cssi/SciSciGPT-SciSciNet huggingface dataset:
Progressive glomerular injury after limited renal infarction in the rat

Wistar Munich rats subjected to partial renal ablation were compared with intact rats. Group 1 rats were subjected to bilateral segmental infarction of 40% of their total renal mass. Group 2 rats underwent uninephrectomy. Group 3 rats underwent sham operation. Micropuncture and morphological studies were performed in each group at 28 wk after operation. In group 1, glomerular capillary pressure was elevated by 7 mmHg and systemic blood pressure was elevated by 31 mmHg despite reduction of nephron number by only 40% and reduction of glomerular filtration rate (GFR) by only 10%. Progressive albuminuria and segmental glomerular sclerosis were associated with elevation of glomerular capillary pressure in this group. In group 2, single-nephron glomerular filtration rate (SNGFR) was higher than in group 1, but systemic and glomerular capillary pressure remained normal. Group 2 rats developed markedly less albuminuria and glomerular sclerosis than group 1 rats despite more pronounced remnant nephron hyperfiltration. These studies support the view that glomerular hypertension is the major hemodynamic derangement contributing to remnant glomerular injury and show that capillary hypertension can initiate remnant glomerular injury even when the majority of the renal mass remains intact.
Deflation and Reflation: The Pre-WW I Impact on NYSE Trading Volumes and Seat Prices

The study analyzes a unique time period of sustained deflation from 1867 to 1896, followed by sustained reflation after 1896. We use these periods to test two hypotheses concerning the impact on NYSE trading volumes and seat prices. The first is the “liquidity-trading” hypothesis, which hypothesizes that liquidity trading, a component of total trading volume, is positively correlated with interest rates. The second is the price-volume relationship, which hypothesizes a positive relationship between stock prices returns and changes in trading volume. These hypotheses suggest that NYSE trading volume should fall (rise) with falling (rising) stock prices and interest rates. We find strong support for both hypotheses, and additionally show that the impact of stock market prices on trading volumes is highly asymmetrical. As well, the study argues and finds evidence that the high level of systematic risk found in the pricing of NYSE seats is another reflection of the price-volume relationship. Therefore, the study finds strong evidence of a link between deflation, reflation and market liquidity as reflected in trading volumes and the pricing of NYSE seats.
The Structure and Function of Centriolar Satellites and Pericentriolar Processes in Cnidarian Sperm

During spermiogenesis cnidarian sperm centrioles associate with a number of accessory structures including microtubular nucleating satellites and pericentriolar processes. These centriolar specializations are particularly well developed in cnidarian sperm and appear to be highly involved in sperm development and function.
Stratified polymorphism

The author considers a spectrum of predicative type abstraction disciplines based on type quantification with stratified levels. These lie in the vast middle ground between parametric abstraction and full impredicative abstraction. Stratified polymorphism has an attractive, unproblematic semantics, and has the potential of offering new approaches to type inference, without sacrificing useful expressive power. He shows that the functions representable in the finitely stratified lambda -calculus are precisely the superelementary functions, i.e., E/sub 4/ in A. Grzegorczyk's (Rozprawy Mate. IV, Warsaw, 1953) subrecursive hierarchy. He also defines methods of transfinite stratification and shows that stratification up to omega /sup omega / has a simple finitary representation, making it a potentially useful concept in programming language design. The author proves that the functions represented by stratified polymorphism up to omega /sup omega / are precisely the primitive recursive functions. He points out that these results imply that the equality problem for finitely stratified lambda -calculus is not superelementary, and that the equality problem for the calculus stratified up to omega /sup omega / is not primitive recursive. >
Racial disparities in treatment of high-grade endometrial cancer in the Medicare population.

OBJECTIVE To examine the patterns of care and survival for African American and white women with high-grade endometrial cancer. METHODS The linked Surveillance, Epidemiology, and End Results and Medicare databases were queried to identify patients diagnosed with grade 3 endometrioid endometrial adenocarcinoma, uterine carcinosarcoma, uterine clear cell carcinoma, and uterine serous carcinoma between 1992 and 2009. The effect of treatment modality on survival was analyzed using the Kaplan-Meier method. Factors predictive of outcome were compared using the Cox proportional hazards model. RESULTS A total of 9,042 patients met study eligibility criteria. African Americans had definitive surgery (76.8% compared with 88.7%; P<.001) less frequently. There was no difference in the rate of adjuvant treatment between the groups. In the crude models for both all-cause mortality and cancer-specific mortality, African American women had an increased overall and disease-specific hazard of death compared with white women. The overall hazard ratio for African American women was 1.6 (95% confidence interval [CI] 1.5-1.7), and the disease-specific hazard ratio was 1.5 (95% CI 1.3-1.6). Over the entire study period, after adjusting for stage, age, period of diagnosis, registry region, urban compared with rural setting, marital status, treatment, surgery, socioeconomic status, and comorbidities, there was no association between race and lower disease-specific survival (hazard ratio 1.1, 95% CI 1-1.2; P=.06). CONCLUSION African American women had lower cancer-specific and all-cause survival compared with white women. Controlling for treatment, sociodemographics, comorbidities, and histopathologic variables eliminated the difference between African American and white women in the disease-specific analysis.
Confirmed Identification of Biotransformed Drugs of Abuse in Urine

