cssi/SciSciGPT-SciSciNet huggingface dataset:
Association between metformin use and progression of monoclonal gammopathy of undetermined significance to multiple myeloma in US veterans with diabetes mellitus: a population-based retrospective cohort study

Summary Background Multiple myeloma is one of the most common haematological malignancies in the USA and is consistently preceded by monoclonal gammopathy of undetermined significance (MGUS). We aimed to assess the association between metformin use and progression of MGUS to multiple myeloma. Methods We did a retrospective cohort study of patients registered in the US Veterans Health Administration database and diagnosed with MGUS between Oct 1, 1999, and Dec 31, 2009. We included patients (aged >18 years) with at least one International Classification of Diseases (9th revision) code for diabetes mellitus and one treatment for their diabetes before MGUS diagnosis. We reviewed patient-level clinical data to verify diagnoses and extract any available data for size of baseline M-protein and type of MGUS. We defined metformin users as patients with diabetes who were given metformin consistently for 4 years after their diabetes diagnosis and before multiple myeloma development, death, or censorship. Our primary outcome was time from MGUS diagnosis to multiple myeloma diagnosis. We used Kaplan-Meier curves and Cox models to analyse the association between metformin use and MGUS progression. Findings We obtained data for 3287 patients, of whom 2003 (61%) were included in the final analytical cohort. Median follow-up was 69 months (IQR 49–96). 463 (23%) participants were metformin users and 1540 (77%) participants were non-users. 13 (3%) metformin users progressed to multiple myeloma compared with 74 (5%) non-users. After adjustment, metformin use was associated with a reduced risk of progression to multiple myeloma (hazard ratio 0·47, 95% CI 0·25–0·87). Interpretation For patients with diabetes diagnosed with MGUS, metformin use for 4 years or longer was associated with a reduced risk of progression of MGUS to multiple myeloma. Prospective studies are needed to establish whether this association is causal and whether these results can be extrapolated to non-diabetic individuals. Funding Barnes-Jewish Hospital Foundation, National Institutes of Health, Agency for Healthcare Research and Quality, American Cancer Society.
Directed Assembly of Polymer Blends Using Nanopatterned Templates

The direct assembly of polymer blends on chemically functionalized surfaces is shown to produce a variety of nonuniform complex patterns. This method provides a powerful tool for easily producing nonuniform patterns in a rapid (30 s), one-step process with high specificity and selectivity for a variety of applications, such as nanolithography, polymeric optoelectronic devices, integrated circuits, and biosensors.
Natural Motion Generation for Humanoid Robots

This paper presents a method of generating natural-looking motion primitives for humanoid robots. An optimization-based approach is used to generate these primitives, but the objective function is tailored to each one and complexity is reduced by identifying relevant degrees of freedom. Several examples are shown in simulation: for an arm movement to reach an object, it is better to minimize the acceleration of key parts of the robot over its entire trajectory; for a single step on flat ground, it is better to minimize the torque and instantaneous angular momentum at every posture. The primitives are precomputed off-line, but might be used by on-line planner either to provide a fixed set of maneuvers or to bias a probabilistic, sample-based search for motions.
Formulation of the Tree Approximation Problem as a Detection Problem and Relation between the AUC and Information Theory Divergences

Abstract This paper looks at graphical models and discusses the quality of tree approximations by ex- amining information measures and formulating the problem as a detection problem. One of the widely used algorithms for tree-structured approximation and modeling is the Chow-Liu algo- rithm. While this algorithm is optimal for Gaussian distributions in the sense of the Kullback- Leibler (KL) divergence, it is not optimal when compared with other information divergences and criteria such as Area Under the detection Curve (AUC) and reverse KL divergence. In this paper, we discuss the optimality of tree approximation methods. We show that different information theory divergences and criteria such as the KL divergence, the Jeffreys divergence and the AUC are all related of the correlation approximation matrix (CAM), Δ. We also show some explicit relations between these different information divergences and criteria and investigate the relation between quality of the tree approximation by formulating a detection problem and considering the AUC and the Jefferys divergence which is a distance between two conditional means, as alternative approaches for the tree approximation. The tree structure approximation algorithms have interesting applications. In general, the tree structured enables us to do distributed algorithms such as belief propagation and also to do inference. Because of computational complexity, it is important to consider simpler graphical models such as trees when modeling systems for many applications. We previously discuss the problem of convergence of the distributed state estimation algorithm for electric distribution grids, “mi- crogrids,” with distributed renewable energy generation. The correlations between distributed renewable energy generators was approximated by a simpler tree-structured graphical model. This paper carries the research further by looking at real spatial solar irradiation data and approximating correlation matrices by a tree structured graph. We also conduct simulations on synthetic data with larger number of nodes.
Issues in interactive orthogonal graph drawing (preliminary version)

Several applications require human interaction during the design process. The user is given the ability to alter the graph as the design progresses. Interactive Graph Drawing gives the user the ability to dynamically interact with the drawing. In this paper we discuss features that are essential for an interactive drawing system. We also describe some possible interactive drawing scenaria and present results on two of them. In these results we assume that the underline drawing is always orthogonal and the maximum degree of any vertex is at most four at the end of any update operation.
Morphometric analysis of calcification and fibrous layer thickness in carotid endarterectomy tissues

