bluuebunny/crossref_metadata_2025 huggingface dataset:
Visible Fat Content of Hotpot Beef Acceptability by New Zealand Chinese, Japanese, and Korean Consumers
Authors: Farouk M. M. , Staincliffe M. , Hopkins D. L. , Wu G. , Che C. , Bekhit A. E. D. , Yoo M. J. Y. , Horita A. , Urquiola G. , Craigie C. , Taukiri K. , Zhang R. , Ho H. , Challies M. J.
Published: October 2019

Hotpot meat is a popular way of meat consumption in some Asian countries. This study was carried out to investigate the effect of visible fat content on consumer acceptability of hotpot meat. Hotpot beef with six visible fat levels (11%–35%) was produced and digitally photographed, and the images were ranked by panels of New Zealand Chinese (110), Japanese (145), and Korean (118) consumers. For all the nationalities, a preference for visible fat was influenced by both gender and age. The Chinese preferred the visibly fattiest hotpot beef, whereas the Koreans preferred the leanest with the Japanese preferring the two fat extremes equally. For individuals in the age range of 19–30 years, both Chinese males and females preferred the higher fat meat (35%), while their Japanese and Korean counterparts preferred the second visibly leanest (14%). For those over 50 years, Chinese females preferred the lower fat meat compared to their male counterparts, whereas there was no gender difference at this age for the Japanese and Koreans preference for the visibly lean hotpot beef. This study indicates that there are subtle differences between nationalities in terms of their preference for the fat content of hotpot beef that may have implications in meat merchandising, product development, and health policies.
Design of Electrodes on Gold Test Strips for Enhanced Accuracy in Glucose Measurement
Authors: Kuo Hsin-Yi , Cheng Yuan-Hwei , Chang Ho , Shaw Jin-Siang , Lee Rahnfong
Published: October 2019

This paper reviews the practical process of designing the electrodes on electroless immersion gold-plated test strips for glucose measurement. We have found that great care must be taken on determining the width and length of the working and reference electrodes, to yield the optimum performance on electroless immersion gold-plated glucose test strips for glucose measurement. Preferably, a width of at least 0.6 mm and a length of at least 24 mm are recommended to prevent variance in electrode resistance during mass production of electroless immersion gold-plated glucose test strips, in order to enhance the accuracy of glucose measurement. This paper also recommended that, if two different geometric sizes of test strips are going to be used on the same glucose meter, both test strips must use different lengths and widths on the working and reference electrodes to yield the same electrical resistance and hence similar electrochemical performance.
Relationship between Random Blood Glucose, Fasting Blood Glucose, and Gensini Score in Patients with Acute Myocardial Infarction
Authors: Qin Yuhan , Yan Gaoliang , Qiao Yong , Ma Changle , Liu Juchuan , Tang Chengchun
Published: October 2019

Objective. To examine the relationship between admission random blood glucose (RBG), fasting blood glucose (FBG), and Gensini score in patients with acute myocardial infarction (AMI) to clarify the effects of RBG and FBG on the severity of coronary artery disease. Method. A total of 958 consecutive AMI patients who underwent emergency coronary angiography at the Cardiology Department of Zhongda Hospital (affiliated with Southeast University) were enrolled in this study from January 1, 2016, to December 31, 2018. The Gensini score of each patient was calculated according to the results of coronary angiography. The RBG, FBG, baseline data, hematological indexes, echocardiography parameters, coronary angiography data, and the use of intra-aortic balloon pump (IABP) were recorded. Patients with an RBG level >11.1 mmol/L were classified into the stress hyperglycemia group, and those with an FBG level >7.0 mmol/L were classified into the elevated FBG group. The Gensini scores in the stress hyperglycemia and elevated FBG groups were compared to those in the control group, and correlations between the RBG and FBG levels and the Gensini scores of AMI patients were evaluated. Independent risk factors for the Gensini score were analyzed by multiple linear and multiple logistic regression analyses. Results. The Gensini scores of the stress hyperglycemia group and the elevated FBG group were higher than those of the control group. RBG and FBG were positively correlated with the Gensini score, and there were significant differences between RBG and FBG in different Gensini score groups. After adjusting for confounding factors, multiple linear regression analysis showed that sex, diabetes, estimated glomerular filtration rate (eGFR), and FBG were independent risk factors for the Gensini score. Multiple logistic regression analysis showed that age and FBG were independent risk factors in group 2 compared to group 1, eGFR and FBG were independent risk factors in group 3, and eGFR and FBG were independent risk factors in group 4. Diabetes and RBG were not independent risk factors for the Gensini score. Conclusion. The Gensini scores of patients in the stress hyperglycemia group and the elevated FBG group were significantly higher than those in the control group. RBG and FBG were positively correlated with the Gensini score in AMI patients, and FBG was an independent risk factor for the Gensini score in AMI patients.
A Novel MYCN-Specific Antigene Oligonucleotide Deregulates Mitochondria and Inhibits Tumor Growth in MYCN-Amplified Neuroblastoma
Authors: Montemurro Luca , Raieli Salvatore , Angelucci Silvia , Bartolucci Damiano , Amadesi Camilla , Lampis Silvia , Scardovi Anna Lisa , Venturelli Leonardo , Nieddu Giammario , Cerisoli Lucia , Fischer Matthias , Teti Gabriella , Falconi Mirella , Pession Andrea , Hrelia Patrizia , Tonelli Roberto
Published: October 2019

