bluuebunny/crossref_metadata_2025 huggingface dataset:
Reconstruction for massive proximal tibial bone defects using patient-customized three-dimensional-printed metaphyseal cones in revision total knee arthroplasty
Authors: Li Yang , Wang Xinguang , Tian Hua
Published: June 2020

Background
The reconstruction of massive bone defects is one of the main challenges in revision total knee arthroplasty (RTKA). Although several methods are available, each of them has its prominent shortcomings. The purpose of this study is to review the clinical outcomes of RTKA with massive proximal tibial bone defects using patient-customized three-dimensional (3D)-printed highly porous metaphyseal cones.
Methods
We retrospectively reviewed seven RTKAs with Anderson Orthopaedic Research Institute (AORI) type III tibial defects using patient-customized 3D-printed highly porous metaphyseal cones, which have been performed at a single institution between 2016 and 2018. The mean length of follow-up was 25.3 months (19–36).
Results
The mean age at diagnosis of the patients was 68 years old (61–77). At the latest follow-up, no aseptic loosening or prosthetic joint infection has been determined. The mean HSS increased from 49 (39–63) to 78 (70–83) (P < 0.01); the mean WOMAC increased from 59 (46–73) to 26 (12–38) (P < 0.01). All patients obtained the range of motion and mechanical alignment improvement postoperatively.
Conclusion
The patient-customized 3D-printed metaphyseal cone could be a promising technique in addressing severe tibial defects in RTKA. Our study shows encouraging short-term clinical and radiological outcomes with no aseptic loosening, periprosthetic infection, or fracture. Nevertheless, further follow-up and the expansion of sample size are needed to demonstrate the advantage of this innovative technique fully.
Acute Encephalopathy in Children with Tuberous Sclerosis Complex
Authors: Numoto Shingo , Kurahashi Hirokazu , Sato Atsushi , Kubota Masaya , Shiihara Takashi , Okanishi Tohru , Tanaka Ryuta , Kuki Ichiro , Fukuyama Tetsuhiro , Kashiwagi Mitsuru , Ikeno Mitsuru , Kubota Kazuo , Akasaka Manami , Mimaki Masakazu , Okumura Akihisa
Published: June 2020

ObjectiveWe examined the clinical manifestations of acute encephalopathy (AE) and identify risk factors for AE in children with tuberous sclerosis complex (TSC).MethodsThe clinical data of 11 children with TSC associated with AE and 109 children with TSC alone aged 4 years or older were collected from 13 hospitals.ResultsOf the 11 children with AE, 5 had histories of febrile seizures (FS), and all had histories of febrile status epilepticus (FSE). AE developed within 24 h after fever onset in all children with seizures lasting 30 min or longer. All children developed coma after seizure cessation. Head magnetic resonance imaging (MRI) revealed widespread abnormalities in the cerebral cortex, subcortical white matter, corpus callosum, basal ganglia, and thalamus. One child died; seven had severe neurological sequelae; and the other three, mild sequelae. Logistic regression analysis revealed that a history of FSE was correlated with the development of AE.SignificanceAE in children with TSC was characterized by sudden onset after fever, followed by coma, widespread brain edema evident on MRI, and poor outcomes. A history of FSE was a risk factor for the development of AE.
Management of life-threatening acute respiratory syndrome and severe pneumonia secondary to COVID-19 in pregnancy: a case report and literature review
Authors: Yaqoub Salwa , Ahmad Shamsa , Mansoori Zeena , Pallivalapila Abdulrouf , Kassem Wessam El , Maslamani Muna , Jubara Mahmoud Abu , Minisha Fathima , Tarannum Asma , Babarinsa Isaac , Abdussalam Ahmed , Sayed Hamdy , Rivero Teresa , Mohammad Aftab , Thomas Binny , Hail Moza Al
Published: June 2020

