bluuebunny/crossref_metadata_2025 huggingface dataset:
Numerical Analysis of Hybrid Steel Beams with Trapezoidal Corrugated Web Nonwelded Inclined Folds
Authors: Alharthi Yasir M. , Sharaky Ibrahim A. , Elamary Ahmed S.
Published: July 2021

Hybrid beams provide the opportunity to implement characterized steel sections by recruiting materials based on yield strength and the type of applied stress. Previous studies demonstrated that steel beams with a trapezoidal corrugated web (SBCWs) were affected by both fatigue cracks initiated along the inclined fold (IF) and the maximal additional stress located in the middle of the IFs. This paper presents a numerical study of hybrid SBCWs and nonwelded IFs. Numerical simulation is presented using the finite element (FE) method with the aid of the ANSYS software package. Three‐dimensional FE models were developed considering the nonlinear properties of materials and geometric imperfection and validated using five hybrid specimens that were fabricated and tested experimentally by the authors. The load‐deflection behavior and failure mechanism of the numerical results were in good agreement with the experimental results. The comparison of the FE models and the experimental results shows the good capability of the FE model to be used as a base for the parametric study. The parametric study focused on the effect of web thickness, flange thickness, web height, and flange and web steel grades. Furthermore, parametric studies are conducted to investigate the effects of the number and depth of the stiffeners on the behavior of hybrid SBCWs. We concluded that the flange thickness, web thickness, web height, and steel grades of flanges significantly affect the capacity and failure mode of hybrid SBCWs. We also concluded that the flange stiffeners have a significant effect on the overall behavior, toughness, and load capacity of SBCWs. Finally, a new equation is proposed to anticipate the shear capacity of SBCW nonwelded IFs based on the length of the welded horizontal fold.
A Miniaturized High-Gain Flexible Antenna for UAV Applications
Authors: Yang Xinhuan , Qi Yanzhu , Yuan Bo , Cao Yazi , Wang Gaofeng
Published: July 2021

A miniaturized high-gain flexible unmanned aerial vehicle (UAV) antenna is presented in this study. The proposed antenna basically comprised of three parts of printed patch in series, etched on dielectric substrate. And, a flexible cable is loaded on the bottom of dielectric substrate. A coplanar waveguide (CPW) with asymmetric ground feeding structure is employed to provide good impedance matching. The surface current can achieve the same phase for the straight-line patch and the flexible cable, through adjusting the dimensions of the meander line patch, which increases radiation gain while maintaining the compact size. As an important merit to be highlighted, the flexible cable can greatly reduce the volume and aerodynamic drag of the antenna. It has a low-profile compact size of 196 × 15 × 0.8 mm3 (excluding flexible cable). The results show that the omnidirectional gain fluctuates within 4.5 ± 0.1 dBi in the desired band (902 MHz–928 MHz), which is high enough for the UAV application. Details of the antenna design and experimental results are presented and discussed.
An Interesting Case of Isolated False-Reactive Hepatitis B Surface Antigen
Authors: Costa Victoria , Zhao Zhen , Racine-Brzostek Sabrina E. , Lalazar Gadi , Yang He S.
Published: July 2021

The standard serologic markers used to diagnose hepatitis B infection include hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), total hepatitis B core antibody (anti-HBc), and IgM antibody to hepatitis B core antigen (IgM anti-HBc). Different markers or combinations of markers are used to identify different phases of HBV infection and determine whether a patient has acute or chronic infection or immunity due to prior infection or vaccination or is seronegative and susceptible to future infection. Isolated HBsAg seropositivity is a peculiar serological pattern that requires investigation. Herein, we present a case of an asymptomatic female without a history of liver disease or evident risk factors for hepatitis, who underwent screening for infectious disease prior to resection of basal cell carcinoma involving her eyelid. The patient’s laboratory testing showed positivity for HBsAg and the HIV 1/2 screen. To investigate, we performed serial dilutions, utilized heterophilicantibody blocking tubes, and repeated analysis using a different commercial assay (Abbott Architect i2000), all in support of a false-positive result attributed to a heterophilic antibody. Hence, we demonstrate that heterophilic antibody interference can result in isolated HBsAg positivity and recommend considering this form of interference in the differential where there is low clinical suspicion for viral infection.
Exosomal lncRNA PVT1/VEGFA Axis Promotes Colon Cancer Metastasis and Stemness by Downregulation of Tumor Suppressor miR‐152‐3p
Authors: Lai Shiue-Wei , Chen Ming-Yao , Bamodu Oluwaseun Adebayo , Hsieh Ming-Shou , Huang Ting-Yi , Yeh Chi-Tai , Lee Wei-Hwa , Cherng Yih-Giun
Published: July 2021

