bluuebunny/crossref_metadata_2025 huggingface dataset:
Spatial data systems support for the internet of things
Authors: Sarwat Mohamed
Published: October 2020

The Internet of Things (IoT) has recently received significant attention. An IoT device may possess an array of sensors that for example monitors the air temperature, carbon monoxide level, wifi signals, and sound intensity. IoT data is initially created on the device, then sent over to a central database system (e.g., the cloud) that organizes and prepares such data for the ongoing use by myriad applications, which include but are not limited to smart home, smart city, the industrial internet, connected cars, and connected health. Data generated by IoT devices is inherently spatial and temporal. For instance, an audio signal represents the variation of the sound intensity (retrieved by a sound sensor) over the time dimension. Furthermore, IoT devices are either installed in a static location (e.g., a building, a traffic intersection) or can be attached to moving objects such as a connected vehicle or a wearable device. In this article, we argue that existing IoT data systems do not properly consider the SpatioTemporal aspect of such data. Hence, the article represents a call for action to the SIGSPATIAL community in order to conduct research on building systems and applications that treat both the spatial and temporal dimensions of IoT data as first class citizens.
GPR40 deficiency is associated with hepatic FAT/CD36 upregulation, steatosis, inflammation, and cell injury in C57BL/6 mice
Authors: Lu Zhongyang , Li Yanchun , Syn Wing-Kin , Li Ai-Jun , Ritter W. Sue , Wank Stephen A. , Lopes-Virella Maria F. , Huang Yan
Published: October 2020

G-protein-coupled receptor 40 (GPR40) is highly expressed in pancreatic islets, and its activation increases glucose-stimulated insulin secretion from pancreas. Therefore, GPR40 is considered as a target for type 2 diabetes mellitus (T2DM). Since nonalcoholic fatty liver disease (NAFLD) is associated with T2DM and GPR40 is also expressed by hepatocytes and macrophages, it is important to understand the role of GPR40 in NAFLD. However, the role of GPR40 in NAFLD in animal models has not been well defined. In this study, we fed wild-type or GPR40 knockout C57BL/6 mice a high-fat diet (HFD) for 20 wk and then assessed the effect of GPR40 deficiency on HFD-induced NAFLD. Assays on metabolic parameters showed that an HFD increased body weight, glucose, insulin, insulin resistance, cholesterol, and alanine aminotransferase (ALT), and GPR40 deficiency did not mitigate the HFD-induced metabolic abnormalities. In contrast, we found that GPR40 deficiency was associated with increased body weight, insulin, insulin resistance, cholesterol, and ALT in control mice fed a low-fat diet (LFD). Surprisingly, histology and Oil Red O staining showed that GPR40 deficiency in LFD-fed mice was associated with steatosis. Immunohistochemical analysis showed that GPR40 deficiency also increased F4/80, a macrophage biomarker, in LFD-fed mice. Furthermore, results showed that GPR40 deficiency led to a robust upregulation of hepatic fatty acid translocase (FAT)/CD36 expression. Finally, our in vitro studies showed that GPR40 knockdown by siRNA or a GPR40 antagonist increased palmitic acid-induced FAT/CD36 mRNA in hepatocytes. Taken together, this study indicates that GPR40 plays an important role in homeostasis of hepatic metabolism and inflammation and inhibits nonalcoholic steatohepatitis by possible modulation of FAT/CD36 expression.
Effect of hypoxic exercise on glucose tolerance in healthy and prediabetic adults
Authors: De Groote Estelle , Britto Florian A. , Balan Estelle , Warnier Geoffrey , Thissen Jean-Paul , Nielens Henri , Sylow Lykke , Deldicque Louise
Published: October 2020

The molecular mechanisms involved in glucose tolerance after acute exercise in hypoxia have not yet been elucidated in human. Due to the reversible character of their status, prediabetic individuals are of particular interest for preventing the development of type 2 diabetes. The present study is the first to investigate muscle molecular mechanisms during exercise and glucose metabolism after exercise in prediabetic and healthy subjects exercising in normoxia and normobaric hypoxia.
Holistic characterization of single-hepatocyte transcriptome responses to high-fat diet
Authors: Park Sung Rye , Cho Chun-Seok , Xi Jingyue , Kang Hyun Min , Lee Jun Hee
Published: October 2020

During nutritional overload and obesity, hepatocyte function is grossly altered, and a subset of hepatocytes begins to accumulate fat droplets, leading to nonalcoholic fatty liver disease (NAFLD). Recent single-cell studies revealed how nonparenchymal cells, such as macrophages, hepatic stellate cells, and endothelial cells, heterogeneously respond to NAFLD. However, it remains to be characterized how hepatocytes, the major constituents of the liver, respond to nutritional overload in NAFLD. Here, using droplet-based, single-cell RNA sequencing (Drop-seq), we characterized how the transcriptomic landscape of individual hepatocytes is altered in response to high-fat diet (HFD) and NAFLD. We showed that the entire hepatocyte population undergoes substantial transcriptome changes upon HFD, although the patterns of alteration were highly heterogeneous, with zonation-dependent and -independent effects. Periportal (zone 1) hepatocytes downregulated many zone 1-specific marker genes, whereas a small number of genes mediating gluconeogenesis were upregulated. Pericentral (zone 3) hepatocytes also downregulated many zone 3-specific genes; however, they upregulated several genes that promote HFD-induced fat droplet formation, consistent with findings that zone 3 hepatocytes accumulate more lipid droplets. Zone 3 hepatocytes also upregulated ketogenic pathways as an adaptive mechanism to HFD. Interestingly, many of the top HFD-induced genes, which encode proteins regulating lipid metabolism, were strongly co-expressed with each other in a subset of hepatocytes, producing a variegated pattern of spatial co-localization that is independent of metabolic zonation. In conclusion, our data set provides a useful resource for understanding hepatocellular alteration during NAFLD at single cell level.
Histone deacetylase 6 inhibition mitigates renal fibrosis by suppressing TGF-β and EGFR signaling pathways in obstructive nephropathy
Authors: Chen Xingying , Yu Chao , Hou Xiying , Li Jialu , Li Tingting , Qiu Andong , Liu Na , Zhuang Shougang
Published: October 2020

