cssi/SciSciGPT-SciSciNet huggingface dataset:
The Molecular Correlation Concept of Neoplasia: Recent Advances and New Challenges

This paper critically evaluates the advances made with the molecular correlation concept as a conceptual and experimental approach in elucidating the biochemical strategy of the cancer cells. New advances made in gaining an insight into the behavior of pyrimidine metabolism are also used to illustrate the method and current status of the molecular correlation concept. Investigation of the hepatomas of different growth rates and comparison with appropriate control systems such as the normal, differentiating and regenerating liver has led to the discovery that in neoplastic cells there is an ordered pattern of enzymatic and metabolic imbalance. We documented in detail the linking of biochemical discriminants with neoplastic transformation and progression in carbohydrate, pentose phosphate, purine, pyrimidine, ornithine and polyamine metabolism and in membrane cAMP systems. We pointed out the importance of selecting for such investigations the analysis of the activity, concentration and isozyme pattern of opposing key enzymes in antagonistic pathways of synthesis and degradation. We demonstrated that the control of gene expression operates through reciprocal regulation of opposing key enzymes in antagonistic and competing metabolic pathways.
The present, past, and future of the gardening metaphor in education

Educators and educational theorists frequently employ a gardening metaphor to capture several child-centred principles about teaching and children, i.e. teachers must respect a child’s unique inter...
Water suppression in the human brain with hypergeometric RF pulses for single-voxel and multi-voxel MR spectroscopy

PURPOSE To develop and investigate a novel water suppression sequence with hypergeometric pulses at 3 T. METHODS Simulations were used to optimize the delays and amplitudes of 5 hypergeometric prepulses, to minimize the residual water over a range of T1 and B1 values. Single-voxel data with hypergeometric water suppression (HGWS) prepulses were acquired in the centrum semiovale, 2 parietal regions, and insula of 7 subjects, and compared with VAPOR water suppression. Magnetic resonance spectroscopic imaging (MRSI) data using both VAPOR and HGWS prepulses were also collected and compared. Water suppression performance was calculated as the residual water peak height relative to the unsuppressed water peak. MRSI voxel-by-voxel comparison was performed by calculating the ratio between HGWS and VAPOR residual water peaks. RESULTS In simulations, HGWS and VAPOR are insensitive to B1 and water T1 variations, but with no B1 variation, HGWS has a lower average residual water fraction (0.0033) than that of VAPOR (0.0091). In single-voxel acquisitions, HGWS performs better than VAPOR in all regions with a 2.3-fold to 5.7-fold lower residual water. In MRSI acquisitions, HGWS performs on average 2.3-fold better than VAPOR in 98.9% of the voxels. CONCLUSION HGWS provides better water suppression than VAPOR in both single-voxel and multivoxel acquisitions with a shorter sequence duration.
Economic and environmental implications of incorporating distillers’ dried grains with solubles in feed rations of growing and finishing swine in Argentina

The Argentinean swine industry has quickly expanded over the past decade, hence increasing the demand for swine feedstuffs. The growing supply of distillers’ dried grains with solubles (DDGS) from the emerging Argentinean corn-based ethanol industry is a potential feedstuff for swine producers. Using a multi-objective linear programming model, this study examined the economic and environmental concerns (i.e. cost and phosphorus content) associated with introducing DDGS in swine feed rations. Results suggest that including DDGS in swine diets concurrently minimized cost and phosphorus content. The results were extrapolated to the entire Argentinean swine industry and show that the inclusion of DDGS in swine rations could potentially save the Argentinean swine industry about 19.21 million US dollars annually and reduce phosphorus content by up to 5%. In addition, sensitivity analysis of DDGS price was conducted and the potential demand for DDGS from swine by growth category was derived.
4th Generational Theories of Intersection: Multicultural Aging

In this chapter, authors asserted that the multifarious reality of older adults’ social positions offer unique opportunities and challenges to our traditional gerontological theories. Authors presented intersectionality as an analytical framework to move readers beyond their disciplinary boundaries towards a 4th generation of theories for co-creation of innovative theories, methods, and interventions. In the co-edited book, The Collective Spirit of Aging Across Cultures, we critically reflect on how chapter authors integrated gerontological theories guided by the philosophical assumptions of intersectionality for addressing multicultural issues of aging, including caregiving, intimacy, elder mistreatment, financial crisis, housing transitions, and technology that span and interact with all social identities at multiple levels. We have invited readers to embrace a lens of intersectionality, and provided a discourse towards a 4th generation of theories to inform trans-disciplinary professionals on how to co-create with collectivist communities aimed at addressing social justice, health and well-being of multicultural older adults.
Problems in Diophantine Approximation

Three partial manuscripts on diverse problems in Diophantine approximation are examined. One is devoted to the Diophantine approximation to \(e^{2/a}\), and is related to Ramanujan’s only publication in the subject, a problem that he published in the Journal of the Indian Mathematical Society. In this partial manuscript, Ramanujan provides the best Diophantine approximation to e, approximately 60 years before the theorem was rediscovered and proved in print.
Deep proteomic network analysis of Alzheimer’s disease brain reveals alterations in RNA binding proteins and RNA splicing associated with disease

