bluuebunny/crossref_metadata_2025 huggingface dataset:
Objective pain stimulation intensity and pain sensation assessment using machine learning classification and regression based on electrodermal activity
Authors: Posada–Quintero Hugo F. , Kong Youngsun , Chon Ki H.
Published: June 2021

An objective measure of pain remains an unmet need of people with chronic pain, estimated to be 1/3 of the adult population in the United States. The current gold standard to quantify pain is highly subjective, based upon self-reporting with numerical or visual analog scale (VAS). This subjectivity complicates pain management and exacerbates the epidemic of opioid abuse. We have tested classification and regression machine learning models to objectively estimate pain sensation in healthy subjects using electrodermal activity (EDA). Twenty-three volunteers underwent pain stimulation using thermal grills. Three different “pain stimulation intensities” were induced for each subject, who reported the “pain sensation” right after each stimulus using a VAS (0–10). EDA data were collected throughout the experiment. For machine learning, we computed validated features of EDA based on time-domain decomposition, spectral analysis, and differential features. Models for estimation of pain stimulation intensity and pain sensation achieved maximum macroaveraged geometric mean scores of 69.7% and 69.2%, respectively, when three classes were considered (“No,” “Low,” and “High”). Regression of levels of stimulation intensity and pain sensation achieved R2 values of 0.357 and 0.47, respectively. Overall, the high variance and inconsistency of VAS scores led to lower performance of pain sensation classification, but regression was better for pain sensation than stimulation intensity. Our results provide that three levels of pain can be quantified with good accuracy and physiological evidence that sympathetic responses recorded by EDA are more correlated to the applied stimuli’s intensity than to the pain sensation reported by the subject.
Carotid body chemosensitivity is not attenuated during cold water diving
Authors: Hess Hayden W. , Hostler David , Clemency Brian M. , St. James Erika , Johnson Blair D.
Published: June 2021

Tonic carotid body (CB) activity is reduced during exposure to cold and hyperoxia. We tested the hypotheses that cold water diving lowers CB chemosensitivity and augments CO2 retention more than thermoneutral diving. Thirteen subjects [age: 26 ± 4 yr; body mass index (BMI): 26 ± 2 kg/m2) completed two 4-h head-out water immersion protocols in a hyperbaric chamber (1.6 ATA) in cold (15°C) and thermoneutral (25°C) water. CB chemosensitivity was assessed with brief hypercapnic ventilatory response ([Formula: see text]) and hypoxic ventilatory response ([Formula: see text]) tests before dive, 80 and 160 min into the dive (D80 and D160, respectively), and immediately after and 60 min after dive. Data are reported as an absolute mean (SD) change from predive. End-tidal CO2 pressure increased during both the thermoneutral water dive [D160: +2 (3) mmHg; P = 0.02] and the cold water dive [D160: +1 (2) mmHg; P = 0.03]. Ventilation increased during the cold water dive [D80: 4.13 (4.38) and D160: 7.75 (5.23) L·min−1; both P < 0.01] and was greater than the thermoneutral water dive at both time points (both P < 0.01). [Formula: see text] was unchanged during the dive ( P = 0.24) and was not different between conditions ( P = 0.23). [Formula: see text] decreased during the thermoneutral water dive [D80: −3.45 (3.61) and D160: −2.76 (4.04) L·min·mmHg−1; P < 0.01 and P = 0.03, respectively] but not the cold water dive. However, [Formula: see text] was not different between conditions ( P = 0.17). In conclusion, CB chemosensitivity was not attenuated during the cold stress diving condition and does not appear to contribute to changes in ventilation or CO2 retention.
Dorsomedial prefrontal neural ensembles reflect changes in task utility that culminate in task quitting
Authors: Porter Blake S. , Hillman Kristin L.
Published: June 2021

When carrying out a physically demanding task, animals must continually assess whether to persist or quit. In this study, we recorded neurons in the dorsomedial prefrontal cortex (dmPFC) of rats as they carried out a challenging weightlifting task, up to the point of quitting. We demonstrate that dmPFC neurons form a representation of the task that is modified, via a decrease in firing rate, by the decreasing the utility of the task that may signal quitting.
Ketamine disrupts gaze patterns during face viewing in the common marmoset
Authors: Selvanayagam Janahan , Johnston Kevin D. , Wong Raymond K. , Schaeffer David , Everling Stefan
Published: June 2021

Face processing, an important social cognitive ability, is impaired in neuropsychiatric conditions such as schizophrenia. The highly social common marmoset model presents an opportunity to investigate these impairments. We administered subanesthetic doses of ketamine to marmosets to model the cognitive symptoms of schizophrenia. We observed a disruption of scan paths during viewing of conspecifics’ faces. These findings support the use of ketamine in marmosets as a model for investigating social cognition in neuropsychiatric disorders.
Estimates of persistent inward currents in tibialis anterior motor units during standing ramped contraction tasks in humans
Authors: Khurram Obaid U. , Negro Francesco , Heckman C. J. , Thompson Christopher K.
Published: June 2021

In the present study, we show that the discharge rate of a lower threshold motor unit at the recruitment onset and offset of a higher threshold motor unit (ΔF) is similar between standing and seated conditions in human tibialis anterior motor units, suggesting that at least for these two upright postures neuromodulatory drive is similar. We also highlight a proposed technological development in using high-density EMG arrays for real-time muscle activity feedback to accomplish standing ramped contraction tasks and demonstrate the validity of the paired motor unit analysis technique during these conditions.
Short-Term Influence of Caffeine and Medium-Chain Triglycerides on Ketogenesis: A Controlled Double-Blind Intervention Study
Authors: Baumeister Anna , Gardemann Joachim , Fobker Manfred , Spiegler Verena , Fischer Tobias
Published: June 2021

