cssi/SciSciGPT-SciSciNet huggingface dataset:
Diabetic nephropathy in a nonobese mouse model of Type 2 diabetes mellitus

A large body of research has contributed to our understanding of the pathophysiology of diabetic nephropathy. Yet, many questions remain regarding the progression of a disease that accounts for nearly half the patients entering dialysis yearly. Several murine models of diabetic nephropathy secondary to Type 2 diabetes mellitus (T2DM) do exist, and some are more representative than others, but all have limitations. In this study, we aimed to identify a new mouse model of diabetic nephropathy secondary to T2DM in a previously described T2DM model, the MKR (MCK-KR-hIGF-IR) mouse. In this mouse model, T2DM develops as a result of functional inactivation of insulin-like growth factor-1 receptor (IGF-1R) in the skeletal muscle. These mice are lean, with marked insulin resistance, hyperinsulinemia, hyperglycemia, and dyslipidemia and thus are representative of nonobese human T2DM. We show that the MKR mice, when under stress (high-fat diet or unilateral nephrectomy), develop progressive diabetic nephropathy with marked albuminuria and meet the histopathological criteria as defined by the Animal Models of Diabetic Complications Consortium. Finally, these MKR mice are fertile and are on a common background strain, making it a novel model to study the progression of diabetic nephropathy.
α-Adrenergic responses in asthma

Using the Baumgartner apparatus, perfusion studies have been carried out with blood from patients with hypercholesterolemia type IIa (n = 5) and IIb (n = 9) and with reconstituted blood containing platelets in which the cholesterol/phospholipid ratio had been modified by incubation with liposomes. With cholesterol-enriched platelets (C/PL 0.869), both platelet adherence and thrombus size were doubled with respect to cholesterol-normal platelets (C/PL 0.587), which in turn had values approximately twice that in cholesterol-depleted platelets (C/PL 0.494), differences statistically significant at p less than 0.02. With blood from patients with hypercholesterolemia, statistically significant values (p less than 0.03) were seen only for increase in adherence of platelets from type IIb patients as compared with controls. These results demonstrate that changes in platelet membrane cholesterol levels can affect interaction with subendothelium in cholesterol-modified platelets but suggest that more restricted differences may occur with platelets from patients with hypercholesterolemia.
Enhanced neointimal fibroblast, myofibroblast content and altered extracellular matrix composition: Implications in the progression of human peripheral artery restenosis.

Abstract Background and aims Neointimal cellular proliferation of fibroblasts and myofibroblasts is documented in coronary artery restenosis, however, their role in peripheral arterial disease (PAD) restenosis remains unclear. Our aim was to investigate the role of fibroblasts, myofibroblasts, and collagens in restenotic PAD. Methods Nineteen PAD restenotic plaques were compared with 13 de novo plaques. Stellate cells (HE p = 0.04) and apoptosis (14.6% ± 1.3 vs. 11.2% ± 0.6; p = 0.03) were increased in restenotic plaques. Finally, SMMHC (2.6 ± 0.12 vs. 1.4 ± 0.15; p = 0.0001), type III collagen density (0.33 ± 0.06 vs. 0.17 ± 0.07; p = 0.0001), IL-6 (2.08 ± 1.7 vs. 1.03 ± 2.0; p = 0.01), and TGF-β (1.80 ± 0.27 vs. 1.11 ± 0.18; p = 0.05) were increased in restenotic plaques. Conclusions Our study suggests proliferation and apoptosis of fibroblast and myofibroblast with associated increase in type III collagen may play a role in restenotic plaque progression. Understanding pathways involved in proliferation and apoptosis in neointimal cells, may contribute to future therapeutic interventions for the prevention of restenosis in PAD.
Molecular Insights into Development in Humans: Studies in Normal Development and Birth Defects.

Molecular Insights into Development in Humans: Studies in Normal Development and Birth Defects
Anti-protozoal efficacy of 3-deoxyanthocyanidins-rich fractionated extracts from Sorghum bicolor

W investigated dried red leaf extracts of S. bicolor for activity against Toxoplasma gondii tachyzoites. S. bicolor red leaf extracts were obtained by bioassay-guided fractionation using ethanol and ethyl acetate as solvents.Analysis of the crude and fractionated extracts using Electrospray Ionization Mass Spectrometry (ESI-MS) showed that they contained significant amounts of apigeninidin, luteolinidin, 7-methoxyapigeninidin, 5-methoxyapigeninidin, 5-methoxyluteolinidin, 5-7-dimethoxyapigeninidin or 5-7-dimethoxyluteolinidin, based on mass per charge (m/z).When tested in vitro, the IC50 values of the inhibitory activity of the ethanol and ethyl acetate extracts against T. gondii’s growth were 2.3and 4-fold, respectively, lower than their cytotoxic IC50 values in mammalian cells. Ethyl acetate extracts fractionated in chloroform-methanol and chloroform had IC50 values against T. gondii that were 56.1and 3-fold lower than their respective cytotoxic IC50 values in mammalian cells. These antiparasitic activities were found to be consistent with those of the respective pure 3-deoxyanthocyanidin compounds identified to be contained in the fractions in significant amounts. Further, we observed that, the position and number of methoxy groups possessed by the 3-deoyanthocyanidins influenced their antiparasitic activity. Together, our findings indicate that S. bicolor red-leaf 3-deoxyanthocyanidins-rich extracts have potent in vitro inhibitory activity against the proliferative stage of T. gondii parasites.
Selective quantification of DOSS in marine sediment and sediment-trap solids by LC-QTOF-MS.

