bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of a Novel LysR-Type Transcriptional Regulator in Staphylococcus aureus That Is Crucial for Secondary Tissue Colonization during Metastatic Bloodstream Infection
Authors: Groma Michaela , Horst Sarah A. , Das Sudip , Huettel Bruno , Klepsch Maximilian , Rudel Thomas , Medina Eva , Fraunholz Martin
Published: August 2020

Staphylococcus aureus
is an important pathogen that can disseminate via the bloodstream and establish metastatic infections in distant organs. To achieve a better understanding of the bacterial factors facilitating the development of these metastatic infections, we used in this study a
Staphylococcus aureus
transposon mutant library in a murine model of intravenous infection, where bacteria first colonize the liver as the primary infection site and subsequently progress to secondary sites such as the kidney and bones. We identified a novel LysR-type transcriptional regulator (LTTR), which was specifically required by
S. aureus
for efficient colonization of secondary organs. We also determined the transcriptional activation as well as the regulon of LTTR, which suggests that this regulator is involved in the metabolic adaptation of
S. aureus
to the host microenvironment found in secondary infection sites.
Multidimensional Proteome Profiling of Blood-Brain Barrier Perturbation by Group BStreptococcus
Authors: Campeau Anaamika , Mills Robert H. , Blanchette Marie , Bajc Kaja , Malfavon Mario , Munji Roeben N. , Deng Liwen , Hancock Bryan , Patras Kathryn A. , Olson Joshua , Nizet Victor , Daneman Richard , Doran Kelly , Gonzalez David J.
Published: August 2020

Group BStreptococcus(GBS) meningitis remains a major cause of poor health outcomes very early in life. Both the host-pathogen relationship leading to disease and the massive host response to infection contributing to these poor outcomes are orchestrated at the tissue and cell type levels. GBS meningitis is thought to result when bacteria present in the blood circumvent the selectively permeable vascular barriers that feed the brain. Additionally, tissue damage subsequent to bacterial invasion is mediated by inflammation and by immune cells from the periphery crossing the blood-brain barrier. Indeed, the vasculature plays a central role in disease processes occurring during GBS infection of the brain. Here, we employed quantitative proteomic analysis of brain vascular substructures during invasive GBS disease. We used the generated data to map molecular alterations associated with tissue perturbation, finding widespread intracellular dysfunction and punctuating the importance of investigations relegated to tissue type over the whole organ.
Emergency care access to primary care records: an observational study
Authors: Bowden Thomas , Lyell David , Coiera Enrico
Published: August 2020

Objective

To measure lookup rates of externally held primary care records accessed in emergency care and identify patient characteristics, conditions and potential consequences associated with access.

Measures

Rates of primary care record access and re-presentation to the emergency department (ED) within 30 days and hospital admission.

Design

A retrospective observational study of 77 181 ED presentations over 4 years and 9 months, analysing 8184 index presentations in which patients’ primary care records were accessed from the ED. Data were compared with 17 449 randomly selected index control presentations. Analysis included propensity score matching for age and triage categories.

Results

6.3% of overall ED presentations triggered a lookup (rising to 8.3% in year 5); 83.1% of patients were only looked up once and 16.9% of patients looked up on multiple occasions. Lookup patients were on average 25 years older (z=−9.180, p<0.001, r=0.43). Patients with more urgent triage classifications had their records accessed more frequently (z=−36.47, p<0.001, r=0.23). Record access was associated with a significant but negligible increase in hospital admission (χ2(1, n=13 120)=98.385, p<0.001, phi=0.087) and readmission within 30 days (χ2(1, n=13 120)=86.288, p<0.001, phi=0.081).

Discussion

Emergency care clinicians access primary care records more frequently for older patients or those in higher triage categories. Increased levels of inpatient admission and re-presentation within 30 days are likely linked to age and triage categories.

Conclusion

Further studies should focus on the impact of record access on clinical and process outcomes and which record elements have the most utility to shape clinical decisions.
Pseudophakic corneal donor tissue in Descemet membrane endothelial keratoplasty (DMEK): implications for cornea banks and surgeons
Authors: Pilger Daniel , Torun Necip , Maier Anna-Karina B , Schroeter Jan
Published: August 2020

Objective

Increasingly, cornea banks are recovering donor tissue from pseudophakic donors. Little is known about their suitability for Descemet membrane endothelial keratoplasty (DMEK) surgery in terms of endothelial cell density (ECD) and preparation failure.

Methods and Analysis

We explored ECD during donor tissue preparation in 2076 grafts. Preparation failure was analysed in 1028 grafts used in DMEK surgery at our clinic. To monitor ECD and functional results, we matched 86 DMEK patients who received pseudophakic donor grafts with similar recipients of phakic donor grafts and followed them up for 36 months.

Results

At recovery, mean ECD in pseudophakic donor grafts was 2193 cells/mm2(SD 28.7) and 2364 cells/mm2(SD 15.7) in phakic donor grafts (p<0.001). After cultivation, the difference increased as pseudophakic donor grafts lost 14% of ECD while phakic lost only 6% (p<0.001). At transplantation, mean ECD in pseudophakic donor grafts was 2272 cells/mm2(SD 250) and 2370 cells/mm2(SD 204) in phakic donor grafts (p<0.001). After transplantation, the difference in ECD increased as pseudophakic donor grafts lost 27.7% of ECD while phakic donor grafts lost only 13.3% (p<0.001). The risk of preparation failure in pseudophakic donor grafts was higher than in phakic donor grafts (OR 4.75, 95% CI 1.78 to 12.67, p=0.02). Visual acuity increased in both groups similarly.

