bluuebunny/crossref_metadata_2025 huggingface dataset:
A COMPARATIVE INVESTIGATION ON CAST AND AGING (T6) RESPONSE ON MECHANICAL AND DRY SLIDING WEAR BEHAVIOR OF Al7075/SiCP METAL MATRIX COMPOSITE
Authors: ASHOK KUMAR R. , DEVARAJU A.
Published: March 2021

The study focuses on the influence of SiC and heat treatment effect on mechanical and wear behavior of Aluminium Metal Matrix Composites (AMMCs), Al7075 is the matrix material and composites were prepared by varying the weight percentage of SiC. The prepared composites are divided into two groups Type A and Q samples while Type Q was artificially aged to T6 condition. In addition to the reinforcement, the hard intermetallic secondary phase that emerges due to heat treatment strengthens the AMMCs with a considerable degree of embrittlement. Both Type A and Q samples were characterized for various mechanical properties such as hardness, tensile strength, impact strength, etc. A new regression mathematical model was developed to predict the mechanical properties. Wear testing was done by varying load for a fixed distance and observed a good percentage of improvement in hardness, tensile strength, impact strength, and specific wear rate for 9% reinforced SiC AMMCs relative base alloy.
Kernels of homomorphisms between uniform quasi-injective modules
Authors: Koşan M. Tamer , Quynh Truong Cong , Žemlička Jan
Published: March 2021

In this paper, we study the behavior of endomorphism rings of indecomposable (uniform) quasi-injective modules. A very natural question here is, for a morphism [Formula: see text], with [Formula: see text] indecomposable (uniform) quasi-injective right [Formula: see text]-modules, and [Formula: see text] an extension of [Formula: see text] where [Formula: see text] denotes the injective hull, what is the relation between kernels of [Formula: see text] and [Formula: see text], their monogeny classes and their upper parts?
Rings all of whose finitely generated ideals are automorphism-invariant
Authors: Quynh Truong Cong , Abyzov Adel Nailevich , Trang Dao Thi
Published: March 2021

Rings in which each finitely generated right ideal is automorphism-invariant (right[Formula: see text]-rings) are shown to be isomorphic to a formal matrix ring. Among other results it is also shown that (i) if [Formula: see text] is a right nonsingular ring and [Formula: see text] is an integer, then [Formula: see text] is a right self injective regular ring if and only if the matrix ring [Formula: see text] is a right [Formula: see text]-ring, if and only if [Formula: see text] is a right automorphism-invariant ring and (ii) a right nonsingular ring [Formula: see text] is a right [Formula: see text]-ring if and only if [Formula: see text] is a direct sum of a square-full von Neumann regular right self-injective ring and a strongly regular ring containing all invertible elements of its right maximal ring of fractions. In particular, we show that a right semiartinian (or left semiartinian) ring [Formula: see text] is a right nonsingular right [Formula: see text]-ring if and only if [Formula: see text] is a left nonsingular left [Formula: see text]-ring.
Analysis of Deposition Efficiency and Distortion During Multitrack Overlay by Plasma Transferred Arc Welding of Co–Cr Alloy on 316L Stainless Steel
Authors: Deshmukh D. D. , Kalyankar V. D.
Published: March 2021

In present investigations, Co–Cr alloy powder is deposited on SS 316L substrate material by plasma transferred arc welding (PTAW) technique. Analysis is carried out by evaluating the different processing conditions as per the design of experiments by response surface methodology. Efforts are made to investigate PTAW overlay process on two compound parametric approaches governing deposition characteristics. First approach focuses on the actual mass of powder deposited by melting over a substrate surface which governs deposition efficiency and second approach reflects the heat energy supplied to the arc region causing melting of both supplied powder and substrate material resulting distortion. The deposition efficiency and distortion of substrate material are measured for each experimental condition and the effect of transferred arc current, travel speed, powder feed rate, oscillation speed and stand-off distance are investigated. For deposition efficiency, the powder feed rate is the most important process parameter and powder feed rate between 8[Formula: see text]g/min and 12[Formula: see text]g/min contributes excellent deposition efficiency. For deformation, the transferred arc current is the most sensitive process parameter and low current conditions, 100–120[Formula: see text]A showed less distortion in the specimen. In order to achieve good deposition efficiency and less distortion, it is recommended to carry out PTAW deposition with arc current 120[Formula: see text]A, travel speed 120[Formula: see text]mm/min, powder feed rate 11[Formula: see text]g/min and stand-off distance 8[Formula: see text]mm.
Non-Probabilistic Reliability Bounds for Series Structural Systems
Authors: Qiao Xinzhou , Wang Bing , Fang Xiurong , Liu Peng
Published: March 2021

Most of the current non-probabilistic reliability methods are applicable for an individual component of a structure. However, a system consisting of interconnected components is involved in many engineering problems and its non-probabilistic reliability analysis remains a major challenge. In this paper, a non-probabilistic reliability method using upper and lower bound techniques is proposed for a series structural system. Based on the failure areas and the joint failure areas of two failure modes, the bounds of the non-probabilistic failure degree for a series system are firstly formulated. A judgement criterion is then presented to determine the joint failure areas of two failure modes. An analytical solution for the joint failure area of two failure modes is further given to simplify the calculation of the bounds. Four numerical examples are used to demonstrate the validity and effectiveness of the presented method.
A Fractal Model of Elastic–Plastic Contact Between Rough Surfaces for a Low-Velocity Impact Process
Authors: Lan Weibin , Fan Shouwen , Fan Shuai
Published: March 2021