Background. Ketone bodies are a highly relevant topic in nutrition and medicine. The influence of medium-chain triglycerides (MCT) on ketogenesis is well known and has been successfully used in ketogenic diets for many years. Nevertheless, the effects of MCTs and coconut oil on the production of ketone bodies have only partially been investigated. Furthermore, the increased mobilisation of free fatty acids and release of catabolic hormones by caffeine suggest an influence of caffeine on ketogenesis. Methods. In a controlled, double-blind intervention study, seven young healthy subjects received 10 mL of tricaprylin (C8), tricaprin (C10), C8/C10 (50% C8, 50% C10), or coconut oil with or without 150 mg of caffeine, in 250 mL of decaffeinated coffee, over ten interventions. At baseline and after every 40 minutes, for 4 h, ßHB and glucose in capillary blood as well as caffeine in saliva were measured. Furthermore, questionnaires were used to survey sensory properties, side effects, and awareness of hunger and satiety. Results. The interventions with caffeine caused an increase in ßHB levels—in particular, the interventions with C8 highly impacted ketogenesis. The effect decreased with increased chain lengths. All interventions showed a continuous increase in hunger and diminishing satiety. Mild side effects (total = 12) occurred during the interventions. Conclusions. The present study demonstrated an influence of caffeine and MCT on ketogenesis. The addition of caffeine showed an additive effect on the ketogenic potential of MCT and coconut oil. C8 showed the highest ketogenicity.
Ulinastatin as an Adjuvant Therapy to Restricting Volumes of Resuscitation Fluid Strategy for Patients with Septic Shock after Initial Management
Authors: Dong Rensong , Zhang Xi , Zhao Zhi
Published: June 2021

Septic shock is the most serious complication of sepsis, leading to unacceptably high morbidity and mortality worldwide. Fluid resuscitation using crystalloids has become the mainstay of early and aggressive treatment of severe sepsis and septic shock, while increased daily fluid balances from day 2 until day 7 have been related with increased mortality. Recently, pharmacological management has been recommended to combine with appropriate fluid resuscitation for the treatment of septic shock. In this study, we compared the clinical efficacy of restricting volumes of resuscitation fluid strategy with or without intravenous infusion of ulinastatin (UTI) in treating patients with septic shock and additionally examined the patient’s changes of the extravascular lung water index (EVLWI), pulmonary vascular permeability index (PVPI), systemic vascular resistance index (SVRI), cardiac function, lactic acid (LA) level, coagulation function, and renal function. The study included 182 patients with septic shock, among which 89 patients had undergone restricting volumes of resuscitation fluid strategy with intravenous infusion of UTI and 93 patients had undergone restricting volumes of resuscitation fluid strategy alone. It was found that patients with septic shock after restricting volumes of resuscitation fluid strategy with intravenous infusion of UTI showed an increased SVRI concomitant with declined PVPI and EVLWI, increased mean artery pressure (MAP), cardiac output (CO), left ventricular ejection fraction (LVEF), stroke volume (SV), and heart rate (HR), declined levels of cardiac troponin I (cTnI), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and C-reactive protein (CRP), reduced LA level along with shortened prothrombin time (PT) and partially activated thrombin time (PATT), and decreased levels of blood urea nitrogen (BUN), creatinine (Cr), and uric acid (UA) when comparable to those after restricting volumes of resuscitation fluid strategy alone (

P
<
0.05

). We also observed fewer scores of the Acute Physiology and Chronic Health Evaluation (APACHE II) and the sequential organ failure assessment (SOFA) in patients undergoing restricting volumes of resuscitation fluid strategy with intravenous infusion of UTI than those undergoing restricting volumes of resuscitation fluid strategy alone (

P
<
0.05

). According to the above data, it is concluded that UTI as an adjuvant therapy for restricting volumes of resuscitation fluid strategy in treating septic shock may decrease the LA level, attenuate the inflammatory response, reduce vascular permeability, prevent pulmonary edema, and restore cardiac and renal functions.
Detection of GAN-Synthesized Image Based on Discrete Wavelet Transform
Authors: Tang Guihua , Sun Lei , Mao Xiuqing , Guo Song , Zhang Hongmeng , Wang Xiaoqin
Published: June 2021

Recently, generative adversarial networks (GANs) and its variants have shown impressive ability in image synthesis. The synthesized fake images spread widely on the Internet, and it is challenging for Internet users to identify the authenticity, which poses huge security risk to the society. However, compared with the powerful image synthesis technology, the detection of GAN-synthesized images is still in its infancy and face a variety of challenges. In this study, a method named fake images discriminator (FID) is proposed, which detects that GAN-synthesized fake images use the strong spectral correlation in the imaging process of natural color images. The proposed method first converts the color image into three color components of R, G, and B. Discrete wavelet transform (DWT) is then applied to RGB components separately. Finally, the correlation coefficient between the subband images is used as a feature vector for authenticity classification. Experimental results show that the proposed FID method achieves impressive effectiveness on the StyleGAN2-synthesized faces and multitype fake images synthesized with the state-of-the-art GANs. Also, the FID method exhibits good robustness against the four common perturbation attacks.
Numerical Investigation on the Hydraulic Fracture Evolution of Jointed Shale
Authors: Men Xiaoxi , Jin Jiaxu
Published: June 2021