We have recently shown that histone deacetylase 6 (HDAC6) is critically involved in the pathogenesis of acute kidney injury. Its role in renal fibrosis, however, remains unclear. In this study, we examined the effect of ricolinostat (ACY-1215), a selective inhibitor of HDAC6, on the development of renal fibrosis in a murine model induced by unilateral ureteral obstruction (UUO). HDAC6 was highly expressed in the kidney following UUO injury, which was coincident with deposition of collagen fibrils and expression of α-smooth muscle actin, fibronectin, and collagen type III. Administration of ACY-1215 reduced these fibrotic changes and inhibited UUO-induced expression of transforming growth factor-β1 and phosphorylation of Smad3 while increasing expression of Smad7. ACY-1215 treatment also suppressed phosphorylation of epidermal growth factor receptor (EGFR) and several signaling molecules associated with renal fibrogenesis, including AKT, STAT3, and NF-κB in the injured kidney. Furthermore, ACY-1215 was effective in inhibiting dedifferentiation of renal fibroblasts to myofibroblasts and the fibrotic change of renal tubular epithelial cells in culture. Collectively, these results indicate that HDAC6 inhibition can attenuate development of renal fibrosis by suppression of transforming growth factor-β1 and EGFR signaling and suggest that HDAC6 would be a potential therapeutic target for the treatment of renal fibrosis.
Renal lymphatic vessel dynamics
Authors: Shelton Elaine L. , Yang Hai-Chun , Zhong Jianyong , Salzman Michele M. , Kon Valentina
Published: October 2020

Similar to other organs, renal lymphatics remove excess fluid, solutes, and macromolecules from the renal interstitium. Given the kidney’s unique role in maintaining body fluid homeostasis, renal lymphatics may be critical in this process. However, little is known regarding the pathways involved in renal lymphatic vessel function, and there are no studies on the effects of drugs targeting impaired interstitial clearance, such as diuretics. Using pressure myography, we showed that renal lymphatic collecting vessels are sensitive to changes in transmural pressure and have an optimal range of effective pumping. In addition, they are responsive to vasoactive factors known to regulate tone in other lymphatic vessels including prostaglandin E2and nitric oxide, and their spontaneous contractility requires Ca2+and Cl−. We also demonstrated that Na+-K+-2Cl−cotransporter Nkcc1, but not Nkcc2, is expressed in extrarenal lymphatic vessels. Furosemide, a loop diuretic that inhibits Na+-K+-2Cl−cotransporters, induced a dose-dependent dilation in lymphatic vessels and decreased the magnitude and frequency of spontaneous contractions, thereby reducing the ability of these vessels to propel lymph. Ethacrynic acid, another loop diuretic, had no effect on vessel tone. These data represent a significant step forward in our understanding of the mechanisms underlying renal lymphatic vessel function and highlight potential off-target effects of furosemide that may exacerbate fluid accumulation in edema-forming conditions.
Extended Spectrum β-Lactamase-Mediated Resistance and Antibiogram of Pseudomonas aeruginosa Isolates from Patients Attending Two Public Hospitals in Khartoum, Sudan
Authors: Omer Thweaba Hassan Salih , Mustafa Samia Ali Mohammed , Mohamed Sagad Omer Obeid
Published: October 2020

Treating infections caused by Pseudomonas aeruginosa is challenging. In addition to its intrinsic ability to develop resistance to multiple classes of antibiotics, it also produces extended-spectrum β-lactamase (ESBL). Continuous update of the antibiograms is required to cope with the rate of the emergence of antibiotic resistance. This study aimed to determine the antimicrobial susceptibility pattern and to determine the frequency of ESBL production among the P. aeruginosa isolates from patients at two public military hospitals in Khartoum, Sudan. A total of 34 isolates of P. aeruginosa obtained from patients with diabetic septic foot wounds were tested for their antibiotic sensitivity patterns. Resistance occurred most commonly to ceftazidime (35%), followed by ciprofloxacin (20.6%) and piperacillin (14.7%). We found that 17.6% of the P. aeruginosa isolates were ESBL producers, but all of these isolates were sensitive to meropenem. The chi-squared test showed a significant association between the ESBL production and antimicrobial resistance to amikacin, ceftazidime, and piperacillin. Our findings strengthen previous reports in which aminoglycosides (amikacin) and carbapenems (meropenem) were found to be highly effective against P. aeruginosa. Our findings highlight the need for effective surveillance and antibiogram-guided antibiotic prescription.
Outer-Convex Dominating Set in the Corona of Graphs as Encryption Key Generator
Authors: Shao Zehui , Kosari S. , Anoos R. , Sheikholeslami S. M. , Dayap J. A.
Published: October 2020

In this paper, we present a new type of symmetric encryption by converting the classical monoalphabetic affine cipher into a polyalphabetic cipher. The proposed encryption utilizes the properties of outer-convex dominating set in the corona of graphs to generate random keys from the shared keyword to every character of the message. The new encryption eliminates the weaknesses of affine cipher, thus increasing the level of confidence for exchanging messages.
SLR-SELinux: Enhancing the Security Footstone of SEAndroid with Security Label Randomization
Authors: Ding Yan , Dong Pan , Li Zhipeng , Tan Yusong , Huang Chenlin , Wei Lifeng , Zuo Yudan
Published: October 2020

