cssi/SciSciGPT-SciSciNet huggingface dataset:
Intraoperative sonography: application in renal cell carcinoma.

AbstractOur ability to detect and potentially to treat renal tumors earlier has increased exponentially during recent years, in part owing to the introduction of more sophisticated imaging modalities. We report 2 cases in which intraoperative sonography was used to localize tumors not palpable at operation. In both cases surgery was performed on solitary kidneys for renal cell carcinoma in otherwise healthy patients.
The prognostic value of serum concentrations of progesterone, estradiol, and luteinizing hormone during superovulation with and without adjunctive leuprolide therapy.

Objective To determine the predictive value of preovulatory serum concentrations of P, E 2 , and LH for pregnancy achieved with IUI after superovulation with and without adjunctive leuprolide acetate (LA) therapy. Design Randomized, crossover study of superovulation with and without LA therapy. Setting Infertility clinic. Patients Subfertile patients referred for superovulation and IUI. Main Outcome Measures Preovulatory serum concentrations of P, E 2 , and LH on the day of hCG administration; pregnancy. Results Preovulatory serum concentrations of P, E 2 , and LH had equivalent predictive value for pregnancy during cycles stimulated without LA therapy. No single parameter was particularly useful in clinical decision making. Threshold P concentrations proposed in other studies as useful in predicting pregnancy did not correlate with cycle fecundity. The predictive value of preovulatory concentrations of P during superovulation with adjunctive LA therapy was significantly worse than P concentrations during superovulation without LA therapy. Conclusions Preovulatory serum P, E 2 , and LH concentrations in superovulation and IUI are not helpful in determining prognosis for pregnancy. The relative utility of predictive parameters may vary for different treatment regimens.
Transition Metal Diborides as Electrode Material for MHD Direct Power Extraction: High-temperature Oxidation of ZrB2-HfB2 Solid Solution with LaB6 Addition

Transition metal borides are being considered for use as potential electrode coating materials in magnetohydrodynamic direct power extraction plants from coal-fired plasma. These electrode materials will be exposed to aggressive service conditions at high temperatures. Therefore, high-temperature oxidation resistance is an important property. Consolidated samples containing an equimolar solid solution of ZrB2-HfB2 with and without the addition of 1.8 mol pct LaB6 were prepared by ball milling of commercial boride material followed by spark plasma sintering. These samples were oxidized at 1773 K (1500 °C) in two different conditions: (1) as-sintered and (2) anodized (10 V in 0.1 M KOH electrolyte). Oxidation studies were carried out in 0.3 × 105 and 0.1 Pa oxygen partial pressures. The anodic oxide layers showed hafnium enrichment on the surface of the samples, whereas the high-temperature oxides showed zirconium enrichment. The anodized samples without LaB6 addition showed about 2.5 times higher oxidation resistance in high-oxygen partial pressures than the as-sintered samples. Addition of LaB6 improved the oxidation resistance in the as-sintered condition by about 30 pct in the high-oxygen partial pressure tests.
Calculation of the Penetration of Gamma Rays Through Slabs by the Method of Invariant Imbedding

The method of invariant imbedding has been applied to the problem of penetration of gamma rays through slabs. The accuracy of the method was examined by comparison with other reliable calculations ...
A group of four related articles

AMA Category 1 credit (2 hr), AAFP Prescribed credit (2 hr), and AOA Category 28 credit (1 hr) may be obtained by reading the articles beginning on pages 66 and 81 and submitting the related quiz. The other articles in this group are followed by self-assessment questions.
Poisson–Boltzmann electrostatics and analytical approximations

In this chapter, firstly we introduce the Poisson–Boltzmann (PB) equation, based on the Debye–Huckel potential of mean force (PMF) approximation for electrostatic interactions for biomolecules in ionic solvent, and then secondly we introduce the concept of electrostatic solvation energy. Several analytical approximation methods for solving electrostatic solvation problems will be discussed. First, the generalized Born approximation is described for the electrostatic solvation energy using Born radii for atoms embedded in molecules. A fast Fourier transform (FFT)-based algorithm for calculating the Born radii is given. Then we present various image approximations to electrostatic reaction fields in the Poisson and Poisson-Boltzmann electrostatic models in the presence of dielectric or perfectly conducting materials with boundaries such as single or multiple planes, with spherical and cylindrical geometries. Poisson–Boltzmann (PB) model for electrostatic solvation The electrostatic force is one of the most important forces in ion–ion, ion–solvent, and solute molecule–solvent interactions (Milner, 1912; Bockris, Reddy, & Gamboa-Aldeco, 2000) for understanding the structure and stability of biomolecules in an aqueous environment. Such interactions are defined as a solvation process of ions or solutes by solvent molecules such as the formation of the hydration shells around ions by water molecules. The classical electrostatic theory can be applied to the system comprising the solute macromolecule and the surrounding ionic solvent environment (Honig & Nicholls, 1995; Fogolari, Brigo, & Molinari, 2002).
Compositional Variations of the Amphiboles

