Miracle-dz/UniFAR-FTUs huggingface dataset:
Risk-based residential HLB/ACP survey for California, Texas and Arizona

The recent discoveries of HLB in the Los Angeles Basin and the Rio Grande Valley of Texas underscore the imminent danger of HLB spread in these two States and the urgent need for highly sensitive survey methods for early detection of new residential infections of HLB combined with rapid intervention to contain and eliminate further spread. The Arizona citrus industry is also at considerable risk due to the proximity to the Mexican border and continued immigration of ACP from Mexico. The 2008 economic downturn has led to dwindling fiscal resources for many regulatory agencies including those tasked with conducting the survey for HLB. Therefore, sampling efforts need to be deployed based on potential risk introduction and threat to commercial citrus to optimize early detection. A risk-based residential survey has recently been constructed and deployed in Southern California and the Rio Grande Valley of Texas, and is being designed for Southern Arizona.
Umami taste perception and preferences of the domestic cat (Felis catus), an obligate carnivore

Abstract The domestic cat (Felis catus) is an obligate carnivore, and as such has a meat-based diet. Several studies on the taste perception of cats have been reported, indicating that their sense of taste has evolved based on their carnivorous diet. Here, we propose that umami (mediated by Tas1r1-Tas1r3) is the main appetitive taste modality for the domestic cat by characterizing the umami taste of a range of nucleotides, amino acids, and their mixtures for cats obtained using complementary methods. We show for the first time that cats express Tas1r1 in taste papillae. The cat umami receptor responds to a range of nucleotides as agonists, with the purine nucleotides having the highest activity. Their umami receptor does not respond to any amino acids alone; however, 11 l-amino acids with a range of chemical characteristics act as enhancers in combination with a nucleotide. l-Glutamic acid and l-Aspartic acid are not active as either agonists or enhancers of the cat umami receptor due to changes in key binding residues at positions 170 and 302. Overall, cats have an appetitive behavioral response for nucleotides, l-amino acids, and their mixtures. We postulate that the renowned palatability of tuna for cats may be due, at least in part, to its specific combination of high levels of inosine monophosphate and free l-Histidine that produces a strong synergistic umami taste enhancement. These results demonstrate the critical role that the umami receptor plays in enabling cats to detect key taste compounds present in meat.
Enumerating soil biodiversity

Significance Soil organisms mediate unique functions we rely on for food, fiber, and human and planetary health. Despite the significance of soil life, we lack a quantitative estimate of soil biodiversity, making it challenging to advocate for the importance of protecting, preserving, and restoring soil life. Here, we show that soil is likely home to 59% of life including everything from microbes to mammals, making it the singular most biodiverse habitat on Earth. Our enumeration can enable stakeholders to more quantitatively advocate for soils in the face of the biodiversity crisis.
Calculation of Phase 2 dose‐finding study sample size for reliable Phase 3 dose selection

Sample sizes of Phase 2 dose‐finding studies, usually determined based on a power requirement to detect a significant dose–response relationship, will generally not provide adequate precision for Phase 3 target dose selection. We propose to calculate the sample size of a dose‐finding study based on the probability of successfully identifying the target dose within an acceptable range (e.g., 80%–120% of the target) using the multiple comparison and modeling procedure (MCP‐Mod). With the proposed approach, different design options for the Phase 2 dose‐finding study can also be compared. Due to inherent uncertainty around an assumed true dose–response relationship, sensitivity analyses to assess the robustness of the sample size calculations to deviations from modeling assumptions are recommended. Planning for a hypothetical Phase 2 dose‐finding study is used to illustrate the main points. Codes for the proposed approach is available at https://github.com/happysundae/posMCPMod.
Early detection of left atrial dysfunction in hypertensive patients: Role of Speckle Tracking imaging.