The root privilege escalation attack is extremely destructive to the security of the Android system. SEAndroid implements mandatory access control to the system through the SELinux security policy at the kernel mode, making the general root privilege escalation attacks unenforceable. However, malicious attackers can exploit the Linux kernel vulnerability of privilege escalation to modify the SELinux security labels of the process arbitrarily to obtain the desired permissions and undermine system security. Therefore, investigating the protection method of the security labels in the SELinux kernel is urgent. And the impact on the existing security configuration of the system must also be reduced. This paper proposes an optimization scheme of the SELinux mechanism based on security label randomization to solve the aforementioned problem. At the system runtime, the system randomizes the mapping of the security labels inside and outside the kernel to protect the privileged security labels of the system from illegal obtainment and tampering by attackers. This method is transparent to users; therefore, users do not need to modify the existing system security configuration. A tamper-proof detection method of SELinux security label is also proposed to further improve the security of the method. It detects and corrects the malicious tampering behaviors of the security label in the critical process of the system timely. The above methods are implemented in the Linux system, and the effectiveness of security defense is proven through theoretical analysis and experimental verification. Numerous experiments show that the effect of this method on system performance is less than 1%, and the success probability of root privilege escalation attack is less than 10−9.
Security Measurement in Industrial IoT with Cloud Computing Perspective: Taxonomy, Issues, and Future Directions
Authors: Shah Sahar , Khan Mahnoor , Almogren Ahmad , Ali Ihsan , Deng Lianwen , Luo Heng , Khan Muazzam A.
Published: October 2020

In recent years, cloud computing has gained massive popularity in information technology and the industrial Internet of things. It provides facilities to the users over the wireless channel. Many surveys have been carried out in cloud security and privacy. The existing survey papers do not specify the classifications on the basis of cloud computing components. Therefore, they fail to provide the techniques with their specialities as well as the previously available literature review is outdated. This paper presents the security for cloud computing models with a new aspect. Unlike the previously existing surveys, the literature review of this paper includes the latest research papers in the field of cloud security. Also, different classifications are made for cloud computing security on the basis of different cloud components that are used to secure the cloud models. Furthermore, a total of eleven (11) classifications are considered, which includes cloud components to secure the cloud systems. These classifications help the researchers to find out the desired technique used in a specific component to secure the cloud model. Moreover, the shortcoming of each component enables the researchers to design an optimal algorithm. Finally, future directions are given to highlight future research challenges that give paths to researchers.
Angio-Based Index of Microcirculatory Resistance for the Assessment of the Coronary Resistance: A Proof of Concept Study
Authors: Tebaldi Matteo , Biscaglia Simone , Di Girolamo Domenico , Erriquez Andrea , Penzo Carlo , Tumscitz Carlo , Campo Gianluca
Published: October 2020

Background. The study of coronary microcirculation has gained increasing consideration and importance in cath lab. Despite the increase of evidence, its use still remains very limited. QFR is a novel angio-based approach for the evaluation of coronary stenosis. The aim of our study was to use the QFR assessment in stable patients to recreate the IMR formula and to correlate the result of the two techniques. Methods. From June 1, 2019, to February 29, 2019, 200 patients with CCS and indication of coronary artery angiography and referred to the cath lab of the University Hospital of Ferrara (Italy) were enrolled. After baseline coronary angiogram, quantitative flow ratio, fractional flow reserve, and index of microcirculatory resistance evaluation were performed. Results. Pearson correlation (r) between angio-based index of microcirculatory resistance (A-IMR) and IMR 0.32 with R2 = 0.098,

P
=
0.03

: McNemar test showed a difference between the two tests of 6.82% with 95% CI from –12.05% to 22.89%, which is not significant (

P
=
0.60

). Bland and Altman plot showed a mean difference of 23.3 (from −26.5 to 73.1). Sensitivity, specificity, NPV, and PPV were 70%, 83.3%, 75%, and 70% for A-IMR value >44.2. The area under the ROC curve for A-IMR was 0.76 (95% CI 0.61–0.88,

P
=
0.0003

). Conclusion. We have validated for the first time the formula of the A-IMR, a tool for the calculation of microvascular resistance which does not require the use of pressure guides and the induction of hyperemia.
Antibiotics Profile, Prevalence of Extended-Spectrum Beta-Lactamase (ESBL), and Multidrug-Resistant Enterobacteriaceae from Different Clinical Samples in Khartoum State, Sudan
Authors: Moglad Ehssan H.
Published: October 2020