The amphiboles may be divided conveniently into three groups, based on the identity of the X cation, that is, the principal occupant of the M4 site: Fe-Mg; Ca; and Na. Of these three groups, calcic amphiboles predominate, both with regard to the number of species recognized and absolute abundance. Sodic amphiboles are moderately widespread, while iron-magnesium amphiboles have a rather restricted occurrence.
Mechanistic Insights into Membrane Bending by Protein Crowding: Understanding the Role of Membrane Composition, Phase Separation and Free Energy of Protein Binding

Morphological changes in lipid membranes are hallmarks of a number of cellular processes like sorting, transport, etc. The dense crowding of the membrane environment with proteins and receptors has motivated many thorough academic investigations into the effects of macromolecular crowding on membrane surfaces. A number of recent studies have indicated that membrane reshaping could be driven by steric pressure between proteins co-localized on membrane domains. While these studies provide conclusive evidence for the membrane bending process, a detailed physical and mechanistic basis for this phenomenon is lacking. We provide a thermodynamic picture for this phenomenon through Isothermal Titration Calorimetry (ITC), Differential Scanning Calorimetry (DSC) and fluorescence microscopy using Ni-Nitrilotriacetic (NTA) acid and His-Tag interaction as a model system. Using ITC, we observe almost an order of magnitude increase in binding affinity for NTA-functionalized liposomes that display gel-fluid phase coexistence, as opposed to homogenous fluid compositions. This elevated affinity could be eliminated by thermal phase transition from gel-fluid to fluid, highlighting the importance of phase separation in modulating the strength of this binding interaction. DSC revealed that protein binding modulates the long-range lipid order substantially. In conjunction with the complicated nature of the binding isotherm, the DSC results indicate that the protein-binding event is coupled to a secondary exothermic process, presumably due to membrane deformation. Further ITC and fluorescence microscopy experiments reveal that the formation of membrane tubules upon protein binding is sensitive to membrane composition, phase separation and free energy of protein binding. Taken together with a predictive theoretical model that is currently under development, we believe that these results significantly advance our current understanding of the thermodynamics of membrane bending by protein crowding.
A functional role for intrinsic disorder in the tau-tubulin complex

Tau is an intrinsically disordered protein with an important role in maintaining the dynamic instability of neuronal microtubules. Despite intensive study, a detailed understanding of the functional mechanism of tau is lacking. Here, we address this deficiency by using intramolecular single-molecule Forster Resonance Energy Transfer (smFRET) to characterize the conformational ensemble of tau bound to soluble tubulin heterodimers. Tau adopts an open conformation on binding tubulin, in which the long-range contacts between both termini and the microtubule binding region that characterize its compact solution structure are diminished. Moreover, the individual repeats within the microtubule binding region that directly interface with tubulin expand to accommodate tubulin binding, despite a lack of extension in the overall dimensions of this region. These results suggest that the disordered nature of tau provides the significant flexibility required to allow for local changes in conformation while preserving global features. The tubulin-associated conformational ensemble is distinct from its aggregation-prone one, highlighting differences between functional and dysfunctional states of tau. Using constraints derived from our measurements, we construct a model of tubulin-bound tau, which draws attention to the importance of the role of tau's conformational plasticity in function.
A benchmarking method to evaluate the accuracy of a commercial proton monte carlo pencil beam scanning treatment planning system

AcurosPT is a Monte Carlo algorithm in the Eclipse 13.7 treatment planning system, which is designed to provide rapid and accurate dose calculations for proton therapy. Computational run-time in minimized by simplifying or eliminating less significant physics processes. In this article, the accuracy of AcurosPT was benchmarked against both measurement and an independent MC calculation, TOPAS. Such a method can be applied to any new MC calculation for the detection of potential inaccuracies. To validate multiple Coulomb scattering (MCS) which affects primary beam broadening, single spot profiles in a Solidwater® phantom were compared for beams of five selected proton energies between AcurosPT, measurement and TOPAS. The spot Gaussian sigma in AcurosPT was found to increase faster with depth than both measurement and TOPAS, suggesting that the MCS algorithm in AcurosPT overestimates the scattering effect. To validate AcurosPT modeling of the halo component beyond primary beam broadening, field size factors (FSF) were compared for multi-spot profiles measured in a water phantom. The FSF for small field sizes were found to disagree with measurement, with the disagreement increasing with depth. Conversely, TOPAS simulations of the same FSF consistently agreed with measurement to within 1.5%. The disagreement in absolute dose between AcurosPT and measurement was smaller than 2% at the mid-range depth of multi-energy beams. While AcurosPT calculates acceptable dose distributions for typical clinical beams, users are cautioned of potentially larger errors at distal depths due to overestimated MCS and halo implementation.
Body of Preemption: Health Law Traditions and the Presumption Against Preemption

