Miracle-dz/UniFAR-FTUs huggingface dataset:
Glucosylceramide is essential for Heartland and Dabie bandavirus glycoprotein-induced membrane fusion

Due to climate changes, there has been a large expansion of emerging tick-borne zoonotic viruses, including Heartland bandavirus (HRTV) and Dabie bandavirus (DBV). As etiologic agents of hemorrhagic fever with high fatality, HRTV and DBV have been recognized as dangerous viral pathogens that likely cause future wide epidemics. Despite serious health concerns, the mechanisms underlying viral infection are largely unknown. HRTV and DBV Gn and Gc are viral surface glycoproteins required for early entry events during infection. Glycosphingolipids, including galactosylceramide (GalCer), glucosylceramide (GlcCer) and lactosylceramide (LacCer), are a class of membrane lipids that play essential roles in membrane structure and viral lifecycle. Here, our genome-wide CRISPR/Cas9 knockout screen identifies that glycosphingolipid biosynthesis pathway is essential for HRTV and DBV infection. The deficiency of UDP-glucose ceramide glucosyltransferase (UGCG) that produces GlcCer resulted in the loss of infectivity of recombinant viruses pseudotyped with HRTV or DBV Gn/Gc glycoproteins. Conversely, exogenous supplement of GlcCer, but not GalCer or LacCer, recovered viral entry of UGCG-deficient cells in a dose-dependent manner. Biophysical analyses showed that GlcCer targeted the lipid-head-group binding pocket of Gc to form a stable protein-lipid complex, which allowed the insertion of Gc protein into host lysosomal membrane lipid bilayers for viral fusion. Mutagenesis showed that D841 residue at the Gc lipid binding pocket was critical for GlcCer interaction and thereby, viral entry. These findings reveal detailed mechanism of GlcCer glycosphingolipid in HRTV and DBV Gc-mediated membrane fusion and provide a potential therapeutic target for tickborne virus infection.
The incidence, duration, risk factors, and age-based variation of missed opportunities to diagnose pertussis: A population-based cohort study

Abstract Objective: To estimate the incidence, duration and risk factors for diagnostic delays associated with pertussis. Design: We used longitudinal retrospective insurance claims from the Marketscan Commercial Claims and Encounters, Medicare Supplemental (2001–2020), and Multi-State Medicaid (2014–2018) databases. Setting: Inpatient, emergency department, and outpatient visits. Patients: The study included patients diagnosed with pertussis (International Classification of Diseases [ICD] codes) and receipt of macrolide antibiotic treatment. Methods: We estimated the number of visits with pertussis-related symptoms before diagnosis beyond that expected in the absence of diagnostic delays. Using a bootstrapping approach, we estimated the number of visits representing a delay, the number of missed diagnostic opportunities per patient, and the duration of delays. Results were stratified by age groups. We also used a logistic regression model to evaluate potential factors associated with delay. Results: We identified 20,828 patients meeting inclusion criteria. On average, patients had almost 2 missed opportunities prior to diagnosis, and delay duration was 12 days. Across age groups, the percentage of patients experiencing a delay ranged from 29.7% to 37.6%. The duration of delays increased considerably with age from an average of 5.6 days for patients aged <2 years to 13.8 days for patients aged ≥18 years. Factors associated with increased risk of delays included emergency department visits, telehealth visits, and recent prescriptions for antibiotics not effective against pertussis. Conclusions: Diagnostic delays for pertussis are frequent. More work is needed to decrease diagnostic delays, especially among adults. Earlier case identification may play an important role in the response to outbreaks by facilitating treatment, isolation, and improved contact tracing.
A proper velocity scale for modeling subgrid-scale eddy viscosities in large eddy simulation

