Miracle-dz/UniFAR-FTUs huggingface dataset:
Intranasal chitosan-g-HPβCD nanoparticles of efavirenz for the CNS targeting

Abstract Incompetence of antiretrovirals (ARV) in complete eradication of HIV from the CNS is the biggest issue in neuro-AIDS treatment. The ineffectiveness is largely due to the poor penetration of ARV. Hence, the present study is attempted to enhance the CNS uptake of efavirenz (EFV) by designing intranasal EFV nanoparticles (EFV-NPs). EFV-NPs were fabricated using chitosan-g-HPβCD by ionic gelation method and optimized using quadratic response surface methodology (RSM) employing two-factor, five-level circumscribed central composite design. NPs containing drug: polymer ratio (1.25:0.79) were spherical with 198 ± 4.4 nm size, 23.28 ± 1.5% drug loading and 38 ± 1.43% entrapment efficiency. NPs showed sustained drug release (99.03 ± 0.30% in 8 h) and followed Fickian diffusion mechanism. It gave 4.76 times greater permeability than plain drug solution through porcine nasal mucosa. Enhanced CNS bioavailability (12.40-fold that of i.v solution) of EFV, high drug-targeting percentage (99.24%) and drug-targeting index (141.3) post-intranasal administration of NPs was observed. These results are corroborated by gamma scintigraphy images, which revealed high CNS uptake. NPs appeared histocompatible with porcine nasal mucosa and non-toxic to L929 cell line. Thus, CS-g-HPβCD served as a potential carrier in developing intranasal mucoadhesive EFV-NPs for the CNS targeting.
Comparative activity of tedizolid and glycopeptide combination therapies for the treatment of Staphylococcus aureus infections: an in vitro and in vivo evaluation against strains with reduced susceptibility to glycopeptides

Purpose. Glycopeptides are widely used for the treatment of meticillin‐resistant Staphylococcus aureus (MRSA) infections. Although difficult to detect, isolates with reduced (GISA), hetero (hGISA) or complete (GRSA) resistance to glycopeptides are increasingly reported. Optimal therapy for such strains is unknown. We compared the in vitro and in vivo activity of tedizolid (TED), a recently licensed oxazolidonone, with vancomycin (VAN) and teicoplanin (TEIC) combined with fusidic acid (FD) or rifampicin (RIF) against S. aureus (SA) with reduced susceptibility to glycopeptides. Methods. Susceptibility was determined for six (GISA, hGISA and GRSA) reference strains and 72 clinical MRSA isolates screened for hGISA/GISA‐like phenotypes. Synergy and bactericidal activity were assessed using chequerboard and time‐kill assays. The G. mellonella wax moth caterpillar model was used to measure the activity of TED and the combinations in vivo. Results. Glycopeptide MICs (VAN/TEIC) ranged from 0.5‐8/4 and 0.125‐1 for TED. No significant synergy was noted when VAN/TEIC were combined with either RIF or FD. Time‐kill assays confirmed that TED was bacteriostatic but superior to VAN and TEIC against GISA strains. In G. mellonella TED was more effective than TEIC monotherapy versus GISA strains. The combination of TEIC with RIF was the most effective combination overall, both in vitro and in vivo. Conclusions. TED had good in vitro activity versus MRSA including those with reduced susceptibility to glycopeptides. Although bacteriostatic, it was effective in the G. mellonella model and superior to TEIC in the treatment of GISA. Although this supports the use of TED for MRSA and GISA, the TEIC/RIF combination also warrants further study.
Tips for reading patents: a concise introduction for scientists

ABSTRACT Many commercial and academic institutions protect their commercially valuable research information using patents, making the patent literature a rich and early source of cutting-edge research. While scientists and students often create the data that finds its way into patents, some rarely read the patent literature. Here, we provide an informal and brief collection of hints and tips that may assist scientists and students who do not regularly read the patent literature to locate the key scientific findings that are disclosed by patentees. These tips will introduce the reader to: (i) the general structure of patents and the sections of the patents that scientists and students may find particularly helpful; and (ii) a few factors to keep in mind when using data disclosed in the patent literature, such as patent lifespans, jurisdictions and the patent review processes. Although this is not a comprehensive and complete guide to reading patents, the accessible nature of this informal introduction to patent reading should assist scientists and students to make more effective use of the cutting-edge research disclosed in patent specifications.
On the existence of a nontrivial equilibrium in relation to the basic reproductive number

