bluuebunny/crossref_metadata_2025 huggingface dataset:
Immune profiling of uveal melanoma identifies a potential signature associated with response to immunotherapy
Authors: Qin Yong , Bollin Kathryn , de Macedo Mariana Petaccia , Carapeto Fernando , Kim Kevin B , Roszik Jason , Wani Khalida M , Reuben Alexandre , Reddy Sujan T , Williams Michelle D , Tetzlaff Michael T , Wang Wei-Lien , Gombos Dan S , Esmaeli Bita , Lazar Alexander J , Hwu Patrick , Patel Sapna P
Published: November 2020

Background

To date, no systemic therapy, including immunotherapy, exists to improve clinical outcomes in metastatic uveal melanoma (UM) patients. To understand the role of immune infiltrates in the genesis, metastasis, and response to treatment for UM, we systematically characterized immune profiles of UM primary and metastatic tumors, as well as samples from UM patients treated with immunotherapies.

Methods

Relevant immune markers (CD3, CD8, FoxP3, CD68, PD-1, and PD-L1) were analyzed by immunohistochemistry on 27 primary and 31 metastatic tumors from 47 patients with UM. Immune gene expression profiling was conducted by NanoString analysis on pre-treatment and post-treatment tumors from patients (n=6) receiving immune checkpoint blockade or 4-1BB and OX40 dual costimulation. The immune signature of UM tumors responding to immunotherapy was further characterized by Ingenuity Pathways Analysis and validated in The Cancer Genome Atlas data set.

Results

Both primary and metastatic UM tumors showed detectable infiltrating lymphocytes. Compared with primary tumors, treatment-naïve metastatic UM showed significantly higher levels of CD3+, CD8+, FoxP3+ T cells, and CD68+ macrophages. Notably, levels of PD-1+ infiltrates and PD-L1+ tumor cells were low to absent in primary and metastatic UM tumors. No metastatic organ-specific differences were seen in immune infiltrates. Our NanoString analysis revealed significant differences in a set of immune markers between responders and non-responders. A group of genes relevant to the interferon-γ signature was differentially up-expressed in the pre-treatment tumors of responders. Among these genes, suppressor of cytokine signaling 1 was identified as a marker potentially contributing to the response to immunotherapy. A panel of genes that encoded pro-inflammatory cytokines and molecules were expressed significantly higher in pre-treatment tumors of non-responders compared with responders.

Conclusion

Our study provides critical insight into immune profiles of UM primary and metastatic tumors, which suggests a baseline tumor immune signature predictive of response and resistance to immunotherapy in UM.
Body mass index (BMI) and outcome of metastatic melanoma patients receiving targeted therapy and immunotherapy: a multicenter international retrospective study
Authors: Rutkowski Piotr , Indini Alice , De Luca Matilde , Merelli Barbara , Mariuk-Jarema Anna , Teterycz Pawel , Rogala Pawel , Lugowska Iwona , Cybulska-Stopa Bożena , Labianca Alice , Di Guardo Lorenza , Del Vecchio Michele , Pigozzo Jacopo , Randon Giovanni , Corti Francesca , Tondini Carlo Alberto , Rulli Eliana , Mandala Mario
Published: November 2020

Background

Obesity is a risk factor for malignancy; however, its prognostic role in patients with metastatic melanoma is controversial. We aim to investigate the prognostic role of body mass index (BMI) in patients with metastatic melanoma receiving mitogen-activated pathway kinase inhibitors (MAPKi), immune checkpoint inhibitors (ICIs) alone or their sequence.

Methods

Data on patients with metastatic melanoma receiving ≥1 line of systemic treatment were retrieved from prospectively collected databases. Progression-free survival (PFS) and overall survival (OS) were analyzed by means of multivariable stratified Cox regression models; disease control rate (DCR) was analyzed by multivariable stratified logistic regression models. Subgroup analyzes according to the type of treatments received, and inBRAF-mutated patients were pre-planned. All multivariable models included BMI, age, gender, American Joint Committee on Cancer stage, performance status, lactate dehydrogenase and treatment sequencing strategy as covariates.

Results

Between November 2010 and November 2018, 688 patients from three Italian and two Polish centers were enrolled. 379 (57%) patients had M1c/d disease, 273 (41%) were female and the mean BMI was 27.1 (SD=4.9). Considering first-line treatment, 446 patients (66.8%) received ICIs and 222 MAPKi. No impact of BMI on OS was detected either considering the first line of ICIs, or ICIs sequencing (HR=1.02, 95% CI: 0.99 to 1.05, p=0.202, and HR=1.02, 95% CI: 0.99 to 1.04, p=0.237, respectively). A late effect of BMI on OS was found in patients treated with MAPKi: for five units increment, a 51% of risk reduction at 18 months and a 76% of risk reduction at 30 months were observed. No significant effect of BMI on PFS and DCR was found in any of the subgroup analyzes.

Conclusion

In patients with metastatic melanoma receiving ICIs, there is no impact of BMI on DCR, PFS and OS. The late prognostic effect of BMI in patients treated with MAPKi should be considered hypothesis generating and needs to be further investigated.
Nuclear imaging-guided PD-L1 blockade therapy increases effectiveness of cancer immunotherapy
Authors: Gao Hannan , Wu Yue , Shi Jiyun , Zhang Xin , Liu Tianyu , Hu Biao , Jia Bing , Wan Yakun , Liu Zhaofei , Wang Fan
Published: November 2020

Objectives

Strategies to improve the responsiveness of programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) checkpoint blockade therapy remain an essential topic in cancer immunotherapy. In this study, we developed a new radiolabeled nanobody-based imaging probe 99mTc-MY1523 targeting PD-L1 for the enhanced therapeutic efficacy of PD-L1 blockade immunotherapy by the guidance of 99mTc-MY1523 SPECT/CT imaging.