Joints are a common structure of heterogeneous shale rock masses, and in situ stress is the environment in which heterogeneous rock masses can be found. The existence of joint plane and confining pressure difference influences the physical properties of shale and propagation of fractures. In this study, jointed shale specimens were simulated under different confining pressures to explore the failure patterns and fracture propagation behavior of hydraulic fracturing. Different from the common research of hydraulic fracturing on signal parallel joint rock mass, the simulations in this study considered three points (parallel joint, multi‐dip angle joint, and no‐joint points). The effects of the single‐dip angle joint, multi‐dip angle joint, and confining pressure difference on the hydraulic fracture evolution and stress evolution of the jointed shale were studied comprehensively. The confining pressure difference coefficient proposed in this study was used to accurately describe the confining pressure difference. Results indicate that the larger is the confining pressure difference, the stronger is the control of the maximum principal stress on fracture evolution; by contrast, the smaller is the confining pressure difference, the stronger is the control of the joint plane on fracture evolution. Under the same confining pressure difference, the hydraulic fracture propagates more easily along the small dip angle joint plane. As the value of the confining pressure difference coefficient moves closer to zero, the hydraulic fracture propagates randomly, the tensile stress region around the fracture tip widens, and the joint planes fractured by tensile increase. This study can offer valuable guidance to the design of unconventional reservoir reconstruction.
Formulation of Insect Chitosan Stabilized Silver Nanoparticles with Propolis Extract as Potent Antimicrobial and Wound Healing Composites
Authors: Al-saggaf Mohammed S.
Published: June 2021

Skin wounds are frequently influenced with microbial infections and inflammation, which need innovative agents for disputing them. Chitosan (Csn) was extracted from larvae of BSF “black soldier fly, Hermetia illucens” and ethanolic propolis extract (Pro) was employed for synthesizing silver nanoparticles (Ag-NPs), using facile biogenic protocol. The BSF-Csn was acquired with a yield of 1.56%, 91.3% deacetylation degree, and 88.600 Dalton molecular weight. The Ag-NPs were effectually biosynthesized using Pro, with a mean diameter of 8.73 nm and zeta potential of -21.34 mV. The antimicrobial activities assessment of insect Csn, Pro, synthesized Ag-NPs with Pro, and their composite against skin pathogens (Staphylococcus aureus and Candida albicans) revealed the elevated efficiency of the individual agents and the superior action of their composite (Csn/Pro/Ag-NPs), with 26.3 and 23.4 mm inhibition zones and inhibitory concentrations of 35.0 and 45.0 μg/mL from the composite toward S. aureus and C. albicans, respectively, which exceeded the actions of commercial antibiotics. The treatment of rat’s wounds with this composite promisingly led to faster healing of wounds and absence of inflammation and infection signs. The powerful actions of Csn/Pro/Ag-NPs as antimicrobial and wound healing composite strongly advocate their applications for skin protection, disinfection, and regeneration.
Hydrostatic Pressure Modulates Intervertebral Disc Cell Survival and Extracellular Matrix Homeostasis via Regulating Hippo-YAP/TAZ Pathway
Authors: Wang Yiyang , Bai Baoshuai , Hu Yanzhu , Wang Haoming , Liu Ningyuan , Li Yibo , Li Pei , Zhou Guangdong , Zhou Qiang
Published: June 2021

Established studies proved that hydrostatic pressure had multiple effects on the biological behavior of the intervertebral disc (IVD). However, the conclusions of the previous studies were inconsistent, due to the difference in hydrostatic loading devices and observing methods used in these studies. The current study is aimed at investigating the role of dynamic hydrostatic pressure in regulating biological behavior of the notochordal nucleus pulposus (NP) and fibrocartilaginous inner annulus fibrosus (AF) and its possible mechanism using our novel self-developed hydrostatic pressure bioreactor. The differences in the biological behavior of the rabbit IVD tissues under different degree of hydrostatic pressure were evaluated via histological analysis. Results revealed that low-loading dynamic hydrostatic pressure was beneficial for cell survival and extracellular matrix (ECM) homeostasis in notochordal NP and fibrocartilaginous inner AF via upregulating N-cadherin (N-CDH) and integrin β1. In comparison, high-magnitude dynamic hydrostatic pressure aggravated the breakdown of ECM homeostasis in NP and inner AF via enhancing the Hippo-YAP/TAZ pathway-mediated cell apoptosis. Moreover, inner AF exhibited greater tolerance to physiological medium-loading degree of hydrostatic pressure than notochordal NP. The potential mechanism was related to the differential expression of mechanosensing factors in notochordal NP and fibrocartilaginous inner AF, which affects the fate of the cells under hydrostatic pressure. Our findings may provide a better understanding of the regulatory role of hydrostatic pressure on the cellular fate commitment and matrix metabolism of the IVD and more substantial evidence for using hydrostatic pressure bioreactor in exploring the IVD degeneration mechanism as well as regeneration strategies.
A Petri Nets Evolution Method that Supports BPMN Model Changes
Authors: Li Zonghua , Ye Zhengwei
Published: June 2021

