cssi/SciSciGPT-SciSciNet huggingface dataset:
Strategies to facilitate the discovery of novel CNS PET ligands

Positron Emission Tomography (PET), as a non-invasive translatable imaging technology, can be incorporated into various stages of the CNS drug discovery process to provide valuable information for key preclinical and clinical decision-making. Novel CNS PET ligand discovery efforts in the industry setting, however, are facing unique challenges associated with lead design and prioritization, and budget constraints. In this review, three strategies aiming toward improving the central nervous system (CNS) PET ligand discovery process are described: first, early determination of receptor density (Bmax) and bio-distribution to inform PET viability and resource allocation; second, rational design and design prioritization guided by CNS PET design parameters; finally, a cost-effective in vivo specific binding assessment using a liquid chromatography-mass spectrometry (LC-MS/MS) "cold tracer" method. Implementation of these strategies allowed a more focused and rational CNS PET ligand discovery effort to identify high quality PET ligands for neuroimaging.
Tangent Spaces to Grassmannians

We have seen that the Grassmannian 𝔾(k, n) is a smooth variety of dimension (k + 1) (n - k). This follows initially from our explicit description of the covering of 𝔾 (k, n) by open sets U Λ ≅ 𝔸(k+1)(n-k), though we could also deduce this from the fact that it is a homogeneous space for the algebraic group PGL n+1 K. The Zariski tangent spaces to G are thus all vector spaces of this dimension. For many reasons, however, it is important to have a more intrinsic description of the space T Λ(𝔾;) in terms of the linear algebra of Λ ⊂ K n+1. We will derive such an expression here and then use it to describe the tangent spaces of the various varieties constructed in Part I with the use of the Grassmannians.
Using CMMI to Improve Earned Value Management

Abstract : For organizations using Earned Value Management (EVM) or that plan to implement EVM during Capability Maturity Model Integration (CMMI) implementation, this technical note provides guidance for cost-effective process improvement and appraisal. Mapping and comparison tables between CMMI and the U.S. national standard on EVM are provided. These tables can be used to identify practices within CMMI that are not included in the EVM standard but, if added to an organization's processes, will strengthen adherence to EVM principles. The tables also can be used to develop instruments that will provide evidence to an appraisal team to enable it to quickly verify and validate specific practices based upon effective implementation of EVM. Furthermore, information such as glossary components, typical work products, and examples are included in this technical note to aid those using CMMI for process improvement. For organizations using technical performance measurement, a primary base measure for earned value, additional guidance and information is provided. Finally, additional references and an EVM glossary are provided.
Cerebral Blood Flow and Migraine

Blood flow in the basilar and internal carotid arteries and diameters of middle meningeal, carotid, and cerebral arteries were measured using 3Tesla magnetic resonance angiography, at baseline, during infusion of nitroglycerin or placebo, and during a provoked attack, at 6 hrs after infusion, in 32 migraineurs, aged 18-55 years, in a study at Leiden University Medical Centre, the Netherlands.
Can Appreciative Inquiry increase positive interactions, student self‐advocacy and turn‐taking during IEP meetings?

This comparative research study in the context of action research documents the effects of Appreciative Inquiry (AI) on positive participant interactions, student turn-taking and self-advocacy interactions during IEP meetings that focused on student transition to post-secondary outcomes. AI was implemented as a written protocol for conducting IEP meetings in one school unit (P) that had been developed from an AI training in a second school unit (E) which also used the protocol. A third unit (C) with neither training nor a protocol to use served as a comparison. 124 IEP meetings in these three units in New York State in the United States were observed and recorded in 10 second increments. Results indicated increases in percentages of positive interactions, student turn-taking, and of student self-advocacy in both the AI trained and protocol unit (E) and in the unit using the protocol alone (P) over the comparison unit (C) and over earlier pilot data (P (Pilot)). AI may be an effective consultative and educational process for encouraging some factors that lead to student success in transitioning to college, career, and life beyond graduation from school.
Development of an electronic medical record–based child physical abuse alert system

Objective Physical abuse is a leading cause of pediatric morbidity and mortality. Physicians do not consistently screen for abuse, even in high-risk situations. Alerts in the electronic medical record may help improve screening rates, resulting in early identification and improved outcomes. Methods Triggers to identify children < 2 years old at risk for physical abuse were coded into the electronic medical record at a freestanding pediatric hospital with a level 1 trauma center. The system was run in "silent mode"; physicians were unaware of the system, but study personnel received data on children who triggered the alert system. Sensitivity, specificity, and negative and positive predictive values of the child abuse alert system for identifying physical abuse were calculated. Results Thirty age-specific triggers were embedded into the electronic medical record. From October 21, 2014, through April 6, 2015, the system was in silent mode. All 226 children who triggered the alert system were considered subjects. Mean (SD) age was 9.1 (6.5) months. All triggers were activated at least once. Sensitivity was 96.8% (95% CI, 92.4-100.0%), specificity was 98.5% (95% CI, 98.3.5-98.7), and positive and negative predictive values were 26.5% (95% CI, 21.2-32.8%) and 99.9% (95% CI, 99.9-100.0%), respectively, for identifying children < 2 years old with possible, probable, or definite physical abuse. Discussion/Conclusion Triggers embedded into the electronic medical record can identify young children with who need to be evaluated for physical abuse with high sensitivity and specificity.
Optimization of Methods for Articular Cartilage Surface Tissue Engineering: Cell Density and Transforming Growth Factor Beta Are Critical for Self-Assembly and Lubricin Secretion