Background. Treating advanced colon cancer remains challenging in clinical settings because of the development of drug resistance and distant metastasis. Mechanisms underlying the metastasis of colon cancer are complex and unclear. Methods. Computational analysis was performed to determine genes associated with the exosomal long noncoding (lncRNA) plasmacytoma variant translocation 1 (PVT1)/vascular endothelial growth factor A (VEGFA) axis in patients with colon cancer. The biological importance of the exosomal lncRNA PVT1/VEGFA axis was examined in vitro by using HCT116 and LoVo cell lines and in vivo by using a patient‐derived xenograft (PDX) mouse model through knockdown (by silencing of PVT1) and overexpression (by adding serum exosomes isolated from patients with distant metastasis (M‐exo)). Results. The in silico analysis demonstrated that PVT1 overexpression was associated with poor prognosis and increased expression of metastatic markers such as VEGFA and epidermal growth factor receptor (EGFR). This finding was further validated in a small cohort of patients with colon cancer in whom increased PVT1 expression was correlated with colon cancer incidence, disease recurrence, and distant metastasis. M‐exo were enriched with PVT1 and VEGFA, and both migratory and invasive abilities of colon cancer cell lines increased when they were cocultured with M‐exo. The metastasis‐promoting effect was accompanied by increased expression of Twist1, vimentin, and MMP2. M‐exo promoted metastasis in PDX mice. In vitro silencing of PVT1 reduced colon tumorigenic properties including migratory, invasive, colony forming, and tumorsphere generation abilities. Further analysis revealed that PVT1, VEGFA, and EGFR interact with and are regulated by miR‐152‐3p. Increased miR‐152‐3p expression reduced tumorigenesis, where increased tumorigenesis was observed when miR‐152‐3p expression was downregulated. Conclusion. Exosomal PVT1 promotes colon cancer metastasis through its association with EGFR and VEGFA expression. miR‐152‐3p targets both PVT1 and VEGFA, and this regulatory pathway can be explored for drug development and as a prognostic biomarker.
An Efficient Scheme for Industrial Internet of Things Using Certificateless Signature
Authors: Muhammad Ali , Amin Noor Ul , Ullah Insaf , Alsanad Ahmed , Hussain Saddam , Al-Hadhrami Suheer , Uddin M. Irfan , Khattak Hizbullah , Khan Muhammad Asghar
Published: July 2021

Currently, hyperelliptic curve cryptography (HECC) got attractions towards low power devices such as Industrial Internet of Things (IIoT). As we all know, it has the capability of utilizing low key size, which can be suitable for IIoT environment. Inspired by the aforementioned property of HECC, we proposed an efficient scheme for IIoT using certificateless signature with the help of HECC. The presented approach is proven to be unforgeable against the challenges of type I and type II attackers. We tested the security of the designed approach through Automated Validation of Internet Security Protocols and Applications (AVISPA). We also performed the computational and communicational cost comparisons with already existed schemes, and it is observed from our analysis that our scheme is computationally efficient and needs low communication cost.
Analysis and Construction of a Competitive Endogenous RNA Regulatory Network of Baicalin‐Induced Apoptosis in Human Osteosarcoma Cells
Authors: Lan Haifeng , Wang Haiyan , Gao Mi , Luo Guan , Zhang Jiahuan , Yi Erkang , Liang Chunxiao , Xiong Xiaoxiao , Chen Xing , Wu Qinghua , Chen Ruikun , Lin Biting , Qian Dongyang , Hong Wei
Published: July 2021

Background. Baicalin is an extract from the traditional Chinese herb Scutellaria baicalensis and has the potential to treat osteosarcoma (OS). However, the transcriptome‐level mechanism of baicalin‐mediated antitumor effects in OS has not yet been investigated. The aim of this study was to analyze the competitive endogenous RNA (ceRNA) regulatory network involved in baicalin‐induced apoptosis of OS cells. Methods. In this study, CCK‐8 and flow cytometry assays were used to detect the antitumor effects of baicalin on human OS MG63 cells. Furthermore, transcriptome sequencing was employed to establish the long noncoding RNA (lncRNA), microRNA (miRNA), and mRNA profiles. Results. Baicalin inhibited MG63 cell proliferation and induced apoptosis. Totals of 58 lncRNAs, 31 miRNAs, and 2136 mRNAs in the baicalin‐treated MG63 cells were identified as differentially expressed RNAs compared to those in control cells. Of these, 2 lncRNAs, 3 miRNAs, and 18 mRNAs were included in the ceRNA regulatory network. The differentially expressed RNAs were confirmed by quantitative real‐time PCR (qRT‐PCR). Conclusions. By identifying the ceRNA network, our results provide new information about the possible molecular basis of baicalin, which has potential applications in OS treatment.
The Stability Analysis of Tunnel Lining Structure with Seismic Excitation Based on the Energy Evaluation Principle
Authors: Wen Yumin , Xin Chunlei , Zhang Xi , Huang Zeming , Shen Yusheng , Lei Wenjie , Gao Bo
Published: July 2021

Earthquakes are vibrations induced by the rapid releases of large quantities of energy from the crustal movements. During seismic excitation, there are kinetic energy, damping energy, and strain energy acting on the tunnel structure. Based on the indexes of the total energy, releasable elastic strain energy, and dissipated energy, this paper proposes three energy evaluation criteria for the tunnel structure, which are applied to the optimization of the aseismic design of the cross‐sectional shape and material property of the tunnel structure. It can be concluded that the peak values and accumulated values of elastic strain energy at the spandrel and arch springing are significantly larger than other positions, which indicates that the strengths of the spandrel and arch springing are the most influential factor for the seismic damage of the tunnel structure. Considering this factor, the width‐to‐height ratio of 1.33 and Poisson’s ratio of 0.3 are determined as the most optimal cross‐sectional shape and material property, respectively. Furthermore, by analyzing the relationship between the internal energy and the input energy of the tunnel structure with seismic excitation and proposing an equation for the evaluation of the dynamic stability of tunnel structure, the stabilities of the tunnel structure with different PGAs are analyzed; it can be concluded that the larger the peak value of seismic wave acceleration, the longer the instable period and the greater the degree of dynamic instability. The derived equations can be used as references for the seismic analysis of the tunnel structure, and the conclusions of this paper can contribute to the aseismic design of tunnel lining.
A Review of Caffeine Adsorption Studies onto Various Types of Adsorbents
Authors: Quintero-Jaramillo Javier Andrés , Carrero-Mantilla Javier Ignacio , Sanabria-González Nancy Rocío
Published: July 2021

