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Malignant peripheral nerve sheath tumors (MPNSTs) are extremely uncommon neoplasms, predominantly seen within the deep soft tissues of the extremities, in close proximity to the nerve trunks. Retroperitoneal MPNSTs are exceedingly rare, usually seen in association with neurofibromatosis type 1 (NF-1), and often result from malignant degeneration of a plexiform neurofibroma. These tumors are highly malignant and the prognosis is worsened if they occur in association with NF-1. Metastasis is not uncommon, but local invasion by these tumors is rarely reported. Renal artery pseudoaneurysms are mostly iatrogenic and rarely result from invasion by retroperitoneal neoplasms. Ultrasonography is a valuable tool in early diagnosis of these neoplasms and vascular complications, particularly in emergency cases requiring immediate operative intervention. To the best of our knowledge, no case of renal artery pseudoaneurysm caused by retroperitoneal MPNST has been reported to date. We present a case of a middle-aged female with Von Recklinghausen disease, complaining of sudden onset of severe abdominal pain, where ultrasound accurately diagnosed renal artery pseudoaneurysm caused by a large retroperitoneal MPNST, and who was later treated by radical excision of the tumor and nephrectomy. [ABSTRACT FROM AUTHOR]

Deletion of phenylalanine 508 (∆F508) of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) anion channel protein is the leading cause of Cystic Fibrosis (CF). Here, we report the analysis of CFTR and ∆F508-CFTR interactomes using BioID (proximity-dependent biotin identification), a technique that can also detect transient associations. We identified 474 high-confidence CFTR proximity-interactors, 57 of which have been previously validated, with the remainder representing novel interaction space. The ∆F508 interactome, comprising 626 proximity-interactors was markedly different from its wild type counterpart, with numerous alterations in protein associations categorized in membrane trafficking and cellular stress functions. Furthermore, analysis of the ∆F508 interactome in cells treated with Orkambi identified several interactions that were altered as a result of this drug therapy. We examined two candidate CFTR proximity interactors, VAPB and NOS1AP, in functional assays designed to assess surface delivery and overall chloride efflux. VAPB depletion impacted both CFTR surface delivery and chloride efflux, whereas NOS1AP depletion only affected the latter. The wild type and ∆F508-CFTR interactomes represent rich datasets that could be further mined to reveal additional candidates for the functional rescue of ∆F508-CFTR. [ABSTRACT FROM AUTHOR]

Hydatid disease, caused by Echinococcus granulosus, is a zoonotic infection encountered worldwide. Though involvement of the liver and lungs is quite common, pelvic involvement is rarely reported, with the incidence being 0.2-2.2 %. Ovarian and broad ligament hydatids are rare entities and are usually seen after rupture of a hepatic hydatid cyst. These cysts are usually asymptomatic, and a high index of clinical suspicion coupled with unequivocal imaging findings is required to make an accurate and timely diagnosis. We present a case of multifocal hydatid disease in a female child involving the lungs and liver and provide an account of the quintessential radiological findings. [ABSTRACT FROM AUTHOR]

Objective: To assess the unit cost of level II neonatal intensive care treatment delivered through public hospitals and its fiscal implications in India. Design: Cost analysis study. Setting: Four Special Care Newborn Units (SCNUs) in public sector district hospitals in three Indian states, i.e. Bihar, Madhya Pradesh and Orissa, for the period 2010. Methods: Bottom-up economic costing methodology was adopted. Health system resources, i.e. capital, equipment, drugs and consumables, non-consumables, referral and overheads, utilized to treat all neonates during 2010 were elicited. Additionally, 360 randomly selected treatment files of neonates were screened to estimate direct out-of-pocket (OOP) expenditure borne by the patients. In order to account for variability in prices and other parameters, we undertook a univariate sensitivity analysis. Main Outcome Measures: Unit cost was computed as INR (Indian national rupees) per neonate treated and INR per bed-day treatment in SCNU. Standardized costs per neonate treatment and per bed day were estimated to incorporate the variation in bed occupancy rates across the sites. Results: Overall, SCNU neonatal treatment costs the Government INR 4581 (USD 101.8) and INR 818 (USD 18.2) per neonate treatment and per bed-day treatment, respectively. Standardized treatment costs were estimated to be INR 5090 (USD 113.1) per neonate and INR 909 (USD 20.2) per bed-day treatment. In the event of entire direct medical expenditure being borne by the health system, we found cost of SCNU treatment as INR 4976 (USD 110.6) per neonate and INR 889 (USD 19.8) per bed-day. Conclusions: Level II neonatal intensive care at SCNUs is cost intensive. Rational use of SCNU services by targeting its utilization for the very low birth weight neonates and maintenance of community based home-based newborn care is required. Further research is required on cost-effectiveness of level II neonatal intensive care against routine pediatric ward care. [ABSTRACT FROM AUTHOR]