Conclusions

Pseudophakic donor grafts have a lower ECD, are more prone to endothelial cell loss during recovery and surgery and are associated with a higher risk of preparation failure. Cornea banks and surgeons should consider this in the planning of graft preparation and transplantation.
Incidence of recreational sports-related sudden cardiac arrest in participants over age 12 in a general African population
Authors: Tchanana Gladys M K , Ngantcha Marcus , Yuyun Matthew F , Ajijola Olujimi A , Mbouh Samuel , Tchameni Steve C T , Suliman Ahmed , Bonny Aimé
Published: August 2020

Background

The incidence of sports-related sudden cardiac arrest (SrSCA) in sub-Saharan Africa is unknown.

Objective

To determine the incidence of sudden cardiac arrest (SCA) in non-competitive athletes in an urban population of Cameroon, a country in sub-Saharan Africa.

Methods

Two study populations in Cameroon were used. A 12-month, multisource surveillance system of 86 189 inhabitants over 12 years old recorded all deaths in two administrative districts of Douala City. All fields of sports, emergency medical service, local medical examiners and district hospital mortuaries were surveyed. Two blinded cardiologists used a verbal autopsy protocol to determine the cause of death. SCA was identified for all deaths occurring within 1 hour of onset of symptoms. A cross-sectional study was conducted among 793 persons in Yaoundé City, which is the second study population aimed at determining the proportion of people who are physically active.

Results

The mean age in the cross-sectional study was 27.3±10.7, with more men (56.2%). The cross-sectional study showed that 69.0% (95% CI 65.8 to 72.2) of the population could be considered to have at least 3 hours of physical activity per week. The surveillance found that among 288 all-cause deaths, 27 (9.4%) were due to SCA. One SrSCA was registered in a 35-year-old woman while running. Merging both sources revealed an SrSCA incidence of 1.7 (95% CI 0.2 to 12.0) cases per 100 000 athletes per year.

Conclusion

This pioneer study reports the incidence estimates of SrSCA in a sub-Saharan African general population and should be regarded as a first step to a big problem.
Pilot study: undergraduate sports & exercise medicine conferences: what role do they play?
Authors: Dadrewalla Arshan Jimmy , Pai Hari Venkatesh , Limaye Neil , Shankarghatta Rohan , Roy-Kundu Shammak , Guest Brendan
Published: August 2020

Objectives

Sports & exercise medicine (SEM) is a specialty encompassing the management of medical problems and injuries related to physical activity through means such as exercise advice and prescription. The field of SEM has been recognised in the UK since 2005 yet there is inadequate exposure of SEM in medical curricula. Conferences may be a way to increase exposure where students meet SEM professionals, gaining greater understanding of SEM career pathways. We therefore carried out a pilot study to assess this.

Methods

The King’s College London Sports & Exercise Medicine Society organised a student-led conference consisting of six lectures. Seventy-five delegates were given questionnaires on their views on SEM before and after the conference, assessed using the 5-point Likert scale. Results were analysed using a Wilcoxon-Signed Rank statistical test.

Results

Questionnaire feedback showed 67.4% of delegates (n=46) had received SEM related teaching in their current degree. Results of our statistical analysis showed an increase in SEM career interest (p=0.0359), an increase in understanding of what a career in SEM involves (p=0.0009) and an increase in delegate’s understanding of what is required to pursue a career in SEM (p=0.0004) after our conference.

Conclusion

The study showed issues regarding poor exposure to SEM in medical curricula and highlighted the value of student conferences. Students felt they learnt more about the roles within the SEM specialty, aiding future career progression. Thus, we suggest that student-led conferences are a good platform to bridge this gap while medical schools introduce more SEM into their curricula.
Daily self-reported and automatically generated smartphone-based sleep measurements in patients with newly diagnosed bipolar disorder, unaffected first-degree relatives and healthy control individuals
Authors: Stanislaus Sharleny , Vinberg Maj , Melbye Sigurd , Frost Mads , Busk Jonas , Bardram Jakob Eyvind , Faurholt-Jepsen Maria , Kessing Lars Vedel
Published: August 2020

Objectives

(1) To investigate daily smartphone-based self-reported and automatically generated sleep measurements, respectively, against validated rating scales; (2) to investigate if daily smartphone-based self-reported sleep measurements reflected automatically generated sleep measurements and (3) to investigate the differences in smartphone-based sleep measurements between patients with bipolar disorder (BD), unaffected first-degree relatives (UR) and healthy control individuals (HC).

Methods

We included 203 patients with BD, 54 UR and 109 HC in this study. To investigate whether smartphone-based sleep calculated from self-reported bedtime, wake-up time and screen on/off time reflected validated rating scales, we used the Pittsburgh Sleep Quality Index (PSQI) and sleep items on the Hamilton Depression Rating Scale 17-item (HAMD-17) and the Young Mania Rating Scale (YMRS).