A systematic literature review of publications from 2000 to 2020 was carried out to identify research trends on adsorbent materials for the removal of caffeine from aqueous solutions. Publications were retrieved from three databases (Scopus, Web of Science, and Google Scholar). Words “adsorption AND caffeine” were examined into titles, abstracts, and keywords. A brief bibliometric analysis was performed with emphasis on the type of publication and of most cited articles. Materials for the removal of caffeine were classified according to the type of material into three main groups: organic, inorganic, and composites, each of them subdivided into different subgroups consistent with their origin or production. Tables resume for each subgroup of adsorbents the key information: specific surface area, dose, pH, maximum adsorption capacity, and isotherm models for the removal of caffeine. The highest adsorption capacities were achieved by organic adsorbents, specifically those with granular activated carbon (1961.3 mg/g) and grape stalk activated carbon (916.7 mg/g). Phenyl-phosphate-based porous organic polymer (301 mg/g), natural sandy loam sediment (221.2 mg/g), composites of MCM-48 encapsulated graphene oxide (153.8 mg/g), and organically modified clay (143.7 mg/g) showed adsorption capacities lower than those of activated carbons. In some activated carbons, a relation between the specific surface area (SSA) and the maximum adsorption capacity (Qmax) was found.
Chemical Screen Identifies Diverse and Novel Histone Deacetylase Inhibitors as Repressors of NUT Function: Implications for NUT Carcinoma Pathogenesis and Treatment
Authors: Shiota Hitoshi , Alekseyenko Artyom A. , Wang Zhipeng A. , Filic Ivona , Knox Tatiana M. , Luong Nhi M. , Huang Yeying , Scott David A. , Jones Kristen L. , Gokhale Prafulla C. , Lemieux Madeleine E. , Cole Philip A. , Kuroda Mitzi I. , French Christopher A.
Published: July 2021

NUT carcinoma (NC), characterized most commonly by the BRD4-NUTM1 fusion, is a rare, aggressive variant of squamous carcinoma with no effective treatment. BRD4-NUT drives growth and maintains the poorly differentiated state of NC by activating pro-growth genes such as MYC, through the formation of massive, hyperacetylated, superenhancer-like domains termed megadomains. BRD4-NUT–mediated hyperacetylation of chromatin is facilitated by the chromatin-targeting tandem bromodomains of BRD4, combined with NUT, which recruits the histone acetyltransferase, p300. Here, we developed a high-throughput small-molecule screen to identify inhibitors of transcriptional activation by NUT. In this dCAS9-based GFP-reporter assay, the strongest hits were diverse histone deacetylase (HDAC) inhibitors. Two structurally unrelated HDAC inhibitors, panobinostat and the novel compound, IRBM6, both repressed growth and induced differentiation of NC cells in proportion to their inhibition of NUT transcriptional activity. These two compounds repressed transcription of megadomain-associated oncogenic genes, such as MYC and SOX2, while upregulating pro-differentiation, non-megadomain–associated genes, including JUN, FOS, and key cell-cycle regulators, such as CDKN1A. The transcriptional changes correlate with depletion of BRD4-NUT from megadomains, and redistribution of the p300/CBP-associated chromatin acetylation mark, H3K27ac, away from megadomains toward regular enhancer regions previously populated by H3K27ac. In NC xenograft models, we demonstrated that suppression of tumor growth by panobinostat was comparable with that of bromodomain inhibition, and when combined they improved both survival and growth suppression.

Implications:

The findings provide mechanistic and preclinical rationale for the use of HDAC inhibitors, alone or combined with other agents, in the treatment of NUT carcinoma.
Recurrent and Spontaneous Release of Epiretinal Membrane in a Toddler
Authors: Xue-qing Bai , Li Li , Yan-hui Cui , Ning-dong Li
Published: July 2021

We report a case of an epiretinal membrane (ERM) in a 3-year-old girl, which was accidently discovered after a strabismus surgery. The ERM occurred twice in 2 years and spontaneously released within 3 months, which has not been previously reported.
Bi-Level Noninvasive Ventilation in Neonatal Respiratory Distress Syndrome. A Systematic Review and Meta-Analysis
Authors: Solevåg Anne Lee , Cheung Po-Yin , Schmölzer Georg M.
Published: July 2021

Background: Bi-level noninvasive ventilation (NIV) has been used in respiratory distress syndrome (RDS) as primary treatment, post-extubation, and to treat apnea. This review summarizes studies on bi-level NIV in premature infants with RDS. Nonsynchronized nasal intermittent positive pressure ventilation (nsNIPPV) and synchronized NIPPV (SNIPPV) use pressure settings ≥ those used during mechanical ventilation (MV), and biphasic continuous positive airway pressure (BiPAP) use two nasal continuous positive airway pressure (NCPAP) levels ≤4 cm H2O apart. Methods: A systematic review (Medline OVID and Pubmed) and meta-analysis of randomized controlled trials. Primary outcomes were bronchopulmonary dysplasia (BPD) and mortality. Secondary outcomes included NIV failure (intubation) and extubation failure (re-intubation). Data were pooled using a fixed-effects model to calculate the relative risk (RR) with 95% confidence interval (CI) between NIV modes (RevMan v 5.3, Copenhagen, Denmark). Results: Twenty-four randomized controlled trials that largely did not correct for mean airway pressure (MAP) and used outdated ventilators were included. Compared with NCPAP, both nsNIPPV and SNIPPV resulted in less re-intubation (RR 0.88 with 95% CI (0.80, 0.97) and RR 0.20 (0.10, 0.38), respectively) and BPD (RR 0.69 (0.49, 0.97) and RR 0.51 (0.29, 0.88), respectively). nsNIPPV also resulted in less intubation (RR 0.57 (0.45, 0.73) versus NCPAP, with no difference in mortality. One study showed less intubation in BiPAP versus NCPAP. Conclusions: Bi-level NIV versus NCPAP may reduce MV and BPD in premature infants with RDS. Studies comparing equivalent MAP utilizing currently available machines are needed.
Neovascular Glaucoma as a Presenting Sign of Catastrophic Antiphospholipid Syndrome with a “Catastrophic” Heart Valve Finding
Authors: Grinberg Anya , Midlij Mohamad , Tiosano Beatrice , Shreter Roni , Kesler Anat
Published: July 2021

