bluuebunny/crossref_metadata_2025 huggingface dataset:
Determination of Physicochemical and Functional Properties of Coconut Oil by Incorporating Bioactive Compounds in Selected Spices
Authors: Perera Dilini N. , Hewavitharana Geeth G. , Navaratne S. B.
Published: July 2020

Lipid oxidation has been identified as a major deterioration process of vegetable oils, which leads to the production of primary and secondary oxidative compounds that are harmful to human health. Oleoresins of ginger, garlic, nutmeg, pepper, cloves, and cinnamon were extracted and incorporated into coconut oil, and change occurrence on physicochemical properties, thermal stability, shelf life, and antioxidant activity was monitored against the same properties of pure coconut oil. Lipid oxidation was assessed in terms of the free fatty acid level and peroxide value. For the comparison purpose, another oil sample was prepared by incorporating vitamin E too. Results revealed that both peroxide value and FFA of pure and flavored coconut oil samples after a one-week storage period were 3.989±0.006 and 3.626±0.002 mEq/kg and 0.646±0.001 and 0.604±0.002 (%), respectively. Saponification value, iodine value, smoke point, and the flashpoint of flavored oil were decreased while increasing the viscosity during storage. The highest phenolic content and DPPH free radical scavenging activity were found in flavored coconut oil. Since spices containing antioxidants, the thermal stability of flavored oil was better than that of pure coconut oil. Both oleoresins and vitamin E-incorporated samples showed the same pattern of increment of FFA and peroxide value during storage; however, those increments were slower than those of pure coconut oil.
Smoking Is a Risk Factor of Coronary Heart Disease through HDL-C in Chinese T2DM Patients: A Mediation Analysis
Authors: Tang Ru , Yang Shanshan , Liu Weiguo , Yang Bo , Wang Shuang , Yang Zhengguo , He Yao
Published: July 2020

Objective. To investigate associations between smoking and cardiovascular and cerebrovascular complications in type 2 diabetes mellitus (T2DM) patients. Methods. This is a cross-sectional study. Of 971 T2DM patients aged 14–93 years old in this study, 182 had ever smoked and 789 never smoked. Propensity score matching (PSM) reduced the confounding bias between groups. Logistic regression analysis was performed on matched data to evaluate coronary heart disease (CHD) and stroke risk. In addition, the mediation analysis was conducted among smoking exposure, HDL-C, and CHD. Results. A total of 139 pairs of patients who had never and ever smoked were matched. Logistic regression analysis showed that compared with patients who never smoked, those who smoked > 20 cigarettes per day (CPD) had a higher risk of CHD (odds ratio [OR]: 3.09, 95% confidence interval [CI]: 1.21–7.89). Additionally, after adjusting for age, sex, origin, occupation, smoking status, body mass index, waist circumference, and diabetes duration, the OR for CHD with >20 years of cumulative smoking (pack-years) was 2.21 (95% CI: 1.05–4.65). Furthermore, we observed a significant dose-response relationship between CPD and lower high-density lipoprotein cholesterol (HDL-C) (P<0.001). Moreover, the mediation analysis showed that the indirect effect mediated by HDL-C accounted for 86% (effect = 0.0187, 95% CI: 0.0100–0.0316). Conclusions. Smoking may be a risk factor for CHD in T2DM patients. T2DM patients should stop smoking or reduce the CPD to prevent the onset of CHD. Moreover, to prevent CHD complications, monitoring HDL-C levels in T2DM patients who smoke may be necessary.
Mechanism Analysis of a Low-Frequency Disc Brake Squeal Based on an Energy Feed-In Method for a Dual Coupling Subsystem
Authors: Wu Yidong
Published: July 2020

Brake squeal is a major component of vehicle noise. To explore the mechanism of the low-frequency brake squeal, a finite element model of an automobile disc brake was established, and a complex mode numerical simulation was performed. According to the unstable modes stemming from the complex modal analysis results, the low-frequency range brake squeal can be determined. Based on an energy feed-in method, the coupling subsystems of the piston-caliper and the disc-pad were established, and a calculation formula for the feed-in energy of the dual coupling subsystem was derived. The results showed that when the feed-in energy of the dual coupling subsystem is close to zero, the complex mode cannot be excited at the corresponding frequency. In addition, the difference in feed-in energy between the two coupling subsystems is positively correlated with the probability of the brake squeal, which can be used to determine the complex mode under which the brake squeal may occur. The greater the feed-in energy of a coupling subsystem is, the more likely it is that the maximum brake vibration mode will appear at this subsystem or its adjacent parts. The increase in brake oil pressure will eliminate some lower-frequency sounds but will not change the frequency of the original low-frequency brake squeals.
Experimental Study on Mechanical Properties and Acoustic Emission Characteristics of Water Bearing Sandstone under Stable Cyclic Loading and Unloading
Authors: Qin Xinzhan , Zhou Yu , He Manchao
Published: July 2020

Due to the adjustment of energy structure, a large number of coal mines are abandoned. Considering the environmental and economic effects, many experts proposed to use the abandoned mine cavern as the reservoir of the pumped storage power station. Furthermore, considering the long-term effects of repeated pumping and drainage and hydrodynamic pressure on the surrounding rock in coal mines, a large amount of sandstone was collected from the Ruineng coal mine in Yan’an city to carry out a series of laboratory tests. Through uniaxial compression testing of rock samples with different water content rates, combined with acoustic emission (AE) analysis, the strength softening and macrodeformation characteristics are obtained, and the influence of water content on acoustic emission characteristics is clarified. The mechanical properties of water bearing rock under cyclic loading and unloading experiments with varying upper limits are obtained using a triaxial test system, and the precursory information of rock failure is captured, providing significant guidance for stability analysis and instability warning for surrounding rock in pumped storage power stations.
Acquired FGFR and FGF Alterations Confer Resistance to Estrogen Receptor (ER) Targeted Therapy in ER+ Metastatic Breast Cancer
Authors: Mao Pingping , Cohen Ofir , Kowalski Kailey J. , Kusiel Justin G. , Buendia-Buendia Jorge E. , Cuoco Michael S. , Exman Pedro , Wander Seth A. , Waks Adrienne G. , Nayar Utthara , Chung Jon , Freeman Samuel , Rozenblatt-Rosen Orit , Miller Vincent A. , Piccioni Federica , Root David E. , Regev Aviv , Winer Eric P. , Lin Nancy U. , Wagle Nikhil
Published: July 2020

Purpose:

To identify clinically relevant mechanisms of resistance to ER-directed therapies in ER+ breast cancer.