Methods

The binding affinity and specificity of nanobody MY1523 were measured in vitro. MY1523 was radiolabeled with 99mTc by a site-specific transpeptidation of Sortase-A, and the biodistribution and single photon emission CT (SPECT)/CT were performed in mice bearing different tumors. We used interferon-γ (IFN-γ) as an intervention means to establish animal models with different levels of PD-L1 expression, then investigated the ability of 99mTc-MY1523 SPECT/CT for the in vivo non-invasive measurement of PD-L1 expression in tumors. Finally, the PD-L1 blockade immunotherapies guided by 99mTc-MY1523 SPECT/CT were carried out in MC-38, A20, and 4T1 tumor-bearing mouse models, followed by the testing of tumor infiltration T cells.

Results

MY1523 exhibited a high binding affinity and specificity to PD-L1 and had no competitive binding with the therapeutic antibody. 99mTc-MY1523 was prepared with high specific activity and radiochemical purity. It was found that tumor PD-L1 expression was dynamically upregulated by IFN-γ intervention in MC-38, A20, and 4T1 tumor-bearing mouse models, as indicated by 99mTc-MY1523 SPECT/CT. The PD-L1 blockade therapy initiated during the therapeutic time window determined by 99mTc-MY1523 SPECT/CT imaging significantly enhanced the therapeutic efficacy in all animal models, while the tumor growth was effectively suppressed, and the survival time of mice was evidently prolonged. A correlation between dynamically upregulated PD-L1 expression and improved PD-L1 blockade therapy effectiveness was revealed, and the markedly increased infiltration of effector T cells into tumors was verified after the imaging-guided therapy.

Conclusion

Our results demonstrated that 99mTc-MY1523 SPECT/CT allowed a real-time, quantitative and dynamic mapping of PD-L1 expression in vivo, and the imaging-guided PD-L1 blockade immunotherapy significantly enhanced the therapeutic efficacy. This strategy merits translation into clinical practice for the better management of combination therapies with radiotherapy or chemotherapy.
Nivolumab and sunitinib combination in advanced soft tissue sarcomas: a multicenter, single-arm, phase Ib/II trial
Authors: Martin-Broto Javier , Hindi Nadia , Grignani Giovanni , Martinez-Trufero Javier , Redondo Andres , Valverde Claudia , Stacchiotti Silvia , Lopez-Pousa Antonio , D'Ambrosio Lorenzo , Gutierrez Antonio , Perez-Vega Herminia , Encinas-Tobajas Victor , de Alava Enrique , Collini Paola , Peña-Chilet Maria , Dopazo Joaquin , Carrasco-Garcia Irene , Lopez-Alvarez Maria , Moura David S , Lopez-Martin Jose A
Published: November 2020

Background

Sarcomas exhibit low expression of factors related to immune response, which could explain the modest activity of PD-1 inhibitors. A potential strategy to convert a cold into an inflamed microenvironment lies on a combination therapy. As tumor angiogenesis promotes immunosuppression, we designed a phase Ib/II trial to test the double inhibition of angiogenesis (sunitinib) and PD-1/PD-L1 axis (nivolumab).

Methods

This single-arm, phase Ib/II trial enrolled adult patients with selected subtypes of sarcoma. Phase Ib established two dose levels: level 0 with sunitinib 37.5 mg daily from day 1, plus nivolumab 3 mg/kg intravenously on day 15, and then every 2 weeks; and level −1 with sunitinib 37.5 mg on the first 14 days (induction) and then 25 mg per day plus nivolumab on the same schedule. The primary endpoint was to determine the recommended dose for phase II (phase I) and the 6-month progression-free survival rate, according to Response Evaluation Criteria in Solid Tumors 1.1 (phase II).

Results

From May 2017 to April 2019, 68 patients were enrolled: 16 in phase Ib and 52 in phase II. The recommended dose of sunitinib for phase II was 37.5 mg as induction and then 25 mg in combination with nivolumab. After a median follow-up of 17 months (4–26), the 6-month progression-free survival rate was 48% (95% CI 41% to 55%). The most common grade 3–4 adverse events included transaminitis (17.3%) and neutropenia (11.5%).

Conclusions

Sunitinib plus nivolumab is an active scheme with manageable toxicity in the treatment of selected patients with advanced soft tissue sarcoma, with almost half of patients free of progression at 6 months.

Trial registration numberNCT03277924.
The Paley ilioischial limb modification of the Dega osteotomy
Authors: Bor Noam , Dujovny Eytan , Rozen Nimrod , Rubin Guy
Published: November 2020

Background

We aim to describe a modified Dega osteotomy technique in detail, emphasizing its eventual advantages in comparison to the original Dega osteotomy and ‘San Diego’ modification. We also present our related literature review on various osteotomy techniques.

Methods

We reviewed the radiological indices of 27 dysplastic hips in 25 children with cerebral palsy and developmental dislocation of the hips (9 boys, 16 girls; mean age, 5 years) who underwent a modified Dega osteotomy according to Paley.

Results

Comparing the radiological indices results between our patients and those reported by the various authors in the literature, the data are almost identical.

