry, but also the binding site of a drug on the plasma protein molecule, because the co-administration of drugs with the same binding site can affect the above-mentioned concentration and as a result the pharmacological behaviour of the drugs and lead to side effects caused by the change in free drug concentration, its toxicity. In this study, the binding characteristics of six drugs with human serum albumin, the most abundant protein in human plasma, were determined by capillary electrophoresis-frontal analysis, and the obtained values of binding parameters were compared with the literature data. The affect of several drugs and site markers on the binding of L-tryptophan and lidocaine to human serum albumin was investigated in subsequent displacement studies which thus demonstrated the usability of capillary electrophoresis as an automated high-throughput screening method for drug-protein binding studies. This article is protected by copyright. All rights reserved.
Porifera (sponges) of Mermaid, Scott and Seringapatam Reefs, north Western Australia.

A quantitative survey documenting the diversity and abundance of sponges at Mermaid, Scott and Seringapatam Reefs, north Western Australia, was conducted in September 2006. Four reef habitats (fore reef slope, channel, lagoon and intertidal reef flat) were surveyed by recording numbers of sponge individuals on replicate transects, providing baseline data of sponge species present and their abundance. In total 132 sponge species were recorded from these reefs. The majority of the species found (79) were unique to one of the reefs, with only 14 species found at all three reefs. A clear difference in the composition of the sponge assemblages between Mermaid and Scott Reefs was detected, which appears to be strongly influenced by the presence of infrequently recorded (rare) species. Intertidal reef flat habitats had lower species richness than subtidal habitats (<3 species at intertidal stations compared to between 6-21 species at subtidal stations). Channels were distinct from other subtidal habitats and were characterized by high abundances of a few common species. Over half of the species found in the study were rare with 56% having five or fewer individuals recorded from all locations in the study. This is the first documentation of the sponge fauna from these reefs and only the second study to date to examine the sponges found on the oceanic reefs off north Western Australia.
Agrobacterium Mediated Transformation Of Sorghum Bicolor For Disease Resistance

Sorghum serves as staple food for millions of people in Asia. It ranks as the sixth most planted crop and it is vulnerable to fungal diseases resulting in decreased grain quality and yield loss. Agrobacterium strains used were LBA4404 harbouring pcambia"ubi"c hi11 (rice chitinase), EHA105 harbouring pcambia"ubi RC7 (rice chitinase) with bar gene and EHA105 harbouring pMKURF2 (rice chitinase gene) having hph gene for producing fungal resistance in sorghum plants. pCRC7 harbouring chitinase gene driven by ubiquitin promoter was found to be more efficient than pCG11 and pMKURF2.Out of the concentrations of acetosyringone tested, 2004M showed maximum transformation efficiency. Out of the two selection agents tested, bialaphos was found as a suitable selection agent. The transgenic nature of the sorghum calli and plants were shown by transient gus expression, their ability to survive in the selection medium and by western blot. The transformation frequency was found to be very low.
Are Waterpipe Café, Vape Shop, and Traditional Tobacco Retailer Locations Associated with Community Composition and Young Adult Tobacco Use in North Carolina and Virginia?

Abstract Purpose We examined whether waterpipe café, vape shop, and traditional tobacco retailer (e.g. stores selling cigarettes, cigars, smokeless tobacco) locations were associated with census tract composition and tobacco use among young adults in North Carolina and Virginia. Methods: We identified waterpipe cafés, vape shops, and traditional tobacco retailers in North Carolina and Virginia and conducted multivariable analyses between community characteristics (gender, race, ethnicity, education, college enrollment, and poverty) and density per 1000 population. Using fall 2017 data from 1099 young adults residing in North Carolina and Virginia, we conducted logistic regression analyses to determine whether tobacco retailer density and proximity were associated with tobacco use. Results: Waterpipe café, vape shop, and traditional retailer density were higher in communities with more people who were Hispanic, college-educated, and college-enrolled (each p < .05). Waterpipe café and traditional retailer density were higher in communities with more people living below the poverty level (each p < .05). Waterpipe café density was higher in communities with more people who were male (p < .05), while traditional retailer density was lower (p < .05). Waterpipe café and vape shop proximity were associated with increased likelihood of waterpipe tobacco use in the past 6 months (each p < .05; unadjusted). Traditional retailer proximity and waterpipe café, vape shop, and traditional retailer density were not associated with tobacco use. Conclusions: Waterpipe cafés and vape shops are located in both impoverished and college-educated communities in North Carolina and Virginia, similar to where traditional tobacco retailers are located. Further research is needed to examine associations with tobacco use.
A preliminary examination of the bacterial, archaeal, and fungal rhizosphere microbiome in healthy and Phellinus noxius‐infected trees