Findings

(1) Self-reported smartphone-based sleep was associated with the PSQI and sleep items of the HAMD and the YMRS. (2) Automatically generated smartphone-based sleep measurements were associated with daily self-reports of hours slept between 12:00 midnight and 06:00. (3) According to smartphone-based sleep, patients with BD slept less between 12:00 midnight and 06:00, with more interruption and daily variability compared with HC. However, differences in automatically generated smartphone-based sleep were not statistically significant.

Conclusion

Smartphone-based data may represent measurements of sleep patterns that discriminate between patients with BD and HC and potentially between UR and HC.

Clinical implication

Detecting sleep disturbances and daily variability in sleep duration using smartphones may be helpful for both patients and clinicians for monitoring illness activity.

Trial registration number

clinicaltrials.gov (NCT02888262).
BokSmart rugby safety education courses are associated with improvements in behavioural determinants in attending coaches and referees: presurvey–postsurvey study
Authors: Brown James Craig , Hendricks Sharief , Lambert Michael Ian , van Mechelen Willem , Verhagen Evert
Published: August 2020

Background/aim

BokSmart is a nationwide injury prevention programme that aims to reduce players’ injury risk mainly through education of coaches and referees in mandatory biennial education courses. These courses are held throughout each rugby season. The objective of this cross-sectional study was to assess whether these courses were associated with improvements in attendees’ behavioural determinants.

Methods

Coaches and referees completed a questionnaire based on the theory of planned behaviour, immediately before and after their 2012 BokSmart courses. Twelve behavioural determinants were assessed on a five-point Likert scale and open-ended questions. A meaningful change was defined as an improvement of ≥1 unit score supported by null hypothesis testing. Odds of improving by ≥1 unit score (compared with not improving) were assessed in attendees using multivariate logistic regression.

Results

In total, 390 coaches and 74 referees completed both questionnaires. ‘Before’ scores were high for most outcomes, except for knowledge. Although there was a significant (p<0.001) improvement in all ‘after’ course scores, the only meaningful change (=1 unit) was in knowledge of scrum techniques/rules.

Conclusion

Although the only meaningful improvement in 2012 BokSmart course attendees was in one outcome, it should be noted that before-course scores were already high, reducing the questionnaire’s ability to assess change because of a ceiling effect. Nonetheless, the knowledge acquisition of these courses was low and not related to previous course attendance or more years of rugby experience. These results justify the biennial nature of this safety course but also indicate that knowledge acquisition is generally low.
Immunohistochemistry with anti-MAL antibody and RNAscope with MAL probes are complementary techniques for diagnosis of primary mediastinal large B-cell lymphoma
Authors: Jacquier Anthony , Syrykh Charlotte , Bedgedjian Isabelle , Monnien Franck , Laurent Camille , Valmary-Degano Séverine , Brousset Pierre
Published: August 2020

Aims

Primary mediastinal large B-cell lymphoma (PMBL) diagnosis can be challenging on needle biopsies. Robust techniques are needed to ensure diagnosis of this lymphoma which is highly sensitive to recently developed therapy protocols.

Methods

In this study, we sought to determine precise PMBL phenotype, compared with diffuse large B-cell lymphoma not otherwise specified, by combining immunohistochemistry with anti-MAL antibody and RNA in situ hybridisation (RNAscope) with specific MAL probes.

Results

The overall MAL positivity level reached 93% (14/15) of cases of PMBL. Among the 15 cases enrolled in the study, 11 were undoubtedly positive for MAL immunostaining whereas 13 were positive by RNA in situ hybridisation. Interestingly, one case that was negative by in situ hybridisation turned out to be positive by immunohistochemistry.

Conclusions

Taken together, our results demonstrate that in situ detection of bothMALtranscripts and protein are complementary and increase the sensitivity and specificity of PMBL diagnosis.
Association between genetic polymorphisms and endometrial cancer risk: a systematic review
Authors: Bafligil Cemsel , Thompson Deborah J , Lophatananon Artitaya , Smith Miriam J , Ryan Neil AJ , Naqvi Anie , Evans D Gareth , Crosbie Emma J
Published: August 2020

Introduction

Endometrial cancer is one of the most commonly diagnosed cancers in women. Although there is a hereditary component to endometrial cancer, most cases are thought to be sporadic and lifestyle related. The aim of this study was to systematically review prospective and retrospective case–control studies, meta-analyses and genome-wide association studies to identify genomic variants that may be associated with endometrial cancer risk.

Methods

We searched MEDLINE, Embase and CINAHL from 2007 to 2019 without restrictions. We followed PRISMA 2009 guidelines. The search yielded 3015 hits in total. Following duplicate exclusion, 2674 abstracts were screened and 453 full-texts evaluated based on our pre-defined screening criteria. 149 articles were eligible for inclusion.

Results

We found that single nucleotide polymorphisms (SNPs) in HNF1B, KLF, EIF2AK, CYP19A1, SOX4 and MYC were strongly associated with incident endometrial cancer. Nineteen variants were reported with genome-wide significance and a further five with suggestive significance. No convincing evidence was found for the widely studied MDM2 variant rs2279744. Publication bias and false discovery rates were noted throughout the literature.