Conclusions

The modified Dega osteotomy is the only technique wherein all two limbs of the triradiate cartilage are true, which becomes a single hinge where the osteotomy turns. Despite the similar results in the radiological indices between our patients and those in the literature, we still consider that the entire triradiate cartilage is a better hinge point for the iliac osteotomy. The difference between the osteotomy adopted in our institution and the modality described by most authors in the literature is that the latter mostly ignore or miss the ischial limb of the triradiate cartilage.
Comparative protective effects of N-acetylcysteine and melatonin against obesity-induced testicular dysfunction in rats
Authors: Khalil Sama S. , Aziz Joseph Amin , Ismail Khadiga Ahmed , El-Malkey Nanees F.
Published: November 2020

N-acetylcysteine (NAC) and melatonin were reported to exert protective effects on testicular tissues. Thus, this study aimed to determine which of these is more efficient against obesity-induced testicular dysfunction in albino rats. A total of 32 adult male rats (195 ± 10 g) were divided into four groups: control, obese rats fed a high-fat diet (HFD), HFD+NAC (150 mg/kg per day, i.p.) and HFD+melatonin (10 mg/kg per day, i.p.), for 5 weeks. Testes and epididymis were weighed. Lipid profile, pituitary-testicular hormones, tumor necrosis factor α (TNFα), epididymal sperm parameters, testicular oxidant–antioxidant system, testicular and the epididymal histopathology and immunohistochemical localization for androgen receptors (AR) and Bax reaction were analyzed. Administration of NAC or melatonin significantly improved the lipid parameters, gonadal hormones, TNFα level, sperm count and abnormal morphology, oxidant–antioxidant system and the absolute testicular and epididymal mass with an enhancement of testicular architecture, AR expression and apoptosis as compared with that in the obese group. Additionally, as compared with the NAC group, the melatonin group had significantly reduced body mass index, total cholesterol, triglyceride, and TNFα and increased testosterone, sperm count, motility, superoxide dismutase activity, mitigated histomorphometrical changes, Bax expression, and increased testicular AR expression. Therefore, melatonin was more efficient than NAC in affording fortification against HFD-induced testicular dysfunction.
A note on the linear stability of black holes in quadratic gravity
Authors: Dioguardi Christian , Rinaldi Massimiliano
Published: November 2020

Black holes in f(R)-gravity are known to be unstable, especially the rotating ones. In particular, an instability develops that looks like the classical black hole bomb mechanism: the linearized modified Einstein equations are characterized by an effective mass that acts like a massive scalar perturbation on the Kerr solution in general relativity, which is known to yield instabilities. In this note, we consider a special class of f(R) gravity that has the property of being scale-invariant. As a prototype, we consider the simplest case $$f(R)=R^2$$

f

(
R
)

=

R
2

and show that, in opposition to the general case, static and stationary black holes are stable, at least at the linear level. Finally, the result is generalized to a wider class of f(R) theories.
Review of combined measurements of Higgs boson production and decay using up to 80 fb−1 of proton–proton collision data at s = 13 TeV collected with the ATLAS experiment
Authors: Yang Hongtao
Published: November 2020

The combined measurements of Higgs boson production and decay are performed based on up to 80 fb[Formula: see text] of proton–proton collision data collected at [Formula: see text] = 13 TeV by the ATLAS detector. The overall signal strength, defined as measured signal yield divided by the Standard Model prediction, is [Formula: see text]. The inclusive and differential cross-sections of gluon–gluon fusion, vector-boson fusion, associated production with vector boson, and associated production with top quarks processes are also measured. The measurements are interpreted with leading-order motivated coupling strength modifiers. No significant deviations from the Standard Model predictions are observed.
Cardioprotective Effects of Taurisolo® in Cardiomyoblast H9c2 Cells under High-Glucose and Trimethylamine N-Oxide Treatment via De Novo Sphingolipid Synthesis
Authors: Lama Stefania , Monda Vincenzo , Rizzo Maria Rosaria , Dacrema Marco , Maisto Maria , Annunziata Giuseppe , Tenore Gian Carlo , Novellino Ettore , Stiuso Paola
Published: November 2020

In addition to high plasma glucose, increased levels of trimethylamine N-oxide (TMAO) have been found in obese subjects, where are considered as a novel risk factor for cardiovascular diseases. The present study aimed to investigate the effect of a novel nutraceutical formulation based on grape polyphenols (registered as Taurisolo®) in counteracting TMAO- and high glucose (HG)-induced cytotoxicity in cardiomyoblast H9c2 cells. Cell damage was induced with HG (HG-H9c2) and HG+TMAO (THG-H9c2); both experimental cell models were, thus, incubated for 72 h in the presence or absence of Taurisolo®. It was observed that Taurisolo® significantly increased the cell viability and reduced lactate dehydrogenase and aspartate transaminase release in both HG- and THG-H9c2 cells. Additionally, through its antioxidant activity, Taurisolo® modulated cell proliferation via ERK activation in THG-H9c2. Furthermore, Taurisolo® was able to induce autophagic process via increasing the expression of LC3II, a protein marker involved in formation of autophagosome and ex novo synthesis of sphingomyelin, ceramides, and their metabolites both in HG- and THG-H9c2 cells. Finally, Taurisolo® reduced hypertrophy and induced differentiation of HG-H9C2 cells into cardiomyocyte-like cells. These data suggest that Taurisolo® counteracts the toxicity induced by TMAO and HG concentrations increasing autophagic process and activating de novo sphingolipid synthesis, resulting in a morphological cell remodeling. In conclusion, our results allow speculating that Taurisolo®, combined with energy restriction, may represent a useful nutraceutical approach for prevention of cardiomyopathy in obese subjects.
Fracture Characteristics and Geometric Fractal of Damaged Sandstone under Impact Load
Authors: Hu Hao , Zheng Qiangqiang , Gao Xin , Cheng Bing , Wang Qianqian , Ni Xian
Published: November 2020