Objective: Lubricin/superficial zone protein (SZP)/proteoglycan4 (PRG4) plays an important role in boundary lubrication in articular cartilage. Lubricin is secreted by superficial zone chondrocytes and synoviocytes of the synovium. The specific objective of this investigation is to optimize the methods for tissue engineering of articular cartilage surface. The aim of this study is to investigate the effect of cell density on the self-assembly of superficial zone chondrocytes and lubricin secretion as a functional assessment. Design: Superficial zone chondrocytes were cultivated as a monolayer at low, medium, and high densities. Chondrocytes at the three different densities were treated with transforming growth factor beta (TGF-β)1 twice a week or daily, and the accumulated lubricin in the culture medium was analyzed by immunoblots and quantitated by enzyme-linked immunosorbent assay (ELISA). Results: Cell numbers in low and medium densities were increased by TGF-β1; whereas cell numbers in high-density ce...
Literature Review and Analysis of Waterless Fracturing Methods

Author(s): Moridis, George | Abstract: This report provides a brief literature review and analysis of several waterless fracturing methods. The methods included in this report are: Liquid CO2/Sand Fracturing; Straight Nitrogen Based Fracturing; Liquefied Petroleum Gas (LPG) Fracturing; Liquefied Natural Gas (LNG) Fracturing; as well as Explosives and Propellant-Based Fracturing. Additional non-water carrier fluids are also identified. A discussion on CO2-Foam Fracturing is given in the separate LBNL report mentioned above (Wan, 2017). The strengths and limitations of each non-water fracture stimulation carrier fluid are described below, and insights are provided on the characteristics of geologic formations amenable to the use of each fluid.
Checkpoint immunotherapy in head and neck cancers

Checkpoint inhibitors have recently gained FDA approval for the treatment of cisplatin-resistant recurrent and metastatic head and neck squamous cell carcinoma (HNSCC) by outperforming standard of care chemotherapy and inducing durable responses in a subset of patients. These monoclonal antibodies unleash the patient's own immune system to target cancer cells. HNSCC is a good target for these agents as there is ample evidence of active immunosurveillance in the head and neck and a number of immune evasion mechanisms by which HNSCCs form progressive disease including via the PD-1/PD-L1 axis. As HNSCCs typically possess a moderately high mutation burden, they should express numerous mutation-derived antigen targets for immune detection. However, with response rates less than 20% in clinical trials, there is a need for biomarkers to screen patients as well as clinical trials evaluating novel combinations to improve outcomes. The aim of this review is to provide historical and mechanistic context for the use of checkpoint inhibitors in head and neck cancer and provide a perspective on the role of novel checkpoints, biomarkers, and combination therapies that are evolving in the near term for patients with HNSCC.
Racial variations in extracorporeal membrane oxygenation use following congenital heart surgery.

Abstract Objectives Previous studies demonstrate racial and ethnic disparities among children undergoing congenital heart surgery. Extracorporeal membrane oxygenation (ECMO) is used to support critically ill children after congenital heart surgery and improve survival. Thus, racial or ethnic variations in postoperative ECMO use following congenital heart surgery may be associated with racial/ethnic disparities in hospital survival. Methods All children in the Pediatric Health Information Systems dataset undergoing congenital heart surgery from 2004 to 2015 were examined. Multivariable, multinomial regression models examining hospital survival without ECMO use, survival after ECMO, death after ECMO, and death without ECMO support were constructed. Results Of 130,860 congenital cardiac surgery patients, 95.4% survived to hospital discharge without requiring ECMO support, whereas 1.3% survived after ECMO support, 1.3% died after ECMO support, and 1.9% died without receiving ECMO support. After adjustment for other covariates, black patients (odds ratio, 1.22; 95% confidence interval [CI], 1.05-1.42) and patients of other race (odds ratio, 1.36; 95% CI, 1.17-1.58) were at increased odds of mortality compared with white patients. In multivariable multinomial models, black patients had increased risk of death without ECMO support (relative risk, 1.31; 95% CI, 1.11-1.56). Patients of other race (relative risk, 1.37; 95% CI, 1.10-1.69) and governmental insurance (relative risk, 1.24; 95% CI, 1.12-1.37) were also at increased risk of death without ECMO. Conclusions Black children and children of other race are at increased odds of mortality after congenital heart surgery. These disparities can be traced to variations in ECMO utilization across racial/ethnic groups.
A case for community health programs for sickle cell anemia in low- to middle-income countries: An integrative review.