This Article makes three main contributions to health law and preemption doctrine. First, it identifies a variant of the presumption against preemption that applies to health laws — referred to throughout as the “tradition presumption.” Unlike the general presumption against preemption on federalism grounds, courts base this tradition presumption on a notion of “state primacy” that is rooted in tradition and unique to health regulation. Therefore, courts assume it is unlikely in most cases that Congress intended to preempt state health laws. Second, this Article explores the tradition presumption’s accuracy as a description of health laws’ history and its utility as a gauge of congressional intent. Investigation reveals that it is unexamined, inaccurately broad, and subjective. Further, its rote perpetuation risks deterring meaningful inquiry into the context of federal health regulations. Even when courts invoke the tradition presumption to save worthy reform efforts from elimination by preemption, this blunt tool’s unstable construction has made it particularly vulnerable to critique. Third, to remedy these infirmities, this Article proposes a “scalpel approach” to health law preemption analysis; it is designed to identify distinct regulatory traditions and reflect the heterogeneity of regulatory topics within the body of “health law.” The scalpel approach promotes a more accurate preemption analysis and a more coherent health law jurisprudence, while reserving the tradition presumption as a tiebreaker for indeterminate cases. By encouraging courts to relinquish monolithic notions of tradition in health law, the scalpel approach enables health law preemption analysis to accommodate the frequent departures from tradition. Investigating health law’s traditions may even reveal a more robust basis for preserving state laws.
Scalable name-based data synchronization for named data networking

In Named Data Networking (NDN), data synchronization plays an important role similar to transport protocols in IP. Many distributed applications, including pub-sub applications such as news and weather services, require a synchronization protocol where each consumer can subscribe to a different subset of a producer's data streams. However, existing Sync protocols support only full-data synchronization, which is a special case of this problem. We propose PSync to efficiently address different types of data synchronization. Names are used in PSync messages to carry producers' latest namespace information and each consumer's subscription information, which allows producers to maintain a single state for all consumers and enables consumers to synchronize with any producer that replicates the same data. We have implemented PSync in the NDN codebase and used it to develop a prototype pub-sub module for building management. Our experimental results show that PSync scales well as the number of consumers, subscriptions, and data streams increases and it outperforms the state-of-the-art Sync protocol in supporting full-data synchronization.
Time Resolved Deposition Measurements in NSTX

Time-resolved measurements of deposition in current tokamaks are crucial to gain a predictive understanding of deposition with a view to mitigating tritium retention and deposition on diagnostic mirrors expected in next-step devices. Two quartz crystal microbalances have been installed on NSTX at a location 0.77 m outside the last closed flux surface. This configuration mimics a typical diagnostic window or mirror. The deposits were analyzed ex-situ and found to be dominantly carbon, oxygen and deuterium. A rear facing quartz crystal recorded deposition of lower sticking probability molecules at 10% of the rate of the front facing one. Time resolved measurements over a 4-week period with 497 discharges, recorded 29.2 {micro}g/cm{sup 2} of deposition, however surprisingly, 15.9 {micro}g/cm{sup 2} of material loss occurred at 7 discharges. The net deposited mass of 13.3 {micro}g/cm{sup 2} matched the mass of 13.5 {micro}g/cm{sup 2} measured independently by ion beam analysis. Monte Carlo modeling suggests that transient processes are likely to dominate the deposition.
Histone deacetylases SRT1 and SRT2 interact with ENAP1 to mediate ethylene-induced transcriptional repression

Ethylene plays pleiotropic roles in plant growth, plant development, and stress responses. Although the effects of ethylene on plants are well documented, little is known about molecular-level events that result in transcriptional repression during the ethylene response. In this study, we found that two histone deacetylases, SRT1 and SRT2, interact with ENAP1, which associates with EIN2 in the nucleus. Genetic and transcriptome analyses revealed that SRT1 and SRT2 are required for negative regulation of certain ethylene-responsive genes. The acetylation of HISTONE3 at K9 (H3K9Ac) is specifically regulated by SRT1 and SRT2 in ethylene-repressed genes. In addition, the srt1 srt2 double mutation in Arabidopsis thaliana suppresses both the ENAP1ox and the EIN3ox constitutive ethylene response phenotypes, and the ethylene-induced transcriptional repression observed in EIN3ox plants is derepressed in the EIN3ox/srt1 srt2 mutant. SRT2 and ENAP1 both bind to promoter regions of genes negatively regulated by ethylene, reducing H3K9Ac levels and resulting in transcriptional repression. This work establishes a mechanism by which histone deacetylases SRT1 and SRT2 interact with ENAP1 to mediate transcriptional repression by regulating the levels of H3K9 acetylation in the ethylene signaling.
Caries outcome following an intensive fluoride varnish treatment regimen for children at high risk for early childhood caries.

PURPOSE To evaluate the caries relapse rate for a cohort of 2- to 4-year-old children at high risk of early childhood caries when treated with an intensive fluoride varnish (FV) regimen. METHODS Eighty paediatric patients were recruited. Forty of these patients were high risk and received the FV treatment (three applications within 2 weeks and additional applications at 1 and 3 months) during 2009-2010. Mutans streptococci (MS) levels in the saliva were evaluated during the treatment period. A comparative group of 40 children, selected from an electronic record search at the New York University College of Dentistry to be of similar age, gender, and ethnicity, but not at elevated risk for ECC, received the standard of care (semi-annual FV treatment). Detailed caries examination and treatment records were obtained for all patients from 2009 to 2014. RESULTS A significant reduction (P < 0.001) in MS levels was observed in the intensive FV treatment group at the 3-month visit compared with baseline. There was no effect of the intensive FV treatment on caries outcome in the anterior teeth, and the overall caries scores were significantly increased on the posterior teeth. CONCLUSION The intensive FV regimen appears insufficient to prevent caries relapse in children at high risk for caries.
Statistical Approaches to Decreasing the Discrepancy of Non-detects in qPCR Data