Abstract Equilibrium analysis in autonomous evolutionary models is of central importance for developing long term treatments. This task typically includes checks on the existence and stability of some equilibria. Prior to touching on the stability, one often attempts to determine the existence where the basic reproductive number ℛ0 plays a critical role as a threshold parameter. When analyzing a nontrivial equilibrium (e.g., an endemic, boundary, or coexistence equilibrium) where ℛ0 is explicit, we usually come across a typical result: if ℛ0 >1, then a nontrivial equilibrium exists in the biological sense. However, for more sophisticated models, ℛ0 can be too complicated to be revealed in terms of the involving parameters; the task of relating the formulation of a nontrivial equilibrium to ℛ0 thus becomes intractable. This paper shows how to mitigate such a problem with the aid of functional analysis, adopting the framework of a nonlinear eigenvalue problem. An equilibrium equation is first to be transformed into a canonical equation in a lower dimension, and then the existence is confirmed under several conditions. Three models are tested showing the applicability of this approach.
Liver fungal infections: an overview of the etiology and epidemiology in patients affected or not affected by oncohematologic malignancies

Fungal infections of the liver, most commonly caused by Candida spp. , often occur in patients with hematologic malignancies treated with chemotherapy. Colonization of the gastrointestinal tract is thought to be the main origin of dissemination of Candida; mucositis and neutropenia facilitate the spread of Candida from the gastrointestinal tract to the liver. Hepatic involvement due to other fungi is a less common infectious complication in this setting. Fungal infections represent a less common cause of hepatic abscesses in non-oncohematologic population and the trend appears to be decreasing in recent years. Understanding of the etiology and epidemiology of fungal infections of the liver is indicated for an appropriate antimicrobial therapy and an overall optimal management of fungal liver infections.
The Effects of Directional Processing on Objective and Subjective Listening Effort.

Purpose The purposes of this investigation were (a) to evaluate the effects of hearing aid directional processing on subjective and objective listening effort and (b) to investigate the potential relationships between subjective and objective measures of effort. Method Sixteen adults with mild to severe hearing loss were tested with study hearing aids programmed with 3 settings: omnidirectional, fixed directional, and bilateral beamformer. A dual-task paradigm and subjective ratings were used to assess objective and subjective listening effort, respectively, in 2 signal-to-noise ratios. Testing occurred in rooms with either low or moderate reverberation. Results Directional processing improved subjective and objective listening effort, although benefit for objective effort was found only in moderate reverberation. Subjective reports of work and tiredness were more highly correlated with word recognition performance than objective listening effort. However, subjective ratings about control were significantly correlated with objective listening effort. Conclusions Directional microphone technology in hearing aids has the potential to improve listening effort in moderately reverberant environments. In addition, subjective questions that probe a listener's desire to exercise control may be a viable method for eliciting ratings that are significantly related to objective listening effort.
The effect of the mechanism and amount of missingness on subset correspondence analysis

ABSTRACT The application of subset correspondence analysis is a relatively new technique to deal with the analysis of categorical data with missingness. A simulation study is used to test the effects of Little and Rubin's missingness mechanisms, as well as missingness up to 50% on subset correspondence analysis. Missingness was simulated across 18 different scenarios and each scenario was repeated 10 times, with outcomes averaged across the 10 simulations. In this application, it was found that while missingness in excess of 30% has some effect on certain outcomes, there is no evidence to suggest that the missingness mechanism significantly affects results.
Complete mitochondrial genome of the Grey nightjar Caprimulgus jotaka (Caprimulgiformes: Caprimulgidae)