Before the rock mass in the engineering is broken under load, it is usually in a state of varying degrees of damage. Aiming at the fracture characteristics of damaged sandstone under impact load, this paper adopts a method of the cyclic static load to cause the sandstone specimens to have varying degrees of damage. Then, the wave velocity of sandstone before and after the damage is measured using the nonmetallic acoustic velocimeter, and the change rule of damage factor is analyzed. Finally, the split Hopkinson pressure bar (SHPB) is used to test the impact dynamics of sandstone with different damage degrees. The broken rock block is screened by a vibrating screen, and the crushing characteristics are analyzed. The results show that not only the damage factor of damaged sandstone but the growth rate increases, with the raising upper limit of stress. Under the impact load of the same incident energy, the fragmentation degree of the damaged sandstone increases with the increase of the upper stress limit, while the average diameter of the broken rock block decreases gradually, and the reduction rate increases first and then decreases.
Effects of Friction Plate Hardness and Surface Orientation on the Frictional Properties of Cereal Grain
Authors: Kaliniewicz Zdzisław , Jadwisieńczak Krzysztof , Żuk Zbigniew , Konopka Stanisław , Frączyk Adam , Krzysiak Zbigniew
Published: November 2020

The objective of this study was to evaluate the effects of the friction plate hardness and surface orientation of a friction plate on the angle and coefficient of static friction of cereal kernels. The angle of static friction of kernels representing four major cereal species was measured on six friction plates with different hardness. The friction plates were placed in position where their surface orientation was perpendicular or parallel relative to their inclination tilt. The experimental material comprised the so-called flat seed units, where each unit consisted of three spaced kernels. The angle of static friction of every flat seed unit was measured with a dedicated device in three replications, and average values of that angle were calculated. The kernels’ angle of static friction varied considerably from 13° to 33° within the analyzed range of changes in the surface characteristics of friction plates. The average angle of static friction was influenced mainly by the surface orientation of the friction plate that came into contact with cereal kernels. The angle of static friction was 17.5% to 56.5% higher when the friction plate had perpendicular rather than parallel surface orientation. The frictional properties of kernels were less influenced by plate hardness, and clear relationships were not observed in this respect. The kernels’ coefficient of static friction remained fairly constant within the analyzed range of plate hardness values, and it was estimated at 0.4 on plates with a perpendicular surface orientation and at 0.3 on plates with a parallel surface orientation.
The Relationship between Learning Styles and Career Decision-Making Self-Efficacy among Medicine and Dentistry Students of Ardabil University of Medical Sciences
Authors: Farhang Robab , Zamani Ahari Ulduz , Ghasemi Samira , Kamran Aziz
Published: November 2020

Background and Objectives. The career decision-making self-efficacy (CDSE) in medical, pharmacy, and dental students is more important than other disciplines due to professional sensitivity, direct involvement in decision-making for the treatment process, and the significant clinical involvement. It is also expected that learning styles can have a significant impact on the academic success, and the CDSE also affects the quality of clinical care. Therefore, the aim of this study was to examine the relationship between the learning styles and the career decision-making self-efficacy among medicine and dentistry students. Materials and Methods. This cross-sectional study was conducted on 235 medical interns and fifth- and sixth-year dental students of Ardabil University of Medical Sciences, Iran. The data were collected using Kolb Learning Style Inventory and Betz and Luzzo career decision-making self-efficacy questionnaire. Statistical tests such as Kolmogorov–Smirnov, Spearman correlation coefficient, Chi-square, one-way ANOVA were used to analyze the data. Results. The mean age of participants was 25.9 ± 1.30; a majority of them were dental students (134 persons, 59.3%), and 92 were medical students (40.7%). The predominant learning styles in dental and medical students were assimilating (40.3%) and converging (47.8%), respectively. There was no significant relationship between students’ learning styles and career decision-making self-efficacy and none of its subscales (

P
>
0.05

). The Chi-square test results showed that a significant difference was observed between the field of study and learning styles of the participants (

P
=
0.024

). Conclusion. This study showed that there was no significant relationship between learning style and career decision-making self-efficacy of the participants.
Prevalence of Angiogenesis, Proliferation, and Apoptosis Markers of Cervical Cancer and Their Correlation with Clinicopathological Parameters
Authors: Ramesh Anita , Chander R. Vimal , Srinivasan Chitra , Vengadassalapathy Srinivasan
Published: November 2020

The aim of the study is to investigate the expression of angiogenesis (VEGF and PDGF), angiogenesis inhibitor markers (angiostatin and endostatin), proliferation (Ki67), and apoptosis markers (p53 and p16) of cervical cancer in Indian population and to correlate them with the clinicopathological profile. It is a descriptive study of consecutive cases of cervical cancer from Saveetha Medical College and Hospital between January 2017 and December 2018. The expression of angiogenesis, angiogenesis inhibitor markers, Ki67, p53, and p16 in 60 cases of cervical sections were detected by the immunohistochemical method and analyzed with clinicopathological data. VEGF expression was positive in 16 cases (26.67%) and negative in 20 cases (33.33%). As of PDGF, 3 cases (3.33%) have shown positivity to PDGF and 33 cases have shown negativity. Angiostatin and endostatin expression was reported to be positive in 10 (16.67%) and 21 (35%) cases, respectively. Most of the cases 57 (95%) have shown both p16 and Ki67 positivity. Although p53 expression was positive in 48 cases (80%), the remaining 12 cases (20%) were p53-negative. The PDGF expression was significantly correlated to the stage of tumors. No statistically significant association was observed between angiogenesis inhibitor markers and clinicopathological parameters. A significant positive correlation was noticed between the Ki67 expression and stage of tumors.
Systemic Inflammation Response Index Predicts Survival Outcomes in Glioblastoma Multiforme Patients Treated with Standard Stupp Protocol
Authors: Topkan Erkan , Kucuk Ahmet , Ozdemir Yurday , Mertsoylu Huseyin , Besen Ali Ayberk , Sezen Duygu , Bolukbasi Yasemin , Pehlivan Berrin , Selek Ugur
Published: November 2020