Conclusion

Endometrial cancer risk may be influenced by SNPs in genes involved in cell survival, oestrogen metabolism and transcriptional control. Larger cohorts are needed to identify more variants with genome-wide significance.
Ethical issues raised by intergenerational monitoring in clinical trials of germline gene modification
Authors: Yeager Austen
Published: August 2020

As research involving gene editing continues to advance, we are headed in the direction of being able to modify the human germline. Should we reach a point where an argument can be made that the benefits of preventing unborn children and future generations from inheriting genetic conditions that cause tremendous suffering outweigh the risks associated with altering the human germline, the next step will be to design clinical trials using this technology in humans. These clinical trials will likely require careful follow-up and monitoring of future generations born with altered genes. This paper addresses some of the ethical issues raised by intergenerational monitoring and sets out to show that these issues can be avoided with careful consideration and clinical trial design.
Analgesic efficacy of infiltration between the popliteal artery and capsule of the knee (iPACK) block added to local infiltration analgesia and continuous adductor canal block after total knee arthroplasty: a randomized clinical trial
Authors: Vichainarong Chutikant , Kampitak Wirinaree , Tanavalee Aree , Ngarmukos Srihatach , Songborassamee Nattaporn
Published: August 2020

Background

A combination of motor-sparing analgesia with local infiltration analgesia (LIA) and continuous adductor canal block (CACB) may improve postoperative pain and functional recovery for total knee arthroplasty (TKA). We hypothesized that the addition of a novel technique for posterior knee block, known as the infiltration between the popliteal artery and capsule of the knee (iPACK) block, to LIA with CACB would reduce opioid requirements.

Methods

In this double-blinded randomized controlled trial, 72 patients were assigned to receive either LIA with CACB (LIA+CACB group) or iPACK block with LIA and CACB (iPACK+LIA+CACB group). The primary outcome was cumulative postoperative intravenous morphine consumption within 24 hours. The secondary outcomes included numerical rating scale pain scores, incidence of posterior knee pain, performance test results, patient satisfaction, length of stay, and adverse events.

Results

Morphine consumption within 24 hours postoperatively showed no significant intergroup difference (LIA+CACB; 1.31±1.85 mg vs iPACK+LIA+CACB; 0.61±1.25 mg, p=0.08). There were no clinically significant differences in the overall pain scores between the groups. The lower Timed Up and Go test scores on postoperative days 1 and 2, along with a shorter duration of hospitalization, were found in the iPACK+LIA+CACB group (p<0.05).

Conclusion

The addition of an iPACK block to the LIA and CACB does not reduce the postoperative opioid consumption nor improve analgesia. However, it may improve immediate functional performance and reduce the length of hospitalization after TKA.

Trial registration number

TCTR20180702001.
Protective effect of club cell secretory protein (CC-16) on COPD risk and progression: a Mendelian randomisation study
Authors: Milne Stephen , Li Xuan , Hernandez Cordero Ana I , Yang Chen Xi , Cho Michael H , Beaty Terri H , Ruczinski Ingo , Hansel Nadia N , Bossé Yohan , Brandsma Corry-Anke , Sin Don D , Obeidat Maen
Published: August 2020

Background

The anti-inflammatory pneumoprotein club cell secretory protein-16 (CC-16) is associated with the clinical expression of chronic obstructive pulmonary disease (COPD). We aimed to determine if there is a causal effect of serum CC-16 level on the risk of having COPD and/or its progression using Mendelian randomisation (MR) analysis.

Methods

We performed a genome-wide association meta-analysis for serum CC-16 in two COPD cohorts (Lung Health Study (LHS), n=3850 and ECLIPSE, n=1702). We then used the CC-16-associated single-nucleotide polymorphisms (SNPs) as instrumental variables in MR analysis to identify a causal effect of serum CC-16 on ‘COPD risk’ (ie, case status in the International COPD Genetics Consortium/UK-Biobank dataset; n=35 735 COPD cases, n=222 076 controls) and ‘COPD progression’ (ie, annual change in forced expiratory volume in 1 s in LHS and ECLIPSE). We also determined the associations between SNPs associated with CC-16 and gene expression using n=1111 lung tissue samples from the Lung Expression Quantitative Trait Locus Study.

Results

We identified seven SNPs independently associated (p<5×10–8) with serum CC-16 levels; six of these were novel. MR analysis suggested a protective causal effect of increased serum CC-16 on COPD risk (MR estimate (SE) −0.11 (0.04), p=0.008) and progression (LHS only, MR estimate (SE) 7.40 (3.28), p=0.02). Five of the SNPs were also associated with gene expression in lung tissue (at false discovery rate <0.1) of several genes, including the CC-16-encoding geneSCGB1A1.

Conclusion

We have identified several novel genetic variants associated with serum CC-16 level in COPD cohorts. These genetic associations suggest a potential causal effect of serum CC-16 on the risk of having COPD and its progression, the biological basis of which warrants further investigation.
Medical management of a penile fracture with presumed pyelonephritis in a juvenile dog
Authors: Petrelli Andrea , Longo Maurizio , Willems Annelies , Liuti Tiziana
Published: August 2020