BackgroundAs COVID-19 continues to infect women of all gestational ages; gravida in labor and the acutely ill parturient are particularly at higher risk of infection. No therapeutic agent or vaccine is approved to treat COVID-19 till date. Thus, managing COVID-19 and associated complications during pregnancy is often challenging and requires a multidisciplinary approach to treatment. Case PresentationWe narrate our perspectives on managing a 32-year-old, critically ill obstetric patient at 32-week gestation, diagnosed with acute respiratory distress syndrome (ARDS) secondary to COVID-19 pneumonia. Upon confirmation of COVID-19, as per the local protocol antivirals, antimalarial, and antibiotics were commenced. Due to rapidly exacerbating maternal respiratory functions, and potential chances of fetal hypoxemia emergency caesarian was performed. Following delivery, the maternal respiratory functions further deteriorated as she required prolonged mechanical ventilation and initiation of extracorporeal membrane oxygenation until she was clinically stable on day 23. The patient also received convalescent plasma and tocilizumab as a part of the treatment protocol. The newborn was shifted to neonatal intensive care for intubation for respiratory distress and was found negative for SARS-CoV-2 and COVID-19 immunoglobulin (Ig). At day 25, the patient was clinically stable and was transferred to step down unit and discharged thereafter. Conclusion Through this case, we present the thought process, multidisciplinary team-based strategy and sequel of managing a complex, critically ill obstetric patient with ARDS and COVID-19 pneumonia. We anticipate that this case report will assist other healthcare institutions to manage critically ill patients with COVID-19 pneumonia.Key words: COVID-19, maternal, pandemic, perinatal, ECMO, convalescent plasma, pharmacological interventions.
Clinical course and outcome of patients with acute pulmonary embolism rescued by veno-arterial extracorporeal membrane oxygenation: a retrospective review of 21 cases
Authors: Chen Yen Yu , Wu Chia-Chen , Yen Hsu-Ting , Huang Kwan-Ru , Sheu Jiunn-Jye , Lee Fan-Yen
Published: June 2020

Background

Veno-arterial extracorporeal membrane oxygenation (ECMO) is increasingly being utilized in patients with massive pulmonary embolism (PE). However, the efficacy and the safety remain uncertain. This study aimed to investigate clinical courses and outcomes in ECMO-treated patients with acute PE.
Methods

Twenty-one patients with acute PE rescued by ECMO from January 2012 to December 2019 were retrospectively analysed. Clinical features, laboratory biomarkers, and imaging findings of these patients were reviewed, and the relationship with immediate outcome and clinical course was investigated.
Results

Sixteen patients (76.2%) experienced refractory circulatory collapse requiring cardiopulmonary resuscitation (CPR) or ECMO support within 2 hours after the onset of cardiogenic shock, and none could receive definitive reperfusion therapy before ECMO initiation. Before or during ECMO support, more than 90% of patients had imaging signs of right ventricular (RV) dysfunction. In normotension patients, the computed tomography (CT) value was a valuable predictor of rapid disease progression compared with cardiac troponin I level. Ultimately, in-hospital death occurred in 10 patients (47.6%) and 90% of them died of prolonged CPR-related brain death. Cardiac arrest was a significant predictor of poor prognosis (p = 0.001).
Conclusions

ECMO appears to be a safe and effective circulatory support in patients with massive PE. Close monitoring in intensive care unit is recommended in patients with RV dysfunction and aggressive use of ECMO may reduce the risk of sudden cardiac arrest and improve clinical outcome.
Physical Frailty and Its Associated Factors Among Elderly Nursing Home Residents in China
Authors: Liu Weiwei , Puts Martine , Jiang Fen , Zhou Chuyi , Tang Siyuan , Chen Sanmei
Published: June 2020