Approximately half of high-risk neuroblastoma is characterized by MYCN amplification. N-Myc promotes tumor progression by inducing cell growth and inhibiting differentiation. MYCN has also been shown to play an active role in mitochondrial metabolism, but this relationship is not well understood. Although N-Myc is a known driver of the disease, it remains a target for which no therapeutic drug exists. Here, we evaluated a novel MYCN-specific antigene PNA oligonucleotide (BGA002) in MYCN-amplified (MNA) or MYCN-expressing neuroblastoma and investigated the mechanism of its antitumor activity. MYCN mRNA and cell viability were reduced in a broad set of neuroblastoma cell lines following BGA002 treatment. Furthermore, BGA002 decreased N-Myc protein levels and apoptosis in MNA neuroblastoma. Analysis of gene expression data from patients with neuroblastoma revealed that MYCN was associated with increased reactive oxygen species (ROS), downregulated mitophagy, and poor prognosis. Inhibition of MYCN caused profound mitochondrial damage in MNA neuroblastoma cells through downregulation of the mitochondrial molecular chaperone TRAP1, which subsequently increased ROS. Correspondingly, inhibition of MYCN reactivated mitophagy. Systemic administration of BGA002 downregulated N-Myc and TRAP1, with a concomitant decrease in MNA neuroblastoma xenograft tumor weight. In conclusion, this study highlights the role of N-Myc in blocking mitophagy in neuroblastoma and in conferring protection to ROS in mitochondria through upregulation of TRAP1. BGA002 is a potently improved MYCN-specific antigene oligonucleotide that reverts N-Myc–dysregulated mitochondrial pathways, leading to loss of the protective effect of N-Myc against mitochondrial ROS.

Significance:

A second generation antigene peptide oligonucleotide targeting MYCN induces mitochondrial damage and inhibits growth of MYCN-amplified neuroblastoma cells.
Targeting Semaphorin 4D in Cancer: A Look from Different Perspectives
Authors: Tamagnone Luca , Franzolin Giulia
Published: October 2019

Semaphorin 4D (Sema4D) plays a role in various cell types including B lymphocytes, differentiating neurons, endothelial cells, and cancer cells. Preclinical and in vitro studies have shown that Sema4D-directed antibodies in combination with immune checkpoint inhibitors reshape the tumor microenvironment by promoting recruitment of effector lymphocytes and antigen-presenting cells, while reducing immunosuppressive cell types, which ultimately leads to tumor rejection. Hence, early-stage clinical trials with combination therapies including anti-Sema4D antibodies are ongoing. In this issue of Cancer Research, Zuazo-Gaztelu and colleagues report an unexpected proinvasive effect induced by anti-Sema4D antibodies in a preclinical model of neuroendocrine pancreatic cancer (Rip1-Tag2), mediated by retrograde signaling of transmembrane Sema4D in macrophages, which increases their recruitment to tumors, SDF-1 secretion, and metastasis-promoting phenotype.

See related article by Zuazo-Gaztelu et al., p. 5328
Genomic Profiling Identifies Association of IDH1/IDH2 Mutation with Longer Relapse-Free and Metastasis-Free Survival in High-Grade Chondrosarcoma
Authors: Zhu Guo Gord , Nafa Khedoudja , Agaram Narasimhan , Zehir Ahmet , Benayed Ryma , Sadowska Justyna , Borsu Laetitia , Kelly Ciara , Tap William D. , Fabbri Nicola , Athanasian Edward , Boland Patrick J. , Healey John H. , Berger Michael F. , Ladanyi Marc , Hameed Meera
Published: October 2019

Purpose:

Chondrosarcomas are the second most common primary malignant bone tumors. Although histologic grade is the most important factor predicting the clinical outcome of chondrosarcoma, it is subject to interobserver variability. Isocitrate dehydrogenase 1 (IDH1) and IDH2 hotspot mutations were recently found to be frequently mutated in central chondrosarcomas. However, a few published articles have been controversial regarding the association between IDH1/IDH2 mutation status and clinical outcomes in chondrosarcomas.

Experimental Design:

We performed hotspot sequencing of IDH1 and IDH2 genes in 89 central chondrosarcomas and targeted next-generation sequencing in 54 of them, and then correlated the IDH1/IDH2 mutation status with the patient's clinical outcome.

Results:

Although no association was discovered between IDH mutation status and the patient's overall survival, IDH1/IDH2 mutation was found to be associated with longer relapse-free and metastasis-free survival in high-grade chondrosarcomas. Genomic profiling reveals TERT gene amplification and ATRX mutation, for the first time, in addition to TERT promoter mutation in a subset (6/30, 20%) of high-grade and dedifferentiated chondrosarcomas. These abnormalities in telomere genes are concurrent with IDH1/IDH2 mutation and with CDKN2A/2B deletion or TP53 mutation, suggesting a possible association and synergy among these genes in chondrosarcoma progression. We found 21% of patients with chondrosarcoma also had histories of second malignancies unrelated to cartilaginous tumors, suggesting possible unknown genetic susceptibility to chondrosarcoma.

Conclusions:

IDH1/IDH2 mutations are associated with longer relapse-free and metastasis-free survival in high-grade chondrosarcomas, and they tend to co-occur with TERT mutations and with CDKN2A/2B and TP53 alterations in a subset of high-grade chondrosarcomas.
Immune Cell PD-L1 Colocalizes with Macrophages and Is Associated with Outcome in PD-1 Pathway Blockade Therapy
Authors: Liu Yuting , Zugazagoitia Jon , Ahmed Fahad Shabbir , Henick Brian S. , Gettinger Scott N. , Herbst Roy S. , Schalper Kurt A. , Rimm David L.
Published: October 2019

Purpose:

Programmed death ligand 1 (PD-L1) is expressed in tumor cells and immune cells, and both have been associated with response to anti-PD-1 axis immunotherapy. Here, we examine the expression of PD-L1 to determine which cell type carries the predictive value of the test.

Experimental Design:

We measured the expression of PD-L1 in multiple immune cells with two platforms and confocal microscopy on three retrospective Yale NSCLC cohorts (425 nonimmunotherapy-treated cases and 62 pembrolizumab/nivolumab/atezolizumab-treated cases). The PD-L1 level was selectively measured in different immune cell subsets using two multiplexed quantitative immunofluorescence panels, including CD56 for natural killer cells, CD68 for macrophages, and CD8 for cytotoxic T cells.