Translin and its interacting partner protein, TRAX, are members of the translin superfamily. These proteins are involved in mRNA regulation and in promoting RISC activity by removing siRNA passenger strand cleavage products, and have been proposed to play roles in DNA repair and recombination. Both homomeric translin and heteromeric translin-TRAX complex bind to ssDNA and RNA; however, the heteromeric complex is a key activator in siRNA-mediated silencing in human and drosophila. The residues critical for RNase activity of the complex reside in TRAX sequence. Both translin and TRAX are well conserved in eukaryotes. In present work, a single translin superfamily protein is detected in Chloroflexi eubacteria, in the known phyla of archaea and in some unicellular eukaryotes. The prokaryotic proteins essentially share unique sequence motifs with eukaryotic TRAX, while the proteins possessing both the unique sequences and conserved indels of TRAX or translin can be identified from protists. Intriguingly, TRAX protein in all the known genomes of extant Chloroflexi share high sequence similarity and conserved indels with the archaeal protein, suggesting occurrence of TRAX at least at the time of Chloroflexi divergence as well as evolutionary relationship between Chloroflexi and archaea. The mirror phylogeny in phylogenetic tree, constructed using diverse translin and TRAX sequences, indicates gene duplication event leading to evolution of translin in unicellular eukaryotes, prior to divergence of multicellular eukayrotes. Since Chloroflexi has been debated to be near the last universal common ancestor, the present analysis indicates that TRAX may be useful to understand the tree of life. [ABSTRACT FROM AUTHOR]

We evaluate a novel low cost sensor network architecture, where sensors are mounted on agents moving without an explicit objective of sensing, for the task of level set estimation. A level set in a planar scalar field is the set of points with field values greater than or equal to a specified value. This problem is of fundamental importance in sensor networking and finds numerous applications in environmental studies, surveillance, habitat monitoring and processing geospatial data. We model the problem as a classification problem and evaluate a heuristic to reduce the amount of communication, assuming that the base station uses a Support Vector Machine classifier. We then develop a fully distributed, low complexity solution which uses opportunistic information exchange to estimate level set boundaries locally at nodes selected using leader election. We observe that the learning rate of the boundary in a locality is inversely proportional to its complexity. Effectiveness of the proposed scheme is evaluated using simulations with data from both synthetic and measured fields. Random way point mobility model is used for node motion and trade-off of accuracy and of coverage with communication costs is studied. [ABSTRACT FROM AUTHOR]

Translin protein is highly conserved in eukaryotes. Human translin binds both ssDNA and RNA. Its nucleic acid binding site results from a combination of basic regions in the octameric structure. We report here the first biochemical characterization of wild-type Drosophila melanogaster (drosophila) translin and a chimeric translin, and present 3.5 Å resolution crystal structures of drosophila P168S mutant translin from two crystal forms. The wild-type drosophila translin most likely exists as an octamer/decamer, and binds to the ssDNA Bcl-CL1 sequence. In contrast, ssDNA binding-incompetent drosophila P168S mutant translin exists as a tetramer. The structures of the mutant translin are identical in both crystal forms, and their C-terminal residues are disordered. The chimeric protein, possessing two nucleic acid binding motifs of drosophila translin, the C-terminal residues of human translin, and serine at position 168, attains the octameric state and binds to ssDNA. The present studies suggest that the oligomeric status of translin critically influences the DNA binding properties of translin proteins. [ABSTRACT FROM AUTHOR]

The problem of empirical data modeling is pertinent to several mechanics domains. Empirical data modeling involves a process of induction to build up a model of the system from which responses of the system can be deduced for unobserved data. Machine learning tools can model underlying non-linear function given training data without imposing prior restriction on the type of function. In this paper, we show how Support Vector Machines (SVM) can be employed to solve design problems involving optimizations over parametric space and parameter prediction problems that are recurrent in engineering domain. The problem considered is diffuser design where the optimal value of pressure recovery parameter can be obtained very efficiently by SVM based algorithm even in a large search space. In addition, locating the position of points on a string vibrating in a damped medium serves as an appropriate prediction problem. A grid-searching algorithm is proposed for automatically choosing the best parameters of SVM, thus resulting in a generic framework. The results obtained by SVM are shown to be theoretically sound and a comparison with other approaches such as spline interpolation and Neural Networks shows the superiority of our framework. [ABSTRACT FROM AUTHOR]

