cssi/SciSciGPT-SciSciNet huggingface dataset:
Combining Hierarchical Inference in Ontologies with Heterogeneous Data Sources Improves Gene Function Prediction

The study of gene function is critical in various genomic and proteomic fields. Due to the availability of tremendous amounts of different types of protein data, integrating these datasets to predict function has become a significant opportunity in computational biology. In this paper, to predict protein function we (i) develop a novel Bayesian framework combining relational,hierarchical and structural information with improvement in data usage efficiency over similar methods, and (ii) propose to use it in conjunction with an integrative protein-protein association network, STRING (Search Tool for the Retrieval of INteracting Genes/proteins), which combines information from seven different sources. At the heart of our work is accomplishing protein data integration in a concerted fashion with respect to algorithm and data source. Method performance is assessed by a 5-fold cross-validation in yeast on selected terms from the Molecular Function ontology in the Gene Ontology database. Results show that our combined use of the proposed computational framework and the protein network from STRING offers substantial improvements in prediction. The benefits of using an aggressively integrative network, such as STRING, may derive from the fact that although it is likely that the ultimate gene interaction matrix (including but not limited to protein-protein, genetic, or regulatory interactions) will be sparse, presently it is still known only incompletely in most organisms, and thus the use of multiple distinct data sources is rewarded.
The Role of Juveniles in Urban Homicide: The Case of Houston, 1990-1994

Youth homicide offending is now regarded as a threat to society at large and inner cities in particular. A leading explanation focuses on gangs, drugs, and guns as the nexus of contemporary youth violence. This study profiles juvenile homicide in one of the nation's largest cities, Houston, Texas, for the period of 1990 to 1994. Following Marvin Wolfgang's precedent, the authors summarize these homicide data in terms of demographic characteristics and victim-offender relationships. They then address the spatial distribution of lethal incidents. The authors find that gang-related killing is a relatively small proportion of all juvenile homicide offending. Also, juveniles are more likely than are adults to use firearms, commit homicide in public and outdoor locations, and engage in lethal violence in relation to other felony offending. The authors conclude with a discussion of criminal justice responses to juvenile violence.
In Vitro Microtubule-Based Organelle Transport in Wild-Type Dictyostelium and Cells Overexpressing a Truncated Dynein Heavy Chain

The transport of vesicular organelles along microtubules has been well documented in a variety of systems, but the molecular mechanisms underlying this process are not well understood. We have developed a method for preparing extracts from Dictyostelium discoideum which supports high levels of bidirectional, microtubule-based vesicle transport in vitro. This organelle transport assay was also adapted to observe specifically the motility of vesicles in the endocytic pathway. Vesicle transport can be reconstituted by recombining a high-speed supernatant with KI-washed organelles, which do not move in the absence of supernatant. Furthermore, a microtubule affinity-purified motor fraction supports robust bidirectional movement of the salt-washed organelles. The plus and minus end-directed transport activities can be separated by exploiting differences in their affinities for microtubules in the presence of 0.3 M KCl. We also used our assay to examine organelle transport in a strain of Dictyostelium overexpressing a 380-kDa C-terminal fragment of the cytoplasmic dynein heavy chain, which displays an altered microtubule pattern (380-kDa cells; [Koonce and Samso, Mol. Biol. Cell 7:935-948, 1996]). We have found that the frequency and velocity of minus end-directed membrane organelle movements were significantly reduced in 380-kDa cells relative to wild-type cells, while the frequency and velocity of plus end-directed movements were equivalent in the two cell types. The 380-kDa C-terminal fragment cosedimented with membrane organelles, although its affinity was significantly lower than that of native dynein. An impaired membrane-microtubule interaction may be responsible for the altered microtubule patterns in the 380-kDa cells.
When Will They Ever Learn?: Coercive Bargaining in Recurrent Crises

A set of hypotheses derived from experiential learning and a realpolitik orientation to crisis bargaining are employed to investigate the bargaining behavior of pairs of states embroiled in recurring crises. It is proposed that in crisis bargaining, experiential learning focuses on the outcome of the preceding crisis, and the lessons drawn from that experience are interpreted in accordance with a realpolitik orientation that stresses the importance of a credible demonstration of power and resolve. The hypotheses predict that in crises between states of relatively equal military capabilities, successful outcomes encourage policymakers to repeat the bargaining strategy employed in the previous crisis, while failures lead to more coercive bargaining in the next crisis. Employing events data from a sample of 18 disputes among 6 pairs of states, each pair having been engaged in three successive crises, a significant pattern of shifts to more coercive bargaining following crises with unsuccessful outcomes was f...
Entropy of N = 2 black holes and their M-brane description

In this paper we discuss the M-brane description for an N=2 black hole. This solution is a result of the compactification of M-5-brane configurations over a Calabi-Yau threefold with arbitrary intersection numbers C{sub ABC}. In analogy with the D-brane description where one counts open string states we count here open M-2-branes which end on the M-5-brane. {copyright} {ital 1997} {ital The American Physical Society}
Statin therapy is associated with superior clinical outcomes after endovascular treatment of critical limb ischemia.