A procedure that has been developed during the past 6 years at the Office of Chief Medical Examiner in New York City for rapid routine identification of drugs of abuse in urine is described. The urine is extracted at acidic, strongly basic, and weakly basic pH; the last, pH 8.5, fraction is hydrolyzed to increase extractable morphine and codeine. The residues are subjected to thin-layer chromatography and suspected spots scraped from the plates and confirmed by microcrystal examination or spectrofluorometry. Amphetamines, quinine, methadone, meperidine, propoxyphene, pentazocine, cocaine, and phenothiazine are present in the strongly basic extract. The acidic drugs, in particular barbiturates and glutethimide, are confirmed by gas–liquid chromatography. This procedure has proved effective for the routine analysis of more than 300 urine specimens daily for court purposes as well as for a variety of drug abuse identification, treatment, and follow-up programs. A rapid sensitive microchromatographic method for detection of marijuana components from teeth and fingers is also described.
CONGENITAL DEFECTS OF THE LONG BONES OF THE LOWER LIMB

1. On the evidence of this series of cases I would suggest that the congenital defects of long bones have no connection at all with outside pressure, but are due solely to interference with growth in the limb buds during the first few weeks of foetal life. 2. Deformities associated with defects of the fibula are usually not so severe as in the case of femur or tibia and it is generally possible to effect improvement by operative and mechanical means. 3. Deformities associated with absence or defect of the tibia are generally very severe, and usually amputation alone is possible. 4. Associated with absence of the tibia are many serious alterations in the muscles, but chiefly such as would be expected under such conditions. There is, however, a strong tendency to persistence and often hypertrophy of a muscle which arises from the fibula and inserts into the same bone. This may be the vestigial tibio-fibular muscle or it may be a very abnormal tibialis posticus. The latter possibility is strengthened by the absence of the tendon of that muscle in the sole. 5. Defects of the femur are usually associated with a normal, or nearly normal, lower segment, and in these cases operation devised to equalize the length of the two femora is well worth consideration.
Genomic Instability in Human Premature Aging

A number of premature aging disorders have been described in humans. In patients with these disorders, aging-like symptoms and age-associated diseases appear much earlier than in the average normal individual; thus, the premature aging disorders are useful models for the study of the aging process (Figure 1). Werner syndrome (WS) is the most characterized premature aging disorder. Patients with WS have a large number of signs and symptoms of normal aging at a younger age than normal individuals. However, not all symptoms of WS resemble the normal aging process, and WS is best described as a segmental progeroid disorder. The premature aging disorders include the DNA repair defective disease, xeroderma pigmentosum (XP), which includes seven complementation groups (separate genetic disorders). In this condition, the deficiency of the DNA repair pathway, nucleotide excision, leads to a severely increased incidence of cancer. In Cockayne syndrome, there is also a DNA repair defect, and in addition to the features of premature aging, these individuals have severe neurological deficits. Rothmund-Thomson disease, Hutchinson-Guilford and progeria are other examples of this category of disorders. All of these diseases are very rare conditions in the general population. In several cases, the disorders are associated with a mutation in a single gene, which has by now been identified, cloned and characterized. This means that molecular biochemical experimentation can be done. Complementation assays with transfected mutant cell lines or purified proteins added to extracts from mutant cell lines can be used to study the basis of molecular genetic defects (Figure 1).
MAOA Influences the Trajectory of Attentional Development.

Attention is vital to success in all aspects of life (Erickson, Thiessen, Godwin, Dickerson, & Fisher, 2015; Meck & Benson, 2002), hence it is important to identify biomarkers of later attentional problems early enough to intervene. Our objective was to determine if any of 11 genes (APOE, BDNF, HTR4, CHRNA4, COMT, DRD4, IGF2, MAOA, SLC5A7, SLC6A3, and SNAP25) predicted the trajectory of attentional development within the same group of children between infancy and childhood. We recruited followup participants from children who participated as infants in visual attention studies and used a similar task at both time points. Using multilevel modeling, we associated changes in the participant’s position in the distribution of scores in infancy to his/her position in childhood with genetic markers on each of 11 genes. While all 11 genes predicted reaction time (RT) residual scores, only MAOA had a significant interaction including time point. We conclude that the MAOA SNP rs1137070 is useful in predicting which girls are likely to develop slower RTs on an attention task between infancy and childhood. This early identification is likely to be helpful in early intervention.
What drives continuous improvement project success in healthcare

Purpose The purpose of this paper is to present findings from a study of factors that affect continuous improvement (CI) project success in hospitals. Design/methodology/approach Quantitative regression analysis was performed on Likert scale survey responses. Qualitative thematic analysis was performed on open-ended survey responses and written reports on CI projects. Findings The paper identifies managerial and employee factors that affect project success. These factors include managerial support, communication, and affective commitment. Affective commitment is the extent to which employees perceive the change as being needed or necessary. Practical implications The results highlight how managerial decisions, approaches to communication - including communication before, during and after CI projects affect project success. The results also show that success depends on the way employees perceive proposed changes. This suggests the need for a more individualized approach to CI, lean, and broader change initiatives. Originality/value This research is the first to fuse project success and sustainability theory to CI projects, beyond Kaizen events, in healthcare environments. The research is particularly important at a time when healthcare organizations are required to make rapid changes with limited resources as they work toward outcome-based assessment and reimbursement rules.
Effect of Bacterial Biofilm on the Osteogenic Differentiation of Stem Cells of Apical Papilla.