Results:

PD-L1 was significantly higher in macrophages in both tumor and stromal compartment compared with other immune cells. Elevated PD-L1 in macrophages was correlated with high PD-L1 level in tumor as well as CD8 and CD68 level (P < 0.0001). High PD-L1 expression in macrophages was correlated with better overall survival (OS; P = 0.036 by cell count/P = 0.019 by molecular colocalization), while high PD-L1 expression in tumor cells was not.

Conclusions:

In nearly 500 non–small cell lung cancer (NSCLC) cases, the predominant immune cell type that expresses PD-L1 is CD68+ macrophages. The level of PD-L1 in macrophages is significantly associated with the level of PD-L1 in tumor cells and infiltration by CD8+ T cells, suggesting a connection between high PD-L1 and “hot” tumors. In anti-PD-1 axis therapy–treated patients, high levels of PD-L1 expression in macrophages are associated with longer OS and may be responsible for the predictive effect of the marker.
Potent Cell-Cycle Inhibition and Upregulation of Immune Response with Abemaciclib and Anastrozole in neoMONARCH, Phase II Neoadjuvant Study in HR+/HER2− Breast Cancer
Authors: Hurvitz Sara A. , Martin Miguel , Press Michael F. , Chan David , Fernandez-Abad María , Petru Edgar , Rostorfer Regan , Guarneri Valentina , Huang Chiun-Sheng , Barriga Susana , Wijayawardana Sameera , Brahmachary Manisha , Ebert Philip J. , Hossain Anwar , Liu Jiangang , Abel Adam , Aggarwal Amit , Jansen Valerie M. , Slamon Dennis J.
Published: October 2019

Purpose:

neoMONARCH assessed the biological effects of abemaciclib in combination with anastrozole in the neoadjuvant setting.

Patients and Methods:

Postmenopausal women with stage I–IIIB HR+/HER2− breast cancer were randomized to a 2-week lead-in of abemaciclib, anastrozole, or abemaciclib plus anastrozole followed by 14 weeks of the combination. The primary objective evaluated change in Ki67 from baseline to 2 weeks of treatment. Additional objectives included clinical, radiologic, and pathologic responses, safety, as well as gene expression changes related to cell proliferation and immune response.

Results:

Abemaciclib, alone or in combination with anastrozole, achieved a significant decrease in Ki67 expression and led to potent cell-cycle arrest after 2 weeks of treatment compared with anastrozole alone. More patients in the abemaciclib-containing arms versus anastrozole alone achieved complete cell-cycle arrest (58%/68% vs. 14%, P < 0.001). At the end of treatment, following 2 weeks lead-in and 14 weeks of combination therapy, 46% of intent-to-treat patients achieved a radiologic response, with pathologic complete response observed in 4%. The most common all-grade adverse events were diarrhea (62%), constipation (44%), and nausea (42%). Abemaciclib, anastrozole, and the combination inhibited cell-cycle processes and estrogen signaling; however, combination therapy resulted in increased cytokine signaling and adaptive immune response indicative of enhanced antigen presentation and activated T-cell phenotypes.

Conclusions:

Abemaciclib plus anastrozole demonstrated biological and clinical activity with generally manageable toxicities in patients with HR+/HER2− early breast cancer. Abemaciclib led to potent cell-cycle arrest, and in combination with anastrozole, enhanced immune activation.
High-Intensity Focused Ultrasound (HIFU) Triggers Immune Sensitization of Refractory Murine Neuroblastoma to Checkpoint Inhibitor Therapy
Authors: Eranki Avinash , Srinivasan Priya , Ries Mario , Kim AeRang , Lazarski Christopher A. , Rossi Christopher T. , Khokhlova Tatiana D. , Wilson Emmanuel , Knoblach Susan M. , Sharma Karun V. , Wood Bradford J. , Moonen Chrit , Sandler Anthony D. , Kim Peter C.W.
Published: October 2019

Purpose:

Immunotherapy promises unprecedented benefits to patients with cancer. However, the majority of cancer types, including high-risk neuroblastoma, remain immunologically unresponsive. High-intensity focused ultrasound (HIFU) is a noninvasive technique that can mechanically fractionate tumors, transforming immunologically “cold” tumors into responsive “hot” tumors.

Experimental Design:

We treated <2% of tumor volume in previously unresponsive, large, refractory murine neuroblastoma tumors with mechanical HIFU and assessed systemic immune response using flow cytometry, ELISA, and gene sequencing. In addition, we combined this treatment with αCTLA-4 and αPD-L1 to study its effect on the immune response and long-term survival.

Results:

Combining HIFU with αCTLA-4 and αPD-L1 significantly enhances antitumor response, improving survival from 0% to 62.5%. HIFU alone causes upregulation of splenic and lymph node NK cells and circulating IL2, IFNγ, and DAMPs, whereas immune regulators like CD4+Foxp3+, IL10, and VEGF-A are significantly reduced. HIFU combined with checkpoint inhibitors induced significant increases in intratumoral CD4+, CD8α+, and CD8α+CD11c+ cells, CD11c+ in regional lymph nodes, and decrease in circulating IL10 compared with untreated group. We also report significant abscopal effect following unilateral treatment of mice with large, established bilateral tumors using HIFU and checkpoint inhibitors compared with tumors treated with HIFU or checkpoint inhibitors alone (61.1% survival, P < 0.0001). This combination treatment significantly also induces CD4+CD44+hiCD62L+low and CD8α+CD44+hiCD62L+low population and is adoptively transferable, imparting immunity, slowing subsequent de novo tumor engraftment.

Conclusions:

Mechanical fractionation of tumors using HIFU can effectively induce immune sensitization in a previously unresponsive murine neuroblastoma model and promises a novel yet efficacious immunoadjuvant modality to overcome therapeutic resistance.
Submucosal Saline Injection Followed by Endoscopic Ultrasound versus Endoscopic Ultrasound Only for Distinguishing between T1a and T1b Esophageal Cancer
Authors: He Long-Jun , Xie Chuanbo , Wang Zi-Xian , Li Yin , Xiao Yi-Tai , Gao Xiao-Yan , Shan Hong-Bo , Luo Lin-Na , Chen Li-Ming , Luo Guang-Yu , Yang Ping , Zeng Shuo-Chun , Xu Guo-Liang , Li Jian-Jun
Published: October 2019

Purpose:

To examine whether submucosal saline injection (SSI) can improve traditional endoscopic ultrasound (EUS) accuracy in distinguishing between T1a and T1b stage esophageal squamous cell carcinoma (ESCC).

Experimental Design:

Patients with T1N0M0 stage ESCC (n = 180) ages 18 to 85 years were enrolled between February 14, 2012 to June 4, 2018 at Sun Yat-sen University Cancer Center (Guangdong, China). They were randomly assigned (1:1) to receive either EUS examination after 3–5 mL SSI or EUS only examination. All the patients were referred to thoracic surgeons to receive endoscopic resection (ER) or esophagectomy 5 to 10 days after EUS examination. Standard EUS criteria were used to preoperatively stage the ESCC cases, and surgical pathology reports after referral were used to postoperatively stage the cases. The primary endpoint was the diagnostic accuracy of T1b staging [defined as the sum of the true positive (T1b) and true negative (T1a) cases divided by the total number of cases].

Results:

Among the per-protocol population, the SSI+EUS group (n = 81) was superior to the EUS-only group (n = 85) in terms of the diagnostic accuracy for T1b staging [93.8% (95% confidence interval (CI), 88.6–99.1) vs. 65.9% (95% CI, 55.8–76.0); P < 0.001]. The positive predictive value of SSI+EUS for diagnosing T1b ESCC reached 90.9% (95% CI, 81.1–100), which was significantly superior to that of EUS only [0.576 (0.450-0.702), P = 0.001].

Conclusions:

SSI significantly improves the diagnostic accuracy of EUS in distinguishing between T1a and T1b ESCC, which might help avoid unnecessary esophagectomy and diagnostic ER.
Mogamulizumab Forecast: Clearer Patients, with a Slight Chance of Immune Mayhem
Authors: Larocca Cecilia , Kupper Thomas S. , LeBoeuf Nicole R.
Published: October 2019

Mogamulizumab, approved by the FDA for relapsed or refractory mycosis fungoides and Sézary syndrome, improves progression-free survival compared with vorinostat in the largest trial to date in cutaneous T-cell lymphoma, with particular efficacy in leukemic disease, but carries a risk of immune-mediated toxicities with concomitant depletion of regulatory T cells.

See related article by Kasamon et al., p. 7275
Early Biomarkers of Fabry Nephropathy: A Review of the Literature
Authors: Riccio Eleonora , Sabbatini Massimo , Capuano Ivana , Pisani Antonio
Published: October 2019

Progressive nephropathy is one of the main features of Fabry disease. Although some clinical signs of Fabry nephropathy are already present in childhood, patients are often diagnosed relatively late in the course of the disease due to the absence of specific clinical markers, while a timely diagnosis and the prompt start of enzyme replacement therapy may be beneficial in stabilizing renal function or slowing its decline. Proteinuria/albuminuria has been accepted as the most important marker for Fabry nephropathy; however, a large proportion of renal impairment occurs in nonalbuminuric state. Therefore, early biomarkers may be useful for early identiﬁcation of kidney involvement. The aim of this article is to review the current available literature on all biomarkers of Fabry nephropathy, with a comprehensive and critical description of their utilization in early recognition of renal damage.
Stereotactic Vacuum-Assisted Breast Biopsy in Ductal Carcinoma in situ: Residual Microcalcifications and Intraoperative Findings
Authors: Krischer Benedict , Forte Serafino , Singer Gad , Kubik-Huch Rahel A. , Leo Cornelia
Published: October 2019

Purpose: The question of overtreatment of ductal carcinoma in situ (DCIS) was raised because a significant proportion of especially low-grade DCIS lesions never progress to invasive cancer. The rationale for the present study was to analyze the value of stereotactic vacuum-assisted biopsy (VAB) for complete removal of DCIS, focusing on the relationship between the absence of residual microcalcifications after stereotactic VAB and the histopathological diagnosis of the definitive surgical specimen. Patients and Methods: Data of 58 consecutive patients diagnosed with DCIS by stereotactic VAB in a single breast center between 2012 and 2017 were analyzed. Patient records from the hospital information system were retrieved, and mammogram reports and images as well as histopathology reports were evaluated. The extent of microcalcifications before and after biopsy as well as the occurrence of DCIS in biopsy and definitive surgical specimens were analyzed and correlated. Results: There was no correlation between the absence of residual microcalcifications in the post-biopsy mammogram and the absence of residual DCIS in the final surgical specimen (p = 0.085). Upstaging to invasive cancer was recorded in 4 cases (13%) but occurred only in the group that had high-grade DCIS on biopsy. Low-grade DCIS was never upgraded to high-grade DCIS in the definitive specimen. Conclusions: The radiological absence of microcalcifications after stereotactic biopsy does not rule out residual DCIS in the final surgical specimen. Since upstaging to invasive cancer is seen in a substantial proportion of high-grade DCIS, the surgical excision of high-grade DCIS should remain the treatment of choice.
Follow-Up of Bone Mineral Density Changes in de novo Kidney Transplant Recipients Treated with Two Doses of the Receptor Activator of Nuclear Factor κB Ligand Inhibitor Denosumab
Authors: Kobel Claudia , Frey Diana , Graf Nicole , Wüthrich Rudolf P. , Bonani Marco
Published: October 2019