A three‐month‐old male entire Bouvier des Flandres was presented for acute onset dysuria, haematuria, lethargy and severe pain on palpation of the penis. Further investigation revealed a parcellar fracture of the cranial separate ossification centre of the os penis and associated urinary tract infection with presumed pyelonephritis. Fluoroscopic retrograde urethrography was performed revealing intermittent urethral obstruction caused by displacement of the cranial bone fragment of the separate ossification centre of the os penis. The urethra was catheterised to realign the fragments and to permit urination and antibiotic treatment was started. The urinary catheter was kept in place for five days. After its removal, normal urination was observed with complete resolution of the clinical signs. Follow‐up radiographs and ultrasound examination confirmed resolution of mechanical obstruction with fusion of part of the separate ossification centre and realignment of the displaced bony fragment.
Inflation with a class of concave inflaton potentials in Randall–Sundrum model
Authors: Loc Ngo Phuc Duc
Published: August 2020

We investigate inflation with a class of concave inflaton potentials of the form $$\sim \phi ^n$$∼ϕn$$(0<n<1)$$(0<n<1) in the Randall–Sundrum model with an infinite extra spatial dimension. We show that this class of models is much more in good agreement with observations compared to the standard inflation. We also find the range of the five-dimensional Planck scale ($$M_5$$M5) and show that large tensor-to-scalar ratios do not eliminate small-field inflation in braneworld cosmology.
Wet Chemical Processing of Ge in Acidic H2O2 Solution: Nanoscale Etching and Surface Chemistry
Authors: Abrenica Graniel Harne A. , Fingerle Mathias , Lebedev Mikhail V. , Arnauts Sophia , Mayer Thomas , Holsteyns Frank , de Gendt Stefan , van Dorp Dennis H.
Published: August 2020

Herein, we investigate wet-chemical etching of Ge (100) in acidic H2O2 solutions for technologically advanced device processing. Nanoscale etching kinetics data were provided by inductively coupled plasma mass spectrometry (ICP-MS) measurements. Rotation rate- dependent measurement showed that the hydrodynamics of the system is important. The dependence of the etch rate on the HCl concentration was considered for the range 0.001–1 M HCl. A stark difference morphologically for >1 M HCl, which resulted in a rough surface confirmed by atomic force microscopy (AFM) images, has been observed. X-ray photoelectron spectroscopy (XPS) measurements provided insight in the surface chemistry of etching for device processing. Electrochemical measurements confirmed that the etching process follows a chemical mechanism. Based on X-ray photoelectron spectroscopy (XPS) data, we present reaction schemes that help to understand the results.
Hyperglycemia does not inhibit insulin’s effects on microvascular perfusion in healthy humans: a randomized crossover study
Authors: Horton William B. , Jahn Linda A. , Hartline Lee M. , Aylor Kevin W. , Patrie James T. , Barrett Eugene J.
Published: August 2020

Diabetes mellitus accelerates vascular disease through multiple biochemical pathways driven by hyperglycemia, with insulin resistance and/or hyperinsulinemia also contributing. Persons with diabetes mellitus experience premature large vessel and microvascular disease when compared with normoglycemic controls. Currently, there is a paucity of clinical data identifying how acutely the vasculature responds to hyperglycemia and whether other physiological factors (e.g., vasoactive hormones) contribute. To our knowledge, no prior studies have examined the dynamic effects of acute hyperglycemia on insulin-mediated actions on both micro- and macrovascular function in the same subjects. In this randomized crossover trial, healthy young adults underwent two infusion protocols designed to compare the effects of insulin infusion during euglycemia and hyperglycemia on micro- and macrovascular function. Both euglycemic- and hyperglycemic-hyperinsulinemia increased skeletal (but not cardiac) muscle microvascular blood volume (each P < 0.02) and blood flow (each P < 0.04) significantly, and these increases did not differ between protocols. Hyperglycemic-hyperinsulinemia trended toward increased carotid-femoral pulse wave velocity (indicating increased aortic stiffness; P = 0.065 after Bonferroni adjustment), whereas euglycemic-hyperinsulinemia did not. There were no changes in postischemic flow velocity or brachial artery flow-mediated dilation during either protocol. Plasma endothelin-1 levels significantly decreased during both protocols (each P < 0.02). In this study, acute hyperglycemia for 4 h did not inhibit insulin’s ability to increase skeletal muscle microvascular perfusion but did provoke a slight increase in aortic stiffness. Hyperglycemia also did not adversely affect myocardial microvascular perfusion or endothelial function or prevent the decline of endothelin-1 during insulin infusion.
Effects of chronic hyperinsulinemia on metabolic pathways and insulin signaling in the fetal liver
Authors: Rozance Paul J. , Jones Amanda K. , Bourque Stephanie L. , D’Alessandro Angelo , Hay William. W. , Brown Laura D. , Wesolowski Stephanie R.
Published: August 2020