The limitations of the commonly used Smagorinsky subgrid‐scale (SGS) eddy viscosity model in large eddy simulation (LES) of turbulent flows are that the model’s eddy viscosity constant must be optimized in different flows, and also that a damping function must be used to account for near‐wall effects. A new SGS model which mitigates these drawbacks is proposed, i.e., a more proper eddy viscosity velocity scale was determined by utilizing the third‐order terms in an anisotropic representation model of the Reynolds stresses [K. Horiuti, Phys. Fluids A 2, 1708 (1990)]. This method utilizes the direct numerical simulation (DNS) database for fully developed turbulent channel flow to show these drawbacks to be inherent in the use of an improper velocity scale, i.e., the total SGS energy component adopted in the Smagorinsky model. As a result, the SGS normal shear stress was alternatively employed as the velocity scale, thereby significantly improving the correlation with DNS data. Methods to correlate the SGS n.
Treatment of depression and borderline personality disorder with 1 Hz repetitive transcranial magnetic stimulation of the orbitofrontal cortex – A pilot study

Abstract Borderline personality disorder (BPD) is characterised by impairments in emotional regulation, impulse control and interpersonal interaction. Comorbid depression is common. The orbitofrontal cortex (OFC) plays a crucial role in the biological substrate of BPD. We investigated the effects of 1 Hz repetitive transcranial magnetic stimulation (rTMS) targeting the OFC on depressive symptoms and symptoms of BPD in 15 patients suffering from both conditions to assess feasibility and effectiveness. Target treatment intensity was 120% of resting motor threshold (RMT) and intended duration four weeks. Treatment improved both symptoms of depression as measured by the Hamilton Depression Rating Scale and of BPD as measured by Borderline Symptom List-23 and Barratt Impulsivity Scale. Drop-out rates were high with 7/15 patients not completing the full course of rTMS, but only two drop-outs were related to treatment. Only a minority of patients tolerated target treatment intensity. Despite the limitations, the results suggest efficacy of treatment and welcome further research.
Asymptotic solution of Fokker–Planck equation for plasma in Paul traps

An exact analytic solution of the Vlasov equation for the plasma distribution in a Paul trap is known to be a Maxwellian and thus, immune to collisions under the assumption of infinitely fast relaxation [K. Shah and H. S. Ramachandran, Phys. Plasmas 15, 062303 (2008)]. In this paper, it is shown that even for a more realistic situation of finite time relaxation, solutions of the Fokker–Planck equation lead to an equilibrium solution of the form of a Maxwellian with oscillatory temperature. This shows that the rf heating observed in Paul traps cannot be caused due to collisional effects alone.
Comparing Brief Measures of Narcissism—Internal Consistency, Validity, and Coverage

Abstract Many measures, varying in breadth and length, have been constructed to measure narcissism. In recent years, super-short forms have become popular in research settings. Although brief measures hold some advantages, their brevity can come at psychometric costs. Participants recruited from Amazon’s Mechanical Turk (N = 473) completed long and brief narcissism measures and criterion measures in a randomized order. Short forms were examined and compared to long forms in terms of their completion times and psychometric properties. Generally, the short forms demonstrated adequate internal consistency, variable convergence with each other, mostly moderate to strong convergence with long forms, and appropriate convergence with external criteria. These findings suggest that some short forms may be used when efficiency of survey administration is particularly important without significant psychometric cost. We discuss the advantages and disadvantages of the brief measures and make recommendations for which to use depending on the priorities of a given study.
Improvement of signal correlation for adaptive imaging using the translating transmit aperture algorithm

Phase aberration correction techniques require highly correlated signals at different receiver positions in order to estimate and correct for the time shifts imposed by the aberrator. The translating transmit aperture algorithm is a technique for improving the signal correlation from speckle signals at different receiver positions. The efficacy of this technique in improving signal correlation is demonstrated both in phantom studies across an inhomogeneous medium, as well as in in vivo studies. The corresponding improvement in time shift estimates and image quality when the translating aperture geometry is used instead of a fixed transmit aperture geometry is also shown. Limitations of the translating aperture algorithm are generated by quantization of the transmit focal delays, depth of field considerations, and a bias in the time shift estimates made using this algorithm.
Evaluation of the in vitro and in vivo effect of liposomal doxorubicin along with oncolytic Newcastle disease virus on 4T1 cell line: Animal preclinical research