Objective The aim of this study was to determine if statin therapy improves clinical outcomes after endovascular intervention in patients with critical limb ischemia (CLI). Methods A retrospective review of all patients undergoing endovascular treatment for CLI was performed. Two groups were created according to whether they were receiving statin therapy at the time of intervention. Demographics, lesion morphology, overall mortality, primary and secondary patency, and limb salvage were compared between these groups. Analysis was performed using multivariate regression and Kaplan-Meier analysis. Results Between 2004 and 2009, 646 patients, 319 receiving statin therapy and 327 without, underwent an endovascular intervention for CLI. The statin group had significantly higher rates of diabetes mellitus, coronary artery disease, congestive heart failure, previous myocardial infarction, and coronary artery bypass grafting (P Conclusions Patients who were receiving statin therapy when they underwent interventions to treat CLI had significantly improved overall survival, primary and secondary patency, and limb salvage rates. Our findings suggest that statins should be part of the periprocedural treatment regimen and support further investigation into the beneficial effects of statins in patients undergoing endovascular treatment of CLI.
Acetylcholine-induced relaxation and hyperpolarization in small bovine adrenal cortical arteries: role of cytochrome P450 metabolites.

The present study characterizes the vascular responses of isolated small bovine adrenal cortical arteries to acetylcholine, an endogenous neurotransmitter in the adrenal gland. Acetylcholine (10−10 to 10−6 m) elicited a concentration-dependent relaxation, with a maximal relaxation of 96 ± 1% and EC50 of 4.2 nm. The relaxation was abolished by endothelial removal and attenuated by the nitric oxide synthase inhibitor N-nitro-l-arginine (L-NA, 30 μm) but not by the cyclooxygenase inhibitor indomethacin (10 μm). The maximal relaxation and EC50 of acetylcholine in the presence of L-NA were 87 ± 4% and 22 nm, respectively. The acetylcholine-induced, indomethacin- and L-NA-resistant relaxation was eliminated by high K+ and markedly inhibited by the cytochrome P450 inhibitors SKF 525A (10 μm) and miconazole (10 μm). The maximal relaxations and EC50s with SKF 525A and miconazole were 56 ± 8 and 72 ± 2% and 0.8 and 0.5 μm, respectively. In indomethacin- and L-NA-treated arteries, acetylcholine induced a smooth musc...
Abstract B2-45: Uncovering coordinated regulation of transcription factors by microRNAs using integrated network models

MicroRNAs (miRNAs) are small non-coding RNAs that play a significant role in development and cancer but induce only moderate repression of direct messenger RNA (mRNA) targets, suggesting that they coordinate with other modes of cellular regulation to affect cellular phenotype. In this work we exhaustively profile the transcriptional and post-transcriptional regulatory changes between an isogenic pair of murine fibroblast cell lines with and without Dicer, an enzyme required for miRNA processing. Through quantitative analysis of diverse high-throughput datasets collected from both cell lines, we were able to decouple transcriptional from post-transcriptional changes reflected in mRNA expression changes between cells with and without miRNAs. We present three major findings. First, we find that direct miRNA-mRNA interactions have a limited impact on gene expression changes upon Dicer deletion when compared to changes at transcription. We then introduce an integrative graphical network approach to identify specific transcription factors that explain the observed changes in gene expression upon loss of Dicer. Validation of this computational model via transcription factor over-expression reveals a subset of the miRNA-mediated transcriptional program that is activated upon Dicer loss, confirming that transcriptional networks amplify the effects of miRNAs. Lastly, we use this network to examine coordination between transcriptional and post-transcriptional regulation. We identify numerous coherent and in-coherent feed-forward loops, network motifs that have been alluded to but only minimally studied in the context of microRNAs and transcription factors, and find that genes regulated within feed-forward loops by microRNAs and transcription factors exhibit distinct properties in development. In summary, our work illustrates how transcriptional networks amplify the effects of microRNAs. We show coordinated regulation of transcription factors by microRNAs that suggests that most gene expression changes attributed to microRNAs in diseases such as cancer are due to changes in transcription rather than microRNA-mediated degradataion. As such, this work has the potential to reframe future studies of microRNAs in the context of cancer by shifting the focus to understanding the impact of microRNAs on transcription factors. Citation Format: Sara JC Gosline, Allan M. Gurtan, Courtney K. JnBaptiste, Andrew Bosson, Pamela Milani, Simona Dalin, Bryan Matthews, Yoon Sing Yap, Phillip A. Sharp, Ernest Fraenkel. Uncovering coordinated regulation of transcription factors by microRNAs using integrated network models. [abstract]. In: Proceedings of the AACR Special Conference on Computational and Systems Biology of Cancer; Feb 8-11 2015; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(22 Suppl 2):Abstract nr B2-45.
“What’s the Matter with You Catholics?” Soundings in Catholic Social Thought: Traditions in Turmoil. By Mary Ann Glendon

