bluuebunny/crossref_metadata_2025 huggingface dataset:
Renal Cell Carcinoma Metastasis to the Breast: A Rare Presentation
Authors: Ali Heba O. E. , Ghorab Tamer , Cameron Iain R. , Marzouk Ahmed M. S. M.
Published: May 2021

Worldwide breast malignancy is the most common cancer in women; however, metastases to the breast from extramammary malignancies are very rare and only a few sporadic cases are reported in the international literature. In this article, the authors report a case of a 73-year-old woman, who underwent nephrectomy for clear cell renal cell carcinoma and 3 years later presented with a breast metastasis from renal cell carcinoma (clear cell type).
Rockburst Prediction on the Superimposed Effect of Excavation Accumulation Energy and Blasting Vibration Energy in Deep Roadway
Authors: Li Qingwen , Xiang Ben
Published: May 2021

In deep mining, much elastic energy is stored in rock mass due to the high geostress. Rockburst will be induced by accumulated energy during excavation. Meanwhile, because of blasting vibration energy in the host rock, there will be an obvious superimposed effect on the probability and intensity of rockburst. To explore the most reasonable and effective method for understanding rockburst problem under blasting, a deep roadway of Sanshandao gold mine was studied. On the basis of in situ geostress data, the accumulated energy of three‐centered arch roadway after quasi‐static excavation was derived. Then, a series of in situ blasting vibration were monitored, and the blasting vibration energy was calculated by employing the equivalent theory of elastic vibration boundary. Finally, the tendentiousness of rockburst was evaluated qualitatively with the superimposed energy. The results indicated that the disaster‐driven energy was increased by 45.1% and 28.2% on different places of roadway. Also, the probability and intensity of rockburst would be raised.
Lack of Association between Interarm Systolic Blood Pressure Difference and Coronary Artery Disease in Patients Undergoing Elective Coronary Angiography
Authors: Mohamadi Mohammad Hosein , Rai Alireza , Rezaei Mansour , Khatony Alireza
Published: May 2021

Aim. Peripheral vascular disease (PVD) and coronary artery disease (CAD) are, in many cases, asymptomatic and not usually diagnosed. The timely diagnosis of peripheral vascular diseases can act as an indicator or practical evidence of CAD. Therefore, this study was conducted to determine the relationship between interarm systolic blood pressure difference (IASBPD) and severity and number of coronary artery stenosis. Methods. The samples in this cross-sectional study consisted of 578 patients who were candidates for coronary angiography, with an average age of 57.5 ± 10.5 years. Patients were classified according to CAD and number and severity of coronary artery stenosis. The relationship between IASBPD and presence or lack of CAD as well as the number and severity of coronary artery stenosis was studied. The sensitivity, specificity, and positive predictive value of IASBPD index were calculated for the detection of CAD using the Kappa coefficient. Results. There was no statistically significant relationship between IASBPD, CAD, and severity and number of coronary artery stenosis. This index had low sensitivity and predictive value in the diagnosis of CAD and stenosis in coronary arteries in comparison with angiography. Conclusion. The results showed that the IASBPD index cannot be a valid criterion for the diagnosis of CAD as well as the number and severity of coronary artery stenosis. More studies with larger sample sizes and different designs are needed in this regard to achieve more conclusive results.
Mesenchymal Stem Cells and COVID-19: Cure, Prevention, and Vaccination
Authors: Afarid Mehrdad , Sanie-Jahromi Fatemeh
Published: May 2021

COVID-19 disease has been a global health problem since late 2019. There are many concerns about the rapid spread of this disease, and yet, there is no approved treatment for COVID-19. Several biological interventions have been under study recently to investigate efficient treatment for this viral disease. Besides, many efforts have been made to find a safe way to prevent and vaccinate people against COVID-19 disease. In severe cases, patients suffer from acute respiratory distress syndrome usually associated with an increased level of inflammatory cytokines, called a cytokine storm. It seems that reequilibrating the hyperinflammatory response of the host immune system and regeneration of damaged cells could be the main way to manage the disease. Mesenchymal stem cells (MSCs) have been recently under investigation in this regard, and the achieved clinical outcomes show promising evidence for stem cell-based therapy of COVID-19. MSCs are known for their potential for immunomodulation, defense against virus infection, and tissue regeneration. MSCs are a newly emerged platform for designing vaccines and show promising evidence in this area. In the present study, we provided a thorough research study on the most recent clinical studies based on stem cells in the treatment of COVID-19 while introducing stem cell exclusivities for use as an immune disorder or lung cell therapy and its potential application for protection and vaccination against COVID-19.
Evaluation of Hydrodynamic Pressure Distribution in Reservoir of Concrete Gravity Dam under Vertical Vibration Using an Analytical Solution
Authors: Pasbani Khiavi Majid , Sari Ali
Published: May 2021

Fluid-structure interaction causes a hydrodynamic force, which can be exerted to the dam and affects its response. The effect of vertical excitation of ground motion on dynamic behavior of concrete gravity dam is the most important because of the interaction between foundation and reservoir. So, the foundation-reservoir interaction should be taken into account in designing concrete dams. In most studies, the effects of the vertical component of vibration have been ignored. While in vertical vibration, due to the interaction of the reservoir and the foundation, a significant hydrodynamic pressure is produced in the tank, which increases the dam response. In this study, the hydrodynamic pressure wave propagation in the reservoir of a concrete gravity dam caused by interaction with the foundation under vertical vibration is investigated using an analytical method. To achieve an analytical solution, the reservoir is assumed to be rectangular, and a harmonic load is vertically applied on the system from the foundation. Considering the acoustic nature of the reservoir fluid under harmonic vibration, a new method using the separation of variables method has been used for solution of hydrodynamic wave equation. The results show a significant effect of the vertical component of earthquake on the amount of induced pressure distributed in the reservoir, which has been omitted in most previous studies. Obtained results of the proposed model can be extended to more complicated models in terms of different loading and geometrical conditions.
Molecular Dynamics Simulations of the Thermal Conductivity of Silicon-Germanium and Silicon-Germanium-Tin Alloys
Authors: Wang Zan , Cai X. Y. , Zhao W. K. , Wang H. , Ruan Y. W.
Published: May 2021

