bluuebunny/crossref_metadata_2025 huggingface dataset:
Bird and hail stone impact resistance analysis on a jet engine composite air inlet
Authors: Doubrava Radek , Oberthor Martin , Bělský Petr , Raška Jan
Published: August 2018

Bird or hail stone impacts are an important phenomenon that must be taken into consideration when designing aircraft. As engines are the sole thrust-providing mechanisms of an aircraft, it is critical that the effects of bird or hail stone strikes on engine inlets and systems be investigated and mitigated to the greatest extent possible. A combination of experiments and numerical simulations is necessary to properly understand the behaviour of a bird or hail stone during impact and the reaction of the impacted material with the structure. A simulation methodology is developed and validated to certify the bird or hail stone strike resistance of composite air ducts designed for a new generation of jet training aircraft. Physical impact tests were performed on real composite parts. Numerical simulation results were compared with test results. Numerical simulation was also used for test preparation and optimization of the test rig design from the point of view of the influence of the stiffness of the surrounding aircraft structure. The validated modelling procedure allows the analysis of numerous impact scenarios, improving the optimization procedures for aircraft component design and reducing the cost of development by reducing the need to manufacture test prototypes.
Endoscopic biliary stenting: indications, choice of stents, and results: European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline – Updated October 2017
Authors: Dumonceau Jean-Marc , Tringali Andrea , Papanikolaou Ioannis , Blero Daniel , Mangiavillano Benedetto , Schmidt Arthur , Vanbiervliet Geoffroy , Costamagna Guido , Devière Jacques , García-Cano Jesús , Gyökeres Tibor , Hassan Cesare , Prat Frédéric , Siersema Peter , van Hooft Jeanin
Published: August 2018

Main Recommendations

ESGE recommends against routine preoperative biliary drainage in patients with malignant extrahepatic biliary obstruction; preoperative biliary drainage should be reserved for patients with cholangitis, severe symptomatic jaundice (e. g., intense pruritus), or delayed surgery, or for before neoadjuvant chemotherapy in jaundiced patients. Strong recommendation, moderate quality evidence.

ESGE recommends the endoscopic placement of a 10-mm diameter self-expandable metal stent (SEMS) for preoperative biliary drainage of malignant extrahepatic biliary obstruction. Strong recommendation, moderate quality evidence.

ESGE recommends SEMS insertion for palliative drainage of of extrahepatic malignant biliary obstruction. Strong recommendation, high quality evidence.

ESGE recommends against the insertion of uncovered SEMS for the drainage of extrahepatic biliary obstruction of unconfirmed etiology. Strong recommendation, low quality evidence.

ESGE suggests against routine preoperative biliary drainage in patients with malignant hilar obstruction. Weak recommendation, low quality evidence.

ESGE recommends uncovered SEMSs for palliative drainage of malignant hilar obstruction. Strong recommendation, moderate quality evidence.

ESGE recommends temporary insertion of multiple plastic stents or of a fully covered SEMS for treatment of benign biliary strictures. Strong recommendation, moderate quality evidence.

ESGE recommends endoscopic placement of plastic stent(s) to treat bile duct leaks that are not due to transection of the common bile duct or common hepatic duct. Strong recommendation, moderate quality evidence.
Osteoarthropathien und Myopathien bei Schilddrüsenerkrankungen
Authors: Nehls Volker
Published: August 2018

Triiodothyronine (T3) is a key regulator of bone, muscle and articular cartilage. Musculoskeletal symptoms of hyperthyroidism include loss of bone mass finally leading to osteoporosis and weakness of the skeletal musculature. Hypothyroidism on the other side frequently leads to muscle stiffness and cramping and, occasionally, results in rhabdomyolysis. To prevent terminal differentiation of chondrocytes with consecutive cartilage degeneration, cartilage probably depends on exact regulation of local T3 availability by the intracellular deiodinase system. Recent findings underline the importance of local T3 generation by deiodinase type 2 and support the existence of local hypo- or hyperthyroidism.

In the review, the implications of the recent literature for current understanding of osteoarthritis, myopathies and diabetic osteoarthropathy will be discussed. Further emphasis will be placed on the association of autoimmune thyroiditis with musculoskeletal diseases and fibromyalgia.
Flow and heat transfer characteristics of an open cubic cavity with different inclinations
Authors: Saxena Ashish , Singh Suneet , Srivastava Atul
Published: August 2018

Natural convection of air in an inclined differentially heated open cubic cavity is studied. From the literature, it can be seen that there is no definite relationship between the Nusselt numbers obtained for square and cubic cavities for different Rayleigh numbers (Ra) and cavity inclinations. For some combinations of Ra and cavity inclinations, the Nusselt numbers are significantly lower in the cubic cavity compared to that of the square cavity, while for other combinations, it is quite the opposite. To understand the cause of these variations, a detailed study of the flow patterns is carried out for different Ra and cavity inclination angles. It is seen that for a lower range of Ra, the finiteness of the cavity reduces the flow, resulting in lower heat transfer for the 3D cavity when compared to the 2D cavity. Similar results are seen for larger inclination angles of the cavity (hot wall close to the vertical) even for higher Ra. However, for the cases with higher Ra and small inclination angles (hot wall close to the horizontal), the flow becomes three-dimensional. The three-dimensionality in the flow is attributed to the weak convection currents that rise from the side adiabatic walls and go down from the center of the cavity. The combination of these convection currents with the predominantly strong convection currents, which are going up from the hot wall, results in the complex three dimensional flow patterns. Due to this phenomenon, the cubic cavity with such a configuration has significantly higher Nusselt number compared to that of the square cavity.
Caging of planktonic rotifers in microfluidic environment for sub-lethal aquatic toxicity tests
Authors: Cartlidge Rhys , Wlodkowic Donald
Published: August 2018