ABSTRACT Primary hydatid disease of breast is a rare entity and is caused by the larval stage of Echinococcus granulosus. The disease is more commonly seen in sheep-rearing populations and imaging plays a pivotal role in its diagnosis. Several imaging signs have been described in relation to hydatid cysts. However, the 'scroll sign,' due to the infolding of the endocyst, has rarely been encountered, with only one similar case in literature, in which the imaging findings were inconclusive. We present a case of primary hydatid disease of breast in a young Asian woman, with the sonographic scroll sign. © 2014 Wiley Periodicals, Inc. J Clin Ultrasound 42:502-504, 2014 [ABSTRACT FROM AUTHOR]

Translationally controlled tumour proteins (TCTPs) are omnipresent in eukaryotes and play important physiological roles. This protein is identified as an allergen in the fungi Alternaria alternata and Cladosporium herbarum, and is involved in maintaining a balance between sexual and asexual differentiation in Aspergillus nidulans. MoTCTP regulates growth and conidiation in the plant pathogen Magnaporthe oryzae. We present here the functions of a TCTP orthologue (Tcp1) in the plant beneficial fungus Trichoderma virens. T. virens Tcp1 shares 42.94% and 39.88% sequence similarity with the evolutionarily distant human TCTP and maize TCTP, respectively. Based on prediction models, the secondary structure elements (α-helices and β-sheets) were found to be very well conserved barring a few insertions/deletions in the loop region. Using homologous recombination, we obtained three independent deletion mutants in this gene and a comparison of phenotypes with the wild type strain revealed that this protein has multiple functions in T. virens. Tcp1 knockout mutants showed slow radial growth and dry weight production. Δtcp1 mutants also lost the ability to overgrow the plant pathogenic fungi Sclerotium rolfsii and Rhizoctonia solani , but retained this property against the oomycete Pythium aphanidermatum reflecting selective loss of antagonistic ability. The mutants also lost the ability to colonize and kill the sclerotia of S. rolfsii. • T. virens mutants in a translationally controlled tumor protein (TCTP) obtained through gene deletion approach. • T. virens TCTP mutants had reduced growth rate and conidiation. • The mutants lost the ability to colonize two soil-borne plant pathogenic fungi. • TCTP mutants lost their ability to parasitize the sclerotia of S. rolfsii. [ABSTRACT FROM AUTHOR]

Trichoderma virens genome harbors two isoforms of GAPDH, one (gGPD) involved in glycolysis and the other one (vGPD) in secondary metabolism. vGPD is expressed as part of the "vir" cluster responsible for the biosynthesis of volatile sesquiterpenes. The secondary metabolism-associated GAPDH is tolerant to the anti-cancer metabolite heptelidic acid (HA), produced by T. virens. Characterizing the HA-tolerant form of GAPDH, thus has implications in cancer therapy. In order to get insight into the mechanism of HA-tolerance of vGPD, we have purified recombinant form of this protein. The protein displays biochemical and biophysical characteristics analogous to the gGPD isoform. It exists as a tetramer with T m of about 56.5 °C, and displays phosphorylation enzyme activity with K m and K cat of 0.38 mM and 2.55 sec−1, respectively. The protein weakly binds to the sequence upstream of the vir 4 gene that codes for the core enzyme (a terpene cyclase) of the "vir" cluster. The EMSA analysis indicates that vGPD may not act as a transcription factor driving the "vir" cluster, at least not by directly binding to the promoter region. We also succeeded in obtaining small crystals of this protein. We have constructed structural models of vGPD and gGPD of T. virens. In silico constrained docking analysis reveals weaker binding of heptelidic acid in vGPD, compared to gGPD protein. • An isoform of GAPDH (vGPD) that is associated with a secondary-metabolism gene cluster has been expressed in E. coli. • Purified vGPD protein showed biophysical and biochemical characteristics similar to gGPD (GAPDH for glycolysis) protein. • The vGPD protein showed non-specific binding to the promoter region of the putative terpene cyclase gene. • Lower affinity of the heptelidic acid with vGPD protein was indicated by docking analysis, in comparison to gGPD protein. [ABSTRACT FROM AUTHOR]