We aimed to describe a case of neovascular glaucoma (NVG) as a first presenting sign of catastrophic antiphospholipid syndrome (CAPS) with heart valve aseptic vegetations known as Libman-Sacks endocarditis. A 39-year-old man was referred for left eye decreased visual acuity and pain, upon examination left eye high intraocular pressure; rubeosis iridis of both eyes (BE); and prominent retinal ischemia. Clinical and fluorescein angiography findings established the diagnosis of left eye NVG with vaso-occlusive disease in BE. Magnetic resonance imaging of the head showed widespread ischemic lesions and hemorrhagic foci. The transesophageal echocardiogram showed 2 big mitral valve lesions consistent with the diagnosis of Libman-Sacks endocarditis. Laboratory and clinical diagnosis of CAPS and suspected SLE was confirmed, and treatment with anticoagulants and IV steroids was initiated. This case demonstrates that severe vaso-occlusive retinopathy with severe brain ischemia should raise the suspicion of systemic autoimmune pro-coagulative diseases with heart valve aseptic vegetations.
A Novel Homozygous ALG12 Mutation in a Patient with CDG Type Ig: New Report of a Case with a Mild Phenotype
Authors: Nicotera Antonio Gennaro , Spoto Giulia , Calì Francesco , Romeo Giusi , Musumeci Antonino , Vinci Mirella , Fiumara Agata , Barone Rita , Di Rosa Gabriella , Musumeci Sebastiano Antonino
Published: July 2021

Congenital disorders of glycosylation (CDG) are a group of rare genetic diseases caused by the deficiency of enzymes involved in the biosynthesis or remodeling of the glycan moieties of glycoconjugates. Most of CDG are autosomal recessive; however, few of them show autosomal dominant or X-linked inheritance. ALG12-CDG is an autosomal recessive inherited defect caused by a deficiency in the α-mannosyltransferase, dolichyl-P-mannose: Man7-GlcNAc-2-PP-dolichyl-alpha-6-mannosyltransferase (mannosyltransferase 8), which determines Man7GlcNAc2-PP-dolichol accumulation in tissues including fibroblasts. The clinical features of ALG12-CDG include dysmorphic features, developmental delay, hypotonia, progressive microcephaly, hypogammaglobulinemia, coagulopathies, and failure to thrive. Herein, we describe the case of a Sicilian patient with a milder phenotype bearing an ALG12 homozygous mutation. To date, including this patient, only 16 cases have been described with this form of CDG. Furthermore, our study contributes to understanding the milder ALG12-CDG cases and to further expanding the genotype-phenotype spectrum.
Carbohydrates to Prevent and Treat Obesity in a Murine Model of Diet-Induced Obesity
Authors: Vercalsteren Ellen , Vranckx Christine , Corbeels Katrien , Van der Schueren Bart , Velde Greetje Vande , Lijnen Roger , Scroyen Ilse
Published: July 2021

Introduction: The biggest risk factor for obesity and its associated comorbidities is a Western diet. This Western diet induces adipose tissue (AT) inflammation, which causes an AT dysfunction. Since AT is a vital endocrine organ, its dysfunction damages other organs, thus inducing a state of chronic inflammation and causing various comorbidities. Even though it is evident a Western diet, high in fat and carbohydrates, induces obesity and its complications, it is not known yet which macronutrient plays the most important role. Therefore, the aim of this study was to investigate the effect of macronutrient composition on obesity and to reverse the Western diet-induced metabolic risk via caloric restriction (CR) or a change of diet composition. Materials and Methods: Male, C57BL/6JRj mice were fed with a diet high in fat, sucrose, fructose, sucrose and fructose, starch, a Western diet, or a control diet for 15 weeks. To assess reversibility of the metabolic risk, mice were first made obese via 15 weeks of WD and then put on either a CR or switched to a sucrose-rich diet. Results: A sucrose-rich and high-starch diet induced less obesity and a better metabolic profile than a Western diet, evidenced by less hepatic steatosis, lower plasma cholesterol, and less insulin resistance. Furthermore, these diets induced less intra-abdominal AT inflammation than a Western diet, since mRNA levels of pro-inflammatory markers were lower and there was less macrophage infiltration. Expression of tight junction markers in colon tissue was higher in the sucrose-rich and high-starch group than the Western group, indicating a better intestinal integrity upon sucrose-rich and high-starch feeding. Additionally, CR induced weight loss and decreased both metabolic abnormalities and AT inflammation, regardless of macronutrient composition. However, effects were more pronounced upon CR with sucrose-rich or high-starch diet. Even without CR, switching obese mice to a sucrose-rich diet induced weight loss and decreased AT inflammation and metabolic aberrations. Discussion: A diet high in sucrose or starch induces less obesity and obesity-associated complications. Moreover, switching obese mice to a sucrose-rich diet elicits weight loss and decreases obesity-induced metabolic complications, highlighting the potential of carbohydrates to treat obesity.
Development of a BMI-Assigned Stunkard Scale for the Evaluation of Body Image Perception Based on Data of the SOS Reference Study
Authors: Parzer Verena , Sjöholm Kajsa , Brix Johanna Maria , Svensson Per-Arne , Ludvik Bernhard , Taube Magdalena
Published: July 2021