Quantification of neuro-behavioural responses of intact small model organisms has been proposed as a sensitive, sub-lethal alternative to conventional toxicity testing. Such bioassays are characterized by a high physiological and ecological relevance, short response times, increased sensitivity, and non-invasive nature. Despite a significant potential for predictive aquatic toxicology analysis of behavioural traits of micro-invertebrates in microfluidic environment has received little attention. In this work, we demonstrate a new Lab-on-a-Chip technology capable of effectively caging freshwater rotifers Brachionus calyciflorus for real-time video-microscopy analysis. We demonstrate that behavioural bioassays performed under microfluidic perfusion can significantly enhance the sensitivity of conventional ecotoxicology test protocols.
Proteomics analysis of intensive exercise-induced disorders of gametogenesis in the testis using isobaric tags for relative and absolute quantification (iTRAQ) analysis
Authors: Guo Yuping , Li Enzhong
Published: August 2018

In the present study we screened a panel of regulatory proteins associated with gametogenesis disorders in the testis that are induced by intensive exercise. Four-week-old Sprague-Dawley male rats were randomly divided into three groups: a control group, a no-load exercise group and an intensive exercise group. Rats in the control group were free to move in their cage. Rats in the no-load exercise and intensive exercise groups swam for 60 min day−1, six times each week, for a total 9-week exercise regimen; rats in the intensive exercise group swam with a load of 6% body mass. After the last exercise session (or at the end of the 9-week period), a sperm count, reproductive hormone assays, histological analysis of the testis and proteomics analysis were performed for each rat. Mean (± s.d.) sperm concentration was significantly lower in the intensive exercise group than in the control and no-load exercise groups (1.36 ± 0.63 vs 2.12 ± 0.53 and 2.57 ± 0.48 × 106 spermatozoa mL−1 respectively; P < 0.05). Serum testosterone concentrations were also significantly lower in the intensive exercise group (P < 0.01), whereas gonadotrophin-releasing hormone, LH and FSH concentrations were slightly decreased in the intensive exercise group, but not significantly (P > 0.05). Histological analysis showed that the number of spermatogenic cells in the seminiferous tubules was lower in the intensive exercise group than in the control and no-load exercise groups. Proteomics analysis identified 54 proteins that were differentially expressed between the control and intensive exercise groups (31 downregulated, 23 upregulated). Pathway enrichment analysis showed that ribosome and extracellular matrix–receptor interaction pathways play an important role in the signal transduction of testicular gametogenic disorders. Four differentially expressed proteins that were involved in the regulation of reproduction were identified by bioinformatics analysis and validated by targeted mass spectrometry analysis, namely vimentin, collagen α-1(I) chain, fatty acid-binding protein 9 and 40S ribosomal protein S3a. The data suggest that changes in the abundance of differentially expressed proteins after long-term intensive exercise affect the cycle and progression of spermatogenesis, resulting in spermatogenic disorders.
Astaxanthin improves the developmental competence of in vitro-grown oocytes and modifies the steroidogenesis of granulosa cells derived from bovine early antral follicles
Authors: Abdel-Ghani M. A. , Yanagawa Y. , Balboula A. Z. , Sakaguchi K. , Kanno C. , Katagiri S. , Takahashi M. , Nagano M.
Published: August 2018

In this study we investigated the effect of astaxanthin (Ax), which exhibits strong antioxidant activity, during invitro growth (IVG) on the developmental competence of oocytes and steroidogenesis of granulosa cells derived from early antral follicles. Bovine oocyte–cumulus–granulosa complexes collected from early antral follicles were cultured for 12 days in the presence or absence (control) of 500µM Ax. The viability of oocytes and antrum formation in the granulosa cell layer during IVG culture were greater in the presence than absence of Ax (P<0.05). Regardless of Ax treatment, 17β-oestradiol production increased during IVG culture; however, progesterone production was significantly lower in the presence than absence of Ax (P<0.05). Reactive oxygen species levels were lower in Ax-treated oocytes than in controls after IVG (P<0.05). Although nuclear maturation and cleavage rates did not differ between the Ax-treated and control groups, Ax treatment led to weaker cathepsin B activity in oocytes and better blastocyst rates than in controls (P<0.05). Accordingly, Ax treatment during IVG increased the total number of cells in blastocysts (P<0.05). These results indicate that Ax supplementation of IVG medium improves the quality of bovine oocytes due to its antioxidative effects on growing oocytes and its suppression of the luteinisation of granulosa cells.
Origin of Jupiter’s cloud-level zonal winds remains a puzzle even after Juno
Authors: Kong Dali , Zhang Keke , Schubert Gerald , Anderson John D.
Published: August 2018

Significance

How the Jovian cloud-level zonal winds are generated and maintained has been a major scientific puzzle for decades. There are two main contenders to explain the origin of the winds: (
i
) They are maintained and generated by deep thermal convection and extend deep into Jupiter’s interior and (
ii
) they are associated with horizontal temperature differences between belts and zones and confined to a very thin stably stratified weather layer below which there exists an unknown convective circulation. We show that the Juno gravitational measurements alone cannot discriminate between these two different scenarios. The origin of the winds is still a mystery.
Personal Problems Questionnaire (PPQ): Normative Data and Utility in Assessing Acquired Neurological Impairment
Authors: van den Broek Martin D , Monaci Linda , Smith Jared G
Published: August 2018

Objective

The Personal Problems Questionnaire (PPQ) is a measure designed to assess acquired cognitive, emotional, and physical complaints. The present study sought to develop a normative database to allow clinicians and researchers to assess self-reported complaints among people with disabilities, and evaluate the response consistency and validity of their self-report.