The complicated cellular and biochemical changes that occur in brain during Alzheimer’s disease are poorly understood. In a previous study we used an unbiased label-free quantitative mass spectrometry-based proteomic approach to analyze these changes at a systems level in post-mortem cortical tissue from patients with Alzheimer’s disease (AD), asymptomatic Alzheimer’s disease (AsymAD), and controls. We found modules of co-expressed proteins that correlated with AD phenotypes, some of which were enriched in proteins identified as risk factors for AD by genetic studies. The amount of information that can be obtained from such systems-level proteomic analyses is critically dependent upon the number of proteins that can be quantified across a cohort. We report here a new proteomic systems-level analysis of AD brain based on 6,533 proteins measured across AD, AsymAD, and controls using an analysis pipeline consisting of isobaric tandem mass tag (TMT) mass spectrometry and offline prefractionation. Our new TMT pipeline allowed us to more than double the depth of brain proteome coverage. This increased depth of coverage greatly expanded the brain protein network to reveal new protein modules that correlated with disease and were unrelated to those identified in our previous network. Differential protein abundance analysis identified 350 proteins that had altered levels between AsymAD and AD not caused by changes in specific cell type abundance, potentially reflecting biochemical changes that are associated with cognitive decline in AD. RNA binding proteins emerged as a class of proteins altered between AsymAD and AD, and were enriched in network modules that correlated with AD pathology. We developed a proteogenomic approach to investigate RNA splicing events that may be altered by RNA binding protein changes in AD. The increased proteome depth afforded by our TMT pipeline allowed us to identify and quantify a large number of alternatively spliced protein isoforms in brain, including AD risk factors such as BIN1, PICALM, PTK2B, and FERMT2. Many of the new AD protein network modules were enriched in alternatively spliced proteins and correlated with molecular markers of AD pathology and cognition. Further analysis of the AD brain proteome will continue to yield new insights into the biological basis of AD.
Laryngeal muscle biology in the Pink1-/- rat model of Parkinson disease.

Pathology of peripheral nerves and muscle has been reported in the larynx and pharynx of humans diagnosed with Parkinson disease (PD); however, it is unknown whether differences of laryngeal muscle...
Safety and Efficacy of Bempedoic Acid to Reduce LDL Cholesterol.

Abstract Background Short-term studies have shown that bempedoic acid, an inhibitor of ATP citrate lyase, reduces levels of low-density lipoprotein (LDL) cholesterol. Data are limited regarding the...
Collaborative research and multi-issue movement building for educational justice: Reflections on the Urban Research Based Action Network (URBAN)

Two long-time scholar-activists reflect on a distinctive approach to research that they call collaborative research for justice, research that is conducted with community leaders and education activists to advance equity and social justice. They argue that by linking research directly with action this kind of research has the power to speak directly to the current crises not only in education, but also in the other institutions of civil society. Drawing on decades of experience in public research universities, local community based organizations, inter/national disciplinary research organizations, and distributed informal networks of engaged scholars, social justice activists, and community leaders, they reflect specifically on the more recent formation of the Urban Research Based Action Network (URBAN), a national network of people enacting a variety of forms of collaborative research for justice, now with more than 1500 members. They outline lessons that might contribute to building the multi-issue movement for educational justice that they believe is required to transform public schools to make them serve the needs of the most disadvantaged, aggrieved, and inequitably treated communities. In its short history URBAN has already impacted the academy through the gatherings and meetings it has hosted as well as through a rigorous publishing agenda, including a special issue of EPAA in which this article appears.
Identidad académica: una franquicia en construcción

L’impacte que exerceixen les universitats sobre el desenvolupament de la societat esdeve rellevant davant les expectatives de justicia i de be comu que mostren els ciutadans. La manera com es vinculen aquestes institucions amb una reflexio que afavoreix la creacio de models nous es una paradoxa, ja que, des de la segona meitat del segle XX, s’ha anat consolidant un capitalisme academic per part d’una industria universitaria, l’abast del qual posa en tensio un debat inacabat. Aquest article preten presentar com es construeixen les identitats fragmentades i en conflicte a partir d’entrevistes amb academics que expliquen la seva evolucio i que refermen la seva posicio apropiant-se d’aquest model, pero interpretant el significat d’un academic universitari. Quatre repertoris articulen una identitat interpel·lada per racionalitats que els modelen i que els organitzen en una performativitat que els allunya i que els acaba desarrelant i convertint en reproductors passius de models basats en indicadors de gestio. A partir d’aqui esdeve urgent incorporar al debat academic la manera com aquesta nova forma de fer universitat promou una xarxa social on el rendiment i l’autogestio impregnen els futurs professionals, tot enfortint models individualistes de la societat que amenacen el benestar dels seus membres.
Hannah Whitall Smith’s Highway of Holiness

Spencer traces the spiritual development and mystical consciousness of Hannah Whitall Smith, nineteenth-century American Quaker, prominent devotional writer, and Holiness preacher. Based on her autobiography, diary, and carefully archived letters, Spencer explores her Quaker roots, evangelical conversion, transatlantic ministry, exploration of new religious movements, and lifelong fascination with the meaning of spirit baptism. Spencer shows how she integrated the mysticism of the historic Quaker tradition, the writings of the French Quietist Jeanne Guyon, the Wesleyan Holiness Movement, and other emerging forms of spirituality in the Victorian era into a final embrace of a practical, rational mysticism that incorporated all her so-called heresies including her reconciling of God’s love and justice in the “restitution of all things,” a Christian universalism.
Grading Herbaceous Biomass for Biorefineries: a Case Study Based on Chemical Composition and Biochemical Conversion