Background: Studies in women with post-menopausal osteoporosis have shown that discontinuation of treatment with denosumab leads to an increased risk of vertebral fractures because of rebound bone turnover and rapid loss of bone mineral density (BMD). Methods: In a post hoc analysis of the Prolia for Osteoporosis of Transplant Operated Patient study, we analyzed the effect of denosumab withdrawal on BMD changes. Twenty-five de novo kidney transplant recipients (KTR) who were treated for 1 year with 2 six-monthly doses of denosumab on top of standard treatment (daily calcium and vitamin D) were compared to a control group of 29 KTR who received standard treatment alone. BMD changes were analyzed by repeated dual-energy X-ray absorptiometry shortly after transplantation (baseline), after 6 and 12 months (active treatment phase) and after 2–6.5 years (follow-up phase). Results: The average BMD at the lumbar spine declined markedly after discontinuation of treatment with denosumab but increased again thereafter. Thus, the average monthly change in lumbar spine BMD from month 12 onward was only 0.1 ± 2.8‰ in the denosumab group but 1.5 ± 1.9‰ in the control group (p = 0.021). The average monthly change in lumbar spine BMD from baseline to follow-up was similar in the control and denosumab group (1.1 ± 1.2‰ vs. 1.5 ± 2.4‰, p = 0.788). Similar results were seen at the total hip. Conclusions: In de novo KTR treated with 2 doses of denosumab, we detect a marked decrease in lumbar spine and hip BMD when denosumab is discontinued. Denosumab treatment should therefore not be discontinued without considering an alternative antiresorptive treatment.
Non Transecting Dorsal Onlay and Ventral Inlay Buccal Mucosal Substitution Urethroplasty for Obliterative Bulbar Urethral Strictures
Authors: Rajaian Shanmugasundaram , Murugavaithianathan Pragatheeswarane , Krishnamurthy Karrthik , Murugasen Lakshman
Published: October 2019

Background: Dorsal or ventral single layer repair can be impractical when there is an inadequate strip of urethra. Staged urethroplasty and non-transecting bilayer substitution urethroplasty are the other alternatives. Objectives: To assess the safety and outcome of non-transecting dorsal onlay and ventral inlay buccal mucosal substitution urethroplasty technique. Method: Between January 2014 and December 2018, 21 patients underwent non-transecting, double-layer, buccal mucosal urethroplasty for inflammatory bulbar urethral strictures. Four weeks after surgery, foley catheters were removed and voiding trial was given. Clinical examination and uroflowmetry (UFM) were done at 1, 3, and 6 months after surgery. Annual follow-up with flow rate and post-void residual assessment were also recorded. Failure was defined as a condition when there was flow rate deterioration (<15 mL/s) or when there is stricture recurrence (<20 Fr). Results: The mean age was 49.5 years. There was no significant difference in comorbidities among the patients. The mean duration of operative time was 259 min. The mean blood loss was 190 mL. The follow-up duration ranged from 12 to 66 months. The average length of stricture was 3.9 cm. The mean diameter of stricture segment was 1.96 mm. Comparison of UFM trend during follow-up was statistically significant (p = 0.05). One patient had Clavien-dindo grade 1, while 2 patients had grade 3b complications. Two patients had soft anastomotic site stricture and were treated successfully with endoscopic internal urethrotomy. The success rate was 90.47%. Conclusions: Non-transecting bilayer substitution urethroplasty is safe and has better short-term outcome in case of obliterative inflammatory urethral strictures.
Complement Factor I Gene Polymorphism in a Turkish Age-Related Macular Degeneration Population
Authors: Bezci Aygun Figen , Kadayıfcılar Sibel , Ozgul Rıza Koksal , Eldem Bora
Published: October 2019

Objective: Evaluation of Complement Factor I (CFI) rs10033900 and rs2285714 polymorphism frequencies in patients with age-related macular degeneration (AMD) and healthy controls in a Turkish population. Methods: A total of 111 eyes of 111 AMD patients and 96 eyes of 96 healthy controls, only one eye of individuals, were included in the study; however, 2 patients’ and 4 controls’ samples were excluded as analyses could not be performed for rs10033900 polymorphism. The AMD patients and control group (>50 years) lacked corneal, lenticular, vitreal opacity. However, these patients did not have any retinal diseases apart from AMD. Venous blood samples of patients were collected. Central macular thickness, subfoveal choroidal thickness (SCT), presence of reticular drusen, epiretinal membrane, and pigment epithelial detachment were investigated using Spectral-Domain Optical Coherence Tomography, and the largest diameter of atrophic areas measured. Drusen properties were documented from fundus photographs. The lesion width was calculated by using fundus fluorescein angiography. Results: There was no difference between patient and control groups and polymorphism distributions. The frequency of the CT allele was higher in patients with dry-type AMD with retinal pigment epithelial abnormality (p = 0.041). SCT was significantly thinner in TT allele carriers with rs2285714 polymorphism (p = 0.030). No significant relationship was found between the other parameters and polymorphism distributions. Con­clusion: CFI rs10033900 and rs2285714 polymorphisms in a Turkish population were not associated with AMD.
Treatment of Pituitary and Other Tumours with Cabergoline: New Mechanisms and Potential Broader Applications
Authors: Lin Shaojian , Zhang Anke , Zhang Xun , Wu Zhe Bao
Published: October 2019

Cabergoline is a dopamine agonist that has been used as the first-line treatment option for prolactin-secreting pituitary adenomas for several decades. It not only suppresses hormone production from these prolactinomas, but also causes tumour shrinkage. Recent studies revealed some novel mechanisms by which cabergoline suppresses tumour cell proliferation and induces cell death. In this article, we review the most recent findings in cabergoline studies, focusing on its anti-tumour function. These studies suggest the potential broader clinical use of cabergoline in the treatment of other tumours such as breast cancer, pancreatic neuroendocrine tumours, and lung cancer.
A coleção de vidros antigos, islâmicos e europeus no Museu de Arqueologia e Etnologia da USP
Authors:   Universidade de São Paulo. Museu de Arqueologia e Etnologia, Montecchi Barbara
Published: October 2019