Method

404 community-dwelling participants (n 200 males, 204 females) completed the PPQ, as well as an acquired brain injury (ABI) group (n 59), mainly following stroke and traumatic brain injuries, and seen for clinical (i.e., non-forensic) evaluations. Multiple regression analyses were conducted to derive norms from the healthy community sample taking into account age, gender, and educational level.

Results

Normative T scores and cut-off points for the Clinical and Validity scales were derived, respectively, and used to assess the responses of the ABI group. The results indicated that the ABI group showed good response consistency and elevated scores on the Clinical scales, indicating that the PPQ is likely to be useful in detecting acquired disabilities. On the other hand, scores on the Validity scales were not elevated, indicating that the measures were unaffected by the ABI participants’ cognitive difficulties.

Conclusions

The PPQ provides a comprehensive assessment of complaints and response validity and the present study provides further data to assist with its use and interpretation.
Twenty years of bioinformatics research for protease-specific substrate and cleavage site prediction: a comprehensive revisit and benchmarking of existing methods
Authors: Li Fuyi , Wang Yanan , Li Chen , Marquez-Lago Tatiana T , Leier André , Rawlings Neil D , Haffari Gholamreza , Revote Jerico , Akutsu Tatsuya , Chou Kuo-Chen , Purcell Anthony W , Pike Robert N , Webb Geoffrey I , Ian Smith A , Lithgow Trevor , Daly Roger J , Whisstock James C , Song Jiangning
Published: August 2018

The roles of proteolytic cleavage have been intensively investigated and discussed during the past two decades. This irreversible chemical process has been frequently reported to influence a number of crucial biological processes (BPs), such as cell cycle, protein regulation and inflammation. A number of advanced studies have been published aiming at deciphering the mechanisms of proteolytic cleavage. Given its significance and the large number of functionally enriched substrates targeted by specific proteases, many computational approaches have been established for accurate prediction of protease-specific substrates and their cleavage sites. Consequently, there is an urgent need to systematically assess the state-of-the-art computational approaches for protease-specific cleavage site prediction to further advance the existing methodologies and to improve the prediction performance. With this goal in mind, in this article, we carefully evaluated a total of 19 computational methods (including 8 scoring function-based methods and 11 machine learning-based methods) in terms of their underlying algorithm, calculated features, performance evaluation and software usability. Then, extensive independent tests were performed to assess the robustness and scalability of the reviewed methods using our carefully prepared independent test data sets with 3641 cleavage sites (specific to 10 proteases). The comparative experimental results demonstrate that PROSPERous is the most accurate generic method for predicting eight protease-specific cleavage sites, while GPS-CCD and LabCaS outperformed other predictors for calpain-specific cleavage sites. Based on our review, we then outlined some potential ways to improve the prediction performance and ease the computational burden by applying ensemble learning, deep learning, positive unlabeled learning and parallel and distributed computing techniques. We anticipate that our study will serve as a practical and useful guide for interested readers to further advance next-generation bioinformatics tools for protease-specific cleavage site prediction.
Binding site matching in rational drug design: algorithms and applications
Authors: Naderi Misagh , Lemoine Jeffrey Mitchell , Govindaraj Rajiv Gandhi , Kana Omar Zade , Feinstein Wei Pan , Brylinski Michal
Published: August 2018

Interactions between proteins and small molecules are critical for biological functions. These interactions often occur in small cavities within protein structures, known as ligand-binding pockets. Understanding the physicochemical qualities of binding pockets is essential to improve not only our basic knowledge of biological systems, but also drug development procedures. In order to quantify similarities among pockets in terms of their geometries and chemical properties, either bound ligands can be compared to one another or binding sites can be matched directly. Both perspectives routinely take advantage of computational methods including various techniques to represent and compare small molecules as well as local protein structures. In this review, we survey 12 tools widely used to match pockets. These methods are divided into five categories based on the algorithm implemented to construct binding-site alignments. In addition to the comprehensive analysis of their algorithms, test sets and the performance of each method are described. We also discuss general pharmacological applications of computational pocket matching in drug repurposing, polypharmacology and side effects. Reflecting on the importance of these techniques in drug discovery, in the end, we elaborate on the development of more accurate meta-predictors, the incorporation of protein flexibility and the integration of powerful artificial intelligence technologies such as deep learning.
Differences in the Associations Between Memory Complaints and Depressive Symptoms Among Black and White Older Adults
Authors: Hill Nikki L , Mogle Jacqueline , Bhargava Sakshi , Whitaker Emily , Bhang Iris , Capuano Ana W , Arvanitakis Zoe , Bennett David A , Barnes Lisa L
Published: August 2018

Objective

To test whether race (specifically Black or White) moderates the relationship between memory complaints and depressive symptoms in cognitively normal older adults, and if these relationships vary by memory complaint characteristics.