This review essay of Mary Ann Glendon's Traditions in Turmoil (2006) explores such topics as tradition, moral discourse, human rights, subsidiarity, natural law, the common good, civil society, and constitutional and statutory interpretation. In doing so, it provides an introduction both to Catholic social thought and to the thought of Bernard Lonergan.
Effects of Several Antianginal Agents on Pacing-Induced S-T Segment Depression in the Atherosclerotic Rabbit

SummarySeveral agents used clinically in the treatment of angina pectoris were studied in an atherosclerotic rabbit model previously shown to be useful in differentiating anti-anginal drug activity. Intravenously administered isosorbide dinitrate afforded protection against pacing-induced S-T segment depression in a dose-related manner. Drugs with no protective effect included penta-erythritol tetranitrate, chromonar, and papa-verine. Propranolol also did not prevent pacing-induced S-T segment depression, due in part to the overriding of the beneficial negative chronotropic effect of this drug by pacing.
Fluorescence in Cochroaches

We have observed hitherto unreported fluorescence in various tissues, organs, and products of 19 species of cockroaches during irradiation with ultraviolet light.
Building the interface between the base-band unit and radio unit of multi-mode base-stations using OBSAI

The unique frame structure of OBSAI can facilitate the transport of different wireless-standard base-band data. The common interface between the base-band unit and radio unit (which is based on the base-band) can eliminate the impact of these standards on data transport link. This common interface allows one hardware platform to easily support every kind of wireless standard. When building the interface between the base-band unit and radio unit of a multi-mode base-station using OBSAI,the base-band unit and radio unit must be changed to support the new wireless standard. It is unnecessary to change the other software ,hardware ,or logic within the units if the optical interface rate stays the same.
From Antarctica Lidar Discoveries to Oasis Exploration

Stunning new science discoveries including neutral thermospheric metal layers in the 100–200 km altitude from McMurdo lidar campaign and other world lidar observations have led to a new initiative in the middle and upper atmosphere science community—the very large-aperture lidar Observatory for Atmosphere Space Interaction Studies (OASIS). These discoveries and the recent technology breakthroughs in Fe and Na Doppler lidars are presented to illustrate the science drivers and technology foundations forming the basis for OASIS.
Expression of phenylethanolamine N-methyltransferase (PNMT) and neuropeptide Y (NPY) in embryonic rat medulla oblongata grown in Oculo.

Expression and development of specific markers of the adrenergic phenotype were studied in central neurons grown in transplant system. Medulla oblongata from embryonic day 12.5 (E12.5) or E18 rat was grafted into the anterior chamber of the eye of adult rat hosts. After two months, grafts were examined for the presence of immunoreactivity (IR) and catalytic activity to the epinephrine-synthesizing enzyme, phenylethanolamine N-methyltransferase (PNMT, E.C. 2.1.1.28), a specific adrenergic marker. In addition, grafts were examined for immunoreactivity to neuropeptide Y (NPY) and tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine synthesis. In E12.5 grafts, PNMT was expressed de novo, enzyme activity developed to levels similar to those in adult rat brainstem and PNMT-IR neurons were observed. TH-IR and NPY-IR neurons were also observed. In contrast, PNMT-IR was not observed in E18 grafts even though these already contained PNMT-IR neurons at the time of grafting. This was not due to poor growth of E18 grafts, in general, since TH-IR neurons were present and the protein content of the grafts was similar to that of E12.5 grafts. These studies suggest that adrenergic neurons survive well in oculo if they are transplanted prior to the age when neuroblasts have initially expressed the adrenergic phenotype, migrated to their final positions and elaborated processes. In addition, these studies establish a transplant system in which factors required for the development of central adrenergic neurons can be more easily studied than in situ.
Molecular Mapping of Quantitative Trait Loci in Tomato

A major objective in modern biology is deciphering the genetic and molecular bases of natural phenotypic variation. Over the past three decades, the tomato clade (Solanum sect. Lycopersicon) has been a model system not only for the identification and positional cloning of quantitative trait loci (QTL), but also for the development of new molecular breeding strategies aimed at a more efficient exploration and exploitation of the rich biodiversity stored in wild germplasm for hundreds of biologically and agronomically relevant quantitative traits. The numerous QTL mapping studies conducted so far have resulted in the detection of several thousands of QTL. Despite this wealth of genetic information, the molecular bases have been revealed for only a handful of major QTL. The release of the tomato genome sequences, along with the rapid development of cost-effective next-generation sequencing (NGS) technologies, new mapping resources, and the evergrowing ‘‘omic’’ platforms, are holding the promise to reverse this trend. This deluge of genomic resources are undoubtedly reshaping QTL analyses also in this crop, allowing a reexamination of the variation and inheritance of complex traits at the intraspecific level, increasing the spectrum of potentially valuable alleles available for breeding. In this framework, precision phenotyping, advanced bioinformatics tools, as well as public phenotype “warehousing” databases are foreseen as the necessary tools to boost our understanding of the genetic and molecular architecture of quantitative traits, and to guarantee sustainable crop improvements in the face of an evergrowing human population and changing climates.
Beyond the Boundaries: Principals, Parents and Communities Shaping the School Environment