Objective The purpose of this review is to determine the factors associated with the outcomes of community health programs with particular focus on low- to middle-income countries. In addition, this review aims to suggest how these factors can affect the creation of a Sickle Cell Anemia health program in sub-Saharan Africa. Design and sample A literature review spanning the last decade (March 2007 to February 2017) was conducted using the Whittemore and Knafl integrative review framework. Results Community ownership, networking, and resource allocation were identified as themes that affect community health program outcomes. Attempts to use a guiding principle or process to implement community health programs were also apparent in the literature. Conclusion More rigorous scientific investigation is needed to ensure that these community health programs are effective and have measurable outcomes. Nursing is well positioned, considering the metaparadigm concepts that guide practice, to forge this research. Nursing scientists could fill the gap in knowledge related to community health program outcomes in low- to middle-income countries while achieving global objectives focused on decreasing noncommunicable disease burden.
MICROSEGREGATION IN CAST ALLOYS

ABSTRACT The importance of microsegregation in solidifying metals is discussed, with particular emphasis on the mathematical models which have been developed to help in the determination of solute concentration profiles and second phase contents after solidification. The predictions of a recently-developed numerical model are compared with other models and experimental data in the Al-Cu system. Results indicate that only the two numerical models were able to reproduce the amount of non-equilibrium second phase accurately. A plot is presented by which the amount of second phase can be estimated for hypoeutectic alloys as a function of cooling rate.
Reliable Low Resolution OFDM Receivers via Deep Learning

This paper develops novel deep learning-based architectures and design methodologies for an orthogonal frequency division multiplexing (OFDM) receiver under the constraint of one-bit complex quantization. Single bit quantization greatly reduces complexity and power consumption, but makes accurate data detection difficult. This is particularly true for multicarrier waveforms, which have high peak-to-average ratio in the time domain and fragile subcarrier orthogonality in the frequency domain. The severe distortion for one-bit quantization typically results in an error floor even at moderately low signal-to-noise-ratio (SNR) such as 5 dB. A neural network-based receiver – specifically, an autoencoder – jointly learns a precoder and decoder for data symbol detection. Since quantization prevents end-to-end training, we propose a two-step sequential training policy for this model. Our proposed design achieves lower bit error rate (BER) in fading than unquantized (full-resolution) OFDM at average SNRs up to 10 dB.
Tools for the 3Cs of Entrepreneurially Minded Learning (EML)

Entrepreneurially Minded Learning is a pedagogical technique that seeks to equip students to be more curious about trends in the changing world, make connections from disparate sources of information to gain insight, and identify unexpected opportunities to create extraordinary value for themselves and their communities. The core of the entrepreneurial mindset can be summarized succinctly by the three Cs: Curiosity, Connections, and Creating value. This interactive workshop will introduce participants to these three Cs using three specific tools that facilitators have successfully used in their engineering classrooms. The workshop is targeted towards a total of 40 participants and will require only projection capabilities for audio-visual equipment.
Preferential quenching of 5d antiferromagnetic order in Sr3(Ir1-x Mn x )2O7.

The breakdown of [Formula: see text] antiferromagnetism in the limit of strong disorder is studied in Sr3(Ir1-x Mn x )2O7. Upon Mn-substitution, antiferromagnetic ordering of the Ir cations becomes increasingly two-dimensional, resulting in the complete suppression of long-range Ir magnetic order above [Formula: see text]. Long-range antiferromagnetism however persists on the Mn sites to higher Mn concentrations (x > 0.25) and is necessarily mediated via a random network of majority Ir sites. Our data suggest a shift in the Mn valence from Mn4+ to Mn3+ at intermediate doping levels, which in turn generates nonmagnetic Ir5+ sites and suppresses long-range order within the Ir network. The collapse of long-range [Formula: see text] antiferromagnetism and the survival of percolating antiferromagnetic order on Mn-sites demonstrates a complex 3d-5d exchange process that surprisingly enables minority Mn spins to order far below the conventional percolation threshold for a bilayer square lattice.
Abstract 3645: Cooperation between canonical Wnt and TGF-beta pathways promotes sarcoma angiogenesis

Local and metastatic progression of solid tumors depends on crosstalk between tumor cells and the tumor microenvironment (TME), including both stromal cells and the extracellular matrix (ECM). We recently showed that high Wnt/beta-catenin activity in Ewing sarcoma correlates with diminished patient survival and that canonical Wnt signaling alters the tumor secretome, influencing ECM protein composition. In light of this, we investigated the hypothesis that Wnt/beta-catenin supports tumor progression by modulating tumor: TME crosstalk. Our results reveal that, in discrete tumor cell sub-populations, beta-catenin activation sensitizes cells to TGF-beta ligands through derepression of the TGF-beta receptor, TGFBR2 , resulting in canonical Wnt-induced, TGF-beta-dependent upregulation of TGF-beta targets. Significantly, these Wnt/TGF-beta responsive targets include multiple AngioMatrix genes that are known to alter the TME to promote angiogenesis, including tenascin-C and collagens. Studies of Ewing sarcoma models, in vitro and in vivo, as well as in two independent patient cohorts, confirm that a direct relationship exists between beta-catenin and TGF-beta activation in tumor cells and angiogenesis in the local TME. Mechanistically, this is due, in part, to tenascin C-mediated promotion of endothelial cell proliferation. Thus, functional cooperation between canonical Wnt and TGF-beta signaling in Ewing cells induces secretion of pro-angiogenic factors. This study reveals a novel link between Wnt and TGF-beta signaling in Ewing sarcoma and illustrates the critical contribution of tumor cell heterogeneity and tumor: TME crosstalk to sarcoma progression. Citation Format: Allegra G. Hawkins, Elisabeth A. Pedersen, Wei Jiang, Sydney Treichel, Colin Sperring, Jay Read, Brian Magnuson, Rajiv M. Patel, Dafydd Thomas, Rashmi Chugh, Elizabeth R. Lawlor. Cooperation between canonical Wnt and TGF-beta pathways promotes sarcoma angiogenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3645.
Bendamustine, Carfilzomib, and Melphalan (BCM) Conditioning Prior to Autologous Hematopoietic Stem Cell Transplantation for Multiple Myeloma: A Feasibility Study