One of the global requirements for controlling the occurrence of resistance to antimicrobial drugs is to understanding the resistivity profile of various clinical isolates. Therefore, this study aimed to deliver the indication of different resistant profiles of clinically isolated Enterobacteriaceae from different sources of samples from Khartoum state, Sudan, and to determine the prevalence rate of extended-spectrum beta-lactamase (ESBL), multidrug-resistant (MDR), extensively drug-resistant (XDR), and pandrug-resistant (PDR) bacteria. A total of 144 Gram-negative bacteria were collected from different sources (vaginal swab, urine, catheter tip, sputum, blood, tracheal aspirate, pus, stool, pleural fluid, and throat swab). Samples were subcultured and identified according to their cultural characteristics and biochemical tests. Antimicrobial susceptibility test was performed for twenty-four antibiotics from eleven categories against all isolated Enterobacteriaceae according to the recommendation of Clinical and Laboratory Standards Institute (CLSI). The result showed that out of 144 isolates, Escherichia coli and Klebsiella pneumoniae were predominant isolates with the percentage of 47.9 and 25%, respectively. The prevalence of ESBL was higher in K. pneumonia (38.9%) than E. coli (34.8%). All isolated E. coli were sensitive to nitrofurantoin and tigecycline. There was a high prevalence of MDR Enterobacteriaceae, and only one isolate was XDR, while PDR was zero for all isolated bacteria. Active antimicrobial-resistant (AMR) observation through constant data sharing and management of all stakeholders is crucial to recognize and control the AMR global burden. Also, effective antibiotic stewardship procedures would be applied to limit the unreasonable expenditure of antibiotics in Sudan.
STAT3-Mediated Astrocyte Reactivity Associated with Brain Metastasis Contributes to Neurovascular Dysfunction
Authors: Sarmiento Soto Manuel , Larkin James R. , Martin Chris , Khrapitchev Alexandre A. , Maczka Melissa , Economopoulos Vasiliki , Scott Helen , Escartin Carole , Bonvento Gilles , Serres Sébastien , Sibson Nicola R.
Published: October 2020

Astrocytes are thought to play a pivotal role in coupling neural activity and cerebral blood flow. However, it has been shown that astrocytes undergo morphologic changes in response to brain metastasis, switching to a reactive phenotype, which has the potential to significantly compromise cerebrovascular function and contribute to the neurological sequelae associated with brain metastasis. Given that STAT3 is a key regulator of astrocyte reactivity, we aimed here to determine the impact of STAT3-mediated astrocyte reactivity on neurovascular function in brain metastasis. Rat models of brain metastasis and ciliary neurotrophic factor were used to induce astrocyte reactivity. Multimodal imaging, electrophysiology, and IHC were performed to determine the relationship between reactive astrocytes and changes in the cerebrovascular response to electrical and physiological stimuli. Subsequently, the STAT3 pathway in astrocytes was inhibited with WP1066 to determine the role of STAT3-mediated astrocyte reactivity, specifically, in brain metastasis. Astrocyte reactivity associated with brain metastases impaired cerebrovascular responses to stimuli at both the cellular and functional level and disrupted astrocyte–endothelial interactions in both animal models and human brain metastasis samples. Inhibition of STAT3-mediated astrocyte reactivity in rats with brain metastases restored cerebrovascular function, as shown by in vivo imaging, and limited cerebrovascular changes associated with tumor growth. Together these findings suggest that inhibiting STAT3-mediated astrocyte reactivity may confer significant improvements in neurological outcome for patients with brain metastases and could potentially be tested in other brain tumors.

Significance:

These findings demonstrate that selectively targeting STAT3-mediated astrocyte reactivity ameliorates the cerebrovascular dysfunction associated with brain metastasis, providing a potential therapeutic avenue for improved patient outcome.
RNA sequencing and Immunohistochemistry Reveal ZFN7 as a Stronger Marker of Survival than Molecular Subtypes in G-CIMP–negative Glioblastoma
Authors: Esteve-Codina Anna , Alameda Francesc , Carrato Cristina , Pineda Estela , Arpí Oriol , Martinez-García Maria , Mallo Mar , Gut Marta , Dabad Marc , Tortosa Avelina , Del Barco Sonia , Capellades Jaume , Puig Josep , Gallego Oscar , Pujol Teresa , Oleaga Laura , Gil-Gil Miquel , de Quintana-Schmidt Cristian , Valduvieco Izaskun , Martinez-Cardús Anna , Bellosillo Beatriz , Muñoz-Marmol Ana Maria , Esteve Anna , Domenech Marta , Camins Angels , Craven-Bartle Jordi , Villa Salvador , Marruecos Jordi , Domenech Sira , de la Iglesia Nuria , Balana Carmen
Published: October 2020

Purpose:

Glioblastoma is the most aggressive brain tumor in adults and has few therapeutic options. The study of molecular subtype classifications may lead to improved prognostic classification and identification of new therapeutic targets. The Cancer Genome Atlas (TCGA) subtype classification has mainly been applied in U.S. clinical trials, while the intrinsic glioma subtype (IGS) has mainly been applied in European trials.

Experimental Design:

From paraffin-embedded tumor samples of 432 patients with uniformly treated, newly diagnosed glioblastoma, we built tissue microarrays for IHC analysis and applied RNA sequencing to the best samples to classify them according to TCGA and IGS subtypes.

Results:

We obtained transcriptomic results from 124 patients. There was a lack of agreement among the three TCGA classificatory algorithms employed, which was not solely attributable to intratumoral heterogeneity. There was overlapping of TCGA mesenchymal subtype with IGS cluster 23 and of TCGA classical subtype with IGS cluster 18. Molecular subtypes were not associated with prognosis, but levels of expression of 13 novel genes were identified as independent prognostic markers in glioma-CpG island methylator phenotype–negative patients, independently of clinical factors and MGMT methylation. These findings were validated in at least one external database. Three of the 13 genes were selected for IHC validation. In particular, high ZNF7 RNA expression and low ZNF7 protein expression were strongly associated with longer survival, independently of molecular subtypes.