Quantitative real-time PCR (qPCR) is one of the most widely used methods to measure gene expression. Despite extensive research in qPCR laboratory protocols, normalization, and statistical analysis, little attention has been given to qPCR non-detects -- those reactions failing to produce a minimum amount of signal. While most current software replaces these non-detects with a value representing the limit of detection, recent work suggests that this introduces substantial bias in estimation of both absolute and differential expression. Recently developed single imputation procedures, while better than previously used methods, underestimate residual variance, which can lead to anti-conservative inference. We propose to treat non-detects as non-random missing data, model the missing data mechanism, and use this model to impute missing values or obtain direct estimates of relevant model parameters. To account for the uncertainty inherent in the imputation, we propose a multiple imputation procedure, which provides a set of plausible values for each non-detect. In the proposed modeling framework, there are three sources of uncertainty: parameter estimation, the missing data mechanism, and measurement error. All three sources of variability are incorporated in the multiple imputation and direct estimation algorithms. We demonstrate the applicability of these methods on three real qPCR data sets and perform an extensive simulation study to assess model sensitivity to misspecification of the missing data mechanism, to the number of replicates within the sample, and to the overall size of the data set. The proposed methods result in unbiased estimates of the model parameters; therefore, these approaches may be beneficial when estimating both absolute and differential gene expression. The developed methods are implemented in the R/Bioconductor package nondetects. The statistical methods introduced here reduce discrepancies in gene expression values derived from qPCR experiments, providing more confidence in generating scientific hypotheses and performing downstream analysis.
The 50 Most Cited Articles in Invasive Neuromodulation.

Objective Bibliometric analysis is a commonly used analytic tool for objective determination of the most influential and peer-recognized articles within a given field. This study is the first bibliometric analysis of the literature in the field of invasive neuromodulation, excluding deep brain stimulation. The objectives of this study are to identify the 50 most cited articles in invasive neuromodulation, provide an overview of the literature to assist in clinical education, and evaluate the effect of impact factor on manuscript recognition. Methods Bibliometric analysis was performed using the Science Citation Index from the Institute for Scientific Information, accessed through the Web of Science. Search terms relevant to the field of invasive neuromodulation were used to identify the 50 most cited journal articles between 1900 and 2016. Results The median number of citations was 236 (range, 173–578). The most common topics among the articles were vagus nerve stimulation ( n = 24), spinal cord stimulation ( n = 9), and motor cortex stimulation ( n = 6). Median journal impact factor was 5.57. Most of these articles ( n = 19) contained level I, II, or III evidence. Conclusions This analysis provides a brief look into the most cited articles within the field, many of which evaluated innovated procedures and therapies that helped to drive surgical neuromodulation forward. These landmark articles contain vital clinical and educational information that remains relevant to clinicians and students within the field and provide insight into areas of expanding research. Journal impact factor may play a significant role in determining the literary relevance and general awareness of invasive neuromodulation studies.
Uterine architecture: building the foundation for a healthy pregnancy.

"The hardest thing to explain is the glaringly evident which everybody has decided not to see." — Ayn Rand, The Fountainhead
Optimization of water-energy nexus: a network representation-based graphical approach.

Abstract We present a scalable and systematic method for the design and optimization of complex water-energy nexus using graph theory-based network representation and a novel water-energy nexus (WEN) diagram. The graph-theoretic approach defines a nexus as a directed bipartite graph with water and energy flows. The network representation allows the decomposition of a complex nexus into its essential and redundant components. We show that for specified external grid demands, the optimal nexus configuration with minimum water and energy generation is the one without any redundant subgraphs. We then propose a systematic method to identify and eliminate redundant cycles, flows and entities within a nexus leading to (i) minimum generation/extraction of water and energy resources from the environment, or (ii) maximum yield of water and energy to meet external demands. Our approach is simple to implement and results in optimal nexus configurations that also satisfy operational constraints, restrictions and water quality specifications. The approach is demonstrated using case studies on water-energy nexus systems focusing on power generation, seawater desalination, groundwater and surface water at regional and national scales.
Oscillations and Chaos in the Pancreatic β-Cell

The voltage across the plasma membrane of the pancreatic 3-cell displays burst activity when glucose between ~8.5 mM and 16.5 mM is added to the perfusion medium (Dean and Mathews, 1970; Ribalet and Beigleman, 1979; Atwater et al., 1980). This consists of an active phase during which spikes are generated and a silent phase during which the membrane is hyperpolarized. In high glucose concentrations above 16.6 mM, the burst pattern disappears and spike activity becomes continuous. The active phase has been associated with the stimulus for the release of insulin (Meissner, 1976; Scott et al., 1981).
Stasis dermatitis as a complication of recurrent levofloxacin-associated bilateral leg edema.