Triple-negative breast cancer (TNBC), characterized by the absence or low expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor (HER2), is the most aggressive subtype of breast cancer. TNBC accounts for about 15% of breast cancer cases in the U.S., and is known for high relapse rates and poor overall survival (OS). Chemo-resistant TNBC is a genetically diverse, highly heterogeneous, and rapidly evolving disease that challenges our ability to individualize treatment for incomplete responders and relapsed patients. Currently, the frontline standard chemotherapy, composed of anthracyclines, alkylating agents, and taxanes, is commonly used to treat high-risk and locally advanced TNBC. Several FDA-approved drugs that target programmed cell death protein-1 (Keytruda) and programmed death ligand-1 (Tecentriq), poly ADP-ribose polymerase (PARP), and/or antibody drug conjugates (Trodelvy) have shown promise in improving clinical outcomes for a subset of TNBC. These inhibitors that target key genetic mutations and specific molecular signaling pathways that drive malignant tumor growth have been used as single agents and/or in combination with standard chemotherapy regimens. Here, we review the current TNBC treatment options, unmet clinical needs, and actionable drug targets, including epidermal growth factor (EGFR), vascular endothelial growth factor (VEGF), androgen receptor (AR), estrogen receptor beta (ERβ), phosphoinositide-3 kinase (PI3K), mammalian target of rapamycin (mTOR), and protein kinase B (PKB or AKT) activation in TNBC. Supported by strong evidence in developmental, evolutionary, and cancer biology, we propose that the K-RAS/SIAH pathway activation is a major tumor driver, and SIAH is a new drug target, a therapy-responsive prognostic biomarker, and a major tumor vulnerability in TNBC. Since persistent K-RAS/SIAH/EGFR pathway activation endows TNBC tumor cells with chemo-resistance, aggressive dissemination, and early relapse, we hope to design an anti-SIAH-centered anti-K-RAS/EGFR targeted therapy as a novel therapeutic strategy to control and eradicate incurable TNBC in the future. [ABSTRACT FROM AUTHOR]

Electric fields are used in biology to address a broad range of questions and through a variety of techniques, including electroporation, gene electrotransfer (GET), electrostimulation (ES), and electrochemotherapy. Each of these modalities requires specific conditions and has drastically different target outcomes on the cell. ES has demonstrated that non-pore forming electric fields alter cell cycle progression. However, pore forming electric fields such as with GET have not been as widely explored despite major clinical advancements. Additionally, the real-time visual analysis of electrical field effects on mammalian cell culture is currently lacking among most commercial systems. To facilitate investigations into these research areas, an electroporation cytometry system was developed including a custom chamber compatible with live cell imaging and exponential decay pulse generator for live cell analysis. The functionality of the system was demonstrated using a recombinant cell line using U-2 OS cells and FUCCI(CA)5 cell cycle reporter. The exposure of the cells to a 180 V pulse in both unsynchronized and synchronized populations revealed an effect on the cell cycle. [ABSTRACT FROM AUTHOR]

The article presents a study that explores scaling DNA data storage with nanoscale electrode wells. It mentions about the advancement in technologies have focused on the development of new encoding algorithms, automation, preservation, and sequencing technologies . It discusses the challenges in deployment of DNA data storage.

Centriolar satellites are small electron‐dense granules that cluster in the vicinity of centrosomes. Satellites have been implicated in multiple critical cellular functions including centriole duplication, centrosome maturation, and ciliogenesis, but their precise composition and assembly properties have remained poorly explored. Here, we perform in vivo proximity‐dependent biotin identification (BioID) on 22 human satellite proteins, to identify 2,113 high‐confidence interactions among 660 unique polypeptides. Mining this network, we validate six additional satellite components. Analysis of the satellite interactome, combined with subdiffraction imaging, reveals the existence of multiple unique microscopically resolvable satellite populations that display distinct protein interaction profiles. We further show that loss of satellites in PCM1‐depleted cells results in a dramatic change in the satellite interaction landscape. Finally, we demonstrate that satellite composition is largely unaffected by centriole depletion or disruption of microtubules, indicating that satellite assembly is centrosome‐independent. Together, our work offers the first systematic spatial and proteomic profiling of human centriolar satellites and paves the way for future studies aimed at better understanding the biogenesis and function(s) of these enigmatic structures. Synopsis: Centriolar satellites are implicated in cellular functions such as centriole duplication, centrosome maturation and ciliogenesis, but their precise composition and assembly properties are still poorly defined. Spatial and proteomic profiling now reveals their interactome and centrosome‐independent features. BioID of 22 centriolar satellite proteins identifies 2113 proximity interactions amongst 660 proteins.Six additional centriolar satellite proteins were identified.There are multiple microscopically‐resolvable satellite subpopulations.Satellite composition is largely unaffected by centriole depletion or disruption of the microtubule cytoskeleton.PCM1 depletion results in a dramatic change in the proximity interaction landscape of centriolar satellite components. [ABSTRACT FROM AUTHOR]