A obra se apresenta como um catálogo representando o resultado de excelente trabalho de pesquisa da dra. Barbara Montecchi, da Universidade de Florença, um singular estudo curatorial que prioriza a tecnologia como ponto de inflexão e inserção desses artefatos e fragmentos em novos circuitos de cultura material, articulando a coleção do MAE a outros conjuntos congêneres de instituições brasileiras e estrangeiras. Esse acervo, formado a partir de coleções particulares sem proveniências precisas, tem características bastante comuns em muitas coleções museológicas. O material é extremamente heterogêneo e cobre um vasto período cronológico do século XIII a.C ao XI d.C. O arranjo do material sob o prisma tecnológico visou também satisfazer a uma das funções básicas de um museu universitário, que são seus propósitos didático-educativos, possibilitando o olhar para muitas produções de vidros diferentes.
Técnica e política na agricultura globalizada: A expansão do setor sucroenergético em Goiás
Authors: Mesquita Fernando Campos , Castillo Ricardo Abid
Published: October 2019

Com a globalização, crescem perspectivas que valorizam o peso de forças externas na dinâmica econômica dos lugares. Essa ideia é ainda mais forte em uma atividade altamente internacionalizada e com elevada presença de empresas multinacionais como o agronegócio. No entanto, o vetor externo é apenas um lado do processo. Seguindo a concepção de Santos (2010), entendemos que algumas categorias de lugares produtivos inseridos na globalização podem sediar pouco do comando político da produção, mas ficam com parcela significativa do comando técnico. Desse modo, ao passo que os centros de decisão do agronegócio são externos às regiões de Cerrado, o desenvolvimento de técnicas que levam ao aprimoramento da agricultura se relaciona com fatores internos. O objetivo é apontar evidências dessa afirmação no crescimento do setor sucroenergético em Goiás, buscando reconhecer o devido valor das condições internas dos lugares e regiões produtivas em sua relação dialética com os vetores da globalização.
Effect of Direct Oral Anticoagulants, Warfarin, and Antiplatelet Agents on Risk of Device Pocket Hematoma
Authors: Essebag Vidal , Healey Jeff S. , Joza Jacqueline , Nery Pablo B. , Kalfon Eli , Leiria Tiago L.L. , Verma Atul , Ayala-Paredes Felix , Coutu Benoit , Sumner Glen L. , Becker Giuliano , Philippon François , Eikelboom John , Sandhu Roopinder K. , Sapp John , Leather Richard , Yung Derek , Thibault Bernard , Simpson Christopher S. , Ahmad Kamran , Toal Satish , Sturmer Marcio , Kavanagh Katherine , Crystal Eugene , Wells George A. , Krahn Andrew D. , Birnie David H. ,   for the BRUISE CONTROL Investigators*
Published: October 2019

Background:

Oral anticoagulant use is common among patients undergoing pacemaker or defibrillator surgery. BRUISE CONTROL (Bridge or Continue Coumadin for Device Surgery Randomized Controlled Trial; NCT00800137) demonstrated that perioperative warfarin continuation reduced clinically significant hematomas (CSH) by 80% compared with heparin bridging (3.5% versus 16%). BRUISE-CONTROL-2 (NCT01675076) observed a similarly low risk of CSH when comparing continued versus interrupted direct oral anticoagulant (2.1% in both groups). Using patient level data from both trials, the current study aims to: (1) evaluate the effect of concomitant antiplatelet therapy on CSH, and (2) understand the relative risk of CSH in patients treated with direct oral anticoagulant versus continued warfarin.

Methods:

We analyzed 1343 patients included in BRUISE-CONTROL-1 and BRUISE-CONTROL-2. The primary outcome for both trials was CSH. There were 408 patients identified as having continued either a single or dual antiplatelet agent at the time of device surgery.

Results:

Antiplatelet use (versus nonuse) was associated with CSH in 9.8% versus 4.3% of patients (
P
<0.001), and remained a strong independent predictor after multivariable adjustment (odds ratio, 1.965; 95% CI, 1.202–3.213;
P
=0.0071). In multivariable analysis, adjusting for antiplatelet use, there was no significant difference in CSH observed between direct oral anticoagulant use compared with continued warfarin (odds ratio, 0.858; 95% CI, 0.375–1.963;
P
=0.717).

Conclusions:

Concomitant antiplatelet therapy doubled the risk of CSH during device surgery. No difference in CSH was found between direct oral anticoagulant versus continued warfarin. In anticoagulated patients undergoing elective or semi-urgent device surgery, the patient specific benefit/risk of holding an antiplatelet should be carefully considered.

Clinical Trial Registration:

URL:
https://www.clinicaltrials.gov
. Unique identifiers: NCT00800137, NCT01675076.
Genetic Association Analyses Highlight
IL6
,
ALPL
, and
NAV1
As 3 New Susceptibility Genes Underlying Calcific Aortic Valve Stenosis
Authors: Thériault Sébastien , Dina Christian , Messika-Zeitoun David , Le Scouarnec Solena , Capoulade Romain , Gaudreault Nathalie , Rigade Sidwell , Li Zhonglin , Simonet Floriane , Lamontagne Maxime , Clavel Marie-Annick , Arsenault Benoit J. , Boureau Anne-Sophie , Lecointe Simon , Baron Estelle , Bonnaud Stéphanie , Karakachoff Matilde , Charpentier Eric , Fellah Imen , Roussel Jean-Christian , Philippe Verhoye Jean , Baufreton Christophe , Probst Vincent , Roussel Ronan , Redon Richard , Dagenais François , Pibarot Philippe , Mathieu Patrick , Le Tourneau Thierry , Bossé Yohan , Schott Jean-Jacques , Balkau B. , Ducimetière P. , Eschwège E. , Alhenc-Gelas F. , Girault A. , Fumeron F. , Marre M. , Bonnet F. , Bonnefond A. , Froguel P. , Rancière F. , Cogneau J. , Born C. , Caces E. , Cailleau M. , Lantieri O , Moreau J.G. , Rakotozafy F. , Tichet J. , Vol S.
Published: October 2019

Background:

Calcific aortic valve stenosis (CAVS) is a frequent and life-threatening cardiovascular disease for which there is currently no medical treatment available. To date, only 2 genes,
LPA
and
PALMD
, have been identified as causal for CAVS. We aimed to identify additional susceptibility genes for CAVS.