Background: Evidence is scarce on the trend in prevalence of physical frailty in China; the primary purpose of this study was to identify the prevalence and correlates of physical frailty among older nursing home residents in China.Methods: Cross-sectional study in 20 nursing homes in Changsha, China. Physical frailty was defined based on the frailty phenotype including weight loss, low grip strength, exhaustion, slow gait speed, and low physical activity. Participants with at least three affected criteria were defined as being frail. Participants with one or two affected criteria were considered as pre-frail, and those with no affected criteria were considered as robust. A total of 1004 nursing home residents aged 60 and over were included in this study. A multinomial logistic regression model was used to analyze the associations of physical frailty with its potential risk factors, including age, sex, education levels, marital status, type of institution, living status, current drinking, current smoking, regular exercise, and self-reported health.Results: The overall prevalence of physical frailty and prefrailty was 55.6%, and 38.5%, respectively. The rate of physical frailty substantially increased with age, and was higher in women than in men (69.5% vs. 30.5%). The multinomial logistic regression analysis showed that older age, being women, living in a private institution, living alone or with unknown person, having no regular exercise (≤ 2 times/week), and poor self-reported health were significantly associated with increased odds of being physically frail. Conclusion: We demonstrated physical frailty is highly prevalent among older residents in nursing homes in China, especially in women. The potential role of those associated factors of physical frailty warrant further investigations to explore their clinical application among elderly nursing home residents.
Distribution and Microstructure Analysis of Ceramic Particles in the Lead-Free Solder Matrix
Authors: Pal Manoj Kumar , Gergely Gréta , Koncz-Horváth Dániel , Gácsi Zoltán
Published: June 2020

The Sn-3.0Ag-0.5Cu solder alloy is a prominent candidate for the Pb-free solder, and SAC305 solder is generally employed in today’s electronic enterprise. In this study, the formation of intermetallic compounds (Cu6Sn5 and Ag3Sn) at the interface, average neighbour’s particle distance, and the morphological mosaic are examined by the addition of SiC and nickel-coated silicon carbide reinforcements within Sn-3.0Ag-0.5Cu solder. Results revealed that the addition of SiC and SiC(Ni) particles are associated with a small change to the average neighbor’s particle distance and a decrease of clustering rate to a certain limit of the Sn-3.0Ag-0.5Cu solder composites. Moreover, the development of the Cu6Sn5 and the structure of the Ag3Sn are improved with the addition of SiC and Ni coated SiC.
Adipokines and risk of rheumatoid arthritis: a Mendelian randomization study
Authors: Zhu Jiahao , Zheng Haiyan , Li Yasong , Wang Tianle , Zhong Yaohong , Fan Chunhong , Li Yingjun
Published: June 2020

Background: Circulating adipokines levels have been reported to be associated with the risk of rheumatoid arthritis (RA). However, it is still unclear whether these associations are causal or biased by reverse causation or residual confounding. This study aimed to assess potential causal roles of five adipokines (namely, adiponectin, leptin, resistin, chemerin, and retinol-blinding protein 4 [RBP4]) in the occurrence of RA.Methods: We conducted a two-sample Mendelian randomization analysis to investigate these associations. We used summary-level data from genome-wide association studies (GWASs) for adipokines in individuals of European ancestry as the exposure, and a separate large-scale meta-analysis of a GWAS which included 14,361 RA cases and 43,923 controls of European ancestry as the outcome. Genetic variants were selected as instrumental variables if robustly genome-wide significant in their associations with adipokines. The causal effects were estimated using the inverse-variance weighted method in the primary analysis. Sensitivity analyses were performed to warrant that bias due to genetic pleiotropy was unlikely.Results: The circulating resistin was found to be the only adipokinetic factor having statistical significance, with higher levels causally associated with the risk of RA (odds ratio: 1.28; 95% confidence interval: [1.07, 1.53] per unit increase in the natural log-transformed resistin). In contrast, associations of adiponectin, leptin, chemerin, and RBP4 with risk of RA were not statistically significant. The MR assumptions did not seem to be violated. Sensitivity analyses yielded consistent findings.Conclusions: Genetically predicted circulating resistin levels were positively associated with RA risk. Our analysis suggested that resistin may play a notable causal role in RA pathogenesis. It would be beneficial for the development of clinical as well as public health strategies that target appropriate levels of resistin for future RA intervention.
Impact of wound irrigation during laparoscopic appendectomy on surgical site infection in acute appendicitis: a multicenter retrospective analysis
Authors: Nam Soomin , Park Youn Young , Jung Yun Tae , Cheong Chinock
Published: June 2020