Conclusions:

TCGA and IGS molecular classifications of glioblastoma have no higher prognostic value than individual genes and should be refined before being applied to clinical trials.
Cellular Functions of HPV16 E5 Oncoprotein during Oncogenic Transformation
Authors: Gutierrez-Xicotencatl Lourdes , Pedroza-Saavedra Adolfo , Chihu-Amparan Lilia , Salazar-Piña Azucena , Maldonado-Gama Minerva , Esquivel-Guadarrama Fernando
Published: October 2020

The human papillomavirus (HPV) is recognized as the main etiologic agent associated with cervical cancer. HPVs are epitheliotropic, and the ones that infect the mucous membranes are classified into low-risk (LR) and high-risk (HR) types. LR-HPVs produce benign lesions, whereas HR-HPVs produce lesions that may progress to cancer. HR-HPV types 16 and 18 are the most frequently found in cervical cancer worldwide. E6 and E7 are the major HPV oncogenic proteins, and they have been profusely studied. Moreover, it has been shown that the HPV16 E5 (16E5) oncoprotein generates transformation, although the molecular mechanisms through which it carries out its activity have not been well defined. In contrast to E6 and E7, the E5 open reading frame is lost during the integration of the episomal HPV DNA into the cellular genome. This suggests that E5 acts at the early stages of the transformation process. In this review, we focused on the biochemical characteristics and functions of the HPV E5 oncoprotein, mainly on its association with growth factor receptors and other cellular proteins. Knowledge of the HPV E5 biology is important to understand the role of this oncoprotein in maintaining the viral cycle through the modulation of proliferation, differentiation, and apoptosis, as well as the alteration of other processes, such as survival, adhesion, migration, and invasion during early carcinogenesis. Finally, we summarized recent research that uses the E5 oncoprotein as a therapeutic target, promising a novel approach to the treatment of cervical cancer in its early stages.
Circulating Long Noncoding RNA HOTAIR is an Essential Mediator of Acute Myocardial Infarction
Authors: Gao Lu , Liu Yuan , Guo Sen , Yao Rui , Wu Leiming , Xiao Lili , Wang Zheng , Liu Yuzhou , Zhang Yanzhou
Published: October 2020

Background/Aims: Acute myocardial infarction (AMI) is one of the leading causes of death in the world. However, specific diagnostic biomarkers have not been fully determined, and candidate regulatory targets for AMI have not been identified to date. Long noncoding RNAs (lncRNAs) are a class of RNA molecules that have diverse regulatory functions during embryonic development, normal life, and disease in higher organisms. However, research on the role of lncRNAs in cardiovascular diseases, particularly AMI, is still in its infancy. HOX antisense intergenic RNA (HOTAIR), a 2.2 kb lncRNA, was initially described as a modulator of HOX gene expression. Recent studies have illustrated the important role of HOTAIR in cancer progression, but few studies have reported its function in cardiac disease, including AMI. In the current study, we aimed to detect the expression of HOTAIR during AMI and to explore its function in hypoxia-induced cardiomyocyte injury in neonatal cardiomyocytes. Methods: In 50 consecutively enrolled AMI patients, we examined the serum expression levels of HOTAIR and analysed its correlation with cardiac troponin I (cTnI) expression. Another 50 age- and sex-matched subjects served as healthy controls. Next, the HOTAIR expression was detected in the serum from C57BL/6J mice subjected to coronary artery ligation and in neonatal rat cardiomyocytes induced by hypoxia. Cultured cardiomyocytes apoptosis were measured by terminal deoxynucleotide transferase dUTP nick end labelling (TUNEL) staining. A search for miRNAs that had complementary base paring with HOTAIR was performed utilizing an online software program, and the interaction between miR-1 and HOTAIR was examined using a luciferase reporter assay. Results: Our study revealed that HOTAIR expression was significantly decreased in the serum of AMI patients compared with that of the healthy controls. Similarly, we observed that HOTAIR was downregulated in the serum of mice subjected to coronary artery ligation and in cultured cardiomyocytes exposed to hypoxia. Furthermore, we observed that the adenovirus vector-driven overexpression of HOTAIR dramatically limited hypoxia-induced myocyte apoptosis, whereas knockdown HOTAIR by AdshHOTAIR (adenoviral short hairpin HOTAIR) exhibited the opposite phenotype. Mechanistically, we discovered that the cardioprotective function of HOTAIR is partly based on the negative regulation of miR-1. Conclusions: Taken together, the results of our study suggest that HOTAIR is a protective factor for cardiomyocytes and that the plasma concentration of HOTAIR may serve as a biomarker for human AMI diagnosis.
KID Syndrome and Hidradenitis Suppurativa: A Rare Association Responding to Surgical Treatment
Authors: Bettoli Vincenzo , Forconi Riccardo , Pezzini Ilaria , Martinello Ruby , Scuderi Valeria , Zedde Piera , Schettini Natale , Pacetti Lucrezia , Corazza Monica
Published: October 2020

Background: Keratitis-ichthyosis-deafness (KID) syndrome is a rare genodermatosis characterized by keratitis, neurosensorial auditory impairment and ichthyosiform skin involvement. Frequent complications of the syndrome are chronic, opportunistic cutaneous infections, and the development of skin cancers. Several cases of association between KID syndrome and other conditions, including hidradenitis suppurativa (HS), are described in the literature. This correlation could be explained by the hyperproliferative state of the epidermis, which occurs in KID syndrome and may favor follicular plugging. Objectives: The aim of this study was to describe a very rare case of association between KID syndrome and HS and its complex therapeutic management. Results: The failure of the drugs commonly used in HS and the excellent results of surgery, although difficult to achieve, were experienced. Conclusion: Despite the technical difficulties related to surgery, namely, cutaneous superinfections, frequent dehisce of the suture, and closure by secondary intention, the authors strongly recommend the surgical approach in these patients.
TrkC Overexpression Protects Sevoflurane-Induced Neurotoxicity in Human Induced Pluripotent Stem Cell-Derived Neurons
Authors: Zhang Jun , Chen Zhifu , Luo Xiaoyan , Yang Zhoujing
Published: October 2020