Author(s): Hyman, Daniel A; Cohen, Philip R | Abstract: Introduction: Several drugs have been associated with the development of peripheral edema. Leg edema can result in dermatitis of the lower extremities. We describe levofloxacin-induced peripheral leg edema, which progressed to stasis dermatitis.Methods: A 76-year-old man with a history of esophageal adenocarcinoma was administered intravenous vancomycin and a combination of piperacillin and tazobactam by injection for treatment of aspiration pneumonia. Prior to discharge, the patient's antibiotic therapy was switched to oral levofloxacin. The patient developed drug-associated bilateral peripheral leg edema and stasis dermatitis. Both the dermatitis and leg edema resolved after withdrawal of levofloxacin and administration of topical corticosteroid therapy. The patient had a similar reaction to levofloxacin one year prior, which had subsided with discontinuation of the drug.Results: Several medications have been documented to cause leg edema and secondary stasis dermatitis. The timing, recurrence, and resolution of edema and stasis dermatitis with respect to the administration and termination of levofloxacin suggest that the leg edema and stasis dermatitis occurred secondary to levofloxacin administration. Discussions: Levofloxacin can be added to the list of drugs associated with the development of peripheral leg edema. Stasis dermatitis proceeded by lower extremity edema can be added to the list of adverse events associated with levofloxacin
Malnutrition and Infection

Severe malnutrition, such as is seen in the developing countries, results from many causes. Insufficiency of food and its consequence, marasmus, and inadequacy of specific nutrients in the diet resulting in a variety of syndromes of malnutrition, such as kwashiorkor, xerophthalmia, and anemia, are the most obvious and dramatic examples of malnutrition. Many other factors, however, contribute primarily or secondarily to the development of malnutrition. These include unfamiliarity with good nutritional practices, cultural food taboos, and faulty management of food distribution. The ultimate consequence of malnutrition is inadequate growth and probably also failure to achieve optimal intellectual potential.
Stress-testing the relationship between T cell receptor/peptide-MHC affinity and cross-reactivity using peptide velcro.

T cell receptors (TCRs) bind to peptide-major histocompatibility complex (pMHC) with low affinity (Kd ∼ μM), which is generally assumed to facilitate cross-reactive TCR “scanning” of ligands. To understand the relationship between TCR/pMHC affinity and cross-reactivity, we sought to engineer an additional weak interaction, termed “velcro,” between the TCR and pMHC to probe the specificities of TCRs at relatively low and high affinities. This additional interaction was generated through an eight-amino acid peptide library covalently linked to the N terminus of the MHC-bound peptide. Velcro was selected through an affinity-based isolation and was subsequently shown to enhance the cognate TCR/pMHC affinity in a peptide-dependent manner by ∼10-fold. This was sufficient to convert a nonstimulatory ultra-low-affinity ligand into a stimulatory ligand. An X-ray crystallographic structure revealed how velcro interacts with the TCR. To probe TCR cross-reactivity, we screened TCRs against yeast-displayed pMHC libraries with and without velcro, and found that the peptide cross-reactivity profiles of low-affinity (Kd > 100 μM) and high-affinity (Kd ∼ μM) TCR/pMHC interactions are remarkably similar. The conservation of recognition of the TCR for pMHC across affinities reveals the nature of low-affinity ligands for which there are important biological functions and has implications for understanding the specificities of affinity-matured TCRs.
Tandem cervical carotid stenting for stenosis with flow diversion embolisation for the treatment of intracranial aneurysms

Background An estimated 2%–3% of the population harbour an intracranial aneurysm. Concomitant atherosclerotic cervical carotid disease is not uncommon. The management of these two entities remains a challenge within the field. Case presentation We report a single case of concomitant carotid stenosis and two ipsilateral unruptured intracranial aneurysms treated with a single-staged cervical carotid stenting and cerebral aneurysm embolisation with the Pipeline embolisation device. Discussion No consensus currently exists to guide endovascular treatment of intracranial aneurysms associated with asymptomatic ipsilateral stenosis. Here, we present a case of asymptomatic moderate carotid stenosis with two ipsilateral intracranial aneurysms and suggest carotid artery stenting takes procedural priority over aneurysm embolisation in single-stage treatment. The rationale for the sequence of neurointerventions is based on the tracking a robust distal access system beyond a stenotic proximal carotid lesion and stabilisation of the ulcerated plaque to avoid thromboembolic complications associated with plaque irritation during aneurysm embolisation. Additional cases and longer follow-up will be needed to further assess the efficacy of this technique.
Identification of potential Zika virus NS2B-NS3 protease inhibitors via docking, molecular dynamics and consensus scoring-based virtual screening

The Zika virus has recently become a subject of acute interest after the discovery of the link between viral infection and microcephaly in infants. Though a number of treatments are under active investigation, there are currently no approved treatments for the disease. To address this critical need, we screened more than 7 million compounds targeting the NS2B-NS3 protease in an attempt to identify promising inhibitor candidates. Starting with commercially and freely available compounds, we identified six hits utilizing an exhaustive consensus screening protocol, followed by molecular dynamics simulation and binding energy estimation using MM/GBSA and MM/PBSA methods. These compounds feature a variety of cores and functionalities, and all are predicted to have good pharmacokinetic profiles, making them promising candidates for screening assays.
Elimination of Acute Myelogenous Leukemic Cells From Marrow and Tumor Suspensions in the Rat With 4-Hydroperoxycyclophosphamide