Internationally, there is increasing interest and emphasis on parental and community involvement as a strategy for improving education. The 1988 Education Reform Act in the United Kingdom, the emergence of self-managing schools in Australia, the increase of local school councils in the United States and the evolution of interagency collaboration between schools and social services, provide only a few examples of programs that promote parental and community advocacy and activism in schools. These changes provide new and different challenges for school principals.
The object class intrinsic filter conjecture

We present the object class intrinsic filter conjecture. The aim of our work is to investigate design principles for machine learning algorithms that demonstrate false positive rates practically equal to zero. Reducing the false positive rate in machine learning algorithms is important in several fields. In cybersecurity for instance, algorithms that demonstrate few to almost zero false positive detections are typically more robust against attacks, where the adversary intentionally modifies the input in order to drive algorithms to some intended misclassification result. The object class intrinsic filter conjecture states that it is possible to augment standard machine learning algorithms with filters which depend on the object class which is being detected, and which, contrary to standard machine learning algorithms, use weight, bias and threshold values which are in part determined through training and in part functions of the runtime input (i.e., the input provided to algorithms at runtime for classification or scoring). This is a departure from some standard machine learning algorithms where weight and threshold values are determined only through training. We investigate the validity of our conjecture experimentally, presenting a hand gesture recognition system augmented with an object class intrinsic filter where the overall system's false positive rate is dropped to practically zero.
4–40 GHz conical spiral antenna recessed in a cavity

This paper considers conical spiral antennas recessed in cavities for 4 to 40 GHz broadside wide beam applications. It is shown that a conical configuration has positive gain within 120 degrees field of view in free space, which is wider compared to a planar spiral. As expected, the cavity greatly affects the antenna radiation, such that field of view is reduced to 100 degrees and broadside gain shows significant variation. Relation between the gain variation and cavity/aperture resonances is discussed. In spite of using absorber for suppressing cavity modes, radiation efficiency is higher than 65%, and it is better than 80% at frequencies above 10 GHz.
Arrested by Skin Color: Evidence from Siblings and a Nationally Representative Sample:

Racial disparities in the criminal justice system are striking, but social scientists know little about skin color inequalities within this system. Research demonstrates that racial minorities with...
High-strain shape memory polymers as practical dry adhesives

Abstract The adhesive benefits of incorporating shape memory polymers (SMPs) in various dry adhesive designs have been well documented in recent years. Chemically-crosslinked SMPs can possess remarkable shape fixity and recovery ability, chemical and thermal stability, a sharp glass transition, and other desirable qualities. However, low failure strain and a relatively rigid rubbery state limit their performance as a dry adhesive component in many practical applications. This work explores the adhesive benefits of using an epoxy-based SMP which has been modified to possess a softer rubbery state and a greatly increased maximum strain before failure. One of the modified SMPs forms the active adhesive surface of a prototype consumer level device.
Predictors of poor neonatal outcomes in prenatally diagnosed multicystic dysplastic kidney disease.

Multicystic dysplastic kidney (MCDK) is one of the most common anomalies detected by prenatal ultrasound. Our objective was to identify factors associated with severe adverse neonatal outcomes of prenatally diagnosed MCDK A retrospective review of prenatally diagnosed MCDK (1 January 2009 to 30 December 2014) from a single academic center was conducted. The primary outcome was death or need for dialysis among live-born infants. Associations between prenatal characteristics and outcome were analyzed by Fisher’s exact test and Mann–Whitney test. A total of 53 cases of prenatally suspected MCDK were included, of which 46 cases were live-born and confirmed postnatally (38 survivors, 8 non-survivors). Prenatally diagnosed extrarenal anomalies, bilateral MCDK, contralateral renal anomalies, and anhydramnios were significantly associated with death or need for dialysis (all p < 0.0001). Prenatally identified findings are associated with adverse neonatal outcome, and can guide counseling and management planning. In the absence of significant associated findings, prenatally diagnosed unilateral MCDK has a benign neonatal course.
Parental overcontrol x OPRM1 genotype interaction predicts school-aged children's sympathetic nervous system activation in response to performance challenge.

Abstract Parental overcontrol (OC), the excessive regulation of a child’s behavior, cognition, and emotion, is associated with the development of child anxiety. While studies have shown that genetic factors may increase sensitivity to stress, genetic vulnerability to parental OC has not been examined in anxiety etiology. A functional polymorphism in the mu opioid receptor OPRM1 (A118G, rs1799971) has been shown to impact stress reactivity. Using a community sample of children (N = 85, 9–12 years old), we examined the main and interactive effects of maternal OC and child OPRM1 genotype in predicting children’s sympathetic nervous system reactivity during a performance stressor. Neither OC nor genotype predicted children’s electrodermal activity (EDA); however, the interaction between OC and child genotype significantly predicted stress reactivity, as indexed by EDA, during the challenging task. Among children with the minor G-allele, higher maternal OC was associated with higher reactivity. In A homozygotes, maternal OC was not associated with EDA, suggesting a diathesis-stress pattern of gene x environment interaction. We discuss implications for anxiety etiology and intervention.
Moving Beyond Biography: Critical Race Theory and the Construction of the Alternative Black Curriculum in Social Studies