Background

Surgical site infection (SSI) is one of the major complications after appendectomy. Among the many efforts to reduce variable risk factors, subcutaneous wound irrigation has been reported in some abdominal surgeries. However, there are no relevant literatures regarding patients who underwent laparoscopic appendectomy. This study aimed to determine the effect of wound irrigation before skin closure when performing laparoscopic appendectomy.
Methods

We included patients who had undergone laparoscopic appendectomy due to acute appendicitis from March 2017 to October 2019 from three hospitals. Clinical data of 333 patients were retrospectively collected, and we divided 333 patients into three groups according to the method of wound irrigation: no irrigation (n = 93), saline irrigation (n = 144), and povidone-iodine (PI) (n = 96) groups.
Results

A total of 15 patients (4.5%) were diagnosed with SSI within postoperative 30 days. There was no difference in the SSI rates (4.3% vs. 5.1% vs. 4.5%, p = 0.953). None of the factors were associated with SSI among the variables (sex, age, ASA, perforated appendicitis, preoperative WBC and hemoglobin levels, operation time, wound irrigation, type of wound closure material, and preoperative and postoperative fever).
Conclusions

Wound irrigation did not affect the SSI rate in patients who underwent laparoscopic appendectomy.
Longitudinal comparison of anxiety and depression between idiopathic pulmonary fibrosis and other interstitial lung diseases: a prospective cohort study
Authors: Bae Won , Cho Jaeyoung , Lee Jinwoo , Park Young Sik , Lee Chang-Hoon , Lee Sang-Min , Yoo Chul-Gyu , Kim Young Whan , Choi Sun Mi
Published: June 2020

Background and objective:

Few studies have investigated the differences in the incidence of anxiety and depression among the interstitial lung diseases (ILDs). We evaluated the differences in the incidence of anxiety and depression between idiopathic pulmonary fibrosis (IPF) and non-IPF ILD, and the changes after a 1-year follow-up period.
Methods

The study participants were patients included in a prospective ILD cohort of Seoul National University Hospital between March 2013 and August 2018. Clinical variables were recorded at baseline and at 1 year. The Hospital Anxiety and Depression Scale was used to assess patient anxiety and depression at baseline and at 1-year follow-up.
Results

A total of 224 patients in the cohort participated in the study (154 [68.8%] with IPF and 70 [31.2%] with non-IPF ILD). Among them, 111 patients completed a follow-up Hospital Anxiety and Depression Scale questionnaire 1 year later (77 in the IPF group, 34 in the non-IPF group). In the IPF group, 20.8% and 27.3% of patients suffered from anxiety and 29.9% and 31.2% suffered from depression at baseline and 1-year follow-up, respectively. In the non-IPF group, 14.3% and 23.5% of patients suffered from anxiety and 24.3% and 17.6% suffered from depression at baseline and 1-year follow-up, respectively. Total score on the St. George’s Respiratory Questionnaire at baseline was associated with depression both at baseline (odds ratio 1.05; 95% confidence interval 1.02–1.08) and at 1-year follow-up (odds ratio 1.03; 95% confidence interval 1.00-1.05), even after adjusting other factors. The interaction of prevalence change of anxiety and depression at baseline and 1-year follow-up between the IPF group and the non-IPF ILD group were not statistically significant (p-value 0.878 for anxiety and 0.376 for depression, respectively).
Conclusion

The prevalence of anxiety and depression at baseline and at 1-year follow-up were not significantly different between patients with IPF and non-IPF ILD. St. George’s Respiratory Questionnaire total score at baseline was associated with depression at baseline and at 1-year follow-up.
Hepatoprotective Role of Berberine on Doxorubicin Induced Hepatotoxicity - Involvement of Cyp
Authors: Sun Bao , Yang Yue , He Mengzi , Jin Yanan , Cao Xiaoyu , Du Xiwei , Yang Ruixia
Published: June 2020

Background:

The liver is one of the major organ involved in drug metabolism. Cytochrome P450s are
predominantly involved in drug metabolism. A wide range of CYPs have been reported in the liver which have been
involved in its normal as well as in diseased conditions. Doxorubicin, one of the most potent chemotherapeutic drugs,
although highly efficacious, also has adverse side effects, with its targets being liver and cardiac tissue.