Abstract The Grey nightjar Caprimulgus jotaka is a species of migratory nightjar found in East Asia. In this study, we determined its complete mtDNA by PCR-based method. The mitochondrial genome of Caprimulgus jotaka is a 17,536 bp circular molecule with the A + T content of 53.82%, which contains 37 typical mitochondrial genes (13 protein-coding genes, 2 rRNAs and 22 tRNAs) and a non-coding control region (D-loop). All protein-coding genes are initiated by ATG codon, except for the ND1 gene starts with GTG codon, and ND3 uses ATA codon. TAA is the most frequent stop codon. All tRNAs possess the classic cloverleaf secondary structure except for tRNASer(AGY) and tRNALeu(CUN), which lacks the ‘‘DHU’’ stem. The D-loop is a 1969 bp long AT-rich region, which located between tRNAGlu and tRNAPhe.
The Pharmacological Basis for Metrifonate’s Favourable Tolerability in the Treatment of Alzheimer’s Disease

Metrifonate, through its pharmacologically active metabolite 2,2-dichlorovinyl dimethylphosphate (DDVP), is a long-acting cholinesterase inhibitor for the symptomatic treatment of mild-to-moderate Alzheimer’s disease. Clinical studies with Alzheimer patients have demonstrated the favourable safety and tolerability profile of this drug. Metrifonate, at therapeutic doses for Alzheimer’s disease, achieves high levels of cholinesterase inhibition, i.e. ≧70%, without the need for dose escalation. This is a consequence of the low rate of fluctuation of enzyme activity during therapy with metrifonate. This, in turn, is due to the protracted hydrolytic transformation of metrifonate into DDVP, the resulting smooth onset of cholinesterase inhibition, and the subsequent long duration of action which far outlasts the presence of the active drug in the body. Both metrifonate and DDVP are rapidly metabolized and eliminated from the body. Further, their metabolism does not involve the cytochrome P450 system and both compounds show low plasma protein binding. These pharmacokinetic features account, at least in part, for the favourable safety and tolerability profile of metrifonate as they suggest a minimal risk of drug-drug interactions with other likely co-medications in the long-term therapy of Alzheimer patients.
Differences Among States in Rural Veterans’ Use of VHA and Non‐VHA Hospitals

PURPOSE To understand how vouchers for non-VHA care of VHA-enrolled veterans might affect rural enrollees, we determined how much enrollees use VHA and non-VHA inpatient care, and whether this use varies substantially between rural and urban residents depending on state of residence. METHODS For veterans listed in the 2007 VHA enrollment file as living in Arizona, Iowa, Louisiana, Tennessee, Florida, South Carolina, Pennsylvania, or New York, we merged 2004-2007 administrative discharge data for all VHA hospitalizations with all non-VHA hospitalizations listed in state health department or hospital association databases. Within states, rural and urban residents (RUCA-defined) were compared on VHA and non-VHA hospitalization rates, overall and for major diagnostic categories. FINDINGS Non-VHA hospital use was much greater than VHA use, though it also was more variable across states. In states with higher proportions of urban enrollees, use of non-VHA hospitals was lower for small or isolated rural town residents than urban residents; in the more rural states, it was greater. Rural enrollees also used VHA hospitals more than urban enrollees if they lived in the South, but they used VHA hospitals less in other states. Findings were consistent across principal diagnoses, except that in every state, rural veterans were hospitalized less often for mental disorders but more for respiratory diseases. Logistic regressions controlling several covariates consistently showed that very rural enrollees relied on VHA hospitals more than urban enrollees. Vouchers would likely increase non-VHA use more in states with greater rural populations. CONCLUSIONS Vouchers for non-VHA inpatient care might have greater impact in rural states.
Surface response to rain events throughout the West African monsoon