This chapter will present a case study of the social studies curriculum of the National Training School for Women and Girls. In 1909, Nannie H. Burroughs created the National Training Schools for Women and Girls in Washington, DC, which was designed to teach African American girls skills needed to be intellectual contributors to the workforce. The leadership of Nannie H. Burroughs is analyzed as she attempts to develop a black history curriculum in her school. Primary source documents such as lesson plans, black history month agendas, and student work are analyzed in this important case study.
PAK1 in Alzheimer’s and Huntington’s Diseases

Among a variety of neurodegenerative diseases, Alzheimer’s disease (AD) and Huntington’s disease (HD) have been particularly well studied at the genetic and molecular levels. The progressive cognitive decline in AD patients is known to be most closely associated with the pathological signature amyloid-β (Aβ) protein deposited in extracellular plaques and intraneuronal neurofibrillary tangles (NFT) consisting largely of tau protein. AD is heterogeneous and can be caused either by rare autosomal dominant mutations elevating aggregation-prone Aβ or by a mix of environmental and genetic risk factors. In contrast, the sole known genetic cause of HD is mutations of the huntingtin gene that lead to the oligomerization of its gene product (huntingtin) with extra oligoGln (also called polyQ) resulting in neurotoxicity. Loss of synapses and dendritic spines in vulnerable areas are early pathological indices related to cognitive deficits in various neurodegenerative diseases, including AD and HD. Aβ aggregates activate GTPases, RAC and CDC42 via Tiam 1 in a Ca 2+- dependent manner, and these GTPases in turn activate the kinase PAK1, which directly activates LIM kinase (LIMK). LIMK inactivates cofilin and F-actin severing protein, and eventually stimulates actin polymerization, disrupting actin dynamics, which can lead to the formation of actin rods and disruption of dendritic spines. Imbalances in actin dynamics can also occur in other cell types, such as through influencing actomyosin-dependent phagocytosis of neurons by microglia. The SRC family Tyr kinase inhibitor PP2, as well as curcumin, block PAK1 activation in Aβ oligomer-treated neurons. Similarly, in HD models, PAK1 activation enhances polyQ oligomerization and neurotoxicity. We discuss the potential of PAK1 as a viable target for the therapy of both AD and HD.
Unresolved, atraumatic breast hematoma: Post-irradiation or secondary breast angiosarcoma

Post-irradiation or secondary angiosarcoma of the breast was first described in the 1980s in patients treated with breast conserving therapy for cancer. The primary management of radiation-induced breast angiosarcoma has focused on surgical resection with an emphasis on achieving negative tumor margins. While surgery remains a key component of treatment, novel therapeutic approaches have surfaced. Despite such advances in treatment, prognosis remains poor.
Stage A prostatic adenocarcinoma

Stage A prostatic adenocarcinoma is defined as prostatic malignancy that cannot be identified by rectal examination and is identified only when an operative procedure is carried out for presumably benign prostatic outflow obstruction. With questions being raised as to the potential impact of transrectal prostatic ultrasonography on the detection of prostatic malignancy that is undefined by rectal examination, it is reasonable to ask whether stage A prostatic adenocarcinoma involves the same biologic hazard as clinically palpable prostatic malignancy or a lower risk. To address this question, several questions are posed.
The Relaxation Response Resiliency Program (3RP) in Patients with Headache and Musculoskeletal Pain: A Retrospective Analysis of Clinical Data.

Abstract Background Headache and musculoskeletal pain are associated with both physical and mental health symptoms, which together are mutually reinforcing. Addressing mental and physical health symptoms (including pain) concomitantly may provide an effective and efficient way to improve outcomes in this population. We tested an evidence-based, eight-session multimodal group program, the Relaxation Response Resiliency Program (3RP), in patients with headache and musculoskeletal pain. A total of 109 adults (30 with headaches, 79 with musculoskeletal pain). Methods Participant were 109 adults (30 with headaches, 79 with musculoskeletal pain) referred by their medical doctor, who completed a battery of questionnaires before and after completion of the 3RP. Results On average, patients with headache and musculoskeletal pain had higher pretreatment scores for anxiety, depression, and somatization symptoms than the nonpatient normative sample for the Symptom Checklist 90—Revised. Significant improvements were identified from pre- to post-treatment in all mental health symptoms (moderate to large effects) and frequency of pain and co-occurring physical health symptoms (small to moderate effects). Patients also reported significant decreases in degree of discomfort and life interference, which were relatively more modest in the musculoskeletal pain group compared with the headache group. Conclusions Overall, results of this study suggest that the 3RP may be an effective treatment for reducing pain and psychological symptoms in patients with headaches and musculoskeletal pain. Future work is needed to evaluate the 3RP via a randomized clinical trial in these patient populations.
The Easix Score Is Associate with Overall Survival and Non-Relapse Mortality after Ex-Vivo CD34+-Selected Allogeneic HCT.