BackgroundAdvanced atherosclerotic lesions are commonly characterized by the presence of calcification. Several studies indicate that extensive calcification is associated with plaque stability, yet recent studies suggest that calcification morphology and location may adversely affect the mechanical stability of atherosclerotic plaques. The underlying cause of atherosclerotic calcification and the importance of intra-plaque calcium distribution remains poorly understood. MethodThe goal of this study was the characterization of calcification morphology based on histological features in 20 human carotid endarterectomy (CEA) specimens. Representative frozen sections (10µm thick) were cut from the common, bulb, internal and external segments of CEA tissues and stained with von Kossa's reagent for calcium phosphate. The morphology of calcification (calcified patches) and fibrous layer thickness were quantified in 135 histological sections. ResultsIntra-plaque calcification was distributed heterogeneously (calcification %-area: bulb segment: 14.2?2.1%; internal segment: 12.9?2.8%; common segment: 4.6?1.1%; p=0.001). Calcified patches were found in 20 CEAs (patch size: 1.0mm2). Calcified patches were most abundant in the bulb and least in the common segment (bulb n=7.30?1.08; internal n=4.81?1.17; common n=2.56?0.56; p=0.0007). Calcified patch circularity decreased with increasing size ( 1.0mm2: 0.51?0.02; p=0.0001). A reduced fibrous layer thickness was associated with increased calcium patch size (p<0.0001). ConclusionsIn advanced carotid atherosclerosis, calcification appears to be a heterogeneous and dynamic atherosclerotic plaque component, as indicated by the simultaneous presence of few large stabilizing calcified patches and numerous small calcific patches. Future studies are needed to elucidate the associations of intra-plaque calcification size and distribution with atherothrombotic events. Calcification is abundant in carotid endarterectomy (CEA) tissues.Calcification is located predominantly in the bulb/bifurcation segments of CEAs.Histologically determined calcified patch sizes span across 4-orders of magnitude.Morphology of calcified patches changes significantly with patch size.
Defining Global Education

As the world is becoming increasingly flat, it has become important for educators to prepare students to understand global perspectives and engage with people from countries and cultures around the...
IFI16, an amplifier of DNA-damage response: Role in cellular senescence and aging-associated inflammatory diseases

DNA-damage induces a DNA-damage response (DDR) in mammalian cells. The response, depending upon the cell-type and the extent of DNA-damage, ultimately results in cell death or cellular senescence. DDR-induced signaling in cells activates the ATM-p53 and ATM-IKKα/β-interferon (IFN)-β signaling pathways, thus leading to an induction of the p53 and IFN-inducible IFI16 gene. Further, upon DNA-damage, DNA accumulates in the cytoplasm, thereby inducing the IFI16 protein and STING-dependent IFN-β production and activation of the IFI16 inflammasome, resulting in the production of proinflammatory cytokines (e.g., IL-1β and IL-18). Increased expression of IFI16 protein in a variety of cell-types promotes cellular senescence. However, reduced expression of IFI16 in cells promotes cell proliferation. Because expression of the IFI16 gene is induced by activation of DNA-damage response in cells and increased levels of IFI16 protein in cells potentiate the p53-mediated transcriptional activation of genes and p53 and pRb-mediated cell cycle arrest, we discuss how an improved understanding of the role of IFI16 protein in cellular senescence and associated inflammatory secretory phenotype is likely to identify the molecular mechanisms that contribute to the development of aging-associated human inflammatory diseases and a failure to cancer therapy.
Steroid balance and tissue cholesterol accumulation in germfree and conventional rats fed diets containing saturated and polyunsaturated fats

Steroid balance studies were conducted on 24 conventional and 12 germfree male rats, 90–120 days old, fed diets containing either 20% safflower or 20% coconut oil. Both germfree and conventional rats fed the safflower oil diets had significantly lower serum cholesterol levels and significantly higher liver cholesterol levels than did the rats fed coconut oil. No significant differences in total fecal neutral sterols, coprostanol, Δ7-cholestenol, or total fecal bile acid excretion were seen between dietary groups of rats of either status. There was no evidence of qualitative differences in fecal bile acid excretion as a function of diet. The increased liver cholesterol was in the ester form, with cholesteryl linoleate the largest single component. There was no significant difference in the cholesterol content of the skin, muscle, adipose tissue, or gastrointestinal tract. The significance of a large increase in liver cholesteryl ester, lowered serum cholesterol, and no change in steroid excretion is discussed.
Large artery remodeling after myocardial infarction.