INTRODUCTION Systemic hypertension is a major health problem worldwide, it is associated with impaired left atrial (LA) function. Myocardial deformation analysis using speckle-tracking echocardiography has emerged as a promising tool to evaluate atrial deformation and function. AIM To evaluate early changes in left atrial longitudinal strain based on speckle tracking echocardiography in patients with hypertension. METHODS LA strain was studied using speckle-tracking echocardiography in 109 hypertensive patients without LA enlargement and 50 agematched controls. Conventional and bidimensional strain echocardiographic assessments were performed and the following parameters were measured: peak atrial longitudinal strain and strain rate during the reservoir, conduit, and contractile periods in four and two-chambers views and time to peak atrial longitudinal strain/strain rate measured in the three phases of LA function. RESULTS LA anteroposterior diameter was within the normal range, no difference between the hypertensive patients and controls was noted (34.35 mm ±4.91 vs 31.82 mm±4.87, p= 0.16). LA maximum volume (41.78ml±10.29 vs 47ml±13.21, p= 0,01), minimum volume (23.95ml±12.18 vs 16.94ml±7.91, p=0,001) were higher in hypertensive patients, and impaired reservoir ( 31.23% ±9.93 vs 46.43% ±11.06, p=0.000) and conduit functions (14.26%±2.91 vs 21.41%±2.8 , p= 0,000) were noted in hypertensive patients compared to normotensive patients. During the contractile period, peak strain (16.73% ±3.84 vs 15.29%±2.75 ,p=0,07) and strain rate (-1.89%±0.16, -1.82%±0.21;p=0,54) were higher in hypertensive patients without reaching the level of significance. Time to peak strain during reservoir period (405.02ms±55.51 vs 387.13ms±47.48, p=0,05) and duration of diastole (163ms±26 vs 146ms±24, p= 0,04) were significantly higher in hypertensive patients compared to controls. A significant relationship between the parameters of the volumetric study and those of the bidimensional strain/strain rate study was noted. CONCLUSION Left atrial longitudinal strain during the reservoir and conduit periods is impaired in patients with hypertension despite normal cavity size and before the detection of other echocardiographic changes. Speckle-tracking echocardiography may be considered a promising tool for the early detection of LA strain abnormalities in these patients.
Downregulation of Krüppel‐like factor 14 accelerated cellular senescence and aging

Aging has been considered as a risk factor in many diseases, thus, comprehensively understanding the cellular and molecular mechanisms of delayed aging is important. Here we investigated whether Krüppel‐like factor 14 (KLF14) is a suppressor of cellular senescence and aging. In our research, KLF14 levels significantly decreased not only in the lymphocytes of healthy people but also in the cells and tissues of mice with aging. We performed in vitro and in vivo experiments on cells and mice to reveal the function of KLF14 in aging. KLF14 deficiency facilitates cellular senescence and aging‐related pathologies in C57BL/6J mice, whereas KLF14 overexpression attenuates cellular senescence. Mechanistically, KLF14 delays aging by binding to the POLD1 promoter to positively regulate POLD1 expression. Remarkably, cellular senescence mediated by KLF14 downregulation could be alleviated by POLD1 expression. In addition, perhexiline, an agonist of KLF14, could delay cellular senescence and aging‐related pathologies in senescence‐accelerated P8 mice by inducing POLD1 expression, as perhexiline could enhance the effect of KLF14's transcription activation to POLD1 by elevating the binding level of KLF14 to the POLD1 promoter. Our data indicate that KLF14 might be a critical element in aging by upregulating POLD1 expression, indicating that the activation of KLF14 may delay aging and aging‐associated diseases.
Diagnosing Noise-Induced Hearing Loss Sustained During Military Service Using Deep Neural Networks

The diagnosis of noise-induced hearing loss (NIHL) is based on three requirements: a history of exposure to noise with the potential to cause hearing loss; the absence of known causes of hearing loss other than noise exposure; and the presence of certain features in the audiogram. All current methods for diagnosing NIHL have involved examination of the typical features of the audiograms of noise-exposed individuals and the formulation of quantitative rules for the identification of those features. This article describes an alternative approach based on the use of multilayer perceptrons (MLPs). The approach was applied to databases containing the ages and audiograms of individuals claiming compensation for NIHL sustained during military service (M-NIHL), who were assumed mostly to have M-NIHL, and control databases with no known exposure to intense sounds. The MLPs were trained so as to classify individuals as belonging to the exposed or control group based on their audiograms and ages, thereby automatically identifying the features of the audiogram that provide optimal classification. Two databases (noise exposed and nonexposed) were used for training and validation of the MLPs and two independent databases were used for evaluation and further analyses. The best-performing MLP was one trained to identify whether or not an individual had M-NIHL based on age and the audiogram for both ears. This achieved a sensitivity of 0.986 and a specificity of 0.902, giving an overall accuracy markedly higher than for previous methods.
CYP2D6 Activity Is Correlated with Changes in Plasma Concentrations of Taurocholic Acid during Pregnancy and Postpartum in CYP2D6 Extensive Metabolizers