The distinct sequence feature and spectral blue-shift (~10 nm) of phycocyanin, isolated from Nostoc sp. R76DM (N-PC), were investigated by phylogenetic and crystallographic analyses. Twelve conserved substitutions in N-PC sequence were found distributed unequally among α- and β-subunit (3 in α- and 9 in β-subunit). The phylogenetic analysis suggested that molecular evolution of α- and β-subunit of Nostoc-phycocyanin is faster than evolution of Nostoc-species. The divergence events seem to have occurred more frequently in β-subunit, compared to α-subunit (relative divergence, 7.38 for α-subunit and 9.66 for β-subunit). Crystal structure of N-PC was solved at 2.35 Å resolution to reasonable R-factors (Rwork/RFree = 0.199/0.248). Substitutions congregate near interface of two αβ-monomer in N-PC trimer and are of compensatory nature. Six of the substitutions in β-subunit may be involved in maintaining topology of β-subunit, one in inter-monomer interaction and one in interaction with linker-protein. The β153Cys-attached chromophore adopts high-energy conformational state resulting due to reduced coplanarity of B- and C-pyrrole rings. Distortion in chromophore conformation can result in blue-shift in N-PC spectral properties. N-PC showed significant in-vitro and in-vivo antioxidant activity comparable with other phycocyanin. Since Nostoc-species constitute a distinct phylogenetic clade, the present structure would provide a better template to build a model for phycocyanins of these species. [ABSTRACT FROM AUTHOR]

Centrosomes control cell motility, polarity and migration that is thought to be mediated by their microtubule-organizing capacity. Here we demonstrate that WNT signalling drives a distinct form of non-directional cell motility that requires a key centrosome module, but not microtubules or centrosomes. Upon exosome mobilization of PCP-proteins, we show that DVL2 orchestrates recruitment of a CEP192-PLK4/AURKB complex to the cell cortex where PLK4/AURKB act redundantly to drive protrusive activity and cell motility. This is mediated by coordination of formin-dependent actin remodelling through displacement of cortically localized DAAM1 for DAAM2. Furthermore, abnormal expression of PLK4, AURKB and DAAM1 is associated with poor outcomes in breast and bladder cancers. Thus, a centrosomal module plays an atypical function in WNT signalling and actin nucleation that is critical for cancer cell motility and is associated with more aggressive cancers. These studies have broad implications in how contextual signalling controls distinct modes of cell migration. Centrosomes function in cell migration by organizing microtubules. Here, Luo et al. surprisingly show that centrosome proteins also control migration after recruitment by Wnt-PCP proteins to the cell cortex, leading to actin remodelling and protrusive activity relevant to aggressive cancer motility. [ABSTRACT FROM AUTHOR]

Phycobiliproteins is a family of chromophore-containing proteins having light-harvesting and antioxidant capacity. The phycocyanin (PC) is a brilliant blue coloured phycobiliprotein, found in rod structure of phycobilisome and has been widely studied for their therapeutic and fluorescent properties. In the present study, the hexameric assembly structure of phycocyanin (Syn-PC) from Synechococcus Sp. R42DM is characterized by X-ray crystallography to understand its light-harvesting and antioxidant properties. The crystal structure of Syn-PC is solved with 2.15 Å resolution and crystallographic R-factors, Rwork/Rfree, 0.16/0.21. The hexamer of Syn-PC is formed by heterodimer of two polypeptide chains, namely, α- and β-subunits. The structure is analysed at atomic level to reveal the chromophore microenvironment and possible light energy transfer mechanism in Syn-PC. The chromophore arrangement in hexamer, deviation angle and distance between the chromophore contribute to the energy transfer efficiency of protein. The structural attributes responsible for the antioxidant potential of Syn-PC are recognized and annotated on its 3-dimensional structure. [ABSTRACT FROM AUTHOR]