Methods

Data from Black (n = 551) and White (n = 1,158) cognitively intact participants (Mage = 77.1, SD = 7.5; 76.6% female) in the Minority Aging Research Study and the Rush Memory and Aging Project were used. Participants completed annual clinical evaluations, including the Center for Epidemiologic Studies Depression scale and two memory complaint questions, over periods of up to 18 years. Ordinal mixed effects models were used to examine within-person relationships between memory complaints and depressive symptoms over time, as well as whether race moderated these associations.

Results

Reports of greater memory change over time were associated with more depressive symptoms for both Black and White older adults. However, reports of greater frequency of memory problems were related to depressive symptoms for Black older adults only.

Conclusion

Findings suggest differential associations between memory complaints and depressive symptoms in cognitively normal Black and White older adults and call for future research to examine the influence of race and related factors on memory complaints and depressive symptoms.
Stability analysis for complicated sampled-data systems via descriptor remodelling
Authors: Zhou Jun , Gao Ketian , Lu Xinbiao
Published: August 2018

A new stability analysis technique is developed in this paper for complicated sampled-data systems with both analogue and digital controllers, by frequency-domain equivalence in the continuous-time sense and time-delayed descriptor (or singular) state-space realization remodelling. The technique is independent of the lifting technique and thus employs neither structural nor spectral features of any discrete-time transfer functions of continuous-time plants. The suggested criteria are stated with frequency-domain conditions, involving neither open-loop unstable poles nor contour/locus-orientation-related encirclements counting. The criteria are implementable graphically with locus plotting or numerically tractable without locus plotting. The descriptor remodelling advantages are further exploited in surmounting infinite dimensionality and structural/spectral features unavailability in multi-rate and time-delayed sampled-data systems. Numerical examples are included to illustrate the main results.
Multilinear Estimates for Calderón Commutators
Authors: Lai Xudong
Published: August 2018

In this paper, we investigate the multilinear boundedness properties of the higher ($n$-th) order Calderón commutator for dimensions larger than two. We establish all multilinear endpoint estimates for the target space $L^{\frac{d}{d+n},\infty }(\mathbb{R}^d)$, including that Calderón commutator maps the product of Lorentz spaces $L^{d,1}(\mathbb{R}^d)\times \cdots \times L^{d,1}(\mathbb{R}^d)\times L^1(\mathbb{R}^d)$ to $L^{\frac{d}{d+n},\infty }(\mathbb{R}^d)$, which is the higher dimensional nontrivial generalization of the endpoint estimate that the $n$-th order Calderón commutator maps $L^{1}(\mathbb{R})\times \cdots \times L^{1}(\mathbb{R})\times L^1(\mathbb{R})$ to $L^{\frac{1}{1+n},\infty }(\mathbb{R})$. When considering the target space $L^{r}(\mathbb{R}^d)$ with $r<\frac{d}{d+n}$, some counterexamples are given to show that these multilinear estimates may not hold. The method in the present paper seems to have a wide range of applications and it can be applied to establish the similar results for Calderón commutator with a rough homogeneous kernel.
Effectiveness of adherence to recommended clinical examinations of diabetic patients in preventing diabetes-related hospitalizations
Authors: Corrao Giovanni , Rea Federico , Di Martino Mirko , Lallo Adele , Davoli Marina , DlE PlALMA Rossana , Belotti Laura , Merlino Luca , Pisanti Paola , Lispi Lucia , Skrami Edlira , Carle Flavia ,   the working group ‘Monitoring and assessing diagnostic-therapeutic paths’ of the Italian Heath Ministry
Published: August 2018

Objective

To validate a set of indicators for quality of diabetes care through their relationship with measurable clinical outcomes.

Design

A retrospective cohort study was carried out from 2010 to 2015.

Setting

Population-based study. Data were retrieved from healthcare utilization databases of three Italian regions (Lombardy, Emilia Romagna and Lazio) on the whole covering 20 million citizens.

Participants

The 77 285 individuals who were newly taken in care for diabetes during 2010 entered into the cohort.

Interventions

Exposure to selected clinical recommendations (i.e. periodic controls for glycated hemoglobin, lipid profile, urine albumin excretion, serum creatinine and dilated eye exams) was recorded.

Main outcomes measures

A composite outcome was employed taking into account hospitalizations for brief-term diabetes complications, uncontrolled diabetes, long-term vascular outcomes and no traumatic lower limb amputation. A multivariable proportional hazards model was fitted to estimate hazard ratio, and 95% confidence intervals (CI), for the exposure-outcome association.

Results

Among the newly taken in care patients with diabetes, those who adhered to almost none (0 or 1), just some (2 or 3) or almost all (4 or 5) recommendations during the first year after diagnosis were 44%, 36% and 20%, respectively. Compared patients who adhered to almost none recommendation, significant risk reductions of 16% (95% CI, 6–24%) and 20% (7–28%) were observed for those who adhered to just some and almost all recommendations, respectively.