Cytochrome P450 2D6 (CYP2D6) is involved in the metabolism of >20% of marketed drugs. CYP2D6 expression and activity exhibit high interindividual variability and is induced during pregnancy. The farnesoid X receptor (FXR) is a transcriptional regulator of CYP2D6 that is activated by bile acids. In pregnancy, elevated plasma bile acid concentrations are associated with maternal and fetal risks. However, modest changes in bile acid concentrations may occur during healthy pregnancy, thereby altering FXR signaling. A previous study demonstrated that hepatic tissue concentrations of bile acids positively correlated with the hepatic mRNA expression of CYP2D6. This study sought to characterize the plasma bile acid metabolome in healthy women (n = 47) during midpregnancy (25–28 weeks gestation) and ≥3 months postpartum and to determine if plasma bile acids correlate with CYP2D6 activity. It is hypothesized that during pregnancy, plasma bile acids would favor less hydrophobic bile acids (cholic acid vs. chenodeoxycholic acid) and that plasma concentrations of cholic acid and its conjugates would positively correlate with the urinary ratio of dextrorphan/dextromethorphan. At 25–28 weeks gestation, taurine-conjugated bile acids comprised 23% of the quantified serum bile acids compared with 7% ≥3 months postpartum. Taurocholic acid positively associated with the urinary ratio of dextrorphan/dextromethorphan, a biomarker of CYP2D6 activity. Collectively, these results confirm that the bile acid plasma metabolome differs between pregnancy and postpartum and provide evidence that taurocholic acid may impact CYP2D6 activity during pregnancy. SIGNIFICANCE STATEMENT Bile acid homeostasis is altered in pregnancy, and plasma concentrations of taurocholic acid positively correlate with CYP2D6 activity. Differences between plasma and/or tissue concentrations of farnesoid X receptor ligands such as bile acids may contribute to the high interindividual variability in CYP2D6 expression and activity.
A novel selenite‐tolerant rhizosphere bacterium Wautersiella enshiensis sp. nov., isolated from Chinese selenium hyperaccumulator, Cardamine hupingshanensis

Selenium (Se) is a dietary essential trace element for humans with various physiological functions and it could also be accumulated by some plant species, like Astragalus bisulcatus, Stanleya pinnata, and Cardamine hupinshanensis. A novel Gram‐stain‐negative, facultatively anaerobic, selenite‐tolerant bacterium, designated strain YLX‐1T, was isolated from the rhizosphere of a Se hyperaccumulating plant, Cardamine hupingshanensis in Enshi, China. Phylogenetic analysis based on 16 S rRNA gene sequences indicated that strain YLX‐1T is a potential new species in the genus Wautersiella. Strain YLX‐1T could grow in the temperature range of 4–37°C (optimally at 28°C) and in the pH range of 5–9 (optimum pH 7), which also could tolerate Se up to 6000 mg Se/L via producing extracellular red nano‐Se with 100–300 nm size. However, it could predominantly accumulate selenocystine (SeCys2) in the cell under lower Se stress (1.5 mg Se/L). These results would help broaden our knowledge about the Se accumulation and transformation mechanism involved in rhizosphere bacteria like strain YLX‐1T in C. hupingshanensis. Based on polyphasic data, we propose the creation of the new species Wautersiella enshiensis sp. nov., strain YLX‐1T ( = CCTCC M 2013671) which will be promising to produce nano‐Se as fertilizer, food additives or medicine.
The distribution of galaxies as a test of primordial non-Gaussianity