At the onset of the 2010 Gulf oil spill, analytical methods for the quantification of the surfactants in Corexit did not exist in the peer-reviewed literature. To date, only a single study reports the presence of bis-(2-ethylhexyl) sodium sulfosuccinate (DOSS) in deep-sea Gulf sediment collected in 2010 from a single location. There are no data on the occurrence of DOSS in association with settling solids (i.e., sediment-trap solids). To address this data gap, DOSS was initially quantified by liquid chromatography tandem quadrupole mass spectrometry (LC-MS/MS) in sediment and sediment-trap solids collected from multiple sites in the Gulf between 2010 and 2013. However, interferences confounded analyses using only a quadrupole (MS/MS) system; therefore, a LC-high mass accuracy quadruple time of flight mass spectrometry (LC-QTOF-MS) method was developed. The LC-QTOF method was validated and applied to eight representative samples of sediment and of sediment-trap solids. The presented method quantifies DOSS in solids of marine origin at concentrations above the limit of quantification of 0.23 μg kg−1 with recoveries of 97 ± 20 % (mean ± 95 CI). Gulf sediment and sediment-trap solids gave DOSS concentrations of <LOQ–25 and 1.5–6.3 μg kg−1, respectively.
CHAPTER 211 – Cyclic Nucleotide Specificity and Cross-Activation of Cyclic Nucleotide Receptors

The homologous cAMP- and cGMP-dependent protein kinases (PKA and PKG) are generally believed to be activated relatively specifically by cAMP and cGMP Certain physiological and pathophysiological conditions may exist in which elevation of one cyclic nucleotide may lead to cross-activation of the opposing kinase. This chapter summarizes the current evidence supporting cAMP and cGMP cross-activation and the structural basis for cyclic nucleotide specificity of the cyclic nucleotide dependent protein kinases. The interaction of cyclic nucleotides with other eukaryotic cyclic nucleotide receptors is also discussed. Further studies of cyclic nucleotide receptors should continue to shed light on the complex interrelationships of intracellular cyclic nucleotide signaling pathways.
Mediators of Weight Loss Maintenance in the Keep It Off Trial

Background An important step toward enhancing the efficacy of weight loss maintenance interventions is identifying the pathways through which successful interventions such as the Keep It Off trial have worked.
Gender difference of ankle stability in the sagittal and frontal planes

This paper offers quantification of ankle stability in relation to simulated haptic environments of varying stiffness. This study analyzes the stability trends of male and female subjects independently over a wide range of simulated environments after subjects were exposed to vigorous position perturbation. Ankle stability was quantified for both degrees-of-freedom of the ankle in the sagittal and frontal planes. Subjects' stability consistently decreased when exposed to environments of negative simulated stiffness. In the frontal plane, male and female subjects exhibited nearly identical stability levels. In the sagittal plane, however, male subjects demonstrated marginally more stability than female subjects in environments with negative stiffness. Results of this study are beneficial to understanding situations in which the ankle is likely to lose stability, potentially resulting in injury.
Evaluation of the Second-Trimester Products of Conception

Second-trimester products of conception with no history of fetal demise, anomalies, or other problems can be handled in much the same way as first trimester specimens, with documentation of intrauterine pregnancy and identification of any unexpected abnormalities. When there are fetal anomalies, additional attention is required to document the specific anomalies present and in some cases, to submit tissue for special testing. Like first trimester specimens, there is marked variability in the type of tissue received and the extent of disruption. If the specimen is delivered spontaneously or after induction of labor, the fetus may be relatively intact, although the placenta often does not survive undamaged. When surgical procedures are performed to terminate the pregnancy or remove uterine contents, both the placenta and fetus can be quite disrupted, making examination problematic. In addition, in cases of fetal demise, autolysis may further hamper evaluation. For these reasons, examination of these specimens creates unique challenges to the pathologist. Although detailed examination for fetal anomalies is beyond the scope of this text, it is the author’s hope that this chapter, covering the general approach and overview to the handling these types of specimens, will assist in initial evaluation of these specimens. The reader is referred to the Selected References at the end of the chapter for several excellent texts detailing fetal examination in the setting of congenital anomalies.
Pharmacy access to Ulipristal acetate in major cities throughout the United States.