Rats with myocardial infarction (MI) after coronary artery ligation (n = 75) and sham operated rats (n = 40) were treated with captopril (2 g/l drinking water), hydralazine (80 mg/l drinking water)...
Methyltransferases excised from trans-AT polyketide synthases operate on N-acetylcysteamine-bound substrates

Methyltransferases excised from trans -AT polyketide synthases operate on N -acetylcysteamine-bound substrates
Proximal femoral replacement for metastatic bone disease

Between 1994 and 2000, 13 patients (8 women and 5 men; 14 hips) underwent proximal femoral replacement secondary to metastatic disease. Average patient age was 62 years (range: 46-77 years). The most common diagnosis was renal cell carcinoma. Seven pathologic fractures were noted. Patients ambulated with full weight bearing postoperatively and wore an abduction brace for 3-4 months. Ten patients died of their diseases at 0.5-3.5 years post-operatively. No dislocations, infections, or reoperations occurred. Proximal femoral replacement provides excellent pain relief and good restoration of function when more simple reconstructive options are not feasible.
Time Independent Solutions to Finite and Half-Infinite Space Cables

In this chapter, the time independent solutions to the finite and half infinite space cables are discussed. The notions of the Thevenin equivalent conductance of the cables is explained.
Teachers learning how to use data: A synthesis of the issues and what is known

Abstract This article provides a synthesis of the articles found in the special issue on data use. The synthetic piece contextualizes how the articles contribute to the knowledge base of how teachers use data. It synthesizes the findings by identifying key common themes. It then describes gaps in the current knowledge base and identifies the requisite steps needed to address those gaps.
Adopting a continuous improvement model for future DSM revisions.

The approach used for making changes to both the DSM and ICD has been up to now to revise the manuals in their entirety at fixed (albeit variable) intervals. Typically, these diagnostic revision efforts have been multi‐year affairs involving the appointment of committees of experts tasked with making changes with the goal of improving the validity, reliability, and clinical utility of the diagnostic systems1, 2.
Educational and Psychosocial Support Needs in Lynch Syndrome: Implementation and Assessment of an Educational Workshop and Support Group

Few reports of educational and counseling support resources exist for Lynch syndrome (LS), a disorder requiring multi-organ cancer screening and specialized medical care throughout adult life. Here we describe the development and efficacy of two resources designed to address this need, the Memorial Sloan Kettering Cancer Center Clinical Genetics Service annual Lynch Syndrome Educational Workshop (LSEW), and a quarterly Lynch Syndrome Patient Advocacy Network (LSPAN) support group. The LSEW and LSPAN were implemented beginning in 2012. Participant survey data evaluating satisfaction, clarity, and unmet needs for each event were retrospectively analyzed and summarized using descriptive statistics. Annual LSEW attendance ranged from 53 to 75 total participants. LSEW year 1 participants indicated a need for a support group, and preferred in-person meetings at a frequency of every 3–6 months. For LSEW year 2–5 participants, >96 % reported satisfaction with the LSEW, and >82 % expressed interest in secure online support. Common themes for improvement included increased time for question and answer sessions and additional introductory genetics education. Responding LSPAN participants (n = 57 total survey responses in 11 meetings) found the meetings helpful (100 %), information clear (91 %), and presence of a genetic counselor useful (67 %). Desired discussion topics included coping with stress and anxiety, development of a support network, family communication about LS, genetic testing decisions, and bereavement. Following genetic counseling, a need exists for ongoing educational and emotional support in LS. Implementation of resources such as the LSEW and LSPAN is feasible and perceived as helpful by participants.
Randomized Clinical Trials and Observational Studies: Guidelines for Assessing Respective Strengths and Limitations

The 2 primary types of studies that are used to test new drugs or procedures or compare competing drugs or types of procedures are randomized clinical trials (RCTs) and observational studies (OS). Although it would appear that RCTs always trump OS because they eliminate selection bias, there are many possible limitations to both types of studies, and these limitations must be carefully assessed when comparing the results of RCTs and OS. This state-of-the art review describes these limitations and discusses how to assess the validity of RCTs and OS that yield different conclusions regarding the relative merit of competing treatments/interventions.
Impaired Epidermal to Dendritic T Cell Signaling Slows Wound Repair in Aged Skin

Summary Aged skin heals wounds poorly, increasing susceptibility to infections. Restoring homeostasis after wounding requires the coordinated actions of epidermal and immune cells. Here we find that both intrinsic defects and communication with immune cells are impaired in aged keratinocytes, diminishing their efficiency in restoring the skin barrier after wounding. At the wound-edge, aged keratinocytes display reduced proliferation and migration. They also exhibit a dampened ability to transcriptionally activate epithelial-immune crosstalk regulators, including a failure to properly activate/maintain dendritic epithelial T cells (DETCs), which promote re-epithelialization following injury. Probing mechanism, we find that aged keratinocytes near the wound edge don't efficiently upregulate Skints or activate STAT3. Notably, when epidermal Stat3, Skints , or DETCs are silenced in young skin, re-epithelialization following wounding is perturbed. These findings underscore epithelial-immune crosstalk perturbations in general, and Skints in particular, as critical mediators in the age-related decline in wound-repair.
Synergistic Activity of the Aurora Kinase Inhibitor MK-0457 (VX-680) with Idarubicin, Ara-C, and Inhibitors of BCR-ABL.