The correctness of the business process modelling notation (BPMN) is essential for software success, and the BPMN formalization is the foundation of the correctness verification process. However, dynamically adapting the formalized BPMN model to changes in the BPMN model and protecting tokens from being lost in the remapping formalization are the main limitations of the BPMN formalization under changing business requirements. To overcome these limitations, an approach for evolving a Petri nets model according to the BPMN changes is proposed in this paper. In this approach, a check algorithm is designed to identify the differences between the original BPMN model and the updated BPMN model. Then, the evolution rules of the extended Petri nets (EPN) model are defined according to the results of the checking program. Finally, these evolution rules are described in the query/view/transformation operational mapping (QVTo) language and implemented in the Eclipse platform. We demonstrate the effectiveness of the evolution of the BPMN formalization using a case study of the Web Payment business system. Moreover, the dynamic evolution of the BPMN formalization can maintain the consistency between the original model and the updated model, and this consistency has been successfully verified.
Network Intrusion Detection System Based on the Combination of Multiobjective Particle Swarm Algorithm‐Based Feature Selection and Fast‐Learning Network
Authors: Einy Sajad , Oz Cemil , Navaei Yahya Dorostkar
Published: June 2021

Given the growth of wireless networks and the increase of the advantages and applications of communication networks, especially mobile ad hoc networks (MANETs), this type of network has attracted the attention of users and researchers more than before. The benefit of these types of networks in various kinds of networks and environments is that MANET does not require to hardware infrastructure to communicate and send and receive data packets within the network. It is one of the main reasons for using these MANET in various fields. On the other hand, the increased popularity of these networks has led to many challenges, one of the most important of which is network security. In this regard, a lack of regulatory and security infrastructure in MANETs has caused some problems in sending and receiving data, where intrusion in the network has been recognized as one of the most important issues. In MANETs, wireless notes act as a link between the source and destination nodes and play the role of relays and routers in the network. Therefore, malicious node penetration and the destruction of information packages become feasible. Today, intrusion detection systems (IDSs) are used as a solution to deal with the problem through remote monitoring of the performance and behaviors of nodes existing in wireless sensor networks. In addition to detecting malicious nodes in the network, IDSs can predict the behavior of malicious nodes in the future in most cases. Therefore, the present study introduced a network IDS (NIDS) entitled MOPSO‐FLN by using a combination of multiobjective particle swarm optimization algorithm‐ (MOPSO‐) based feature subset selection (FSS) and fast‐learning network (FLN). In this work, we used the KDD Cup99 and dataset to select features, train the network, and test the model. According to the simulation results, this method was able to improve the performance of the IDS in terms of evaluation criteria, compared to other previous methods, by creating a balance between the objectives of the number of representative features and training errors based on the evolutionary power of MOPSO.
Differential Expression Study of Lysine Crotonylation and Proteome for Chronic Obstructive Pulmonary Disease Combined with Type II Respiratory Failure
Authors: Gan Qing , Tang Donge , Yan Qiang , Chen Jiejing , Xu Yong , Xue Wen , Xiao Lu , Zheng Fengping , Xu Huixuan , Fu Yingyun , Dai Yong
Published: June 2021

Introduction. The modification of lysine crotonylation (Kcr) is another biological function of histone in addition to modification of lysine acetylation (Kac), which may play a specific regulatory role in diseases. Objectives. This study compared the expression levels of Kcr and proteome between patients with chronic obstructive pulmonary disease (COPD) combined with type II respiratory failure (RF) to study the relationship between Kcr, proteome, and COPD. Methods. We tested the Kcr and proteome of COPD combined with type II RF and normal control (NC) using croton acylation enrichment technology and liquid chromatography tandem mass spectrometry (LC-MS/MS) with high resolution. Results. We found that 32 sites of 23 proteins were upregulated and 914 sites of 295 proteins were downregulated. We performed Kyoto Encyclopedia of Genes and Genomes (KEGG), protein domain, and Gene Ontology (GO) analysis on crotonylated protein. In proteomics research, we found that 190 proteins were upregulated and 151 proteins were downregulated. Among them, 90 proteins were both modified by differentially expressed crotonylation sites and differentially expressed in COPD combined with type II RF and NC. Conclusion. Differentially expressed crotonylation sites may be involved in the development of COPD combined with type II RF. 90 proteins modified by crotonylation and differentially expressed in COPD combined with type II RF can be used as markers for the study of the molecular pathogenesis of COPD combined with type II RF.
Small-Range High-Precision Positioning Based on Two-Point Coordination for Robot
Authors: Li Zhengping , Qin Chaoliang , Shi Hao
Published: June 2021

This paper proposed a two-point coordinated positioning algorithm. Based on the assumption that the distance between two points was constant, a fusion algorithm was introduced into the positioning process to enhance the positioning accuracy. The simulation results showed that the proposed algorithm could reduce the RMS error to about 50% of the improved sinc interpolation-based positioning algorithm when the sampling frequency was 500 MHz and the interpolation number was 19.
CCL24 Protects Renal Function by Controlling Inflammation in Podocytes
Authors: Wang Youdi , Wu Xue , Geng Mengya , Ding Jiamin , Lv Kangjia , Du Hui , Ding Jiahui , Pei Wenjun , Hu Xin , Gu Jing , Wang Lizhuo , Zhang Yao , Gao Jialin
Published: June 2021