Under the low-velocity impact conditions, in order to study the contact load variation law of the ellipsoid elastic bodies, an elastic–plastic contact analysis model of rough ellipsoid surfaces is provided based on elastic–plastic fractal theory. A spherical elastic–plastic fractal model considering friction factors is established, and the spherical diameter density distribution function and elastic contact mechanics are used as the solution methods. The two contact surfaces are taken as the research object, and the influence of relevant variables on the contact intensity is analyzed. The analysis results show that the fractal dimension and roughness have a greater effect on contact performance, the contact load is positively related to the surface roughness, and the lower friction coefficient has a weaker effect on the contact load, and the correctness of the present model is verified by comparing finite element simulation results and other studies. The modified spherical contact load function provides a theoretical basis for the friction and wear of the microscopic surface, it can be applied for solving the sliding contact problems with different impact velocities and the surface bearing capacity of the impact parts can be improved.
Improved Integrated Robotic Intraocular Snake: Analyses of the Kinematics and Drive Mechanism of the Dexterous Distal Unit
Authors: Jinno Makoto , Iordachita Iulian
Published: March 2021

Retinal surgery can be performed only by surgeons possessing advanced surgical skills because of the small, confined intraocular space, and the restricted free motion of the instruments in contact with the sclera. Snake-like robots may be essential for use in retinal surgery to overcome this problem. Such robots can approach the target site from suitable directions and operate on delicate tissues during retinal vein cannulation, epiretinal membrane peeling, and so on. We propose an improved integrated robotic intraocular snake (I2RIS), which is a new version of our previous IRIS. This study focused on the analyses of the kinematics and drive mechanism of the dexterous distal unit. This unit consists of small elements with reduced contact stress achieved by changing wire-hole positions. The kinematic analysis of the dexterous distal unit shows that it is possible to control the bending angle and direction of the unit by using two pairs of drive wires. The proposed drive mechanism includes a new pull-and-release wire mechanism in which the drive pulley is mounted at a right angle relative to the actuation direction (also, relative to the conventional direction). Analysis of the drive mechanism shows that compared to the previous drive mechanism, the proposed mechanism is simpler and easier to assemble and yields higher accuracy and resolution. Furthermore, considering clinical use, the instrument of the I2RIS is detachable from the motor unit easily for cleaning, sterilization, and attachment of various surgical tools. Analyses of the kinematics and drive mechanism and the basic functions of the proposed mechanism were verified experimentally on actual-size prototypes of the instrument and motor units.
In vitro chronic glycation induces AGEs accumulation reducing insulin-stimulated glucose uptake and increasing GLP1R in adipocytes
Authors: Chilelli Nino-Cristiano , Faggian Alessia , Favaretto Francesca , Milan Gabriella , Compagnin Chiara , Dassie Francesca , Bettini Silvia , Roverso Marco , Seraglia Roberta , Lapolla Annunziata , Vettor Roberto
Published: March 2021

Intracellular AGEs accumulation increases RAGE and GLP1R and reduces glucose uptake in adipocytes.
Liver glycogen-induced enhancements in hypoglycemic counterregulation require neuroglucopenia
Authors: Warner Shana O. , Wadian Abby M. , Smith Marta , Farmer Ben , Dai Yufei , Sheanon Nicole , Edgerton Dale S. , Winnick Jason J.
Published: March 2021

It is well known that iatrogenic hypoglycemia is a barrier to optimal glycemic regulation in patients with diabetes. Our data confirm that increasing liver glycogen content 75% above fasting levels enhances hormonal responses to insulin-induced hypoglycemia and demonstrate that this enhanced hormonal response does not occur in the absence of hypoglycemia in the brain. These data demonstrate that information from the liver regarding glycogen availability is integrated in the brain to optimize the counterregulatory response.
Performance of GGBS Cement Concrete under Natural Carbonation and Accelerated Carbonation Exposure
Authors: Zhao Jun , Shumuye Eskinder Desta , Wang Zike , Bezabih Gashaw Assefa
Published: March 2021

One of the primary problems related to reinforced concrete structures is carbonation of concrete. In many cases, depth of carbonation on reinforced concrete structures is used to evaluate concrete service life. Factors that can substantially affect carbonation resistance of concrete are temperature, relative humidity, cement composition, concentration of external aggressive agents, quality of concrete, and depth of concrete cover. This paper investigates the effect of varying the proportions of blended Portland cement (ordinary Portland cement (OPC) and ground granulated blast-furnace slag (GGBS)) on mechanical and microstructural properties of concrete exposed to two different CO2 exposure conditions. Concrete cubes cast with OPC, and various percentages of GGBS (0%, 30%, 50%, and 70%) were subjected to natural (indoor) and accelerated carbonation exposure. The aim of this paper is to present the research findings and authenticate the literature results of carbonation by using GGBS cement in partial replacement of OPC. The concretes with OPC are compared to concretes with various percentages of GGBS, to assess the carbonation depth as well as rate of carbonation of GGBS-based concretes, under both accelerated carbonation and natural carbonation exposure conditions. Even though GGBS cement increases the carbonation depth, the results are not the same with different GGBS replacement percentages. A correlation is made between concrete samples exposed to 15 ± 2% carbon dioxide (CO2) concentration and those exposed to natural CO2 concentration. The results reveal that the products formed by carbonation are similar under both exposure conditions. The experimental tests also revealed that GGBS cement concrete has a lower carbonation resistance than OPC concrete, due to the consumption of portlandite by the pozzolanic reaction. The combination of 70% OPC and 30% GGBS behaved well enough with respect to accelerated carbonation exposure, the depth of carbonation being roughly equivalent to that of control group (100% OPC). The results also show that rate of carbonation becomes more sensitive as the percentage of GGBS replacement increases (binder ratio), rather than duration of curing. Concretes exposed to natural carbonation (indoor) achieved lower carbonation rates than those exposed to accelerated carbonation.
A Novel Adjacent Sensors-Based Mechanism to Increase Performance of Wireless Sensor Networks
Authors: Al-Shalabi Mohammed , Ababneh Jafar , Abdulraheem Waled
Published: March 2021