Abstract MK-0457 (VX-680) is a reversible small molecule kinase inhibitor that targets Aurora A, B, and C with Ki values of 0.7, 18, and 4.6 nM, respectively. MK-0457 also inhibits Flt3 (Ki = 30 nM), and both the wild type and the T315I mutant of BCR-ABL (Ki = 30 and 40 nM, respectively). Clinical trials are ongoing in patients with solid tumors and hematological malignancies. Recent data show that MK-0457 is active in patients against subtypes of AML, BCR-ABL T315I mutant CML, and Philadelphia positive (Ph+) ALL. To support multi-agent clinical trials, the activity of MK-0457 in combination with idarubicin, Ara-C, and BCR-ABL inhibitors was investigated. The viability of a panel of AML, ALL, and CML cell lines was assessed following single agent and either simultaneous or sequential combinations of agents. Combination effects were evaluated using the Bliss Independence Model. MK-0457 as a single agent markedly inhibited leukemia cell viability (at 72 hrs) with an IC50 range of 20–300 nM for MV4-11, Molt-4, Molm-13, K562, LAMA-84, MEG-01, and KU812F cells. Additionally, MK-0457 inhibited the viability of BaF3 cells transformed by wild type, T315I, or Y253F mutants of BCR-ABL with similar IC50s (approximately 300 nM). The sequential combination of MK-0457 followed by either idarubicin or Ara-C showed greater synergy than simultaneous combinations in a cell line dependent manner. MK-0457 displayed strong synergy in simultaneous combination with Gleevec (imatinib mesylate) in a panel of human CML-derived cell lines and BaF3 cells expressing wild type BCR-ABL. MK-0457 enhanced the Gleevec-mediated cell death of K562 leukemia cells as evidenced by increased caspase activity, PARP cleavage, and induction of the sub-G1 population. At concentrations where synergy was observed by cell viability analysis, the MK-0457/Gleevec combination resulted predominantly in aneuploidy and G2/M arrest, consistent with inhibition of Aurora kinases by MK-0457. These results support the clinical evaluation of MK-0457 combined with idarubicin and Ara-C in AML and with BCR-ABL inhibitors in CML and Ph+ ALL.
Efficiency and Solution Approaches to Bicriteria Nonconvex Programs

A new nonlinear scalarization specially designed for bicriteria nonconvex programming problems is presented. The scalarization is based on generalized Lagrangian duality theory and uses an augmented Lagrange function. The new concepts, q_i-approachable points and augmented duality gap, are introduced in order to determine the location of nondominated solutions with respect to a duality gap as well as the connectedness of the nondominated set.
Hypertension: From GWAS to functional genomics-based precision medicine.

Several recent studies have provided insights into the genetic regulation of blood pressure. A new study extends these findings by coupling genome-wide association study data with functional validation approaches to identify and explore loci associated with blood pressure, and by generating a genetic risk score model to predict future cardiovascular risk.
Rasch analysis of alcohol abuse and dependence diagnostic criteria in persons with spinal cord injury.

Cross-sectional. The objective of the study is to examine whether alcohol use disorders should be conceptualized categorically as abuse and dependence as in the 'Diagnostic and Statistical Manual of Mental Disorders' 4th edition or on a single continuum with mild to severe category ratings as in the 'Diagnostic and Statistical Manual of Mental Disorders' 5th edition in people with spinal cord injury (SCI). United States of America. Data from 379 individuals who sustained SCI either traumatically or non-traumatically after the age of 18 and were at least 1 year post injury. Rasch analyses used the alcohol abuse and dependence modules of the Structured Clinical Interview for DSM-IV-TR Axis I Disorders Non-patient Edition (SCID-I/NP). Fifty-seven percent (n=166) of the entire sample endorsed criteria for alcohol abuse, and 25% (n=65) endorsed criteria for alcohol dependence. Fit values were generally acceptable except for one item (for example, alcohol abuse criterion 2), suggesting that the items fit the expectation of unidimensionality. Examination of the principal components analysis did not provide support for unidimensionality. The item–person map illustrates poor targeting of items. Alcohol abuse and dependence criterion appear to reflect a unidimensional construct, a finding that supports a single latent construct or factor consistent with the DSM-5 diagnostic model.
Indexing 'Entrustment': An Analysis of the Japanese Formulaic Construction [N da yo N]

Japanese conversations are known to contain a large amount of unexpressed information. When a speaker speaks with elliptical information, he or she assumes that the addressee will understand what is not overtly expressed based on the knowledge that is supposed to be shared textually, personally or culturally. The addressee, on the other hand, must determine what is not being expressed overtly using such shared knowledge. At the heart of this kind of communication is the existence of trust assumed among the interlocutors. Using the term ‘entrustment’, we will examine how one particular Japanese formulaic construction, [Noun (da) yo Noun], ‘It’s Noun, you know, Noun’, indexes mutual trust to manage conversational interaction. We will argue that this meta-pragmatic awareness needs to be recognized beyond surface interactional patterns identified in conversation.
Exploring the Relationship Between Volume and Outcomes in Hospital Cardiovascular Care.