Methods:

A GWAS (genome-wide association study) meta-analysis of 4 cohorts, totaling 5115 cases and 354 072 controls of European descent, was performed. A TWAS (transcriptome-wide association study) was completed to integrate transcriptomic data from 233 human aortic valves. A series of post-GWAS analyses were performed, including fine-mapping, colocalization, phenome-wide association studies, pathway, and tissue enrichment as well as genetic correlation with cardiovascular traits.

Results:

In the GWAS meta-analysis, 4 loci achieved genome-wide significance, including 2 new loci:
IL6
(interleukin 6) on 7p15.3 and
ALPL
(alkaline phosphatase) on 1p36.12. A TWAS integrating gene expression from 233 human aortic valves identified
NAV1
(neuron navigator 1) on 1q32.1 as a new candidate causal gene. The CAVS risk alleles were associated with higher mRNA expression of
NAV1
in valve tissues. Fine-mapping identified rs1800795 as the most likely causal variant in the
IL6
locus. The signal identified colocalizes with the expression of the
IL6
RNA antisense in various tissues. Phenome-wide association analyses in the UK Biobank showed colocalized associations between the risk allele at the
IL6
lead variant and higher eosinophil count, pulse pressure, systolic blood pressure, and carotid artery procedures, implicating modulation of the IL6 pathways. The risk allele at the
NAV1
lead variant colocalized with higher pulse pressure and higher prevalence of carotid artery stenosis. Association results at the genome-wide scale indicated genetic correlation between CAVS, coronary artery disease, and cardiovascular risk factors.

Conclusions:

Our study implicates 3 new genetic loci in CAVS pathogenesis, which constitute novel targets for the development of therapeutic agents.
Myocardial Fibrosis and Prognosis in Heart Transplant Recipients
Authors: Hughes Andrew , Okasha Osama , Farzaneh-Far Afshin , Kazmirczak Felipe , Nijjar Prabhjot S. , Velangi Pratik , Akçakaya Mehmet , Martin Cindy M. , Shenoy Chetan
Published: October 2019

Background:

Myocardial fibrosis is a well-described histopathologic feature in heart transplant recipients. Whether myocardial fibrosis in heart transplant recipients is independently associated with clinical outcomes is unclear. We sought to determine whether myocardial fibrosis on late gadolinium enhancement cardiovascular magnetic resonance imaging in heart transplant recipients was independently associated with all-cause death or major adverse cardiac outcomes in the long-term.

Methods:

Using a cohort of consecutive heart transplant recipients that had cardiovascular magnetic resonance imaging, we determined the prevalence and the patterns of myocardial fibrosis and analyzed associations between myocardial fibrosis and a composite end point of all-cause death or major adverse cardiac events: retransplantation, nonfatal myocardial infarction, coronary revascularization, and heart failure hospitalization.

Results:

One hundred and fifty-two heart transplant recipients (age, 54±15 years; 29% women; 5.0±5.4 years after heart transplantation) were included. Myocardial fibrosis was present in 18% (37% infarct pattern, 41% noninfarct pattern, and 22% both). Its prevalence was positively associated with cardiac allograft vasculopathy grade. With a median follow-up of 2.6 years, myocardial fibrosis was independently associated with all-cause death or major adverse cardiac events (hazard ratio, 2.88; 95% CI, 1.59–5.23;
P
<0.001) after adjustment for cardiac allograft vasculopathy, history of rejection, time since transplantation, left ventricular ejection fraction, and indexed right ventricular end-diastolic volume. Every 1% increase in myocardial fibrosis was independently associated with a 6% higher hazard for all-cause death or major adverse cardiac events (hazard ratio, 1.06; 95% CI, 1.03–1.09;
P
<0.001). The addition of myocardial fibrosis variables to models with cardiac allograft vasculopathy, history of rejection, time since transplantation, left ventricular ejection fraction, and indexed right ventricular end-diastolic volume resulted in significant improvements in model fit, suggesting incremental prognostic value.

Conclusions:

In heart transplant recipients, myocardial fibrosis is seen on late gadolinium enhancement cardiovascular magnetic resonance imaging in 18%. Both the presence and the extent of myocardial fibrosis are independently associated with the long-term risk of all-cause death or major adverse cardiac events.
Bone Marrow-Derived Cells Restore Functional Integrity of the Gut Epithelial and Vascular Barriers in a Model of Diabetes and ACE2 Deficiency
Authors: Duan Yaqian , Prasad Ram , Feng Dongni , Beli Eleni , Li Calzi Sergio , Longhini Ana Leda F. , Lamendella Regina , Floyd Jason L. , Dupont Mariana , Noothi Sunil K. , Sreejit Gopalkrishna , Athmanathan Baskaran , Wright Justin , Jensen Amanda R. , Oudit Gavin Y. , Markel Troy A. , Nagareddy Prabhakara R. , Obukhov Alexander G. , Grant Maria B.
Published: October 2019

Rationale:

There is incomplete knowledge of the impact of bone marrow cells on the gut microbiome and gut barrier function.

Objective:

We postulated that diabetes mellitus and systemic ACE2 (angiotensin-converting enzyme 2) deficiency would synergize to adversely impact both the microbiome and gut barrier function.