Wireless Sensor Networks are widely used nowadays to support the decision-makers in different applications by monitoring and collecting the environmental parameters in specific areas. Sensors are deployed in such areas either randomly or formally. In a high-density Wireless Sensor Network, several sensors are randomly deployed in a small area. This will make the adjacent sensors collect same data and send them to the sink, which will increase the power consumption in those sensors. Adjacent sensors are considered critical because of their effect on the network performance. In this paper, the effect of the adjacent sensors is minimized because of the above-mentioned criticality and performance influence of these sensors. The proposed mechanism is evaluated by using MATLAB simulator and is then compared with the low-energy adaptive clustering hierarchy (LEACH) protocol. Results prove that the proposed mechanism outperforms the LEACH protocol by 21% in terms of the network lifetime and by 18% in terms of the number of the transmitted packets to the cluster heads and reduces the number of the transmitted packets to the base station by approximately 3% by avoiding the duplicated packets.
Analyses of PD-L1 and Inflammatory Gene Expression Association with Efficacy of Nivolumab ± Ipilimumab in Gastric Cancer/Gastroesophageal Junction Cancer
Authors: Lei Ming , Siemers Nathan O. , Pandya Dimple , Chang Han , Sanchez Teresa , Harbison Christopher , Szabo Peter M. , Janjigian Yelena , Ott Patrick A. , Sharma Padmanee , Bendell Johanna , Evans Thomas R. Jeffry , de Braud Filippo , Chau Ian , Boyd Zachary
Published: March 2021

Purpose:

In advanced gastric cancer/gastroesophageal junction cancer (GC/GEJC), there is a need to identify biomarkers of response to therapies, such as immune checkpoint inhibitors.

Patients and Methods:

In post hoc exploratory analyses from CheckMate 032 (GC/GEJC cohort), we evaluated associations between nivolumab ± ipilimumab (NIVO ± IPI) efficacy and programmed death ligand 1 (PD-L1) expression, defined by tumor cells (% TC) or combined positive score (CPS; sum of PD-L1–staining TCs + immune cells, divided by total viable TCs, × 100) using the Dako PD-L1 IHC 28-8 pharmDx assay, or inflammatory gene expression.

Results:

There was a trend toward increased efficacy (objective response and overall survival) when PD-L1 expression was determined by CPS compared with % TC at higher cutoffs of ≥5 and ≥10 in the pooled analysis of all treatment regimens. In this analysis, 19% and 26% of patients with PD-L1–positive tumors at a CPS cutoff of ≥5 and ≥10, respectively, had an objective response compared with 8% and 9% of patients at the equivalent % TC cutoffs. Longer survival was demonstrated in patients with PD-L1–positive (defined by CPS cutoffs of ≥5 and ≥10) versus PD-L1–negative status. Similar results were observed in the NIVO 1 mg/kg + IPI 3 mg/kg subgroup. Multiple inflammatory gene signatures/transcripts, including a signature consisting of four genes (CD274, CD8A, LAG3, and STAT1), showed associations with response to NIVO ± IPI.

Conclusions:

This study suggests a greater association of PD-L1 expression by CPS with NIVO ± IPI efficacy compared with % TC PD-L1 expression in patients with GC/GEJC. Inflammatory signatures were also associated with NIVO ± IPI response, warranting further investigation.

See related commentary by Moutafi and Rimm, p. 3812
Therapeutic Efficacy of Combined JAK1/2, Pan-PIM, and CDK4/6 Inhibition in Myeloproliferative Neoplasms
Authors: Rampal Raajit K. , Pinzon-Ortiz Maria , Somasundara Amritha Varshini Hanasoge , Durham Benjamin , Koche Richard , Spitzer Barbara , Mowla Shoron , Krishnan Aishwarya , Li Bing , An Wenbin , Derkach Andriy , Devlin Sean , Rong Xianhui , Longmire Tyler , Eisman Shira Esther , Cordner Keith , Whitfield Justin T. , Vanasse Gary , Cao Zhu A. , Levine Ross L.
Published: March 2021

Purpose:

The JAK1/2 inhibitor ruxolitinib has demonstrated significant benefits for patients with myeloproliferative neoplasms (MPN). However, patients often lose response to ruxolitinib or suffer disease progression despite therapy with ruxolitinib. These observations have prompted efforts to devise treatment strategies to improve therapeutic efficacy in combination with ruxolitinib therapy. Activation of JAK–STAT signaling results in dysregulation of key downstream pathways, notably increased expression of cell-cycle mediators including CDC25A and the PIM kinases.

Experimental Design:

Given the involvement of cell-cycle mediators in MPNs, we sought to examine the efficacy of therapy combining ruxolitinib with a CDK4/6 inhibitor (LEE011) and a PIM kinase inhibitor (PIM447). We utilized JAK2-mutant cell lines, murine models, and primary MPN patient samples for these studies.

Results:

Exposure of JAK2-mutant cell lines to the triple combination of ruxolitinib, LEE011, and PIM447 resulted in expected on-target pharmacodynamic effects, as well as increased apoptosis and a decrease in the proportion of cells in S-phase, compared with ruxolitinib. As compared with ruxolitinib monotherapy, combination therapy led to reductions in spleen and liver size, reduction of bone marrow reticulin fibrosis, improved overall survival, and elimination of disease-initiating capacity of treated bone marrow, in murine models of MPN. Finally, the triple combination reduced colony formation capacity of primary MPN patient samples to a greater extent than ruxolitinib.

Conclusions:

The triple combination of ruxolitinib, LEE011, and PIM447 represents a promising therapeutic strategy with the potential to increase therapeutic responses in patients with MPN.
On the Nature of Hearing Loss in Méniere’s Disease
Authors: Gacek Richard R.
Published: March 2021

Objective: To explain the pathophysiology of the hearing loss in Ménière’s disease (MD). Background: In a previous report, we described a dramatic recovery of hearing in 12/31 patients with MD using antiviral (AV) drugs. The hearing loss in the remaining 19 patients with a longer history of MD remained unchanged or else worsened. Vertigo control was complete in the group with improved hearing but poorer in the group with greater hearing loss (and a longer MD history). Since achieving the recovery of hearing and control of the vertigo using AV drugs in these patients with a shorter history (≤2 years) of MD, we have continued to record dramatic hearing recovery in MD when patients have a shorter history of symptoms. We describe this here in 5 representative MD patients. We feel that the most likely explanation for the outcome is the removal of viral nucleic acids (NA) from the organ of Corti. Summary: A likely explanation for the sensorineural hearing loss in MD is paralysis of the cochlear amplifier function of the outer hair cells due to the toxicity ofNA. These NA are released from neurotropic viruses located in the vestibular nerve ganglion. Key Messages: (1) Viruses (Herpes family) are the cause of the symptoms in MD. (2) Hearing loss is the result of viral NA in the organ of Corti. (3) A short history of MD symptoms (<2 years) favors hearing recovery.
Preventive Interventions for Young Adults in Nightlife: Coproduction for a Systematic Literature Assessment Followed by a Stakeholder Dialogue Process
Authors: Brunn Judith , Brunner Sibylle , Mütsch Margot
Published: March 2021

Introduction: The nightlife-associated illicit drug and alcohol use presents diverse problems and includes different areas. In the Canton of Zurich, Switzerland, young adults in the nightlife setting were recently set as a priority group for preventive interventions. Method: Based on the predefined protocol, we systematically collated evidence on preventive interventions regarding young adults’ use of alcohol and illicit drugs in nightlife. EBSCO Medline, Embase, PsycInfo, and PsyIndex were searched for reviews (1990–2016) and primary studies (2012–2016). Additional sources and experts were consulted, and stakeholders involved throughout the research process. Interventions were summarized according to the before-, at- and after-the-party stages. Results: Before the party, good-quality studies were found for social media interventions, indicating positive effects on alcohol consumption. For the at-the-party stage, good evidence of low to medium quality was presented for crisis interventions and medical care at festivals and for multi-sector approaches. The after-the-party setting was mainly covered by gray literature, and evidence remained limited for designated drivers and street safety interventions in the target group. The stakeholder dialogue was a structured exchange and favored the following evidence-informed preventive intervention fields: personalized feedback via social media, sustaining awareness among nightlife managers, focus on public nighttime transportation, and multi-sector approaches. Conclusion: The systematic involvement of stakeholders was an inspiring means for identifying evidence relevant for practice and policy in nightlife and fostering implementation. Especially, individual-based interventions, such as personalized feedback via social media and guided reflection on alcohol or drug use, and broader networking, were considered promising.
Whole Heart Engineering: Advances and Challenges
Authors: Morrissey Jacquelynn , Mesquita Fernanda C.P. , Hochman-Mendez Camila , Taylor Doris A.
Published: March 2021

Bioengineering a solid organ for organ replacement is a growing endeavor in regenerative medicine. Our approach – recellularization of a decellularized cadaveric organ scaffold with human cells – is currently the most promising approach to building a complex solid vascularized organ to be utilized in vivo, which remains the major unmet need and a key challenge. The 2008 publication of perfusion-based decellularization and partial recellularization of a rat heart revolutionized the tissue engineering field by showing that it was feasible to rebuild an organ using a decellularized extracellular matrix scaffold. Toward the goal of clinical translation of bioengineered tissues and organs, there is increasing recognition of the underlying need to better integrate basic science domains and industry. From the perspective of a research group focusing on whole heart engineering, we discuss the current approaches and advances in whole organ engineering research as they relate to this multidisciplinary field’s 3 major pillars: organ scaffolds, large numbers of cells, and biomimetic bioreactor systems. The success of whole organ engineering will require optimization of protocols to produce biologically-active scaffolds for multiple organ systems, and further technological innovation both to produce the massive quantities of high-quality cells needed for recellularization and to engineer a bioreactor with physiologic stimuli to recapitulate organ function. Also discussed are the challenges to building an implantable vascularized solid organ.
Mechanism of α1-Adrenergic Receptor-Induced Increased Contraction of Rat Mesenteric Artery in Aging Hypertension Rats
Authors: Wei Xiaoyu , Lan Ting , Zhou Yuanqun , Cheng Jun , Li Pengyun , Zeng Xiaorong , Yang Yan
Published: March 2021