Abstract. This study analyses the response of the continental surface to rain events, taking advantage of the long-term near-surface measurements over different vegetation types at different latitudes, acquired during the African Monsoon Multidisciplinary Analysis (AMMA) by the AMMA-CATCH observing system. The simulated surface response by nine land surface models involved in AMMA Land Model Intercomparison Project (ALMIP), is compared to the observations. The surface response, described via the evaporative fraction (EF), evolves in two steps: the immediate surface response (corresponding to an increase of EF occurring immediately after the rain) and the surface recovery (characterized by a decrease of EF over several days after the rain). It is shown that, for all the experimental sites, the immediate surface response is mainly dependent on the soil moisture content and the recovery period follows an exponential relationship whose rate is strongly dependent on the vegetation type (from 1 day over bare soil to 70 days over forest) and plant functional type (below and above 10 days for annual and perennial plants, respectively). The ALMIP model ensemble depicts a broad range of relationships between EF and soil moisture, with the worst results for the drier sites (high latitudes). The land surface models tend to simulate a realistic surface recovery for vegetated sites, but a slower and more variable EF decrease is simulated over bare soil than observed.
The Reductions in Sweetened Milk Intake Induced by Interleukin-1 and Endotoxin Are Not Prevented by Chronic Antidepressant Treatment

Administration of interleukin-1 (IL-1) and endotoxin (lipopolysaccharide, LPS) to rodents can decrease food intake, a behavioral response resembling the diminution of appetite observed in human depression. IL-1 and LPS are known to affect cerebral neurotransmission involving norepinephrine and serotonin, both of which have been implicated in feeding behavior and in the pharmacotherapy of depression in man. The ability of chronic antidepressant treatment to attenuate LPS-induced depressed feeding in rats has been cited as evidence that cytokines may be involved in human depression. Thus, we studied the effects of chronic treatment with the tricyclic antidepressant, imipramine, and the novel antidepressant, venlafaxine, on the sweetened milk intake challenged with intraperitoneally injected IL-1β and LPS. Chronic (from 2 to 8 weeks) treatment of the mice with imipramine (10 mg/kg once or twice daily) or venlafaxine (10 and 20 mg/kg/day) did not significantly alter the decreases in milk intake in response to mIL-1β or LPS. In some experiments, chronic imipramine slightly decreased body weight and slightly increased milk intake, but not food pellet intake. Venlafaxine had none of these effects. Analysis of variance did not indicate any significant interactions between the antidepressant and IL-1 or LPS treatments. These results indicate that chronic treatment with antidepressants does not significantly alter the responses to IL-1 or LPS in the mouse sweetened milk model of sickness behavior.
Cognisant computing and 'lean' practices: interactions with 21st century businesses and implications

Cognisant computing and 'lean' practices portend great promises for savvy businesses of the 21st century, with the potential to create huge savings and returns, guarantee global competitiveness, enhance efficiency of manufacturing and process chain operations, and boost financial performance, productivity and products' market performance. Until now, the nexus between these twain paradigms remained blurred, with very little knowledge of how both can be combined and harnessed to ensure business success in the 21st century. The dawn of the Industry 4.0 revolution necessitates that these twain concepts be re-investigated to uncover a possible nexus between them that could guarantee the success, competitive advantage and sustainability of businesses in the industrial revolution. This study utilises the exploratory research methodology due to the relatively new and emergent nature of the domain of discourse. Cognisant computing is introduced, illuminating prospects for businesses, and how 'lean' practices could be integrated to guarantee business success.
Eimeria taggarti N. Sp., a Novel Coccidian (Apicomplexa: Eimeriorina) in the Prostate of an Antechinus flavipes

Abstract A novel coccidian species was discovered in the prostate of an Antechinus flavipes (yellow-footed antechinus) in South Australia during the period of postmating male antechinus immunosuppression and mortality. This novel coccidian is unusual because it develops extraintestinally and sporulates endogenously within the prostate gland of its mammalian host. Histological examination of prostatic tissue revealed dense aggregations of spherical and thin-walled tetrasporocystic, dizoic, sporulated coccidian oocysts within tubular lumina, with unsporulated oocysts and gamogonic stages within the cytoplasm of glandular epithelial cells. This coccidian was observed occurring concurrently with dasyurid gammaherpesvirus 1 infection of the antechinus' prostate. Eimeria-specific 18S small-subunit ribosomal (r)DNA polymerase chain reaction amplification was used to obtain a partial 18S rDNA nucleotide sequence from the antechinus coccidian. Bayesian phylogenetic analysis based on 18S rDNA gene sequences revealed that the novel coccidian clusters with reptile-host coccidians, forming an ancestral basal lineage of the eimeriid clade. The species has been named Eimeria taggarti n. sp. on the basis of both sporulated oocyst morphology and molecular characterization. It is suspected that E. taggarti is sexually transmitted via excretion of sporulated oocysts or free sporocysts with prostatic secretions in semen.
Realization of a half-metallic state on bilayer WSe2 using doping transition metals (Cr, Mn, Fe, Co, Ni) in its interlayer