Objectives. We endeavored to retrospectively assess the prognostic merit of pretreatment systemic immune response index (SIRI) in glioblastoma multiforme (GBM) patients who underwent postoperative partial brain radiotherapy (RT) and concurrent plus adjuvant temozolomide (TMZ), namely, the Stupp protocol. Methods. The records of 181 newly diagnosed GBM patients who received the postoperative Stupp protocol were retrospectively analyzed. The SIRI value for each eligible patient was calculated by utilizing the platelet, neutrophil, and lymphocyte measures obtained on the first day of treatment:

SIRI
=
Neutrophils
×
Monocytes
/
Lymphocytes

. The ideal cutoff values for SIRI connected with the progression-free- (PFS) and overall survival (OS) results were methodically searched through using the receiver operating characteristic (ROC) curve analysis. Primary and secondary end-points constituted the potential OS and PFS distinctions among the SIRI groups, respectively. Results. The ROC curve analysis labeled the ideal SIRI cutoffs at 1.74 (Area under the curve (AUC): 74.9%; sensitivity: 74.2%; specificity: 71.4%) and 1.78 (AUC: 73.6%; sensitivity: 73.1%; specificity: 70.8%) for PFS and OS status, individually. The SIRI cutoff of 1.78 of the OS status was chosen as the common cutoff for the stratification of the study population (Group 1:

SIRI
≤
1.78

(

N
=
96

) and

SIRI
>
1.78

(

N
=
85

)) and further comparative PFS and OS analyses. Comparisons between the two SIRI cohorts manifested that the

SIRI
≤
1.78

cohort had altogether significantly superior median PFS (16.2 versus 6.6 months;

P
<
0.001

) and OS (22.9 versus 12.2 months;

P
<
0.001

) than its

SIRI
>
1.78

counterparts. The results of multivariate Cox regression analyses ratified the independent and significant alliance between a low SIRI and longer PFS (

P
<
0.001

) and OS (

P
<
0.001

) durations, respectively. Conclusions. Present results firmly counseled the pretreatment SIRI as a novel, sound, and independent predictor of survival outcomes in newly diagnosed GBM patients intended to undergo postoperative Stupp protocol.
Severe Dental Disease as a Presenting Sign of Relapsed 6q24-Related Transient Neonatal Diabetes Mellitus
Authors: Delamerced Anna , Massingham Lauren J. , Quintos Jose Bernardo
Published: November 2020

Transient neonatal diabetes mellitus (TNDM) is a rare form of diabetes that presents in infancy and is characterized by intrauterine growth restriction and hyperglycemia without ketones on urinalysis. Patients are treated with insulin until remission, usually within the first year. Relapse to a permanent state may occur later in life, with a mean age of 14 years. The most common cause of TNDM is a chromosome 6q24 mutation that affects pancreatic β-cell function. Reports of relapse have been limited. We describe a case of an adolescent female with TNDM due to 6q24 hypomethylation who relapsed at 15 years of age with severe dental disease as the presenting sign.
Hardware Prototyping and Modelling of Prototype Filter for FBMC
Authors: Çalişir Bircan , Akbal Ayhan
Published: November 2020

Filter bank multicarrier (FBMC) is one of the effective candidates for the fifth generation of wireless communication networks. 5G (5th-generation wireless systems) is accepted as the next major stage of mobile telecommunication technology. The extent of 5G will be expanded mobile broadband services to next-generation automobiles and connected machines. In particular, filter bank multicarrier with offset quadrature amplitude modulation (FBMC/OQAM) is determined as the future generation 5G air interface by researchers recently. Filter bank multicarrier (FBMC) is admitted as one of the alternative technologies for multicarrier modulation. Compared to orthogonal frequency-division multiplexing (OFDM), FBMC has better spectrum shape and supports mobility. Therefore, efficient hardware implementations have highly interested researchers. Cyclic prefix (CP) and guard band are used for orthogonal frequency-division multiplexing (OFDM) and this causes loss of spectral efficiency, but FBMC applications do not need CP and guard band. Due to the fact that FBMC has offset QAM (OQAM) and band-limited filtering features on each subcarrier, the need for CP and guard band is eliminated. In this paper, novel pipelined hardware architecture of the filter design of FBMC/OQAM modulator has been proposed.
NAC Supplementation of Hyperglycemic Rats Prevents the Development of Insulin Resistance and Improves Antioxidant Status but Only Alleviates General and Salivary Gland Oxidative Stress
Authors: Zalewska Anna , Zięba Sara , Kostecka-Sochoń Paula , Kossakowska Agnieszka , Żendzian-Piotrowska Małgorzata , Matczuk Jan , Maciejczyk Mateusz
Published: November 2020