Introduction: Vasoconstriction is triggered by an increase in intracellular-free calcium concentration. Growing evidence indicates that contraction is also regulated by calcium-independent mechanisms involving RhoA-Rho kinase (ROCK), protein kinase C (PKC), and so on. In this study, we studied the changes of vascular reactivity as well as the underlying signaling pathways in aging spontaneously hypertensive rats (SHRs). Methods: The artery tension induced by α1-adrenergic receptor activator (α1-AR) phenylephrine (PE) was measured in the absence or presence of myosin light chain kinase (MLCK), PKC, and ROCK inhibitors. The α1-AR, PKC, ROCK, phosphorylation of myosin light chain (MLC), and PKC-potentiated phosphatase inhibitors of 17 kDa (CPI-17) of rat mesenteric arteries were analyzed at the mRNA level or protein level. Results: The vascular tension measurements showed that there was a significant increase in the mesenteric artery contraction induced by PE in old SHR. MLCK inhibitor ML-7 can similarly inhibit PE-induced vasoconstriction. PKC inhibitor GF109203X has the weakest inhibitory effect on PE-induced contraction in old SHR. At the presence of ROCK inhibitor H1152, PE-induced contraction was significantly reduced in young Wistar-Kyoto (WKY) rats, but this phenomenon disappeared in other rats. Furthermore, in old SHR the protein expression of α1-AR decreased and phosphorylation of MLC and CPI-17 were upregulated and MLC phosphatase (MLCP) activity was significantly lower. The expressions of PKC were upregulated in SHR and old rats. In addition, the expression of ROCK-1 was decreased and ROCK-2 was significantly upregulated with age in SHR. Conclusion: In aging hypertension, the expression/activity of PKC or ROCK-2/CPI-17 excessively increased, MLCP activity decreased and MLC phosphorylation enhanced, leading to increased α1-AR-induced vasoconstriction.
Prognostic Factors and Survival Outcomes among Patients with Breast Cancer and Brain Metastases at Diagnosis: A National Cancer Database Analysis
Authors: Zimmerman Brittney S. , Seidman Danielle , Cascetta Krystal P. , Ru Meng , Moshier Erin , Tiersten Amy
Published: March 2021

Introduction: The aim of this study was to assess for clinicopathologic and socioeconomic features that predict improved survival for patients with advanced breast cancer with synchronous brain metastases at diagnosis. Methods: We utilized the National Cancer Database (NCDB) to identify all patients with brain metastases present at diagnosis, with adequate information on receptor status (ER, PR, Her2), clinical T stage of cT1-4, clinical M1, with 3,943 patients available for analysis. The association between brain metastases patterns and patient/disease variables was examined by robust Poisson regression model. Cox proportional hazards model was used to quantify the associations between overall survival (OS) and these variables. Results: In univariable analysis, OS was significantly associated with the number of sites of metastases (p < 0.0001). Patients with 2 or more additional extracranial sites of metastases had significantly worse OS (median 8.8 months, 95% confidence interval [CI] 7.8, 9.9) than patients with brain metastases only (median OS 10.6 months, 95% CI 9.4, 12.9) or brain metastases plus one other extracranial site of metastases (median OS 13.1 months, 95% CI 11.8, 14.4). Risk factors which predicted poor prognosis included triple-negative disease, high comorbidity score, poorly differentiated tumors, invasive lobular histology, multi-organ involvement of metastases, and government or lack of insurance. Factors which improve survival include younger age and Hispanic race. Discussion/Conclusion: Using a large NCDB, we identified various factors associated with prognosis for patients with brain metastases at the time of breast cancer diagnosis. Insurance status and related socioeconomic challenges provide potential areas for improvement in care for these patients. This information may help stratify patients into prognostic categories at the time of diagnosis to improve treatment plans.
Sensitization against Fungi in Patients with Airway Allergies over 20 Years in Germany
Authors: Forkel Susann , Beutner Caroline , Schröder Silke S. , Bader Oliver , Gupta Sidhi , Fuchs Thomas , Schön Michael P. , Geier Johannes , Buhl Timo
Published: March 2021

Background: Fungal spores are ubiquitous allergens. Severe forms of asthma are particularly highly associated with fungal sensitization. National and international asthma guidelines recommend the implementation of allergen immunotherapy if indicated. Thus, detection and treatment of relevant allergies are key components of primary care of these patients. Objectives: The aims of the study were (i) to investigate trends in the prevalence of sensitization to twelve fungi in central Germany over the last 20 years and (ii) to dissect specific sensitization patterns among the 3 most important fungi: Aspergillus, Alternaria, and Cladosporium. Methods: This single-center study evaluated skin prick test (SPT) results of 3,358 patients with suspected airway allergies over a period of 20 years (1998–2017). Results: While 19.2% of all study patients had positive test results to at least 1 of the 3 fungi (Alternaria, Aspergillus, or Cladosporium) in the first study decade, this rate increased to 22.5% in the second decade. Slight increases in sensitization rates to almost all fungi were observed over the 20-year period. In the last decade, polysensitization to Alternaria, Aspergillus, and Cladosporium increased significantly. Sensitization to fungi is age-dependent and peaks in the age-group of 21–40 years during the second decade. Conclusion: Fungi are relevant allergens for perennial and seasonal allergy symptoms. We currently recommend including Aspergillus, Alternaria, and Cladosporium in the standard series of SPTs for airway allergies.
High-Dose-Rate Interstitial Brachytherapy (Interventional Radiotherapy) for Conjunctival Melanoma with Orbital Extension
Authors: Pagliara Monica Maria , Tagliaferri Luca , Savino Gustavo , Fionda Bruno , D’Aviero Andrea , Lanza Angela , Lancellotta Valentina , Midena Giulia , Gambacorta Maria Antonietta , Blasi Maria Antonietta
Published: March 2021

Purpose: To evaluate local control and functional and cosmetic outcomes of postoperative high-dose-rate interventional radiotherapy (HDR-IRT) in patients affected by conjunctival melanoma with orbit invasion. Methods: A retrospective study was conducted in 2 patients affected by conjunctival melanoma infiltrating the orbit, treated with surgical excision and HDR-IRT. The treatment procedures consisted of surgical excision of the orbital infiltrating nodule followed, 1 month after surgery, by adjuvant HDR-IRT. A target dose of 34 Gy was delivered in 10 twice-a-day fractions over 5 consecutive days. Data analysis included local tumor control and metastatic rate, acute and late toxicity, functional and aesthetic results. Results: In both patients, treatment was well tolerated, and there was no orbital recurrence at a median follow-up of 37–40 months. There was an excellent functional outcome, without no significant acute or late side effects. Conclusions: HDR-IRT could be considered a promising, feasible, successful, and well-tolerated option for selected patients affected by ocular tumors with orbital invasion.
Safety Management of Dialysis Fluid in Japan: Important Duties and Responsibilities of Clinical Engineers
Authors: Shibata Masanori
Published: March 2021

Dialysis therapy is the predominant choice for renal failure in Japan, and almost 30% of the patients with renal failure have been treated for 10 years or more. Dialysis became the standard procedure to treat renal failure nationwide in the 1980s. However, at that time, managing the increased number of patients on maintenance hemodialysis as well as operating and maintaining the newly developed advanced medical technologies at extensive numbers of clinical sites proved problematic. To help address this, the clinical engineer system was established in 1987 and certain aspects of the clinical engineers’ role remain unique to Japan today. For the last 30 years, clinical engineers have worked as frontline medical personnel not only operating dialysis-related devices but also placing their hands directly on patients when providing care, routinely performing puncture, and administering drugs through the blood circuit under physicians’ instructions. As part of their work, they crucially maintain the use of central dialysis fluid delivery systems (CDDSs) – also unique to Japan – which prepare and deliver a large quantity of dialysis fluid through a central circuit to individual dialysis consoles. CDDSs are widely used because they effectively alleviated the early confusion at clinical sites caused by the rapidly increasing hemodialysis population and the serious shortage in medical personnel. Moreover, clinical engineers alone have the technical ability to provide safe dialysis fluids adjusted to strict standards at clinical sites. In this review article, we focus on the crucial roles that clinical engineers have in maintaining the safety of dialysis-related medical devices and the preparation and delivery of dialysis fluid at many dialysis facilities across the country.
Obesity Can Contribute to Severe Persistent Allergic Rhinitis in Children through Leptin and Interleukin-1β
Authors: Han Myung Woul , Kim Song Hee , Oh Inbo , Kim Yang Ho , Lee Jiho
Published: March 2021

Background: Obesity/overweight is associated with a higher risk of allergic rhinitis (AR) in children. Objective: This study aimed at exploring the mechanisms by which obesity affects the severity of AR through leptin and interleukin (IL)-1β were investigated. Methods: In all, 210 subjects with AR and 82 subjects without AR were included in this study. The levels of leptin and inflammatory biomarkers were measured in the serum to investigate the correlation with the severity of AR. Additionally, we analyzed whether changes in BMI regulate the severity of AR through serial follow-up of obese children. Results: IL-1β, which is a biomarker of active inflammation in AR, was significantly higher in individuals with AR than in those without and higher in subjects in the obesity group than in those in the normal weight group. A regression analysis showed that the leptin level was associated with increased IL-1β expression in children with AR. In the multivariate analysis, only parental AR (9.2-fold increase in risk), elevated leptin (11.3-fold increase in risk), and high expression of IL-1β (5.8-fold increase in risk) emerged as significant risk factors of moderate to severe persistent allergic rhinitis. We also found that children with an increase or decrease in BMI showed changes in IL-1β and AR symptoms, which these changes were dependent on leptin and BMI. Conclusions: These results suggest that obesity is an important risk factor for the exacerbation of symptoms and leptin can exacerbate inflammation as well as severe and persistent symptoms through IL-1β in AR.
Estimating the Odds of Ulcerative Colitis-Associated Pyoderma Gangrenosum: A Population-Based Case-Control Study
Authors: Kridin Khalaf , Damiani Giovanni , Ludwig Ralf J. , Tzur Bitan Dana , Cohen Arnon D.
Published: March 2021

Background: Ulcerative colitis (UC) is a well-known underlying comorbidity of pyoderma gangrenosum (PG). However, the risk conferred by UC for the subsequent development of PG is yet to be elucidated. We aimed to estimate the magnitude of the association between UC and the subsequent occurrence of PG, which would enable us to assess the odds of PG developing in individuals with a history of UC. Methods: A population-based case-control study was conducted to compare PG patients (n = 302) and age-, sex- and ethnicity-matched control subjects (n = 1,497) regarding the presence of UC. Logistic regression models were utilized for univariate and multivariate analyses. Results: The prevalence of preexisting UC was greater in patients with PG than in controls (7.3 vs. 0.5%; p < 0.001). A 15-fold increase in the odds of PG in individuals with preexisting UC was observed (OR 14.62, 95% CI 6.45–33.18). The greatest risk of developing PG occurred in the first years following the diagnosis of UC (OR 35.50, 95% CI 4.35–289.60), and decreased thereafter to 10.03 (95% CI 1.83–55.03), 6.69 (95% CI 1.49–30.02), and 10.03 (95% CI 1.83–55.03) at 1–5, 5–10, and 10–15 years after the diagnosis of UC, respectively. This association retained its statistical significance following the adjustment for confounding factors (adjusted OR 10.78, 95% CI 4.55–25.52). Patients with both PG and UC were younger and had a lower prevalence of smoking than the remaining patients with PG. Conclusions: UC increases the odds of developing PG by 15-fold, with the highest probability of developing PG occurring within the first year after the diagnosis of UC. Patients with UC may be advised to avoid additional precipitating factors for the development of PG.
Applications of the Chick Chorioallantoic Membrane as an Alternative Model for Cancer Studies
Authors: Chu Pei-Yu , Koh Angele Pei-Fern , Antony Jane , Huang Ruby Yun-Ju
Published: March 2021

A variety of in vivo experimental models have been established for the studies of human cancer using both cancer cell lines and patient-derived xenografts (PDXs). In order to meet the aspiration of precision medicine, the in vivomurine models have been widely adopted. However, common constraints such as high cost, long duration of experiments, and low engraftment efficiency remained to be resolved. The chick embryo chorioallantoic membrane (CAM) is an alternative model to overcome some of these limitations. Here, we provide an overview of the applications of the chick CAM model in the study of oncology. The CAM model has shown significant retention of tumor heterogeneity alongside increased xenograft take rates in several PDX studies. Various imaging techniques and data analysis have been applied to study tumor metastasis, angiogenesis, and therapeutic response to novel agents. Lastly, to practically illustrate the feasibility of utilizing the CAM model, we summarize the general protocol used in a case study utilizing an ovarian cancer PDX.
Efficacy of Sodium Carboxymethylcellulose Compared to Sodium Hyaluronate as Submucosal Injectant for Gastric Endoscopic Submucosal Dissection: A Randomized Controlled Trial
Authors: Nakamura Jun , Hikichi Takuto , Watanabe Ko , Hashimoto Minami , Kato Tsunetaka , Takagi Tadayuki , Suzuki Rei , Sugimoto Mitsuru , Takasumi Mika , Sato Yuki , Irie Hiroki , Kobashi Ryoichiro , Kikuchi Hitomi , Waragai Yuichi , Kobayakawa Masao , Yamasaki Masahiro , Ohira Hiromasa
Published: March 2021

Introduction: Sodium hyaluronate (SH) is a useful submucosal injectant for gastric endoscopic submucosal dissection (ESD). On the other hand, sodium carboxymethylcellulose (SCMC), which has high viscosity, has also been applied clinically. We evaluated the efficacy of SCMC compared to that of SH in gastric ESD. Methods: A prospective randomized controlled trial was conducted to assess the efficacy of 1.0% SCMC as the injectant (SCMC group) compared to 0.4% SH (SH group) for ESD of gastric neoplasms. The primary end point was the procedure time of ESD. Secondary end points were treatment outcomes such as en bloc and R0 resection rates, number of hemostases, amount of injectant, ease of treatment (visual analog scale, 1–10 points), adverse events, and rate of ulcer healing 8 weeks after ESD. Results: A total of 60 patients were enrolled between October 2014 and October 2018, and 30 patients were allocated in each group. The procedure time (mean ± SD, minutes) was not significantly different between the SCMC (74.7 ± 54.5) and SH groups (67.1 ± 41.4) (p = 0.547). Furthermore, there were no differences between the 2 groups in terms of en bloc and R0 resection rates, number of hemostases, amount of injectant, ease of treatment, and rate of ulcer healing. No serious adverse events were observed in either group. Conclusion: SCMC was comparable to SH in terms of procedure time, treatment outcome, and ease and safety of treatment in gastric ESD. Further studies are needed to demonstrate the differences between the 2 injectants.
KM55 Monoclonal Antibody Staining in IgA-Dominant Infection-Related Glomerulonephritis
Authors: Zhang Minfang , Zhou Wenyan , Liu Shaojun , Zhang Liyin , Ni Zhaohui , Hao Chuanming
Published: March 2021

Introduction: IgA-dominant infection-related glomerulonephritis (IgA-IRGN) is a unique form of IRGN, which needs to be distinguished from IgA nephropathy (IgAN), due to overlapping clinical and pathological features. The key factor in the pathogenesis of IgAN is galactose-deficient IgA1 (Gd-IgA1). However, the mechanism of glomerular IgA deposition in patients with IgA-IRGN is unclear. Therefore, we evaluated whether Gd-IgA1 could be a useful biomarker to distinguish between these 2 diseases. Methods: A case-control study was conducted to analyze the clinical and pathological characteristics of 12 patients with IgA-IRGN. The intensity and distribution of glomerular Gd-IgA1 (KM55) staining in renal biopsies were assessed. The control group consisted of 15 patients diagnosed with IgAN and an additional 17 patients with glomerulopathy involving IgA deposition. Results: The main clinical manifestations of patients with IgA-IRGN were nephrotic-range proteinuria, hematuria, acute renal injury, and hypocomplementemia. Active lesions were the leading pathological feature, while focal segmental sclerosis was rare. Half of the patients exhibited hump-shaped subepithelial deposits. Glomerular KM55 staining was negative in 7 patients, trace in 4 patients, and 2+ in 1 patient. The median intensity of KM55 staining in IgA-IRGN patients was 0 (range 0∼2+), which was significantly lower than that of primary IgAN patients (median 2+, range 1+∼3+). The receiver operating characteristic analysis demonstrated that the optimal cutoff level to identify these 2 diseases was 0.5+. Conclusions: Glomerular KM55 staining intensity might be helpful to distinguish IgA-IRGN from primary IgAN. Weak or negative staining may favor IgA-IRGN. In addition, integrated analysis including clinical data, pathological findings, and prognostic information would further improve the differential diagnosis.
A Novel Standardized Method of Renal Biopsy in Mice
Authors: Mao Xinyue , Wang Chang , Xu Zhihui , He Yixin , Hou Yanpei , Li Bing
Published: March 2021