Background The EASIX (Endothelial Activation and Stress Index) score has been shown to be associated with NRM and overall survival (OS) after reduced intensity alloHCT. We aimed to validate EASIX in patients who underwent a calcineurin-inhibitor (CNI)-free alloHCT using ex-vivo CD34-selection. Design We included 364 adult patients who underwent first CD34-selected alloHCT between July 2006-December 2016 using the CliniMACS CD34 Reagent System (Miltenyi Biotech) as GVHD prophylaxis. The EASIX score (LDH*Creatinine/platelet counts) was calculated at several timepoints (pre-HCT [day -30 to day -10], day 30, day 100 and onset of acute GVHD). For EASIX scores post-HCT, a landmark analysis was conducted at the given timepoint. A log transformation using base 2 (log2) was applied to all EASIX variables to reduce skew. The Kaplan-Meier and cumulative incidence methods were used to estimate OS and NRM/acute GVHD, respectively. Cox models (cause-specific for NRM and acute GVHD) were used to evaluate differences in outcomes. Relapse and death or relapse, were considered competing risks for NRM and acute GVHD, respectively. Results Median age was 55 years (range 19-73). Most patients had myeloid diseases (47% AML, 28% MDS and 4% CML) and all patients received myeloablative conditioning (MAC). With a median follow-up among survivors of 4.7 years (range, 0.7-11.8), 1 and 3-year OS was 78.6% (95% confidence interval [CI], 74.0-82.4) and 61.8% (95% CI, 56.5-66.7), respectively. The cumulative incidence of NRM at 1 and 3 years was 15.1% (95% CI, 11.7-19.0) and 24.2% (95% CI, 19.9-28.8), respectively. The 1-year cumulative incidences of grades 1-4, 2-4, and 3-4 acute GVHD were 40.1% (95% CI, 35.1-45.1), 29.4% (95% CI, 24.8-34.1) and 11.0% (95% CI, 8.0-14.5), respectively. Pre-HCT EASIX was not significantly associated with OS, NRM, or acute GVHD. A higher day 30 EASIX score was significantly associated with increased risk of death (HR=1.35 [95% CI, 1.19-1.52], p Conclusions EASIX score at day 30 and at day 100 post-ex-vivo CD34-selected alloHCT is associated with higher NRM and inferior OS. Despite a CNI-free platform, endothelial injury is an important contributor to poorer outcomes after MAC. EASIX provides a simple, complimentary tool to predict allo-HCT outcomes in these patients.
Assessment of Individual versus Composite Endpoints of Acute Graft-versus-Host Disease in Determining Long-Term Survival after Allogeneic Transplantation.

ABSTRACT The overall composite of graft-versus-host disease (GVHD)-free, relapse-free survival (GRFS), defined as survival free of grade III-IV acute GVHD (aGVHD), chronic GVHD (cGVHD) requiring systemic immunosuppressive therapy (IST), or relapse, has emerged as a useful composite in clinical trials and to capture clinically meaningful events that impact quantity and quality of survival after allogeneic hematopoietic cell transplantation (HCT). We reviewed 565 consecutive patients aged ≥18 years undergoing HCT for hematologic malignancy to analyze how baseline incidence, specifics of clinical definitions, and proposed reductions in any one individual event may dynamically alter the overall performance of the composite To determine the relative impact of each GRFS event (excluding death), we accounted for competing risks using Fine and Gray methods, and correlated each event with overall survival (OS) using Kaplan-Meier methods. The consequences of modulating individual or composite endpoints on OS, such as hypothesized reductions of events of an HCT interventional trial, were examined using Monte Carlo simulations. The median age of the cohort was 54 years (range, 18 to 73 years). The majority of patients received HLA-matched unrelated donor HCT (53%), consisting of peripheral blood stem cell grafts (90%) after myeloablative conditioning (68%). Relapse conferred the greatest risk for death (hazard ratio [HR], 7.89; 95% confidence interval [CI], 5.83 to 10.69), followed by grade III-IV aGVHD (HR, 6.16; 95% CI, 4.42 to 8.56) and cGVHD requiring IST (HR, 1.69; 95% CI, 1.16 to 2.46). The overall GRFS composite correlated with an HR of 4.81 (95% CI, 3.61 to 6.41), which was lower compared with either relapse or grade III-IV aGVHD. Statistical simulations found that modulating the combined risk of both relapse and grade III-IV aGVHD predicted the greatest change in 5-year OS. These simulations suggest that GRFS as currently defined may be less optimal for correlating with OS, and further refinement of composite endpoints is needed. Nonetheless, composite endpoints may be particularly helpful in mitigating potential difficulties in interpretation when competing risks are present, most commonly seen in HCT studies.
Statistical testing in a Linear Probability Space