Diabetic nephropathy (DN) is one of the most lethal complications of diabetes mellitus with chronic inflammation. We have examined the role of the inflammatory chemokine CCL24 in DN. We observed that serum levels of CCL24 were significantly elevated in patients with DN. Not only that, the expression of CCL24 was significantly increased in the kidneys of DN mice. The kidney of DN mice showed increased renal fibrosis and inflammation. We characterized an in vitro podocyte cell model with high glucose. Western blot analysis showed that expression of CCL24 was significantly increased under high-glucose conditions. Stimulation with high glucose (35 mmol/L) resulted in an increase in CCL24 expression in the first 48 hours but changed little after 72 hours. Moreover, with glucose stimulation, the level of podocyte fibrosis gradually increased, the expression of the proinflammatory cytokine IL-1β was upregulated, and the expression of the glucose transporter GLUT4, involved in the insulin signal regulation pathway, also increased. It is suggested that CCL24 is involved in the pathogenesis of DN. In order to study the specific role of CCL24 in this process, we used the CRISPR-Cas9 technique to knock out CCL24 expression in podocytes. Compared with the control group, the podocyte inflammatory response induced by high glucose after CCL24 knockout was significantly increased. These results suggest that CCL24 plays a role in the development of early DN by exerting an anti-inflammatory effect, at least, in podocytes.
Glycoprotein IIb/IIIa Inhibitors May Modulate the Clinical Benefit of Radial Access as Compared to Femoral Access in Primary Percutaneous Coronary Intervention: A Meta-Regression and Meta-Analysis of Randomized Trials
Authors: Rigattieri Stefano , Cristiano Ernesto , Giovannelli Francesca , Tommasino Antonella , Cava Francesco , Citoni Barbara , Zardi Domenico Maria , Berni Andrea , Volpe Massimo
Published: June 2021

Objectives. Several randomized controlled trials (RCTs) consistently reported better clinical outcomes with radial as compared to femoral access for primary percutaneous coronary intervention (PCI). Nevertheless, heterogeneous use of potent antiplatelet drugs, such as Gp IIb/IIIa inhibitors (GPI), across different studies could have biased the results in favor of radial access. We performed an updated meta-analysis and meta-regression of RCTs in order to appraise whether the use of GPI had an impact on pooled estimates of clinical outcomes according to vascular access. Methods. We computed pooled estimates by the random-effects model for the following outcomes: mortality, major adverse cardiovascular events (death, myocardial infarction, stroke, and target vessel revascularization), and major bleedings. Additionally, we performed meta-regression analysis to investigate the impact of GPI use on pooled estimates of clinical outcomes. Results. We analyzed 14 randomized controlled trials and 11090 patients who were treated by radial (5497) and femoral access (5593), respectively. Radial access was associated with better outcomes for mortality (risk difference 0.01 (0.00, 0.01),

p
=
0.03

), MACE (risk difference 0.01 (0.00, 0.02),

p
=
0.003

), and major bleedings (risk difference 0.01 (0.00, 0.02),

p
=
0.02

). At meta-regression, we observed a significant correlation of mortality with both GPI use (

p
=
0.011

) and year of publication (

p
=
0.0073

), whereas no correlation was observed with major bleedings. Conclusions. In this meta-analysis, the use of radial access for primary PCI was associated with better clinical outcomes as compared to femoral access. However, the effect size on mortality was modulated by GPI rate, with greater benefit of radial access in studies with larger use of these drugs.
Acupuncture for Parkinson’s Disease: Efficacy Evaluation and Mechanisms in the Dopaminergic Neural Circuit
Authors: Zhao Yadan , Zhang Zichen , Qin Siru , Fan Wen , Li Wei , Liu Jingyi , Wang Songtao , Xu Zhifang , Zhao Meidan
Published: June 2021

Parkinson’s disease (PD) is a chronic and progressive neurodegenerative disease caused by degeneration of dopaminergic neurons in the substantia nigra. Existing pharmaceutical treatments offer alleviation of symptoms but cannot delay disease progression and are often associated with significant side effects. Clinical studies have demonstrated that acupuncture may be beneficial for PD treatment, particularly in terms of ameliorating PD symptoms when combined with anti-PD medication, reducing the required dose of medication and associated side effects. During early stages of PD, acupuncture may even be used to replace medication. It has also been found that acupuncture can protect dopaminergic neurons from degeneration via antioxidative stress, anti-inflammatory, and antiapoptotic pathways as well as modulating the neurotransmitter balance in the basal ganglia circuit. Here, we review current studies and reflect on the potential of acupuncture as a novel and effective treatment strategy for PD. We found that particularly during the early stages, acupuncture may reduce neurodegeneration of dopaminergic neurons and regulate the balance of the dopaminergic circuit, thus delaying the progression of the disease. The benefits of acupuncture will need to be further verified through basic and clinical studies.
Antiskin Cancer and Antioxidant Activities of Formulated Agar from Brown Seaweed Laminaria digitata (Hudson) in Dimethyl Benzanthracene-Induced Swiss Albino Mice
Authors: George Jeneesha , Thabitha A. , Vignesh N. , Manigandan V. , Saravanan R. , Daradkeh Ghaji , Qoronfleh M. Walid
Published: June 2021