Abstract Background Breast cancer is one of the most common malignancies in women, with one in 20 globally. Oncolytic viruses have recently been the first step in the biological treatment of cancer, either genetically engineered or naturally occurring. They increase specifically inside cancer cells and destroy them without damaging normal tissues or producing a host immune response against tumour cells or expressing transgenes. One of the most known members of this family is the Newcastle disease virus (NDV), a natural oncolytic virus that selectively induces apoptosis and DNA fragmentation in human cancer cells. Methods This study performed biochemical and molecular investigations with variable doses of NDV (32, 64, 128 HAU) and liposomal doxorubicin (9 mg/kg) on mouse triple‐negative mammary carcinoma cell line 4T1 and BALB/c models tumours for the first time. Results Real‐time quantitative PCR analysis in NDV‐treated animal tumours showed increased expression of P21, P27 and P53 genes and decreased expression of CD34, integrin Alpha 5, VEGF and VEGF‐R genes. Additional assessments in treated mouse models also showed that NDV increased ROS production, induced apoptosis, reduced tumour size and significantly improved prognosis, with no adverse effect on normal tissues. Conclusions These findings all together might indicate that NDV in combination with chemotherapy drugs could improve prognosis in cancer patients although many more conditions should be considered.
Two Hippo signaling modules orchestrate liver size and tumorigenesis

The Hippo pathway is a central regulator of organ size and tumorigenesis and is commonly depicted as a kinase cascade, with an increasing number of regulatory and adaptor proteins linked to its regulation over recent years. Here, we propose that two Hippo signaling modules, MST1/2–SAV1–WWC1‐3 (HPO1) and MAP4K1‐7–NF2 (HPO2), together regulate the activity of LATS1/2 kinases and YAP/TAZ transcriptional co‐activators. In mouse livers, the genetic inactivation of either HPO1 or HPO2 module results in partial activation of YAP/TAZ, bile duct hyperplasia, and hepatocellular carcinoma (HCC). On the contrary, inactivation of both HPO1 and HPO2 modules results in full activation of YAP/TAZ, rapid development of intrahepatic cholangiocarcinoma (iCCA), and early lethality. Interestingly, HPO1 has a predominant role in regulating organ size. HPO1 inactivation causes a homogenous YAP/TAZ activation and cell proliferation across the whole liver, resulting in a proportional and rapid increase in liver size. Thus, this study has reconstructed the order of the Hippo signaling network and suggests that LATS1/2 and YAP/TAZ activities are finetuned by HPO1 and HPO2 modules to cause different cell fates, organ size changes, and tumorigenesis trajectories.
A genetic clustering algorithm guided by a descent algorithm

This paper considers a clustering problem where distorted images are allocated into a specific number of clusters such that each cluster is composed of images that are similar. Similarity is determined by summing the mean squared error of each image of a cluster with the centroid of that cluster. A genetic algorithm guided by a descent algorithm is presented to minimise this error. Tabu search is also employed to maintain genetic diversity and improve efficiency. Experiments use monochrome, greyscale and colour images.
On Variance Estimation With Imputed Survey Data: Comment

Unit nonresponse and item nonresponse both occur frequently in surveys. Unit nonresponse is customarily handled by weighting adjustment, whereas item nonresponse is usually treated by some form of imputation. In particular, deterministic or stochastic imputation is often used to assign values for missing item responses. We provide an account of some recent work on jackknife variance estimation based on adjusted imputed values, using only a single imputation and hence a single completed data set. We also present linearized versions of the jackknife variance estimators. We study both stratified simple random sampling and stratified multistage sampling. Existing computer programs for jackknife and linearization variance estimation can be modified to implement the proposed variance estimators without requiring the creation and permanent retention of supplemental data sets. But for secondary analyses, the completed data set must include information on response status for each item as well as on the imputation class.
Functional Fractional Calculus For System Identification And Controls