Imagine that you could calculate of posttest probabilities, i.e. Bayes theorem with simple addition. This is possible if we stop thinking of probabilities as ranging from 0 to 1.0. There is a naturally occurring linear probability space when data are transformed into the logarithm of the odds ratio (log10 odds). In this space, probabilities are replaced by W (Weight) where W=log10(probability/(1-probability)). I would like to argue the multiple benefits of performing statistical testing in a linear probability space: 1) Statistical testing is accurate in linear probability space but not in other spaces. 2) Effect size is called Impact (I) and is the difference in means between two treatments (I=Wmean2-Wmean1). 3) Bayes theorem is simply Wposttest=Wpretest+Itest. 4) Significance (p value) is replaced by Certainty (C) which is the W of the p value. Methods to transform data into and out of linear probability space are described.
Approaching Ideals through Innovation: Twentieth and Twenty-First Century Mass Media Technology and American Democracy

From the moment our First Amendment was adopted, America’s ideal of democracy has been firmly intertwined with media communications between the President and the citizenry. Over time, technological advancements have altered the way this communication is facilitated, increasing the public’s access to the Office of the Presidency, and visa versa, via new forms of media. Through an examination of Franklin Delano Roosevelt’s use of the radio, the first televised debate between John F. Kennedy and Richard Nixon in 1960, and Barack Obama’s use of Social Media and the Internet, this thesis will seek to answer the question of whether the greater access gained from new communication mediums has enhanced American democracy. While any increase in dialogue between the Office of the President and citizens undoubtedly brings us closer to our democratic ideals, it will likewise be demonstrated that each new form of media has been uniquely suited to increase transparency into the political process in ways relevant to the era in which politicians adopted them.
Author's Reply to “Reader's Response to ‘There Have Been Inadequate Warnings That Erectile Dysfunction Drugs Can Cause Blindness’”

To the Editor, In addition to our study showing an 18-fold increased rate of reports to the FDA [US Food and Drug Administration] of nonarteritic anterior ischemic optic neuropathy (NAION) per million prescriptions with sildenafil (Viagra) compared with atorvastatin (Lipitor),[1] a recent case-control study found that for those men with either hypertension or a history of myocardial infarction (MI), the use of sildenafil or tadalafil (Cialis) conferred an increased risk for NAION, 10.7-fold increased risk and statistically significant for those with a history of MI and 6.9-fold increased risk but not quite statistically significant for those with hypertension.[2] Thus, in the face of increased cardiovascular risk, such as seen with hypertension or MI, there is an increased risk for NAION for those using these erectile dysfunction drugs. If Dr. Stone[1] would read the book that he describes his patients as “clutching” Worst Pills, Best Pills (also available at worstpills.org), he would find that we do indeed describe why people with globally increased cardiovascular risk for strokes or heart attacks should be treated. But whenever we describe a drug as do not use, we always refer the patient to the pages in the book in which the safer, equally effective, and often less expensive alternative is described. With respect to our opportunity to educate the public, we will “use that position to responsibly educate the public in the future” as we have for the past 35 years. Readers are encouraged to respond to George Lundberg, MD, Editor of MedGenMed, for the editor's eye only or for possible publication via email: ten.epacsdem@grebdnulg
Probing the Underlying Structure of Modern Expectancy-Value Theory in Multicultural Education: A Bayesian Exploratory Factor Analysis

Expectancy-Value (EV) theory has been widely used in a plethora of domains except for multicultural education, a distinct and critical field in many countries due to increasing student diversity. In light of the domain-specific nature of the EV theory and the discrepancy between the theoretical framework and empirical models found in previous studies, the purpose of the present study was to explore the factors of the EV theory in multicultural education. Participants were 187 college students who completed the Multicultural Expectancy-Value Scale (EVS). Exploratory factor analysis (EFA) with Bayes estimation and GEOMIN rotation resulted in two factors: Value and Expectancy. The two factors had a positive significant correlation of .42, p<.001. Participants with a Master’s or Doctoral degree had significantly higher Expectancy beliefs in multicultural education than those with a Bachelor’s degree (t(47.727)=-2.90, p<.01). Although our finding was consistent with the major tenets of the theory that expectancy and value beliefs are two primary motivating factors, it did not fully support the theoretical model, indicating a more parsimonious factor structure may be more appropriate. The distinct factor model in our study suggests a need for further research in examining the structural validity of the EV theory in multicultural education
Pedagogies of Protest: African American Teachers and the History of the Civil Rights Movement, 1940–1963:

Background/ContextAlthough the dominant narrative of the civil rights movement marginalizes the role of black educators, revisionist scholars have shown that a significant number of black teachers ...
Be Prepared for the Unexpected: Importance of Careful Intraprocedural Transesophageal Echocardiography Assessment During MitraClip.