This study explores the antiskin cancer effect of formulated agar (FA) from Laminaria digitata on dimethyl benzanthracene- (DMBA-) induced skin cancer mice. The agar was extracted and formulated (emulgel), and FA was biochemically characterized. The in vitro cytotoxicity of FA was tested using NTT 3T3 mice fibroblast cells. The mice were divided into 5 groups: group 1 served as control mice, group 2 mice were considered as DMBA-induced cancer control, group 3 mice were FA pretreated (low dose) + DMBA-induced mice, group 4 mice were FA pretreated (high dose) + DMBA-induced mice, and group 5 were positive control + DMBA-induced mice. The behaviour and biochemical markers of cancer were significantly decreased in group 2 (DMBA-induced) mice, which were brought to near normalcy by FA pretreated mice (groups 3 and 4). The levels of p53 and keratin were significantly elevated in group 2 mice and these levels were decreased in 3 and 4 mice as well. The histopathological examination of DMBA-induced mice was shown degenerated cervical patches in the skin, cirrhosis in liver, oedema in the renal tissue, and swollen and damage in cardiac tissue, which were reduced for the mice applied with FA. This confirms that FA pretreatment offered potential antiskin cancer property.
The Therapeutic Potential of Wogonin Observed in Preclinical Studies
Authors: Sharifi-Rad Javad , Herrera-Bravo Jesús , Salazar Luis A. , Shaheen Shabnum , Abdulmajid Ayatollahi Seyed , Kobarfard Farzad , Imran Muhammad , Imran Ali , Custódio Luísa , Dolores López María , Schoebitz Mauricio , Martorell Miquel , Kumar Manoj , Ansar Rasul Suleria Hafiz , Cho William C.
Published: June 2021

Wogonin is a flavonoid found in different plants such as roots of Scutellaria baicalensis Georgi distributed mainly in Asia and Europe. Dried root extracts of S. baicalensis with high content of wogonin, popularly known as “Huang-Qin” or Chinese or baical skullcap, have been used for long time in traditional Chinese medicine. Several health benefits are attributed to wogonin and derivatives showing anti-inflammatory, antiviral, anticancer, and antioxidant effects and more recently antineurodegenerative properties. Preclinical pharmacological activities of wogonin against diverse types of cancer such as breast, colorectal, and human gastric cancer will be presented in this review. In addition, studies on oxidative stress and bioavailability of wogonin will be discussed together with antineurodegenerative potential with special focus on Alzheimer’s disease. Outcomes extracted from the last preclinical studies related to therapeutic applications of wogonin will be commented and updated in this review. The scientific evidence collected in this review aims to encourage transfer of the preclinical evidence of wogonin to new clinical studies.
Unmasking New Promises: Expanding the Antigen Landscape For Antibody–Drug Conjugates
Authors: Oberoi Honey K. , Garralda Elena
Published: June 2021

Cross-reactivity with normal tissues is one of the key concerns for target selection for antibody–drug conjugates. Probody therapeutics are masked antibodies that can selectively be activated by proteases in the tumor. CX-2029, is a first-in-class Probody targeting CD71 with preliminary efficacy and a tolerable safety profile.

See related article by Johnson et al., p. 4521
Masked Hypertension in Adolescents with Type 1 Diabetes Mellitus: An Exploratory Study
Authors: Afandi Bachar , Bernieh Bassam , Roubi Sana , Al Kaabi Juma
Published: June 2021

Introduction: Masked hypertension (MHTN) is the finding of elevated out-of-office blood pressure (BP) measurement. This is a pilot study to evaluate the prevalence of MHTN in adolescents with type 1 diabetes mellitus (T1DM). Patients and Methods: Normotensive, adolescents with T1DM were recruited from Tawam Adolescents Diabetes Clinic at Tawam hospital, Al Ain, UAE. They consented to wear the ambulatory BP monitoring (ABPM) device. The heart rate and ambulatory BP were recorded at 15-min intervals for 24 h. Abnormal systolic BP (SBP) and diastolic BP (DBP) were defined as readings above 135 and 85 mm Hg; respectively. Results: Thirteen patients (10 females) were recruited from “Tawam Adolescents Diabetes Clinic.” The median age was 17 (15–19) years, median BMI 21.4 (14.8–29), and median diabetes duration 9 (3–12) years. All patients had normal retinal examination within the past 12 months. Family history of hypertension (HTN) was present in 6/13 (46%) patients. Office BP measurements revealed a mean DBP ± SD of 72 ± 6.9 mm Hg and mean SBP ± SD116 ± 5.5 mm Hg. The median HbA1c was 8.4% (5.6–13.7) and median GFR 125 mL/min/m2 (87–134). Two patients had microalbuminuria. Twenty-four hour ABPM revealed elevated SBP and DBP in 12.2 and 5.8% of the values; respectively. Further analysis confirmed MHTN in 4 (30%) patients, nondipping pattern of BP in 5 (38%) patients, and elevated pulse pressure in 8 (61.5%) patients. Only 4 (30%) patients had normal studies. Conclusions: ABPM uncovered a very high prevalence of MHTN in our patients. Whenever available, ABPM provides an excellent tool for diagnosis and hence early evaluation and management of HTN in adolescents with T1DM. Well-designed large-scale studies are needed to examine the magnitude of MHTN among adolescents with T1DM.
Relationship between the FTO Genotype and Early Chronic Kidney Disease in Type 2 Diabetes: The Mediating Role of Central Obesity, Hypertension, and High Albuminuria
Authors: Marchetti Júlia , Balbino Karla P. , Hermsdorff Helen Hermana M. , Juvanhol Leidjaira L. , Martinez José Alfredo , Steemburgo Thais
Published: June 2021