Conclusions

Tight control of patients with diabetes through regular clinical examinations must to be considered the cornerstone of national guidance, national audits and quality improvement incentives schemes.
Vaccine Hesitancy, History, and Human Nature: The 2018 Stanley A. Plotkin Lecture
Authors: Marshall Gary S
Published: August 2018

Navigating the waters of vaccine hesitancy requires a view towards history and a deep understanding of how humans think. Getting children vaccinated is as much, or more, about connecting with people as it is about communicating scientific information.
Kidney size in relation to ageing, gender, renal function, birthweight and chronic kidney disease risk factors in a general population
Authors: Piras Doloretta , Masala Marco , Delitala Alessandro , Urru Silvana A M , Curreli Nicolò , Balaci Lenuta , Ferreli Liana P , Loi Francesco , Atzeni Alice , Cabiddu Gianfranca , Racugno Walter , Ventura Laura , Zoledziewska Magdalena , Steri Maristella , Fiorillo Edoardo , Pilia Maria G , Schlessinger David , Cucca Francesco , Rule Andrew D , Pani Antonello
Published: August 2018

Background

The relationship of kidney size to ageing, kidney function and kidney disease risk factors is not fully understood.

Methods

Ultrasound length and parenchymal kidney volume were determined from a population-based sample of 3972 Sardinians (age range 18–100 years). We then identified the subset of 2256 ‘healthy’ subjects to define age- and sex-specific reference ranges (2.5–97.5 percentile) of kidney volume. Logistic regression (accounting for family clustering) was used to identify the clinical characteristics associated with abnormally large kidneys or abnormally small kidneys.

Results

In the healthy subset, kidney volume and length increased up to the fourth to fifth decade of life followed by a progressive decrease in men, whereas there was a gradual kidney volume decrease throughout the lifespan of women. In the whole sample, independent predictors of lower kidney volume (<2.5 percentile for age and sex) were male sex, low body mass index, short height, low waist:hip ratio and high serum creatinine (SCr); the independent predictors of larger kidney volume (>97.5 percentile for age and sex) were younger age, female sex, diabetes, obesity, high height, high waist:hip ratio and lower SCr. Estimated heritability for kidney volume was 15%, and for length 27%; kidney volume correlated strongly with birthweight.

Conclusions

Overall, in a general healthy population, kidney measures declined with age differently in men and women. The determinants of kidney parenchymal volume include genetic factors and modifiable clinical factors.
Voxel-wise radiogenomic mapping of tumor location with key molecular alterations in patients with glioma
Authors: Tejada Neyra Miguel Angel , Neuberger Ulf , Reinhardt Annekathrin , Brugnara Gianluca , Bonekamp David , Sill Martin , Wick Antje , Jones David T W , Radbruch Alexander , Unterberg Andreas , Debus Jürgen , Heiland Sabine , Schlemmer Heinz-Peter , Herold-Mende Christel , Pfister Stefan , von Deimling Andreas , Wick Wolfgang , Capper David , Bendszus Martin , Kickingereder Philipp
Published: August 2018

Background

This study aims to evaluate the impact of tumor location on key molecular alterations on a single voxel level in patients with newly diagnosed glioma.

Methods

A consecutive series of n = 237 patients with newly diagnosed glioblastoma and n = 131 patients with lower-grade glioma was analyzed. Volumetric tumor segmentation was performed on preoperative MRI with a semi-automated approach and images were registered to the standard Montreal Neurological Institute 152 space. Using a voxel-based lesion symptom mapping (VLSM) analysis, we identified specific brain regions that were associated with tumor-specific molecular alterations. We assessed a predefined set of n = 17 molecular characteristics in the glioblastoma cohort and n = 2 molecular characteristics in the lower-grade glioma cohort. Permutation adjustment (n = 1000 iterations) was used to correct for multiple testing, and voxel t-values that were greater than the t-value in >95% of the permutations were retained in the VLSM results (α = 0.05, power > 0.8).

Results

Tumor location predilection for isocitrate dehydrogenase (IDH) mutant tumors was found in both glioblastoma and lower-grade glioma cohorts, each showing a concordant predominance in the frontal lobe adjacent to the rostral extension of the lateral ventricles (permutation-adjusted P = 0.021 for the glioblastoma and 0.013 for the lower-grade glioma cohort). Apart from that, the VLSM analysis did not reveal a significant association of the tumor location with any other key molecular alteration in both cohorts (permutation-adjusted P > 0.05 each).

Conclusion

Our study highlights the unique properties of IDH mutations and underpins the hypothesis that the rostral extension of the lateral ventricles is a potential location for the cell of origin in IDH-mutant gliomas.
The Impact of Acute Kidney Injury on the Risk of Mortality and Health Care Utilization Among Patients Treated With Polymyxins for Severe Gram-Negative Infections
Authors: Baradaran Sarah , Black Douglas J , Keyloun Katelyn R , Hansen Ryan N , Gillard Patrick J , Devine Beth
Published: August 2018

Background

With the rise of antibiotic resistance, polymyxin use has re-emerged but with a concern of renal toxicity. This study aims to assess mortality, length of stay, and total hospitalization cost associated with acute kidney injury (AKI) among recipients of intravenous (IV) sodium colistimethate (CMS) or IV polymyxin B (PMB).

Methods

We conducted a retrospective database analysis using the Premier database from January 1, 2012, through September 30, 2015. Adults ≥18 years of age who were admitted for inpatient treatment with ≥3 consecutive days of CMS or PMB were included. Generalized linear models compared patients who developed AKI with those who did not. Models were adjusted for patient and clinical characteristics.

Results

A total of 4886 patients were included; 4103 patients received CMS, and 783 received PMB. In the multivariable analyses, the presence of AKI was associated with higher in-hospital mortality in both the CMS cohort (adjusted odds ratio [aOR], 2.3; 95% confidence interval [CI], 1.9–2.7; P < .001) and the PMB cohort (aOR, 2.7; 95% CI, 1.8–4.2; P < .001). In both cohorts, patients who developed AKI experienced longer hospital stays (9.7 days and 11.6 days in the CMS and PMB cohorts, respectively; P < .001). The mean total hospitalization costs for patients who developed AKI were $47 820 higher (95% CI, $34 918–$60 722) in the CMS cohort and $35 244 higher (95% CI, $17 561–$52 928) in the PMB cohort.