In this work, we investigate the thermal conductivity properties of

Si

1
−
x

Ge

x

and

Si

0.8

Ge

0

Sn

2
y

alloys. The equilibrium molecular dynamics (EMD) is employed to calculate the thermal conductivities of

Si

1
−
x

Ge

x

alloys when

x

is different at temperatures ranging from 100 K to 1100 K. Then nonequilibrium molecular dynamics (NEMD) is used to study the relationships between

y

and the thermal conductivities of

Si

0.8

Ge

0.2

Sn

2
y

alloys. In this paper, Ge atoms are randomly doped, and tin atoms are doped in three distributing ways: random doping, complete doping, and bridge doping. The results show that the thermal conductivities of

Si

1
−
x

Ge

x

alloys decrease first, then increase with the rise of

x

, and reach the lowest value when

x

changes from 0.4 to 0.5. No matter what the value of

x

is, the thermal conductivities of

Si

1
−
x

Ge

x

alloys decrease with the increase of temperature. Thermal conductivities of

Si

0.8

Ge

0.2

alloys can be significantly inhibited by doping an appropriate number of Sn atoms. For the random doping model, thermal conductivities of

Si

0.8

Ge

0.2

Sn

y

alloys approach the lowest level when

y

is 0.10. Whether it is complete doping or bridge doping, thermal conductivities decrease with the increase of the number of doped layers. In addition, in the bridge doping model, both the number of Sn atoms in the [001] direction and the penetration distance of Sn atoms strongly influence thermal conductivities. The thermal conductivities of

Si

0.8

Ge

0.2

Sn

y

alloys are positively associated with the number of Sn atoms in the [001] direction and the penetration distance of Sn atoms.
Importance of Altered Gene Expression of Metalloproteinases 2, 9, and 16 in Acute Myeloid Leukemia: Preliminary Study
Authors: Pietrzak Jacek , Mirowski Marek , Świechowski Rafał , Wodziński Damian , Wosiak Agnieszka , Michalska Katarzyna , Balcerczak Ewa
Published: May 2021

Acute myeloid leukemia is a group of hematological neoplasms characterized by a heterogeneous course and high mortality. The important factor in the neoplastic process is metalloproteinases, proteolytic enzymes capable of degrading various components of the extracellular matrix, which take an active part in modifying the functioning of the cell, including transformation to cancer cell. They interact with numerous signaling pathways responsible for the process of cell growth, proliferation, or apoptosis. In the present study, changes in the expression of MMP2, MMP9, and MMP16 genes between patients with AML and people without cancer were examined. The impact of cytogenetic changes in neoplastic cells on the expression level of MMP2, MMP9, and MMP16 was also assessed, as well as the impact of the altered expression on the effectiveness of the first cycle of remission-inducing therapy. To evaluate the expression of all studied genes MMP2, MMP9, and MMP16, SYBR Green-based real-time PCR method was used; the reference gene was GAPDH. For two investigated genes MMP2 and MMP16, the lower expression level was observed in patients with AML when compared to healthy people. The MMP9 gene expression level did not differ between patients with AML and healthy individuals which may indicate a different regulation of gene expression in acute myeloid leukemia. However, no correlation was observed between the genes’ expression of all tested metalloproteinases and the result of cytoreductive treatment or the presence of cytogenetic changes. The obtained results show that the expression of MMP2 and MMP16 genes is reduced while the expression of MMP9 is unchanged in patients with acute myeloid leukemia. This may indicate a different regulation of the expression of these genes, and possible disruptions in gene transcription or posttranscriptional mechanisms in the MMP2 and MMP16 genes, however, do not affect the level of MMP9 expression. Obtained results in AML patients are in contrary to various types of solid tumors where increased expression is usually observed.
[Retracted] Low‐Power Indoor Positioning Algorithm Based on iBeacon Network
Authors: Zhang Xiaona , Zhang Shufang , Huai Shuaiheng
Published: May 2021

In this article, we use a low‐power iBeacon network to conduct an in‐depth analysis and research on the principle of indoor positioning and adopt an efficient and fast positioning algorithm. Secondly, based on the obtained analysis, an iBeacon‐based indoor positioning system is proposed to analyze how to use iBeacon for accurate positioning and whether it can effectively compensate for the current mainstream positioning system. We analyze the requirements of the iBeacon‐based indoor positioning system and propose the design of this positioning system. We analyze the platform and environment for software development, design the general framework of the positioning system, and analyze the logical structure of the whole system, the structure of data flow, and the communication protocols between each module of the positioning system. Then, we analyze the functions of the server module and the client module of the system, implement the functions of each module separately, and debug the functions of each module separately after each module is implemented. The feasibility of the algorithm and the performance improvement are confirmed by the experimental data. Our results show that the communication distance is improved by approximately 20.25% and the accuracy is improved by 5.62% compared to other existing results.
A Risk Signature with Autophagy-Related Long Noncoding RNAs for Predicting the Prognosis of Clear Cell Renal Cell Carcinoma: Based on the TCGA Database and Bioinformatics
Authors: Xuan Yundong , Chen Weihao , Liu Kan , Gao Yu , Zuo Shidong , Wang Baojun , Ma Xin , Zhang Xu
Published: May 2021