Abstract Objective Ulipristal acetate (UPA) is a prescription emergency contraceptive pill (ECP). Despite the potential for UPA to reduce the risk of unintended pregnancies, a recent study in Hawaii demonstrated less than 3% of pharmacies stocked UPA and less than 23% reported the ability to order it. The primary outcome of our study was to assess the availability of UPA in a sample of large cities nationwide. Study design We conducted a telephone-based secret shopper study of 533 retail pharmacies sampled proportionally from 10 large cities in five geographic regions across the US. Callers represented themselves as uninsured 18-year-old women attempting to fill prescriptions for UPA between February and May 2016. Using a semi-structured questionnaire, callers inquired regarding availability and use of UPA. Results Less than 10% (33/344; 95% CI: 6.5–12.7%) of pharmacies indicated the ability to immediately fill a UPA prescription, while 72% (224/311; 95% CI: 65.0–77.0%) of pharmacies without immediate availability reported the ability to order UPA, with the median predicted wait time of 24 h (IQR: 21.5 to 26.0 h). Conclusion Despite evidence for increased efficacy of UPA over levonorgestrel (LNG) ECPs, the availability of UPA in a sample of US major cities is extremely limited. Given that ECPs should be taken as soon as possible after unprotected sex, the long wait times when ordering UPA present an access barrier. Efforts to improve the availability of UPA are important to optimize the potential of ECPs to decrease unintended pregnancy following unprotected sex. Implications Interventions are needed to address barriers to obtaining UPA from retail pharmacies nationwide.
Rejuvenating the Face: An Analysis of 100 Absorbable Suture Suspension Patients.

Background Absorbable suture suspension (Silhouette InstaLift, Sinclair Pharma, Irvine, CA) is a novel, minimally invasive system that utilizes a specially manufactured synthetic suture to help address the issues of facial aging, while minimizing the risks associated with historic thread lifting modalities. Objectives The purpose of the study was to assess the safety, efficacy, and patient satisfaction of the absorbable suture suspension system in regards to facial rejuvenation and midface volume enhancement. Methods The first 100 treated patients who underwent absorbable suture suspension, by the senior author, were critically evaluated. Subjects completed anonymous surveys evaluating their experience with the new modality. Results Survey results indicate that absorbable suture suspension is a tolerable (96%) and manageable (89%) treatment that improves age related changes (83%), which was found to be in concordance with our critical review. Conclusions Absorbable suture suspension generates high patient satisfaction by nonsurgically lifting mid and lower face and neck skin and has the potential to influence numerous facets of aesthetic medicine. The study provides a greater understanding concerning patient selection, suture trajectory, and possible adjuvant therapies. Level of Evidence 4
Stem growth during seed production in soybean: Implications for pod yield

In soybean (Glycine max (L.) Merr.), stems remain a competitive carbon resource sink during reproduction. Radial stem expansion after termination of axial stem growth requires resources to produce ...
Pathological Gamblers in the Workplace: A Primer for Employers

Abstract Commercial gaming is a thriving and popular industry. Increasingly, emerging technologies like the Internet provide unlimited access to gambling at work. This article provides an overview of pathological gambling and its associated adverse financial, legal, and psychosocial consequences with implications for the workplace. It also offers recommendations for safeguarding company resources, limiting liability and preventing potential abuses, identifying potential pathological gamblers, and devising effective intervention strategies and referral networks to assist employees with gambling problems.
Direct oral anticoagulant and antiplatelet combination therapy: Hemorrhagic events in coronary artery stent recipients

Direct oral anticoagulant (DOAC) use is growing as monotherapy and combined with platelet inhibitors. The safety of such combination therapy, especially in comparison to regimens including warfarin, in real world populations remains uncertain. We investigated hemorrhage associated with DOAC and antiplatelet combination therapy in a cohort of elderly coronary artery stent recipients. We employed Medicare data 2010-2013 for a 40% random sample of beneficiaries enrolled in inpatient, outpatient and prescription benefits. We used Cox proportional hazards models to examine the association of the combination anticoagulant (DOAC or warfarin) plus antiplatelets with major hemorrhage events (upper gastrointestinal or intracranial) in the 12 months following stent placement. We identified 70,900 stent recipients. 14.4% had atrial fibrillation (AF) diagnosis preoperatively. Among the 24.5 million observation days, exposure distribution was: 73.8% antiplatelets only, 4.7% antiplatelets plus warfarin, 0.6% antiplatelets plus DOAC, 2.2% warfarin only, 0.3% DOAC only and 18.4% no observed antiplatelets or anticoagulant. Overall, 8,029 patients (11.3%) experienced major hemorrhage. Among AF patients, compared to antiplatelets only, DOAC plus antiplatelets was associated with increased hemorrhage risk (HR, 1.94; 95%CI, 1.48-2.54); warfarin plus antiplatelets conferred comparable bleed risk (HR, 1.69; 95%CI, 1.47-1.94). In the non-AF group, compared to antiplatelets alone, combination DOAC plus antiplatelets (HR, 3.09; 95%CI, 2.15-4.46), and warfarin plus antiplatelets (HR, 2.21; 95%CI, 1.97-2.48) conferred greater bleed risk. Among elderly coronary artery stent recipients with AF, the two drug combinations, DOAC plus antiplatelets and warfarin plus antiplatelets, were associated with similarly increased risk of major hemorrhage compared to antiplatelets alone.
Clinical Implementation and Validation of Automated Human Genome Variation Society (HGVS) Nomenclature System for Next-Generation Sequencing–Based Assays for Cancer