Methods and Results:

Bacterial 16S rRNA sequencing and metatranscriptomic analysis were performed on fecal samples from wild-type, ACE2
−/y
, Akita (type 1 diabetes mellitus), and ACE2
−/y
-Akita mice. Gut barrier integrity was assessed by immunofluorescence, and bone marrow cell extravasation into the small intestine was evaluated by flow cytometry. In the ACE2
−/y
-Akita or Akita mice, the disrupted barrier was associated with reduced levels of myeloid angiogenic cells, but no increase in inflammatory monocytes was observed within the gut parenchyma. Genomic and metatranscriptomic analysis of the microbiome of ACE2
−/y
-Akita mice demonstrated a marked increase in peptidoglycan-producing bacteria. When compared with control cohorts treated with saline, intraperitoneal administration of myeloid angiogenic cells significantly decreased the microbiome gene expression associated with peptidoglycan biosynthesis and restored epithelial and endothelial gut barrier integrity. Also indicative of diabetic gut barrier dysfunction, increased levels of peptidoglycan and FABP-2 (intestinal fatty acid-binding protein 2) were observed in plasma of human subjects with type 1 diabetes mellitus (n=21) and type 2 diabetes mellitus (n=23) compared with nondiabetic controls (n=23). Using human retinal endothelial cells, we determined that peptidoglycan activates a noncanonical TLR-2 (Toll-like receptor 2) associated MyD88 (myeloid differentiation primary response protein 88)-ARNO (ADP-ribosylation factor nucleotide-binding site opener)-ARF6 (ADP-ribosylation factor 6) signaling cascade, resulting in destabilization of p120-catenin and internalization of VE-cadherin as a mechanism of deleterious impact of peptidoglycan on the endothelium.

Conclusions:

We demonstrate for the first time that the defect in gut barrier function and dysbiosis in ACE2
−/y
-Akita mice can be favorably impacted by exogenous administration of myeloid angiogenic cells.
Associations Between Sleep Apnea and Subclinical Carotid Atherosclerosis
Authors: Zhao Ying Y. , Javaheri Sogol , Wang Rui , Guo Na , Koo Brian B. , Stein James H. , Korcarz Claudia E. , Redline Susan
Published: October 2019

Background and Purpose—

Many health effects of sleep apnea (SA) may be mediated through accelerated atherosclerosis. We examined the associations of snoring and several measurements of SA with subclinical carotid atherosclerosis in a large multiethnic population sample.

Methods—

This analysis included 1615 participants (mean age, 68 years) from examination 5 (2010–2013) of the MESA study (Multi-Ethnic Study of Atherosclerosis). Sleep measures including SA (apnea-hypopnea index [4%], ≥15 events/hour) were derived from full in-home polysomnography. Carotid atherosclerosis was measured using high-resolution B-mode ultrasound. Multivariable linear and logistic regression models were used to evaluate the associations between sleep exposures with carotid intima-media thickness and the presence of carotid plaque, respectively. Effect modification by age, sex, and race/ethnicity was examined.

Results—

In multivariable analysis, SA was associated with an increased odds of carotid plaque presence in individuals aged <68 years (odds ratio, 1.47; 95% CI, 1.05–2.06) but not in older individuals (odds ratio, 0.95; 95% CI, 0.67–1.37;
P
interaction=0.078). Greater hypoxemia (sleep time <90% saturation) was associated with increasing carotid intima-media thickness in younger (0.028±0.014 mm) but not in older individuals (−0.001±0.013 mm;
P
interaction=0.106). Self-reported snoring was not associated with carotid atherosclerosis. In assessing race-specific outcomes, greater hypoxemia was associated with increased carotid intima-media thickness in blacks (0.049±0.017 mm;
P
interaction=0.033).

Conclusions—

In this large multiethnic population-based sample, sleep disturbances are associated with subclinical carotid atherosclerosis in both men and women, particularly in those <68 years of age. The mechanisms underlying the association between SA and carotid atherosclerosis may differ for carotid plaque and carotid intima-media thickness.
Association of Socioeconomic Status With Ischemic Stroke Survival
Authors: Vivanco-Hidalgo Rosa Maria , Ribera Aida , Abilleira Sònia
Published: October 2019

Background and Purpose—

The aim of the study was to determine the impact of individuals’ socioeconomic status and their Primary Care Service Area Socioeconomic Index on survival after ischemic stroke.

Methods—

We conducted a nationwide population-based cohort study in Catalonia, Spain. We included all patients with first ischemic stroke admitted to a public hospital between January 1, 2015, and December 31, 2016. We measured both individual socioeconomic status (categorized as exempts, <€18 000 [$US 20 468] income per year, and >€18 000 income per year) and Primary Care Service Area Socioeconomic Index (from 0 to 100 categorized in quartiles).

We used mixed-effects logistic and survival models to estimate odds ratios and hazard ratios for the short- (30 days) and the long-term (3 years) all-cause case fatality rates by individuals’ socioeconomic status groups.

Results—

The cohort consisted of 16 344 ischemic stroke patients with 24 638 person-years of follow-up. We did not find an association between the lowest socioeconomic individual status and short-term survival (odds ratio, 1.03; 95% CI, 0.76–1.40), although we found it in patients with <€18 000 income/year (odds ratio, 1.26; 95% CI, 1.10–1.45). At long-term, after adjustment, we observed a gradient in mortality risk with decreasing individual socioeconomic status (hazard ratio, 1.52; 95% CI, 1.30–1.77). The Primary Care Service Area Socioeconomic Index had only an influence on short-term survival (odds ratio, 1.19; 95% CI, 1.03–1.37).

Conclusions—

Individuals’ socioeconomic status was associated with short- and long-term survival in patients with ischemic stroke. Conversely, Primary Care Service Area Socioeconomic Index measures had an influence only in short-term survival. A small fraction of this association is due to differences in comorbidity and cardiovascular risk factors. Interventions addressing both individuals’ and primary care service socioeconomic aspects might eventually affect differently short- and long-term survival.