Background. Disorders of autophagic processes have been reported to affect the survival outcome of clear cell renal cell carcinoma (ccRCC) patients. The purpose of our study was to identify and validate the candidate prognostic long noncoding RNA signature of autophagy. Methods. Transcriptome profiles were obtained from The Cancer Genome Atlas. The autophagy gene list was obtained from the Human Autophagy Database. Based on coexpression analysis, we obtained a list of autophagy-related lncRNAs (ARlncRNAs). GO enrichment analysis and KEGG pathway analysis were conducted to explore the functional annotation of these ARlncRNAs. Univariate and multivariate Cox regression analyses were conducted to elucidate the correlation between overall survival and the expression level of each ARlncRNAs. We then established a prognostic signature that was a linear combination of the regression coefficients from the multivariate Cox regression model (

β

) multiplied by the expression levels of the respective ARlncRNAs in the training cohort. The predictive performance was tested in the validation cohort. Additionally, the independence of the risk signature was assessed, and the relationship between the risk signature and conventional clinicopathological features was explored. Results. Seven autophagy-related lncRNAs with prognostic value (SNHG3, SNHG17, MELTF-AS1, HOTAIRM1, EPB41L4A-DT, AP003352.1, and AC145423.2) were identified and integrated into a risk signature, dividing patients into low-risk and high-risk groups. The risk signature was independent of conventional clinical characteristics as a prognostic indicator of ccRCC (HR, 1.074, 95% confidence interval: 1.036-1.113,

p
<
0.001

) and was valuable in the prediction of ccRCC progression. Conclusion. Our risk signature has potential prognostic value in ccRCC, and these ARlncRNAs may play a significant role in ccRCC tumor biology.
Optimization of the Structural Parameters and the Teeth Shape of Slip in Drill Rig
Authors: Zhang Hua , Zhu Qianwei , Gao Bin
Published: May 2021

In order to improve the performance of slip and reduce the extrusion damage of the drill pipe in the drill rig, the optimization of structural parameters and teeth shape of the slip while clamping the drill pipe had been researched in this article. On the macroscale, the structural parameters of the slip had been optimized with response surface method (RSM) and Multiobjective Genetic Algorithm (MOGA). The optimized result showed that the single weight of the slip had been reduced from 3.99 kg to 2.91 kg and the maximum deformation of the drill pipe was reduced from 3.75 mm on both sides to 2.56 mm on both sides. On the microscale, a mathematical model for the single slip teeth while clamping the drill pipe had been established to give a detailed description to calculate the equivalent coefficient of friction and provide the relationship between the frictional torque with the allowable compression strength. In addition, the finite element model that had been set up by ABAQUS was used to verify the mathematical model, and the comparison of results had shown the accuracy of the mathematical model of the slip teeth while clamping the drill pipe. According to the mathematical model of the slip teeth in the drill rig, while clamping the drill pipe, the optimal shape of the slip teeth in the drill rig was achieved under the following condition: the slope of the slip teeth θ is 60°, the top width of the slip teeth

w

h

is 1.5 mm, and the depth of the slip teeth clamping the drill pipe d is 0.5 mm. The equivalent coefficient of friction

f

v

can be increased from 1.73 to 2.06, and the optimal result

f

v

increases 11.3%.
Intermittent Sampled Data Control for Time‐Varying Formation‐Containment of the Multiagent System with/without Time Delay
Authors: Chi Ming , Wang Xu-Long , Dou Yangming , Liu Zhi-Wei
Published: May 2021

Time‐varying formation‐containment problems for a second‐order multiagent system (SOMAS) are studied via pulse‐modulated intermittent control (PMIC) in this paper. A distributed control framework utilizing the neighbors’ positions and velocities is designed so that leaders in the multiagent system form a formation, and followers move to the convex hull formed by each leader. Different from the traditional formation‐containment problems, this paper applies the PMIC framework, which is more common and more in line with the actual control scenarios. Based on the knowledge of matrix theory, algebraic graph theory, and stability theory, some sufficient conditions are given for the time‐varying formation‐containment problem of the second‐order multiagent system. Some numerical simulations are proposed to verify the effectiveness of the results presented in this paper.
Mechanical Characteristics of Coal and Rock in Mining under Thermal-Hydraulic-Mechanical Coupling and Dynamic Disaster Control
Authors: Ma Haifeng , Wang Lingjie , Niu Xin'gang , Yao Fanfan , Zhang Kexue , Chang Jucai , Li Yingming , Zhang Xiangyang , Li Chaunming , Hu Zuxiang
Published: May 2021