Human Genome Variation Society (HGVS) nomenclature is a de facto clinical standard for reporting DNA sequence variants. With increasing use of high-throughput sequencing, manual generation of HGVS nomenclatures for all variants is impractical and error-prone. It is therefore beneficial to include one or more HGVS generator tools in next-generation sequencing (NGS) bioinformatics pipelines to enable automated, consistent, and accurate generation of HGVS nomenclature after appropriate validation. The authors implemented an HGVS nomenclature tool, the hgvs package, by integrating it into their custom-developed NGS variant management and reporting software. Use of Docker containers provided a strategic advantage to the integration process. Clinical implementation of the hgvs package was validated using a cohort of 330 variants that appropriately represented cancer-related genes and clinically important variant types. The hgvs package was able to generate HGVS-compliant variant nomenclature (both c. and p.) for 308 of the 330 (93.3%) variants, including all those in the coding and untranslated regions, and 32 of 35 (91.4%) in the consensus splice site region. Discrepant HGVS nomenclature involved variants in the intronic (16 of 40) and consensus splice site (3 of 35) regions with repeat sequences. Overall, implementation of the hgvs package in the clinical NGS workflow improved consistency and accuracy of reporting HGVS nomenclature.
Psychological Factors Affecting Physical Conditions, Somatoform Disorders, Conversion, Dissociation, and Factitious Syndromes

An 11-year-old girl was admitted to the pediatrics service for inability to walk due to paralysis of her left lower extremity. One morning, upon awakening, she found that she was unable to move her left thigh and leg and had to stay in bed. On admission, she had flaccid paralysis of her thigh and legs as well as stocking-like hypoesthesia. All labs and imaging studies were within normal limits except for slight anemia. The Hoover sign (see Chapter 29) was positive. The patient told the psychiatric consultant that she and her family had recently moved from another city, and she had enrolled in a new school where she had no friends. She missed her old friends, particularly a boy with whom she was close, which she kept a secret from her parents. As she talked about how much she missed her old school, 13
Effect of processing on fumonisin content of corn.

Fumonisins (FBs) are a family of mycotoxins produced by Fusarium moniliforme and F. proliferatum, predominant corn pathogens, and are found in most corn-containing foods. The FBs are heat stable, resistant to ammoniation, and unlike most mycotoxins, are water-soluble. The levels in corn and corn-containing foods will be presented ranging from 2 ppm. Washing of contaminated FB-corn with water did not reduce the measured FB levels of significantly. The traditional processing step to make tortilla flour, nixtamalization [Ca(OH)2 cooking] to produce masa, reduced FB levels but produced hydrolyzed FB which was almost as toxic as FB. Retorting sweet corn in brine apparently produced hydrolyzed FB. Fermentation of corn to ethanol did not alter FB levels but distillation yielded FB-free ethanol. Attempts to enzymatically modify FB with several enzymes were unsuccessful. Reactions between FB and reducing sugars (glucose or fructose) to produce Schiff’s bases yielded products that were not toxic. The effects of these processing treatments must be evaluated both chemically and biologically.
Nosocomial Infections in the Intensive Care Unit

Catheter-associated sepsis is defined as bloodstream infection due to an organism that has colonized a vascular catheter. Approximately 5% of patients with indwelling vascular catheters (uncoated) will develop bloodstream infection (≈10 infections per 1000 catheter days). The incidence of catheter-associated sepsis increases with the length of time the catheter is in situ, the number of ports, and the number of manipulations. Approximately 25% of catheters become colonized (>15 colony-forming units, CFU) and approximately 20% to 30% of colonized catheters will result in catheter sepsis. Staphylococcus aureus and coagulase-negative staphylococci are the most common infecting (and colonizing) organisms, followed by enterococci, gram-negative bacteria, and Candida species. Antibiotic-coated catheters significantly reduce catheter colonization and catheterassociated bloodstream infection. Femoral catheters are not associated with a higher infection rate. Similarly, neither the type of occlusive dressing nor the frequency of dressing change affects the incidence of catheter-associated sepsis.
Metabolic underpinnings of leukemia pathology and treatment.

Background Carcinogenic transformation of white blood cells during hematopoiesis leads to the development of leukemia, a cancer characterized by incompetent immune cells and a disruption of normal bone marrow function. Leukemias are diverse in type, affected population, prognosis, and treatment regimen, yet a common theme in leukemia is the dysregulated metabolism of leukemic cells and leukemic stem cells with respect to their noncancerous counterparts. Recent findings In this review, we highlight current findings that elucidate metabolic traits unique to the four major types of leukemia, which confer carcinogenic survival but can be potentially exploited for therapeutic intervention. These metabolic features can work in conjunction with or be independent of unique aspects of the bone marrow microenvironment that can also influence cell survival and proliferation, thus sustaining carcinogenesis. Conclusion Deepening our understanding of the interactions of leukemias with their niche environments in vivo will inform future treatments for leukemia, particularly for those that are refractive to tyrosine kinase inhibitors and other therapeutic mainstays.
A Controlled Study of Group-Based Exposure Therapy with Vietnam-Era Veterans

AbstractEighty-one Vietnam-era Veterans with PTSD were randomly assigned to either Group-Based Exposure Therapy (GBET) or Present-Centered Group Therapy (PCGT) and assessed blind to treatment condi...
A Duration-based Solution to the Problem of Stress Realization in Turkish