BACKGROUND Management theories of learning and experience curve effects state that greater levels of scale produce learnings and improved performance. In cardiovascular care, guidelines suggest that high-volume facilities produce better patient outcomes; yet, there are contradictory findings from the few studies conducted. Our goals were to assess the volume-outcome relationship for interventional cardiovascular care. METHODS We examined 9360 patients with ST-segment elevation myocardial infarction who underwent percutaneous intervention (PCI). We analyzed 6 years of data (2010-2015) using systematic extracts provided by 33 PCI-capable hospitals in the Dallas Texas region from the National Cardiovascular Data Registry. We stratified hospitals into 3 procedural volume categories (low, intermediate, and high) to identify changes in 2 key outcome metrics (ie, door-to-balloon times and mortality). Multivariate analyses and tests of differences were utilized. RESULTS Door-to-balloon performance outcome was significantly different between volume categories, with the highest-volume hospitals performing significantly better than intermediate- and low-volume hospitals (47, 60, and 75 minutes, respectively; P < .001). Mortality followed a similar pattern, with a 3.3% unadjusted absolute lower mortality rate for the high-volume hospitals. Multivariate regressions confirm that volume is statistically significant in both mortality and treatment times. CONCLUSIONS Higher-volume PCI hospitals have 37% shorter treatment times and 53% lower mortality rates than smaller facilities. This study provides evidence of a positive volume-outcome relationship in interventional cardiovascular care.
Abstract 2083: Development of novel targeted adjuvant therapy for triple negative breast cancer

There is an unmet clinical need for targeted adjuvant therapy in Triple Negative Breast Cancer (TNBC) to overcome its poor prognosis, short disease-free interval and metastatic dissemination. We previously reported that blocking interactions between the PAH2 domain of chromatin regulator Sin3 and Sin3 interaction domain (SID) containing proteins like PF1 and TGIF1 by SID decoys (peptides and small molecule, C16) decreased the cancer stem cell population, invasion, EMT, and metastases. This, programmed upregulation of retinoid signaling that sensitized TNBC cells to AM80, a novel clinically available RARα-specific agonist. Here we report preclinical investigations on effects of SID decoys and AM80 treatments on cellular heterogeneity, primary tumors, metastatic dissemination, minimum residual disease (MRD) and host microenvironment. Using CyTOF2, we made single cell measurements of markers of differentiation, proliferation and stemness in CSC-enriched 4T1 tumorspheres. Treatment with SID peptide decreased cell populations expressing nanog, sox2, vimentin and β-catenin with increase in γH2AX. Addition of AM80 in combination with C16, resulted in populations with increased expression of differentiation marker CD24 with decrease in vimentin, β-catenin and Ki-67. To interrogate the neo-adjuvant effects of C16-AM80 treatments, primary 4T1 tumors in Balb/c mice were treated with C16 and AM80 alone or in combination. Compared to DMSO, ~40 % decrease in tumor weight, 60% decrease in ALDH activity and 60% decrease in lung metastasis was seen in mice treated with C16-AM80 combination. In post-surgical adjuvant settings, in both 4T1 and MMTV-myc xenografts, we observed 100% disease-free survival and absence of macrometastasis in mice receiving minimally toxic adjuvant therapy with the C16-AM80 combination for 90 days. However, MRD was found consisting of a small number of single CK8+ cells which failed to form colonies when recovered from the bone marrow and selectively cultured in vitro. Upon stopping the treatments, 20-40% animals developed macrometastases within the first three months. To test the influence of C16-AM80 to condition the host microenvironment to prevent macrometastases mice received only pretreatment with C16 and AM80 followed by 4T1 cells injected in the tail vein. The percentage of parenchyma occupied by metastatic nodules were: DMSO = 50%; AM80 = 25%; C16 >10% and C16-AM = Citation Format: Nidhi Bansal, Eduardo Farias, Veronica Gonzalez, Garry Nolan, Samuel Waxman. Development of novel targeted adjuvant therapy for triple negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2083. doi:10.1158/1538-7445.AM2017-2083
Conflicts of Semantic Warrants in Cataloging Practices

This study presents preliminary themes surfaced from an ongoing ethnographic study. The research question is: how and where do cultures influence the cataloging practices of using U.S. standards to catalog Chinese materials? The author applies warrant as a lens for evaluating knowledge representation systems, and extends the application from examining classificatory decisions to cataloging decisions. Semantic warrant as a conceptual tool allows us to recognize and name the various rationales behind cataloging decisions, grants us explanatory power, and the language to "visualize" and reflect on the conflicting priorities in cataloging practices. Through participatory observation, the author recorded the cataloging practices of two Chinese catalogers working on the same cataloging project. One of the catalogers is U.S. trained, and another cataloger is a professor of Library and Information Science from China, who is also a subject expert and a cataloger of Chinese special collections. The study shows how the catalogers describe Chinese special collections using many U.S. cataloging and classification standards but from different approaches. The author presents particular cases derived from the fieldwork, with an emphasis on the many layers presented by cultures, principles, standards, and practices of different scope, each of which may represent conflicting warrants. From this, it is made clear that the conflicts of warrants influence cataloging practice. We may view the conflicting warrants as an interpretation of the tension between different semantic warrants and the globalization and localization of cataloging standards.
Risk Stratification in Newly Diagnosed Transplant-Eligible Multiple Myeloma