In order to reduce the risk of coal and rock dynamic disasters in the coal mine production process, the coupling mechanics characteristics of coal and rock produced in the process of coal mining in the Dingji Coal Mine are taken as the research object, and the experimental study on the deformation characteristics and the variation rule of mechanical parameters of raw coal under multifield coupling (temperature, gas, and stress coupling) was carried out. The results show that the elastic modulus, peak strain, and peak stress of raw coal samples under the thermal-hydraulic-mechanical coupling have the same change law in the test temperature range and all of them show a linear decreasing law as the temperature increases. Under the same temperature gradient increasing condition, the elastic modulus, peak strain, and peak stress show a nongradient decreasing trend as the temperature increases. Both the deformation modulus and the lateral expansion coefficient show a linear increase as the temperature increases, while the deformation modulus and the lateral expansion coefficient show a nongradient increase trend as the temperature increases under the same temperature gradient increasing condition. Under the action of the thermal-hydraulic-mechanical coupling, unloading confining pressure obviously accelerated the yield process of the coal sample, and the confining capacity of confining pressure on transverse strain of the coal sample decreased. To prevent the occurrence of coal and gas outburst, it is necessary to take specific prevention measures according to the change law of triaxial compression mechanics of a raw coal specimen under the action of the thermal-hydraulic-mechanical coupling.
Single-cell Profiles and Prognostic Impact of Tumor-Infiltrating Lymphocytes Coexpressing CD39, CD103, and PD-1 in Ovarian Cancer
Authors: Laumont Céline M. , Wouters Maartje C.A. , Smazynski Julian , Gierc Nicole S. , Chavez Elizabeth A. , Chong Lauren C. , Thornton Shelby , Milne Katy , Webb John R. , Steidl Christian , Nelson Brad H.
Published: May 2021

Purpose:

Tumor-infiltrating lymphocytes (TIL) are strongly associated with survival in most cancers; however, the tumor-reactive subset that drives this prognostic effect remains poorly defined. CD39, CD103, and PD-1 have been independently proposed as markers of tumor-reactive CD8+ TIL in various cancers. We evaluated the phenotype, clonality, and prognostic significance of TIL expressing various combinations of these markers in high-grade serous ovarian cancer (HGSC), a malignancy in need of more effective immunotherapeutic approaches.

Experimental Design:

Expression of CD39, CD103, PD-1, and other immune markers was assessed by high-dimensional flow cytometry, single-cell sequencing, and multiplex immunofluorescence of primary and matched pre/post-chemotherapy HGSC specimens.

Results:

Coexpression of CD39, CD103, and PD-1 (“triple-positive” phenotype) demarcated subsets of CD8+ TIL and CD4+ regulatory T cells (Treg) with a highly activated/exhausted phenotype. Triple-positive CD8+ TIL exhibited reduced T-cell receptor (TCR) diversity and expressed genes involved in both cytolytic and humoral immunity. Triple-positive Tregs exhibited higher TCR diversity and a tumor-resident phenotype. Triple-positive TIL showed superior prognostic impact relative to TIL expressing other combinations of these markers. TIGIT was uniquely upregulated on triple-positive CD8+ effector cells relative to their CD4+ Treg counterparts.

Conclusions:

Coexpression of CD39, CD103, and PD-1 demarcates highly activated CD8+ and CD4+ TIL with inferred roles in cytolytic, humoral, and regulatory immune functions. Triple-positive TIL demonstrate exceptional prognostic significance and express compelling targets for combination immunotherapy, including PD-1, CD39, and TIGIT.
Intrahepatic Cholangiocarcinoma with Lymph Node Metastasis: Treatment-Related Outcomes and the Role of Tumor Genomics in Patient Selection
Authors: Jolissaint Joshua S. , Soares Kevin C. , Seier Kenneth P. , Kundra Ritika , Gönen Mithat , Shin Paul J. , Boerner Thomas , Sigel Carlie , Madupuri Ramyasree , Vakiani Efsevia , Cercek Andrea , Harding James J. , Kemeny Nancy E. , Connell Louise C. , Balachandran Vinod P. , D'Angelica Michael I. , Drebin Jeffrey A. , Kingham T. Peter , Wei Alice C. , Jarnagin William R.
Published: May 2021

Purpose:

Lymph node metastasis (LNM) drastically reduces survival after resection of intrahepatic cholangiocarcinoma (IHC). Optimal treatment is ill defined, and it is unclear whether tumor mutational profiling can support treatment decisions.

Experimental Design:

Patients with liver-limited IHC with or without LNM treated with resection (N = 237), hepatic arterial infusion chemotherapy (HAIC; N = 196), or systemic chemotherapy alone (SYS; N = 140) at our institution between 2000 and 2018 were included. Genomic sequencing was analyzed to determine whether genetic alterations could stratify outcomes for patients with LNM.

Results:

For node-negative patients, resection was associated with the longest median overall survival [OS, 59.9 months; 95% confidence interval (CI), 47.2–74.31], followed by HAIC (24.9 months; 95% CI, 20.3–29.6), and SYS (13.7 months; 95% CI, 8.9–15.9; P < 0.001). There was no difference in survival for node-positive patients treated with resection (median OS, 19.7 months; 95% CI, 12.1–27.2) or HAIC (18.1 months; 95% CI, 14.1–26.6; P = 0.560); however, survival in both groups was greater than SYS (11.2 months; 95% CI, 14.1–26.6; P = 0.024). Node-positive patients with at least one high-risk genetic alteration (TP53 mutation, KRAS mutation, CDKN2A/B deletion) had worse survival compared to wild-type patients (median OS, 12.1 months; 95% CI, 5.7–21.5; P = 0.002), regardless of treatment. Conversely, there was no difference in survival for node-positive patients with IDH1/2 mutations compared to wild-type patients.