A duration-based solution to the problem of stress realization in Turkish Anne Pycha University of California, Berkeley Department of Linguistics pycha@berkeley.edu I. Introduction In this paper, I argue that the realization of Turkish stress makes crucial reference not to syllable types (such as heavy versus light), but to syllable durations. In agreement with previous work, I show that fundamental frequency (F0) acts as a primary acoustic correlate of stress in the language. Contrary to what we might expect, however, F0 contours realize themselves fully on syllables closed by a sonorant consonant (abbreviated here as CVR), but are “clipped” on syllables with long vowel nuclei (CVV). This presents a puzzle for any theory of phonological weight, whereby CVV syllables should certainly be heavier, and therefore more capable of hosting prosodic information, than CVR syllables. The puzzle resolves itself when we examine phonetic duration: the F0-carrying portion of CVV syllables is in fact consistently shorter than that of CVR syllables. Following Gordon (1999), these findings suggest that exceptions to typological tendencies in syllable weight can find a principled explanation within phonetic implementation. 2. Background Turkish has at least three ways of assigning stress (Sezer 1981, Inkelas & Orgun 1998, Inkelas 1999, Kabak & Vogel 2001, Inkelas & Orgun 2003, and references cited therein). Final stress is the default. Certain morphemes, however, condition the presence of non-final stress; an example is the negative morpheme -mA, which conditions stress on the syllable preceding itself. Place names undergo a totally different stress placement algorithm, dubbed “Sezer stress” after Sezer (1981): here, stress falls on the antepenultimate syllable if it is heavy and the penultimate syllable is light, otherwise it falls on the penultimate syllable. (1a) git-'ti-m go-P AST -1 SG ‘I went’ (1b) 'git-me-di-m go-N EG -P AST -1 SG ‘I didn’t go’ (1c) 'ankara, is'tanbul ‘Ankara’, ‘Istanbul’ In this paper, I will not consider Sezer stress, but will be concerned only with final and non-final stress. Previous researchers who have investigated the acoustic correlates of Turkish stress have concurred that F0 acts as a primary correlate (Konrot 1981, Konrot 1987, Levi 2005), but have also noted that final and non-final stress seem to get realized very differently. Konrot (1981) identified both F0 and intensity as correlates, but only in words with non-final stress. In words with final stress, he found no robust correlates at all. Levi (2005) identified F0, intensity, and duration as correlates, when averaging over words with final and non-final stress. But she too encountered the non-robustness of correlates for final stress, as revealed by her algorithm for
An Integrated Working Memory Model for Time‐Based Resource‐Sharing

The time-based resource-sharing (TBRS) model envisions working memory as a rapidly switching, serial, attentional refreshing mechanism. Executive attention trades its time between rebuilding decaying memory traces and processing extraneous activity. To thoroughly investigate the implications of the TBRS theory, we integrated TBRS within the ACT-R cognitive architecture, which allowed us to test the TBRS model against both participant accuracy and response time data in a dual task environment. In the current work, we extend the model to include articulatory rehearsal, which has been argued in the literature to be a separate mechanism from attentional refreshing. Additionally, we use the model to predict performance under a larger range of cognitive load (CL) than typically administered to human subjects. Our simulations support the hypothesis that working memory capacity is a linear function of CL and suggest that this effect is less pronounced when articulatory rehearsal is available.
Comparability of biological aging measures in the National Health and Nutrition Examination Study, 1999-2002.

Abstract Background Biological processes of aging are thought to be modifiable causes of many different chronic diseases. Measures of biological aging could provide sensitive endpoints for studies of risk factors hypothesized to shorten healthy lifespan and/or interventions that extend it. But uncertainty remains about how to measure biological aging and if proposed measures assess the same thing. Method We tested four proposed measures of biological aging that could be quantified with available data from the National Health and Nutrition Examination Survey (NHANES), Klemera-Doubal method (KDM) Biological Age, homeostatic dysregulation, Levine Method (LM) Biological Age, and leukocyte telomere length. Results We analyzed data collected during 1999–2002, when all four biological aging meausres could be taken. Participants’ KDM biological ages, homeostatic dysregulation levels, LM biological ages, and telomere length were all correlated with their chronological ages. KDM Biological Age, homeostatic dysregulation, and LM Biological Age were all correlated with one another, but these measures were uncorrelated with telomere length. Participants’ with more advanced biological aging performed worse on tests of physical, cognitive, and perceptual functioning and reported more limitations to their daily activities and more pain, and rated themselves as being in worse health. In parallel, participants with risk factors for shorter healthy lifespan exhibited more advanced biological aging. In both sets of analyses, effect-sizes tended to be larger for KDM Biological Age, homeostatic dysregulation, and LM Biological Age as compared to telomere length. Discussion The cellular-level aging biomarker telomere length may measure different aspects of the aging process as compared to the patient-level physiological composite measures KDM Biological Age, homeostatic dysregulation, and LM Biological Age. Studies aiming to test if risk factors accelerate aging or if interventions may slow aging should not treat proposed measures of aging as interchangeable.
203 A mismatch repair genetic variant is linked to the development of lupus