Background: The standard face-to-face training for the integrated management of childhood illness (IMCI) continues to be plagued by concerns of low coverage of trainees, the prolonged absence of trainees from the health facility to attend training and the high cost of training. Consequently, the distance learning IMCI training model is increasingly being promoted to address some of these challenges in resource-limited settings. This paper examines participants' accounts of the paper-based IMCI distance learning training programme in three district councils in Mbeya region, Tanzania. Methods: A cross-sectional qualitative descriptive design was employed as part of an endline evaluation study of the management of possible serious bacterial infection in Busokelo, Kyela and Mbarali district councils of Mbeya Region in Tanzania. Key informant interviews were conducted with purposefully selected policymakers, partners, programme managers and healthcare workers, including beneficiaries and training facilitators. Results: About 60 key informant interviews were conducted, of which 53% of participants were healthcare workers, including nurses, clinicians and pharmacists, and 22% were healthcare administrators, including district medical officers, reproductive and child health coordinators and programme officers. The findings indicate that the distance learning IMCI training model (DIMCI) was designed to address concerns about the standard IMCI model by enhancing efficiency, increasing outputs and reducing training costs. DIMCI included a mix of brief face-to-face orientation sessions, several weeks of self-directed learning, group discussions and brief face-to-face review sessions with facilitators. The DIMCI course covered topics related to management of sick newborns, referral decisions and reporting with nurses and clinicians as the main beneficiaries of the training. The problems with DIMCI included technological challenges related to limited access to proper learning technology (e.g., computers) and unfriendly learning materials. Personal challenges included work-study-family demands, and design and coordination challenges, including low financial incentives, which contributed to participants defaulting, and limited mentorship and follow-up due to limited funding and transport. Conclusion: DIMCI was implemented successfully in rural Tanzania. It facilitated the training of many healthcare workers at low cost and resulted in improved knowledge, competence and confidence among healthcare workers in managing sick newborns. However, technological, personal, and design and coordination challenges continue to face learners in rural areas; these will need to be addressed to maximize the success of DIMCI. [ABSTRACT FROM AUTHOR]

Background Chronic pancreatitis (CP) is a pathological fibroinflammatory response to persistent inflammation or stress to the pancreas. The effect of frailty on outcomes in patients with CP has not been previously examined. In this study, we examined the effect of frailty on outcomes in hospitalized patients with CP. Methods Records of patients with a primary or secondary discharge diagnosis of CP (ICD10-CM codes K86.0, K86.1) between January 2016 and December 2019 were obtained from the National Inpatient Sample database. Data were collected on patient demographics, hospital characteristics, comorbidities, and etiology of CP. The relationship between frailty and outcomes, including mortality, intensive care unit (ICU) admission, sepsis, shock, length of stay (LOS), and total hospitalization charges (THC), were analyzed using multivariate analysis. Results 722,160 patients were included in the analysis. Patients with a high hospital frailty risk score had a higher mortality risk (adjusted odds ratio [aOR] 12.57, 95% confidence interval [CI] 10.42-15.16; P<0.001) compared to patients with low frailty scores. Patients with high frailty scores also had a higher risk of sepsis (aOR 5.75, 95%CI 4.97-6.66; P<0.001), shock (aOR-26.25, 95%CI-22.83-30.19; P<0.001), ICU admission (aOR 25.86, 95% CI-22.58-29.62; P<0.001), and acute kidney injury (aOR 24.4, 95%CI 22.39-26.66; P<0.001). They also had a longer LOS (7.04 days, 95%CI 6.57-7.52; P<0.001) and higher THC ($72,200, 95%CI 65,904.52-78,496.66; P<0.001). Conclusions Frail patients, as determined by their hospital frailty risk score, are at high risk of worse outcomes. This data suggests opportunities for physicians to risk-stratify patients and predict outcomes. [ABSTRACT FROM AUTHOR]