Abstract Introduction Although clinical success in regenerative endodontics is substantially high, histological success is limited to finding bone/cementum-like tissue instead of dentin within the canal space. The aims of this study were to investigate (1) the effect of bacterial biofilm on osteogenic gene expression in stem cells of the apical papilla (SCAP) and (2) the effect of bacterial antigens on the functional differentiation of SCAP into a mineralizing phenotype. Methods Using an ex vivo organotypic root canal model and an American Association of Endontists-recommended regenerative endodontic procedures, we evaluated SCAP differentiation in the presence and absence of an Enterococcus faecalis biofilm. Gene expression analysis for dentinogenic and osteoblastic markers was performed with real-time polymerase chain reaction. The effect of E. faecalis antigens on SCAP differentiation into mineralizing cells in vitro was evaluated with 2 functional assays: Alizarin Red and alkaline phosphatase activity assays. Results After regenerative endodontic procedures, residual bacteria continued to sustain within the root canal system. SCAP in the presence of E. faecalis biofilm significantly downregulated dentinogenic genes such as dentin sialophosphoprotein and upregulated osteoblastic genes such as bone sialoprotein, osteocalcin, distal-less homeobox 5, and runt-related transcription factor 2. E. faecalis antigens significantly inhibited SCAP differentiation into a mineralizing phenotype when alizarin red staining and alkaline phosphatase assays were used in vitro. Conclusions Current disinfection protocols were ineffective in eliminating bacteria from root tips and the levels of the residual bacterial biofilm, and its byproducts, were able to significantly alter osteogenic-differentiation of SCAP.
International Review of Precipitants to Patient Assaults on Staff, 2013–2017

In studying psychiatric patient assaults, assessing the person x event x environment interaction is important in enhancing safety and ensuring quality care. Precipitants to patient assaults have traditionally received less attention than the patient characteristics of such assaults. Reviews of inpatient precipitants from 1960 to 2012 noted acute psychosis, denial of services, and substance abuse as commonly occurring precipitants. The present study reviewed the literature on precipitants from 2013 to 2017. A variety of precipitants, including acute psychosis, substance abuse, and denial of services were observed. The literature in this review broke new ground in subjects, methodologies, and precipitants. These new findings and a detailed methodological inquiry are presented.
The Bush Administration and Latin America: The Pragmatic Style and the Regionalist Option

After 8 Years of United States unilateralism in Central America and ideological confrontation on Capitol Hill, by 1989, newly-elected leaders in Latin America and Democrats in Congress yearned for a US president who would listen to their concerns, not just lecture them on the contras. George Bush's pragmatic style was therefore a welcome departure from the ideological intensity of his predecessor. With the democratic and pragmatic leaders of Latin America, Bush grappled with debt, democratic transitions, and drug trafficking, and together they sought new ways to relate the Hemisphere to a rapidly changing world.
The Clinton Administration's Development and Implementation of Rendition (1993–2001)

A firestorm of protest greeted revelations of the rendition program when it was made public during the George W. Bush administration. The operational and political basis for the rendition initiativ...
Elongator and codon bias regulate protein levels in mammalian peripheral neurons.

Familial dysautonomia (FD) results from mutation in IKBKAP/ELP1, a gene encoding the scaffolding protein for the Elongator complex. This highly conserved complex is required for the translation of codon-biased genes in lower organisms. Here we investigate whether Elongator serves a similar function in mammalian peripheral neurons, the population devastated in FD. Using codon-biased eGFP sensors, and multiplexing of codon usage with transcriptome and proteome analyses of over 6,000 genes, we identify two categories of genes, as well as specific gene identities that depend on Elongator for normal expression. Moreover, we show that multiple genes in the DNA damage repair pathway are codon-biased, and that with Elongator loss, their misregulation is correlated with elevated levels of DNA damage. These findings link Elongator’s function in the translation of codon-biased genes with both the developmental and neurodegenerative phenotypes of FD, and also clarify the increased risk of cancer associated with the disease. Familial dysautonomia is linked to mutations in IKBKAP, a scaffolding protein for the Elongator complex, which regulates codon-biased gene translation in yeast. Here the authors show in mammalian neurons that IKBKAP loss alters expression of codon-biased genes, including some involved in DNA damage.
Dislocation dynamics simulations of precipitation-strengthened Ni- and Co-based superalloys