Background: Inhaled anesthetic sevoflurane (SEVO) may induce cortical neurotoxicity and memory dysfunction in both animals and humans. In this study, we investigated the toxic effects of SEVO on human induced pluripotent stem cell (iPS)-derived neurons. Methods: Human iPS-derived neurons were exposed to SEVO in vitro. SEVO-induced toxic effects were examined with the viability, live caspase 3/7, and neurite density assays, respectively. The effects of SEVO on the receptors of the tyrosine kinases TrkA, TrkB, and TrkC were assessed by qRT-PCR. TrkA, TrkB, and TrkC were ectopically overexpressed in human iPS-derived neurons. Their functional effects on SEVO-induced human iPS-derived neuron toxicity were further investigated. Results: SEVO induced dose-dependent cell death, caspase 3/7 elevation, neurite degeneration, and the downregulation of Trk receptors in human iPS-derived neurons. Adenovirus-mediated Trk receptor overexpression selectively upregulated endogenous TrkA, TrkB, or TrkC gene expressions in human iPS-derived neurons. Specifically, TrkC overexpression, but not TrkA or TrkB overexpression was found to overcome the neurotoxic effects of SEVO in human iPS-derived neurons. Conclusions: SEVO may induce neurotoxicity in human iPS-derived neurons, and its neurotoxic damage could be protected by the overexpression of TrkC.
Syndecan-1 and Glypican-1 Knockout Alters Body Water Balance and Urine Response to Fluid Challenge in Mice
Authors: Dull Randal O. , Patel Milan , Isbatan Ayman , Hahn Robert G.
Published: October 2020

Syndecan-1 (Sdc-1) and glypican-1 (Gpc-1) are 2 important proteoglycans found in the glycocalyx and believed to govern transvascular distribution of fluid and protein. In this translational study, we assessed Sdc-1 and Gpc-1 knockout (KO) on whole body water balance after an intravenous volume challenge. Sdc-1 and Gpc-1 KO mice had higher starting blood water content versus strain-matched controls. Sdc-1 KO mice exhibited a significantly higher diuretic response (87%; p < 0.05), higher excreted volume/infusion volume ratio (p < 0.01), higher extravascular/infused ratio, and greater tissue water concentration (60 vs. 52%). Collectively, these suggest differences in kidney response and greater fluid efflux from peripheral vessels. The CD1 strain and Gpc-1 KO had a 2–3-fold larger urine output relative to C57 strain, but Gpc-1 KO reduced the excreted/infused ratio relative to controls (p < 0.01) and they maintained plasma dilution longer. Thus, genetic KO of Sdc-1 and Gpc-1 resulted in markedly different phenotypes. This work establishes the feasibility of performing fluid balance studies in mice.
Elevated Circulating Cell-Free DNA in Hemodialysis-Treated Patients Is Associated with Increased Mortality
Authors: Einbinder Yael , Shnaider Alla , Ghanayem Khaled , Basok Anna , Rogachev Boris , Lior Yotam , Haviv Yosef Shmuel , Cohen-Hagai Keren , Nacasch Naomi , Rozenberg Ilan , Benchetrit Sydney , Zitman-Gal Tali , Douvdevani Amos
Published: October 2020

Background: Predicting the mortality risk of patients un­dergoing hemodialysis (HD) is challenging. Cell-free DNA (cfDNA) is released into circulation from dying cells, and its elevation is predictive of unfavorable outcome. In a pilot study, we found post-HD cfDNA level to be a predictor of all-cause mortality. Thus, the aim of this study was to confirm the prognostic power of cfDNA in a larger prospective cohort study conducted at 2 medical centers. Methods: CfDNA levels were measured by a rapid fluorometric assay on sera obtained before and after 1 HD session. One hundred fifty-three patients were followed up to 46 months for mortality during which time 47 patients died. We compared the predictive value of cfDNA to age, comorbidities, and standard blood tests. Results: Examining standard blood tests, only post-HD cfDNA levels were elevated in the non-survivor group compared to survivors (959 vs. 803 ng/mL, p = 0.04). Pre- and post-HD cfDNA levels correlated with age and diabetes. Patients with elevated cfDNA (>850 ng/mL) showed lower survival than those with normal levels. A Cox proportional hazard regression model demonstrated a significant hazard ratio of 1.92 for post-HD cfDNA levels. Logistic regression models showed that post-HD cfDNA was a significant predictor of mortality at 1–3 years with odd ratios of 4.61, 4.36, and 6.22, respectively. Conclusions: Post-HD cfDNA level was superior to standard blood tests and could serve as a biomarker to assist in decision-making for HD-treated patients.
Outcomes of Airway Management in Micrognathia and Retrognathia Patients Born at Fetal versus Nonfetal Centers
Authors: Shahi Niti , Phillips Ryan , Meier Maxene , Grover Theresa , Galan Henry , Zaretsky Michael , Meyers Mariana , Kelley Peggy , Marwan Ahmed I.
Published: October 2020