Conclusions:

There was no difference in OS for patients with node-positive IHC treated by resection versus HAIC, and both treatments had better survival than SYS alone. The presence of high-risk genetic alterations provides valuable prognostic information that may help guide treatment.
The CHA2DS2-VASc Score and Its Association with Long-Term Outcome in a Cardiac Resynchronization Therapy Population
Authors: Reitan Christian , Platonov Pyotr G. , Borgquist Rasmus
Published: May 2021

Background: Cardiac resynchronization therapy (CRT) is commonly used in patients with heart failure and left ventricular dyssynchrony. Several scoring systems have been tested in order to predict long-term outcome. Although intended for use in patients with atrial fibrillation, we sought to assess the performance of the CHA2DS2-VASc score in a CRT population. Methods: Data on 796 consecutive CRT patients were retrospectively gathered from hospital records and healthcare registries. CHA2DS2-VASc scores were calculated, as well as other stratification scores for comparison. The outcomes were crude mortality, time to first heart failure hospitalization, and a composite of the 2. CHA2DS2-VASc score was evaluated against the end points with survival analyses and compared to other risk stratification scores. Results: The CHA2DS2-VASc score was significantly correlated with both outcomes in univariable and multivariable analysis adjusting for other known predictors of CRT outcome (unadjusted HR 1.28, 95% CI 1.21–1.36 and HR 1.19, 95% CI 1.13–1.25 for the mortality and heart failure hospitalization end points, respectively). Its performance compared well to other validated scores for the mortality end point (Harrell’s C: 0.61, range for other scoring systems: 0.57–0.65), as well as the heart failure hospitalization end point (Harrell’s C: 0.57, range of other scoring systems: 0.58–0.62). It correlated to 5- and 10-year survival with an area under the curve of 0.63 and 0.73, respectively. Conclusion: When tested for association with outcome in a CRT population, the CHA2DS2-VASc score correlates to increased mortality and risk of heart failure hospitalization. It performs similarly to CRT-specific scores. However, the results of this study indicate that all tested scores should be used with caution in CRT patients.
Diagnosing Paraproteinemic Keratopathy: A Case Report
Authors: Mok Eugenie , Kam Ka Wai , Aldave Anthony J. , Young Alvin L.
Published: May 2021

A 65-year-old man presented with bilateral, painless, progressive blurring of vision over 9 years. Slit-lamp examination revealed bilateral subepithelial corneal opacities in clusters located at the mid-periphery. Anterior segment optical coherence tomography, in vivo confocal microscopy (IVCM), serum protein electrophoresis, and molecular genetic testing were performed to evaluate the cause of corneal opacities. Anterior segment optical coherence tomography revealed a band-like, hyperreflective lesion in the Bowman layer and anterior stroma of both corneas. IVCM revealed hyperreflective deposits in the epithelium, anterior stroma, and endothelium. Serum protein electrophoresis identified the presence of paraproteins (immunoglobulin kappa), and molecular genetic testing revealed absence of mutations in the transforming growth factor beta-induced gene (TGFBI) and collagen type XVII alpha 1 gene (COL17A1). The ocular diagnosis of paraproteinemic keratopathy eventually led to a systemic diagnosis of monoclonal gammopathy of undetermined significance by our hematologist/oncologist. Paraproteinemic keratopathy is a rare differential diagnosis in patients with bilateral corneal opacities and therefore may be misdiagnosed as corneal dystrophy or neglected as scars. In patients with bilateral corneal opacities of unknown cause, serological examination, adjunct anterior segment imaging, and molecular genetic testing play a role in establishing the diagnosis.
Dexmedetomidine Exerts Renal Protective Effect by Regulating the PGC-1α/STAT1/IRF-1 Axis
Authors: Song Ying-Chun , Liu Ran , Li Ru-Hong , Xu Fei
Published: May 2021

Background: Ischemia-reperfusion (I/R) injury is the main cause of acute kidney injury (AKI), and its incidence and mortality increase year by year in the population. Dexmedetomidine (DEX) can improve AKI by regulating inflammation and oxidative stress, but its mechanism is still unclear. Methods: A hypoxia/reoxygenation (H/R) model of HK-2 cells and a kidney I/R model of C57BL/6J mice were established. In the experiment, cells were transfected with sh-PGC-1α to inhibit PGC-1α expression. The changes of ROS level and mitochondrial membrane potential (MMP) were analyzed. HE staining was used to assess kidney damage in mice. Concentration of kidney injury markers serum creatinine and blood urea nitrogen and expression of inflammatory factors were detected by ELISA. qPCR analysis was used to detect mRNA levels of related proteins in cells and mouse kidney tissues. The protein intracellular content and phosphorylation levels were determined by Western blotting. Result: The production of inflammatory factors and ROS was increased in HK-2 cells treated with H/R, while MMP, cell viability, and mitochondrial-related protein levels were decreased. DEX attenuated pathological changes induced by H/R, while knockdown of PGC-1α eliminated the mitigation effect. DEX inhibited the damage of I/R to the kidneys of mice and increased the expression of mitochondrial-related proteins and PGC-1α in the kidneys, while inhibiting the phosphorylation of STAT1 and the expression of IRF-1. Conclusions: DEX appears to inhibit mitochondrial damage and cellular inflammation by upregulating PGC-1α to affect STAT1 phosphorylation level and IRF-1 expression, thereby preventing AKI.
Noninvasive Home Mechanical Ventilation in Adult Myotonic Dystrophy Type 1: A Systematic Review
Authors: Vosse Bettine A. H. , Seijger Charlotte , Cobben Nicolle , van Engelen Baziel , van Kuijk Sander M. J. , Faber Catharina , Wijkstra Peter
Published: May 2021