Conclusions

The clinical and economic burden of AKI in the context of polymyxin use is substantial. The use of effective antibiotics with limited toxicity should remain a priority.
Side-to-Side Anastomosis Training Model Using Rat Common Carotid Arteries
Authors: Tayebi Meybodi Ali , Aklinski Joseph , Gandhi Sirin , Preul Mark C , Lawton Michael T
Published: August 2018

BACKGROUND

The side-to-side anastomosis is one of the difficult bypass configurations that may be used in various complex cerebral vascular and neoplastic cases. Few pure arterial models exist for practicing this bypass subtype.

OBJECTIVE

To provide an optimized side-to-side anastomosis training model using rat common carotid arteries (CCA).

METHODS

Bilateral CCAs were exposed in the neck of 10 anesthetized Sprague–Dawley rats. The arteries were juxtaposed in parallel, using temporary aneurysm clips applied proximally and distally. CCA caliber and the length of CCA juxtaposition were measured. Side-to-side anastomosis was completed and ischemia time was recorded. Unintended complications were recorded for further analysis.

RESULTS

Anastomosis was completed successfully in all animals. The CCAs were approximated in all animals without any difficulty or undue tension. In 2 rats, death occurred prior to completion of anastomosis, which was attributed to injury to the external jugular vein during vessel exposure. Mean ischemia time was 35 min with an average of 22 sutures done to complete the anastomosis. The average CCA caliber was 1.1 ± 0.2 mm and the arteries could be juxtaposed for an average length of 10.2 ± 1.5 mm.

CONCLUSION

Full exposure of the cervical segment of the CCAs enables tension-free approximation of adequate length of the vessel for a side-to-side anastomosis. Avoiding complications during exposure helps in prevention of animal death during the ischemia period.
Transgressive Segregation and Long-Term Consistency for High TSWV Field Resistance in the ‘Georgia-06G’ Peanut Cultivar
Authors: Branch W. D. , Culbreath A. K.
Published: August 2018

Tomato spotted wilt disease caused by tomato spotted wilt virus (TSWV) is a major peanut (Arachis hypogaea L.) production problem in the United States. TSWV has become endemic since the mid-1980s in the southeastern U.S. peanut production area. ‘Georgia-06G’ is a large-seeded, TSWV-resistant, runner-type peanut cultivar, whereas ‘Georgia Greener’ is a sister line with a smaller seed size than Georgia-06G. Both Georgia-06G and Georgia Greener have greater TSWV general field resistance with higher yields, total sound mature kernels grade, and dollar values than the parents (‘Georgia Green’ and ‘C-99R’), which shows transgressive segregation for these desirable quantitative traits. Therefore, the objective of this 12-year study was to evaluate the higher TSWV host-plant resistance found in the Georgia-06G over time compared with many other runner- and virginia-type peanut cultivars and advanced breeding lines. Despite yearly variability in TSWV and total disease incidence, the data indicate that Georgia-06G exhibited long-term high TSWV and total disease field resistance at midseason and late season, respectively. Georgia-06G was also found to have among the highest pod yield and dollar value every year. The higher general TSWV field resistance of Georgia-06G appears to be consistent across many years and locations, similar to the moderate TSWV resistance in Georgia Green.
Vitamin D/VDR signaling suppresses microRNA‐802‐induced apoptosis of keratinocytes in oral lichen planus
Authors: Zhao Bin , Xu Na , Li Ran , Yu Feiyan , Zhang Fang , Yang Fang , Ge Xuejun , Li Yan Chun , Du Jie
Published: August 2018

Vitamin D is known to play a protective role in inflammatory diseases. Although the suppressive effect of vitamin D/vitamin D receptor (VDR) signaling has been shown in the context of oral lichen planus (OLP), the molecular basis of its regulatory function remains poorly understood. Herein, we reported that miR‐802 over‐expression in OLP could aggravate apoptosis of oral keratinocytes by targeting B‐cell lymphoma 2 mRNA. In addition, vitamin D/VDR signaling was able to suppress miR‐802 expression in LPS‐treated or activated CD4+ T cell‐stimulated human oral keratinocytes by blocking NF‐κB pathways, thereby inhibiting OLP apoptosis. Consistent with the results in vitro, we showed that miR‐802 expression was enhanced in oral keratinocytes from VDR‐/‐ mice, and an inverse correlation between VDR and miR‐802 was found in human biopsy specimens of OLP. Collectively, our data suggest that vitamin D/VDR signaling suppresses oral keratinocyte apoptosis by targeting miR‐802.—Zhao, B., Xu, N., Li, R., Yu, F., Zhang, F., Yang, F., Ge, X., Li, Y. C., Du, J. Vitamin D/VDR signaling suppresses microRNA‐802‐induced apoptosis of keratinocytes in oral lichen planus. FASEB J. 33, 1042–1050 (2019). www.fasebj.org
Effect of Equipotent Doses of Propofol versus Sevoflurane Anesthesia on Regulatory T Cells after Breast Cancer Surgery
Authors: Oh Chung-Sik , Lee Jaemoon , Yoon Tae-Gyoon , Seo Eun-Hye , Park Hyun-Jun , Piao Liyun , Lee Seung-Hyun , Kim Seong-Hyop
Published: August 2018

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New

Background

Clusters of differentiation 39 and 73, enzymes expressed on the surface of regulatory T cells, promote cancer recurrence and metastasis by suppressing immune cells. The authors hypothesized that propofol is less immunosuppressive than volatile anesthetics. The objective of this randomized trial was to compare the changes in cluster of differentiation 39 and 73 expression on regulatory T cells between propofol- and sevoflurane-based anesthesia during breast cancer surgery.

Methods

A total of 201 patients having breast cancer surgery were randomly assigned and analyzed (n = 99 for propofol, n = 102 for sevoflurane). Blood samples were obtained immediately before anesthesia induction and 1 and 24 h postoperatively. The frequency of cluster of differentiation 39 and 73 expression on circulating regulatory T cells (primary outcome) and the frequency of circulating type 1 and type 17 helper T cells, natural killer cells, and cytotoxic T cells were investigated. Serum cytokines and the neutrophil-to-lymphocyte ratio were also evaluated.

Results

Changes in cluster of differentiation 39 and 73 expression on regulatory T cells over time did not differ with propofol and sevoflurane groups (difference [95% confidence interval]: 0.01 [−2.04 to 2.06], P = 0.995 for cluster of differentiation 39; −0.93 [−3.12 to 1.26], P = 0.403 for cluster of differentiation 73). There were no intergroup differences in type 1, type 17 helper T cells, natural killer cells, cytotoxic T cells, cytokines, or the neutrophil-to-lymphocyte ratio.

Conclusions

Changes in immune cells were similar with propofol and sevoflurane during breast cancer surgery. The effect of anesthetics on the perioperative immune activity may be minimal during cancer surgery.
Repeat Screening for Syphilis in the Third Trimester of Pregnancy
Authors: Hersh Alyssa R. , Megli Christina J. , Caughey Aaron B.
Published: August 2018

OBJECTIVE:

To estimate the cost-effectiveness of screening all women during the first and third trimesters compared with screening just once during pregnancy.

METHODS:

We used a theoretical cohort of 3.9 million women in the United States to model syphilis screening approaches in pregnancy, particularly comparing one-time screening with repeat third-trimester screening. Outcomes of syphilis infection included in the model were congenital syphilis, intrauterine fetal demise, neonatal death, and total quality-adjusted life-years (QALYs). Probabilities, utilities, and costs were obtained from the literature, and a cost-effectiveness threshold was set at $100,000 per QALY. A societal perspective was assumed.

RESULTS:

Our model demonstrated that repeat screening in the third trimester for syphilis in pregnancy will result in fewer maternal and neonatal adverse outcomes and higher QALYs when compared with screening once in the first trimester. Specifically, we demonstrated that repeat screening results in 41 fewer neonates with evidence of congenital syphilis, 73 fewer cases of intrauterine fetal demise, 27 fewer neonatal and infant deaths, in addition to a cost savings of $52 million and 4,000 additional QALYs.

CONCLUSION:

Using our baseline assumptions, our data support that in pregnancy, repeat screening for syphilis is superior to single screening during the first trimester and is both cost-effective and results in improvement in maternal and neonatal outcomes. When screening policies are being created for pregnant women, the cost-effectiveness of repeat screening for syphilis should be considered.
RETINAL ARTERIAL DILATION IS IMPAIRED IN EYES WITH DRUSEN AND RETICULAR PSEUDODRUSEN
Authors: Rabiolo Alessandro , Benatti Lucia , Tomasso Livia , Zucchiatti Ilaria , Gelormini Francesco , Casaluci Marco , Querques Lea , Sacconi Riccardo , Bandello Francesco , Querques Giuseppe
Published: August 2018

Purpose:

To analyze static characteristics and dynamic functionality of retinal vessels in eyes with drusen and reticular pseudodrusen (RPD) using dynamic vessel analyzer.

Methods:

Patients with clinical diagnosis of isolated RPD or medium-large drusen and healthy controls were enrolled in the study between July 2016 and May 2018. Participants underwent complete ophthalmologic examination, including enhanced depth imaging structural optical coherence tomography, dynamic retinal vessel analysis, and static retinal vessel analysis.

Results:

Twenty-eight eyes of 23 patients with drusen (9 men, mean age 77 ± 6 years), 22 eyes of 16 patients with RPD (7 men, mean age: 76 ± 6 years), and 22 eyes of 22 control subjects (11 men, mean age of 75 ± 6 years) were enrolled. Static retinal vessel analysis did not show any significant difference between the three groups for the central retinal artery equivalent (P = 0.11), the central retinal vein equivalent (P = 0.27), and the arteriovenous ratio (P = 0.30). Dynamic vessel analysis showed significantly reduced arterial dilation in eyes with drusen (P = 0.0001) and RPD (P = 0.015) compared with control subjects. No significant difference was seen between drusen and RPD groups (P = 0.32). Dynamic vessel analysis of retinal veins showed no differences between the three groups (P = 0.10).