Abstract High-dose melphalan (M) followed by autologous hematopoietic stem cell transplantation (AHSCT) remains the standard treatment for multiple myeloma in eligible patients, even in the era of novel agents. However, the majority of patients ultimately relapse and succumb to their disease. Several studies have explored integrating novel agents into the conditioning regimen prior to AHSCT in order to improve complete remission rates and ultimately overall survival. We aimed to assess the feasibility of adding bendamustine (B) and carfilzomib (C) to melphalan (BCM) and performed a phase I dose escalation study. Thirteen patients were enrolled between June 2014 and June 2016. All patients received C at a fixed dose (20 mg/m2) on days (d) -29, -28, -22, -21, -15, -14. The conditioning regimen and doses administered for each cohort were as described in the table below. Due to excessive toxicity, the study was amended after the first 6 patients. Per oversight of a data safety monitoring board, the dose of M was reduced to 140 mg/m2 and C dose on d +6 was omitted. Median age was 58 years (39-68). There were 8 males and 5 females. Performance status was ≥ 80% in all patients. Per the International Staging System (ISS), 3 patients had stage I disease, 5 had stage II, 4 had stage III, and 1 had unknown staging. Three patients had high-risk cytogenetics: 2 with t(4;14) and 1 with deletion 17p. Three patients had received prior AHSCT. Disease status prior to study treatment was stable disease (SD) (n=2), partial response (PR) (n=8), or very good partial response (VGPR) (n=3). Median CD34+ cell dose was 3.24x106/kg (2.23-6.92x106). Median follow-up was 14.2 months (1-24.5). Median time to neutrophil engraftment was 12 d (11-15). One patient died before achieving platelet engraftment. For the remaining patients, median time to platelet engraftment was 16 d (12-20). Non-hematologic toxicities included grade 3 acute mucositis (n=1), lower GI complications (n=6), electrolyte disturbances (n=6), transaminase elevation (n=1) renal insufficiency (n=1), pulmonary edema (n=1), prolonged QTc (n=1), atrial fibrillation (n=1), and elevated troponin (n=1) and grade 4 acute sepsis (n=2), resulting in 1 death in cohort 2 on d +44. Seven patients went on to receive maintenance therapy: 3 with bortezomib, 3 with lenalidomide, and 1 with lenalidomide, dexamethasone, and C. Post-transplant disease status was assessed per protocol by SPEP, SPIF, and serum free light chains and light chain ratio. Nine patients were evaluable on d +100. One patient had SD, 6 had VGPR, and 2 had complete response (CR). Six out of 7 (86%) evaluable patients on d +365 remain disease progression-free. In summary, BCM conditioning prior to AHSCT at the doses described in cohort 3b seems feasible with manageable toxicities. Five additional patients are being enrolled at the same dose level. Download : Download high-res image (93KB) Download : Download full-size image Disclosures No relevant conflicts of interest to declare.
LIVING WITH MULTIPLE MYELOMA: SELF-MANAGEMENT STRATEGIES

Multiple myeloma (myeloma), is an incurable cancer of the plasma cells that affects many older adults. Over 30,000 new diagnoses and over 12,000 deaths are attributed to myeloma annually in the United States, where the median age of diagnosis is 69 years old. Dramatic improvements in survival over the past fifteen years have transformed myeloma into a chronic disease for many. The disease and its toxic, ongoing treatment lead to significant challenges for patients. In this study we explore the self-management strategies patients use to address the challenges of living with myeloma through semi-structured one-on-one interviews with myeloma patients and clinicians. Fifteen myeloma patients and ten myeloma clinicians were interviewed between September 2017 and September 2018. Self-management strategies emerged in five major categories; managing uncertainty, finding emotional strength, seeking support, medication management, and activity management. The care of MM patients has made great strides as new and more effective treatments have extended survival for many patients. Effective self-management strategies are critical in addressing the challenges of this increasingly chronic disease. Our study explores the ways myeloma patients address the many challenges they face due to their disease and its’ treatment. Findings from this study could inform the development of interventions to optimize and support patients living with myeloma self-management.
Warning Signs in Communicating the Machine Learning Detection Results of Misinformation with Individuals.

With the prevalence of misinformation online, researchers have focused on developing various machine learning algorithms to detect fake news. However, users' perception of machine learning outcomes and related behaviors have been widely ignored. Hence, this paper proposed to bridge this gap by studying how to pass the detection results of machine learning to the users, and aid their decisions in handling misinformation. An online experiment was conducted, to evaluate the effect of the proposed machine learning warning sign against a control condition. We examined participants' detection and sharing of news. The data showed that warning sign's effects on participants' trust toward the fake news were not significant. However, we found that people's uncertainty about the authenticity of the news dropped with the presence of the machine learning warning sign. We also found that social media experience had effects on users' trust toward the fake news, and age and social media experience had effects on users' sharing decision. Therefore, the results indicate that there are many factors worth studying that affect people's trust in the news. Moreover, the warning sign in communicating machine learning detection results is different from ordinary warnings and needs more detailed research and design. These findings hold important implications for the design of machine learning warnings.
Taxonomic revision of the genus Machleida Fåhraeus, 1870 (Tenebrionidae, Pimeliinae, Asidini).