Previous studies based on animal models demonstrated that N-acetylcysteine (NAC) prevents oxidative stress and improves salivary gland function when the NAC supplementation starts simultaneously with insulin resistance (IR) induction. This study is the first to evaluate the effect of a 4-week NAC supply on the antioxidant barrier and oxidative stress in Wistar rats after six weeks of high-fat diet (HFD) intake. Redox biomarkers were evaluated in the parotid (PG) and submandibular (SMG) salivary glands and stimulated whole saliva (SWS), as well as in the plasma and serum. We demonstrated that the activity of salivary peroxidase and superoxide dismutase and total antioxidant capacity were significantly higher in PG, SMG, and SWS of IR rats treated with NAC. It appears that in PG and SMG of rats fed an HFD, N-acetylcysteine supplementation abolishes oxidative modifications to proteins (evidenced by decreased content of advanced oxidation protein products (AOPP) and advanced glycation end products (AGE)). Simultaneously, it does not reverse oxidative modifications of lipids (as seen in increased concentration of 8-isoprostanes and 4-hydroxynonenal vs. the control), although it reduces the peroxidation of salivary lipids in relation to the group fed a high-fat diet alone. NAC administration increased protein levels in PG and SMG but did not affect saliva secretion, which was significantly lower compared to the controls. To sum up, the inclusion of NAC supplementation after six weeks of HFD feeding was effective in improving the general and salivary gland antioxidant status. Nevertheless, NAC did not eliminate salivary oxidative stress and only partially prevented salivary gland dysfunction.
A Rare Complication of Noncompliance Status Post-Transhiatal Esophagectomy and Esophago-Gastroanastomosis
Authors: Ramirez Daniel , Appelbe Graham , Vattipally Venkatramana , Miller Justin
Published: November 2020

Gastropleural fistulas are a complication of peptic ulcers in hiatal hernias, trauma, infections, surgical complications, and malignancy. Presenting symptoms may include gastric and chest pain with respiratory failure in the setting of pneumonitis, hydropneumothorax, or tension pneumothorax. We describe a 57-year-old male with a history of transhiatal esophagectomy and esophago-gastroanastomosis who presented in the setting of dyspnea and dark orogastric tube output. Upper endoscopy revealed multiple gastric ulcers with a dominant ulceration communicating with an adjacent space, and a fistulous tract was demonstrated on computed tomography chest, confirming a gastropleural fistula, a rare life-threatening condition.
The Function of SUMOylation and Its Role in the Development of Cancer Cells under Stress Conditions: A Systematic Review
Authors: Zhao Qi , Ma Ying , Li Zugui , Zhang Kexin , Zheng Minying , Zhang Shiwu
Published: November 2020

Malignant tumors still pose serious threats to human health due to their high morbidity and mortality. Recurrence and metastasis are the most important factors affecting patient prognosis. Chemotherapeutic drugs and radiation used to treat these tumors mainly interfere with tumor metabolism, destroy DNA integrity, and inhibit protein synthesis. The upregulation of small ubiquitin-like modifier (SUMO) is a prevalent posttranslational modification (PTM) in various cancers and plays a critical role in tumor development. The dysregulation of SUMOylation can protect cancer cells from stresses exerted by external or internal stimuli. SUMOylation is a dynamic process finely regulated by SUMOylation enzymes and proteases to maintain a balance between SUMOylation and deSUMOylation. An increasing number of studies have reported that SUMOylation imbalance may contribute to cancer development, including metastasis, angiogenesis, invasion, and proliferation. High level of SUMOylation is required for cancer cells to survive internal or external stresses. Downregulation of SUMOylation may inhibit the development of cancer, making it an important potential clinical therapeutic target. Some studies have already begun to treat tumors by inhibiting the expression of SUMOylation family members, including SUMO E1 or E2. The tumor cells become more aggressive under internal and external stresses. The prevention of tumor development, metastasis, recurrence, and radiochemotherapy resistance by attenuating SUMOylation requires further exploration. This review focused on SUMOylation in tumor cells to discuss its effects on tumor suppressor proteins and oncoproteins as well as classical tumor pathways to identify new insights for cancer clinical therapy.
Different Approximation Algorithms for Channel Scheduling in Wireless Networks
Authors: Ni Qiufen , Huang Chuanhe , Pardalos Panos M. , Ye Jia , Fu Bin
Published: November 2020

We introduce a new two-side approximation method for the channel scheduling problem, which controls the accuracy of approximation in two sides by a pair of parameters

f
,
g

. We present a series of simple and practical-for-implementation greedy algorithms which give constant factor approximation in both sides. First, we propose four approximation algorithms for the weighted channel allocation problem: 1. a greedy algorithm for the multichannel with fixed interference radius scheduling problem is proposed and an one side

O

1

-IS-approximation is obtained; 2. a greedy

O

1

,
O

1

-approximation algorithm for single channel with fixed interference radius scheduling problem is presented; 3. we improve the existing algorithm for the multichannel scheduling and show an

E

O

d
/
ε

time

1
−
ϵ

-approximation algorithm; 4. we speed up the polynomial time approximation scheme for single-channel scheduling through merging two algorithms and show a

1
−
ϵ
,
O

1

-approximation algorithm. Next, we study two polynomial time constant factor greedy approximation algorithms for the unweighted channel allocation with variate interference radius. A greedy

O

1

-approximation algorithm for the multichannel scheduling problem and an

O

1

,
O

1

-approximation algorithm for single-channel scheduling problem are developed. At last, we do some experiments to verify the effectiveness of our proposed methods.
[Retracted] Analysis of Antiapoptosis Effect of Netrin‐1 on Ischemic Stroke and Its Molecular Mechanism under Deleted in Colon Cancer/Extracellular Signal‐Regulated Kinase Signaling Pathway
Authors: Wang Kai , Rong Liangqun , Wei Xiu’e , Zhang Qingxiu
Published: November 2020