Cell suspensions of normal rat marrow mixed with rat acute myelogenous leukemic cells were prepared and incubated in vitro with graded doses of 4-hydroperoxycyclophosphamide (4HC). The cell suspensions were injected into rats prepared with a lethal dose of total body irradiation. Animals injected with these cells survived fatal irradiation induced aplasia. In a dose related manner 4HC was able to “purge” tumor cells from the cell mixtures. Thus, animals given cell suspensions incubated with the lower doses of 4HC showed prolonged survival before death from leukemia and animals given cell suspensions incubated with higher doses of 4HC survival lethal irradiation without the subsequent appearance of leukemia. These studies clearly establish that tumor cells may be eliminated from normal marrow suspensions without completely destroying the pluripotent stem cells.
A 44-Year-Old Man With Dyspnea and a Pulmonary Artery Filling Defect.

Case Presentation A 44-year-old man with a history of coronary artery disease, type 2 diabetes mellitus, and OSA reported progressively worsening dyspnea on exertion over a 6-week period. Outpatient CT angiogram revealed a pulmonary artery filling defect. He was sent to the ED where he was started on a heparin drip for unprovoked pulmonary embolism (PE). Echocardiogram revealed normal cardiac function without evidence of right heart strain. Lower extremity ultrasound was negative for DVT. He improved symptomatically, and no risk factors for PE were identified. He was discharged on apixaban. Five weeks later, the patient returned to the ED with hemoptysis. He reported compliance with anticoagulation and improvement of his dyspnea on exertion. History remained negative for recent travel, trauma, surgery, clotting disorders, thromboembolic disease, and alcohol or drug use. He had a 60 pack-year cigarette smoking history and quit 3 months prior.
Bortezomib Induces Proliferation of Mesenchymal Progenitor Cells and Promotes Differentiation towards Osteoblastic Lineage.

Bortezomib is a first-in-class proteasome inhibitor approved for the therapy of relapsed, refractory multiple myeloma (MM). Two large registration trials (SUMMIT and APEX) of bortezomib in MM revealed an increase in the serum levels of bone-specific alkaline phosphatase ( b-ALP ) and osteocalcin ( ocn ) in bortezomib-responsive patients, raising the prospect that bortezomib may influence the bone marrow (BM) microenvironment in association with its anti-myeloma effect,. However, the precise cellular target of bortezomib within the BM milieu remains unknown. We hypothesized that the observed rise in b-ALP and ocn was the result of direct effects of bortezomib on osteoblast-lineage committed cells. The effect of bortezomib on osteoblastic cells was first evaluated in in vitro . When bortezomib was added to freshly isolated primary BM mononuclear cells, the CFU-Ob (osteoblastic colony-forming units) was unchanged, but the colony size was increased, with a maximum effect observed at 1 nM. In particular, bortezomib increased the number of CD45−/CD51+ cells 1.8 fold (P in vitro and lacked the expression of Sca1 and Collagen-II, suggesting that they were of osteoblastic lineage. When mice were treated with bortezomib (0.1mg/kg biw for 3 weeks), a significant increase in CD45−/CD51+ cells was observed in the bone marrow suggesting bortezomib increases the number of osteoblast-lineage cells in vivo . Next, we sought to identify the target cell for bortezomib activity. We treated CD45− BMSCs with bortezomib in vitro for 7 days and then exposed these cells to either adipogenic or osteogenic media (with bortezomib now removed). Interestingly, both differentiated osteoblasts (i.e Van-Kossa+ cells) and adipocytes (Oil-Red staining cells) were increased, suggesting that bortezomib increases the proliferation of a bipotent MPC. We then studied the impact of bortezomib on the commitment of MPCs towards osteoblastic or adipocytic lineages by culturing CD45− cells in osteogenic and adipogenic media with concurrent treatment with bortezomib. In these conditions, we found an increased number of Alk-Phos + osteoblasts in bortezomib-treated cells and a decreased number of adipocytes in adipogenic media. These data suggest that bortezomib (a) increases the proliferation of uncommitted MPCs and (b) promotes the differentiation towards osteoblastic lineage. To investigate the mechanism of bortezomib action, we studied the effect of forskolin, a cyclic AMP analogue known to accelerate the ubiquitin-mediated degradation of RUNX-2, the master-regulator of osteogenic differentiation. Forskolin treatment abrogated the effect of bortezomib on CD45− BMSCs, suggesting that bortezomib activity is influenced by the adenylate cyclase pathway, possibly through bortezomib-mediated inhibition of RUNX-2 degradation. Bortezomib alters primitive mesenchymal cell function causing increased osteoblast lineage cells.
Least-Squares Methods

Least-squares is described as a method for solving problems where there is an excess of information available. This is often the case in experimental mechanics. The method can be used to include information from different sources; experimental and theoretical. The method is applied to curve fitting problems and to more general situations. Nonlinear least squares methods are described for fitting of approximation functions.
US trends in prevalence of sleep problems and associations with chronic kidney disease and mortality