Objective:

The study aims to evaluate the reversal potentials of berberine on Doxorubicin induced cyp conversion.

Methodology:

In the present study, the interplay between anti-oxidants, cytochrome and inflammatory markers in
DOX induced liver toxicity and its possible reversal by berberine was ascertained.

Results:

DOX administration significantly elevated serum as well as tissue stress, which was reverted by berberine
treatment. A similar response was observed in tissue inflammatory mediators as well as in serum cytokine levels.
Most profound reduction in the cytochrome expression was found in Cyp 2B1, 2B2, and 2E1. However, 2C1, 2C6,
and 3A1 although showed a decline, but it did not revert the expression back to control levels.

Conclusion:

It could be concluded that berberine may be an efficient anti-oxidant and immune modulator. It
possesses low to moderate cytochrome modulatory potentials.
Preclinical Evidence for the Pharmacological Actions of Glycyrrhizic Acid: A Comprehensive Review
Authors: Rehman Muneeb U. , Farooq Adil , Ali Rayeesa , Bashir Sana , Bashir Nazirah , Majeed Samia , Taifa Syed , Ahmad Sheikh Bilal , Arafah Azher , Sameer Aga Syed , Khan Rehan , Qamar Wajhul , Rasool Saiema , Ahmad Anas
Published: June 2020

Glycyrrhiza glabra L. (Family: Fabaceae) is one of the important traditional medicinal plant used extensively in folk medicine. It is known for its ethnopharmacological value in curing a wide variety of ailments. Glycyrrhizin, an active compound of G. glabra, possesses anti-inflammatory activity due to which it is mostly used in traditional herbal medicine for the treatment and management of chronic diseases. The present review is focused extensively on the pharmacology, pharmacokinetics, toxicology, and potential effects of Glycyrrhizic Acid (GA). A thorough literature survey was conducted to identify various studies that reported on the GA on PubMed, Science Direct and Google Scholar.
The Advances on the Protective Effects of Ginsenosides on Myocardial Ischemia and Ischemia-Reperfusion Injury
Authors: Wang Jiazhen , Wang Huiyun , Mou Xiaodong , Luan Mingzhu , Zhang Xiaofan , He Xiuting , Zhao Fenglan , Meng Qingguo
Published: June 2020

Ginseng is a traditional medicine with a complex chemical composition, wide bioactivity
and unique pharmacological action. Many studies have confirmed that ginsenosides are the active ingredients
of ginseng, and ginsenosides have always been the focus of different researchers. With the
development of modern separation and analysis technology, more than 150 kinds of ginsenosides have
been isolated. The ginsenosides Rb1, Rb2, Rc, Rg1 and Re account for more than 80% of total ginsenosides,
and other saponins, such as Rd, Rg3 and Rh2, which are minor constituents, accounting for
only a small portion of the total amount. In recent years, ginsenosides have been found to possess
strong pharmacological activities, such as antioxidation, clearing of oxygen free radicals, reducing calcium
overload and anti-apoptosis. Ginsenosides play a protective role in ischemia-reperfusion injury.
This paper reviews the protective effects of ginsenosides on myocardial ischemia and ischemiareperfusion
injury.
Structure-Activity Relationships of Natural and Synthetic Indole-Derived Scaffolds as α-Glucosidase Inhibitors: A Mini-Review
Authors: Wang Jiangming , Lu Silei , Sheng Ruilong , Fan Junting , Wu Wenhui , Guo Ruihua
Published: June 2020