Due to the highly variable nature of biomass resources, establishing a quantitative system for evaluating biomass quality offers tangible benefits for emerging bioeconomy markets. This paper demonstrates an approach for developing a grading system, based on inherent biomass characteristics, to inform markets on how natural variability impacts conversion performance. The case study considers a biochemical biorefining pathway, in which monomeric sugars are fermented to mainly ethanol, while the preliminary demonstration is based on five grass types, typically used as feedstock in this type of biorefinery. Samples of the biomass resources were characterized and converted to carbohydrates using dilute-acid pretreatment and enzymatic hydrolysis. The approach involved three steps: (1) identify key biomass compositional characteristics that impact biochemical conversion performance and fermentable sugar yields using a linear regression approach, (2) assess the range of variability for the key characteristics using a diverse set of biomass resources, and (3) grade ranges of variability based on predicted conversion yields. It was demonstrated that five chemical characteristics, structural glucan, hemicellulose carbohydrates, acid-soluble lignin, acid-insoluble lignin, and total ash, could be used to estimate conversion performance. Five grades were established using a hierarchical cluster analysis. Future research is needed to confirm that these characteristics can predict product yields over multiple pretreatment methods and enzymatic hydrolysis/fermentation conditions. In addition, it would be beneficial to extend a grading system to include other biomass characteristics that impact preprocessing operations, such as grinding and conveying.
Sitagliptin for the prevention of stress hyperglycemia in patients without diabetes undergoing coronary artery bypass graft (CABG) surgery

Aims To determine if treatment with sitagliptin, a dipeptidyl peptidase-4 inhibitor, can prevent stress hyperglycemia in patients without diabetes undergoing coronary artery bypass graft (CABG) surgery. Methods We conducted a pilot, double-blinded, placebo-controlled randomized trial in adults (18–80 years) without history of diabetes. Participants received sitagliptin or placebo once daily, starting the day prior to surgery and continued for up to 10 days. Primary outcome was differences in the frequency of stress hyperglycemia (blood glucose (BG) >180 mg/dL) after surgery among groups. Results We randomized 32 participants to receive sitagliptin and 28 to placebo (mean age 64±10 years and HbA1c: 5.6%±0.5%). Treatment with sitagliptin resulted in lower BG levels prior to surgery (101±mg/dL vs 107±13 mg/dL, p=0.01); however, there were no differences in the mean BG concentration, proportion of patients who developed stress hyperglycemia (21% vs 22%, p>0.99), length of hospital stay, rate of perioperative complications and need for insulin therapy in the intensive care unit or during the hospital stay. Conclusion The use of sitagliptin during the perioperative period did not prevent the development of stress hyperglycemia or need for insulin therapy in patients without diabetes undergoing CABG surgery.
Safety and efficacy outcomes of left atrial posterior wall isolation compared to pulmonary vein isolation and pulmonary vein isolation with linear ablation for the treatment of persistent atrial fibrillation.

Background Pulmonary wall isolation (PWI) is increasingly used as an adjunctive lesion set to compliment pulmonary vein isolation (PVI), especially in patients with persistent atrial fibrillation (AF). The objective was to compare outcomes of catheter ablation in patients with persistent AF undergoing PVI with and without adjunctive PWI. Methods We performed a retrospective study of 558 patients who underwent de novo and repeat ablation for persistent AF. Subjects were matched using propensity score adjustments. Outcomes were freedom from recurrent atrial arrhythmia and adverse events. Results Among 558 patients who underwent ablation for persistent AF, 78 (14%) underwent PVI + PWI, 255 (46%) underwent PVI, and 225 (40%) underwent PVI + linear ablation. Stratified logistic regression analysis with propensity matching revealed higher odds of recurrent arrhythmia with PVI + PWI when compared to PVI (odds ratio [OR] 2.25, 95% CI 1.08-4.69, P = .030) and when compared to PVI + linear (OR 2.31, 95% CI 1.01-5.28, P = .048). Within the PVI + PWI group, 57.7% of subjects were in normal sinus rhythm at 6 months compared to 73.9% and 72.2% in PVI and PVI + linear groups, respectively. Adverse events were rare, with 19 events total identified across all groups. Conclusions PVI + PWI does not appear to be as effective as PVI or PVI + linear ablation in reducing the recurrence of arrhythmia within 6 months of the index procedure in patients with persistent AF. A prospective, randomized controlled trial comparing these ablation techniques is needed to clarify the role of extensive substrate modification for treatment of persistent AF. Condensed Abstract PWI is increasingly used as an adjunctive lesion set to compliment PVI in patients with persistent AF. We performed a retrospective study of 558 patients who underwent de novo and repeat ablation for persistent AF to compare the outcomes between PVI with and without adjunctive PWI. We found an increased incidence in recurrence of AF and other atrial arrhythmias at 6 months in the PVI + PWI cohort compared to PVI with or without additional linear ablation. A prospective, randomized controlled trial comparing these ablation techniques is needed to clarify the role of extensive substrate modification for treatment of persistent AF.
Role of Systemic Lupus Erythematosus Risk Variants With Opposing Functional Effects as a Driver of Hypomorphic Expression of TNIP1 and Other Genes Within a Three-Dimensional Chromatin Network.