Background: To better understand the relation between sleep problems and chronic kidney disease (CKD), we examined temporal trends in the prevalence of self-reported sleep problems in US adults and their associations with CKD and all-cause mortality. Methods: Using data from 27,365 adult participants in 5 biannual National Health and Examination Surveys (2005-6 through 2013-14), we studied 5 self-reported sleep problems: trouble sleeping, sleep disorder, nocturia (urinating ≥2 times/night), inadequate sleep ( 9 hours/night); plus a composite index. We conducted 3 types of analysis: temporal trends in the prevalence of each sleep measure by CKD status, using model-based standardization; cross-sectional analysis of associations between 4 CKD measures and each sleep measure, using logistic regression; and survival analysis of the association between each sleep measure and mortality, using Cox regression. Results: The prevalence of trouble sleeping and sleep disorder increased over the 5 surveys by 3.6% and 2.8%, respectively, while the other sleep problems remained relatively stable. All sleep problems, except inadequate sleep, were more common during the study period among adults with CKD than without CKD (40.3% vs. 21.4% for nocturia; 5.0% vs 1.9 % for excessive sleep; 30.0% vs. 25.2% for trouble sleeping; and 11.6% vs. 7.9% for sleep disorder). Both eGFR 9 vs. 7-9 hours/night = 1.7; 95% CI: 1.3, 2.1; and for nocturia=1.2; 95% CI: 1.1, 1.4). Conclusion: The high prevalence of sleep problems among persons with CKD and their associations with mortality suggest their potential importance to clinical practice. Future work could examine the health effects of identifying and treating sleep problems in CKD patients.
Effects of Transcutaneous Electric Nerve Stimulation on Upper Extremity Proprioceptive Function

Electrical stimulation of the vagus nerve has been shown to enhance cortical plasticity and may benefit upper extremity rehabilitation following stroke. As an initial step towards assessing the potential of other craniocervical nerves as neuromodulation targets during rehabilitation, we explored the ability of non-invasive stimulation of cervical spine afferents, paired with a proprioceptive discrimination task, to improve sensory function in neurologically intact human subjects. On each trial, subjects’ arms were moved by a robot from a test position, along a random path, to a judgment position located 1-4 cm away. Subjects responded ‘same’ if the judgment position was the same as the test or ‘different’ if it was not. These responses were used to compute proprioceptive sensitivity and bias. Three groups of 20 subjects received transcutaneous electric nerve stimulation to the C3/C4 cervical spine at one of three frequencies (30 Hz, 300 Hz, 3 kHz) for 10 minutes prior to task performance. A fourth group served as a sham. We found a statistically significant interaction between stimulation frequency and displacement distance on proprioceptive sensitivity. In summary, stimulation of cervical spine afferents may enhance arm proprioceptive function, though in unimpaired subjects these gains depend on both stimulation frequency and discrimination distance.Clinical Relevance— This study provides preliminary data on the potential for non-invasive stimulation of cervical spine afferents to enhance recovery of function following stroke and other neurological disorders
Computational molecular docking and virtual screening revealed promising SARS-CoV-2 drugs

The pandemic of novel coronavirus disease 2019 (COVID-19) is rampaging the world with more than 1 4 million of confirmed cases and more than 85,000 of deaths across world by April 9th, 2020 There is an urgent need to identify effective drugs to fight against the virus Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) belongs to the family of coronaviruses consisting of four structural and 16 non-structured proteins Three non-structural proteins such as main protease, papain like protease, and RNA-dependent RNA polymerase are believed to play a crucial role in the virus replication We applied a computational ligand-receptor binding modeling and performed a comprehensive virtual screening on the FDA-approved drugs against these three SARS-CoV-2 proteins using AutoDock Vina Our computational studies indicated that Simeprevir, Ledipasvir, Idarubicin, Saquinavir, Ledipasivir, Partitaprevir, Glecaprevir, and Velpatasvir are all promising inhibitors, which displayed a lower binding energy (higher inhibitory effect) than Remdesivir, Lopinavir, and Ritonavir However, we found that chloroquine and hydroxychloroquine, which showed efficacy in treating the COVID-19 in recent clinical studies, had high binding energy with all three proteins, suggesting they may work through a different mechanism We also identified several novel drugs as potential inhibitors against SARS-CoV-2, including antiviral Raltegravir;antidiabetic Amaryl;antibiotics Retapamulin, Rifimixin, and Rifabutin;antiemetic Fosaprepitant and Netupitant In summary, our computational molecular docking approach and virtual screening identified some promising candidate SARS-CoV-2 drugs that may be considered for further clinical studies
Combined analysis of the moderating effect of a GRIK1 polymorphism on the effects of topiramate for treating alcohol use disorder.