Abstract Two-dimensional dislocation dynamics (DD) simulations are carried out to simulate the increase in yield stress of nickel- and cobalt-based superalloys by order-strengthened γ’(L12)-precipitates, under conditions where precipitates are sheared and/or looped by single and super-dislocations. Parametric studies are performed for precipitate volume fractions between 5 and 70% and radii between 1 and 100 nm, resulting in yield stress increments due to a mixture of precipitate bypassing and shearing by single and super-dislocations of edge or screw character. DD yield stresses are compared to a variety of analytical models for strengthening by ordered precipitates showing that the closed-form solutions do not agree with DD predictions over all regimes of precipitate sizes and volume fractions. The DD yield stresses, converted to hardness values, are also compared to experimental hardnesses from archival literature on binary Ni-13Al (at. %) as well as Ni-10Al-8Cr(-2 W) (at.%) alloys aged at various temperatures and times, for which γ’(L12)-precipitate radii and volume fractions had been measured via atom-probe tomography and scanning electron microscopy. DD predictions are within 5–10% of experimental hardnesses in underaged alloys, but they typically overestimate hardness for peak and overaged samples. Finally, DD is used to predict the hardnesses for a γ’(L12)-strengthened Co-8.8Al-7.3 W (at. %) superalloy for 50–130 nm average precipitate radii within 10% of experimental values.
A Bias-aware EnKF Estimator for Aerodynamic Flows

Ensemble methods can integrate measurement data and CFD-based models to estimate the state of fluid systems in a robust and cost-efficient way. However, discretization errors can render numerical solutions a biased representation of reality. Left unaccounted for, biased forecast and observation models can lead to poor estimator performance. In this work, we propose a low-rank representation for the bias whose dynamics is represented by a colorednoise process. System state and bias parameters are simultaneously corrected on-line with the Ensemble Kalman Filter (EnKF) algorithm. The proposed methodology is demonstrated to achieve a 70% error reduction for the problem of estimating the state of the two-dimensional low-Re flow past a flat plate at high angle of attack using an ensemble of coarse-mesh simulations and pressure measurements at the surface of the body, compared to a bias-blind estimator. Strategies to determine the bias statistics and to deal with nonlinear observation functions in the context of ensemble methods are discussed.
Phase transformations in Ti-Nb-Ta and Ti-Nb-Ta-Zr alloys

Phase transformations in solution treated and quenched Ti-(13-26) Nb-(22-38) Ta (wt.%) and Ti-(13-35.5) Nb-(5-22) Ta-(4-7.2) Zr alloys have been studied. It has been observed that phase transformations in these alloys are sensitive to both composition and cooling rate. In ternary alloys, water and oil quenching resulted in the formation of orthorhombic martensite (α′′) in a retained β + ωathermal matrix, whereas slower cooling showed evidence of fine α and ωisothermal formation within the β matrix. Increase of Nb + Ta content decreases the volume percentage of martensite. Moreover, addition of Zr stabilized the β phase, lowered the martensite start temperature and suppressed ω formation. Finally, dynamic moduli of air cooled quaternary alloys showed that the modulus was sensitive to the composition, a minima at Nb/Ta ratio of 12.0 and 5 at% Zr being observed, this minimum in dynamic modulus being consistent with ω phase suppression.
Gender, Education, and Occupation: How Founder Experiences Influence Firm Outcomes

This study analyzes the gender, education, and occupational backgrounds of high-technology firm founders and the outcomes of their firms by asking three main questions: 1) What are the backgrounds ...
Moderation of the Association Between Chronic Medical Conditions and Functional Limitations Over Time by Physical Activity: Effects of Age

BACKGROUND: Age-related accumulation of chronic medical conditions increases disability in older adults. Physical activity potently combats chronic conditions and disability. However, it is unclear whether activity maintenance alleviates the effects of chronic conditions on disability and if this buffering effect differs with age. This study examined whether long-term physical activity can forestall functional limitations in the face of accumulating chronic conditions among middle-aged and older adults. METHODS: Participants (n = 2,119; 54.7% female) were from the Survey of Midlife Development in the United States. Self-reported physical activity, number of chronic conditions, and functional limitations were obtained across 18-20 years. Functional limitations were regressed against the change in chronic conditions, physical activity, and their interaction over time in a multilevel model of change. Baseline age was added as an additional moderator. RESULTS: Faster accumulation of chronic conditions [B(SE) = 2.08(0.32), p < .001] and steeper declines in activity [B(SE) = -2.29(0.41), p < .001] were associated with greater increases in functional limitations over time. Among those with faster-than-average increases in conditions, those who maintained activity had a slower progression of functional limitations, compared to those whose activity declined more rapidly [B(SE) = -11.18(3.96), p = .005]. Baseline age moderated the buffering effect of activity maintenance; older adults were protected against functional limitations only when conditions accumulated slowly [B(SE) = 0.23(0.08), p = .005]. CONCLUSION: This study provides evidence for an age-dependent buffering effect of activity maintenance on the longitudinal relationship between chronic conditions and functional limitations. Intervention strategies using physical activity to forestall disability should target midlife adults and consider the rate of condition accumulation.
Adenosine deaminase, terminal deoxynucleotidyl transferase (TdT), and cell surface markers in childhood acute leukemia

The purpose of this report is to compare measurements of enzymatic activities and cell surface markers as methods of distinguishing subtypes of lymphoid leukemias of childhood. Twenty-six children ages 2-15 yr were studied. Terminal deoxynucleotidyl transferase (TdT) activity was high in blasts from all 20 children with either null or T cell acute lymphoblastic leukemia. The activity of adenosine deaminase per cell was higher (P less than 0.005) and that of TdT lower (p less than 0.05) in T than in null cell lymphoblasts, although there was some overlap in values. Blasts from 3 children with acute lymphoid leukemia were positive for surface-associated immunoglobulins. The neoplastic lymphoid cells from these children differed from T and null cell leukemic lymphoblasts by having very low levels of TdT and adenosine deaminase activity. Measurements of adenosine deaminase and TdT may complement measurements of cell surface markers and distinguish biochemical subtypes of acute lymphoid leukemia.
Variation in Hospital-Based Rehabilitation Services Among Patients With Ischemic Stroke in the United States.