OBJECTIVE Genetic variants in the region of tumor necrosis factor-induced protein 3-interacting protein 1 (TNIP1) are associated with autoimmune disease and reduced TNIP1 gene expression. The aim of this study was to define the functional genetic mechanisms driving TNIP1 hypomorphic expression imparted by the systemic lupus erythematosus-associated TNIP1 H1 risk haplotype. METHODS Dual luciferase expression and electrophoretic mobility shift assays were used to evaluate the allelic effects of 11 risk variants on enhancer function and nuclear protein binding in immune cell line models (Epstein-Barr virus [EBV]-transformed human B cells, Jurkat cells, and THP-1 cells), left in a resting state or stimulated with phorbol 12-myristate 13-acetate/ionomycin. HiChIP was used to define the regulatory 3-dimensional (3-D) chromatin network of the TNIP1 haplotype by detecting in situ long-range DNA contacts associated with H3K27ac-marked chromatin in EBV B cells. Then, quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to determine the expression of genes within the 3-D chromatin network. RESULTS Bioinformatics analyses of 50 single-nucleotide polymorphisms on the TNIP1 H1 risk haplotype identified 11 non-protein-coding variants with a high likelihood of influencing TNIP1 gene expression. Eight variants in EBV B cells, 5 in THP-1 cells, and 2 in Jurkat cells exhibited various allelic effects on enhancer activation, resulting in a cumulative suppressive effect on TNIP1 expression (net effect of risk variants -7.14 fold, -6.80 fold, and -2.44 fold, respectively; n > 3). Specifically, in EBV B cells, only 2 variants (rs10057690 and rs13180950) exhibited allele-specific loss of both enhancer activity and nuclear protein binding (each P < 0.01 relative to nonrisk alleles). In contrast, the rs10036748 risk allele reduced binding affinities of the transcriptional repressors basic helix-loop-helix family member 40/differentially expressed in chondrocytes 1 (bHLHe40/DEC1) (P < 0.05 relative to nonrisk alleles) and CREB-1 (P not significant) in EBV B cells, resulting in a gain of enhancer activity (P < 0.05). HiChIP and qRT-PCR analyses revealed that overall transcriptional repression of the TNIP1 haplotype extended to the neighboring genes DCTN4 and GMA2, both of which also showed decreased expression in the presence of the TNIP1 risk haplotype (P < 0.001 and P < 0.01, respectively, relative to the nonrisk haplotype); notably, it was found that these genes share a 3-D chromatin network. CONCLUSION Hypomorphic TNIP1 expression results from the combined concordant and opposing effects of multiple risk variants carried on the TNIP1 risk haplotype, with the strongest regulatory effect in B lymphoid lineage cells. Furthermore, the TNIP1 risk haplotype effect extends to neighboring genes within a shared chromatin network.
Smart Literacy Learning in the Twenty-First Century: Facilitating PBSL Pedagogic Collaborative Clouds

Prevalent in the literature are the components of smart education, learning, and literacies; smart pedagogies are encouraged, but practical examples are scant. A gap between education and the workplace has been acknowledged; how can smart pedagogy fill the void? This chapter provides an example of an innovative educational process bridging the interval utilizing an online problem-based service learning (PBSL) instructional approach and a pedagogic collaborative cloud, a smart pedagogic collaborative cloud (PCC). Educators collaborating together are a crucial component of the changing praxis. In a university course using a PBSL approach, students collaboratively identified a problem—lack of time. A literacy pedagogic collaborative cloud was identified as the solution to the problem. A pilot study was performed (n = 12) to ascertain interest in the idea and warrant conducting a study. A triangulated qualitative study (n = 45) was implemented; a broad constructive theoretical framework provided support for smart education, PBSL, and the pedagogic collaborative cloud. The research questions were: (1) Does the interest or need exist to create a literacy collaborative cloud for graduate students and alumnae? (2) What was the best format to encourage participation? Four types of data were collected and quality checks instituted. The findings revealed 80% of the participants agreed with the creation of a literacy pedagogic collaborative cloud (LPCC); 100% of the participants preferred to collaborate with a group of professionals in their field, and 100% agreed collaboration improved teaching practice. A private literacy PCC was created on Facebook; the implications are clear—smart pedagogy can fill the university/workplace void.
Impact of PTFE-covered stent position and extension on TIPS patency.