Over the past two decades, there has been a major shift in how we understand and treat multiple myeloma (MM). As a result, molecular complete response, prolonged remission duration, and extended survival have become realistic goals with a possibility of cure in a small but increasing number of patients. Triplet induction using a proteasome inhibitor and an immunomodulatory drug, followed by early high-dose melphalan-autologous stem cell transplant, remains the preferred treatment strategy for transplant-eligible patients. Interestingly, not all patients derive the same benefit with this strategy, underscoring the fact that MM is a mixed bag of molecular subtypes, each with a distinct pathogenesis and clinical course. Numerous prognostic markers have been described, some of which form the basis of existing risk prediction models. No prognostic marker has solely been found to completely explain the heterogeneity in this disease. Important prognostic markers in MM are based on staging, chromosomal abnormalities, and gene expression profile classifiers. Patients can be classified into three distinct prognosis groups: standard, intermediate, and high. Risk classification assists in patient counseling, clinical trial design and outcome reporting, and, to some extent, in therapeutic decision making. In light of recent advances, the risk classification systems as well as risk-based therapeutic strategies for transplant-eligible MM patients are reviewed here.
Targeted therapy in nonsmall cell lung cancer

Activating mutations in the epidermal growth factor receptor gene and rearrangement of the anaplastic lymphoma kinase gene exemplify the molecular characterization of nonsmall cell lung cancer (NSCLC), particularly adenocarcinoma, and its therapeutic relevance. Several genetic alterations with prognostic and predictive role, including ROS, RET, MET, KRAS, have now been identified in adenocarcinoma and some such as DDR2 and fibroblast growth factor receptor 1 in squamous cell carcinoma. This has heralded the development of agents targeted against these aberrations. Better knowledge of tumor biology and development of targeted agents has ushered an era of personalized treatment strategies in NSCLC, leading to improvements not only in tumor control and duration of life but also in quality of life.
Eric Wittkower and the foundation of Montréal's Transcultural Psychiatry Research Unit after World War II.

Eric Wittkower founded McGill University’s Transcultural Psychiatry Unit in 1955. One year later, he started the first international newsletter in this academic field: Transcultural Psychiatry. However, at the beginning of his career Wittkower gave no signs that he would be interested in social sciences and psychiatry. This paper describes the historical context of the post-war period, when Wittkower founded the research unit in Montreal. I focus on the history of scientific networks and the circulation of knowledge, and particularly on the exchanges between the French- and English-speaking academic cultures in North America and Europe. Because the history of transcultural psychiatry is a transnational history par excellence, this leads necessarily to the question of the reception of this academic field abroad.
Anterior Skull Base Reconstruction: Does Fat Preparation Matter?

Objectives This article aims (1) to determine whether there is any difference in cerebrospinal fluid (CSF) leak rate after anterior skull base autologous fat reconstruction based on how the fat is prepared, and (2) to measure impact on surgical times by reconstruction type. Design Translational animal model surgical technique 3-arm trial, comparing two different methods of autologous fat skull base reconstruction versus a nonreconstructed control group. Setting Animal study. Subjects Adult Sprague-Dawley rats. Main Outcome Measures Resolution of CSF rhinorrhea after repair of a surgically created anterior skull base defect. Results Both wet (uncompressed) and dry (compressed) fat reconstruction of an anterior skull base defect demonstrated lower CSF leak rates than nonreconstructed defects. Dry fat reconstruction achieved significance in superiority of controlling CSF leak over no reconstruction (64% success vs. 31%); while wet fat reconstruction trended toward significance (50% vs. 31%). Reconstruction procedure time was longer than nonreconstructed controls, but there was no significant difference between type of fat preparation in surgical time. Conclusions This study demonstrates that drying and compressing the fat graft improves autologous fat reconstruction success for anterior skull base defects, and does not add significantly to surgical time over nonprepared fat.
Discovery of a Diazo-Forming Enzyme in Cremeomycin Biosynthesis.

The molecular architectures and potent bioactivities of diazo-containing natural products have attracted the interest of synthetic and biological chemists. Despite this attention, the biosynthetic enzymes involved in diazo group construction have not been identified. Here, we show that the ATP-dependent enzyme CreM installs the diazo group in cremeomycin via late-stage N–N bond formation using nitrite. This finding should inspire efforts to use diazo-forming enzymes in biocatalysis and synthetic biology as well as enable genome-based discovery of new diazo-containing metabolites.
Population health challenges in primary care: What are the unfinished tasks and who should do them?