The effect of chronic of hyperinsulinemia in the fetal liver is poorly understood. Here, we produced hyperinsulinemia with euglycemia for ∼8 days in fetal sheep [hyperinsulinemic (INS)] at 0.9 gestation. INS fetuses had increased insulin and decreased oxygen and amino acid (AA) concentrations compared with saline-infused fetuses [control (CON)]. Glucose (whole body) utilization rates were increased, as expected, in INS fetuses. In the liver, however, there were few differences in genes and metabolites related to glucose and lipid metabolism and no activation of insulin signaling proteins (Akt and mTOR). There was increased p-AMPK activation and decreased mitochondrial mass ( PGC1A expression, mitochondrial DNA content) in INS livers. Using an unbiased multivariate analysis with 162 metabolites, we identified effects on AA and one-carbon metabolism in the INS liver. Expression of the transaminase BCAT2 and glutaminase genes GLS1 and GLS2 was decreased, supporting decreased AA utilization. We further evaluated the roles of hyperinsulinemia and hypoxemia, both present in INS fetuses, on outcomes in the liver. Expression of PGC1A correlated only with hyperinsulinemia, p-AMPK correlated only with hypoxemia, and other genes and metabolites correlated with both hyperinsulinemia and hypoxemia. In fetal hepatocytes, acute treatment with insulin activated p-Akt and decreased PGC1A, whereas hypoxia activated p-AMPK. Overall, chronic hyperinsulinemia produced greater effects on amino acid metabolism compared with glucose and lipid metabolism and a novel effect on one-carbon metabolism in the fetal liver. These hepatic metabolic responses may result from the downregulation of insulin signaling and antagonistic effects of hypoxemia-induced AMPK activation that develop with chronic hyperinsulinemia.
Protein disulfide isomerase inhibition impairs Keap1/Nrf2 signaling and mitochondrial function and induces apoptosis in renal proximal tubular cells
Authors: Pokkunuri Indira D. , Lokhandwala Mustafa F. , Banday Anees Ahmad
Published: August 2020

Renal proximal tubular apoptosis plays a critical role in kidney health and disease. However, cellular molecules that trigger renal apoptosis remain elusive. Here, we evaluated the effect of inhibiting protein disulfide isomerase (PDI), a critical thioredoxin chaperone protein, on apoptosis as well as the underlying mechanisms in human renal proximal tubular (HK2) cells. HK2 cells were transfected with PDI-specific siRNA in the absence and presence of an antioxidant, tempol. PDI siRNA transfection resulted in a decrease of ~70% in PDI protein expression and enzyme activity. PDI inhibition increased caspase-3 activity and induced profound cell apoptosis. Mitochondrial function, as assessed by mitochondrial cytochrome c levels, mitochondrial membrane potential, oxygen consumption, and ATP levels, was significantly reduced in PDI-inhibited cells. Also, PDI inhibition caused nuclear factor erythroid 2-related factor 2 (Nrf2; a redox-sensitive transcription factor) cytoplasmic sequestration, decreased superoxide dismutase and glutathione- S-transferase activities, and increased oxidative stress. In PDI-inhibited cells, tempol reduced apoptosis, caspase-3 activity, and oxidative stress and also restored Nrf2 nuclear translocation and mitochondrial function. Silencing Nrf2 in the cells abrogated the beneficial effect of tempol, whereas Kelch-like ECH-associated protein 1 (an Nrf2 regulatory protein) silencing protected cells from PDI inhibitory effects. Collectively, our data indicate that PDI inhibition diminishes Nrf2 nuclear translocation, causing oxidative stress that further triggers mitochondrial dysfunction and renal cell apoptosis. This study suggests an important role for PDI in renal cell apoptosis involving Nrf2 and mitochondrial dysfunction.
C57BL/6 mice require a higher dose of cisplatin to induce renal fibrosis and CCL2 correlates with cisplatin-induced kidney injury
Authors: Sears Sophia M. , Sharp Cierra N. , Krueger Austin , Oropilla Gabrielle B. , Saforo Douglas , Doll Mark A. , Megyesi Judit , Beverly Levi J. , Siskind Leah J.
Published: August 2020

C57BL/6 mice are one of the most commonly used mouse strains in research, especially in kidney injury studies. However, C57BL/6 mice are resistant to chronic kidney disease-associated pathologies, particularly the development of glomerulosclerosis and interstitial fibrosis. Our laboratory and others developed a more clinically relevant dosing regimen of cisplatin (7 mg/kg cisplatin once a week for 4 wk and mice euthanized at day 24) that leads to the development of progressive kidney fibrosis in FVB/n mice. However, we found that treating C57BL/6 mice with this same dosing regimen does not result in kidney fibrosis. In this study, we demonstrated that increasing the dose of cisplatin to 9 mg/kg once a week for 4 wk is sufficient to consistently induce fibrosis in C57BL/6 mice while maintaining animal survival. In addition, we present that cohorts of C57BL/6 mice purchased from Jackson 1 yr apart and mice bred in-house display variability in renal outcomes following repeated low-dose cisplatin treatment. Indepth analyses of this intra-animal variability revealed C-C motif chemokine ligand 2 as a marker of cisplatin-induced kidney injury through correlation studies. In addition, significant immune cell infiltration was observed in the kidney after four doses of 9 mg/kg cisplatin, contrary to what has been previously reported. These results indicate that multiple strains of mice can be used with our repeated low-dose cisplatin model with dose optimization. Results also indicate that littermate control mice should be used with this model to account for population variability.
Impaired renal hemodynamics and glomerular hyperfiltration contribute to hypertension-induced renal injury
Authors: Fan Letao , Gao Wenjun , Nguyen Bond V. , Jefferson Joshua R. , Liu Yedan , Fan Fan , Roman Richard J.
Published: August 2020