To analyze the regulatory effect of Netrin‐1 in ischemic stroke and its influence on Deleted in Colon Cancer (DCC)/Extracellular Signal‐regulated Kinase (ERK) signaling pathway, 20 male rats were selected to construct the rat model of middle cerebral artery occlusion (MCAO), 10 normal rats were selected as healthy controls (Normal Saline (NS)), and they were divided into the MCAO+Netrin‐1 group, MCAO group, and NS group according to different treatment schemes. The positive expression of Netrin‐1 was detected by immunostaining, magnetic resonance imaging (MRI) was adopted to detect the percentage of rat cerebral infarct volume in the cerebral hemispheres, and Modified Neurological Severity Score (mNSS) was adopted to evaluate postoperative neurological function in rats. Besides, a tunnel staining experiment was applied to detect the apoptosis rate of rat neurons, the sticker removal test was applied to evaluate the postoperative sensory function of rats, and fluorescence staining was adopted to detect the expression of DCC and ERK in rats. The results showed that the percentage of cerebral infarction volume in the cerebral hemispheres of the MCAO+Netrin‐1 group was higher than that of the MCAO and NS groups (P < 0.05); in the MCAO+Netrin‐1 group, the MCAO mNSS scoring and the time spent in the sticker removal test were lower than the MCAO group (P < 0.05); the apoptosis rate of rats in the MCAO+Netrin‐1 group was lower than that in the MCAO group (P < 0.05); the average fluorescence intensity of DCC and p‐ERK in the MCAO+Netrin‐1 group was higher than that in the MCAO group (P < 0.05); the average fluorescence intensity of p‐ERK in the MCAO+Netrin‐1 group was higher than that in the MCAO group (P < 0.05). In short, Netrin‐1 can effectively reduce the brain tissue damage in rats with ischemic stroke, improve the nerve function and sensory function of rats, and inhibit neuronal cell apoptosis. Netrin‐1 can promote DCC expression and ERK phosphorylation, and the EPK signaling pathway may be involved in the antiapoptotic effect of Netrin‐1.
Isotropic Gravastar Model in Rastall Gravity
Authors: Abbas G. , Majeed K.
Published: November 2020

In the present paper, we have introduced a new model of gravastar with an isotropic matter distribution in Rastall gravity by the Mazur–Mottola (2004) mechanism. Mazur–Mottola approach is about the construction of gravastar which is predicted as an alternative to black hole. By following this convention, we define gravastar in the form of three phases. The first one is an interior phase which has negative density; the second part consists of thin shell comprising ultrarelativistic stiff fluid for which we have discussed the length, energy, and entropy. By the graphical analysis of entropy, we have shown that our proposed thin shell gravastar model is potentially stable. The third phase of gravastar is defined by the exterior Schwarzschild geometry. For the interior of gravastar, we have found the analytical solutions free from any singularity and the event horizon in the framework of Rastall gravity.
Chemical Composition and Microbial Contaminants of Poha Beer: A Local Nonalcoholic Beverage in the Bolgatanga Municipality, Ghana
Authors: Dongdem Julius T. , Abugri James , Asakedola Clement A.
Published: November 2020

Microbial and physicochemical analysis was performed on randomly sampled Poha Beer manufactured and vended in the Bolgatanga Municipality, Ghana. Poha Beer as it is referred to in Dagbani, is a Tamarindus indica fruit extract, a local nonalcoholic beverage originally processed and sold by rural women of the Dagomba ethnic descend. Morphological examination of bacterial cultures, Gram staining, and biochemical confirmatory tests were used to detect the presence of microbial pathogens in 45 samples of Poha Beer. A refractometer, a flame photometer and an atomic absorption spectrometer were used for the elemental analysis. All Poha Beer samples obtained from the Bolgatanga Municipality were positive for yeast, E. coli, Enterobacter sp. and Bacillus cereus. Pb was not detected in any of the samples. Chemical components detected include Zn2+ (average, 0.154 mg/L), Cd2+ (0.056 mg/L), Na+ (1.723 mg/L), Ca2+ (2.262 mg/L) and K+ (3.96 mg/L). All samples were acidic with an average pH value of 3.55. The Brix value of samples, however, was between 9.0 and 11.4 % per 40 mL of Poha Beer. Therefore, Poha Beer processed and sold in the Bolgatanga Municipality is acidic and contains detrimental amounts of Cd2+ and bacterial pathogens which may render it unwholesome for human consumption.
Sodium-Glucose Cotransporter 2 Inhibitors Improve Chronic Diabetic Macular Edema
Authors: Takatsuna Yoko , Ishibashi Ryoichi , Tatsumi Tomoaki , Koshizaka Masaya , Baba Takayuki , Yamamoto Shuichi , Yokote Koutaro
Published: November 2020

Purpose. Diabetic macular edema (DME) is a vision-threatening condition that develops in diabetic patients. The first-line therapy for DME is intravitreal injections of antivascular endothelial growth factor (anti-VEGF) agents; however, the high frequency of repeat injections, invasiveness of the procedure, and high cost are drawbacks for this treatment. The purpose of this report is to present our findings in 3 patients with chronic DME whose edema was resolved soon after oral doses of sodium-glucose cotransporter-2 (SGLT2) inhibitors were used. Case Presentation. Case 1 was a 66-year-old woman diagnosed with moderate nonproliferative diabetic retinopathy (DR) with DME that had developed a decade earlier. The DME persisted for 4 years in the left eye. The addition of oral empagliflozin, a SGLT2 inhibitor, led to a marked improvement of the DME after one month, and this improvement continued over two years. Case 2 was a 68-year-old woman who was diagnosed with preproliferative DR with bilateral DME. The addition of oral dapagliflozin led to the improvement of the DME after two months, and this improvement continued over one year. Case 3 was a 61-year-old woman who was diagnosed with moderate nonproliferative DR with DME. Oral luseogliflozin was given which led to better glycemic control, and her left central retinal thickness (CRT) was markedly reduced after only two weeks. This reduction was maintained in her left eye for six months without any additional ophthalmic procedures. Conclusions. Although this study involved only three cases, our findings indicate that SGLT2 inhibitors might have possible efficacy for chronic DME.
Dynamic Transitions of Epilepsy Waveforms Induced by Astrocyte Dysfunction and Electrical Stimulation
Authors: Zhang Honghui , Shen Zhuan , Zhao Qiangui , Yan Luyao , Du Lin , Deng Zichen
Published: November 2020