Background Recent analysis of exome chip data indicates that genetic variants (GVs) in DNA repair genes are enriched in individuals diagnosed with systemic lupus erythematosus (SLE). Methods Specifically, we analyzed 1364 single nucleotide polymorphisms (SNPs) within 41 genes that function in DNA repair. In a comparison of 1,201 SLE cases to 597 controls, corrected for ancestry, we identified 9 GVs with odds ratios (ORs) ranging from 1.1–4.6 in genes that function in mismatch repair as being significantly enriched in SLE cases versus controls. We followed up this analysis with replication studies, by analyzing a second cohort of individuals with 1298 SLE cases and 633 controls, and we were able to replicate our initial findings with full ORs ranging from 2 to 8.393. Results One of the variants that emerged from our exome chip (eChip) studies is the MSH6 GV. This variant is a single amino acid change in the DNA binding domain of the MSH6 protein that is predicted to be damaging using the POLYPHEN algorithm. The MSH6 GV is eight times more prevalent in human SLE versus control cases after correcting for ancestry (odds ratio [OR]=8.393; p=0.0398). Remarkably, among the 2499 cases in the combined cohort, patients harboring the MSH6 GV are diagnosed with lupus 11.2 years earlier than SLE patients not harboring this allele (p=0.004). To determine if the MSH6 GV is linked to the development of lupus, we employed CRISPr/cas9 gene-editing technology to construct a mouse harboring this variant. Initial characterization of the mice shows that they develop significantly increased levels of antinuclear antibodies versus wild-type controls. Our data also suggest that the MSH6 GV identified in lupus-prone individuals results in the accumulation of mutations at A in the WA hotspot (W is A or T; adenine or thymine, respectively; A is adenine) motif. Therefore, these mutations are likely to be the result of processing of the activation induced cytidine deaminase (AID)-generated U:G mispair by the MSH2/6 complex followed by error-prone DNA synthesis by DNA polymerase eta. Conclusions Importantly, these types of mutations likely result in an overall increase in positively charged amino acids in the autoantibodies that are produced, a trait that is commonly found in anti-DNA antibodies. In summary, our results suggest that the MSH6 GV has strong potential to be associated with the development of lupus. Funding Source(s): 5 R01 ES019179-08 ; R21 AI124055-01 The MSH6GV mice develop antinuclear antibodies at 6 months of age. +/+are WT; Mut/+are heterozygotes and Mut/Mut are homozygotes.
Public Preferences for New Information on Opioids

CONTEXT Educating the public through information campaigns is a commonly used policy approach to public health problems. Yet, experimental methods that assess the impact of information campaigns may misestimate their effects by failing to account for respondents' willingness to receive new information. METHODS This article uses a doubly randomized survey experiment conducted on a nationally representative sample, where some subjects are randomly assigned to an informational treatment about opioids while other subjects are given the choice of whether to receive treatment or not, to examine how public willingness to seek new information shapes the way they update their preferences about policies related to the opioid epidemic. FINDINGS Among those likely to receive information, treatment has a large positive effect on increasing support for policies that address the opioid epidemic by about one half of a standard deviation. Among those who would avoid this information, preferences appear to be unmoved by treatment. These effects would be missed by standard experimental designs. CONCLUSION While redressing information asymmetries is only one part of a public health strategy for addressing the opioid epidemic, our findings highlight the importance of access to and receptiveness toward new information.
NiCo–N-doped carbon nanotubes based cathode catalyst for alkaline membrane fuel cell

Abstract For alkaline fuel cell, development of highly efficient catalysts based on non-noble metal for oxygen reduction reaction is of high significance. In this work, synthesis of nitrogen doped carbon nanotubes (NCNTs) derived from Zeolitic Imidazolate Frameworks (ZIFs) and their performance for oxygen reduction reaction (ORR) in alkaline medium are studied. The NiCo/NCNTs (nitrogen doped carbon nanotubes) showing excellent ORR performance in KOH with current density of −5.6 mA cm−2 and onset potential of 0.98 V vs RHE. The improved electrochemical performance and stability is credited to the synergetic effect of the nitrogen doped carbon nanotubes (NCNTs) and the Ni/Co active sites. The alkaline fuel cell performance of NiCo/NCNTs as cathode catalyst was 65 mW cm−2, which is slightly higher than the commercial Pt/C as cathode (60 mW cm−2). These results indicate that NiCo/NCNTs are promising electrocatalysts for ORR in alkaline fuel cell.
Four Lines and a Rectangle

This paper presents some configuration theorems concerning rectangles inscribed in four lines.
Transient motions of floating bodies at zero forward speed

Linear, time-domain analysis is used to solve the radiation problem for the forced motion of a floating body at zero forward speed. The velocity potential due to an impulsive velocity (a step change in displacement) is obtained by the solution of a pair of integral equations. The integral equations are solved numerically for bodies of arbitrary shape using discrete segments on the body surface. One of the equations must be solved by time stepping, but the kernel matrix is identical at each step and need only be inverted once. The Fourier transform of the impulse-response function gives the more conventional added-mass and damping in the frequency domain. The results for arbitrary motions may be found as a convolution of the impulse response function and the time derivatives of the motion. Comparisons are shown between the time-domain computations and published results for a sphere in heave, a sphere in sway, and a right circular cylinder in heave. Theoretical predictions and experimental results for the heave motion of a sphere released from an initial displacement are also given.
Using Wikipedia for project-based learning in information literacy instruction