Introduction: Stunkard’s figure rating scale is a widely used tool to assess weight status and, more recently, body image perception in people with obesity. However, large population-based studies on Europeans linking this scale’s silhouettes with measured BMI values are lacking. Therefore, we used measured weight and height data from the Swedish Obese Subjects (SOS) reference cohort to assign a mean BMI to each of the 9 Stunkard Scale silhouettes and to define silhouette cutoff values for categorizing people with obesity and overweight. Methods: A total of 1,128 participants from the SOS reference cohort were included (54% females, BMI = 25.2 [ranging from 17.6 to 45.4] ±3.8 kg/m2, and age = 50 [ranging from 36 to 62] ±7 years [means ± standard deviation]). Patients estimated their own body size by choosing a silhouette of the Stunkard Scale. A mean BMI, based on measured weight and height, was assigned to each male and female silhouette of the Stunkard Scale. Measured BMI values were compared with BMI values calculated by simple linear regression analysis. ROC analysis was used to test accuracy of discrimination and the Youden index to assess optimal cutoff. Results: Figure ratings and BMI were strongly correlated in men, r (518) = 0.76, p < 0.001 and women, r (606) = 0.80, p < 0.001. Silhouette selection significantly predicted BMI values in men, β = 16.03, t (518) = 25.30, p < 0.001, and women, β = 12.06, t (606) = 32.98, p < 0.001, and explained a significant proportion of variance in BMI values in men, R2 = 0.55, F (1, 518) = 639.98, p < 0.001, and women, R2 = 0.64, F (1, 606) = 1,087.88, p < 0.001. ROC curve analyses resulted in an optimal cutoff value of 6 for identifying people with obesity and 5 for overweight. Conclusion: Stunkard’s figure rating scale can be used with confidence to assess weight status. Silhouette selection accurately classifies subjects as overweight or obese.
High-Risk Histopathologic Features of Retinoblastoma Treated at a Tertiary Hospital in West Java, Indonesia
Authors: Sari Nur Melani , Hadiputri Regina , Kuntorini Maya Sari , Agustina Hasrayati , Mardianty Friska
Published: July 2021

Purpose: To evaluate the histopathological characteristics of clinically advanced retinoblastoma (RB) and its relationship with tumor differentiation. Methods: This was a cross-sectional study of primary enucleated group D/E intraocular RB using medical records from 2017 to 2020 in a tertiary referral hospital. Cases with incomplete histopathological results were excluded. Tumors were classified into well, moderately, and poorly differentiated and undifferentiated. High-risk histopathological features were classified as per Thaung and Karaa [Community Eye Health. 2018;31(101):17–3]. Results: This study included 121 patients (129 eyes), of which 32.2% were diagnosed at 25–36 months. High-risk features (HRFs) were found in 100/129 eyes, and of 73 complete histopathological results, the 2 most common HRFs were postlaminar optic nerve invasion and massive choroidal invasion. RB was poorly differentiated in 69.9% and well differentiated in 12.3% of eyes. There was no statistically significant association between any HRFs and tumor differentiation, with age >2 years associated with tumor differentiation (p < 0.05). Conclusion: The frequency of HRFs is 77.5% of primary enucleated eyes, mainly poorly and undifferentiated cells, particularly in children aged >2 years old.
Post-Chemotherapy Histiocyte-Rich Pseudotumors: Radiologic and Endoscopic Mimics of Residual Lymphoma
Authors: Goebel Maximilian , Brynes Russell K. , Yau David C. , Chan Randall Y. , Hamidi Sepehr , Alspach Amy , Ho Cynthia H. , Vergara-Lluri Maria E.
Published: July 2021

Development of post-chemotherapy histiocyte-rich pseudotumor (PHP) is an underrecognized event following therapy in lymphoma patients and may mimic residual tumor using current therapy monitoring protocols. We report a series of 5 patients with PHP along with a review of the literature. In our series, we describe 3 patients with persistent hypermetabolic masses by positron emission tomography-computed tomography, one with persistent terminal ileal nodules on endoscopy, and one with bone marrow involvement, a site not associated with mass-like disease. Twenty-three patients with long-term follow-up were identified from our series and review of the literature. Forty-four percent of patients received additional therapy, and only 4% of patients died of lymphoma. This study illustrates that PHPs are not identified using current lymphoma therapy monitoring algorithms and may result in overtreatment with risk for additional therapy-related complications. The need for confirmatory tissue biopsy in this setting is recommended.
Timing of Nonculprit Percutaneous Coronary Intervention after ST-Elevation Myocardial Infarction
Authors: Arnold Joshua H. , Bental Tamir , Greenberg Gabriel , Vaknin-Assa Hana , Kornowski Ran , Perl Leor
Published: July 2021

Introduction: Complete revascularization of ST-elevation myocardial infarction (STEMI) patients with multivessel disease (MVD) has recently shown to reduce risk of adverse cardiovascular events, including cardiovascular death. Optimal timing of revascularization of nonculprit lesions remains controversial. We aimed to measure cardiac outcomes related to duration between primary percutaneous coronary intervention (pPCI) of the culprit lesion and staged PCI (sPCI) of nonculprit lesions. Methods: From a prospectively collected consecutive registry of 3,002 patients treated for STEMI by pPCI, 1,555 patients with MVD requiring sPCI were identified. Patients were placed into quartiles of duration to sPCI: 0–7 days (Q1), 7–22 days (Q2), 22–42 days (Q3), >42 days (Q4), excluding those who had complete revascularization at the index event. Major adverse cardiac events (MACEs) included all-cause mortality, myocardial infarction, target vessel revascularization, and coronary artery bypass surgery. Cox regression and propensity score matching were performed correcting for confounding factors. Results: The average age at presentation was 65.7 ± 11.5 years. 333 were female (21.4%). Mean time between pPCI and sPCI was 28.3 days (±24.8). Rates of MACE were Q1 - 16.5%, Q2 - 21.2%, Q3 - 25.8%, and Q4 - 30.1% (log-rank <0.001). Following regression analysis, sPCI remained an independent risk factor for MACE (hazard ratio [HR] = 1.226 [95% confidence interval {CI}: 1.129–1.331, p < 0.001]). There was no association between the time interval up to sPCI with all-cause death (HR = 1.022 [95% CI: 0.925–1.129, p = 0.671]). Conclusions: Patients with MVD are at increased risk of experiencing MACE after revascularization of nonculprit vessels with increasing time delay between pPCI and sPCI.
Indication for Active Surveillance in the Era of MRI-Targeted Prostate Biopsies
Authors: Wetterauer Christian , Federer-Gsponer Joel R. , Leboutte Francois D.J.P. , Mona Robin , Ebbing Jan , Rentsch Cyrill A. , Manka Lukas , Seifert Hans H. , Wyler Stephen , Recker Franz , Kwiatkowski Maciej
Published: July 2021