Experimental studies have shown that astrocytes participate in epilepsy through inducing the release of glutamate. Meanwhile, considering the disinhibition circuit among inhibitory neuronal populations with different time scales and the feedforward inhibition connection from thalamic relay nucleus to cortical inhibitory neuronal population, here, we propose a modified thalamocortical field model to systematically investigate the mechanism of epilepsy. Firstly, our results show that rich firing activities can be induced by astrocyte dysfunction, including high or low saturated state, high- or low-frequency clonic, spike-wave discharge (SWD), and tonic. More importantly, with the enhancement of feedforward inhibition connection, SWD and tonic oscillations will disappear. In other words, all these pathological waveforms can be suppressed or eliminated. Then, we explore the control effects after different external stimulations applying to thalamic neuronal population. We find that single-pulse stimulation can not only suppress but also induce pathological firing patterns, such as SWD, tonic, and clonic oscillations. And we further verify that deep brain stimulation can control absence epilepsy by regulating the amplitude and pulse width of stimulation. In addition, based on our modified model, 3 : 2 coordinated reset stimulation strategies with different intensities are compared and a more effective and safer stimulation mode is proposed. Our conclusions are expected to give more theoretical insights into the treatment of epilepsy.
Hypoxia-Inducible Factor-1: A Potential Target to Treat Acute Lung Injury
Authors: Liu Yang , Xiang Du , Zhang Hengcheng , Yao Hanlin , Wang Yanfeng
Published: November 2020

Acute lung injury (ALI) is an acute hypoxic respiratory insufficiency caused by various intra- and extrapulmonary injury factors. Presently, excessive inflammation in the lung and the apoptosis of alveolar epithelial cells are considered to be the key factors in the pathogenesis of ALI. Hypoxia-inducible factor-1 (HIF-1) is an oxygen-dependent conversion activator that is closely related to the activity of reactive oxygen species (ROS). HIF-1 has been shown to play an important role in ALI and can be used as a potential therapeutic target for ALI. This manuscript will introduce the progress of HIF-1 in ALI and explore the feasibility of applying inhibitors of HIF-1 to ALI, which brings hope for the treatment of ALI.
Low-Cyclic Loading Tests of Self-Centering Variable Friction (SCVF) Brace
Authors: He Qingguang , Bai Yanxia , Wu Weike , Du Yongfeng
Published: November 2020

A novel assembled self-centering variable friction (SCVF) brace is proposed which is composed of an energy dissipation system, a self-centering system, and a set of force transmission devices. The hysteretic characteristics and energy dissipation of the SCVF brace with various parameters from low-cyclic loading tests are presented. A finite element model was constructed and tested under simulated examination for comparative analysis. The results indicate that the brace shows an atypical flag-type hysteresis curve. The SCVF brace showed its stable self-centering ability and dissipation energy capacity within the permitted axial deformation under different spring and friction plates. A larger deflection of the friction plate will make the variable friction of this SCVF brace more obvious. A higher friction coefficient will make the energy dissipation capacity of the SCVF brace stronger, but the actual friction coefficient will be lower than the design value after repeated cycles. The results of the fatigue tests showed that the energy dissipation system formed by the ceramic fiber friction blocks and the friction steel plates in the SCVF brace has a certain stability. The finite element simulation results are essentially consistent with the obtained test results, which is conducive to the use of finite element software for calculation and structural analysis in actual engineering design.
Atypical Presentation of Anti-Phospholipid Antibody Syndrome with Seizure and Atrial Mass
Authors: Shil Rajish Sanjit Kumar , Al Dhuhoori Amal Abdallah , Thomachan Vipin Mughilassery , Teir Jamal Ali , Radhakrishnan Renganathan
Published: November 2020

Anti-phospholipid antibody syndrome (APS) has a broad spectrum of thrombotic and nonthrombotic clinical manifestations. The diagnosis requires a set of clinical criteria of thrombosis along with persistently positive anti-phospholipid antibody tests. In this report, we are presenting a case of APS, who is a 38-year-old male, presented with complains of seizures and found to have stroke, which on further investigation revealed to have been caused possibly from a left atrial mass. Therefore, high index of suspicion is required for the diagnosis of APS in young patients, who present with various neurological and cardiovascular manifestations, mostly secondary to thrombosis.
Polynomial Decay Rate for a Coupled Lamé System with Viscoelastic Damping and Distributed Delay Terms
Authors: Doudi Nadjat , Boulaaras Salah Mahmoud , Alghamdi Ahmad Mohammed , Cherif Bahri
Published: November 2020

In this paper, we prove a general energy decay results of a coupled Lamé system with distributed time delay. By assuming a more general of relaxation functions and using some properties of convex functions, we establish the general energy decay results to the system by using an appropriate Lyapunov functional.