Wikipedia holds an ambiguous position in information literacy instruction. Long the go-to example of an untrustworthy online source to avoid, librarians are increasingly using it to illustrate the application of a variety of information literacy concepts. Beginning in Fall 2017, students enrolled in a credit-bearing information literacy course at Cal Poly Pomona were given as a final project, a Wikipedia stub (a basic, incomplete article) and assigned to apply the concepts they had been taught throughout the semester to add information, sources and images, in order to “improve” it. This paper discusses the incorporation of Wikipedia into a credit-bearing course as a form of project-based learning, the development of the course final over several quarters/semesters of class, the benefits and drawbacks of the use of online tutorials and observation of the results of student engagement with the assignment.
Intermediate- and High-Velocity Ionized Gas toward zeta Orionis

We combine UV spectra obtained with the HST/GHRS echelle, IMAPS, and Copernicus to study the abundances and physical conditions in the predominantly ionized gas seen at high (-105 to -65 km/s) and intermediate velocities (-60 to -10 km/s) toward zeta Ori. We have high resolution (FWHM ~ 3.3-4.5 km/s) and/or high S/N spectra for at least two significant ions of C, N, Al, Si, S, and Fe -- enabling accurate estimates for both the total N(H II) and the elemental depletions. C, N, and S have essentially solar relative abundances; Al, Si, and Fe appear to be depleted by about 0.8, 0.3-0.4, and 0.95 dex, respectively. While various ion ratios would be consistent with collisional ionization equilibrium (CIE) for T ~ 25,000-80,000 K, the widths of individual high-velocity absorption components indicate that T ~ 9000 K -- so the gas is not in CIE. Analysis of the C II fine-structure excitation equilibrium yields estimated densities (n_e ~ n_H ~ 0.1-0.2 cm^{-3}), thermal pressures (2 n_H T ~ 2000-4000 cm^{-3}K), and thicknesses (0.5-2.7 pc) for the individual clouds. We compare the abundances and physical properties derived for these clouds with those found for gas at similar velocities toward 23 Ori and tau CMa, and also with several models for shocked gas. While the shock models can reproduce some features of the observed line profiles and some of the observed ion ratios, there are also significant differences. The measured depletions suggest that \~10% of the Al, Si, and Fe originally locked in dust in the pre-shock medium may have been returned to the gas phase, consistent with predictions for the destruction of silicate dust in a 100 km/s shock. The near-solar gas phase abundance of carbon, however, seems inconsistent with the predicted longer time scales for the destruction of graphite grains.
Competitive Quality Choice and Remanufacturing

We consider an original equipment manufacturer (OEM) who faces competition from an independent remanufacturer(IR). The OEM decides the quality of the new product, which also determines the quality of the competing remanufactured product. The OEM and the IR then competitively determine their production quantities. We explicitly characterize how the OEM competes with the IR in equilibrium. Specifically, we show that the OEM relies more on quality as a strategic lever when it has a stronger competitive position (determined by the relative cost and value of new and remanufactured products), and in contrast it relies more heavily on limiting quantity of cores when it has a weaker competitive position. The IR’s entry threat as well as its successful entry can decrease the consumer surplus. Furthermore, our results illustrate that ignoring the competition or the OEM’s quality choice leads to overestimating benefits of remanufacturing for consumer and social welfare. In addition, we show an IR with either a sufficiently weak competitive position (so the OEM deters entry) or a sufficiently strong one (so the OEM is forced to limit quantity of cores) is desirable for reducing the environmental impact. Comparing our results with the benchmark in which the OEM remanufactures suggests that encouraging IRs to remanufacture in lieu of the OEMs may not benefit the environment. Furthermore, the benchmark illustrates that making remanufacturing more attractive improves the environmental impact when the remanufacturer is the OEM, while worsening it when remanufacturing is done by the IR.
Robust Learning of Recurrent Neural Networks in Presence of Exogenous Noise.

Recurrent Neural networks (RNN) have shown promising potential for learning dynamics of sequential data. However, artificial neural networks are known to exhibit poor robustness in presence of input noise, where the sequential architecture of RNNs exacerbates the problem. In this paper, we will use ideas from control and estimation theories to propose a tractable robustness analysis for RNN models that are subject to input noise. The variance of the output of the noisy system is adopted as a robustness measure to quantify the impact of noise on learning. It is shown that the robustness measure can be estimated efficiently using linearization techniques. Using these results, we proposed a learning method to enhance robustness of a RNN with respect to exogenous Gaussian noise with known statistics. Our extensive simulations on benchmark problems reveal that our proposed methodology significantly improves robustness of recurrent neural networks.
Citizen Science Data Collection for Integrated Wildlife Population Analyses