The structural, electronic and magnetic properties of Cr, Mn, Fe, Co and Ni-doped bilayer WSe2 are predicted by using first principles calculations. The doped transition-metal (TM) atoms show a covalent-binding with the nearest Se atoms. The calculated electronic structures reveal that the TM Cr, Mn, Fe and Co-doped bilayer WSe2 exhibits a half-metallic character with a 100% spin polarization at the Fermi level, and the reason is ascribed to the strong hybridization peak between the transition metals and the parent W and Se atoms. The Ni-doped bilayer WSe2 is still a semiconductor with nonmagnetism. The Fe-doped system has a robust stability of half-metallicity because there are three connected states peak spanning the Fermi level. The doping of Cr, Mn, Fe and Co atoms leads to a prominent total magnetism (0.93–3.65 μ B moment per unit cell), and an induced ∼0.3 μ B moment in parent W atoms is found in addition to the main contribution of TM atomic magnetism (0.71–3.33 μ B moment per atom). The predicted Cr, Mn, Fe and Co-doped bilayer WSe2 should be the candidate materials for spintronic devices due to their magnetic and half-metallic nature.
Downlink statistical precoding scheme for spatially correlated massive MIMO systems

In this paper, we consider spatial beamforming for massive multiple-input multiple-output (MIMO) systems in frequency division duplexing (FDD). In order to reduce channel state information (CSI) feedback overhead of users, near-by users that have similar statistical channel correlation are put into a group and channel correlation matrix based precoding scheme is proposed. More specifically, we propose to employ two-stage precoder at a base station (BS): Outer precoder and inner precoder. The former is designed to minimize inter-group interference by considering the statistical channel correlation. The latter is designed to minimize intra-group interference by utilizing modified statistical channel correlation and instantaneous channel state information (ICSI). The inner precoder is composed of three steps: precoded pilot signal transmission phase at the BS, effective channel gain calculation and feedback stage at the mobile user, and data transmission stage at the BS.
Runx1 is sufficient for blood cell formation from non-hemogenic endothelial cells in vivo only during early embryogenesis

ABSTRACT Hematopoietic cells differentiate during embryogenesis from a population of endothelial cells called hemogenic endothelium (HE) in a process called the endothelial-to-hematopoietic transition (EHT). The transcription factor Runx1 is required for EHT, but for how long and which endothelial cells are competent to respond to Runx1 are not known. Here, we show that the ability of Runx1 to induce EHT in non-hemogenic endothelial cells depends on the anatomical location of the cell and the developmental age of the conceptus. Ectopic expression of Runx1 in non-hemogenic endothelial cells between embryonic day (E) 7.5 and E8.5 promoted the formation of erythro-myeloid progenitors (EMPs) specifically in the yolk sac, the dorsal aorta and the heart. The increase in EMPs was accompanied by a higher frequency of HE cells able to differentiate into EMPs in vitro. Expression of Runx1 just 1 day later (E8.5-E9.5) failed to induce the ectopic formation of EMPs. Therefore, endothelial cells, located in specific sites in the conceptus, have a short developmental window of competency during which they can respond to Runx1 and differentiate into blood cells. Summary: Runx1 expression in non-hemogenic endothelial cells promotes blood cell formation in ectopic sites in the mouse conceptus, but only if Runx1 is expressed before embryonic day 8.5.
Reply to: Macrophages Driving Heterotopic Ossification: Convergence of Genetically‐Driven and Trauma‐Driven Mechanisms

Michael R Convente, Salin A Chakkalakal, EnJun Yang, Robert J Caron, Deyu Zhang, Taku Kambayashi, Frederick S Kaplan, and Eileen M Shore Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA The Center for Research in FOP and Related Disorders, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA