bluuebunny/crossref_metadata_2025 huggingface dataset:
Aerodynamic Optimization of a UAV Wing subject to Weight, Geometric, Root Bending Moment, and Performance Constraints
Authors: Körpe Durmuş Sinan , Kanat Öztürk Özdemir
Published: October 2019

In this study, the optimization of a low-speed wing with functional constraints is discussed. The aerodynamic analysis tool developed by the coupling of the numerical nonlinear lifting-line method to Xfoil is used to obtain lift and drag coefficients of the baseline wing. The outcomes are compared with the results of the solver based on the nonlinear lifting-line theory implemented into XLFR5 and the transition shear stress transport model implemented into ANSYS-Fluent. The agreement between the results at the low and moderate angle of attack values is observed. The sequential quadratic programming algorithm of the MATLAB optimization toolbox is used for the solution of the constrained optimization problems. Three different optimization problems are solved. In the first problem, the maximization of CL3/2/CD is the objective function, while level flight condition at maximum CL3/2/CD is defined as a constraint. The functional constraints related to the wing weight, the wing planform area, and the root bending moment are added to the first optimization problem, and the second optimization problem is constructed. The third optimization problem is obtained by adding the level flight condition and the available power constraints at the maximum speed and the level flight condition at the minimum speed of the baseline unmanned air vehicle to the second problem. It is demonstrated that defining the root bending moment, the wing area, and the available power constraints in the aerodynamic optimization problems leads to more realistic wing planform and airfoil shapes.
Treating Clinically Node-Negative Insular Thyroid Carcinoma without Prophylactic Central Compartment Neck Dissection Is Associated with Decreased Survival Regardless ofTStaging and Administration of Radioactive Iodine Therapy: The First Evidence
Authors: Yu Peng-Cheng , Shi Xiao , Ma Ben , Li Cui-Wei , Tan Li-Cheng , Hu Wei-Ping , Wang Yu , Wei Wen-Jun , Wang Yu-Long , Ji Qing-Hai
Published: October 2019

Forthe rare but aggressive insular thyroid carcinoma (ITC), there's no clear evidence to determine whether prophylactic central compartment neck dissection (CCND) is necessary for cN0 disease. This study provides the first evidence that treating cN0 ITC without prophylactic CCND is associated with decreased survival regardless ofTstaging and administration of RAI therapy.Background. Regarding the rare but aggressive insular thyroid carcinoma (ITC), the value of prophylactic central compartment neck dissection (CCND) for clinically node-negative (cN0) disease is unclear. We aimed to provide the first evidence.Methods. N0 and pN1a ITC patients were identified from the Surveillance, Epidemiology, and End Results database. These patients were divided intothyroid-surgery + CCND group (pN0/pN1a patients confirmed by CCND) andthyroid-surgerygroup (cN0 patients without CCND). Differences in overall survival (OS) and disease-specific survival (DSS) between the two groups were evaluated. Subgroup analyses were also conducted.Results. Of the overall 112 patients, 44 (39.3%) received CCND. On multivariate analyses, thelobectomy ± isthmusectomy/total-thyroidectomy(Lob/TT) group demonstrated poorer OS and DSS than the Lob/TT + CCND group (P<0.05). When we separately analyzed patients treated by TT, multivariate analyses showed the TT group still revealed compromised OS and DSS than the TT + CCND group (P<0.05). Furthermore, absence of CCND independently predicted decreased OS no matter whether radioactive iodine (RAI) was administered. Similar results were obtained for T3/T4 patients. Moreover, for T1/T2 patients receiving CCND, 0/12 died during the study period, while for T1/T2 patients without CCND, 8/23 (34.8%) died, 5/23 (21.7%) due to ITC.Conclusion. Regardless ofTstaging and RAI treatment, cN0-ITC patients without CCND had decreased survival compared with pN0/pN1a patients receiving CCND. Therefore, if a cN0 patient is diagnosed with ITC, prophylactic CCND may be considered as a secondary procedure (postoperatively diagnosed) or a primary procedure (preoperatively/intraoperatively diagnosed). Prospective studies are expected to validate the conclusion.
Mortality and Morbidity of Beef Calves in Free-Range Farms in Alentejo, Portugal—A Preliminary Study
Authors: Santos Rute , Cachapa Ana , Carvalho Graça P. , Silva Carolina B. , Hernández Laura , Costa Lina , Pereira Luísa S. , Minas Miguel , Vala Helena
Published: October 2019

Extensive cow-calf beef cattle farms play a significant role in Portuguese livestock production, but records of important production variables, such as calf mortality, are scarce. To assess herd-level calf mortality and its potential economic impact, farmers from the Alentejo region were asked to fill a questionnaire regarding herd size, feeding and reproductive management practices, calf mortality (from birth to weaning), and detection of the main morbidity causes, as well as of sudden, unexplained deaths during the previous 12 months. Farmers were also requested to quantitatively assess the economic impact of calf mortality on their annual revenue. In the majority of farms, the herd size was larger than 100 animals. The median stocking rate was 0.41 adult animals/hectare, and 70% of farmers stated their farm was self-sufficient in forage. The percent of live births that resulted in weaned calves averaged 94.3%, which led to the assumption of a 5.7% calf mortality rate from birth to weaning. In the previous 12 months, 78.8% of the farms identified at least one case of calf diarrhea, 60.7% identified at least one case of respiratory disease, and 82.1% had at least one sudden, unexplained calf death. As expected, farmers that assessed a higher impact of calf losses on their annual economic revenue were also those who reported higher incidences of calf diarrhea, respiratory disease, and sudden, unexplained deaths. One-quarter of the farmers were unable to assess the economic impact of calf mortality on the farm’s revenue. Herd size appears to have a predictive value on calf mortality in the first month of life, and from 30 days to weaning. The number of sudden, unexplained calf deaths seems to have a predictive value on overall calf mortality (from birth to weaning), suggesting that the farms’ management practices probably play an important role in calf mortality throughout the suckling period. Further studies are needed to fully understand calf mortality in Portuguese extensive rearing systems.
Correlation of Power Consumption of Double Impeller Based on Impeller Spacing in Laminar Region
Authors: Furukawa Haruki , Kamiya Toshiki , Kato Yoshihito
Published: October 2019

Power consumption is an important parameter for the design of mixing equipment. The aim of this study is to develop a new correlation of the power consumption of a double impeller. The effect of impeller spacing on the double-impeller flow pattern and power consumption was investigated in the laminar region. As a result, the effect of impeller spacing on the flow pattern was described based on the ratio of impeller spacing to the impeller blade height. Moreover, the power consumption of a double impeller could be correlated with the same ratio.
Modelling and Assessing the Performance of Hybrid PV-CSP Plants in Morocco: A Parametric Study
Authors: Bousselamti Loubna , Cherkaoui Mohamed
Published: October 2019

Based on the examination of the efficiency of solar plants, this study focuses on three main plants: a photovoltaic (PV) plant, a concentrated solar power (CSP) plant, and a hybrid PV/CSP plant. The modelling of the three plants has been implemented to evaluate the influence of design parameters (orientation angles, solar multiple (SM), thermal energy storage capacity (TES), and fraction of hybridization) on them. Several simulations have been recreated and discussed in details to study the optimal configuration of the two first plants and the profitability of the PV/CSP plants for Ouarzazate (Morocco) location. The findings demonstrate that the optimal orientation angles and TES/SM, respectively, affect the performances of PV and CSP plants, and they also reveal that PV/CSP systems have the benefits to increase the annual energy produced, reduce the cost, and offer a high dispatchability to supply a baseload. The implementing of optimal PV/CSP plant has a great economic impact on Ouarzazate city.
Weakening Relationship between East Asian Summer Monsoon and Asian-Pacific Oscillation after 1990s
Authors: Hua Wei , Lin Zouxin , Wang Xin , Fan Guangzhou
Published: October 2019

The East Asian summer monsoon (EASM), which is an important influencing summer climate of East Asia, is associated with large-scale change of the land-sea thermal contrast. The Asian-Pacific Oscillation (APO) can modulate the EASM because it not only represents the upper-tropospheric zonal land-sea thermal contrast over Asia and the Pacific region, but it also affects the sea surface temperature (SST) over the North Pacific, which can tune the land-sea thermal contrast for the EASM. This study revealed weakening of the APO-EASM relationship since the 1990s. It was found that the relationship between the APO and the EASM during 1948–1990 (1991–2016) was statistically significant (insignificant). Further study indicated that the APO was concurrent with significant positive SST in the central North Pacific and subtropical central-western Pacific during 1948–1990, which contributed to the shift of the Pacific Decadal Oscillation (PDO) from its cold to warm phase and led to a weakened EASM. The APO-related SST and atmospheric circulation anomalies were found statistically to be insignificant during 1991–2016, which indicates a weakening of influence of the APO on shift of the PDO, and even a weaker link to the EASM.
Development and FEM Modeling of a New Severe Plastic Deformation Process according to the Reverse Shear Scheme
Authors: Tarasov Alexander F. , Altukhov Alexander V. , Gribkov Eduard P. , Abdulov Aleksandr R.
Published: October 2019

Industrial commercial use of SPD processes is in some cases hindered by the complexity of equipment and high loads on the tool associated with high hydrostatics upon implementation of existing deformation processes. New and modified SPD schemes are offered relatively often, so the methods for their creation, modeling, and ways of improvement are of particular interest. Therefore, the article provides a classification of SPD schemes, which are divided into several groups depending on the nature of the material flow in the deformation zone. The second attribute of the fission process is the volume of the metal, contemporaneously located in the plastic deformation zone. An analysis of the influence of SPD schemes on the features of formation of a plastic deformation zone allows us to identify promising ways to modify them. A new SPD process is proposed, called as the “Reverse Shear” (RS), in which the workpiece is deformed under conditions of flat deformed state, uniform in each cross section along the entire length of the workpiece. The RS process allows us to change the paths of deformation to redistribute strain within the workpiece volume due to different positioning of a workpiece in a die. To justify the proposed deformation scheme, the SPD processes are divided into groups and an analysis of the deformation schemes’ features, which are analogs of RS, is performed. Simulation of the considered SPD processes was performed using FEM, implemented in specialized QForm CAE-system. A study of the influence of a tool with inclined surfaces on formation of a deformation zone in a workpiece during RS and analogues has been carried out. The degree of deformation nonuniformity in a cross section for the considered deformation schemes has been determined, and the possibilities of the proposed process are shown in comparison with analogues. The advantage of the RS scheme is the absence of unformed edges of the workpiece, which reduces material consumption, increasing the accumulated degree of deformation by one operation and reducing the tooling complexity to obtain workpieces with a desired structure. It also provides an opportunity to deform workpieces by various routes (RS-60 and RS-180) and to more specifically develop or select SPD schemes based on modeling. Changing the aspect ratio of the workpiece cross section also allows us to manage the change in its stress-strain state during deformation. Comparisons with the experiment carried out for three operations of deformation of a Cu-ETP copper sample by the RS-60 route show that the simulation results correspond to the real process.
Vector Sum Analysis Method of Loess Slope Stability under Rising Groundwater Level Conditions
Authors: Xue Haibin , Dang Faning , Li Yanlong , Yin Xiaotao , Lei Man
Published: October 2019

The stability analysis of loess slopes with a rising groundwater level is a problem that integrates unsaturated and transient seepage, stress analysis, and stability prediction. For this purpose, a sequentially coupled method of seepage‐softening‐stability was used. First, seepage analysis of a loess slope with a rising groundwater level was conducted according to unsaturated and transient seepage analysis theory. Second, the spatial distribution of the deformation and strength parameters of the soil, both of which were based on the calculated results of the seepage analysis, were adjusted according to the water‐induced structural deterioration equation. Third, the vector sum analysis method of loess slope stability, which was based on the temporal‐spatial distribution laws of effective unit weight, elastic modulus, Poisson’s ratio, cohesion, internal friction angle, and seepage force, was performed by the body force method. To verify the proposed method, the limit equilibrium method of loess slope stability was conducted by the surface force method. Finally, the progressive failure process of a loess slope with a rising groundwater level on the White Deer Plain was presented as an example. A comparison analysis of the calculated results of the two methods revealed that the proposed method was reasonable and reliable.
A Phase I Trial of Berberine in Chinese with Ulcerative Colitis
Authors: Xu Li , Zhang Yujie , Xue Xianmin , Liu Jie , Li Zeng-Shan , Yang Guang-Yu , Song Ying , Pan Yan , Ma Yueyun , Hu Sijun , Wen Aidong , Jia Yanyan , Rodriguez Luz Maria , Tull Mary Beth , Benante Kelly , Khan Seema A. , Cao Ying , Jovanovic Borko , Richmond Ellen , Umar Asad , Bergan Raymond , Wu Kaichun
Published: October 2019

The Chinese natural product, berberine, has biological properties that support its potential efficacy as a colon cancer prevention agent. Its longstanding use in China to treat gastrointestinal tract and rheumatologic disorders is generally regarded as safe, supporting initial investigations in an at-risk population, such as individuals with ulcerative colitis. However, the safety of berberine in this population is not established. Individuals living in China with biopsy-proven ulcerative colitis, ≤grade 2 dysplasia, and with a ulcerative colitis disease activity index (UCDAI) score ≤1 on mesalamine, were randomized 3:1 in a double-blind phase I trial to berberine 900 mg/day or placebo for 3 months, with the primary objective of assessing safety. Blood samples and biopsies of the colorectum, from prespecified locations, were collected prior to and following therapy. Secondary endpoints included changes in UCDAI score, and in tissue and plasma markers of inflammation. Of toxicities at least possibly related, one episode of grade 3 elevation in transaminases and one episode of grade 1 nausea were observed among 12 individuals on berberine, and none were observed among 4 on placebo. The mean plasma berberine concentration was 3.5 nmol/L after berberine treatment, significantly higher than 0.5 nmol/L with placebo. Berberine significantly decreased the Geboes grade in colonic tissue, but had a nonsignificant effect on other tissue or blood biomarkers related to cell growth and inflammation. The combination of berberine and mesalamine is well tolerated in Chinese with ulcerative colitis and may enhance mesalamine's anti-inflammatory effects in colonic tissue.
Ubiquitin-Specific Protease 8 Mutant Corticotrope Adenomas Present Unique Secretory and Molecular Features and Shed Light on the Role of Ubiquitylation on ACTH Processing
Authors: Sesta Antonella , Cassarino Maria Francesca , Terreni Mariarosa , Ambrogio Alberto G. , Libera Laura , Bardelli Donatella , Lasio Giovanni , Losa Marco , Pecori Giraldi Francesca
Published: October 2019

Background: Somatic mutations in the ubiquitin-specific protease 8 (USP8) gene have recently been shown to occur in ACTH-secreting pituitary adenomas, thus calling attention to the ubiquitin system in corticotrope adenomas. Objectives: Assess the consequences of USP8 mutations and establish the role of ubiquitin on ACTH turnover in human ACTH-secreting pituitary adenomas. Methods: USP8 mutation status was established in 126 ACTH-secreting adenomas. Differences in ACTH secretion and POMC expression from adenoma primary cultures and in microarray gene expression profiles from archival specimens were sought according to USP8 sequence. Ubiquitin/ACTH coimmunoprecipitation and incubation with MG132, a proteasome inhibitor, were performed in order to establish whether ubiquitin plays a role in POMC/ACTH degradation in corticotrope adenomas. Results: USP8 mutations were identified in 29 adenomas (23%). Adenomas presenting USP8 mutations secreted greater amounts of ACTH and expressed POMC at higher levels compared to USP wild-type specimens. USP8 mutant adenomas were also more sensitive to modulation by CRH and dexamethasone in vitro. At microarray analysis, genes associated with endosomal protein degradation and membrane components were downregulated in USP8 mutant adenomas as were AVPR1B, IL11RA, and PITX2. Inhibition of the ubiquitin-proteasome pathway increased ACTH secretion and POMC itself proved a target of ubiquitylation, independently of USP8 sequence status. Conclusions: Our study has shown that USP8 mutant ACTH-secreting adenomas present a more “typical” corticotrope phenotype and reduced expression of several genes associated with protein degradation. Further, ubiquitylation is directly involved in intracellular ACTH turnover, suggesting that the ubiquitin-proteasome system may represent a target for treatment of human ACTH-secreting adenomas.
Comparison of Vessel Density Reduction in the Deep and Superficial Capillary Plexuses in Branch Retinal Vein Occlusion
Authors: Kim Jee Taek , Chun Yeon Sook , Lee Jeong Kyu , Moon Nam Ju , Yi Dae Yong
Published: October 2019

Purpose: To quantify the susceptibility of the deep capillary plexus (DCP) in comparison with that of the superficial capillary plexus (SCP) in eyes with branch retinal vein occlusion (BRVO) using swept-source optical coherence tomography angiography (SS-OCTA). Methods: SS-OCTA (TritonTM; Topcon, Tokyo, Japan) scans (3 × 3 mm) of 41 patients with BRVO were retrospectively analyzed. The mean vessel densities (VDs) of the SCP and the DCP were calculated in eyes with BRVO using the ImageJ program (National Institutes of Health, Bethesda, MD, USA) and compared with those in the normal fellow eye without any morbidity or unaffected sector in the BRVO eye. Results: The reduction rate of mean VD in SCP and DCP between the affected and unaffected sector of eyes with BRVO was 13.88 and 24.60%, respectively. Additionally, the reduction rate of mean VD in the SCP and DCP in the affected sector of BRVO eyes versus the corresponding sector of fellow eyes was 13.31 and 24.49%, respectively. Conclusion: The DCP was 1.77–1.84 times more affected than the SCP by ischemic damage in eyes with BRVO.
Inhibition of MicroRNA-9 Improves Fracture Healing by Modulating the Bone Morphogenetic Protein-7 Pathway
Authors: Deng Jianhua , Wu Jun , Zhu Yuchang
Published: October 2019

We evaluated the effect of microRNA (miR)-9 inhibition on fracture healing in a rat model of femoral fracture. The rats were divided into sham, negative control and miR-9 inhibitor groups. The miR-9 inhibitor group received 30 pmol/mL inhibitor intrathecally for 8 consecutive weeks following surgery-induced femoral fracture. The effect of miR-9 inhibition on fracture healing was estimated by determining the bone mineral density (BMD) and by performing X-ray analysis of the fractured bone. The serum levels of markers of bone formation were estimated by enzyme-linked immunosorbent assay and reverse transcription polymerase chain reaction, and western blotting and immunohistochemical analysis were performed to assess the effect of miR-9 inhibition on fracture healing. The BMD at the fracture site was significantly higher in the miR-9 inhibitor group than in the negative control group. Inhibition of miR-9 blocked the fracture gap and resulted in new callus formation at the fracture site. The serum levels of osteocalcin and bone GLA protein were increased and that of alkaline phosphatase was decreased by inhibition of miR-9 compared to levels in the negative control. However, inhibition of miR-9 significantly increased the mRNA levels of runt-related transcription factor 2 (Runx2) and bone morphogenetic protein 7 (BMP-7) in the bone tissue at the fracture site compared to the negative control group; this result was confirmed by western blotting. In conclusion, ­miR-9 inhibition enhanced fracture healing by modulating the BMP-7/Runx2 signalling pathway in a rat model of femoral fracture.
Mechanisms and Risk Factors Contributing to Visual Field Deficits following Stereotactic Laser Amygdalohippocampotomy
Authors: Voets Natalie L. , Alvarez Ivan , Qiu Deqiang , Leatherday Christopher , Willie Jon T. , Sotiropoulos Stamatios , Gleichgerrcht Ezequiel , Bonilha Leonardo , Pedersen Nigel P. , Kadom Nadja , Saindane Amit M. , Gross Robert E. , Drane Daniel L.
Published: October 2019

Selective laser amygdalohippocampotomy (SLAH) is a minimally invasive surgical treatment for medial temporal lobe epilepsy. Visual field deficits (VFDs) are a significant potential complication. The objective of this study was to determine the relationship between VFDs and potential mechanisms of injury to the optic radiations and lateral geniculate nucleus. We performed a retrospective cross-sectional analysis of 3 patients (5.2%) who developed persistent VFDs after SLAH within our larger series (n = 58), 15 healthy individuals and 10 SLAH patients without visual complications. Diffusion tractography was used to evaluate laser catheter penetration of the optic radiations. Using a complementary approach, we evaluated evidence for focal microstructural tissue damage within the optic radiations and lateral geniculate nucleus. Overablation and potential heat radiation were assessed by quantifying ablation and choroidal fissure CSF volumes as well as energy deposited during SLAH.SLAH treatment parameters did not distinguish VFD patients. Atypically high overlap between the laser catheter and optic radiations was found in 1/3 VFD patients and was accompanied by focal reductions in fractional anisotropy where the catheter entered the lateral occipital white matter. Surprisingly, lateral geniculate tissue diffusivity was abnormal following, but also preceding, SLAH in patients who subsequently developed a VFD (all p = 0.005).In our series, vision-related complications following SLAH, which appear to occur less frequently than following open temporal lobe ­surgery, were not directly explained by SLAH treatment parameters. Instead, our data suggest that variations in lateral geniculate structure may influence susceptibility to indirect heat injury from transoccipital SLAH.
A Novel Method for Assessing Enamel Thickness Distribution in the Anterior Dentition as a Signal for Gouging and Other Extractive Foraging Behaviors in Gummivorous Mammals
Authors: Selig Keegan R. , López-Torres Sergi , Hartstone-Rose Adam , Nash Leanne T. , Burrows Anne M. , Silcox Mary T.
Published: October 2019

Gummivory poses unique challenges to the dentition as gum acquisition may often require that the anterior teeth be adapted to retain a sharp edge and to resist loading because they sometimes must penetrate a highly obdurate substrate during gum extraction by means of gouging or scraping. It has been observed previously that the enamel on the labial surface of the teeth used for extraction is thicker relative to that on the lingual surface in taxa that extract gums, while enamel is more evenly distributed in the anterior teeth of taxa that do not regularly engage in extractive behaviors. This study presents a quantitative methodology for measuring the distribution of labial versus lingual enamel thickness among primate and marsupial taxa in the context of gummivory. Computed microtomography scans of 15 specimens representing 14 taxa were analyzed. Ten measurements were taken at 20% intervals starting from the base of the crown of the extractive tooth to the tip of the cutting edge across the lingual and labial enamel. A method for including worn or broken teeth is also presented. Mann-Whitney U tests, canonical variates analysis, and between-group principal components analysis were used to examine variation in enamel thickness across taxa. Our results suggest that the differential distribution of enamel thickness in the anterior dentition can serve as a signal for gouging behavior; this methodology distinguishes between gougers, scrapers, and nonextractive gummivores. Gouging taxa are characterized by significantly thicker labial enamel relative to the lingual enamel, particularly towards the crown tip. Examination of enamel thickness patterning in these taxa permits a better understanding of the adaptations for the extraction of gums in extant taxa and offers the potential to test hypotheses concerning the dietary adaptations of fossil taxa.
Reproducibility of Foveal Avascular Zone and Superficial Macular Retinal Vasculature Measurements in Healthy Eyes Determined by Two Different Scanning Protocols of Optical Coherence Tomography Angiography
Authors: Xiao Hui , Liu Xing , Liao Lingling , Tan Kaixin , Ling Yunlan , Zhong Yimin
Published: October 2019

Purpose: To assess the reproducibility of quantitative measurements of the foveal avascular zone (FAZ) and retinal vasculature determined by different scanning protocols of optical coherence tomography angiography (OCTA) in healthy volunteers. Method: All participants were scanned by two trained operators using an AngioPlex OCTA. Both angiography protocols (6 × 6 mm and 3 × 3 mm) were performed three times on the same eye by operator A and one additional time by operator B. The FAZ area and perimeter, retinal vessel length density (VLD) and perfusion density (PD) of different regions were analysed. Results: Fifty-two eyes from 52 subjects were recruited for this study. The repeated measurements of FAZ, VLD, and PD parameters obtained by the same operator, as well as by different operators, were not significantly different when the same protocol was used (p > 0.05). The intra- and inter-operator intraclass correlation coefficients (ICCs) of the FAZ and central VLD and PD parameters (range, 0.99–0.95) were better than the intra- and inter-operator ICCs of VLD and PD in the inner and outer rings (range, 0.86–0.90). The FAZ area, perimeter, and VLDs obtained by the 3 × 3 mm protocol were larger than those obtained by the 6 × 6 mm protocol (p < 0.01), but the PDs obtained by the 3 × 3 mm protocol were smaller than those obtained by the 6 × 6 mm protocol (p < 0.001). All of the corresponding parameters obtained by the two protocols were positively correlated (r = 0.64–0.99, p < 0.001). Conclusion: Both the 6 × 6 and 3 × 3 mm protocols of the AngioPlex OCTA provide good reproducibility for assessing the FAZ and superficial retinal vasculature. However, the values obtained by these different protocols cannot be compared directly.
Implementation of Urgent Start Peritoneal Dialysis Reduces Hemodialysis Catheter Use and Hospital Stay in Patients with Unplanned Dialysis Start
Authors: Artunc Ferruh , Rueb Sandra , Thiel Karolin , Thiel Christian , Linder Katarzyna , Baumann Dorothea , Bunz Hanno , Muehlbacher Thomas , Mahling Moritz , Sayer Michael , Petsch Marlies , Guthoff Martina  , Heyne Nils
Published: October 2019

Background: Unplanned start of renal replacement therapy is common in patients with end-stage renal disease and often accomplished by hemodialysis (HD) using a central venous catheter (CVC). Urgent start using peritoneal dialysis (PD) could be an alternative for some of the patients; however, this requires a hospital-based PD center that offers a structured urgent start PD (usPD) program. Methods: In this prospective study, we describe the implementation of an usPD program at our university hospital by structuring the process from presentation to PD catheter implantation and start of PD within a few days. For clinical validation, we compared the patient flow before (2013–2015) and after (2016–2018) availability of usPD. Results: In the 3 years before the availability of usPD, 14% (n = 12) of incident PD patients (n = 87) presented in an unplanned situation and were initially treated with HD using a CVC. In the 3 years after implementation of the usPD program, 18% (n = 18) of all incident PD patients (n = 103) presented in an unplanned situation of whom n = 12 (12%) were treated with usPD and n = 6 (6%) with initial HD. usPD significantly reduced the use of HD by 57% (p = 0.0005). Hospital stay was similar in patients treated with usPD (median 9 days) compared to those with elective PD (8 days), and significantly lower than in patients with initial HD (26 days, p = 0.0056). Conclusions: Implementation of an usPD program reduces HD catheter use and hospital stay in the unplanned situation.
Inhibition of Canonical Transient Receptor Potential 5 Channels Polarizes Macrophages to an M1 Phenotype
Authors: Tao Lerong , Guo Gang , Qi Yanyan , Xiong Yong , Ma Xueyu , Wu Nan , Dong Chao , Yang Cui
Published: October 2019

Background: Transient receptor potential (TRP) channels are widely expressed in the mammals. However, the functions of canonical TRP (TRPC) in inflammatory responses are largely unknown. The present study was focused on the effect of canonical TRP5 (TRPC5) channel on the polarization of macrophage to an M1 phenotype. Methods: Polarization of macrophages was studied in TRPC5 knockout (TRPC5–/–) mice and in Raw264.7, a mouse macrophage cell line. Indicators of M1 type polarized macrophage were measured in the aorta of mice. Inhibition of TRPC5 in macrophages was achieved by the administration of ML204 (a non-selective TRPC5 antagonist) or the silencing of the TRPC5 gene with short hairpin RNA. Lipopolysaccharide (LPS) was used to stimulate Raw264.7 cells to an M1 type polarization. Proinflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 were measured in mice or cells, and protein expressions of Akt, phosphorylated (p)-Akt, IκBα, p-IκBα, and NF-κB were analyzed in Raw264.7 cells. Results: In TRPC5–/– mice the number of M1 type polarization of macrophages infiltrating into the aortic walls were significantly increased. The serum levels of inflammatory cytokines, TNF-α and IL-6 were also increased. Furthermore, after treated with ML204 or silenced the gene of TRPC5, the releases of TNF-α, IL-1β and IL-6 from lipopolysaccharide-stimulated RAW264.7 cells were signiﬁcantly increased. Meanwhile, phosphorylations of Akt and IκBα were upregulated, and the shift of NF-κB from the cytoplasm to nucleus was markedly enhanced. Conclusion: The activation of TRPC5 may inhibit the polarization of macrophage to an M1 phenotype by regulating Akt/IκB/NF-κB signaling pathways.
Fibrosing Alopecia in a Pattern Distribution: A Case Report and Literature Review
Authors: Triyangkulsri Korn , Srisuwanwattana Ploychompoo , Sriphojanart Tueboon , Suchonwanit Poonkiat
Published: October 2019

Fibrosing alopecia in a pattern distribution (FAPD) is a relatively new entity in the family of cicatricial alopecia. It has been categorized as a member of the lichen planopilaris (LPP) group due to its similarity in clinical and histopathological presentation. Nonetheless, the disease earns its own entity due to its lichenoid inflammation exclusively involving miniaturized hair and area of involvement mimicking pattern hair loss which differentiates itself from other types of LPP or pattern hair loss. Since its first introduction by Zinkernagel and Trüeb in 2000, there have been only few case reports and series of FAPD. We herein report a case of FAPD in a postmenopausal woman who had progressive hair loss over the course of 10 years.
Визначення показань та протипоказань до симультанних оперативних втручань у пацієнтів з поєднанням ендокринної та іншої хірургічної патології
Authors: Zavgorodnii S. M. , Kubrak M. A. , Danyluk M. B. , Rylov A. I. , Yareshko N. O.
Published: October 2019

Мета роботи: розробити показання та протипоказання до виконання симультанних оперативних втручань на прикладі пацієнтів з поєднаною патологією щитоподібної залози (ЩЗ) та жовчнокам’яною хворобою (ЖКХ) / поліпозом жовчного міхура, з використанням шкали функціонального стану P-POSSUM.

Матеріали і методи. За період з січня 2015 до вересня 2018 року обстежено та прооперовано 35 пацієнтів з поєднаною патологією щитоподібної залози та ЖКХ / поліпозом жовчного міхура. На доопераційному етапі, а також на першу добу післяопераційного періоду всім пацієнтам проводили оцінку функціонального стану за шкалою P-POSSUM.

Результати досліджень та їх обговорення. У 22 (62,9 %) пацієнтів, функціональний стан яких до втручання оцінювався за фізіологічною субшкалою (ФС) ≤ 17 балів, мали місце післяопераційні зміни стану здоров’я з різницею середніх 0,13 бала, Т (Z) = 1,21, р = 0,225. У всіх цих хворих складність оперативного втручання за хірургічною субшкалою (ХС) шкали P-POSSUM була оцінена ≤ 14 балів. У 13 (37,1 %) хворих, стан яких був оцінений в ˃ 17 балів за ФС, виявлені значущі зміни функціонального стану здоров’я до та після операції з різницею середніх 1,15 бала, Т (Z) = 2,67; р = 0,0077. Складність операцій у них коливалася від 14 до 16 балів за ХС.
Етапний підхід у хірургічному лікуванні хворих з обтураційною непрохідністю товстої кишки бластоматозного генезу
Authors: Ioffe O. Yu. , Stets M. M. , Perepadja V. M. , Antoniv V. R. , Tsiura Y. P.
Published: October 2019

Мета роботи: поліпшити результати хірургічного лікування хворих з обтураційною непрохідністю товстої кишки бластоматозного генезу шляхом удосконалення алгоритму лікувально-діагностичної тактики.

Матеріали і методи. За період 2009–2018 рр. у хірургічній клініці КМКЛ № 3 проліковано 127 хворих з обтураційною непрохідністю товстої кишки пухлинного генезу, що складає 5,1 % (2485 пацієнтів) від загальної кількості хворих із невідкладною хірургічною допомогою. Жінки становили 66,2 % (84 хворі), чоловіки склали 33,8 % (43 пацієнти). Середній вік хворих становив (68,2±15,4) року. Етіологічно причинами обтурації просвіту кишечника в 10 (7,9 %) хворих була пухлина сліпої кишки, у 11 (8,7 %) – висхідної ободової кишки, у 5 (3,9 %) – печінкового згину ободової кишки, у 6 (4,7 %) – поперечноободової кишки, у 5 (3,9 %) – селезінкового згину ободової кишки, у 18 (14,2 %) – низхідної ободової кишки, у 32 пацієнтів (25,2 %) рівень перешкоди локалізувався у сигмоподібній кишці та у 30 (23,6 %) – на рівні прямої кишки. Крім цього, у 10 (7,9 %) пацієнтів непрохідність зумовили проростання пухлин матки, яєчників або сечового міхура в дистальні відділи товстої кишки.

Результати досліджень та їх обговорення. Представлено результати лікування 127 хворих з обтураційною непрохідністю товстої кишки пухлинного генезу, що проходили лікування в хірургічній клініці КМКЛ № 3 за період 2009 – 2018 рр. Розроблено лікувально-діагностичний алгоритм етапності надання хірургічної допомоги пацієнтам із даною патологією. Етапний підхід та використання малоінвазивних методик декомпресії кишечника у вигляді стентування, реканалізації та заведення зонда проксимальніше стенозу збільшило відсоток відтермінованих оперативних втручань (до 37,8 %) та зменшило летальність на 14 %.
Вплив різних моделей іммобілізаційного стресу на функціональні зміни в серці високо- і низькостійких до гострої гіпоксичної гіпоксії щурів різної статі
Authors: Denefil O. V. , Ordynskyi Iu. M.
Published: October 2019

Мета роботи: визначити вплив різних моделей іммобілізаційного стресу на зміни показників електрокардіограми (ЕКГ) у самців і самиць щурів з високою і низькою стійкістю до гіпоксії (ВГ, НГ).

Матеріали і методи. У дослід взяли 135 щурі. Тварин поділено на три групи – контрольну та дві дослідні (які зазнали іммобілізаційного стресу). Стрес моделювали 4 рази одногодинною м’якою іммобілізацією щурів спинкою донизу з інтервалом 24 години (стрес 1) і 72 години (стрес 2). Дослідження проводили через 24 години після останньої іммобілізації. У всіх піддослідних тварин під наркозом реєстрували ЕКГ.

Результати досліджень та їх обговорення. При аналізі показників ЕКГ у щурів спостерігали незначні зміни тривалості та амплітуди зубців та інтервалів. Так, при порівнянні груп контрольних ВГ і НГ самців достовірних показників на ЕКГ не виявлено. Аналогічно не було достовірної різниці між досліджуваними ЕКГ показниками у ВГ і НГ самиць. Стрес 1 призвів до зниження відхилення сегмента ST від ізолінії порівняно з контрольними значеннями у ВГ самців і у ВГ самиць. У НГ самиць зросла ЧСС, зменшилися тривалість інтервалу RR та показник QTc. У ВГ самців, порівняно з ВГ самицями, була менша амплітуда зубця R. Стрес 2, порівняно з контролем, у ВГ самців спричинив підвищення амплітуди зубця R. У ВГ самців, порівняно з НГ, спостерігали більше відхилення сегмента ST від ізолінії; у НГ самиць зросла ЧСС, зменшилися тривалість інтервалу RR, тривалість та амплітуда зубця Р, тривалість інтервалу QT та QTc. У ВГ самиць, порівняно з НГ, була більша тривалість інтервалу QT. Після стресу 2 встановили, що у ВГ самців, порівняно з самицями, були більшими амплітуда зубця R і відхилення сегмента ST від ізолінії. У НГ самців, порівняно з НГ самицями, була більшою тривалість інтервалу QT.
Characterizing Patient‐Centered Postoperative Recovery After Adult Cardiac Surgery: A Systematic Review
Authors: Mori Makoto , Angraal Suveen , Chaudhry Sarwat I. , Suter Lisa G. , Geirsson Arnar , Wallach Joshua D. , Krumholz Harlan M.
Published: October 2019

Background

Improving postoperative recovery is important, with a national focus on postacute care, but the volume and quality of evidence in this area are not well characterized. We conducted a systematic review to characterize studies on postoperative recovery after adult cardiac surgery using patient‐reported outcome measures.

Methods and Results

From
MEDLINE
and Web of Science, studies were included if they prospectively assessed postoperative recovery on adult patients undergoing cardiac surgery using patient‐reported outcome measures. Six recovery domains were defined by prior literature: nociceptive symptoms, mental health, physical function, activities of daily living, sleep, and cognitive function. Of the 3432 studies, 105 articles met the inclusion criteria. The studies were small (median sample size, 119), and mostly conducted in single‐center settings (n=81; 77%). Study participants were predominantly men (71%) and white (88%). Coronary artery bypass graft was included in 93% (n=98). Studies commonly selected for elective cases (n=56; 53%) and patients with less comorbidity (n=67; 64%). Median follow‐up duration was 91 (interquartile range, 42–182) days. Studies most commonly assessed 1 domain (n=42; 40%). The studies also varied in the instruments used and differed in their reporting approach. Studies commonly excluded patients who died during the follow‐up period (n=48; 46%), and 45% (n=47) did not specify how those patients were analyzed.

Conclusions

Studies of postoperative patient‐reported outcome measures are low in volume, most often single site without external validation, varied in their approach to missing data, and narrow in the domains and diversity of patients. The evidence base for postoperative patient‐reported outcome measures needs to be strengthened.
Abstract 106: Cardiac Fibroblast as a Critical Constituent of the Cellular Niche Driving Cardiac Maturation
Authors: Yao Fang
Published: October 2019

Rationale:
Cardiac maturation lays the foundation of postnatal heart development and disease, yet little is known about the contributions of the microenvironment to cardiomyocyte maturation.

Objective:
To identify non-cardiomyocyte cell types and important signaling pathways central to cardiomyocyte maturation.