Abstract Transesophageal echocardiography plays a central role in the evaluation and guidance of mitral valve interventions. Our case highlights the importance of thorough intraprocedural valve eva...
Recent trends and associated factors of amphetamine-type stimulant overdoses in emergency departments

Abstract Background Emerging data indicate a resurgence of availability and harms of amphetamine-type stimulant (ATS) use. This study examined ATS overdose-involved emergency department (ED) visit trends and visit characteristics associated with ATS overdose. Methods Data from the Healthcare Cost and Utilization Project’s (HCUP) 2010–2017 Nationwide Emergency Department Sample identified ATS overdose-involved visits. Predicted trend lines from 2010 to 2015 were fit using weighted logistic regression forany or only ATS-involved overdose using ICD-9-CM discharge diagnosis codes; percentage change from 2016 to 2017 used ICD-10-CM. Multivariable logistic regression examined characteristics in 2017 associated with only ATS-involved overdoses compared to drug overdoses not involving ATS. Results Every year from 2010 to 2015 the odds of any ATS overdose-involved ED visits increased 11 % (odds ratio [OR]: 1.11, 95 % CI: 1.09, 1.14) and 7 % for only ATS overdose-involved visits (OR: 1.07, 95 % CI: 1.04, 1.10). From 2016 to 2017, any and only ATS overdose-involved visit rates increased 19.1 % and 20.5 %, respectively (P Conclusions Our findings, coupled with the rising availability of ATS and related harms, underscore the expansion of current substance use and overdose prevention and response efforts to address stimulant use, particularly among groups at risk. Research to identify additional individual and community-level risk factors for increasing ATS overdose is warranted.
Driving Team-Based Critical Thinking Using an ED-specific Pediatric Assessment Tool

Introduction Missing the signs of early sepsis in the pediatric ED can result in delayed diagnosis and treatment, complications, and death. We have introduced a pediatric ED assessment tool to improve the recognition of sepsis and critically-ill children, team critical thinking, time to treatment, and ultimately, patient outcomes. Local Problem Delayed recognition and poor nurse-provider communication were identified as a common challenge in the timely treatment of children at high risk with infection-related etiologies. Methods This is a single-site time series QI project at an academic free-standing children’s hospital ED with an annual census of 50,000. Development of the Children At High Risk Alert Tool …
The complete electronic structure and mechanism of the methionine synthase process as determined by the MCSCF method

Abstract The methionine synthase process is regenerating the methionine from cysteine in the S-adenosylmethionine cycle running throughout several interactions and electron transfers between methylcobalamin cofactor and substrates. The methionine synthase process in connection with the methionine synthase reductase process can run, in principle, unlimited number of turnovers without side products or effects. This raises questions about the energy barriers of the methionine synthase process reactions. The CASSCF geometry optimization with 13 electrons and 13 orbitals in the active zone of the methylco(II)balamin cofactor species was used to calculate the full mechanism of the methionine synthase process. We have shown that the anticipated reaction of the methionine synthase process is the cleavage of the Co-N (dimethylbenzimidazole) axial bond under the influence of the homocysteine ion and the histidine substrates. Our results also show that the active species in the methylation of homocysteine is a base-on methylco(II)balamin cofactor with the dimethylbenzimidazole ligand substituted by the histidine trans ligand. This methylation process takes place during the methylco(II)balamin cofactor interaction with the homocysteine negative ion, proving that this reaction is of SN2. We have shown that the triggering factor of this process is the initial electron transfer from a homocysteine negative ion to a base-on methylco(II)balamin-histidine cofactor particle. Another step of the methionine synthase process is the N-C(CH3) bond cleavage in the protonated 5-methyltetrahydrofolate systems under the influence of the negative total (and the atomic charges of the central part) of the co(I)balamin cofactor. Simultaneously, the cleaved methyl (+1) positive particle is leaving an electron back to tetrahydrofolate. The no energy barrier and the minimum energy of the in-vivo reaction products have been proved for all the methionine synthase process reactions. Finally, the full mechanism of the methionine synthase process has been drawn.
Immune and malignant cell phenotypes of ovarian cancer are determined by distinct mutational processes

ABSTRACT High-grade serous ovarian cancer (HGSOC) is an archetypal cancer of genomic instability patterned by distinct mutational processes, intratumoral heterogeneity and intraperitoneal spread. We investigated determinants of immune recognition and evasion in HGSOC to elucidate co- evolutionary processes underlying malignant progression and tumor immunity. Mutational processes and anatomic sites of tumor foci were key determinants of tumor microenvironment cellular phenotypes, inferred from whole genome sequencing, single-cell RNA sequencing, digital histopathology and multiplexed immunofluorescence of 160 tumor sites from 42 treatment-naive HGSOC patients. Homologous recombination-deficient (HRD)-Dup (BRCA1 mutant-like) and HRD- Del (BRCA2 mutant-like) tumors harbored increased neoantigen burden, inflammatory signaling and ongoing immunoediting, reflected in loss of HLA diversity and tumor infiltration with highly- differentiated dysfunctional CD8+ T cells. Foldback inversion (FBI, non-HRD) tumors exhibited elevated TGFβ signaling and immune exclusion, with predominantly naive/stem-like and memory T cells. Our findings implicate distinct immune resistance mechanisms across HGSOC subtypes which can inform future immunotherapeutic strategies. HIGHLIGHTS Multi-region, multi-modal profiling of malignant and immune cell phenotypes in ovarian cancer Anatomic site specificity is a determinant of cancer cell and intratumoral immune phenotypes Tumor mutational processes impact mechanisms of immune control and immune evasion Spatial topology of HR-deficient tumors is defined by immune interactions absent from immune inert HR-proficient subtypes