Gravimetry-based direct measurements of mass concentration require offline analysis which is not suited for field campaigns. Hence such campaigns rely on the estimation of mass concentration by indirect methods mostly calibrated in controlled laboratory conditions. Optical particle counter (OPC) employs algorithms converting the measured number concentration to mass concentration using appropriate conversion factors. The accuracy of such conversion has not been validated for widely varying atmospheric conditions. This study compares the mass concentration estimated by OPC with those directly obtained from gravimetry-based instruments for outdoor samples collected in Bathinda City, Punjab, India from January 2022 to November 2023. The difference in the gravimetrically measured and OPC predicted values quantified in terms of ratios (gravimetric to optically estimated mass concentration), came out to be 1.42 ± 0.77, 0.99 ± 0.51, and 1.17 ± 0.58 for PM10, PM2.5 and PM1, respectively. This difference when estimated with the back-up filter of OPC itself (C Factor), was 1.37 ± 0.66. More than half of the samples showed ratios outside the 0.8–1.2 range thus indicating under or over-estimation in the OPC predicted values. The probable role of variation in density, shape, and refractive index of atmospheric aerosol particles towards the observed inaccuracy of estimated mass concentration has been highlighted. In the absence of clear guidelines and protocols, the study suggests ways to improve the accuracy via periodic measurement of the C Factor and/or incorporating calibration factors in such measurements. [Display omitted] • Estimation of mass concentration by optical counters has been compared with PM1, PM2.5 and PM10 gravimetric samplers. • Results in terms of difference in different size fractions. • Possible reasons could be variation in ambient aerosol density, refractive index and shape. • Incorporating correction and calibration factor improves OPC data accuracy. [ABSTRACT FROM AUTHOR]

Background Alcohol-related hepatitis is one of the most severe manifestations of alcohol-related liver disease and has been associated with significant morbidity, mortality and financial burden. Patients with alcohol use disorders are at risk of leaving against medical advice (LAMA); however, there is currently a lack of data in the literature to show which patients are at higher risk. In this study, we investigated the specific demographic factors and comorbidities associated with LAMA. Methods Patients with a primary or secondary discharge diagnosis of alcohol-related hepatitis (ICD10-CM codes K70.4 and K70.1) between January 2016 and December 2019 were included in this study. Demographics, comorbidities, complications and interventions were studied in for patients who LAMA. Multivariate analysis was conducted to elucidate factors contributing to the increased risk of alcohol-related hepatitis. Results A total of 538,750 patients were admitted with a diagnosis of alcohol-related hepatitis. Of these, 31,500 (5.84%) patients LAMA. Older age, Hispanic race, private insurance, and higher income status were associated with a lower risk of LAMA, while younger age, African American race, lack of insurance and being in the lowest income quartile were associated with the highest risk. Conclusions Our findings demonstrated that significant differences exist between patients with alcohol-related hepatitis who LAMA and those who remain hospitalized until discharge. We believe that this study will help healthcare providers identify patients at risk of LAMA, and help promote the targeted education of specific subgroups to improve their understanding of their disease state and decrease adverse events. [ABSTRACT FROM AUTHOR]

The Nucleocapsid (N) protein of SARS-CoV-2 plays a crucial role in viral replication and pathogenesis, making it an attractive target for developing antiviral therapeutics. In this study, we used differential scanning fluorimetry to establish a high-throughput screening method for identifying high-affinity ligands of N-terminal domain of the N protein (N-NTD). We screened an FDA-approved drug library of 1813 compounds and identified 102 compounds interacting with N-NTD. The screened compounds were further investigated for their ability to inhibit the nucleic-acid binding activity of the N protein using electrophoretic mobility-shift assays. We have identified three inhibitors, Ceftazidime, Sennoside A, and Tannic acid, that disrupt the N protein's interaction with RNA probe. Ceftazidime and Sennoside A exhibited nano-molar range binding affinities with N protein, determined through surface plasmon resonance. The binding sites of Ceftazidime and Sennoside A were investigated using [1H, 15N]-heteronuclear single quantum coherence (HSQC) NMR spectroscopy. Ceftazidime and Sennoside A bind to the putative RNA binding site of the N protein, thus providing insights into the inhibitory mechanism of these compounds. These findings will contribute to the development of novel antiviral agents targeting the N protein of SARS-CoV-2. [Display omitted] • High-throughput screening against SARS-CoV-2 Nucleocapsid (N) protein • Differential scanning fluorimetry was used for screening of high-affinity ligands. • Screened compounds were assessed for the inhibition of nucleic-acid binding of N protein. • Three inhibitors: Ceftazidime, Sennoside A, and Tannic acid identified • Ceftazidime and Sennoside A bind RNA binding site, disrupting N protein's function. [ABSTRACT FROM AUTHOR]