The objectives of this study were to determine the effects of expanded polytetrafluoroethylene (PTFE)-covered stent location and TIPS extension on primary patency. This retrospective cohort study examined patients with PTFE-covered TIPS creation between 07/2002 and 06/2016. Clinical information and patency outcomes at 24 months were extracted. At TIPS creation, extension was performed at the discretion of the operator. Kaplan–Meier curves of primary patency were generated with conditional variables of HVO-HCJ distance, extension status, and covered versus uncovered extensions. Additional logistic regression analyses of distances were performed. Of 393 patients, 115 patients (29%) underwent stent extension, 79 (20% of total cohort) of which were at the HVO end alone. Primary patency for all TIPS was 75%, 68%, and 54% at 3, 6, and 12 months. The data endpoint were transplant or death in 92 (23%) and 116 (30%). Kaplan–Meier curves showed no statistically significant difference between the variables and primary patency at 12 and 24 months: distance up to versus greater than 10 mm (p = 0.32, 0.81); extension versus no extension (p = 0.83, 0.85); uncovered versus covered extensions (p = 0.58, 0.70). Logistic regression analyses showed a trend toward statistical significance. In the setting of PTFE-covered TIPS creation, extended TIPSs and unextended well-positioned TIPSs have no difference in primary patency rates. Stent position and extension length may have an effect on primary patency, but were likely obscured by “user recognition” effects.
Doctorates and Employability: New Perspectives for Doctoral Education

Profound processes of change are affecting doctorates all over the world, above all, to provide broader employment prospects. However, the link between the transformations of a doctorate and employability is complex, and entails re-thinking formative pathways for doctorates by focusing on the professional identity of a PhD
Maternal Dietary Factors and the Risk of Autism Spectrum Disorders: A Systematic Review of Existing Evidence

Prenatal maternal diet is a critical factor in offspring neurodevelopment. Emerging evidence suggests that prenatal diet may also play a role in the etiology autism spectrum disorder (ASD). This review summarizes studies published in English that examined prenatal nutrients or maternal diet in association with ASD from PubMed as of July 2020. Thiry-six studies from nine countries were included in this systematic review; these focused on multivitamin (n = 5), prenatal vitamin (n = 3), folic acid (FA; n = 14), Vitamin D (n = 11), polyunsaturated fatty acid or fish/supplement intake (n = 7), iron (n = 3), Vitamin B12 (n = 1), calcium (n = 1), magnesium (n = 1), and broad maternal dietary habits (n = 3). Overall, higher or moderate intake of prenatal/multivitamin, FA, and Vitamin D was associated with reductions in odds of ASD, though results have not been uniform and there is a need to clarify differences in findings based on biomarkers versus reported intake. Evidence was inconclusive or insufficient for other nutrients. Differences in the timing and measurement of these dietary factors, as well as potential residual confounding, may contribute to existing discrepancies. Key areas for future research to better understand the role of maternal diet in ASD include the need to address potential critical windows, examine the combined effect of multiple nutrients, and consider interactions with genetic or environmental factors. LAY SUMMARY: Maternal diet during pregnancy is important for child neurodevelopment. We reviewed 36 studies examining maternal diet and autism spectrum disorder (ASD) and found that prenatal vitamin/multivitamin use and adequate intake of folic acid and Vitamin D were each associated with lower likelihood of having a child with ASD. Future studies on these and other dietary factors are needed to better understand the role of maternal diet in the development of ASD. Autism Res 2020, 13: 1634-1658. © 2020 International Society for Autism Research and Wiley Periodicals LLC.
Abstract 13873: Arterial Stiffness in Response to Eight Weeks of Exercise Training in African Americans versus Caucasians

Introduction: Arterial stiffness predicts risks of cardiovascular disease in apparently healthy individuals. Exercise training decreases risks of cardiovascular disease, potentially via reductions ...
ATR activation is regulated by dimerization of ATR activating proteins.

The checkpoint kinase ATR regulates DNA repair, cell cycle progression, and other DNA damage and replication stress responses. ATR signaling is stimulated by an ATR activating protein, and in metazoan cells, there are at least two ATR activators: TOPBP1 and ETAA1. Current evidence indicates TOPBP1 and ETAA1 activate ATR via the same biochemical mechanism, but several aspects of this mechanism remain undefined. For example, ATR and its obligate binding partner ATR interacting protein (ATRIP) form a tetrameric complex consisting of two ATR and two ATRIP molecules, but whether TOPBP1 or ETAA1 dimerization is similarly required for ATR function is unclear. Here, we show that fusion of the TOPBP1 and ETAA1 ATR activation domains (AADs) to dimeric tags makes them more potent activators of ATR in vitro. Furthermore, induced dimerization of both AADs using chemical dimerization of a modified FKBP tag enhances ATR kinase activation and signaling in cells. ETAA1 forms oligomeric complexes mediated by regions of the protein that are predicted to be intrinsically disordered. Induced dimerization of a "mini-ETAA1" protein that contains the AAD and Replication Protein A (RPA) interaction motifs enhances ATR signaling, rescues cellular hypersensitivity to DNA damaging agents, and suppresses micronuclei formation in ETAA1-deficient cells. Together, our results indicate that TOPBP1 and ETAA1 dimerization is important for optimal ATR signaling and genome stability.
Ambulatory noninsulin treatment of type 2 diabetes mellitus in the United States, 2015 to 2019