The taxonomic concept of the genus Machleida Fahraeus, 1870 is tested and revised based on newly identified material. The following new species are described: Machleida banachi, M. flagstaffensis, M. tarskii, and M. zofiae Kaminski. Machleida capillosa Wilke, 1925 is considered as a junior subjective synonym of Asida devia Peringuey, 1899. Asida lecta Peringuey, 1899 (= Pseudomachla recurva Wilke, 1925) (transferred to Afrasida), Machleida nossibiana Fairmaire, 1897 (transferred to Scotinesthes), and Machleida tuberosa Wilke, 1925 (interpreted as incertae sedis in Asidini) are excluded from Machleida. An identification key for the species of the newly revised Machleida is provided. The present paper brings the total number of species within the genus to six (M. banachisp. nov.; M. devia (Peringuey, 1899); M. flagstaffensissp. nov.; M. nodulosa Fahraeus, 1870; M. tarskiisp. nov.; M. zofiae Kaminski sp. nov.). The morphology of female terminalia (ovipositor and genital tubes) is described for the genus for the first time.
Impact of Life Events on Short-Term Change in BMI in Early and Middle Childhood.

Objective The accumulation of adverse events in childhood is linked to obesity, although the short-term (1 to 2 years) dynamics of weight change during life events has not been investigated. Methods In the Eunice Kennedy Shriver National Institute of Child Health and Human Development Study of Early Child Care and Youth Development, mothers reported life events in the past year when their children were 54 months, 9 years, and 11 years old. Children's height and weight were measured, and BMI-for-age z scores were calculated at 36 and 54 months and at 7, 9, 10, and 11 years. The estimated 1- and 2-year change in BMI z score of being in the highest quartile of negative and total life events was modeled using linear regression accounting for repeated measures. Results Analyses included 1,074 children. The highest quartile of negative life events was not statistically associated with BMI z score change at 2 years compared with those below the highest quartile (estimate: 0.069, 95% CI: -0.006, 0.144). Similarly, the highest quartile of total events was not related to BMI z score change (estimate: 0.029, 95% CI: -0.054, 0.114). The developmental period of the child did not moderate the association. Conclusions No significant change in BMI z score was observed in 1 to 2 years for children experiencing many life events.
Comparative in vitro transcriptomic analyses of COVID-19 candidate therapy hydroxychloroquine suggest limited immunomodulatory evidence of SARS-CoV-2 host response genes

ABSTRACT Hydroxychloroquine (HCQ) has emerged as a potential and controversial antiviral candidate therapy for COVID-19. While many clinical trials are underway to test the efficacy of HCQ as a treatment for COVID-19, underlying mechanisms of HCQ in the setting of COVID-19 remain unclear. Hence, we examined differential gene expression signatures of HCQ exposure, in vitro SARS-CoV-2 infection, and host signatures of COVID-19 in blood, bronchoalveolar lavage, and postmortem lung to evaluate whether HCQ transcriptome signatures associate with restoration of SARS-CoV-2-related host transcriptional responses. Here, we show that 24 hours of in vitro treatment of peripheral blood mononuclear cells(PBMC) with HCQ significantly impacted transcription of 16 genes involved in immune regulation and lipid metabolism. Using transcriptome data from in vitro SARS-CoV-2 infected NHBE and A549 cells and PBMC derived from confirmed COVID-19 infected patients, we determined that only 0.24% of the COVID-19 PBMC differentially expressed gene set and 0.39% of the in vitro SARS-CoV-2 cells differentially expressed gene set overlapped with HCQ-related differentially expressed genes. Moreover, we observed that HCQ treatment significantly impacted transcription of 159 genes in human primary monocyte-derived macrophages involved in cholesterol biosynthetic process and chemokine activity. Notably, when we compared the macrophage HCQ-related gene lists with genes transcriptionally altered during SARS-CoV-2 infection and in bronchoalveolar lavage of COVID-19+ patients, the CXCL6 gene was impacted in all three transcriptional signatures revealing evidence in favor of chemokine modulation. HCQ-related transcriptional changes minimally overlapped with host genes altered in postmortem lung biopsies from COVID-19 participants. These results may provide insight into the immunomodulation mechanisms of HCQ treatment in the setting of COVID-19 and suggest HCQ is not a panacea to SARS-CoV-2 infection.
Interpreting Life Impact Burn Recovery Evaluation (LIBRE) profile scores for use by clinicians burn survivors and researchers