Objectives: There is a paucity of evidence to guide the perinatal management of difficult airways in fetuses with micrognathia. We aimed to (1) develop a postnatal grading system based on the extent of airway intervention required at birth to assess the severity of micrognathic airways and (2) compare trends in airway management and outcomes by location of birth [nonfetal center (NFC), defined as a hospital with or without an NICU and no fetal team, versus fetal center (FC), defined as a hospital with an NICU and fetal team]. Methods: We retrospectively reviewed the prenatal and postnatal records of all neonates diagnosed with micrognathia from January 2010 to April 2018 at a quaternary children’s hospital. We developed a novel grading scale, the Micrognathia Grading Scale (MGS), to grade the extent of airway intervention at birth from 0 (no airway intervention) to 4 (requirement of EXIT or advanced airway instrumentation for airway securement). Results: We identified 118 patients with micrognathia. Eighty-nine percent (105/118) were eligible for grading using the MGS. When the MGS was applied, the airway grades were as follows: grade 0 (30%), grade 1 (10%), grade 2 (9%), grade 3 (48%), and grade 4 (4%). A quarter of micrognathic patients with grade 0–2 airways had postnatal hospital readmissions for airway obstruction after birth, of which all were born at NFC. Over 40% of patients with grade 3–4 micrognathic airways required airway intervention within 24 h of birth. Overall, NFC patients had a readmission rate of (27%) for airway obstruction after birth compared to FC patients (17%). Conclusions: Due to the high incidence of grade 3–4 airways on the MGS in micrognathic patients, fetuses with prenatal findings suggestive of micrognathia should be referred to a comprehensive fetal care center capable of handling complex neonatal airways. For grade 0–2 airways, infants frequently had postnatal complications necessitating airway intervention; early referral to a multidisciplinary team for both prenatal and postnatal airway management is recommended.
Subungual Elastofibroma
Authors: Haneke Eckart
Published: October 2020

Cutaneous elastofibroma is part of the connective tissue nevus complex. Two subungual cases remotely similar to the one presented here have been described before. This patient presented with an unusual form of subungual elastofibroma of the big toe, which was surgically removed. Histopathology revealed a connective tissue tumor extremely rich in very fine elastic fibers. Their relationship to oxytalan and elaunin fibers is discussed as is the potential association of this nail bed lesion with the onychodermis.
Quality of Life Is Associated with Cardiac Biomarkers, Echocardiographic Indices, and Mortality in CKD Stage 4–5 Patients Not on Dialysis
Authors: Hakamäki Markus , Lankinen Roosa , Hellman Tapio , Koivuviita Niina , Pärkkä Jussi P. , Saarenhovi Maria , Metsärinne Kaj , Järvisalo Mikko J.
Published: October 2020

Introduction: Patients with CKD have an impaired health-related quality of life (QoL). Most studies have been conducted on dialysis patients, and less is known about QoL and its determinants in predialysis patients. We studied the association between QoL and comorbidities, cardiac biomarkers, echocardiography, and mortality in patients with CKD stage 4–5 not on dialysis. Methods: A total of 140 patients enrolled in the Chronic Arterial Disease, Quality of Life and Mortality in Chronic Kidney Injury (CADKID) study filled the Kidney Disease Quality of Life Short Form (KDQOL-SF) at the beginning of the study. Echocardiography and biochemical parameters were obtained at baseline. Patients were followed up for at least 2 years or until death. Results: The median age was 66 years, and 51 (36%) patients were female. The median estimated glomerular filtration rate was 13 mL/min per 1.73 m2. Obesity, diabetes, atrial fibrillation, and congestive heart failure were associated with lower QoL scores in multiple KDQOL-SF domains. Cardiac biomarkers, troponin T (p = 0.02), N-terminal pro-B-type natriuretic peptide (p = 0.006), and the echocardiographic parameter of cardiac systolic function left ventricular global longitudinal strain (p = 0.02) were significant predictors of lower physical component summary (PCS) score in multivariable regression models after controlling for age, BMI, and diabetes. A low PCS score predicted mortality in a multivariable Cox proportional hazards model [HR 0.96 (95% CI 0.92–0.99), p = 0.03]. QoL was not associated with kidney disease progression. Conclusion: Impaired QoL in CKD stage 4–5 patients not on dialysis is associated with cardiac biomarker levels, echocardiographic indices, and mortality.
Abdominal Surgery in Crohn’s Disease: Risk Factors for Complications
Authors: Sakurai Kimura Cintia Mayumi , Scanavini Neto Arceu , Queiroz Natalia Sousa Freitas , Horvat Natally , Camargo Mariane Gouvea Monteiro , Borba Marcelo Rodrigues , Sobrado Carlos Walter , Cecconello Ivan , Nahas Sergio Carlos
Published: October 2020

Introduction: Abdominal surgery in patients with Crohn’s disease (CD) is challenging, especially in the biologic era. The aim of this study was to evaluate factors associated with increased risk for postoperative complications in CD. Methods: A retrospective study was conducted with consecutive patients who underwent abdominal surgery for CD from January 2012 to January 2018. Results: Of 103 patients, 32% had postoperative complications. Gender, age, disease location and phenotype, hemoglobin and albumin levels, previous abdominal surgery, and preoperative optimization did not differ between the groups with or without complications. Thirty-five percent of the patients were under anti-TNF therapy, and this medication was not associated with increased risk for postoperative complications. Time since the onset of the disease was significantly higher in patients with complications (12.9 vs. 9.4, p = 0.04). In multivariate analysis, creation of ostomy and urgent surgery were the only variables independently associated with increased risk for complications (OR 3.2, 95% CI 1.12–9.46 and OR 2.94, 95% CI 0.98–9.09, respectively). Conclusion: Urgent surgery for CD should preferably be performed in specialized centers, and creation of stoma is not necessarily associated with lower rate of postoperative complications but rather less severe complications.
Diagnostik von Lungentumoren: Mit Mutationsanalysen die Aussagekraft der bronchoalveolären Lavage steigern
Authors: Wagner Manfred , Brückl Wolfgang
Published: October 2020