Recently, we reported a mutation in γ-adducin (ADD3) was associated with an impaired myogenic response of the afferent arteriole and hypertension-induced chronic kidney disease (CKD) in fawn hooded hypertensive (FHH) rats. However, the mechanisms by which altered renal blood flow (RBF) autoregulation promotes hypertension-induced renal injury remain to be determined. The present study compared the time course of changes in renal hemodynamics and the progression of CKD during the development of DOCA-salt hypertension in FHH 1BNcongenic rats [wild-type (WT)] with an intact myogenic response versus FHH 1BNAdd3KO ( Add3KO) rats, which have impaired myogenic response. RBF was well autoregulated in WT rats but not in Add3KO rats. Glomerular capillary pressure rose by 6 versus 14 mmHg in WT versus Add3KO rats when blood pressure increased from 100 to 150 mmHg. After 1 wk of hypertension, glomerular filtration rate increased by 38% and glomerular nephrin expression decreased by 20% in Add3KO rats. Neither were altered in WT rats. Proteinuria doubled in WT rats versus a sixfold increase in Add3KO rats. The degree of renal injury was greater in Add3KO than WT rats after 3 wk of hypertension. RBF, glomerular filtration rate, and glomerular capillary pressure were lower by 20%, 28%, and 19% in Add3KO rats than in WT rats, which was associated with glomerular matrix expansion and loss of capillary filtration area. The results indicated that impaired RBF autoregulation and eutrophic remodeling of preglomerular arterioles increase the transmission of pressure to glomeruli, which induces podocyte loss and accelerates the progression of CKD in hypertensive Add3KO rats.
Network Security Situation Assessment Model Based on Extended Hidden Markov
Authors: Liao Yiwei , Zhao Guosheng , Wang Jian , Li Shu
Published: August 2020

A network security situation assessment system based on the extended hidden Markov model is designed in this paper. Firstly, the standard hidden Markov model is expanded from five-tuple to seven-tuple, and two parameters of network defense efficiency and risk loss vector are added so that the model can describe network security situation more completely. Then, an initial algorithm of state transition matrix was defined, observation vectors were extracted from the fusion of various system security detection data, the network state transition matrix was created and modified by the observation vectors, and a solution procedure of the hidden state probability distribution sequence based on extended hidden Markov model was derived. Finally, a method of calculating risk loss vector according to the international definition was designed and the current network risk value was calculated by the hidden state probability distribution; then the global security situation was assessed. The experiment showed that the model satisfied practical applications and the assessment result is accurate and effective.
An Age-Structured Model of HIV Latent Infection with Two Transmission Routes: Analysis and Optimal Control
Authors: Qin Chunyang , Wang Xia , Rong Libin
Published: August 2020

In addition to direct virus infection of target cells, HIV can also be transferred from infected to uninfected cells (cell-to-cell transmission). These two routes might facilitate viral production and the establishment of the latent virus pool, which is considered as a major obstacle to HIV cure. We studied an HIV infection model including the two infection routes and the time since latent infection. The basic reproductive ratio R0 was derived. The existence, positivity, and boundedness of the solution are proved. We investigated the existence of steady states and their stability, which were shown to depend on R0. We established the global asymptotic dynamical behavior by proving the existence of the global compact attractor and uniform persistence of the system and by applying the method of Lyapunov functionals. In the end, we formulated and solved the optimal control problem for the age-structured model. The necessary condition for minimization of the viral level and the cost of drug treatment was obtained, and numerical simulations of various optimal control strategies were performed.
Computing Vertex-Based Eccentric Topological Descriptors of Zero-Divisor Graph Associated with Commutative Rings
Authors: Ahmadini Abdullah Ali H. , Koam Ali N. A. , Ahmad Ali , Bača Martin , Semaničová–Feňovčíková Andrea
Published: August 2020

The applications of finite commutative ring are useful substances in robotics and programmed geometric, communication theory, and cryptography. In this paper, we study the vertex-based eccentric topological indices of a zero-divisor graphs of commutative ringℤp2×ℤq, wherepandqare primes.
A Novel EMD Mutation Identified by Whole-Exome Sequencing in Twins with Emery–Dreifuss Muscular Dystrophy
Authors: Dai Xiafei , Luo Rong , Chen Yang , Zheng Chenqing , Tang Yibin , Zhang Hongmei , Su Ye , He Tao , Li Xiaoping
Published: August 2020

This case reports a novel hemizygous frameshift EMD mutation (c.487delA, p.Ser163fs) in twins of an Emery–Dreifuss muscular dystrophy family with severe cardiac involvement and mild muscle weakness. Their mother carried the same heterozygous mutation.
Spatial and Temporal Characteristics of Rurality in Urban Suburb Town and Its Driving Factors Based on Land Use Transformation
Authors: Yang Zhiheng , Li Chenxi
Published: August 2020

Rurality highlights the intrinsic differences between urban and rural communities. The comprehensive rurality evaluation index system is difficult to obtain indicators that reflect purely rural or urban characteristics; in addition, most of the data used in the evaluation index system come from statistical data, and the authenticity of the data cannot be guaranteed. Taking 25 towns in Lixia County and Shanghe County in Jinan city as the study area and using land use data and economic statistics data, the rurality evaluation system based on the land use transformation was constructed, the changes of the rurality index and intensity from 2009 to 2015 were calculated, and the driving factors of the rurality were analyzed. The results showed that, from 2009 to 2015, the rurality difference among towns in Lixia County decreased, the rurality difference among towns in Shanghe County increased, the rurality intensity of Lixia County was lower than that of Shanghe County, and the rurality index gap between the two counties was increasing. In 2009, the rurality grade of Lixia County was dominated by weak intensity (84.62%), and the rurality of the county changed greatly in 2015, with a large proportion (76.92%) still being weak intensity. In 2009, the proportion of relatively strong intensity was dominated (33.33%) in Shanghe County; in 2015, weak intensity accounted for a large proportion (41.67%). Changes of rurality intensity in Lixia County and Shanghe County were different. There was a significant correlation between the rurality index and geographical elevation, GDP, and the distance from the center of the town government, the road construction level, the urbanization level, and the education level. This paper can provide an empirical reference for rurality index research.
Research on the Dynamic Erosion Wear Characteristics of a Nozzle Flapper Pressure Servo Valve Used in Aircraft Brake System
Authors: Chu Yuanbo , Yuan Zhaohui , Chang Wenchao
Published: August 2020