Cosmic inflation is a paradigm that successfully seeds large scale structure in a big bang cosmology whilst causing the Universe to be statistically isotropic. Inflation occurred at energy scales that are too high to be accessible with accelerator experiments, thus we have to rely entirely on cosmological observations to rule out classes of inflationary models and get insight into the physics of the early Universe. One way to distinguish these models is by measuring how close their predicted primordial fluctuations are to being Gaussian distributed, described at first order by the parameter fNL. Local primordial non-Gaussianity alters the biasing law between darkmatter halos and the underlying massdensity field at the largest scales [1, 2]. Currently, the tightest constraints on the local fNL = 0.8± 5.0 come from the cosmic microwave background experiment Planck [3]. Next generation ground-based experiments will be limited by cosmic variance, and we need a different approach to independently confirm these results, and to further narrow down our constraints on the inflationary epoch. Galaxy clustering studies so far could not compete with the precision of the fNL results from the microwave background, but upcoming galaxy surveys will come close to independently confirm the Planck results. Combining future galaxy clustering and Cosmic Microwave Background data will improve fNL constraints such that they will provide physically interesting results. This will only be possible if some challenges can be addressed properly, of which two are addressed in this thesis. The first problem is that fNL measurements take place at the very largest scales, which are close to maximum scale fitting into the survey volume. This means that we have to rely on a low number of modes and we therefore cannot assume the likelihood of our power spectrum measurement to be Gaussian. The Inverse Cubic Normal distribution is a very good approximation to what we expect for the true likelihood
Isoleucine epimerisation and stable isotope ratio studies of cassowary, megapode and aepyornis eggshells: biogeochemical and palaeonenvironmental implications

Previous researchers have used the extent of isoleucine epimerisation and stable carbon, oxygen and nitrogen isotope ratios of ostrich ( Struthio ), emu ( Dromaius ) and Genyornis eggshells to provide geochronological control and palaeoenvironmental information on the Quaternary sequences from which these sample types are recovered. This thesis expanded this field of research by examining isoleucine epimerisation and the stable isotopes ratios of cassowary ( Casuarius ), megapode (principally the Australian brush-turkey, Alectura lathami ) and Aepyornis eggshells. The aims of the research were to (1) increase our understanding of the ancient habitats of Casuarius , megapodes and Aepyornis in order to provide information on how these ecosystems functioned, as well as the nature and timing of the environmental change they have experienced, and (2) to document the amino acid and stable isotope biogeochemistry of avian eggshells in novel contexts in order to better understand the processes that influence these attributes. , Aepyornis eggshells were heated at 143 and 160 These experiments were used to determine the temperature sensitivity of isoleucine epimerisation in these eggshell types, expressed in terms of Arrhenius parameters, and to characterise the thermal stability of amino acids. the stratified and Lisa to short-term high temperature heating events associated with campfires complicated interpretation of the extent of isoleucine epimerisation in Casuarius and megapode eggshells in terms of time and temperature. The extent of isoleucine epimerisation in Alectura lathami eggshells Hay Cave
Robust cross-cohort gut microbiome associations with COVID-19 severity

ABSTRACT Although many recent studies have examined associations between the gut microbiome and COVID-19 disease severity in individual patient cohorts, questions remain on the robustness across international cohorts of the biomarkers they reported. Here, we performed a meta-analysis of eight shotgun metagenomic studies of COVID-19 patients (comprising 1,023 stool samples) and 23 > 16S rRNA gene amplicon sequencing (16S) cohorts (2,415 total stool samples). We found that disease severity (as defined by the WHO clinical progression scale) was associated with taxonomic and functional microbiome differences. This alteration in gut microbiome configuration peaks at days 7–30 post diagnosis, after which the gut microbiome returns to a configuration that becomes more similar to that of healthy controls over time. Furthermore, we identified a core set of species that were consistently associated with disease severity across shotgun metagenomic and 16S cohorts, and whose abundance can accurately predict disease severity category of SARS-CoV-2 infected subjects, with Actinomyces oris abundance predicting population-level mortality rate of COVID-19. Additionally, we used relational diet-microbiome databases constructed from cohort studies to predict microbiota-targeted diet patterns that would modulate gut microbiota composition toward that of healthy controls. Finally, we demonstrated the association of disease severity with the composition of intestinal archaeal, fungal, viral, and parasitic communities. Collectively, this study has identified robust COVID-19 microbiome biomarkers, established accurate predictive models as a basis for clinical prognostic tests for disease severity, and proposed biomarker-targeted diets for managing COVID-19 infection.
Subtilisin 3 production from Microsporum canis is independent of keratin substrate availability