The Life Impact Burn Recovery Evaluation (LIBRE) Profile is a patient-reported outcome measure developed to assess social participation in adult burn survivors. This study identified numeric score cut-points that define different levels of social participation ability and described each level. Methods An expert panel identified numeric score cut-points that distinguish different levels of social participation for the six LIBRE Profile domains. Methods employed an iterative, modified-Delphi approach and bookmarking to review calibrated item banks. Analyses (using calibration sample data and repeated in a validation sample) examined means, standard deviations, and sample distributions for each level. Analyses of Variance (ANOVAs) examined score differences between levels. The panel developed descriptions for each established level. Results Initial cut-points resulted in four levels for five domains (Social Activities, Social Interactions, Romantic Relationships, Sexual Relationships, Work & Employment), and five levels for the sixth domain (Relationships with Family & Friends). Comparisons demonstrated significant differences between level mean scores for all domains (p Conclusion Score cut-points and descriptions identify different levels of social participation, providing a relevant context for interpreting LIBRE Profile numeric scores. Applicability of research to practice LIBRE Profile Social Participation levels will help clinicians and persons with burn injury interpret LIBRE Profile numeric scores and promote use of this important new assessment.
Astrocytic Neurexin-1 Orchestrates Functional Synapse Assembly

ABSTRACT At tripartite synapses, astrocytes surround synaptic contacts, but how astrocytes contribute to the assembly and function of synapses remains unclear. Here we show that neurexin-1α, a presynaptic adhesion molecule that controls synapse properties, is also abundantly expressed by astrocytes. Strikingly, astrocytic neurexin-1α, but not neuronal neurexin-1α, is highly modified by heparan sulfate. Moreover, astrocytic neurexin-1α is uniquely alternatively spliced and invariably contains an insert in splice-site #4, thereby restricting the range of ligands to which it binds. Deletion of neurexin-1 from astrocytes or neurons does not alter synapse numbers or synapse ultrastructure, but differentially impairs synapse function. At hippocampal Schaffer-collateral synapses, neuronal neurexin-1 is essential for normal NMDA-receptor-mediated synaptic responses, whereas astrocytic neurexin-1 is required for normal AMPA-receptor-mediated synaptic responses and for long-term potentiation of these responses. Thus, astrocytes directly shape synapse properties via a neurexin-1-dependent mechanism that involves a specific molecular program distinct from that of neuronal neurexin-1.
Marital Quality and Well-Being Among Older Adults: A Typology of Supportive, Aversive, Indifferent, and Ambivalent Marriages.

A large body of work has linked marital quality to the health and well-being of older adults, but there is a lack of agreement on how to best measure dimensions of marital quality. Drawing on a str...
Transfer of printed electronic structures using graphene oxide and gelatin enables reversible and biocompatible interface with living cells

Abstract We present a low-cost, easy-to-implement platform for printing materials and interfacing them with eukaryotic cells. We show that thermal or chemical reduction of a graphene oxide thin film allows water-assisted delamination of the film from glass or plastic. The chemical and physical properties and permeability of the resulting film are dependent on the method of reduction and deposition of the graphene oxide, with thermal reduction removing more oxidized carbon functionality than chemical reduction. We also developed a method to attach the films onto cell surfaces using a thin layer of gelatin as an adhesive. In general, the films are highly impermeable to nutrients and we observed a significant amount of cell death when gelatin was not used; gelatin enables diffusion of nutrients for sustained cell viability. The combination of nanoscale membranes with a low melting point biopolymer allows us to reversibly interface cells with cargo transferred by graphene oxide while maintaining cell viability. To demonstrate delivery of electronic structures, we modified a commercial off-the-shelf printer to print a silver-based ink directly onto the reduced graphene oxide films which we then transferred to the surface of the cells.
Comparison of 30-Day Outcomes in Patients with Cervical Spine Metastasis Undergoing Corpectomy Versus Posterior Cervical Laminectomy and Fusion: A 2006-2016 ACS-NSQIP Database Study.

Background Patients with metastatic disease to the cervical spine have historically had poor outcomes, with an average survival of 15 months. Every effort should be made to avoid complications of surgical intervention for stabilization and decompression. Methods We identified patients who had undergone anterior cervical corpectomy and fusion (ACCF) or posterior cervical laminectomy and fusion (PCLF) for metastatic disease of the cervical spine using the American College of Surgeons National Surgical Quality Improvement Program database from 2006 to 2016. Patients meeting the inclusion criteria were subsequently propensity matched 1:1. We compared the overall complications, intensive care unit level complications, mortality, and return to the operating room between the 2 groups. Results After identifying the patients who met the inclusion criteria and propensity matching, a cohort of 240 patients was included, with 120 (50%) in the ACCF group and 120 (50%) in the PCLF group. The patients in the ACCF group were more likely to have experienced any complication (odds ratio, 2.1; 95% confidence interval, 1.1–4.1; P = 0.026) but not severe complications or a return to the operating room (P = 0.406 and P = 0.450, respectively). Conclusion In the present study, we found that anterior surgical approaches (ACCF) for metastatic cervical spine disease resulted in a significantly greater rate of overall complications (2.1 times more) compared with PCLF in the first 30 days. Although more studies are required to further elucidate this relationship, the general belief that the anterior approach is better tolerated by patients might not apply to patients with metastatic tumors.
Intraoperative Characterization of Subthalamic Nucleus-to-Cortex Evoked Potentials in Parkinson's Disease Deep Brain Stimulation