Introduction: Active surveillance (AS) strategies were established to avoid overtreatment of low-risk prostate cancer (PCa) patients. Low tumor volume represents one indication criteria; however, applying this criterion after MRI-targeted prostate biopsies may lead to overestimation of tumor volume; wherefore, patients suitable for AS would be exposed to the risk of overtreatment. Methods: This retrospective analysis included 318 patients in which PCa was detected by MRI-TRUS fusion prostate biopsy. Classic and extended indication for AS included Gleason 6 and Gleason 3 + 4 cancer, respectively. We assessed the effect of targeted biopsies and temporary rating strategies on eligibility for AS and developed new “composite” algorithms to more accurately assess eligibility for AS. Results: Forty-four (13.8%) and 60 (18.9%) of the 318 patients qualified for AS according to “classic” and “extended” criteria, respectively. Application of the “composite 1” definition led to AS eligibility of 52 of 248 patients (20.97%) in the classic and of 77 of 248 patients (31.05%) in the “extended” group. Conclusions: We could demonstrate that classic algorithms led to ineligibility of patients for AS. We propose a new rating algorithm to improve tumor assessment for a more accurate indication for AS.
Cytological Appearances of Ovarian Seromucinous Borderline Tumor in Ascites: Presentation of 2 Cases
Authors: Kai Keita , Hashiguchi Mariko , Kurihara Makiko , Tanaka Yuya , Kitamura Sho , Nakamura Mitsuo , Shichijo Chika , Yamamoto-Rikitake Mihoko , Okuma Ryoichi , Hikari Takako , Okuma Emi , Uchiyama Michiko , Aoki Shigehisa , Nakao Yoshifumi , Yokoyama Masatoshi , Aishima Shinichi
Published: July 2021

Background: Seromucinous borderline tumor (SMBT) is a rare neoplasm which was newly defined in the 2014 WHO classification. Although the clinical and histopathological characteristics of SMBT have been well described, its cytological characteristics have not. We recently experienced 2 cases of SMBT which were defined by cytological findings of ascites. Case Presentation: Case 1 was a 65-year-old Japanese woman. Preoperative imaging studies revealed abundant ascites and a cystic tumor, with a solid component measuring 13 cm on the left ovary. Radical surgery was performed during the intraoperative diagnosis of ovarian borderline tumor, made by histological examinations of frozen tumor sections. The cytological smears of preoperatively and intraoperatively collected ascites showed many atypical cells resembling reactive mesothelial cells. Alcian-blue staining of cell block sections revealed intracytoplasmic mucin, and the results of immunohistochemistry were consistent with SMBT. The final pathological diagnosis of tumor was SMBT. Case 2 was a 28-year-old Japanese woman. Preoperative imaging studies revealed a small amount of ascites and cystic tumors with solid components in the bilateral ovaries. She initially underwent fertility preservation surgery. SMBT was suspected by cytological examination of smears of intraoperatively collected ascites and the findings of cell block. She underwent additional radical surgery based on a final pathological diagnosis of SMBT. Conclusion: In our experience, the tumor cells of SMBT in ascites mimicked reactive mesothelial cells. The nuclear atypia of SMBTs was intermediate between that of reactive mesothelial cells and serous carcinoma. The immunohistochemistry and mucin staining using cell block were very helpful for facilitating the cytodiagnosis of SMBT.
Comparative Evaluation of Orthostatic Hypotension in Patients with Diabetic Nephropathy
Authors: Aytaş Gamze , Kazancıoğlu Rümeyza , Elçioğlu Ömer C. , Gürsu Meltem , Artan A. Serra , Yabacı Ayşegül , Soysal Pinar , Bilgi Kadir , Özçelik Semra
Published: July 2021

Introduction: Orthostatic hypotension (OH) affects 5–20% of the population. Our study investigates the presence of OH in diabetic nephropathy (DNP) patients and the factors affecting OH in comparison with nondiabetic chronic kidney disease (NDCKD) patients. Method: Patients presented to the nephrology clinic, and those who consented were included in the study. DNP was defined by kidney biopsy and/or clinical criteria. NDCKD patients of the same sex, age, and eGFR were matched to DNP patients. Demographic parameters and medications were obtained from the records. OH was determined by Mayo clinic criteria. The same researcher used an electronic device to measure blood pressure (BP). All samples were taken and analyzed the same day for biochemical and hematologic parameters and albuminuria. Results: 112 (51 F, 61 M, mean age: 62.56 ± 9.35 years) DNP and 94 (40 F, 54 M, mean age: 62.23 ± 10.08 years) NDCKD patients were included. There was no significant difference between DNP and NDCKD groups in terms of OH prevalence (70.5 vs. 61.7%, p = 0.181). Male patients had significantly higher OH prevalence than female patients (74.7 vs. 60.0%, p = 0.026). There was no significant difference in change in systolic BP between the groups (24.00 [10.00–32.00] mm Hg vs. 24.00 [13.75–30.25] mm Hg, p = 0.797), but the change in diastolic BP was significantly higher in the DNP group (8.00 [2.00–13.00] mm Hg vs. 6.00 [2.00–9.00] mm Hg, p = 0.025). In the DNP group, patients with OH had significantly higher uric acid levels than those without OH (7.18 ± 1.55 vs. 6.36 ± 1.65 mg/dL, p = 0.017). And, 73.7% of patients on calcium channel blockers developed OH (p = 0.015), and OH developed in 80.6% of 36 patients on alpha-blockers (p = 0.049). Conclusion: OH prevalence is very high in CKD, and etiology of CKD does not have a statistically significant effect on the frequency of OH, despite a difference that could be meaningful clinically. Therefore, patients with CKD are checked for OH, with or without concurrent diabetes mellitus. Evaluation of postural BP changes should be a part of nephrology practice.
Efficacy of the Treatment of Intraperitoneal Bladder Perforation during Transurethral Resection of Bladder Tumor with the Urethral Catheter Alone: Retrospective Analysis of over 15 Years Using the Clinical Data Warehouse System
Authors: Lee Junghoon , Suh Jungyo , Jeong Chang Wook , Kwak Cheol , Kim Hyeon Hoe , Ku Ja Hyeon
Published: July 2021

Introduction: We investigated the efficacy of a urethral catheter alone for intraperitoneal perforation during transurethral resection of bladder tumor (TURBT). Patients and Methods: We retrospectively evaluated the medical records of 4,543 patients who underwent TURBT from January 2000 to December 2017 using the Clinical Data Warehouse system. The clinicopathologic characteristics, recurrence-free survival, and progression-free survival were compared between the patient groups with intraperitoneal perforation treated with the Foley catheter alone, extraperitoneal perforation, and matched control TURBT. Results: Intraperitoneal perforation and extraperitoneal perforation were observed in 16 (35.6%) and 29 (64.4%) patients, respectively. In the intraperitoneal perforation group, 11 (68.8%), 2 (12.5%), and 3 (18.8%) patients were treated with the Foley catheter alone, additional percutaneous drainage, and delayed open surgery, respectively. The use of the Foley catheter alone in patients with intraperitoneal perforation of smaller size than the cystoscope or no pelvic radiotherapy history showed improved efficacy without sequelae or therapeutic delay. One of the 2 patients with the size of the intraperitoneal perforation larger than the cystoscope was successfully treated with the Foley catheter alone, whereas the other patient underwent delayed surgical repair. There was no difference in recurrence-free survival and progression-free survival of the intraperitoneal perforation treated with the Foley catheter alone compared to those of the matched control TURBT (p = 0.909, p = 0.518) and the extraperitoneal perforation (p = 0.458, p = 0.699). Conclusions: Intraperitoneal perforation rarely occurred during TURBT. In the case of intraperitoneal perforation of size smaller than cystoscopy or without pelvic radiotherapy history, treatment with the Foley alone showed successful improvement and safe oncological results. Therefore, treatment with the urethral catheter alone can be carefully considered when an intraperitoneal perforation smaller than the cystoscope size or without pelvic radiotherapy history occurs.
Cognitive Impairment in Multiple System Atrophy Is Related to White Matter Damage Detected by the T1-Weighted/T2-Weighted Ratio
Authors: Sugiyama Atsuhiko , Cooper Graham , Hirano Shigeki , Yokota Hajime , Mori Masahiro , Shimizu Keisuke , Yakiyama Masatsugu , Finke Carsten , Brandt Alexander U. , Paul Friedemann , Kuwabara Satoshi
Published: July 2021

Introduction: This study aimed to use a novel MRI contrast, the standardized T1-weighted/T2-weighted (sT1w/T2w) ratio, to assess damage of the white matter and gray matter in multiple system atrophy (MSA). Furthermore, this study investigated whether the sT1w/T2w ratio was associated with cognitive impairment in MSA. Methods: The white matter and gray matter sT1w/T2w ratio of 37 MSA patients and 19 healthy controls were measured. Correlation analyses were used to evaluate the relationship between sT1w/T2w ratio values and clinical variables, and a multivariate analysis was used to identify independent factors associated with cognitive impairment in MSA. Results: MSA patients showed a higher white matter sT1w/T2w ratio value than controls (p < 0.001), and the white matter sT1w/T2w ratio value was significantly correlated with the International Cooperative Ataxia Rating Scale score (r = 0.377, p = 0.021) and the Addenbrooke’s cognitive examination III score (r = −0.438, p = 0.007). Cognitively impaired MSA patients had a significantly higher white matter sT1w/T2w ratio value than cognitively preserved MSA patients (p = 0.010), and the multiple logistic regression analysis revealed that the median white matter sT1w/T2w ratio value was independently associated with cognitive impairment in MSA. Conclusion: The sT1w/T2w ratio is sensitive to degenerative changes in the white matter that is associated with cognitive ability in MSA patients.
Flexible Cystoscopy in the Setting of Macroscopic Hematuria: Do the Findings Justify Its Use?
Authors: Ben-David Reuben , Morgan Samuel , Savin Ziv , Dekalo Snir , Sofer Mario , Beri Avi , Yossepowitch Ofer , Mano Roy
Published: July 2021