Introduction: Chronic hypercapnic respiratory failure induces considerable morbidity and mortality in patients with myotonic dystrophy type 1 (DM1). This study systematically reviews the effects of noninvasive home mechanical ventilation (HMV) on gas exchange, quality of life, survival, and compliance in DM1 patients. Methods: A systematic Medline and Embase search was performed (January 1995 to January 2020). Records were screened for eligibility criteria, data were extracted from included studies, and risk of bias was assessed. We present findings mainly using a narrative synthesis. Results: Twenty-eight relevant full-text articles were screened for eligibility criteria. Nine studies were included. Randomized controlled trials were not found. Studies had either an observational (n = 8) or interventional (n = 1) design. In the pooled data analysis, HMV showed to improve mean oxygen saturation with 4.8% and decreased mean carbon dioxide values with 3 mm Hg. Compliance varied widely between studies, from no use to more than 12 h per day. Quality of life was not studied extensively, but some studies reported positive effects of HMV on symptoms of chronic respiratory failure. HMV may improve survival in DM1 patients with chronic hypercapnic respiratory failure. Conclusion: This review shows that HMV can improve gas exchange and relieve symptoms with a possible survival benefit in DM1 patients with chronic hypercapnic respiratory failure. Future studies should focus on developing strategies to optimize the timing of HMV initiation and to promote compliance.
Long-Term Outcomes of Patients with Hydrocephalus Secondary to Tectal Plate Glioma versus Idiopathic Aqueductal Stenosis: Results from a Single Center
Authors: Niknejad Hamid Reza , Frederickx Melissa , Salaets Emiel , Lemiere Jurgen , Lagae Lieven , Van Calenbergh Frank
Published: May 2021

Introduction: Tectal plate gliomas (TPG) constitute a distinct entity of benign tumors of the brain stem which show an indolent clinical course. Adequate treatment of secondary hydrocephalus is undoubtedly a major factor in the outcome. However, little is known about to what degree the tumor itself determines the long-term outcome of these patients. Methods: We retrospectively analyzed and compared the clinical and radiological data of 16 pediatric TPG patients with data of 12 pediatric idiopathic aqueductal stenosis (IAS) patients treated in our center from 1988 to 2018. For both groups, we assessed the long-term outcome in terms of hydrocephalus management, and for the TPG group, we assessed tumor growth during follow-up. In a separate prospective part of the study, we performed a neuropsychological evaluation in a subgroup of patients using a standardized testing battery, covering intelligence, learning, memory, executive functions, and an inventory on depression. Results: In the TPG group, the mean clinical and radiological follow-up was 84 and 70 months, respectively. On average, the maximum diameter of the tumor increased by 11% (p = 0.031) and the estimated tumor volume with 35% (p = 0.026) on radiological follow-up. The fronto-occipital horn ratio (FOHR) decreased by 23% on average after treatment. In the IAS group, the mean clinical and radiological follow-up was 117 and 85 months, respectively. In this group, the FOHR decreased by 21% on average. Neurocognitive testing revealed significant higher scores in the TPG group on global intelligence (TPG = 109, IAS = 85.5, U = 3, p < 0.01, z = −2.71), performance (TPG= 100, IAS = 85, U = 7, p = 0.03, z = −2.2), and verbal intelligence (TPG = 122, IAS = 91.5, U = 2, p < 0.00, z = −2.87) as well as working memory (TPG = 109.5, IAS = 77, U = 0.5, p = 0.01, z = −2.46). Conclusion: Our results suggest that the long-term outcome in TPG patients is acceptable and that cognition is substantially better preserved than in patients with IAS. This puts the idea of a significant contribution of the tumoral mass to disease outcome on the long term in question. Adequate and prompt management of hydrocephalus is the most important factor in long-term cognitive outcome.
MiR-182 Promotes Ischemia/Reperfusion-Induced Acute Kidney Injury in Rat by Targeting FoxO3
Authors: Du Yang , Ning Jin-zhuo
Published: May 2021

Background: Renal ischemia/reperfusion (I/R) injury (RIRI) is the main cause of acute kidney injury (AKI) in patients. We investigated the role of miR-182 after renal ischemia/reperfusion (I/R) in rat to characterize the microRNA (miRNA) network activated during development and recovery from RIRI. Methods and Results: 12 h after lethal (45 min) renal ischemia, AKI was verified by renal histology (tubular necrosis and regeneration), blood urea nitrogen level, and renal mRNA expression in Wistar rats. We found that miR-182 markedly increased after renal I/R. In cell hypoxia/reoxygenation model, we found similar upregulation of miR-182. In function gain/loss assay, we confirmed an impaired effect of miR-182 and identified Forkhead box O3 (FoxO3) as a direct downstream target of it. By using miR-182 antagomir, the I/R injury was markedly ameliorated. Conclusions: Our results demonstrate that miR-182 promotes cell apoptosis and I/R injury through directly binding to FoxO3. The present study will provide potential therapeutic targets for renal I/R-induced AKI, and open a new avenue for AKI treatment by manipulating miRNAs levels.
68Ga-Prostate-Specific Membrane Antigen Positron Emission Tomography-Computed Tomography-Based Primary Staging and Histological Correlation after Extended Pelvic Lymph Node Dissection in Intermediate-Risk Prostate Cancer
Authors: Kopp Daniela , Kopp Johannes , Bernhardt Eugen , Manka Lukas , Beck Andreas , Gerullis Holger , Karakiewicz Pierre I. , Salomon Georg , Wiggermann Philipp , Hammerer Peter , Schiffmann Jonas
Published: May 2021