Citizen science, or community science, has emerged as a cost-efficient method to collect data for wildlife monitoring. To inform research and conservation, citizen science sampling designs should collect data that match the robust statistical analyses needed to quantify species and population patterns. Further increasing the contributions of citizen science, integrating citizen science data with other datasets and datatypes can improve population estimates and expand the spatiotemporal extent of inference. We demonstrate these points with a citizen science program called iSeeMammals developed in New York state in 2017 to supplement costly systematic spatial capture-recapture sampling by collecting opportunistic data from one-off observations, hikes, and camera traps. iSeeMammals has initially focused on the growing population of American black bear (Ursus americanus), with integrated analysis of iSeeMammals camera trap data with systematic data for a region with a growing bear population. The triumvirate of increased spatial and temporal coverage by at least two-fold compared to systematic sampling, an 83% reduction in annual sampling costs, and improved density estimates when integrated with systematic data highlight the benefits of collecting presence-absence data in citizen science programs for estimating population patterns. Additional opportunities will come from applying presence-only data, which are oftentimes more prevalent than presence-absence data, to integrated models. Patterns in data submission and filtering also emphasize the importance of iteratively evaluating patterns in engagement, usability, and accessibility, especially focusing on younger adult and teenage demographics, to improve data quality and quantity. We explore how the development and use of integrated models may be paired with citizen science project design in order to facilitate repeated use of datasets in standalone and integrated analyses for supporting wildlife monitoring and informing conservation.
Identification of a novel HLA-A*24 allele, A*24:537, identified in three individuals in an Indian family

The novel HLA-A*24:537 allele differs from HLA-A*24:02:01:01 by a nucleotide change at gDNA 294 C → T.
Alterations in resting-state functional connectivity in pediatric patients with tuberous sclerosis complex.

Objective To investigate resting-state functional connectivity (FC) in pediatric patients with tuberous sclerosis complex and intractable epilepsy requiring surgery. Methods Resting-state functional MRI was utilized to investigate functional connectivity in 13 pediatric patients with tuberous sclerosis complex (TSC) and intractable epilepsy requiring surgery. Results The majority of patients demonstrated a resting-state network architecture similar to those reported in healthy individuals. However, preoperative differences were evident between patients with high versus low tuber burden, as well as those with good versus poor neurodevelopmental outcomes, most notably in the cingulo-opercular and visual resting-state networks. One patient with high tuber burden and poor preoperative development and seizure control had nearly normal development and seizure resolution after surgery. This was accompanied by significant improvement in resting-state network architecture just one day postoperatively. Significance Although many patients with tuberous sclerosis complex and medically refractory epilepsy demonstrate functional connectivity patterns similar to healthy children, relationships within and between RSNs demonstrate clear differences in patients with higher tuber burden and worse outcomes. Improvements in resting-state network organization postoperatively may be related to epilepsy surgery outcomes, providing candidate biomarkers for clinical management in this high-risk population.
Emesis of an enteral bullet: A rare case of bullet embolism to the thoracic esophagus

A case of migration of a foreign body from the stomach to the thoracic esophagus is described. The bullet was successfully retrieved endoscopically after exploratory laparotomy was performed to address the patient's injuries. Enteral migration of bullets is a rare phenomenon that should be considered when the location of retained ballistic fragments is inconsistent with gunshot wounds and expected trajectories.
Recurrent fibrin associated diffuse large B-cell lymphoma: A case report

Abstract Fibrin- associated diffuse large B cell lymphoma (FA-DLBCL) is a rare entity, often incidental finding, categorized under “diffuse large B cell lymphoma associated with chronic inflammation (DLBCL-CI)“ in 2017 World Health Organization (WHO) classification of tumors of hematopoietic and lymphoid tissues. Here we report a 48-year-old male with FA-DLBCL who experienced recurrence within one year from initial presentation. The patient had a history of an abdominal aortic aneurism and underwent an endovascular aneurysm repair (EVAR) in 2013. Later in 2019, he was found by CT aortogram to have endoleak of the aneurysm repair. He underwent an open abdominal aortic aneurysm repair with explant of the endovascular stent. The explanted graft was sent to pathology and was found on gross examination to have ample adherent tissue. On microscopic examination this tissue was composed of abundant fibrinous material with several foci of large pleomorphic lymphocytes with enlarged round to polyhedral nuclei, prominent nucleoli, open chromatin, and scanty cytoplasm. Necrosis was also seen in a largest focus of tumor infiltrate. By immunohistochemistry, the atypical, large lymphocytes expressed CD20 and MUM-1; and positive for EBV, by Epstein-Barr virus (EBV) in situ hybridization (EBER-ISH). Together, the diagnosis for FA-DLBCL was made. Further work up by PET scan showed no active disease. The patient re-presented 10 months later with right lower extremity ischemia due to the vascular graft thrombosis. The thrombectomy specimen showed identical findings of his initial FA- DLBCL. Here we discuss the clinicopathologic findings of this entity and the importance of clinical follow up.
REGULATION OF PHOSPHORYIASE b TO a CONVERSION IN MUSCLE

Publisher Summary This chapter describes the regulation of phosphorylase b to a conversion in muscle. Epinephrine stimulates phosphorylase b to a conversion in skeletal muscle which has been explained by a sequence of reactions starting with augmentation of the activity of adenylate cyclase. Increased intracellular cyclic AMP concentrations stimulate cyclic AMP dependent protein kinase activity to catalyze the conversion of phosphorylase b kinase to the activated form. The activated phosphorylase b kinase then catalyzes phosphorylase a formation, which in turn catalyzes glycogenesis. Support for this hypothesis has been obtained from the experiments in which relatively large doses of catecholamines were used in vivo. However, results at variance with this scheme were obtained when low concentrations of isoproterenol were used to stimulate phosphorylase b to a conversion in the autoperfused rabbit gracilis muscle. Three phases of phosphorylase b to a conversion were observed as functions of time and dose of isoproterenol.