Background Little is known about variation in use of rehabilitation services provided in acute care hospitals for people who have had a stroke. Objective The objective was to examine patient and hospital sources of variation in acute care rehabilitation services provided for stroke. Design This was a retrospective, cohort design. Methods The sample consisted of Medicare fee-for-service beneficiaries with ischemic stroke admitted to acute care hospitals in 2010. Medicare claims data were linked to the Provider of Services file to gather information on hospital characteristics and the American Community Survey for sociodemographic data. Chi-square tests compared patient and hospital characteristics stratified by any rehabilitation use. We used multilevel, multivariable random effect models to identify patient and hospital characteristics associated with the likelihood of receiving any rehabilitation and with the amount of therapy received in minutes. Results Among 104,295 patients, 85.2% received rehabilitation (61.5% both physical therapy and occupational therapy; 22.0% physical therapy only; and 1.7% occupational therapy only). Patients received 123 therapy minutes on average (median [SD] = 90.0 [99.2] minutes) during an average length of stay of 4.8 [3.5] days. In multivariable analyses, male sex, dual enrollment in Medicare and Medicaid, prior hospitalization, ICU stay, and feeding tube were associated with lower odds of receiving any rehabilitation services. These same variables were generally associated with fewer minutes of therapy. Patients treated by tissue plasminogen activator, in limited-teaching and nonteaching hospitals, and in hospitals with inpatient rehabilitation units, were more likely to receive more therapy minutes. Limitation The findings are limited to patients with ischemic stroke. Conclusion Only 61% of patients with ischemic stroke received both physical therapy and occupational therapy services in the acute setting. We identified considerable variation in the use of rehabilitation services in the acute care setting following a stroke.
A review of wearable heart rate sensors in research

This paper explores types of wearable heart rate sensors and their reliability. An overview of data collection, brands, and recent findings are included. Wearable sensors, especially those on the wrist in activity trackers and smartwatches are a non-invasive way to track heart rate and receive other measurements of health and activity. Heart rate is based on the amount of activity someone does, but can also be linked to emotions including stress and the external environment. Wearable heart rate sensors are proving increasing accuracy and continue to be prominent in the consumer and research environment.
Insulin-like growth factor receptor signaling pathways and resistance to tarceva (erlotinib) in non-small cell lung cancer cells

1697 Purpose: The Epidermal Growth Factor Receptor (EGFR) is an important target for anticancer therapy. However, not all NSCLC cells respond to treatment with EGFR inhibitors, and the mechanism of resistance to EGFR inhibitors is poorly understood. Therefore, we studied the molecular mechanism that interferes with the activities of tarceva (Erlotinib), a selective EGFR tyrosin kinase inhibitor that has shown antitumor activities in patients with NSCLC as second / third line therapy. Methods: The effects of tarceva and its combination with inhibitors of IGF-1R signaling components on proliferation and apoptosis were assessed in a subset of NSCLC cell lines in vitro and in vivo, by using the MTT assay, anchorage-independent growth assay in soft agar, clonogenic survival assay, a flow cytometry-based TUNEL assay, western blot analyses, and a NSCLC xenograft tumor model. Results: Tarceva treatment exhibited an activation of IGF-IR signaling components, such as IGF-1R, Akt, and MAPK, in the resistant NSCLC cell lines, but not in the sensitive cell lines. Dual targeting of EGFR and IGF-1R signaling pathways through combined treatment of tarceva and inhibitors of upstream and downstream of IGF-1R signaling components showed enhanced antiproliferative activities in NSCLC cells in vitro and in vivo. Conclusion: The combination of tarceva and inhibitors of IGF-1R signaling components induced enhanced antiproliferative activities in NSCLC cells via increased apoptosis in vitro and in vivo. These results suggest that activation of IGF-1R signaling pathway confer resistance to tarceva treatment in NSCLC cells, and that simultaneous treatment with inhibitors of IGF-1R and EGFR signaling pathways might be an effective therapeutic strategy against NSCLC. Supported in part by the DAMD17-01-1-0689 from the Department of Defense (to W. K. Hong); W81XWH-04-1-0142-01-VITAL from the Department of Defense (to W. K. Hong); National Institutes of Health Grants R01 CA109520-01 (to H-Y. Lee) and CA100816-01A1 (to H-Y. Lee), National American Cancer Society, RSG-04-082-01-TBE 01(to H-Y. Lee)
Inhibitor of myogenic differentiation family isoform a, a new positive regulator of fibronectin production by glomerular mesangial cells.