Objective: The objective of this study is to evaluate prostate-specific membrane antigen positron emission tomography-computed tomography (PSMA PET/CT)-based primary staging in exclusively D′Amico intermediate-risk prostate cancer (PCa) patients. Patients and Methods: We relied on the Braunschweig institutional database and retrospectively identified D′Amico intermediate-risk PCa patients who were administered to 68Ga-PSMA PET/CT-based primary staging prior to consecutive radical prostatectomy and extended lymph node dissection. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for the detection of lymph node metastases were analyzed per-patient (n = 39), per-pelvic side (n = 78), and per-anatomic-region (external iliac artery and vein left/right vs. obturator fossa left/right vs. internal iliac artery left/right) (n = 203), respectively. Results: Sensitivity, specificity, PPV, and NPV per-patient were 20.0, 94.1, 33.3, and 88.9%, respectively. Sensitivity, specificity, PPV, and NPV per-pelvic-side were 16.7, 97.2, 33.3, and 93.3%, respectively. Sensitivity, specificity, PPV, and NPV per-anatomic-region were 16.7, 99.0, 33.3, and 97.5%, respectively. Conclusions: We recorded high rates of specificity and NPV for 68Ga-PSMA PET/CT-based primary staging in D′Amico intermediate-risk PCa patients. Conversely, the sensitivity and PPV were lower than anticipated. Larger and favorably prospective trials are needed to verify our results and to unravel possible bias from such smaller studies.
Assessing the Possible Influence of Residues of Ractopamine, a Livestock Feed Additive, in Meat on Alzheimer Disease
Authors: Fan Frank S.
Published: May 2021

The feed additive ractopamine, a β-adrenergic agonist, has been approved for use in livestock for nearly 2 decades. Studies of its possible adverse effects in humans have concentrated exclusively on cardiovascular disease and cardiovascular functional disorders in the past. In this article, whether and how ractopamine may affect neurodegeneration, either to promote or to reduce the incidence of Alz­heimer disease, will be discussed based on the recent controversial findings that β-adrenoreceptor activation not only can stimulate Alzheimer-pathogenic amyloid-β accumulation but also are able to enhance hippocampal neurogenesis and ameliorate mouse memory deficits in independent laboratory studies. Furthermore, environmental enrichment has been found to prevent impairment of memory-related hippocampal long-term potentiation and microglia-mediated neuroinflammation induced by amyloid-β. These beneficial effects are achieved mainly through enhanced β-adrenergic signaling and can be imitated by β agonist isoprotenerol. Finally, it has been demonstrated that the β-adrenergic agonist salbutamol could bind directly to tau protein and interfere with the tau filament formation seen in the prodromal phase of Alzheimer disease. These complex but interesting issues lead to contradictory speculations of possible effects of ractopamine residue in meat on Alzheimer disease. Hypotheses derived from this review surely deserve carefully designed laboratory investigations and clinical studies in the future.
Antibiotic Use and Risk of Multiple Sclerosis: A Nested Case-Control Study in Emilia-Romagna Region, Italy
Authors: Baldin Elisa , Zenesini Corrado , Antonazzo Ippazio Cosimo , Bartolomei Ilaria , Caniatti Luisa , Costa Manuela , Curti Erika , Ferraro Diana , Foschi Matteo , Granella Franco , Guareschi Angelica , Immovilli Paolo , Lugaresi Alessandra , Malagù Susanna , Mancinelli Luca , Montepietra Sara , Mussuto Vittoria , Neri Walter , Pasquinelli Marco , Pellegrino Lisa , Pesci Ilaria , Poluzzi Elisabetta , Pugliatti Maura , Ravasio Alessandro , Riise Trond , Salvi Fabrizio , Santangelo Mario , Sireci Francesca , Sola Patrizia , Strumia Silvia , Tsantes Elena , Vignatelli Luca , Vitetta Francesca , Viti Beatrice , D’Alessandro Roberto ,   on behalf of AS_MS_Risk Group
Published: May 2021

Introduction: Known risk factors for multiple sclerosis (MS) include smoking, a low vitamin D status, obesity, and EBV, while the inflammatory feature of the disease strongly suggests the presence of additional infectious agents. The association between use of antibiotics and MS risk that could shed light on these factors is still undetermined. We aimed to evaluate the association between antibiotics and MS risk, in the Emilia-Romagna region (RER), Italy. Methods: All adult patients with MS seen at any RER MS center (2015–2017) were eligible. For each of the 877 patients included, clinical information was collected and matched to 5 controls (RER residents) (n = 4,205) based on age, sex, place of residence, and index year. Information on antibiotic prescription was obtained through the linkage with the RER drug prescription database. Results: Exposure to any antibiotic 3 years prior to the index year was associated with an increased MS risk (OR = 1.52; 95% CI = 1.29–1.79). Similar results were found for different classes. No dose-response effect was found. Discussion/Conclusions: Our results suggest an association between the use of antibiotics and MS risk in RER population. However, further epidemiological studies should be done with information on early life and lifestyle factors.
Podocytic Infolding Glomerulopathy in a Patient with Phospholipase A2 Receptor-Positive Membranous Nephropathy and Review of the Literature
Authors: Pandit Amar P. , Rennke Helmut G. , Denker Bradley M.
Published: May 2021

Podocytic infolding glomerulopathy (PIG) is a rare diagnosis based on characteristic histopathologic findings on renal biopsy and was proposed as a new entity about a decade ago. It is a type of podocytic injury, characterized by invagination of the podocyte cell membrane (cytoplasmic projections from podocytes) into the glomerular basement membrane. The presence of microspheres and/or microtubules on electron microscopy is the characteristic finding. PIG is most often associated with autoimmune conditions like systemic lupus erythematosus. We report pathologic findings typical of PIG in a patient with phospholipase A2 receptor antibody-positive membranous nephropathy. She was treated with rituximab and responded well with decrease in proteinuria to the sub-nephrotic range.
Effect of Delayed Cord Clamping on Neurodevelopment at 3 Years: A Randomized Controlled Trial
Authors: Berg Johan Henrik Martin , Isacson Manuela , Basnet Omkar , Gurung Rejina , Subedi Kalpana , KC Ashish , Andersson Ola
Published: May 2021