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Unraveling the Gene Regulatory Networks of the Global Regulators VeA and LaeA in Aspergillus nidulans

Fungal development and metabolism are genetically programmed events involving specialized cellular differentiation, cellular communication, and temporal and spatial regulation of gene expression. In genus Aspergillus, the global regulators VeA and LaeA govern developmental and metabolic processes by affecting the expression of downstream genes, including multiple transcription factors and signaling elements. ABSTRACT In the filamentous fungus Aspergillus nidulans, the velvet family protein VeA and the global regulator of secondary metabolism LaeA govern development and secondary metabolism mostly by acting as the VelB/VeA/LaeA heterotrimeric complex. While functions of these highly conserved controllers have been well studied, the genome-wide regulatory networks governing cellular and chemical development remain to be uncovered. Here, by integrating transcriptomic analyses, protein–DNA interactions, and the known A. nidulans gene/protein interaction data, we have unraveled the gene regulatory networks governed by VeA and LaeA. Within the networks, VeA and LaeA directly control the expression of numerous genes involved in asexual/sexual development and primary/secondary metabolism in A. nidulans. Totals of 3,190 and 1,834 potential direct target genes of VeA and LaeA were identified, respectively, including several important developmental and metabolic regulators such as flbA·B·C, velB·C, areA, mpkB, and hogA. Moreover, by analyzing over 8,800 ChIP-seq peaks, we have revealed the predicted common consensus sequences 5′-TGATTGGCTG-3′ and 5′-TCACGTGAC-3′ that VeA and LaeA might bind to interchangeably. These findings further expand the biochemical and genomic studies of the VelB/VeA/LaeA complex functionality in the gene regulation. In summary, this study unveils genes that are under the regulation of VeA and LaeA, proposes the VeA- and LaeA-mediated gene regulatory networks, and demonstrates their genome-wide developmental and metabolic regulations in A. nidulans. IMPORTANCE Fungal development and metabolism are genetically programmed events involving specialized cellular differentiation, cellular communication, and temporal and spatial regulation of gene expression. In genus Aspergillus, the global regulators VeA and LaeA govern developmental and metabolic processes by affecting the expression of downstream genes, including multiple transcription factors and signaling elements. Due to their vital roles in overall biology, functions of VeA and LaeA have been extensively studied, but there still has been a lack of knowledge about their genome-wide regulatory networks. In this study, employing the model fungus A. nidulans, we have identified direct targets of VeA and LaeA and their gene regulatory networks by integrating transcriptome, protein–DNA interaction, and protein–protein interaction analyses. Our results demonstrate the genome-wide regulatory mechanisms of these global regulators, thereby advancing the knowledge of fungal biology and genetics.
Comparative study on the performance of monoolein cubic nanoparticles and trimyristin solid lipid nanoparticles as carriers for docetaxel

Abstract Nowadays the application of lipid nanoparticles as carriers for the delivery of anticancer drugs gained great attention in cancer therapy. Solid lipid nanoparticles (SLNs) and cubic nanoparticles (cubosomes) are considered as promising carriers in cancer therapy. The comparison of these two lipid nanoparticles as efficient carriers for the anticancer drug docetaxel was our main goal in this study. Both nanoparticles were prepared by the hot melt homogenization technique followed by measurement of particle size, zeta potential, entrapment efficiency and in vitro release of docetaxel. An advanced technique has been applied to measure the release of docetaxel from these nanoparticles using small unilamellar vesicles (SUVs) as acceptor particles which resemble many compartments in our body. All prepared nanoparticles revealed a neutral zeta potential with particle sizes of about 200 nm. While SUVs showed a negative surface charge with a zeta potential of −55 mV, cubosomes showed higher entrapment efficiency and a slower docetaxel release compared to SLNs. Additionally, cubosomes improved in vitro cytotoxicity as well as the in vivo antitumor inhibition of docetaxel compared to SLNs and docetaxel solution. Overall, our results showed that incorporation of docetaxel into cubosomes could enhance its in vitro and in vivo performance compared to docetaxel incorporated into SLNs. Graphical Abstract
Assessment of Patients With ARFID Presenting to Multi-Disciplinary Tertiary Care Program