Importance Tens of millions of individuals in the United States have Type 2 diabetes, and most require treatment with glucose-lowering medications to manage the disease. Objective To examine trends in non-insulin drug treatment of Type 2 diabetes, including first-line and second-line therapies on top of metformin, from 2015 to 2019. Design, setting and participants We conducted a descriptive analysis of cross-sectional data using the IQVIA National Disease and Therapeutic Index (NDTI), a nationally representative audit of ambulatory physician practices in the United States. We focused on the use of non-insulin pharmacologic treatments for Type 2 diabetes among individuals age 35 years and older between January 1st 2015 and December 31st 2019. Main outcome and measures Type 2 diabetes visits where a prescription drug was used ("treatment visit"). Results Ambulatory diabetes visits decreased from 30.1 million (M) treatment visits in 2015 to 29.5 M treatment visits in 2019. Among treatment visits where a single drug was prescribed, use of metformin declined from 57.0% of monotherapy in 2015 to 46.0% of monotherapy in 2019, while during the same period the share of monotherapy accounted for by Glucagon-like peptide -1 (GLP-1) agonists increased from 4.3% to 8.5% and the share accounted for by sodium-glucose cotransporter-2 (SGLT-2) inhibitors increased from 7.3% to 19.5%. Among treatment visits where metformin plus another drug was prescribed, the share of second line therapy accounted for by dipeptidyl peptidase-4 (DPP-4) inhibitors decreased from 21.9% of treatment visits in 2015 to 20.8% of treatment visits in 2019; sulfonylurea use declined from 45.2% to 32.7%, use of SGLT-2 inhibitors increased from 14.5% to 21.2% and use of GLP-1 agonists increased from 9.8% to 18.2%. Conclusions and relevance Significant changes in the landscape of ambulatory care for diabetes have taken place during the past six years, including moderate declines in metformin monotherapy, moderate declines in second-line sulfonylurea use, and large increases in SGLT-2 use. These changes underscore the dynamic nature of drug utilization for diabetes in the United States, and reflect the effects of emerging evidence, evolving clinical guidelines and evolving regulatory and payment policies. This article is protected by copyright. All rights reserved.
Changes in secondary outcomes associated with brief interventions for problem gambling in methadone patients

Abstract Background Patients in methadone maintenance treatment (MMT) with problem gambling (PG) experience worse psychosocial outcomes than their non-PG counterparts. Interventions targeting PG in MMT may enhance psychosocial functioning beyond gambling reduction and abstinence. The present study was a secondary data analysis that examined the trajectories of non-gambling outcomes of three brief PG interventions (i.e., brief psychoeducation, brief advice, motivational enhancement therapy plus cognitive-behavioral therapy [MET + CBT]) among MMT patients. Methods Participants (N = 109) were engaged in substance use disorder treatment, met criteria for PG, and had a current or lifetime history of MMT. Latent growth curve models examined outcome trajectories of psychiatric, medical, legal, employment, and social problems, as well as psychological distress and quality of life. Follow-up analyses examined clinically significant change. Results MET + CBT patients reported lower medical problems at baseline and over time than the brief interventions. There was no evidence of differences between interventions on the other outcomes. Psychiatric problems and psychological distress decreased over time for the entire sample, regardless of the PG intervention. About 24% and 13% of the sample demonstrated clinically significant improvements in psychological distress from baseline to 5 months, and 5 months to 12 months, respectively. Nearly 21% of the sample showed clinically significant improvements in psychiatric problems from 5 months to 12 months. Among all patients, men and those with more severe opioid dependence symptoms demonstrated the greatest psychological improvements. Conclusions Many patients in MMT with PG experience improvements in psychological problems, including long-term improvement, regardless of the PG intervention offered.
Operationalizing the Role of Context in Language Variation: The Role of Perspective Alignment in the Spanish Imperfective Domain

We present a cognitively grounded analysis of the pattern of variation that underlies the ​use of two aspectual markers in Spanish (the Simple-Present marker, Ana baila ‘Ana dances’, and the Present-Progressive marker, Ana esta bailando ‘Ana is dancing’) when they express an event-in-progress reading. This analysis is centered around one fundamental communicative goal, which we term perspective alignment: the bringing of the hearer’s perspective closer to that of the speaker. Perspective alignment optimizes the tension between two nonlinguistic constraints: Theory of Mind, which gives rise to linguistic expressivity, and Common Ground, which gives rise to linguistic economy. We propose that, linguistically, perspective alignment capitalizes on lexicalized meanings, such as the progressive meaning, that can bring the hearer to the “here and now”. In Spanish, progressive meaning can be conveyed with the Present-Progressive marker regardless of context. By contrast, if the Simple-Present marker is used for that purpose, it must be in a context of shared perceptual access between speaker and hearer; precisely, a condition that establishes perspective alignment non-linguistically. Support for this analysis comes from a previously observed yet unexplained pattern of contextually-determined variation for the use of the Simple-Present marker in Iberian and Rioplatense (vs. Mexican) Spanish—in contrast to the preference across all three varieties for the use of the Present-Progressive marker—to express an event-in-progress reading.
ERGO: A Scalable Edge Computing Architecture for Infrastructureless Agricultural Internet of Things

In this paper, we propose ERGO (edge architecture for Ag-IoT), an edge-computing architecture for infrastructureless smart agriculture environments. We also develop Ag-IoT application APIs and the associated microservice infrastructure. Our implementation and evaluations show that ERGO can operate independently of cloud-backed assistance, is highly scalable, modular, and affords composability benefits to Ag-IoT systems. We also demonstrate that ERGO outperforms traditional infrastructure in response latencies and transactional throughput, on average, by over 54% and 77%, respectively.
Realization of the Zn3+ oxidation state