Introduction: Iron deficiency (ID) is associated with poor neurodevelopment. We have previously shown that delayed umbilical cord clamping (CC) improves iron stores at 8 months and neurodevelopment at 1 year in term, healthy infants in Nepal. Objective: The aim of this study was to assess the effects of delayed CC (≥180 s) compared to early CC (≤60 s) on neurodevelopment using the Ages and Stages Questionnaire (ASQ) at age 3 years. Methods: In 2014, 540 healthy Nepalese infants born at term were randomized in a 1:1 ratio to delayed or early CC. At 3 years of age, ASQ assessment was performed by phone interviews with parents. A score >1 standard deviation below the mean was defined as “at risk” for developmental impairment. Results: At 3 years of age, 350 children were followed up, 170 (63.0%) in the early CC group and 180 (66.7%) in the delayed CC group. No significant differences in ASQ scores in any domains between groups were found. However, more girls were “at risk” for affected gross motor development in the early CC group: 14 (18.9%) versus 6 (6.3%), p = 0.02. Conclusion: There were no significant differences in ASQ scores in any domains between groups. In the subgroup analysis, fewer girls who underwent delayed CC were “at risk” for delayed gross motor development. Due to the pronounced difference in iron stores at 8 months postpartum in this cohort, follow-up studies at an older age are motivated since neurodevelopmental impairment after early ID may be more detectable with increasing age.
Pediatric Intrathecal Baclofen Pumps: A Descriptive Analysis of Hospital Course and Associated Costs
Authors: Dallas Jonathan , Naftel Robert P. , Shannon Chevis N.
Published: May 2021

Introduction: The purpose of this study was to identify predictors of increased cost and postoperative length-of-stay (LOS) following intrathecal baclofen pump (ITBP) placement. Methods: Patients were derived from the 2009/2012 kids’ inpatient database. Inclusion criteria were selected for patients with ICD-9 codes 343.X (infantile cerebral palsy), 86.06 (infusion pump insertion), 03.90 (spinal catheter insertion), and elective hospitalizations. Nonparametric univariate analysis and subsequent gamma log-link general linear modeling were used to identify significant predictors of cost/LOS (p < 0.05). Results: 529 unweighted patients (787 with survey weights applied) met criteria. Median LOS was 3.00 days, and median cost was USD 23,284. Following multivariate modeling, predictors of increased LOS (in days) included increased hospital ITBP volume (p = 0.027), small hospital size (+0.55, p = 0.004), device complications (+0.95, p < 0.001), procedural complications (+1.40, p < 0.001), additional procedures (+0.86, p < 0.001), electrolyte abnormalities (+3.74, p < 0.001), and neurological comorbidities (+1.60, p < 0.001). Factors associated with decreased LOS were paralysis (−0.53, p < 0.001), Northeastern hospital region (−0.55, p = 0.018), and investor-owned hospital status (−0.75, p = 0.001). Similarly, predictors of increased cost included race of Hispanic (+USD 1,156, p = 0.033) or “other” (+USD 2,158, p = 0.001), Northeast hospital region (+USD 4,120, p < 0.001), small (+USD 4,139, p < 0.001) or medium (+USD 3,368, p < 0.001) hospital sizes, additional procedures (+USD 1,649, p < 0.001), neurological comorbidities (+USD 3,222, p = 0.003), and increased LOS (p < 0.001). Factors associated with decreased cost included Western hospital region (–USD 1,594, p = 0.001), government hospitals (–USD 1,391, p = 0.019), and investor-owned hospitals (–USD 2,057, p = 0.021). Conclusion: This study found multiple variables associated with increased cost/LOS following ITBP placement. Broadly, this analysis demonstrates national trends associated with increased cost following ITBP placement.
Plasma Amino Acids and Risk of Impaired Lower-Extremity Function and Role of Dietary Intake: A Nested Case-Control Study in Older Adults
Authors: Caballero Francisco Félix , Struijk Ellen A. , Buño Antonio , Vega-Cabello Verónica , Rodríguez-Artalejo Fernando , Lopez-Garcia Esther
Published: May 2021

Introduction: Amino acids are key elements in the regulation of the aging process which entails a progressive loss of muscle mass. The health effects of plasma amino acids can be influenced by dietary intake. This study assessed the prospective association between amino acid species and impaired lower-extremity function (ILEF) in older adults, exploring the role of diet on this association. Methods: This is a case-control design comprising 43 incident cases of ILEF and 85 age- and sex-matched controls. Plasma concentrations of 20 amino acid species were measured at baseline using liquid chromatography-tandem mass spectrometry, and incident cases of ILEF were measured after 2 years by means of the Short Physical Performance Battery. Conditional logistic regression models were used to assess longitudinal relationships. Results: After adjusting for potential confounders, higher levels of tryptophan were associated with a decreased 2-year risk of ILEF (OR per 1-SD increase = 0.64, 95% CI = [0.42, 0.97]), while glutamine and total essential amino acids were linked to higher ILEF risk (OR = 1.57, 95% CI = [1.01, 2.45]; OR = 1.89, 95% CI = [1.18, 3.03], respectively). Those with a lower adherence to a Mediterranean diet, a higher BMI, a higher consumption of red meat, and a lower consumption of nuts and legumes had an increased risk of ILEF associated with higher levels of essential amino acids. Discussion/Conclusion: Some amino acid species could serve as risk markers for physical function decline in older adults, and healthy diet might attenuate the excess risk of ILEF linked to essential amino acids.