The nozzle flapper pressure servo valve is a kind of high-precision hydraulic component that can be widely used in the aircraft brake system. In actual service, the dynamic erosion wear behavior will occur at the pilot stage because of the gradual contamination of oil and the variable distance between nozzle and flapper. For this purpose, the paper proposes a dynamic erosion wear characteristics analysis and service life prediction method in which firstly the structural feature and working principle of the nozzle flapper pressure valve are analyzed using the brake cavity as the load blind cavity. Secondly, the dynamics simulation model and the performance experiment system of the pressure valve are separately constructed, and then the validation of the constructed model is conducted by contrasting the results between simulation and experiment. Finally, the mathematical models of the degradation process induced by the dynamic erosion wear are established, and then the dynamic erosion wear characteristics under dynamic structural distance and contamination conditions are analyzed, which are combined with the failure threshold value determined by the dynamics simulation to finish the service life prediction of the nozzle flapper pressure servo valve.
Circular Antenna Array Synthesis Using Multiverse Optimizer
Authors: Taser Ahmet Emre , Guney Kerim , Kurt Erhan
Published: August 2020

Antenna array synthesis is one of the most popular topics in the electromagnetic field. Since achieving a desired antenna radiation pattern is a mathematical problem, in the literature, there are various optimization algorithms applied to the synthesis process of different kinds of antenna arrays. In this study, Multiverse Optimizer (MVO) and modified MVO (MMVO) are used to perform circular antenna array (CAA) synthesis. During the exploration, exploitation, and local search phases of calculation, MVO uses three concepts in cosmology; white hole, black hole, and wormhole. Convergence capability of this nature-inspired algorithm is employed for finding optimum amplitude and position values of CAA elements in order to achieve an array pattern with low maximum sidelobe level (MSL) and minimum circumference. The performance of MVO and MMVO was tested on five design examples of pattern synthesis, and the obtained results were compared with ten different algorithms. The simulation results show that MVO and MMVO provide low MSLs with small circumferences.
A New Method to Calculate Additional Damping Ratio considering the Effect of Excitation Frequency
Authors: Xu Weizhi , Du Dongsheng , Wang Shuguang , Li Weiwei
Published: August 2020

The additional damping ratio (ADR) is an important indicator for evaluating the damping effect of structures with energy‐dissipation devices. Most existing methods for determining the ADR require an analysis of the structural dynamic response and complex iterative calculations. An innovative simplified calculation method for determining the ADR of a structure supplemented by nonlinear viscous dampers is proposed. This method does not require the dynamic response of the structure to be calculated and only requires the structural characteristics, excitation frequency, and damper parameters. In this study, several typical calculation methods for the ADR were analysed. Then, a calculation formula for the ADR was derived with consideration of harmonic excitation under the condition where the excitation frequency is equal to the structural natural frequency, without calculation of the structural dynamic response or an iterative process. The effect of the excitation frequency on the calculated value of the ADR with different damping exponents was studied. Accordingly, the response spectrum average period (RSAP) was considered as the excitation period of ground motion to evaluate the excitation frequency, and a simplified calculation method for the ADR considering the effect of the excitation frequency characterised by the RSAP of the ground motion was established. Finally, the accuracy and effectiveness of the proposed method were verified by comparison with ADRs calculated using other methods.
Hybrid Position/Force Control for Dual-Machine Drilling and Riveting System
Authors: Liu Yi , Fang Qiang , Ke Yinglin
Published: August 2020

The deformation of riveting machine caused by riveting force during rivet formed makes the riveting tool out of positioning, which leads to gapping underneath the rivet manufactured head and insufficient rivet drive head. This paper proposes a hybrid position/force riveting control method for the dual-machine drilling and riveting system to eliminate the negative effects of machine deformation. The cooperative work of two-side machine tool is realized by a hybrid position/force control strategy, which compensates for the force-induced deformation error without an accurate stiffness model of the riveting system. The position of pressing foot relative to the machine which represents the deformation of skin-side machine is obtained for the compensation to the displacement of skin-side actuator. Simultaneously, the advanced force control is adopted for the stringer-side actuator. The dynamics model of the stringer-side actuator in consideration of the machine deformation is established and identified. The disturbance observer (DOB) and feedforward controller are introduced as the model-based control algorithm to achieve the high-performance force control. Also, contrast experiments are conducted to validate the effectiveness of the proposed riveting control method. The results show that the rivet manufactured head can be seated in the countersink during the forming process and the gapping under the head is eliminated. The driven head height tolerance of ±0.1 mm is achieved by accurate force control.