Due to unfilled d-shells, transition metal atoms exhibit multiple oxidation states and rich chemistry. While zinc is often classified as a transition metal, electrons in its filled 3d10 shell do not participate in chemical reactions; hence, its oxidation state is +2. Using calculations based on density functional theory, we show that the chemistry of zinc can fundamentally change when it is allowed to interact with highly stable super-electrophilic trianions, namely, BeB11(CN)123− and BeB23(CN)223−, which lie 15.85 eV and 18.49 eV lower in energy than their respective neutral states. The fact that Zn exists in +3 oxidation states while interacting with these moieties is evidenced from its large binding energies of 6.33 and 7.04 eV with BeB11(CN)123− and BeB23(CN)223−, respectively, and from a comprehensive analysis of its bonding characteristics, charge density distribution, electron localization function, molecular orbitals and energy decomposition, all showing a strong involvement of its 3d electrons in chemical bonding. The replacement of CN with BO is found to increase the zinc binding energy even further.
One-Pot Enzymatic Synthesis of Heparin from N-Sulfoheparosan.

Heparin, a glycosaminoglycan-based anticoagulant drug, is prepared as an extract of animal tissues. Heparosan, an Escherichia coli (E. coli) K5 capsular polysaccharide with the structure →4)-β-D-glucuronic acid (1 → 4)-β-D-N-acetylglucosamine (1→, corresponds to the precursor backbone in the Golgi-based biosynthesis of heparin. Anticoagulant heparin is prepared in a one-pot synthesis using a chemically prepared derivative of heparosan called N-sulfoheparosan (NSH), recombinant Golgi enzymes expressed in E. coli, and the 3-phosphoadenosine-5-phosphosulfate (PAPS) cofactor.
Is There a Benefit to Head Size Greater Than 36 mm in Total Hip Arthroplasty

This study compares the rate of dislocation and revision for instability between 36-mm and anatomic femoral heads (large diameter metal-on-metal THA, dual-mobility bearings, and hip resurfacing arthroplasty) in patients at high risk for dislocation. A total of 501 high-risk patients, over a 10-year period, were identified (282 36-mm THA, 24 dual-mobility bearings, 83 metal-on-metal arthroplasty, and 112 hip resurfacing arthroplasty). There were 13 dislocations in the 36-mm group compared to 1 in the anatomic group (4.6% vs 0.5%; P = .005). Four patients dislocated more than once in the 36-mm group (1.4% vs 0%; P = .04), and 2 patients in the 36-mm group required a revision for instability (0.7% vs 0%; P = .11). These results suggest that anatomic head sizes significantly lower the risk of dislocation in high-risk patients.
Machine Learning from Structured Objects

Abstract Machine learning techniques applied to structured objects frequently use a predicate calculus representation to model the world. Unless careful attention is given to the semantics of this model, the results of inductive inference over descriptions of structured objects have unanticipated interpretations. In this paper, a motivation is given for the importance of careful attention to the semantics that underly descriptions of structured examples and categories of such examples. Particular attention is given to the use of must not clauses and the ability to determine relevant attributes. An example from INDUCE/NE is used to illustrate must not clauses with the INDUCE algorithm. An example from CLUSTER/CA is used to illustrate the use of knowledge about relevant attributes in learning.
Bangladesh's Privatization Policy

This paper provides an overview of Bangladesh's Privatization Policy. The present policies can be improved if the terms and conditions of the sale are well-defined and upheld. Discipline in the financial sector is a necessary condition for the success of the privatization program. Without financial sector discipline, privatization may offer avenues for rent-seeking. The tendering process for selling enterprises should be strengthened to attract many potential buyers. The proceeds from privatization could be used for workers' compensation and labor training. Privatized monopolies have to be well regulated. The issues of time framework, program effectiveness, and the role of the capital market in privatization are also discussed. Privatization policy must be accompanied by other policy measures to ensure that the buyer profits from productive endeavors because privatization is not an end itself. (JEL L330, L980, H800)
A novel co-infection model with Toxoplasma and Chlamydia trachomatis highlights the importance of host cell manipulation for nutrient scavenging.

Toxoplasmaand Chlamydia trachomatis are obligate intracellular pathogens that have evolved analogous strategies to replicate within mammalian cells. Both pathogens are known to extensively remodel the cytoskeleton, and to recruit endocytic and exocytic organelles to their respective vacuoles. However, how important these activities are for infectivity by either pathogen remains elusive. Here, we have developed a novel co-infection system to gain insights into the developmental cycles of Toxoplasma and C. trachomatis by infecting human cells with both pathogens, and examining their respective ability to replicate and scavenge nutrients. We hypothesize that the common strategies used by Toxoplasma and Chlamydia to achieve development results in direct competition of the two pathogens for the same pool of nutrients. We show that a single human cell can harbor Chlamydia and Toxoplasma. In co-infected cells, Toxoplasma is able to divert the content of host organelles, such as cholesterol. Consequently, the infectious cycle of Toxoplasma progresses unimpeded. In contrast, Chlamydia’s ability to scavenge selected nutrients is diminished, and the bacterium shifts to a stress-induced persistent growth. Parasite killing engenders an ordered return to normal chlamydial development. We demonstrate that C. trachomatis enters a stress-induced persistence phenotype as a direct result from being barred from its normal nutrient supplies as addition of excess nutrients, e.g., amino acids, leads to substantial recovery of Chlamydia growth and infectivity. Co-infection of C. trachomatis with slow growing strains of Toxoplasma or a mutant impaired in nutrient acquisition does not restrict chlamydial development. Conversely, Toxoplasma growth is halted in cells infected with the highly virulent Chlamydia psittaci. This study illustrates the key role that cellular remodeling plays in the exploitation of host intracellular resources by Toxoplasma and Chlamydia. It further highlights the delicate balance between success and failure of infection by intracellular pathogens in a co-infection system at the cellular level.
Plasma corticoids in the respiratory distress syndrome and in normal infants.