Overproduction of extracellular matrix proteins, including fibronectin by mesangial cells (MCs), contributes to diabetic nephropathy. Inhibitor of myogenic differentiation family isoform a (I-mfa) ...
Cardiovascular safety outcomes of once-weekly GLP-1 receptor agonists in people with type 2 diabetes.

WHAT IS KNOWN AND OBJECTIVE People with type 2 diabetes (T2D) are at increased risk of cardiovascular disease (CVD), which in turn is associated with increased morbidity and mortality. The impact of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) on cardiovascular (CV) outcomes has been investigated in CV outcomes trials (CVOTs). This review aims to help pharmacists and other healthcare professionals (HCPs) gain a better understanding of such CVOTs in T2D with a primary focus on the once-weekly (QW) GLP-1 RAs. METHODS This narrative review mainly focuses on the evaluation of the similarities and differences in the design and results of CVOTs involving currently approved and marketed QW GLP-1 RAs-semaglutide subcutaneous, exenatide extended-release (ER) and dulaglutide. Results from CVOTs of dipeptidyl peptidase-4 inhibitors (DPP4is) and sodium-glucose cotransporter-2 inhibitors (SGLT2is) are also included. RESULTS AND DISCUSSION Three CVOTs of QW GLP-1 RAs were identified for inclusion in this review: SUSTAIN 6 (semaglutide), EXSCEL (exenatide ER) and REWIND (dulaglutide), all of which varied in terms of trial design, patient demographics and other baseline characteristics. Results from these CVOTs demonstrated the CV safety of QW GLP-1 RAs compared with standard of care. Additionally, CV and renal benefits were demonstrated for semaglutide and dulaglutide, but not for exenatide ER. The CV safety of four DPP4is and three SGLT2is was demonstrated. None of the DPP4is had a CV or renal benefit, whereas all three SGLT2is were associated with CV and renal benefits. WHAT IS NEW AND CONCLUSION This article provides an overview of the results from QW GLP-1 RA CVOTs, including the recently published results for dulaglutide, and places them within the broader T2D treatment landscape to help HCPs make informed decisions in daily practice. The QW GLP-1 RAs with benefits reaching beyond glycaemic control can provide a comprehensive treatment option for people with T2D at high risk of CVD, with CVD or chronic kidney disease.
Welches Gesundheitssystem wir uns wünschen

Es ist nicht die Menge an Geld, die wir in unser Gesundheitssystem investieren, die uber unsere Gesundheit entscheidet. Die USA haben weltweit die mit weitem Abstand hochsten Gesundheitsausgaben, dabei ist ihre Lebenserwartung, die seit einigen Jahren sogar rucklaufig ist, im Vergleich nur mittelmasig, zudem gehoren Amerikaner zu den am starksten gestressten und nur masig glucklichen Menschen. Bedeutsame soziale Determinanten von Gesundheit werden vom amerikanischen Gesundheitssystem vollig ignoriert. Regierungen, die die Gesundheit eines Volkes erhalten und steigern wollen, mussen soziookonomische Unterschiede verringern, Armut bekampfen und fur bestmogliche Bildung fur alle sorgen. Ein gutes Gesundheitssystem entwickelt sich von einem primar kurativen zu einem praventiven System.
Impact of Virtual Synchronous Generator (VSG) on Sub Synchronous Control Interaction (SSCI) in DFIG Systems Using Sequence Domain Impedance Method

Wind energy, as a promising renewable and clean energy resource, has caused problems including power quality issues and electromagnetically oscillations such as sub-synchronous resonance. Virtual synchronous generator (VSG) has been proposed as a solution to improve dynamic frequency stability in wind turbines, but its impact on the risk of sub-synchronous resonance has not been investigated so far. This study, for the first time, presented that while VSG control helps tracking the rated frequency in normal operations and reviving the frequency during disturbances in the power grid, it increases the risk of occurrence of SSCI.
The nonorientable $4$–genus for knots with $8$ or $9$ crossings

The nonorientable 4–genus of a knot in the 3–sphere is defined as the smallest first Betti number of any nonorientable surface smoothly and properly embedded in the 4–ball with boundary the given knot. We compute the nonorientable 4–genus for all knots with crossing number 8 or 9. As applications we prove a conjecture of Murakami and Yasuhara and compute the clasp and slicing number of a knot.
Plant response to fungal root endophytes varies by host genotype in the foundation species Spartina alterniflora