Experimental Design:

We conducted a genome-scale functional screen spanning 10,135 genes to investigate genes whose overexpression confer resistance to selective estrogen receptor degraders. In parallel, we performed whole-exome sequencing in paired pretreatment and postresistance biopsies from 60 patients with ER+ metastatic breast cancer who had developed resistance to ER-targeted therapy. Furthermore, we performed experiments to validate resistance genes/pathways and to identify drug combinations to overcome resistance.

Results:

Pathway analysis of candidate resistance genes demonstrated that the FGFR, ERBB, insulin receptor, and MAPK pathways represented key modalities of resistance. The FGFR pathway was altered via FGFR1, FGFR2, or FGF3 amplifications or FGFR2 mutations in 24 (40%) of the postresistance biopsies. In 12 of the 24 postresistance tumors exhibiting FGFR/FGF alterations, these alterations were acquired or enriched under the selective pressure of ER-directed therapy. In vitro experiments in ER+ breast cancer cells confirmed that FGFR/FGF alterations led to fulvestrant resistance as well as cross-resistance to the CDK4/6 inhibitor palbociclib. RNA sequencing of resistant cell lines demonstrated that FGFR/FGF induced resistance through ER reprogramming and activation of the MAPK pathway. The resistance phenotypes were reversed by FGFR inhibitors, a MEK inhibitor, and/or a SHP2 inhibitor.

Conclusions:

Our results suggest that FGFR pathway is a distinct mechanism of acquired resistance to ER-directed therapy that can be overcome by FGFR and/or MAPK pathway inhibitors.
Abundance of CD163-Positive Tumor-Associated Macrophages in the Early Gastric Cancer Predicts the Recurrence after Curative Resection
Authors: Zhou Wenxing , Zhang Yiyang , He Fei , Lv Shaohua , Zhang Xiaodong , Fei Chunming
Published: July 2020

Background: We aimed to investigate the prognostic value of M2 macrophages to predict the recurrence of early gastric cancer (EGC). Methods: A retrospective analysis was carried out among EGC patients (95 non-recurrence and 78 recurrence) who underwent surgery at Luhe People’s Hospital of Nanjing. A 5-year recurrence status was utilized to classify the patients into the recurrence group and non-recurrence group. CD163 and proliferating cell nuclear antigen were utilized as markers to detect M2 macrophages and proliferation. Cumulative tumor recurrence curve was adopted to analyze the association between the number of tumor-associated macrophages (TAMs) and the recurrence of EGC. Colony formation and invasion abilities of MKN45 (JCRB0254, human gastric epithelial cell line) with or without M2 macrophage coculture were detected in vitro, and the xenograft model was utilized to detect in vivo effect of M2 macrophages on tumor growth. Results: The number of CD163+ macrophages and expression of transforming growth factor-β1, matrix metallopeptidase 9, and vascular endothelial growth factor A were significantly different between the EGC recurrence and non-recurrence group. The cumulative tumor recurrence rate was found to be dependent on the infiltration number of TAMs. M2 macrophages promoted the proliferation and invasion of human MKN45 cells in vitro, as well as tumor growth in the xenograft model. Conclusion: The abundance of CD163+-positive TAMs in EGC predicts the recurrence after curative resection.
Chronic Kidney Disease in Adolescents after Surgery for Congenital Heart Disease
Authors: Bojan Mirela , Pieroni Laurence , Mirabile Cristian , Froissart Marc , Bonnet Damien
Published: July 2020

Background: The onset of chronic kidney disease (CKD) is an important prognostic factor in young adults with congenital heart disease (CHD). Although it is likely that CKD is manifest early in CHD patients, the prevalence among adolescents is still unknown. The National Kidney Foundation’s Kidney Disease Improving Global Outcomes guidelines 2012 recommend new equations for the estimated glomerular filtration rate (eGFR) and highlight the importance of albuminuria for CKD screening. The objective of the present study was to estimate the prevalence of CKD in CHD adolescents. Methods: This observational cross-sectional study included 115 patients aged 10–18 years attending the cardiologic outpatient clinic at our institution as a follow-up after cardiac surgery in infancy related to various CHDs. CKD assessment used the CKD criteria 2012, including eGFR equations based on serum creatinine and cystatin C, and measurement of albuminuria. Results: No patient had an eGFR <60 mL min–1 1.73 m–2. However, 28.7% of all patients (95% CI 20.7–37.9) had eGFRbetween 60 and 89 mL min–1 1.73 m–2 when estimated by the bedside Schwartz creatinine-based equation,and 17.4% (95% CI 11.2–24.1) had eGFRbetween 60 and 89 mL min–1 1.73 m–2 when estimated by the Zappitelli equation, combining creatinine and cystatin C. Of all patients, 20.0% (95% CI 12.1–26.7) had orthostatic proteinuria, and none had persistent albuminuria. Conclusions: There was no evidence of CKD in the present population aged 10–18 years. The significance of an eGFR between 60 and 90 mL min–1 1.73 m–2 is not concordant for this age range and requires further investigations.
Long Non-Coding RNA NEAT1 Regulates Pyroptosis in Diabetic Nephropathy via Mediating the miR-34c/NLRP3 Axis
Authors: Zhan Jin-Feng , Huang Hong-Wei , Huang Chong , Hu Li-Li , Xu Wen-Wei
Published: July 2020

Introduction: Diabetic nephropathy (DN) is a serious complication of diabetes mellitus and is considered to be a sterile inflammatory disease. Increasing evidence suggest that pyroptosis and subsequent inflammatory response play a key role in the pathogenesis of DN. However, the underlying cellular and molecular mechanisms responsible for pyroptosis in DN are largely unknown. Methods: The rat models of DN were successfully established by single 65 mg/kg streptozotocin treatment. Glomerular mesangial cells were exposed to 30 mmol/L high glucose media for 48 h to mimic the DN environment in vitro. Gene and protein expressions were determined by quantitative real-time PCR and Western blot. Cell viability and pyroptosis were measured by MTT assay and flow cytometry analysis, respectively. The relationship between lncRNA NEAT1, miR-34c, and Nod-like receptor protein-3 (NLRP3) was confirmed by luciferase reporter assay. Results: We found that upregulation of NEAT1 was associated with the increase of pyroptosis in DN models. miR-34c, as a target gene of NEAT1, mediated the effect of NEAT1 on pyroptosis in DN by regulating the expression of NLRP3 as well as the expressions of caspase-1 and interleukin-1β. Either miR-34c inhibition or NLRP3 overexpression could reverse the accentuation of pyroptosis and inflammation by sh-NEAT1 transfection in the in vitro model of DN. Conclusions: Our findings suggested NEAT1 and its target gene miR-34c regulated cell pyroptosis via mediating NLRP3 in DN, providing new insights into understanding the molecular mechanisms of pyroptosis in the pathogenesis of DN.
Yttrium-90 Radioembolization Therapy for Combined Hepatocellular and Cholangiocarcinoma
Authors: Badar Wali , Van Ha Thuong , Zangan Steven , Navuluri Rakesh , Pillai Anjana , Baker Talia , Ahmed Osman
Published: July 2020

Purpose: To report outcomes of transarterial radioembolization (TARE) using glass microspheres for the treatment of mixed hepatocellular-cholangiocarcinoma (HCC-CC) in a propensity-matched study. Material and Methods: Between 2013 and 2019, 10 consecutive patients with histologically confirmed HCC-CC received TARE of a targeted territory using glass microspheres as a primary initial treatment. Baseline demographics in addition to tumor distribution, Child Pugh score, and BCLC were recorded. Tumor response was assessed according to modified RECIST criteria. The HCC-CC cohort was matched to the HCC cohort, and objective response and survival analysis was performed. Results: In the HCC-CC cohort, patients had a 70% objective response rate (ORR), and in the HCC cohort, patients had a 90% ORR after matching (p = 0.54). The median overall survival (OS) for HCC patients was 12.3 months (95% CI: 6.0–17.4 months) in the matched population, and for HCC-CC patients, the median OS was 15.2 months (95% CI: 2.7–20.2 months) (p = 0.98). The median progression-free survival (PFS) for HCC patients was 11.6 months (95% CI: 2.53–19.3 months) in the matched population, and for HCC-CC patients, the median PFS was 15.2 months (95% CI: 2.7–20.2 months) (p = 0.94). The median transplant-free survival (TFS) for HCC patients was 12.3 months (95% CI: 6.0–17.4 months) in the matched population, and for HCC-CC patients, the median TFS was 15.2 months (95% CI: 2.7–20.2 months) (p = 0.98). Conclusions: While outcomes of combined HCC-CC are poor and optimal treatment remains undefined, TARE appears to represent an effective locoregional treatment with survival outcomes similar to that of HCC treated by TARE.
A Rare Manifestation of a Bleeding Tubulovillous Duodenal Polyp Presenting as an Upper Gastrointestinal Hemorrhage
Authors: Khalid Yaser , Dasu Neethi , Suga Herman , Itidiare Michael , Walters Richard
Published: July 2020

Duodenal polyps have been reported in <1.5% of individuals who undergo esophagogastroduodenoscopy (EGD). We present a case of a 76-year-old male with recurrent hematemesis who was found to have an intestinal-type, pedunculated tubulovillous adenoma in the descending duodenum. An isolated occurrence of nonampullary sporadic duodenal adenoma is a rare finding. Presentation as an upper gastrointestinal hemorrhage is also extremely uncommon. Our patient’s polyp was pedunculated, which is atypical, because most sporadic duodenal adenomas are morphologically flat or sessile. The purpose of this case is to present a rare cause of upper gastrointestinal bleeding and to depict characteristics of an isolated duodenal tubulovillous adenoma and its treatment options.
Fatal Hepatitis-Associated Aplastic Anemia in a Young Male
Authors: Božić Ozretić Dorotea , Piplović Vuković Tonka , Vuković Jonatan , Madunić Sanja , Podrug Kristian , Puljiz Željko
Published: July 2020

Hepatitis-associated aplastic anemia is a rare syndrome in which bone marrow failure occurs within weeks to 1 year after attack of acute hepatitis. Studies suggest that cytotoxic T lymphocytes play a central role in bone marrow destruction, but the exact etiology remains unknown. Bone marrow transplantation or immunosuppressive therapy are primary curative options. We present a case of a young male who was admitted to the Department of Gastroenterology and Hepatology for acute hepatitis of an unknown cause. Liver biopsy revealed extensive inflammatory process with hepatocyte necrosis. Forty days later, new onset pancytopenia was identified. Bone marrow biopsy showed severe hypocellularity, and he was diagnosed with severe hepatitis-associated aplastic anemia. Treatment with cyclosporine was initiated, but with inadequate response, and pretransplant evaluation was started. Due to severe neutropenia, following alveotomy procedure, the patient developed deep neck infection with consequent airway obstruction. Despite urgent treatment, his condition deteriorated to sepsis with lethal outcome.
Systemic Botulism Toxicity Caused by Pyloric Botox Injection to Treat Gastroparesis
Authors: Bensen Gordon P. , Rutherford Cristina C. , Gardner Timothy B.
Published: July 2020

Systemic botulism resulting from therapeutic Botox (OnabotulinumtoxinA) injection has been rarely reported, and never in the context of pylorus injection to treat gastroparesis. We report the case of a 27-year-old female with Emery-Dreifuss muscular dystrophy who developed severe systemic botulism toxicity following the intrapyloric injection of 100 units of Botox to treat gastroparesis. The patient eventually made a full recovery.
Recommendations on Surveillance for Differentiated Thyroid Carcinoma in Children with PTEN Hamartoma Tumor Syndrome
Authors: Jonker L.A. , Lebbink C.A. , Jongmans M.C.J. , Nievelstein R.A.J. , Merks J.H.M. , Nieveen van Dijkum E.J.M. , Links T.P. , Hoogerbrugge N. , van Trotsenburg A.S.P. , van Santen H.M.
Published: July 2020

Background: PTEN hamartoma tumor syndrome (PHTS) represents a group of syndromes caused by a mutation in the PTEN gene. Children with a germline PTEN mutation have an increased risk of developing differentiated thyroid carcinoma (DTC). Several guidelines have focused on thyroid surveillance in these children, but studies substantiating these recommendations are lacking. Objective: The present study intends to provide the available evidence for a thyroid carcinoma surveillance program in children with PHTS. Methods: An extensive literature search was performed to identify all studies on DTC in pediatric PHTS patients. Two pediatric cases are presented to illustrate the pros and cons of thyroid carcinoma surveillance. Recommendations for other patient groups at risk for DTC were evaluated. Consensus within the study team on recommendations for children with PHTS was reached by balancing the incidence and behavior of DTC with the pros and cons of thyroid surveillance, and the different surveillance methods. Results: In 5 cohort studies the incidence of DTC in childhood ranged from 4 to 12%. In total 57 cases of DTC and/or benign nodular disease in pediatric PHTS patients were identified, of which 27 had proven DTC, with a median age of 12 years (range 4–17). Follicular thyroid carcinoma (FTC) was diagnosed in 52% of the pediatric DTC patients. No evidence was found for a different clinical behavior of DTC in PHTS patients compared to sporadic DTC. Conclusions: Children with PHTS are at increased risk for developing DTC, with 4 years being the youngest age reported at presentation and FTC being overrepresented. DTC in pediatric PHTS patients does not seem to be more aggressive than sporadic DTC. Recommendations: Surveillance for DTC in pediatric PHTS patients seems justified, as early diagnosis may decrease morbidity. Consensus within the study team was reached to recommend surveillance from the age of 10 years onwards, since at that age the incidence of DTC seems to reach 5%. Surveillance for DTC should consist of yearly neck palpation and triennial thyroid ultrasound. Surveillance in children with PHTS should be performed in a center of excellence for pediatric thyroid disease or PHTS.
Immunsuppression und postoperative Risiken chirurgischen Eingriffe bei Patienten mit rheumatoider Arthritis
Authors: Mihai Carmen-Marina
Published: July 2020

Objectives: The impact of immunosuppression on postoperative outcomes has primarily been studied in patients undergoing joint replacement surgery. We aimed to evaluate the impact of biologics and glucocorticoids on outcomes after other major surgeries. Methods: This retrospective cohort study used Medicare data 2006–2015 to identified adults with rheumatoid arthritis undergoing hip fracture repair, abdominopelvic surgery (cholecystectomy, hysterectomy, hernia, appendectomy, colectomy) or cardiac surgery (coronary artery bypass graft, mitral/aortic valve). Logistic regression with propensity-score-based inverse probability weighting compared 90-day mortality and 30-day readmission in patients receiving methotrexate (without a biologic or targeted synthetic disease-modifying antirheumatic drug (tsDMARD)), a tumour necrosis factor inhibitor (TNFi) or a non-TNFi biologic/tsDMARD <8 weeks before surgery. Similar analyses evaluated associations between glucocorticoids and outcomes. Results: We identified 10 777 eligible surgeries: 3585 hip fracture, 5025 abdominopelvic and 2167 cardiac surgeries. Compared with patients receiving methotrexate, there was no increase in the risk of 90-day mortality or 30-day readmission among patients receiving a TNFi (mortality adjusted OR (aOR) 0.83 (0.67 to 1.02), readmission aOR 0.86 (0.75 to 0.993)) or non-TNFi biologic/tsDMARD (mortality aOR 0.78 (0.49 to 1.22), readmission aOR 1.02 (0.78 to 1.33)). Analyses stratified by surgery category were similar. Risk of mortality and readmission was higher with 5–10 mg/day of glucocorticoids (mortality aOR 1.41 (1.08 to 1.82), readmission aOR 1.26 (1.05 to 1.52)) or >10 mg/day (mortality aOR 1.64 (1.02 to 2.64), readmission aOR 1.60 (1.15 to 2.24)) versus no glucocorticoids, although results varied when stratifying by surgery category. Conclusion: Recent biologic or tsDMARD use was not associated with a greater risk of mortality or readmission after hip fracture, abdominopelvic or cardiac surgery compared with methotrexate. Higher dose glucocorticoids were associated with greater risk.
Morphogo: An Automatic Bone Marrow Cell Classification System on Digital Images Analyzed by Artificial Intelligence
Authors: Fu Xinyan , Fu May , Li Qiang , Peng Xiangui , Lu Ju , Fang Fengqi , Chen Mingyi
Published: July 2020

Introduction: The nucleated-cell differential count on the bone marrow aspirate smears is required for the clinical diagnosis of hematological malignancy. Manual bone marrow differential count is time consuming and lacks consistency. In this study, a novel artificial intelligence (AI)-based system was developed to perform cell automatic classification of bone marrow cells and determine its potential clinical applications. Materials and Methods: Bone marrow aspirate smears were collected from the Xinqiao Hospital of Army Medical University. First, an automated analysis system (Morphogo) scanned and generated whole digital images of bone marrow smears. Then, the nucleated marrow cells in the selected areas of the smears at a magnification of ×1,000 were analyzed by the software utilizing an AI-based platform. The cell classification results were further reviewed and confirmed independently by 2 experienced pathologists. The automatic cell classification performance of the system was evaluated using 3 categories: accuracy, sensitivity, and specificity. Correlation coefficients and linear regression equations between automatic cell classification by the AI-based system and concurrent manual differential count were calculated. Results: In 230 cases, the classification accuracy was above 85.7% for hematopoietic lineage cells. Averages of sensitivity and specificity of the system were found to be 69.4 and 97.2%, respectively. The differential cell percentage of the automated count based on 200–500 cell counts was correlated with differential cell percentage provided by the pathologists for granulocytes, erythrocytes, and lymphocytes (r ≥ 0.762, p < 0.001). Discussion/Conclusion: This pilot study confirmed that the Morphogo system is a reliable tool for automatic bone marrow cell differential count analysis and has potential for clinical applications. Current ongoing large-scale multicenter validation studies will provide more information to further confirm the clinical utility of the system.
A Different and Novel Alternative (ADANA) Renal Access Technique when CT or USG Guidance Is Inadequate in Case of Retro-Renal Colon
Authors: Gurbuz Zafer Gokhan , Ercil Hakan , Alma Ergun , Vuruskan Ediz , Ayhan Lokman , Unal Umut
Published: July 2020

Introduction: Computed tomography (CT) or ultrasonography (USG)-guided renal access for percutaneous nephrolithotomy (PNL) is not suitable in all cases with retro-renal colon (RRC) due to anatomical and technical restrictions. We would like to describe our novel technique that permits standard subcostal renal access with a small incision for these patients. Methods: This method was performed on adult patients with severe RRC and complex renal stones who were not suitable for renal access with CT or USG guidance. Time from skin incision to puncture needle insertion, incision length, stone-free rate (SFR), and complications were evaluated. Surgical Technique: The appropriate renal calyx for renal access was identified with retrograde pyelography. The skin closest to the identified calyx was incised and retroperitoneum visualized. The RRC was swept laterally by blunt dissection to obtain a safe puncture line. The retractors were placed to keep the colon away from the incision. Then, the puncture needle was placed over Gerota’s fascia. After this, the puncture needle was inserted into the targeted calyx under fluoroscopic guidance. The insertion of guidewire and the rest of the procedure such as dilatation and insertion of Amplatz sheath were performed under same maneuver. Results: A total of 1,348 patients were treated with PNL between January 2016 and November 2019. Our group consisted of 16 adult patients with a median age of 44.8 years (7 females and 9 males) who underwent PNL with our new access technique. SFR and clinically insignificant residual fragment (CIRF) rate were 72.5 and 14.2%, respectively. The median access time was 22.2 min (range: 15–30 min). The median skin incision length was 3.7 (range: 3.0–4.5) cm. The average skin incision length was 3.7 cm. The SFR and CIRF rate were 72.5 and 14.2%, respectively. We did not observe any complication related to our access technique. Conclusion: Our novel access technique created a safe anatomical route for standard subcostal renal access with acceptable incision length and very low complication rate.
Organisierende Pneumonie als seltene, unerwünschte Wirkung von Tocilizumab bei der Therapie von rheumatoider Arthritis
Authors: Kahn Nicolas Carlos
Published: July 2020

Interstitial lung disease is a significant extra-articular manifestation of rheumatoid arthritis, due to its prevalence, morbidity and mortality. Biological therapies are widely used for rheumatoid arthritis treatment. However, some biological agents have been related to the induction or exacerbation of interstitial lung disease. We report a 51-year-old woman with knee arthralgia, hand and foot joint deformities. Although there were no respiratory symptoms, rheumatoid arthritis and interstitial lung disease were diagnosed. High-resolution computed tomography (HRCT) detected a radiological pattern of nonspecific interstitial pneumonia. After tocilizumab therapy for nine months, a second HRCT detected a worsening of interstitial lung disease, presenting a pattern of organizing pneumonia. Tocilizumab was discontinued and prednisone (1 mg/kg/day) was introduced. After two months, a further HRCT detected a significant improvement in organizing pneumonia. There are few similar cases in the literature of tocilizumab-induced organizing pneumonia in patients with rheumatoid arthritis. Despite being a rare adverse effect, knowledge of this association is important for monitoring the use of tocilizumab.
Evaluation of the Diagnostic and Predicative Values of 8-Iso-Prostaglandin F2α as a Biomarker of Breast Cancer
Authors: Nour Eldin Essam Eldin Mohamed , Nour Eldein Mohamed Mahmoud , El-Readi Mahmoud Zaki , Mirza Ahmad A. , Fatani Sameer Hasan , Al-Amodi Hiba Saeed , Althubiti Mohammad Ahmad , Al-Ezzi Esmail M.  , Eid Safaa Yehia , Kamel Hala Fawzy Mohammed
Published: July 2020

Background: Breast cancer (BC) is a commonly reported cancer that is widely prevalent among women. Its early detection improves patient survival and results in better outcomes. For diagnosis and follow-up care, tumor markers are one of the feasible investigations to be ordered. 8-Iso-prostaglandin F2α (8-iso-PGF2α) serves as a serum marker reflecting oxidative stress and subsequent damaging of DNA. In the present study, we aimed to evaluate both diagnostic and predictive values of 8-iso-PGF2α in BC patients. Materials and Methods: Serum levels of 8-iso-PGF2α were assessed for 66 women with benign breast tumors and 65 women who had malignant BC. To compare the patients who had breast tumors with healthy individuals, 63 women free of breast diseases were selected as controls. Results: The serum level of 8-iso-PGF2α in the BC patients (57.92 pg/mL) was significantly higher compared to those with benign tumors (18.89 pg/mL) (p < 0.001). In addition, individuals with no breast diseases had less 8-iso-PGF2α (4.02 pg/mL) compared to those who had developed a tumor (p < 0.001). Serum 8-iso-PGF2α was found to be positively correlated with both carcinoembryonic antigen (r = 0.74, p < 0.001) and cancer antigen 15-3 (r = 0.80, p < 0.001). Furthermore, serum 8-iso-PGF2α showed high diagnostic performance in BC (AUC = 0.999, sensitivity = 100%, specificity = 99.2% at a cutoff value of 36.18 pg/mL). Conclusions: Our study found that the high level of serum 8-iso-PGF2α helps to provide a non-invasive indicator to detect BC. Future work with a larger sample size and various phases of BC can confirm the current results which provide insights into the early detection of cancer.
A Plasma Protein Biomarker Strategy for Detection of Small Intestinal Neuroendocrine Tumors
Authors: Kjellman Magnus , Knigge Ulrich , Welin Staffan , Thiis-Evensen Espen , Gronbaek Henning , Schalin-Jäntti Camilla , Sorbye Halfdan , Joergensen Maiken Thyregod , Johanson Viktor , Metso Saara , Waldum Helge , Søreide Jon Arne , Ebeling Tapani , Lindberg Fredrik , Landerholm Kalle , Wallin Goran , Salem Farhad , Schneider Maria del Pilar , Belusa Roger
Published: July 2020

Background: Small intestinal neuroendocrine tumors (SI-NETs) are difficult to diagnose in the early stage of disease. Current blood biomarkers such as chromogranin A (CgA) and 5-hydroxyindolacetic acid have low sensitivity (SEN) and specificity (SPE). This is a first preplanned interim analysis (Nordic non-interventional, prospective, exploratory, EXPLAIN study [NCT02630654]). Its objective is to investigate if a plasma protein multi-biomarker strategy can improve diagnostic accuracy (ACC) in SI-NETs. Methods: At the time of diagnosis, before any disease-specific treatment was initiated, blood was collected from patients with advanced SI-NETs and 92 putative cancer-related plasma proteins from 135 patients were analyzed and compared with the results of age- and sex-matched controls (n = 143), using multiplex proximity extension assay and machine learning techniques. Results: Using a random forest model including 12 top ranked plasma proteins in patients with SI-NETs, the multi-biomarker strategy showed SEN and SPE of 89 and 91%, respectively, with negative predictive value (NPV) and positive predictive value (PPV) of 90 and 91%, respectively, to identify patients with regional or metastatic disease with an area under the receiver operator characteristic curve (AUROC) of 99%. In 30 patients with normal CgA concentrations, the model provided a diagnostic SPE of 98%, SEN of 56%, and NPV 90%, PPV of 90%, and AUROC 97%, regardless of proton pump inhibitor intake. Conclusion: This interim analysis demonstrates that a multi-biomarker/machine learning strategy improves diagnostic ACC of patients with SI-NET at the time of diagnosis, especially in patients with normal CgA levels. The results indicate that this multi-biomarker strategy can be useful for early detection of SI-NETs at presentation and conceivably detect recurrence after radical primary resection.
Stabilizer Cell Gene Therapy
Authors: Liu Michael B. , Priori Silvia G. , Qu Zhilin , Weiss James N.
Published: July 2020

Background:

In cardiac gene therapy to improve contractile function, achieving gene expression in the majority of cardiac myocytes is essential. In preventing cardiac arrhythmias, however, this goal may not be as important since transduction efficiencies as low as 40% suppressed ventricular arrhythmias in genetically modified mice with catecholaminergic polymorphic ventricular tachycardia.

Methods:

Using computational modeling, we simulated 1-, 2-, and 3-dimensional tissue under a variety of conditions to test the ability of genetically engineered nonarrhythmogenic stabilizer cells to suppress triggered activity due to delayed or early afterdepolarizations.

Results:

Due to source-sink relationships in cardiac tissue, a minority (20%–50%) of randomly distributed stabilizer cells engineered to be nonarrhythmogenic can suppress the ability of arrhythmogenic cells to generate delayed and early afterdepolarizations–related arrhythmias. Stabilizer cell gene therapy strategy can be designed to correct a specific arrhythmogenic mutation, as in the catecholaminergic polymorphic ventricular tachycardia mice studies, or more generally to suppress delayed or early afterdepolarizations from any cause by overexpressing the inward rectifier K channel Kir2.1 in stabilizer cells.

Conclusions:

This promising antiarrhythmic strategy warrants further testing in experimental models to evaluate its clinical potential.
Novel CineECG Derived From Standard 12-Lead ECG Enables Right Ventricle Outflow Tract Localization of Electrical Substrate in Patients With Brugada Syndrome
Authors: van Dam Peter M. , Locati Emanuela T. , Ciconte Giuseppe , Borrelli Valeria , Heilbron Francesca , Santinelli Vincenzo , Vicedomini Gabriele , Monasky Michelle M. , Micaglio Emanuele , Giannelli Luigi , Mecarocci Valerio , Ćalović Žarko , Anastasia Luigi , Pappone Carlo
Published: July 2020

Background:

In Brugada syndrome (BrS), diagnosed in presence of a spontaneous or ajmaline-induced type-1 pattern, ventricular arrhythmias originate from the right ventricle outflow tract (RVOT). We developed a novel CineECG method, obtained by inverse electrocardiogram (ECG) from standard 12-lead ECG, to localize the electrical activity pathway in patients with BrS.

Methods:

The CineECG enabled the temporospatial localization of the ECG waveforms, deriving the mean temporospatial isochrone from standard 12-lead ECG. The study sample included (1) 15 patients with spontaneous type-1 Brugada pattern, and (2) 18 patients with ajmaline-induced BrS (at baseline and after ajmaline), in whom epicardial potential duration maps were available; (3) 17 type-3 BrS pattern patients not showing type-1 BrS pattern after ajmaline (ajmaline-negative); (4) 47 normal subjects; (5) 18 patients with right bundle branch block (RBBB). According to CineECG algorithm, each ECG was classified as Normal, Brugada, RBBB, or Undetermined.

Results:

In patients with spontaneous or ajmaline-induced BrS, CineECG localized the terminal mean temporospatial isochrone forces in the RVOT, congruent with the arrhythmogenic substrate location detected by epicardial potential duration maps. The RVOT location was never observed in normal, RBBB, or ajmaline-negative patients. In most patients with ajmaline-induced BrS (78%), the RVOT location was already evident at baseline. The CineECG classified all normal subjects and ajmaline-negative patients at baseline as Normal or Undetermined, all patients with RBBB as RBBB, whereas all patients with spontaneous and ajmaline-induced BrS as Brugada. Compared with standard 12-lead ECG, CineECG at baseline had a 100% positive predictive value and 81% negative predictive value in predicting ajmaline test results.

Conclusions:

In patients with spontaneous and ajmaline-induced BrS, the CineECG localized the late QRS activity in the RVOT, a phenomenon never observed in normal, RBBB, or ajmaline-negative patients. The possibility to identify the RVOT as the location of the arrhythmogenic substrate by the noninvasive CineECG, based on the standard 12-lead ECG, opens new prospective for diagnosing patients with BrS.
Complete Electroanatomic Imaging of the Diastolic Pathway Is Associated With Improved Freedom From Ventricular Tachycardia Recurrence
Authors: Hadjis Alexios , Frontera Antonio , Limite Luca Rosario , Bisceglia Caterina , Bognoni Ludovica , Foppoli Luca , Lipartiti Felicia , Paglino Gabriele , Radinovic Andrea , Tsitsinakis Georgio , Calore Federico , Della Bella Paolo
Published: July 2020

Background:

The development of multielectrode mapping catheters has expanded the spectrum of mappable ventricular tachycardias (VTs). Full diastolic pathway recording has been associated with a high rate of VT termination during radiofrequency ablation as well as noninducibility at study end. However, the role of diastolic pathway mapping on VT recurrence has yet to be clearly elucidated. We aimed to explore the role of complete diastolic pathway activation mapping on VT recurrence.

Methods:

Eighty-five consecutive patients who underwent VT ablation guided by high-density mapping were enrolled. During activation mapping, the presence of electrical activity in all segments of diastole defined the evidence of having had recorded the whole diastolic interval. Patients were categorized as having recorded the full diastolic pathway, partial diastolic pathway, or no diastolic pathway map performed. Recurrences of VT were defined as appropriate implantable cardioverter defibrillator therapies or on the basis of ECG-documented arrhythmia.

Results:

Eighty-five patients were included. Complete recording of the diastolic pathway was achieved in 36/85 (42.4%) patients. Partial recording of the diastolic pathway of the clinical VT was achieved in 24/85 (28.2%) patients. No recording of the diastolic pathway of the clinical VT was feasible in 25/85 patients (29.4%). At a mean of 12.8 months, freedom from VT recurrence was 67% in the overall cohort. At a mean of 12.8 months, freedom from VT recurrence was 88%, 50%, and 55% in patients who had full diastolic activity recorded, partial diastolic activity recorded, or underwent substrate modification, respectively; the observed differences were statistically significant (
P
=0.02).

Conclusions:

Mapping of the entire diastolic pathway was associated with a higher freedom from VT recurrence as compared with partial diastolic pathway recording and substrate modification. The use of multielectrode mapping catheters in recording diastolic activity may help predict those VTs employing intramural circuits and further optimize ablation strategies.
Heart Rate Variability Triangular Index as a Predictor of Cardiovascular Mortality in Patients With Atrial Fibrillation
Authors: Hämmerle Peter , Eick Christian , Blum Steffen , Schlageter Vincent , Bauer Axel , Rizas Konstantinos D. , Eken Ceylan , Coslovsky Michael , Aeschbacher Stefanie , Krisai Philipp , Meyre Pascal , Vesin Jean‐Marc , Rodondi Nicolas , Moutzouri Elisavet , Beer Jürg , Moschovitis Giorgio , Kobza Richard , Di Valentino Marcello , Corino Valentina D. A. , Laureanti Rita , Mainardi Luca , Bonati Leo H. , Sticherling Christian , Conen David , Osswald Stefan , Kühne Michael , Zuern Christine S. ,   Swiss‐AF Study Investigators
Published: July 2020

Background

Impaired heart rate variability (HRV) is associated with increased mortality in sinus rhythm. However, HRV has not been systematically assessed in patients with atrial fibrillation (AF). We hypothesized that parameters of HRV may be predictive of cardiovascular death in patients with AF.

Methods and Results

From the multicenter prospective Swiss‐AF (Swiss Atrial Fibrillation) Cohort Study, we enrolled 1922 patients who were in sinus rhythm or AF. Resting ECG recordings of 5‐minute duration were obtained at baseline. Standard parameters of HRV (HRV triangular index, SD of the normal‐to‐normal intervals, square root of the mean squared differences of successive normal‐to‐normal intervals and mean heart rate) were calculated. During follow‐up, an end point committee adjudicated each cause of death. During a mean follow‐up time of 2.6±1.0 years, 143 (7.4%) patients died; 92 deaths were attributable to cardiovascular reasons. In a Cox regression model including multiple covariates (age, sex, body mass index, smoking status, history of diabetes mellitus, history of hypertension, history of stroke/transient ischemic attack, history of myocardial infarction, antiarrhythmic drugs including β blockers, oral anticoagulation), a decreased HRV index ≤ median (14.29), but not other HRV parameters, was associated with an increase in the risk of cardiovascular death (hazard ratio, 1.7; 95% CI, 1.1–2.6;
P
=0.01) and all‐cause death (hazard ratio, 1.42; 95% CI, 1.02–1.98;
P
=0.04).

Conclusions

The HRV index measured in a single 5‐minute ECG recording in a cohort of patients with AF is an independent predictor of cardiovascular mortality. HRV analysis in patients with AF might be a valuable tool for further risk stratification to guide patient management.

Registration

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT02105844.
Biomechanics of Aortic Dissection: A Comparison of Aortas Associated With Bicuspid and Tricuspid Aortic Valves
Authors: Chung Jennifer C.‐Y. , Wong Edwin , Tang Mingyi , Eliathamby Daniella , Forbes Thomas L. , Butany Jagdish , Simmons Craig A. , Ouzounian Maral
Published: July 2020

Background

Current methods for aortic dissection risk assessment are inadequate for patients with ascending aortic aneurysms associated with either bicuspid aortic valves (BAVs) or tricuspid aortic valves (TAVs). Biomechanical testing of aortic tissue may provide novel insights and biomarkers.

Methods and Results

From March 2017 to August 2019, aneurysmal ascending aortas (BAV=23, TAV=23) were collected from elective aortic surgery, normal aortas from transplant donors (n=9), and dissected aortas from surgery for aortic dissection (n=7). These aortas underwent delamination testing in simulation of aortic dissection. Biaxial tensile testing was performed to determine modulus of elasticity (aortic stiffness), and energy loss (a measure of efficiency in performing the Windkessel function). Delamination strength (
S
d
) was lowest in dissected aortas (18±6 mN/mm) and highest in normal aortas (58±16 mN/mm), and aneurysms fell in between, with greater
S
d
in the BAV group (37±10 mN/mm) than the TAV group (27±10 mN/mm) (
P
<0.001). Bicuspid aortopathy was associated with greater stiffness (
P
<0.001), while aneurysms with TAV demonstrated greater energy loss (
P
<0.001).
S
d
decreased by 7.8±1.2 mmol/L per mm per decade of life (
r
2
=0.45,
P
<0.001), and it was significantly lower for patients with hypertension (
P
=0.001).
S
d
decreased by 6.1±2.1 mmol/L per mm with each centimeter increase in aortic diameter (
r
2
=0.15,
P
=0.007). Increased energy loss was associated with decreased
S
d
(
r
2
=0.41), whereas there was no relationship between
S
d
and aortic stiffness.

Conclusions

Aneurysms with BAV had higher
S
d
than those with TAV, suggesting that BAV was protective. Energy loss was lower in aneurysms with BAV, and inversely associated with
S
d
, representing a potential novel biomarker.
A Basic Framework of View Systems Allowing Teleoperators to Pre-Acquire Spatial Knowledge from Survey and Route Perspectives
Authors: Sato Ryuya , Kamezaki Mitsuhiro , Sugano Shigeki , Iwata Hiroyasu
Published: July 2020

One of the most important problems in teleoperation of heavy machinery is that the work efficiency of teleoperation is lower than half that of a typical boarding operation. This difference is primarily caused by operators' difficulty in creating mental representations (i.e., cognitive maps) of work sites. Operators have two opportunities to acquire information, namely before work and during work, because the introduction of teleoperation requires about one week. Therefore, we have developed a view system to be used before work to provide environmental information concerning work sites on the basis of human spatial cognition. Cognitive maps can be built by acquiring knowledge from two perspectives—the survey perspective and the route perspective. We display an external view from any viewpoint to acquire knowledge from a survey perspective and a view from an operator's viewpoint, which can be modified by the operator's intention to acquire knowledge from the route perspective. Experimental results using a simulator suggested that a proposed view system could help operators acquire cognitive maps, which may lead to a decrease in task time, the number of stops, and the moving distance and an increase in speed during grasping.
Environment-sensitive hydrogels as potential drug delivery systems for the treatment of periodontitis
Authors: Huang Jie , Wang Zirun , Krishna Sigdel , Hu Qin , Xuan Ming , Xie Huixu
Published: July 2020

Periodontitis is an inflammatory disease caused by pathogenic microorganisms colonized in periodontal pocket. The disease leading to the destruction of periodontal tissues including gums, periodontal ligaments, dental cementum and alveolar bone has been regarded as a latent risk factor
of other medical problems. The therapeutic effects of periodontitis are unsatisfactory currently, though a great many strategies have been used to enhance the results of its treatments. Recently, environment-sensitive hydrogels have been proposed to be drug delivery systems for this disease,
which possesses environment-response, less system side effects as well as reduced treatment frequency. In this mini-review, we present the changes of periodontitis micro-environment, and then introduce various environment-sensitive hydrogels as drug delivery systems in the treatment of periodontitis.
Finally, the limitations and aspects to improve of this vehicle applied to the treatment of periodontitis are discussed. We hope this review will provide better understanding of the hydrogel applications in periodontitis therapy.