Phellinus noxius is a pathogenic fungus that causes brown root rot disease, resulting in a widespread tree and crop mortality in the tropics and subtropics. Early stages of this disease are largely asymptomatic, hindering early diagnosis and effective treatment. We hypothesized that P. noxius infection would alter the rhizosphere microbiome of infected trees, based on which diagnostic biomarkers could be developed. Here, we examined for the first time the bacterial, archaeal, and fungal rhizosphere microbiome in four species of healthy and P. noxius‐infected trees (Ficus microcarpa, Celtis sinensis, Mallotus paniculatus, and Cinnamomum camphora) using high‐throughput amplicon sequencing. Results revealed the dominance of Proteobacteria and Actinobacteria in bacteria, Crenarchaeota and Euryarchaeota in archaea, and Ascomycota and Basidiomycota in fungi. Phellinus noxius infection did not affect the alpha diversity of the bacterial rhizosphere microbiome in all four tree species but affected that of archaea and fungi in a tree species‐dependent manner. Infection with P. noxius only affected the bacterial rhizosphere composition in M. paniculatus but not the other three tree species. By contrast, P. noxius infection affected the composition of the archaeal and fungal rhizosphere microbiome in all four tree species. Collectively, these results suggest that potential diagnostic biomarkers for brown root rot disease are tree species‐specific and should be developed based on different taxonomic groups. Our study has provided insights into the rhizosphere microbiome in healthy and P. noxius‐infected trees and laid a solid foundation for future comprehensive studies.
Prevalence and risk factors of Salmonella in commercial poultry farms in Nigeria

Salmonella is an important human pathogen and poultry products constitute an important source of human infections. This study investigated prevalence; identified serotypes based on whole genome sequence, described spatial distribution of Salmonella serotypes and predicted risk factors that could influence the prevalence of Salmonella infection in commercial poultry farms in Nigeria. A cross sectional approach was employed to collect 558 pooled shoe socks and dust samples from 165 commercial poultry farms in North West Nigeria. On-farm visitation questionnaires were administered to obtain information on farm management practices in order to assess risk factors for Salmonella prevalence. Salmonella was identified by culture, biotyping, serology and polymerase chain reaction (PCR). PCR confirmed isolates were paired-end Illumina- sequenced. Following de novo genome assembly, draft genomes were used to obtain serotypes by SeqSero2 and SISTR pipeline and sequence types by SISTR and Enterobase. Risk factor analysis was performed using the logit model. A farm prevalence of 47.9% (CI95 [40.3–55.5]) for Salmonella was observed, with a sample level prevalence of 15.9% (CI95 [12.9–18.9]). Twenty-three different serotypes were identified, with S. Kentucky and S. Isangi as the most prevalent (32.9% and 11%). Serotypes showed some geographic variation. Salmonella detection was strongly associated with disposal of poultry waste and with presence of other livestock on the farm. Salmonella was commonly detected on commercial poultry farms in North West Nigeria and S. Kentucky was found to be ubiquitous in the farms.
Development and Application of a Mass Spectrometry Method for Quantifying Nylon Microplastics in Environment.

The quantitative detection methods for many microplastics (MPs) polymers in the environment are inadequate. For example, effective detection methods of nylon (polyamide, PA), a widely used plastic, in different environmental samples is still lacking. In the present study, a method based on acid depolymerization-liquid chromatography-tandem mass spectrometry (LC-MS/MS) and without the separation of MPs from samples was developed to quantify nylon MPs. After removing the background monomer compounds, PA6 and PA66 were efficiently depolymerized to 6-aminocaproic acid and adipic acid and detected by LC-MS/MS, respectively. Accordingly, the quantity of nylon MPs was accurately calculated. By using the proposed method, the recovery of spiked PA6 and PA66 MPs in the environmental samples ranged from 90.8% to 98.8%. The limits of quantification for PA6 and PA66 MPs were 0.680 and 4.62 mg/kg, respectively. PA MPs were widely detected in indoor dust, sludge, marine sediment, freshwater sediment, fishery sediment, and fish guts and gills with concentrations of 0.725-321 mg/kg. Extremely high concentrations of PA66 MPs were detected in indoor dust and fish guts and gills, indicating the unequivocal risk of human exposure through dust ingestion and dietary exposure.
An Optimal Energy Efficiency of a Two-tier Network in Control-Data Separation Architecture