Premise Root-associated fungi provide a wide range of functions for their host plants, including nutrient provisioning, pathogen protection, and stress alleviation. In so doing, they can markedly influence host-plant structural and physiological traits, although the degree to which these effects vary within particular plant host species is not well understood. Methods We conducted a 7-month common-garden inoculation experiment to test the potential effects of a marine fungus (Lulwoana sp.) on the phenotypic traits of different genotypes of the host, the salt marsh plant species Spartina alterniflora. Lulwoana belongs to the dark septate endophytes (DSE), a polyphyletic group of fungi that are commonly found colonizing healthy plant roots, though their ecological role remains unclear. Results We documented significant impacts of Lulwoana on S. alterniflora morphology, biomass, and biomass allocation. For most traits in our study, these impacts varied significantly in direction and/or magnitude across S. alterniflora genotypes. Effects that were consistent across genotype were generally negative. Plant response was not predicted by the percentage of roots colonized, consistent with findings that dark septate endophytes do not necessarily influence plant growth responses through direct contact with roots. Conclusions The observed changes in stem height, biomass, and biomass allocation have important effects on plant competitive ability, growth, and fitness, suggesting that plant-fungal interactions have community and ecosystem level effects in salt marshes.
The tissue protective functions of interleukin-22 can be decoupled from pro-inflammatory actions through structure-based design

Summary Interleukin-22 (IL-22) acts on epithelial cells to promote tissue protection and regeneration, but can also elicit pro-inflammatory effects, contributing to disease pathology. Here, we engineered a high-affinity IL-22 super-agonist that enabled the structure determination of the IL-22–IL-22Rα–IL-10Rβ ternary complex to a resolution of 2.6 A. Using structure-based design, we systematically destabilized the IL-22–IL-10Rβ binding interface to create partial agonist analogs that decoupled downstream STAT1 and STAT3 signaling. The extent of STAT bias elicited by a single ligand varied across tissues, ranging from full STAT3-biased agonism to STAT1/3 antagonism, correlating with IL-10Rβ expression levels. In vivo, this tissue-selective signaling drove tissue protection in the pancreas and gastrointestinal tract without inducing local or systemic inflammation, thereby uncoupling these opposing effects of IL-22 signaling. Our findings provide insight into the mechanisms underlying the cytokine pleiotropy and illustrate how differential receptor expression levels and STAT response thresholds can be synthetically exploited to endow pleiotropic cytokines with enhanced functional specificity.
Plasminogen activator receptor assemblies in cell-signaling, innate immunity, and inflammation.

Tissue-type plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA) are serine proteases and major activators of fibrinolysis in mammalian systems. Because fibrinolysis is an ess...
Cosmogenic nuclide exposure age scatter records glacial history and processes in McMurdo Sound, Antarctica

Abstract. The preservation of cosmogenic nuclides that accumulated during periods of prior exposure but were not subsequently removed by erosion or radioactive decay complicates interpretation of exposure, erosion, and burial ages used for a variety of geomorphological applications. In glacial settings, cold-based, non-erosive glacier ice may fail to remove inventories of inherited nuclides in glacially transported material. As a result, individual exposure ages can vary widely across a single landform (e.g., moraine) and exceed the expected or true depositional age. The surface processes that contribute to inheritance remain poorly understood, thus limiting interpretations of cosmogenic nuclide datasets in glacial environments. Here, we present a compilation of new and previously published exposure ages of multiple lithologies in local Last Glacial Maximum (LGM) and older Pleistocene glacial sediments in the McMurdo Sound region of Antarctica. Unlike most Antarctic exposure chronologies, we are able to compare exposure ages of local LGM sediments directly against an independent radiocarbon chronology of fossil algae from the same sedimentary unit that brackets the age of the local LGM between 12.3 and 19.6 ka . Cosmogenic exposure ages vary by lithology, suggesting that bedrock source and surface processes prior to, during, and after glacial entrainment explain scatter. 10Be exposure ages of quartz in granite, sourced from the base of the stratigraphic section in the Transantarctic Mountains, are scattered but young, suggesting that clasts entrained by sub-glacial plucking can generate reasonable apparent exposure ages. 3He exposure ages of pyroxene in Ferrar Dolerite, which crops out above outlet glaciers in the Transantarctic Mountains, are older, which suggests that clasts initially exposed on cliff faces and glacially entrained by rock fall carry inherited nuclides. 3He exposure ages of olivine in basalt from local volcanic bedrock in the McMurdo Sound region contain many excessively old ages but also have a bimodal distribution with peak probabilities that slightly pre-date and post-date the local LGM; this suggests that glacial clasts from local bedrock record local landscape exposure. With the magnitude and geological processes contributing to age scatter in mind, we examine exposure ages of older glacial sediments deposited by the most extensive ice sheet to inundate McMurdo Sound during the Pleistocene. These results underscore how surface processes operating in the Transantarctic Mountains are expressed in the cosmogenic nuclide inventories held in Antarctic glacial sediments.
Linking Physical and Mental Health Summary Scores from the Veterans RAND 12-Item Health Survey (VR-12) to the PROMIS(®) Global Health Scale

Background Global health measures represent an attractive option for researchers and clinicians seeking a brief snapshot of a patient’s overall perspective on his or her health. Because scores on different global health measures are not comparable, comparative effectiveness research (CER) is challenging.
Black boxes and gray spaces: how illegal dwellings find regulatory loopholes