Background: Patients hospitalized due to gross hematuria frequently complete evaluation in the outpatient setting. The use of office flexible cystoscopy during hospitalization may lead to prompt diagnosis and treatment but can be limited due to low visualization and artifacts that can hamper diagnostic ability. Objective: The objective of this study was to assess flexible cystoscopy findings and yield performed in patients hospitalized due to gross hematuria. Methods: Medical records of patients who underwent flexible cystoscopy while hospitalized during September 2018–December 2019 were reviewed. Cystoscopic findings were categorized into (1) suspicious mass in the bladder or prostate, (2) nonsuspicious changes in the bladder, and (3) nondiagnostic exam. Descriptive statistics were used to report the clinical characteristics of the study cohort and the findings of cystoscopy. Univariate logistic regression analyses were used to identify predictors of malignant findings. Results: The study cohort consisted of 69 patients (median age of 76 years). Initial cystoscopy findings were suspicious for malignancy in 26/69 patients (38%), nonsuspicious for malignancy in 34/69 patients (49%), and nondiagnostic in 9/69 patients (13%). The median follow-up time was 9 months (range 4–14 months). Twenty patients (29%) were diagnosed with malignancy (sensitivity of 75% and specificity of 78%). The procedure led to either diagnosis or treatment of 39 patients (57%). However, in 30 patients (43%), the initial cystoscopy did not aid in the diagnosis, led to misdiagnoses, or required a follow-up cystoscopy. On univariate analyses, none of the precystoscopy variables were predictive of bladder malignancy. Conclusion: Flexible cystoscopy in the setting of acute hematuria requiring hospitalization did not lead to diagnosis or treatment in over 40% of cases. In this setting, consideration should be given to performing an upfront cystoscopy under anesthesia.
Myeloid Sarcoma: Diagnostic and Treatment Tools from a Monocentric Retrospective Experience
Authors: Bianchi Simona , Capria Saveria , Trisolini Silvia Maria , Crisanti Erica , De Propris Maria Stefania , Diverio Daniela , Moleti Maria Luisa , Foà Robin , Testi Anna Maria
Published: July 2021

Myeloid sarcoma (MS) is a very rare disease in both adults and children. Prognosis is poor in adults; in the pediatric age, the prognostic impact of extramedullary disease is controversial. Systemic therapy represents the mainstay of treatment even in isolated MS, but a comparison between different induction regimens is very limited in the literature. To date, it is still not clear if induction treatment should differ from that of other acute myeloid leukemias and stem cell transplant is considered for consolidation in both leukemic patients and in those with isolated disease. Our study describes a retrospective series of 13 cases of MS (adults and children), diagnosed and treated at our institute over 18 years. We report the results of immunophenotypic, cytogenetic and molecular studies, therapeutic approaches, and outcome, in order to establish the best strategy for patients’ workup.
A Case of Acquired von Willebrand Syndrome Complicated by Acute Myelomonocytic Leukemia
Authors: Fukatsu Masahiko , Ohkawara Hiroshi , Takahashi Hiroshi , Mori Hirotaka , Yaginuma Mai , Endo Mamiko , Shichishima-Nakamura Akiko , Sano Takahiro , Harada-Shirado Kayo , Kimura Satoshi , Ogawa Kazuei , Hashimoto Yuko , Ikezoe Takayuki
Published: July 2021

We here report a 21-year-old male who presented with acute myelomonocytic leukemia (AMML) associated with acquired von Willebrand syndrome (AVWS). To our knowledge, this is the first case of AVWS caused by AMML. In our case, following remission-induction chemotherapy combined with idarubicin and cytarabine, the patient showed remarkable improvement of bleeding symptoms due to AVWS. Moreover, after an allogeneic stem cell transplantation from a sibling donor, both AMML and AVWS maintain complete remission.
Sweeping Up Dying Cells during Tissue Injury
Authors: Arai Yohei , Yamaoka Yusuke , Morioka Sho
Published: July 2021

Various forms of cell death have been identified, and billions of cells die during development and daily in adult organisms. Clearing dead cells and associated cellular debris is an integral part of tissue homeostasis. While diverse types of phagocytes remove various forms of dying cells during acute kidney injury (AKI), it remains unknown whether boosting removal of a specific form of dying cell would provide a benefit and which cell type should be targeted for phagocytosis-mediated therapy. As there is a lack of viable strategies for the prevention and treatment of AKI, novel therapies and innovative approaches are required. There is a strong demand on developing and analyzing novel models to boost, monitor, and stop phagocytosis of dying cells.
Advanced Gastric Cancer: Current Treatment Landscape and a Future Outlook for Sequential and Personalized Guide: Swiss Expert Statement Article
Authors: Siebenhüner Alexander R. , De Dosso Sara , Helbling Daniel , Astaras Christoforos , Szturz Petr , Moosmann Peter , Pederiva Stefanie , Winder Thomas , Von Burg Philippe , Borner Markus
Published: July 2021

Background: Gastric cancer is a leading cause of cancer-related deaths worldwide. Several treatment possibilities have been investigated, but only a few show clinically meaningful results. Summary: Systemic treatment options for advanced gastric cancer (aGC) have evolved over the recent years, implementing the growing molecular knowledge of this heterogeneous disease. Molecular profiling (at least for HER-2-expression, microsatellite instability status, Epstein-Barr virus expression, and programmed death ligand-1 expression/combined positive score [CPS]) is recommended for all therapy-fit patients prior to the start of a systemic treatment and is crucial for decisions on treatment strategy and drug selection. Various examples like the application of trastuzumab in the HER-2-positive subgroup underline the benefits of this approach starting from the first-line setting. A combination of platinum and fluoropyrimidine remains the first-line chemotherapy backbone in the treatment of advanced gastric cancer. Triplet combinations adding taxanes to the doublet regimen are reserved for certain scenarios. Unfortunately, almost all patients who receive first-line treatment (with or without anti-HER-2 blockade) progress and <70% are eligible for a second-line therapy. The addition of monoclonal antibodies has substantially improved outcomes in this setting. As such, ramucirumab has led to significant and clinically meaningful advancements in the second-line treatment. Furthermore, immuno-oncology with checkpoint inhibition and immune stimulation has evolved in the field of aGC. Recent first-line data show a significant survival benefit in aGC patients with a CPS ≥ 5 under immunochemotherapy. Nonetheless, the impact of immunotherapy combinations and immunochemotherapy remains an area of investigation. Key Message: In this review, we highlight recent improvements in the treatment landscape of advanced gastric cancer, the heterogeneity of this disease, and possible personalized targets.