Abstract Background In an initial study, we reported that topiramate reduced heavy drinking among individuals who sought to reduce their drinking and that the effect was moderated by a single nucleotide polymorphism (SNP; rs2832407) in GRIK1, which encodes the kainate GluK1 receptor subunit ( Kranzler et al., 2014 ). In a subsequent study that prospectively randomized patients to medication group based on their rs2832407 genotype, we replicated the main effect of topiramate but not the moderating effect of the SNP ( Kranzler et al., 2021 ). Given the similar design of the two studies, here we combined the findings to provide greater statistical power to test the pharmacogenetic effect. Material and methods This secondary analysis of two 12-week, randomized controlled trials of topiramate included a total of 292 European-ancestry individuals (67.1 % male; topiramate: 48.3 %, placebo: 51.7 %) with problematic alcohol use. Using MANOVA, we examined changes in self-reported alcohol consumption, problems resulting from alcohol use, and quality of life, and the biomarker γ-glutamyltransferase. To test the pharmacogenetic hypothesis, all patients were genotyped for rs2832407. Results There was a significant overall effect of topiramate on the alcohol-related outcomes (partial η2 = 0.134, p Conclusions Although topiramate is an efficacious medication for reducing drinking and alcohol-related problems among patients with problematic alcohol use, rs2832407 does not appear to moderate its therapeutic effects. www.clinicaltrials.gov registrations: NCT00626925 and NCT02371889
Conservative Treatment of Avulsion Injuries of the Lesser Trochanter in Adolescent Athletes

BACKGROUND Avulsion injuries of the lesser trochanter apophysis are relatively uncommon injuries and there have been no peer-reviewed case series dedicated to the evaluation and treatment of this injury. The purpose of this study is to characterize avulsion injuries of the lesser trochanter apophysis, review treatment protocols, and time to return to sport. Methods: We reviewed 30 confirmed avulsion fractures of the lesser trochanter. Clinical data were reviewed to evaluate treatment protocols, duration, and time to return to sport. Radiographs were reviewed to confirm lesser trochanter avulsion and fracture displacement. RESULTS There were 26 males and 4 females, with the average age at the time of injury being 14.2 years. Treatment modalities consisted of protective weight-bearing, discontinuation of the patient's sport in all cases, and formal physical therapy in 18 cases. The average treatment duration was 30.7 days. The mean follow-up time was 102 days. The radiographic assessment demonstrated an average fracture displacement of 5.1 mm. The average return to sport was 11 weeks. CONCLUSION This is the first large case series studying avulsion injuries of the lesser trochanter. We have shown that these athletes can be managed non-surgically and can successfully return back to sport within three months.
Reliability based Design of MEMS Accelerometer Considering Residual Stress and Temperature Variations

This work presents the design and system level simulations of a reliable dual axis capacitive MEMS accelerometer. The reliability of accelerometer is analyzed with respect to temperature and residual stresses. The temperature reliability of proposed MEMS accelerometer allows it to work in temperature range of −40 °C to 100 °C. The residual stresses are characterized by FEM simulations to observe their effect on frequency of system. The simulation results show that the effect of residual stresses on the performance characteristics of MEMS accelerometer is negligible and can be ignored. The device is integrated with readout circuit to observe the variation in capacitance for various input accelerations. The proposed MEMS accelerometer can detect an input acceleration in the range of ± 50 g and has a capacitive sensitivity of 38 fF/g.
Trajectories of unsecured debt and health at midlife.

Abstract Background Unsecured debt — debt not tied to an asset — is a financial stressor that undermines health, but prior research has not investigated relationships between group-based trajectories of unsecured debt and pain and disability at midlife. Methods US respondents of the National Longitudinal Study of Youth-1979 cohort reported unsecured debt and income between ages 28–40. We used these measures to identify group-based trajectories of unsecured debt and unsecured debt-to-income ratio. We then used trajectory membership to predict three pain and disability-related health outcomes at age 50, adjusting for lagged health and other covariates. Results Group-based trajectory models divided the sample of 7850 respondents into 6 unsecured debt trajectories and 5 unsecured debt-to-income trajectories. In fully adjusted unsecured debt models, compared to people with constant low debt, those who paid down debt over time, carried constant debt, experienced debt cycling, or accumulated debt later in life were more likely to report pain interference with activities or joint pain or stiffness at age 50 (pain interference ORs ranging from 1.33 to 1.76; joint pain or stiffness ORs ranging from 1.27 to 1.45). In fully adjusted unsecured debt-to-income models, compared to those with constant low debt, those with constant high debt or accumulating debt later in life were more likely to report pain interference or joint pain or stiffness (pain interference ORs ranging from 1.30 to 1.91; joint pain or stiffness ORs ranging from 1.19 to 1.33). Conclusion The amount, timing, and duration of unsecured debt accumulation and repayment have important health implications and may exacerbate midlife health inequalities.
Venous Thromboembolism: Management Guidelines from the American Society of Hematology.

The American Society of Hematology has updated recommendations for management of VTE, which includes deep venous thrombosis (DVT) and pulmonary embolism (PE).
Liposomal Bupivacaine Injection in Nuss Procedure Allows Narcotic Avoidance and Improved Outcomes.

Background: The Nuss procedure has provided a minimally invasive surgical solution for pectus excavatum with excellent long-term outcomes. However, opioid avoidance, cost reduction, and length of s...