Methods and Results:
Through building cell-cell interactomes and signaling regulatory networks from single-cell RNA-sequencing data of mouse hearts at various postnatal stages, we identified switching of fibroblast subclusters state as a key driving force behind cardiac maturation. Molecular and functional maturation of immature (neonatal) mouse cardiomyocytes or human embryonic stem cell-derived cardiomyocytes were considerably enhanced when co-cultured with their corresponding adult cardiac fibroblasts
in vitro
. Further, single-cell analysis of the cardiac maturation trajectory revealed highly conserved signaling pathways and ligands in fibroblast-induced cardiomyocyte maturation
in vivo
and
in vitro
. Targeting these signaling pathways using inhibitors significantly delayed cardiac maturation in postnatal hearts, and markedly induced cardiomyocyte proliferation in infarcted hearts.

Conclusions:
Our study unveiled cardiac fibroblasts as a major constituent in the microenvironment driving cardiac maturation. Targeting signaling pathways and ligand-receptor interactions involved in their crosstalk with cardiomyocytes may yield useful strategies to modulate cardiomyocyte maturation state in cardiac diseases and for regeneration purposes.

Keywords:
Cardiac Maturation, Fibroblast, Single-Cell RNA-Sequencing
Abstract 114: Myocardial B Cells Regulate the Composition of Leukocytes in the Heart as Well as Myocardial Growth
Authors: Adamo Luigi , Rocha-Resende Cibele , Evans Sarah , Williams Jesse , Dun Hao , Li Wenjun , Mpoy Cedric , Rogers Buck , Kreisel Daniel , Lavine Kory , Randolph Gwendalyn , Mann Douglas L
Published: October 2019

Background:
B cells are the second most prevalent leukocyte in the murine naïve heart. However, since current models state that B cells continually recirculate between primary and secondary lymphoid organs without accumulating in peripheral tissues, the origin and function of this sizeable myocardial leukocyte pool remains unknown.

Goal:
To investigate the origin and function of myocardial B cells in the naïve heart.

Results:
Bone marrow transplant experiments showed that the murine myocardium harbors a large population of bone marrow derived B cells and a small population of embryo derived B cells. Parabiosis, heart transplant, and adoptive transfer experiments showed that all myocardial B cells recirculate between the heart, the spleen, and likely other organs. Immunohistochemistry showed that the vast majority of myocardial B cells resides in the myocardial microcapillaries and make intimate contact with the endothelium. 10X single cell RNA sequencing showed that myocardial B cells are heterogeneous and have a specific gene expression pattern different from that of peripheral blood B cells.
Ex vivo
perfusion of hearts from B cell deficient mice with wild type peripheral blood suggested that myocardial B cells “adhere” to the microvascular endothelium.
In vivo
microscopy confirmed that a subgroup of circulating B cells pauses on microvascular endothelial cells. Finally, analysis of B cell deficient and B cell depleted mice showed that B cells modulate the composition of the myocardial leukocyte pool and myocardial growth.

Conclusions:
Myocardial B cells are an accumulation of a heterogeneous subgroup of circulating B lymphocytes that, upon arrival in the heart, makes intimate contact with the microvascular endothelium. Myocardial B cells regulate the composition of the myocardial leukocyte pool and myocardial mass. These findings highlight a novel unexpected relationship between B cells and myocardial physiology and suggest a paradigm shift in our current understanding of B cell biology in the naïve state.
Abstract 130: Development of Bioinspired Synthetic Exosomes With Proangiogenic Potential
Authors: Aday Sezin , Halevy Inbal , Anwar Maryam , Madeddu Paolo , Sahoo Susmita , Petretto Enrico , Peer Dan , Emanueli Costanza
Published: October 2019

Exosomes with variable microRNA cargos are released from different cell types and stimulate angiogenesis in animal models. Therefore, exosomes are currently considered for their potential to represent a safer and easier biological-based alternative to stem cell therapies. However, the limited amount of exosomes that can be reproducibly prepared from cultured stem cells and the complexity of the cargo of endogenous exosomes make them difficult to develop as off-the-shelf “pharmaceutical products” and limit their clinical potential. These issues could be surpassed by the use of artificial (i.e. nanoparticles mimicking the natural product) exosomes carrying a therapeutic cargo. In consideration of the possibility that not all cargo components of exosomes are required for their therapeutic functions, we reasoned that bioinspired artificial exosomes (AEs) incorporating key therapeutically relevant molecules and devoid of potentially negative or indifferent factors could further improve their therapeutic potential. Therefore, we developed and tested AEs containing exosomal proangiogenic miRNAs as a “proof-of-concept” for therapeutic angiogenesis. In order to achieve this, we: (1) characterized the common microRNA cargo of endogenous proangiogenic exosomes (from stem cells, pericytes and pericardial fluid) using bioinformatics, (2) exploited this knowledge to develop off-the-shelf artificial exosomes (AEs) with proangiogenic capacities, (3) validated the angiogenic potential of the bioinspired AEs. Bioinformatics analyses integrating data of miRNA arrays and panels of proangiogenic exosomes confirmed the enrichment of let-7 family in these exosomes. After testing the angiogenic potential of different members of let-7 family, we produced AEs containing let-7b (the most potent in the family) by microfluidic micromixing. The AEs were uptaken by human ECs cultured under hypoxic conditions, without causing toxicity. let-7b-AEs transferred functional let-7b, thus decreased the expression of validated targets of let-7b in recipient cells. let-7b-AEs improved EC survival, proliferation and angiogenesis
in vitro
and
in vivo
. These data suggest the therapeutic potential of bioinspired AEs containing let-7b.