Conclusion:

Dynamic vessel analysis in eyes with drusen and RPD revealed an impaired retinal arterial dilation in response to flicker light stimulation, which further supports the relationship between cardiovascular risk and age-related macular degeneration.
Assessment and Validation of Syndromic Case Definitions for Respiratory Syncytial Virus Testing in a Low Resource Population
Authors: Omer Saad B. , Bednarczyk Robert , Kazi Momin , Guterman L. Beryl , Aziz Fatima , Allen Kristen E. , Yildirim Inci , Ali S. Asad
Published: August 2018

Standardized case definitions are needed in decision-making regarding respiratory syncytial virus control strategies, including vaccine evaluation. A syndromic case definition comprising of “wheeze or apnea or cyanosis” could be useful for community-based surveillance of moderate respiratory syncytial virus infection among young infants particularly in resource-limited settings. However, this definition showed modest specificity (29.2%–49.6%), indicating that community-based surveillance may need augmentation with other data.
Valvular Regurgitation in a Biventricular Mock Circulatory Loop
Authors: Shehab Sajad , Allida Sabine M. , Newton Phillip J. , Robson Desiree , Macdonald Peter S. , Davidson Patricia M. , Jansz Paul C. , Hayward Christopher S.
Published: August 2018

Aortic regurgitation (AR), mitral regurgitation (MR), and tricuspid regurgitation (TR) after continuous-flow left ventricular assist device (LVAD) are common and may increase with prolonged LVAD support. The aim of this study was to simulate severe valvular regurgitation (AR, MR, and TR) within a 4-elemental pulsatile mock circulatory loop (MCL) and observe their impact on isolated LVAD and biventricular assist device (BiVAD) with HeartWare HVAD. Aortic regurgitation, MR, and TR were achievedviathe removal of one leaflet from bileaflet mechanical valve from the appropriate valves of the left or right ventricles. The impact of alteration of LVAD pump speed (LVAD 2200–4000 RPM, right ventricular assist device [RVAD] 2400 RPM) and altered LVAD preload (10–25 mm Hg) was assessed. With each of the regurgitant valve lesions, there was a decrease in isolated LVAD pump flow pulsatility. Isolated LVAD provided sufficient support in the setting of severe MR or TR compared with control, and flows were enhanced with BiVAD support. In severe AR, there was no benefit of BiVAD support over isolated LVAD, and actual loop flows remained low. High LVAD flows combined with low RVAD flows and dampened aortic pressures are good indicators of AR. The 4-elemental MCL successfully simulated several control and abnormal valvular conditions using various pump speeds. Current findings are consistent with conservative management of MR and TR in the setting of mechanical support, but emphasize the importance of the correction of AR.
Simulated Performance of the Cleveland Clinic Continuous-Flow Total Artificial Heart Using the Virtual Mock Loop
Authors: Miyamoto Takuma , Horvath David J. , Horvath Dennis W. , Karimov Jamshid H. , Byram Nicole , Kuban Barry D. , Fukamachi Kiyotaka
Published: August 2018

Our new Virtual Mock Loop (VML) is a mathematical model designed to simulate the human cardiovascular system and gauge performance of mechanical circulatory support devices. We aimed to mimic the hemodynamic performance of Cleveland Clinic’s self-regulating continuous-flow total artificial heart (CFTAH) via VML and evaluate VML’s accuracy versus bench data from our standard mock circulatory loop. The VML reproduced 23 hemodynamic conditions. Systemic/pulmonary vascular resistances and pump rotational speed were set for VML from bench test data. We compared outputs (pump flow, left/right pump pressure rise, normalized pump performance, and atrial pressure difference) of the two methods. Data from pump flow and left pump pressure rise were similar, but right pump pressure rise slightly differed. Left pump normalized pump performance curves were similar. Right pump VML results were within the same performance range indicated by bench tests. The plots of atrial pressure differences of VML versus bench-test data were similar, but slightly differed in the midrange of systemic/pulmonary gradients. Virtual Mock Loop successfully reproduced results from our mock circulatory loop of CFTAH test conditions. The CFTAH’s self-regulation feature of right pump performance was also calculated effectively. We foresee using versions of the VML for training, simulating physiologic cardiac conditions, and patient monitoring.
LVAD Pulsatility Assesses Cardiac Contractility: In Vitro Model Utilizing the Total Artificial Heart and Mock Circulation
Authors: Mikail Philemon , Crosby Jessica R. , Slepian Marvin J. , Smith Richard , Khalpey Zain
Published: August 2018

There is a need for a consistent, reproducible, and cost-effective method of determining cardiac recovery in patients who receive emerging novel therapeutics for advanced and end-stage heart failure (HF). With the increasing use of ventricular assist devices (VADs) in end-stage HF, objective device diagnostics are available for analysis. Pulsatility, one of the accessible diagnostic measures, is a variable gage of the differential between peak systolic and minimum diastolic flow during a single cardiac cycle. Following implantation of the VAD, HeartWare’s HVAD records pulsatility regularly. Thus, we hypothesize that this measurement relates to the contractility of the heart and could be utilized as a metric for determining patient response to various therapeutics. In this study, therefore, we develop a translatable and effective predictive model characterizing pulsatility to determine HF status and potential HF recovery using the SynCardia Total Artificial Heart (TAH) in conjunction with a Donovan Mock Circulation System to create a simulation platform for the collection of pulsatility data. We set the simulation platform to patient conditions ranging from critical heart failure to a normal operating condition through the variation preload, afterload, and left ventricular (LV) pumping force or TAH “contractility.” By manipulating these variables, pulsatility was found to accurately indicate significant (p < 0.05) improvements in LV contractility at every recorded afterload and preload, suggesting that it is a valuable parameter for the assessment of cardiac recovery in patients.