Background: The rate of diagnosis of advanced lung adenocarcinoma must be improved. In this study, we compared the detection rates of EGFR-tyrosine kinase inhibitor-sensitizing mutations (mEGFRs) in bronchial washing fluid (BWF) and the plasma of patients with lung adenocarcinoma using the tissue genotype as the standard reference. Methods: Paired blood and BWF specimens were collected from 73 patients with lung cancer. The tumor EGFR mutation status was determined by genotyping of the plasma and BWF samples using droplet digital PCR (ddPCR). Results: The study cohort included 26, 10, 10, and 27 patients with stage I, II, III, and IV disease. Of the 73 cases, 35 had a wild-type EGFR, and 19 had the L858R substitution and exon 19 deletion mutations. The areas under the receiver operator characteristic curves for sensitivity vs. specificity of ddPCR were 0.895 [95% confidence interval (CI): 0.822–0.969] for BWF and 0.686 (95% CI: 0.592–0.780) for plasma (p < 0.001). The fractional abundance was higher in BWF of the mEGFR-positive cases than in the plasma (p  =  0.004), facilitating easy threshold setting and discrimination between mEGFR-positive and negative cases. When genotyping results obtained using plasma and BWF were compared for early lung cancer (stages I–IIIA), the diagnostic yields were significantly higher for BWF ddPCR, and the same tendency was observed for the advanced stages, suggesting that the BWF data may reflect the genotype status in early-stage patients. Conclusions: The mEGFR genotyping results obtained using BWF showed a higher diagnostic efficacy than did those obtained using the plasma. Thus, BWF-based genotyping may be a useful substitute for that using plasma in lung cancer.
Avifaunal diversity along the riverine habitats of Papikonda National Park, Andhra Pradesh, India
Authors: Ray Paromita , Malla Giridhar , Manral Upma , J.A. Johnson  , K. Sivakumar
Published: October 2020

This study was carried out to record the avifaunal diversity of the riverine habitats along the Godavari River in Papikonda National Park, during a short survey conducted from 2017 to 2018.  A total of 63 bird species belonging to 25 families were recorded during the survey.  The study resulted in the recording of eight globally threatened avian species including the Endangered Black-bellied Tern Sterna acuticauda, and seven Near Threatened species, viz.: Painted Stork Mycteria leucocephala, Black-headed Ibis Threskiornis melanocephalus, Great Thick Knee Esacus recurvirostris, River Lapwing Vanellus duvaucelli, Malabar Pied Hornbill Anthracoceros coronatus, Grey-headed Fish Eagle Haliaeetus ichthyaetus, and Oriental Darter Anhinga melanogaster.  Species including Black-bellied Tern Sterna acuticauda, Grey-headed Fish Eagle Haliaeetus ichthyaetus, Indian Eagle-owl Bubo bengalensis, and Black Eagle Ictinaetus malaiensis were recorded for the first time along the riverine habitats of Papikonda National Park.  Sand mining of the riverbed and discharge of effluents into the Godavari River has already negatively impacted the associated habitats and avifaunal diversity.
A highway to hell: a proposed, inessential, 6-lane highway (NH173) that threatens the forest and wildlife corridors of the Western Ghats, India
Authors: Sagar H.S. Sathya Chandra , Mrunmayee
Published: October 2020

A globally, extensive road network combined with increasing vehicular traffic poses a significant threat to local wildlife, environment, economy, and socio-politics.  India, with nearly 5.9 million kilometers of road, has the second-highest road network in the world; and has plans to exponentially increase its national highways.  In this study, we use a combination of collation of official documents, literature review, and GIS mapping to outline the possible environmental and socio-economic impacts caused by a proposed 6-lane national highway (NH 173).  This highway is set to cut through the low elevation evergreen forests of the central Western Ghats between Mudigere and Nelliyadi towns of Chikkamagaluru and Dakshina Kannada districts, of Karnataka State, respectively.  We further outline the insignificance of the project and recommend workable alternatives that could be considered in the wider public’s interest.
Cirsium wallichii DC. (Asteraceae): a key nectar source of butterflies
Authors: Boruah Bitupan , Kumar Amit , Das Abhijit
Published: October 2020

Abstract: Butterfly diversity and abundance depend on the diversity of foraging resources and nectar characteristics.  Several wild plants of the family Asteraceae often considered as weeds, are important nectar sources for butterflies.  The present communication reports Cirsium wallichii as a key nectar source for a large number of butterfly species during the summer season in Benog Wildlife Sanctuary, Mussoorie, western Himalaya.  Of the total recorded species of butterflies (62), a maximum species (22) belongs to the Nymphalidae family followed by Hesperiidae (13), and Lycaenidae (11) that visits C. wallichii.  Therefore, it is suggested that Cirsium wallichii has an important role in sustaining butterfly diversity.

 

Keywords: Mussoorie, Lepidoptera, .
Medetomidine may cause heart murmur in Cougars and Jaguars: case report
Authors: Thiago Cavalheri Luczinski  , Gediendson Ribeiro de Araújo  , Matheus Folgearini Silveira  , Murillo Daparé Kirnew  , Navarrete Roberto Andres , Salomão-Jr Jorge Aparecido , Letícia Alecho Requena  , Jairo Antonio Melo dos Santos  , Marcell Hideki Koshiyama  , Cristiane Schilbach Pizzutto  , Jorge-Neto Pedro Nacib
Published: October 2020

We report heart murmur in Jaguars and Cougars found during reproductive procedures for semen and oocyte collection.  Two male Cougars (n=2) and three female Jaguars (n=3) were examined.  Anesthesia was performed with ketamine and medetomidine in males.  Females also received propofol and were maintained with isoflurane.  The animals were evaluated during anesthetic monitoring with multiparameter monitor alongside clinical examination, ambulatory electrocardiogram and echocardiogram.  All animals presented mitral valve regurgitation under anesthesia, but without morphological changes in the cardiac structure or hemodynamic changes.  Medetomidine may cause transitory heart murmur in healthy Jaguars and Cougars.