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a clinically effective tool for treating medically refractory Parkinson's disease (PD), but its neural mechanisms remain debated. Previous work has demonstrated that STN DBS results in evoked potentials (EPs) in the primary motor cortex (M1), suggesting that modulation of cortical physiology may be involved in its therapeutic effects. Due to technical challenges presented by high-amplitude DBS artifacts, these EPs are often measured in response to low-frequency stimulation, which is generally ineffective at PD symptom management. This study aims to characterize STN-to-cortex EPs seen during clinically relevant high-frequency STN DBS for PD. Intraoperatively, we applied STN DBS to 6 PD patients while recording electrocorticography (ECoG) from an electrode strip over the ipsilateral central sulcus. Using recently published techniques, we removed large stimulation artifacts to enable quantification of STN-to-cortex EPs. Two cortical EPs were observed - one synchronized with DBS onset and persisting during ongoing stimulation, and one immediately following DBS offset, here termed the "start" and the "end" EPs respectively. The start EP is, to our knowledge, the first long-latency cortical EP reported during ongoing high-frequency DBS. The start and end EPs differ in magnitude (p < 0.05) and latency (p < 0.001), and the end, but not the start, EP magnitude has a significant relationship (p < 0.001, adjusted for random effects of subject) to ongoing high gamma (80-150 Hz) power during the EP. These contrasts may suggest mechanistic or circuit differences in EP production during the two time periods. This represents a potential framework for relating DBS clinical efficacy to the effects of a variety of stimulation parameters on EPs.
Clinical and genetic spectrum in Chinese families with Fabry disease: a single-centre case series.

AIMS Fabry disease (FD) is an X-linked genetic disease caused by mutations in the GLA gene that leads to deficient activity of lysosomal enzymes, accumulation of globotriaosylceramide in multi-organ systems, and variant clinical manifestations. We aimed to detail the clinical and genetic spectrum of FD in Chinese families. METHODS AND RESULTS Five male probands with unexplained left ventricular hypertrophy and their family members were investigated. Genetic screening was available in 11 subjects of the 5 families, 10 of whom proved to be carriers of either GLA gene mutation, including 3 previous reported missense mutations (c.128G > A, c.811G > A, c.950T > C), 1 novel missense mutation (c.37G > C), and 1 novel deletion mutation (c.1241delT). A total of 17 patients were definitely or possibly diagnosed of FD, given their clinical manifestations and hereditary nature of FD. Echocardiography demonstrated normal cardiac structure and function in six female patients. Electrocardiographic pre-excitation occurred in 80% (4/5) of men and 16.7% (1/6) of women. Six patients (6/14, 42.9%) had chronic kidney disease with decreased renal function and all were male (6/7, 85.7%). Six patients presented with acroparesthesia, hypohidrosis, or both. Three female patients and two male patients experienced sudden death, and one male patient with the mutation (c.128G > A) died of progressive heart failure, between 41 and 66 years of age. CONCLUSIONS We reported five unrelated families of FD with different GLA mutations. Clinical manifestations were highly heterogeneous between male and female patients even within the same family. Female patients showed relatively low risks of structural heart disease and renal insufficiency. However, the long-term outcomes might be adverse in both sexes. Our study underlines the importance of molecular screening of the GLA gene for early identification and clinical decision making in patients with FD.
Discovery of highly reactive self-splicing group II introns within the mitochondrial genomes of human pathogenic fungi.

Fungal pathogens represent an expanding global health threat for which treatment options are limited. Self-splicing group II introns have emerged as promising drug targets, but their development has been limited by a lack of information on their distribution and architecture in pathogenic fungi. To meet this challenge, we developed a bioinformatic workflow for scanning sequence data to identify unique RNA structural signatures within group II introns. Using this approach, we discovered a set of ubiquitous introns within thermally dimorphic fungi (genera of Blastomyces, Coccidioides and Histoplasma). These introns are the most biochemically reactive group II introns ever reported, and they self-splice rapidly under near-physiological conditions without protein cofactors. Moreover, we demonstrated the small molecule targetability of these introns by showing that they can be inhibited by the FDA-approved drug mitoxantrone in vitro. Taken together, our results highlight the utility of structure-based informatic searches for identifying riboregulatory elements in pathogens, revealing a striking diversity of reactive self-splicing introns with great promise as antifungal drug targets.
Analgesics and Opioids

Analgesia may be enhanced with non-opioid and opioid analgesics, as well as coanalgesic agents. Non-opioid analgesics and short-acting opioids in chronic pain should be limited to infrequent, intermittent use for severe pain flares. Long-term risk for gastric and renal toxicity with analgesics is minimized with opioid analgesics. Medication abuse behavior occurs in 25–30% of patients with chronic pain treated with opioids.
Properties of the Polyoma Viruses Induced from BHK-21 Cells Transformed by A Gene Mutants

Polyoma viruses induced to replicate at 31 degrees C in BHK-21 cells transformed by polyoma A gene mutants retain the thermosensitive growth characteristics and genome structure of the original mutants used for transformation.
Upconversion and reduced /sup 4/F/sub 3/2/ upper-state lifetimes in intensely pumped Nd:YLF