In this paper, we propose to maximize the Energy Efficiency (EE) of a two-tier network by jointly optimizing the number of active small cell base stations (SBSs) and the usercell association. We apply the concept of signaling and data separation where a macro cell base station (MBS) provides full coverage while the SBSs provide high data transmission. First, we model the spatial distributions of the SBSs and mobile users following two independent Poisson Point Processes (PPP) and derive the expressions for the Signal-to-Interference Ratio (SIR), user cell associations, power consumption and energy efficiency of the Heterogeneous Network (HetNet). Then, we formulate the EE maximization problem and solve it by proposing the Switching off Decision and User Association (SODUA) algorithm. The algorithm associates a mobile user to an SBS that offers the highest SIR and calculates the load of each SBS. The algorithm, then, decides to switch off the SBSs that have fewer mobile users than a threshold value, where the mobile users will be offloaded to a nearby SBS that offers the highest SIR. Finally, we calculate the EE of the HetNet. We compare the EE achieved by the proposed algorithm (i.e. after offloading) and that "without offloading". The results show that the proposed algorithm improves the EE of the HetNet and that the EE cannot be further improved by switching off more SBSs than a certain number. 
Diagnostic Accuracy of Usual Cognitive Screening Tests Versus Appropriate Tests for Lower Education to Identify Alzheimer Disease

Introduction: The accuracy of commonly used screening tests for Alzheimer’s disease (AD) has not been directly compared to those that could be more appropriate for lower schooling. Objective: To compare the diagnostic accuracy of usual screening tests for AD with instruments that might be more appropriate for lower schooling among older adults with low or no literacy. Methods: The study included a clinical sample of 117 elderly outpatients from a Geriatric Clinic classified as literate controls (n = 39), illiterate controls (n = 30), literate AD (n = 30) and illiterate AD (n = 18). The tests were compared as follows: Black and White versus Colored Figure Memory Test; Clock Drawing Test versus Clock Reading Test; Verbal Fluency (VF) animal versus grocery category; CERAD Constructional Praxis versus Stick Design Test. Results: The means of literate and illiterate controls did not differ in the Black and White Figure Memory Test (immediate recall), Colored Figure Memory Test (delayed recall), Clock Reading Test and VF animals and grocery categories. The means of the clinical groups (controls versus AD), in the 2 schooling levels, differed significantly in most of the tests, except for the CERAD Constructive Praxis and the Stick Design Test. Diagnostic accuracy was not significantly different between the compared tests. Conclusion: Commonly used screening tests for AD were as accurate as those expected to overcome the education bias in a sample of older adults with lower or no education.
Risk prediction of delirium in hospitalized patients using machine learning: An implementation and prospective evaluation study

OBJECTIVE Machine learning models trained on electronic health records have achieved high prognostic accuracy in test datasets, but little is known about their embedding into clinical workflows. We implemented a random forest-based algorithm to identify hospitalized patients at high risk for delirium, and evaluated its performance in a clinical setting. MATERIALS AND METHODS Delirium was predicted at admission and recalculated on the evening of admission. The defined prediction outcome was a delirium coded for the recent hospital stay. During 7 months of prospective evaluation, 5530 predictions were analyzed. In addition, 119 predictions for internal medicine patients were compared with ratings of clinical experts in a blinded and nonblinded setting. RESULTS During clinical application, the algorithm achieved a sensitivity of 74.1% and a specificity of 82.2%. Discrimination on prospective data (area under the receiver-operating characteristic curve = 0.86) was as good as in the test dataset, but calibration was poor. The predictions correlated strongly with delirium risk perceived by experts in the blinded (r = 0.81) and nonblinded (r = 0.62) settings. A major advantage of our setting was the timely prediction without additional data entry. DISCUSSION The implemented machine learning algorithm achieved a stable performance predicting delirium in high agreement with expert ratings, but improvement of calibration is needed. Future research should evaluate the acceptance of implemented machine learning algorithms by health professionals. CONCLUSIONS Our study provides new insights into the implementation process of a machine learning algorithm into a clinical workflow and demonstrates its predictive power for delirium.