Introduction: Single nucleotide polymorphisms (SNP) in the fat mass and obesity-associated (FTO) gene have been associated with type 2 diabetes (T2D) and its complications. The aim of the present research was to investigate which and how (directly or indirectly) clinical and metabolic variables mediate the association between fat mass and the FTO gene and early chronic kidney disease (CKD) in individuals with T2D. Methods: This cross-sectional study was conducted in a sample of 236 participants with T2D (53.4% women, mean age 60 ± 10 years). DNA samples were genotyped for the rs7204609 polymorphism (C/T) in the FTO gene. Clinical, anthropometric, and metabolic data were collected. Path analysis was used to evaluate the associations. Results: Of the sample, 78 individuals with T2D had CKD (33%). Presence of the risk allele (C) was higher among participants with CKD (21.8 vs. 10.8%; p = 0.023). This polymorphism was positively associated with higher waist circumference, which in turn was associated with higher glycated hemoglobin and higher blood pressure. A higher blood-pressure level was associated with higher urinary albumin excretion (UAE) and as expected, higher UAE was associated with CKD. Path analysis showed an indirect relationship between the FTO gene and early CKD, mediated by waist circumference, blood-pressure levels, and UAE. Conclusions: These findings suggest that the C allele may contribute to genetic susceptibility to CKD in individuals with T2D through the presence of central obesity, hypertension, and high albuminuria.
A Lytic Lesion in Proximal Phalanx of Hand: A Case Report and Diagnostic Approach
Authors: Sreenivas Kalyan Deepak , Parthasarathy Sathyanarayanan , Ajayakumar Akashdeep Ambikakumari
Published: June 2021

Lytic lesions arising in the hand can be confused with an enchondroma. Enchondroma is the most common tumor of the hand and can present with varied features. It often requires only observation. A dilemma arises when surgically treatable lesions like aneurysmal bone cyst (ABC) present in uncommon locations like the hand. To diagnose a lytic lesion in the hand, percutaneous biopsy is commonly done. But, percutaneous biopsy is unnecessary in enchondroma and may not be useful in conditions like simple bone cyst and ABC. In such situations, magnetic resonance imaging (MRI) can differentiate between the most frequent benign lesions of the hand thereby reducing the need for invasive procedures. We present a 25-year-old lady who presented with a painless right index finger swelling for the past 6 months. Radiographs revealed a lytic expansile lesion in the proximal phalanx of the hand. MRI showed multiple fluid-fluid levels. Curettage and autologous iliac crest bone grafting was done. Histopathology confirmed the diagnosis of an ABC. The patient was followed up for 12 months without any recurrence. We briefly review the paucity of literature on the diagnostic approach to benign lytic lesions of the hand.
Social Disconnection and Living Arrangements among Older Adults: The Singapore Chinese Health Study
Authors: Barrenetxea Jon , Yang Yi , Pan An , Feng Qiushi , Koh Woon-Puay
Published: June 2021

Introduction: Although living alone is associated with social disconnection, older adults could be socially disconnected despite living with others. Understanding the factors associated with social disconnection by living arrangement could help identify vulnerable older adults in the community. We examined the sociodemographic and health factors associated with social disconnection among two groups of older adults: those living alone and those living with others. Methods: We used data from 16,943 community-dwelling older adults from the third follow-up of the Singapore Chinese Health Study (mean age: 73 years, range: 61–96 years). We defined social disconnection as having no social participation and scoring in the lowest decile on the Duke Social Support Scale of perceived social support. We ran logistic regression models to study the sociodemographic (age, gender, and education) and health (self-rated health, instrumental limitations, cognitive function, and depression) factors associated with social disconnection, stratified by living arrangement. Results: About 6% of our participants were socially disconnected. Although living alone was significantly associated with social disconnection (OR 1.93, 95% CI: 1.58–2.35), 85.6% of socially disconnected older adults lived with others, most of them (92%) with family. Lower education level, cognitive impairment, fair/poor self-rated health, instrumental limitations, and depression were independently associated with social disconnection. Among those living alone, men were more likely to experience social disconnection than women (OR 2.18, 95% CI: 1.43–3.32). Discussion/Conclusion: Though living alone is associated with social disconnection, most socially disconnected individuals lived with family. Community interventions could focus on those in poor health despite living with family and older men living alone.
Knowledge, Attitude, and Practice toward COVID-19 among UAE Residents: An Online Cross-Sectional Survey
Authors: Lutfi Lubna , AlMansour Alma , AlMarzouqi AlReem , Hassan Syeda Hira , Salman Zainab , Hamad Hiba , Farghaly Samia , AlAjmani Dina
Published: June 2021

Background: COVID-19 is an emerging respiratory virus which was initially reported to the WHO on December 31, 2019 and declared as a public health emergency by the WHO on March 11, 2020. Aim: The aim of the study was to investigate the public knowledge, attitudes, and practice toward COVID-19. Method: This is an online cross-sectional study. The questionnaire was in both Arabic and English languages and consisted of 4 segments (demographic, knowledge, attitude, and practice). The results were collected anonymously. The data were entered in Excel sheets and then exported and analyzed using SPSS software. Results: A total of 1,602 UAE residents completed the questionnaire. The mean knowledge score is 71%, which reflects good knowledge. The mean attitude score is 78%, which reflects a positive attitude. The mean practice score is 76%, which reflects good practice. Ninety-four percent of the population avoid handshakes, 93.3% wear face masks regularly, 85.5% use hand sanitizers, and 66% wash their hands, 22.7% drink honey with ginger, 13% still prefer to take garlic, and 82% chose to constantly update themselves with information about COVID-19; however, only 10% relied on purely medical sources. Conclusions: This study showed that UAE residents have satisfactory knowledge and favorable practice, with an overall high positive attitude. However, it is still encouraged to continue efforts in spreading awareness and public health education across all platforms, as well as increase awareness campaigns and correct misconceptions circulating on nonmedical platforms since they are a major source of information for the public.
Statin Intake and All-Cause Mortality among Older Nursing Home Residents
Authors: De Spiegeleer Anton , Van Migerode Jordi , Bronselaer Antoon , Wynendaele Evelien , Peelman Milan , Vandaele Filip , Byttebier Geert , De Tré Guy , Belmans Luc , Van De Wiele Christophe , Sathekge Mike , Van Dijck Diemer , Saxberg Bo , Alexander Myriam , Fedson David , Elewaut Dirk , Van Den Noortgate Nele , De Spiegeleer Bart
Published: June 2021