Summary form only given. Intense diode-pumping of Nd-doped active elements in Q-switched lasers is a common approach to improve system efficiency, reliability, and reducing size. Compact laser devices using highly doped active elements with short pump absorption depths are particularly attractive for high average power applications since the thermal loads are more easily dissipated from the small-volume active elements. The /sup 4/F/sub 3/2/ upper-state lifetime, /spl tau/, is an important parameter for engineering such lasers since it affects the achievable stored-energy density for a given pumping scheme and ultimately determines the output energy of the system. Energy transfer upconversion (ETU) and sequential two-photon excitation processes (STEP) have been identified as important upconversion mechanisms. The same upconversion processes observed to reduce 1 /spl mu/m upper laser lifetime in Nd:YLF may also offer the potential for diode-pumped visible and near-UV laser sources in this material.
Evaluations of HPF for Practical Scientific Algorithms on T3E

HPF coding examples of practical scientific algorithms are examined in detail, with the idea that on these simple but non-trivial examples, we can fairly well understand issues related to different data distributions, different parallel constructs, and different programming styles (static vs dynamic allocations). Coding examples include 2D stencils solution of PDEs, N-body problem, LU factorization, several vector/matrix library routines, 2D and 3D array redistribution.The performances of HPF codes are close to hand-written message passing MPI codes, for LU factorization, vector/matrix routines, array redistributions. But for less regular data/communication patterns, the stencils calculation and the N-body problem, HPF codes perform considerably less efficient, about 2-4 times slower. Scaling of HPF codes is not as good as MPI codes. Some of the HPF codes performances are highly inconsistent, i.e., minor change of code could results in factor of 10 change in performance. Many peculiarities of HPF coding will be discussed.
Abstract 20295: Key Role of Integrin Alpha6/Beta4 in Endothelial Cell Barrier Regulation

The dynamic regulation of lung endothelial cell (EC) barrier integrity is essential in the initiation and resolution of inflammation during acute lung injury (ALI) and ventilator-induced lung injury (VILI). In previous studies, we identified integrin beta β4 (ITGβ4) as a key focal adhesion (FA) component, involved in human lung EC barrier enhancement by simvastatin. The clear functional role and key contribution of ITGβ4 in endothelial barrier regulation vascular permeability is largely unknown. We demonstrated that reduced ITGβ4 expression (siRNA attenuated sphingosine-1-phosphate (S1P, 1 μM) or hepatocyte growth factor (HGF, 25 ng/ml) mediated endothelial barrier enhancement. At the same time, S1P receptor 1 (S1PR1) or HGF receptor cMet knockdown also attenuated S1P- or HGF-mediated endothelial barrier enhancement. Consistent with these findings, in situ proximity ligation assays revealed that ITGβ4, S1PR1, and cMet, translocated together to the cell periphery as co-localized proteins after HGF treatment. We further confirmed that the interaction of c-Met and S1PR1 with ITGβ4 was dependent upon ITGβ4 phosphorylation, which is essential for HGF-mediated barrier enhancement. The selective antibody targeting integrin α6 (ITGα6, 10 μg/ml), the only binding partner of ITGβ4, attenuates S1P-mediated endothelial barrier enhancement. Furthermore, this antibody retarded barrier recovery after thrombin (0.5 U/ml), an EC barrier disruptor. These findings highly suggest ITGβ4 is essential participant in EC barrier regulation and paracellular gap closure. We next exposed genetically-engineered mice expressing a mutant ITGβ4 that lacks the cytoplasmic tail to ventilator-induced lung injury (VILI). The absence of the cytoplasmic tail conferred significant attenuation of inflammatory lung injury compared to wild-type controls with reduced BAL protein and cell counts and lung inflammation. These data suggest that the ITGβ4 cytoplasmic domain is an important participant in both pro- and anti-inflammatory responses to the excessive mechanical stress produced by VILI. In summary, ITGβ4 is a central regulator of endothelial barrier function, and a novel therapeutic target for acute lung inflammation.
Migration, Incorporation, and Change in an Interconnected World

Written in engaging and approachable prose, Migration, Incorporation, and Change in an Interconnected World covers the bulk of material a student needs to get a good sense of the empirical and theoretical trends in the field of migration studies, while being short enough that professors can easily build their courses around it without hesitating to assign additional readings. Taking a unique approach, Ali and Hartmann focus on what they consider the important topics and the potential route the field is going to take, and incorporate a conceptual lens that makes this much more than a simple relaying of facts.
Interatomic Potentials for Metals

Many processes in materials, such as plastic deformation, fracture, diffusion and phase transformations, involve large ensembles of atoms and/or require statistical averaging over many atomic events. Computer modeling of such processes is made possible by the use of semi-empirical interatomic potentials allowing fast calculations of the total energy and classical interatomic forces. Due to their computational efficiency, interatomic potentials give access to systems containing millions of atoms and enable molecular dynamics simulations for tens or even hundreds of nanoseconds. State-ofthe-art potentials capture the most essential features of interatomic bonding, reaching the golden compromise between computational speeds and accuracy of modeling. This article reviews interatomic potentials for metals and metallic alloys. The basic concepts used in this area are introduced, the methodology commonly applied to generate atomistic potentials is outlined, and capabilities as well as limitations of atomistic potentials are discussed. Expressions for basic physical properties within the embedded-atom formalism are provided in a form convenient for computer coding. Recent trends in this field and possible future developments are also discussed.