Background:There are numerous recommendations from expert sources that help guide primary care providers in cancer screening, infectious disease screening, metabolic screening, monitoring of drug l...
Deletion of Nrf2 enhances susceptibility to eosinophilic sinonasal inflammation in a murine model of rhinosinusitis

Background Oxidative stress exacerbates lower airway diseases including asthma and chronic obstructive pulmonary disease (COPD); however, its role in upper airway (sinonasal) chronic inflammatory disorders is less clear. Nuclear erythroid 2 p45-related factor (Nrf2) is an endogenous mechanism that upon activation invokes an antioxidant response pathway via nuclear translocation and upregulation of cytoprotective genes. We sought to determine whether deletion of Nrf2 enhances susceptibility to allergic sinonasal inflammation in vivo. Methods Nrf2-/- mice were subjected to the ovalbumin (Ova)-induced murine model of rhinosinusitis and indices of sinonasal inflammation and epithelial barrier dysfunction were assessed. Results We show that deletion of Nrf2 results in enhances indices of allergen-induced sinonasal inflammation including aggravated eosinophil accumulation and goblet cell hyperplasia. An exaggerated increase in epithelial derived inflammatory cytokines including interleukin 33 (IL-33) and thymic stromal lymphopoietin (TSLP) was observed in the nasal lavage fluid and sinonasal mucosal tissue of Nrf2-/- mice. Furthermore, Nrf2-/- mice showed heightened Ova-induced barrier dysfunction as measured by serum albumin accumulation in nasal lavage fluid of mice. Conclusion These data show that the endogenous Nrf2 pathway limits Ova-induced sinonasal inflammation, epithelial derived inflammatory cytokine production, and epithelial barrier dysfunction in vivo and identify a potential therapeutic target in the management of allergic sinonasal inflammatory disorders. This is the first study to our knowledge which shows that Nrf2 regulates allergic inflammation in the sinonasal cavity in vivo.
Potassium Iodide Reversal of Silver Diamine Fluoride Staining: A Case Report

This article describes the clinical protocol of using potassium iodide (KI) to reverse staining caused by silver diamine fluoride (SDF). SDF contains silver, fluoride, and ammonia. It has been used to arrest dental caries mainly in pediatric applications. The major drawback of SDF application is the dark staining of both teeth and restorative materials. Hence, its use on adult dentition is limited. Improving the esthetic outcome by stain reduction would greatly enhance the opportunity for SDF's universal use. This case demonstrates how KI can effectively reverse the staining.
Precision Grasp Control with a Pneumatic Gripper and a Novel Fingertip Force Sensor

Grippers equipped with tactile sensors are very important in high performance robotic manipulation tasks, where the robot must adapt to shape and characteristics of unknown objects. Such adaptability reduces cycle time and cost, eliminates the need for customization and tool changers, and enhances the automation process. In addition, while handling fragile objects, it may be necessary to regulate the grip force to avoid slipping, dropping, or breaking the object being manipulated. In this study, a pneumatic gripper was augmented with a novel custom-fabricated compliant skin sensor packaged in the gripper fingertip. The sensor is a strain gauge printed onto a Kapton substrate, patterned with a polymer piezo-resistive material, and encased in an elastic Silicone encapsulant. Using feedback from this sensor, a model-free explicit force control scheme was implemented and compared to the native pressure regulation scheme to control gripping force. Experiments were performed to investigate the performance of this gripper compared against similar data obtained from a commercial load cell. Results indicate that the augmented gripper can maintain a more precise control of the force applied and can better accommodate grasp transitions.
Congregations and Communities

Week after week, in cities, suburbs, small towns, and countryside byways, more Americans gather in religious congregations than in any other voluntary association or local organization. In mosques, synagogues, ashrams, temples, and sanctuaries, in small house meetings and in large arena-style auditoriums, about 60 percent of American adults attend a service within a religious congregation in a given year. About 25 percent of adults attend a service in any given week (Chaves, 2004). Fully half of Americans hold memberships in a local religious congregation (Finke & Stark, 1992).
Wolbachia Acquisition by Drosophila yakuba -Clade Hosts and Transfer of Incompatibility Loci Between Distantly Related Wolbachia .

Maternally transmitted Wolbachia infect about half of insect species, yet the predominant mode(s) of Wolbachia acquisition remains uncertain. Species-specific associations could be old, with Wolbachia and hosts codiversifying (i.e., cladogenic acquisition), or relatively young and acquired by horizontal transfer or introgression. The three Drosophila yakuba-clade hosts [(D. santomea, D. yakuba) D. teissieri] diverged ∼3 MYA and currently hybridize on the West African islands Bioko and Sao Tome. Each species is polymorphic for nearly identical Wolbachia that cause weak cytoplasmic incompatibility (CI)-reduced egg hatch when uninfected females mate with infected males. D. yakuba-clade Wolbachia are closely related to wMel, globally polymorphic in D. melanogaster We use draft Wolbachia and mitochondrial genomes to demonstrate that D. yakuba-clade phylogenies for Wolbachia and mitochondria tend to follow host nuclear phylogenies. However, roughly half of D. santomea individuals, sampled both inside and outside of the Sao Tome hybrid zone, have introgressed D. yakuba mitochondria. Both mitochondria and Wolbachia possess far more recent common ancestors than the bulk of the host nuclear genomes, precluding cladogenic Wolbachia acquisition. General concordance of Wolbachia and mitochondrial phylogenies suggests that horizontal transmission is rare, but varying relative rates of molecular divergence complicate chronogram-based statistical tests. Loci that cause CI in wMel are disrupted in D. yakuba-clade Wolbachia; but a second set of loci predicted to cause CI are located in the same WO prophage region. These alternative CI loci seem to have been acquired horizontally from distantly related Wolbachia, with transfer mediated by flanking Wolbachia-specific ISWpi1 transposons.
Extended meshfree method for elastic and inelastic media