Dermatophytes are highly infectious fungi that cause superficial infections in keratinized tissues in humans and animals. This group of fungi is defined by their ability to digest keratin and encompasses a wide range of species. We investigated a critical adhesion protein, subtilisin 3, utilized by Microsporum canis during initial stages of infection, analyzing its production and expression under varying growth conditions. Additionally, as this protein must be expressed and produced for dermatophyte infections to occur, we developed and optimized a diagnostic antibody assay targeting this protein. Subtilisin 3 levels were increased in culture when grown in baffled flasks and supplemented with either l‐cysteine or cat hair. As subtilisin 3 was also produced in cultures not supplemented with keratin or cysteine, this study demonstrated that subtilisin 3 production is not reliant on the presence of keratin or its derivatives. These findings could help direct future metabolic studies of dermatophytes, particularly during the adherence phase of infections.
Metabolite and Lipid Biomarkers Associated With Intraocular Pressure and Inner Retinal Morphology: 1H NMR Spectroscopy Results From the UK Biobank

Purpose The purpose of this study was to assess metabolites associated with intraocular pressure (IOP) and inner retina structure. Methods We cross-sectionally assessed 168 non-fasting plasma metabolites measured by nuclear magnetic resonance (NMR) spectroscopy with IOP (n = 28,195), macular retinal nerve fiber layer thickness (mRNFL; n = 10,584), and macular ganglion cell inner plexiform layer thickness (mGCIPL; n = 10,554) in the UK Biobank. We used multiple linear regression models adjusting for various covariates with probit-transformed metabolite levels as predictors for each outcome. Each estimate represents the difference in outcome variable per standard deviation increase in the probit-transformed metabolite values. We used the number of effective (NEF) tests and false discovery rate (FDR) to adjust for multiple comparisons for metabolites and metabolite classes, respectively. Results In individual metabolite analysis, multiple amino acids, especially branched-chain amino acids, were associated with lower IOP (−0.12 mm Hg; 95% confidence interval = −0.16 to −0.07; NEF = 2.7E-05). Albumin, 3 hydroxybutyrate, lactate, and several lipids were associated with higher IOP (range = 0.07 to 0.18 mm Hg, NEF = ≤ 0.039). In IOP-adjusted analyses, five HDL-related metabolites were associated with thinner mRNFL (−0.15 microns for all metabolites, NEF = ≤ 0.027), whereas five LDL-related metabolites were associated with thicker mGCIPL (range = 0.17 to 0.20 microns; NEF = ≤ 0.044). In metabolite class analysis, the lipid components of lipoproteins (cholesterol, triglycerides, etc.) were not associated with our outcomes (FDR > 0.2 for all); yet multiple lipoproteins were significantly (FDR < 0.05) associated with all outcomes. Conclusions Branched-chain amino acids were associated with lower IOP, HDL metabolites were associated with thinner mRNFL, and LDL metabolites were associated with thicker mGCIPL.
Myocardial structural and functional changes in cardiac amyloidosis: insights from a prospective observational patient registry

Abstract Aims The pathophysiological hallmark of cardiac amyloidosis (CA) is the deposition of amyloid within the myocardium. Consequently, extracellular volume (ECV) of affected patients increases. However, studies on ECV progression over time are lacking. We aimed to investigate the progression of ECV and its prognostic impact in CA patients. Methods and results Serial cardiac magnetic resonance (CMR) examinations, including ECV quantification, were performed in consecutive CA patients. Between 2012 and 2021, 103 CA patients underwent baseline and follow-up CMR, including ECV quantification. Median ECVs at baseline of the total (n = 103), transthyretin [(ATTR) n = 80], and [light chain (AL) n = 23] CA cohorts were 48.0%, 49.0%, and 42.6%, respectively. During a median period of 12 months, ECV increased significantly in all cohorts [change (Δ) +3.5% interquartile range (IQR): −1.9 to +6.9, P < 0.001; Δ +3.5%, IQR: −2.0 to +6.7, P < 0.001; and Δ +3.5%, IQR: −1.6 to +9.1, P = 0.026]. Separate analyses for treatment-naïve (n = 21) and treated (n = 59) ATTR patients revealed that the median change of ECV from baseline to follow-up was significantly higher among untreated patients (+5.7% vs. +2.3%, P = 0.004). Survival analyses demonstrated that median change of ECV was a predictor of outcome [total: hazard ratio (HR): 1.095, 95% confidence interval (CI): 1.047–1.0145, P < 0.001; ATTR: HR: 1.073, 95% CI: 1.015–1.134, P = 0.013; and AL: HR: 1.131, 95% CI: 1.041–1.228, P = 0.003]. Conclusion The present study supports the use of serial ECV quantification in CA patients, as change of ECV was a predictor of outcome and could provide information in the evaluation of amyloid-specific treatments.