Serial plasma samples for corticoid determination were obtained during the neonatal period in 16 infants with RDS (eight of whom died) and 44 healthy babies. The median corticoid level in the eight infants with fatal RDS was considerably higher than that of patients with RDS who survived, or the normal babies. The median corticoid level in the surviving RDS infants was statistically greater than that of the normal controls, but the actual difference was only 1.9 µg/100 ml. Simultaneous pH, Pco2, Po2,, HCO3 and corticoid measurements were obtained serially in five patients with fatal RDS. However, the correlation between plasma corticoids and the acid-base determination was poor in all but one infant. It is concluded that infants are able to respond to severe physical stress in the neonatal period with an appropriate rise in plasma corticoid concentration, but lesser degrees of illness may cause only minimal changes in corticoid levels.
The effects of amino acid substitution at position E7 (residue 64) on the kinetics of ligand binding to sperm whale myoglobin.

Association and dissociation rate constants were measured for O2, CO, and alkyl isocyanide binding to a set of genetically engineered sperm whale myoglobins with site-specific mutations at residue 64 (the E7 helical position). Native His was replaced by Gly, Val, Leu, Met, Phe, Gln, Arg, and Asp using the synthetic gene and expression system developed by Springer and Sligar (Springer, B. A., and Sligar, S. G. (1987) Proc. Natl. Acad. Sci. U.S.A. 84, 8961-8965). The His64----Gly substitution produced a sterically unhindered myoglobin that exhibited ligand binding parameters similar to those of chelated protoheme suspended in soap micelles. The order of the association rate constants for isocyanide binding to the mutant myoglobins was Gly64 (approximately 10(7) M-1 s-1) much greater than Val64 approximately Leu64 (approximately 10(6) M-1 s-1) greater than Met64 greater than Phe64 approximately His64 approximately Gln64 (10(5)-10(3) M-1 s-1) and indicates that the barrier to isocyanide entry into the distal pocket is primarily steric in nature. The bimolecular rates of methyl, ethyl, n-propyl, and n-butyl isocyanide binding to the His64----Arg and His64----Asp mutants were abnormally high (1-5 x 10(6) M-1 s-1), suggesting that Arg64 and Asp64 adopt conformations with the charged side chains pointing out toward the solvent creating a less hindered pathway for ligand binding. In contrast to the isocyanide data, the association rate constants for O2 and CO binding exhibited little dependence on the size of the E7 side chain. The values for all the mutants except His64----Gln approached or were larger than those for chelated model heme (i.e. approximately 1 x 10(8) M-1 s-1 for O2 and approximately 1 x 10(7) M-1 s-1 for CO), whereas the corresponding rate parameters for myoglobin containing either Gln64 or His64 were 5- to 10-fold smaller. This result suggests that a major kinetic barrier for O2 and CO binding to native myoglobin may involve disruption of polar interactions between His64 and water molecules found in the distal pocket of deoxymyoglobin. Finally, the rate and equilibrium parameters for O2 and CO binding to the His64----Gln, His64----Val, and His64----Leu mutants were compared to those reported previously for Asian elephant myoglobin (Gln-E7), Aplysia limacina myoglobin (Val-E7), and monomeric Hb II from Glycera dibranchiata (Leu-E7).
Uterine arcuate artery Doppler and decidual microvascular pathology in pregnancies complicated by type I diabetes mellitus.

The objective was to correlate Doppler indices from the uterine arcuate arteries with an analysis of the decidual vascular histology in patients with type I diabetes. Pulsed wave Doppler was used to sample the uterine arcuate artery system beneath the placenta within 8 days of delivery in 47 patients with type I diabetes mellitus. A placental pathologist, without knowledge of either clinical outcome or Doppler information, classified the histological appearance of the decidual arteries as normal, type A (hyalinization, mural thickening), or type B (fibrinoid necrosis, atherosis, thrombosis). Patients were then grouped according to the histology of the decidual arteries. An analysis of variance (ANOVA) of the systolic/diastolic (S/D) ratios (log. S/D) showed significant variation (p < 0.025). A multiple range comparison test showed that patients with normal or only mildly abnormal (type A) vessels had similar values, whereas those with severe vasculopathy (type B) had significantly higher S/D ratios (p < 0.05). The study confirmed a relationship between arcuate artery Doppler indices and downstream decidual vascular pathology. Copyright © 1996 International Society of Ultrasound in Obstetrics and Gynecology