Background: Statins are progressively accepted as being associated with reduced mortality. However, few real-world statin studies have been conducted on statin use in older people and especially the most frail, that is, the nursing home residents. Objective: The aim of this study was to evaluate the impact of statin intake in nursing home residents on all-cause mortality. Method: This is a cross-sectional study of 1,094 older people residing in 6 nursing homes in Flanders (Belgium) between March 1, 2020 and May 30, 2020. We considered all residents who were taking statins for at least 5 days as statin users. All-cause mortality during the 3 months of data collection was the primary outcome. Propensity score overlap-weighted logistic regression models were applied with age, sex, functional status, diabetes, and cardiac failure/ischemia as potential confounders. Results: 185 out of 1,094 residents were on statin therapy (17%). The statin intake was associated with decreased all-cause mortality: 4% absolute risk reduction; adjusted odds ratio 0.50; CI 0.31–0.81, p = 0.005. Conclusions: The statin intake was associated with decreased all-cause mortality in older people residing in nursing homes. More in-depth studies investigating the potential geroprotector effect of statins in this population are needed.
Prospective Single-Center Study of SuperPulsed Thulium Fiber Laser in Retrograde Intrarenal Surgery: Initial Clinical Data
Authors: Taratkin Mark , Azilgareeva Camilla , Korolev Dmitry , Barghouthy Yazeed , Tsarichenko Dmitry , Akopyan Gagik , Chinenov Denis , Ali Stanislav , Kozlov Vasiliy , Mikhailov Vasiliy , Enikeev Dmitry
Published: June 2021

Introduction: The objective of this study was to present our clinical experience of using the thulium fiber laser in retrograde intrarenal surgery (RIRS). Methods: A prospective clinical study performed after the IRB approval (Sechenov University, Russia). Patients with stones <30 mm were treated with SuperPulsed thulium fiber laser (SP TFL) (NTO IRE-Polus, Russia) through a 200-μm-diameter fiber. Stone size, density, the duration of the operation, and laser on time (LOT) were measured. Based on the surgeon’s feedback, retropulsion and intraoperative visibility were also assessed (Likert scale). Stone-free rates (SFRs) were assessed with a low-dose CT scan 90 days after the operation. Results: Between January 2018 and December 2019, 153 patients (mean age 54 ± 2.8 years) underwent RIRS with SP TFL (mean stone density 1,020 ± 382 HU). Median stone volume was 279.6 (139.4–615.8) mm3. Median LOT was 2.8 (IQR 1.6–6.6) min with median total energy for stone ablation 4.0 (IQR 2.1–7.17) kJ, median ablation speed was 1.7 (1.0–2.8) mm3/s, median ablation efficacy was 13.3 (7.3–20.9) J/mm3, and energy consumption was 170.3 (59.7–743.3) J/s. Overall, the SFR (at 3 months) was 89%. The overall complication rate was 8.4%. Retropulsion was present in 23 (15.1%) patients. Visibility was estimated as optimal in most patients, with poor visibility reported in only 13 (8.5%) patients. Conclusion: The SP TFL is a safe and efficient tool in lithotripsy, irrespective of the stone type and density. Retropulsion is minimal and visibility is maintained with SP TFL. Nonetheless, further clinical studies are needed to ensure optimal comparison with conventional holmium:YAG lithotripsy.
Long-Term Follow-Up after Radiotherapy of Hidradenitis Suppurativa
Authors: Boer Jurr
Published: June 2021

Background: Patients with hidradenitis suppurativa (HS) are still often disappointed with the current treatments offered and there is a clear demand for more effective options. Since the late 1990s there has been a revival in the use of radiotherapy (RT) for different benign diseases, including HS. During the past 20 years one case series and some scattered case reports have described promising results of RT. Objectives: To evaluate the long-term efficacy of RT in early-stage HS. Methods: A postal survey-based long-term follow-up with simple factual questions of partly retrospective and partly contemporary characteristics was performed. Sixty-four patients (96 axillae), diagnosed with mild to moderate HS were irradiated with a orthovoltage unit with 100 kV, 3 mm Al or 200 kV, 0.5 Cu filtering, respectively. Four to six biweekly fractional doses ranging from 0.75 to 1 Gy up to a total dose of 6 Gy in one series, and in chronic cases followed by four daily fractions of 2 Gy up to a total dose of 14 Gy, were given. Late treatment toxicity and the rate of remission of the disease were evaluated. Results: The overall response rate of the survey was 64.1% with 40.6% (26/64) valid, complete questionnaires. In total, 40 axillae were irradiated in these 26 patients. After a median follow-up of 40 years (range 32–52) complete remission of the lesions occurred in 34 of the 40 sites (85%). None of the 26 patients with 40 irradiated sites reported adverse effects at the time of the survey. Conclusions: RT appears to be an effective treatment for early and mild HS in the majority of patients. In this case series, no side effects were reported after a median follow-up period of 40 years.