In Honolulu, the building permit process has been likened to a black box, synonymous with regulatory barriers and unbearable delays. In response, homeowners cultivate gray spaces: ambiguous accessory spaces such as "Hobby,” "TV” or "Rumpus Rooms” that are issued permits and then frequently converted illegally into an independent dwelling unit. In essence, these Illegal Accessory Dwellings function as non-permitted second units on land zoned for single-family use. This paper proposes to quantify the number of Illegal Accessory Dwellings in Honolulu, based on the number of residential buildings permits issued for spaces that could be easily converted into a separate rental unit. Using building permit data provides a systematic method to analyze all legally sanctioned building activity, pinpointing only those residential layouts that are highly suspicious for being converted into a separate rental unit. In so doing, this paper makes a key distinction: a structure can be built to code, but its occupancy – how it is used – can still be illegal. From 2005-2012, this paper found that Illegal Accessory Dwellings comprised a low of 30% upto 46% of all new one and two-family dwellings units created. The highest rate of production was in 2008, during the Great Recession. Thus, this paper suggests that Illegal Accessory Dwellings contribute a substantial number of units to the overall housing supply. This paper also raises questions such as – How are these units being counted in the official US Census? Are they counted as separate households or as part of the primary residence? Given the significant number of this type of housing, how Illegal Accessory Dwellings are characterized could potentially shift the landscape of where urban growth is occurring. Research methods include correlational research, GIS mapping and case studies, to explain how homeowners circumvent the rules.
Analysis of lorazepam and its glucoronide metabolite by electron-capture gas—liquid chromatography

Abstract This paper describes a rapid and sensitive method for analysis of lorazepam and its glucuronide metabolite in plasma and urine following therapeutic doses of lorazepam in humans. After addition of the structurally related benzodiazepine derivative, oxazepam, as the internal standard, 1-ml samples of plasma or urine are extracted twice at neutral pH with benzene (containing 1.5% isoamyl alcohol). The combined extracts are evaporated to dryness, reconstituted, and subjected to gas chromatographic analysis using a 3% OV-17 column and an electron-capture detector. Lorazepam glucuronide in urine is similarly analyzed following enzymatic cleavage with Glusulase. The sensitivity limits are 1–3 ng of lorazepam per ml of original sample, and the variability of identical samples is 5% or less. The applicability of the method to pharmacokinetic studies of lorazepam is demonstrated.
Ionospheric Electric Fields from Stratospheric Balloon‐Borne Probes

The balloon-borne, double Langmuir probe technique for measuring vector electric fields in the stratosphere has been used successfully since the late 1960s. The cost effectiveness, flexibility and relatively high time resolution of the technique has resulted in stratospheric electric field measurements being used to address a wide variety of ionospheric and magnetospheric problems. Indeed, the technique continues to hold certain advantages over other measurements for some types of problems and remains an important tool in the 1990s where it is being used by a growing number of groups. Experience gained from a large number of flights, using modern electronics and telemetry is summarized here to describe the technique, provide examples of its use, and to discuss its advantages and limitations.
Oversight mechanisms for clinical research.

Clinical research provides a critical mechanism for the transformation of health care into a cost-effective and evidence-based system. Oversight of clinical research will require development of coherent means of protecting the rights of human subjects without unduly adding bureaucratic hurdles and costs that can hinder the protection intended.
Functional compartmentation of acetaldehyde oxidation in rat liver.

Abstract Perfused rat liver and suspensions of isolated rat liver cells have been used to study the influence of the transaminase inhibitors aminooxyacetate and dl-cycloserine on the rate of acetaldehyde utilization, and the effects of acetaldehyde on the state of reduction of cytosolic and mitochondrial pyridine nucleotides. In the presence of 4-methylpyrazole to inhibit acetaldehyde reduction to ethanol, acetaldehyde removal was constant over the range from 0.1 to 0.4 mm at a rate of approximately 400 µmoles per g dry weight per hour. Between 0.4 and 10 mm acetaldehyde, the rate of acetaldehyde uptake increased by 60% with increasing acetaldehyde concentrations, with a half-maximum increment of uptake being achieved at about 1 mm acetaldehyde. dl-Cycloserine had no effect on acetaldehyde uptake at low concentrations of acetaldehyde but almost completely inhibited the stimulation of uptake observed at high concentrations. Neither dl-cycloserine nor aminooxyacetate had any inhibitory effect on the reduction of mitochondrial pyridine nucleotides induced by acetaldehyde. At high acetaldehyde concentrations (3 to 4 mm) pyruvate stimulated acetaldehyde uptake, but little effect was observed at low acetaldehyde concentrations (0.3 mm). Acetaldehyde uptake was inhibited by fatty acids, β-hydroxybutyrate, and amobarbital, and stimulated by acetoacetate. Oxidation of endogenous fatty acid was diminished by acetaldehyde. These data indicate that oxidation of acetaldehyde by rat liver occurs almost entirely in the mitochondrial compartment when the mean arterial-venous acetaldehyde concentration is below about 0.4 mm. At higher acetaldehyde concentrations, oxidation occurs also in the cytosol, and reducing equivalents generated in the cytosol by a high Km NAD-linked aldehyde dehydrogenase are transported to the mitochondria mainly by the malate-aspartate cycle. It may be concluded that acetaldehyde generated during ethanol metabolism is oxidized to acetate predominantly in the mitochondria, so that only 1 eq of NADH is generated in the cytosol per mole of ethanol oxidized via alcohol dehydrogenase.