There are no standard assessment approaches for Avoidant Restrictive Food Intake Disorder (ARFID). We describe our approach to multidisciplinary assessment after assessing more than 550 patients with ARFID. We collected online survey (ARFID-specific instruments, measures of anxiety, depression) measures. Electronic medical record data (mental health and gastrointestinal diagnoses, micronutrient and bone density assessments, and growth parameters) were extracted for the 239 patients with ARFID seen between 2018 and 2021 with both parent and patient responses to online surveys. We identified 5 subtypes/combinations of subtypes: low appetite; sensory sensitivity; fear + sensory sensitivity; fear + low appetite; fear + sensory sensitivity + low appetite. Those with appetite-only subtype had higher mean age (14.0 years, P < 0.01) and the lowest average body mass index z score (–1.74, P < 0.01) compared to other subtypes. Our experience adds to understanding of clinical presentations in patients with ARFID and may aid in assessment formulation.
The German version of the Revised Children's Anxiety and Depression Scale—Psychometric properties and normative data for German 8‐ to 17‐year‐olds

Anxiety and depression are internalizing mental disorders often commencing in childhood and manifesting in adolescence. The Revised Anxiety and Depression Scale (RCADS) is an internationally widely used standardized diagnostic tool, but the German version has only been validated in a pediatric chronic pain sample; normative data are not available. The aim of this study is to test its reliability (internal consistency) and validity (factorial, convergent, known‐groups) in a representative German school sample and to provide norm data.
Psychiatric onset of prodromal dementia with Lewy bodies: Current insights into neuroimaging tools

Abstract Purpose Our article is dedicated to describing the state-of-the-art in imaging techniques for assessing prodromal dementia with Lewy bodies (pro-DLB) with a psychiatric-onset. Materials and methods Imaging biomarker techniques are discussed. Results (123)-I-2-ß-carbomethoxy-3ß-(4-iodophenyl)-N-(3-fluoropropyl) nortropane single photon emission computed tomography (123I-FP-CIT SPECT) seems to be a promising method as it reveals abnormalities in pro-DLB with a psychiatric-onset. New potential biomarkers can be revealed via novel techniques, such as manual segmentation in magnetic resonance imaging (MRI), which helps detect atrophy of the substantia innominata in pro-DLB with a psychiatric-onset as opposed to an onset with mild cognitive impairment (MCI). FDG-PET can also help us distinguish patients with mixed pro-DLB from those pro-DLB patients with a psychiatric-onset or MCI-onset. Changes in large-scale networks in the posterior standard mode and in attentional networks could be early signs in resting-state functional MRI to characterise pro-DLB. Conclusions In conclusion, there is a wide range of techniques that need to be explored in large-scale studies and are of promising value in understanding pro-DLB with a psychiatric-onset.
Confidence intervals for the length of the receiver-operating characteristic curve based on a smooth estimator

A good diagnostic test should show different behavior on both the positive and the negative populations. However, this is not enough for having a good classification system. The binary classification problem is a complex task, which implies to define decision criteria. The knowledge of the level of dissimilarity between the two involved distributions is not enough. We also have to know how to define those decision criteria. The length of the receiver-operating characteristic curve has been proposed as an index of the optimal discriminatory capacity of a biomarker. It is related not with the actual but with the optimal classification capacity of the considered diagnostic test. One particularity of this index is that its estimation should be based on parametric or smoothed models. We explore here the behavior of a kernel density estimator-based approximation for estimating the length of the receiver-operating characteristic curve. We prove the asymptotic distribution of the resulting statistic, propose a parametric bootstrap algorithm for confidence intervals construction, discuss the role that the bandwidth parameter plays in the quality of the provided estimations and, via Monte Carlo simulations, study its finite-sample behavior considering four different criteria for the bandwidth selection. The practical use of the length of the receiver-operating characteristic curve is illustrated through two real-world examples.