In this paper, an extended meshfree method [9] for solving elastic boundary value problems is summarized, and its extension to the elasto-plasticity problem is presented. In extended meshfree method, the solution is decomposed into particular solution and homogeneous solution. The particular solution without satisfying boundary conditions is obtained analytically, while a homogeneous problem with auxiliary boundary conditions is then solved under a Galerkin framework with moving least-squares reproducing kernel approximation. The proposed method for linear differential operator in Poisson, elasticity, and Mindlin-Reissner problems is first summarized. The extension to differential equations with nonlinear self-adjoint differential operator is then introduced, and the application to elasto-plasticity problem is presented. Numerical results of an elasto-plasticity problem demonstrate a significant accuracy gain in the solution of extended meshfree method compared to that of the conventional Galerkin meshfree approach.
It Takes a Village to Break Up a Match: A Systemic Analysis of Formal Youth Mentoring Relationship Endings

Although early closure of formal youth mentoring relationships has recently begun to receive some attention, more information about factors that contribute to premature endings, and how those factors interact, is needed so that empirically-based program practices can be developed and disseminated to prevent such endings and to ensure that youth reap the benefits mentoring can provide. This qualitative interview study applies a systemic model of youth mentoring relationships (Keller in J Prim Prev 26:169–188, 2005a) to the study of mentoring relationship endings in community-based mentoring matches to understand why these matches ended. Mentors, parents/guardians and program staff associated with 36 mentoring matches that had ended were interviewed about their experiences of these relationships and their understanding of why they had ended. Thematic analysis of the interview transcripts and mentoring program case notes for each match followed by systemic modeling of the relationships yielded three major findings. A strong mentor–youth relationship is necessary but not sufficient for match longevity. The mentor–youth relationship, even when relatively strong, is unlikely to withstand disruptions in other relationships in the system. Agency contextual factors, such as program practices and policies and staffing patterns, have a critical role to play in sustaining mentoring matches, as they directly influence all of the relationships in the mentoring system. These findings highlight the importance of considering not just the mentoring dyad but also the parent/guardian and program context when trying to prevent match closures. They also point to several program practices that may support longer mentoring relationships.
Field trials to detect drainage pipe networks using thermal and RGB data from unmanned aircraft

Abstract The use of drainage pipe is documented as far back as 200 B. C. and continues to be used in poorly drained agricultural regions throughout the world. While good for crop production, the eco-hydrologic impacts of this modification have been shown to adversely affect natural drainage networks. Identifying the exact location of drainage pipe networks is essential to developing groundwater and surface water models. The geometry of drainage pipe networks installed decades ago has often been lost with time or was never well documented in the first place. Previous work has recognized that drainage pipes can be observed for certain soil types in visible spectrum (RGB) remote sensing data due to changes in soil albedo. In this work, small Unmanned Aerial Systems (sUAS) were used to collect high resolution RGB and thermal data to map subsurface drainage pipe. Within less than 96 h of a small (
Downregulation of Estrogen Receptor Beta1 Expression in Sessile Serrated Adenomas.

OBJECTIVE CpG island methylator phenotype (CIMP)-positive colorectal cancers (CRC) and CRC with microsatellite instability (MSI) were reported to have a decreased expression of estrogen receptor, beta1 (ER-β1), and methylation accompanied by decreased expression for the caudal-related homeobox, transcription factor 2 (CDX2). While precursor lesions of these cancers, known as sessile serrated adenomas (SSA), were found to have decreased CDX2 expression, the status of ER-β1 expression in SSA is unknown. The aim of this study is to determine ER-β1 expression in SSA and its relation to CDX2 expression. METHODS Sections of formalin fixed and paraffin embedded tissue from 62 consecutive cases of SSA were stained by immunohistochemistry for ER-β1 and CDX2. SSA with ER-β1 or CDX2 expression similar to that of a normal colon were scored as 0, while those with a loss of expression in 75% of the SSA crypts scored as 5. RESULTS There is a significant correlation between a loss of CDX2 and the loss of ER-β1 scores in SSA (p<0.001). The downregulation of CDX2 was greater in SSA arising from the right colon compared to the left colon and rectum (p=0.012). Similarly, downregulation of ER-β1 was greater in SSA arising in the right colon compared to the left colon and rectum (p=0.014). CONCLUSIONS Our findings show significant downregulation of both ER-β1 and CDX2 expression in SSA, especially in the right colon. These findings suggest that ER-β1 downregulation plays a significant role in the malignant progression of SSA.
RadGrad: Removing the "Extra" from Extracurricular to Improve Student Engagement, Diversity, and Retention

RadGrad is a curriculum initiative implemented via a web-based application that combines features of social networks, degree planners, and serious games. RadGrad redefines the traditional meaning of "progress" and "success" in the undergraduate computer science degree program, with the ultimate goal of improving student engagement, diversity, and retention. In this paper, we relate RadGrad to other curriculum initiatives, overview its key functionality, present results from an evaluation conducted during its first year of deployment, and discuss our lessons learned and future directions.