Introduction: In animal models, it can be difficult to confirm therapeutic effects due to technical inconsistencies and other reasons. Although renal biopsy is widely used in clinical diagnosis, it is rarely used in animal experimental models, especially in mice, because the problems of surgery-induced renal injury and bleeding have not been solved. Methods: We developed an easy-to-use method of renal biopsy in mice and evaluated whether 3 consecutive renal biopsies can be performed in the same kidney in a standardized manner. This method was verified using 2 mouse models, a healthy mouse model and a unilateral ureteral obstruction (UUO) mouse model, and evaluated based on renal function and histological changes. Results: There were no perioperative complications in any of the model mice. There was no significant difference in serum Cr, 24-h urine protein, or kidney/body weight ratio between the biopsy and control groups. Each biopsy sample contained sufficient renal tissue. The damage to the operated tissue was limited to the tissue near the biopsy site. Compared with renal tissues in the corresponding control group, the renal tissues obtained from the 3 biopsies (healthy model days 0, 4, and 7 and UUO model days 3, 7, and 10) and the remnant renal tissues after the biopsy showed no significant difference in the glomerular sclerosis index, degree of renal tubular damage, inflammatory response and renal fibrosis in these 2 models. Conclusions: Our new standardized method of renal biopsy in mice is a safe and cost-saving approach that allows repeated renal biopsies and ensures minimal trauma and sufficient sample size to quality in experimental disease models.
Endoscopic Third Ventriculostomy in Infants Less than One Year of Age: A Short Series of 14 Cases
Authors: Chowdhary Sarita , Sharma Shyamendra Pratap , Panigrahi Pranaya , Yadav Manoj Kumar , Sharma Shiv Prasad
Published: March 2021

Background: Endoscopic third ventriculostomy (ETV) is currently considered as an alternative to cerebrospinal fluid (CSF) shunt systems in the treatment of obstructive hydrocephalus. This procedure allows the CSF to drain in the basal cisterns and reabsorbed by arachnoid granulations, and avoiding implantation of exogenous material. Aims and Objectives: The purpose of this study was to assess the success rate of ETV in infants less than 1 year of age with congenital noncommunicating hydrocephalus. Material and Methods: This study was a 2-year prospective study from August 2017 to July 2019. ETVs were performed in 14 patients younger than 1 year with diagnosis of noncommunicating hydrocephalous. A failure was defined as the need for shunt implantation after ETV. Phase-contrast MRI of the brain was done after 6 months to see patency of ETV fenestration and CSF flow through ventriculostomy. Results: ETV was tried in 18 patients and successfully performed in 14 patients. Out of the 14 patients, shunt implantation after ETV was performed in 3 patients (failed ETV). In the successful cases, etiology was idiopathic aqueductal stenosis in 8, shunt complications in 2, and 1 case was a follow-up case of occipital encephalocele; the mean age was 7.7 months (range 3–12). In the 3 failed cases, etiology was aqueductal stenosis, mean age was 7.6 months (range 3–11). In all ETVs, failed patients MPVP shunting was done. Follow-up of nonshunted patients was done from 6 to 24 months (mean 15 months). There was no mortality or permanent morbidity noted following ETV. Conclusion: ETV is a good surgical procedure for less than 1-year-old children.
Higher Cancer Mortality in Rural Upper Urinary Tract Urothelial Carcinoma Patients
Authors: Collà Ruvolo Claudia , Stolzenbach Lara F. , Nocera Luigi , Deuker Marina , Wenzel Mike , Tian Zhe , La Rocca Roberto , Creta Massimiliano , Capece Marco , Saad Fred , Shariat Shahrokh F. , Tilki Derya , Briganti Alberto , Mirone Vincenzo , Karakiewicz Pierre I.
Published: March 2021

Objective: The aim of the study was to investigate differences in the stage at presentation and cancer-specific mortality (CSM) between rural area (RA) and urban area (UA) residence status in nonmetastatic upper urinary tract urothelial carcinoma (UTUC) patients. Methods: Newly diagnosed T1–3N0M0 UTUC patients with available residence status were abstracted from the Surveillance, Epidemiology, and End Results database (2004–2016). Propensity score (PS) matching (1 RA vs. 3 UA) accounted for age (interval ≤2 years), T stage (exact matching: T1, T2, and T3), and tumor grade (exact matching: high grade, low grade/unknown). Cumulative incidence plots and multivariable competing risk regression models focused on CSM, after adjustment for other-cause mortality. Results: Of 6,012 patients, 125 (2.1%) resided in RAs and 5,887 (97.9%) in UAs. RA patients were younger than UA patients (median age 72 vs. 75 years, p = 0.03). No differences were recorded in tumor location, T stage, tumor grade, or surgical treatment between RA and UA patients. After 1:3 PS matching, 125 RA patients and 375 UA patients were assessable. At 5 years of follow-up, CSM rates were 26.7 versus 15.7% according to RA versus UA, respectively. After additional multivariable adjustment for age, sex, tumor location, and surgical treatment, RA remained an independent predictor of higher CSM (hazard ratio 1.75, p = 0.02). Conclusions: Despite no differences in cancer characteristics, UTUC patients in RA are at higher risk of CSM than their UA counterparts. This suggests suboptimal care delivery and compliance as possible causes. Complex and/or rare disease should be centralized to expert centers, which are often in UAs.