α-Glucosidase plays an important role in carbohydrate metabolism and is an attractive drug
target for the treatment of diabetes, obesity and other related complications. Currently, acarbose, miglitol
and voglibose have been approved by the FDA for the treatment of diabetes by oral α-glucosidase inhibitors.
With the development of anti-diabetic drugs, the emergence of novel drugs with various chemotypes
has overshadowed α-glucosidase inhibitors. Since the 1990s, the FDA has not approved new chemical
entities against α-glucosidase, which has resulted in restricted clinical medication. Nevertheless,
this type of inhibitors possess several unparalleled advantages over other drugs, especially mild side
effects (non-systemic gastrointestinal side effects and occasional allergic reactions). Additionally,
α-glucosidase inhibitors for monotherapy or in combination with other drugs have been proved to be a
feasible approach for the treatment of diabetes. In the last decade, the discovery of natural or synthetic
indole derivatives possessing the inhibitory activity of α-glucosidase has received great attention.
Herein, we have summarized indoles as inhibitors of α-glucosidase activity, their mechanism of action,
synthetic methodologies and structure-activity relationships. Moreover, we have compared the inhibitory
potencies of all compounds under their corresponding positive control as well as oral absorption
in silico evaluated by tPSA. This review will provide a medium on which future drug design and development
for the treatment of diabetes may be modeled as many drug candidates with present great
potential as effective anti-diabetic chemotherapy.
Harnessing Drug Repurposing for Exploration of New Diseases: An Insight to Strategies and Case Studies
Authors: Jain Priti , Jain Shreyans K. , Jain Munendra
Published: June 2020

Background:

Traditional drug discovery is time consuming, costly, and risky process. Owing to the large investment, excessive attrition, and declined output, drug repurposing has become a blooming approach for the identification and development of new therapeutics. The method has gained momentum in the past few years and has resulted in many excellent discoveries. Industries are resurrecting the failed and shelved drugs to save time and cost. The process accounts for approximately 30% of the new US Food and Drug Administration approved drugs and vaccines in recent years.

Methods:

A systematic literature search using appropriate keywords were made to identify articles discussing the different strategies being adopted for repurposing and various drugs that have been/are being repurposed.

Results:

This review aims to describe the comprehensive data about the various strategies (Blinded search, computational approaches, and experimental approaches) used for the repurposing along with success case studies (treatment for orphan diseases, neglected tropical disease, neurodegenerative diseases, and drugs for pediatric population). It also inculcates an elaborated list of more than 100 drugs that have been repositioned, approaches adopted, and their present clinical status. We have also attempted to incorporate the different databases used for computational repurposing.

Conclusion:

The data presented is proof that drug repurposing is a prolific approach circumventing the issues poised by conventional drug discovery approaches. It is a highly promising approach and when combined with sophisticated computational tools, it also carries high precision. The review would help researches in prioritizing the drugrepositioning method much needed to flourish the drug discovery research.
Efficient and Green Synthesis of Bis(indolyl)Methanes using Thiamine Hydrochloride as an Organocatalyst: A Parallel Scrutiny of Microwave Irradiation versus Ultrasonicator Heating in Water
Authors: Thorat Nitin M. , Dhawale Kiran D. , Kasar Sandeep B. , Thopate Manali S. , Patil Limbraj R. , Thopate Shankar R.
Published: June 2020

Thiamine hydrochloride is reported to be a highly competent promoter for the synthesis of
bis(indolyl)methanes under solvent free conditions using microwave irradiation and ultrasonicator heating in
aqueous media. Vitamin B1 is an economical, non-toxic, nonflammable and water soluble green organocatalyst.
Moreover, the simple approach, easily operational, short reaction time, high yield and using a little quantity of
thiamine hydrochloride makes this method an alternative approach. Present protocol is a simple and eco-friendly
approach for the synthesis of bis(indolyl)methanes under microwave and ultrasonicator conditions.
Xanthone: A Promising Antimycobacterial Scaffold
Authors: Elsaman Tilal , Mohamed Malik Suliman , Eltayib Eyman Mohamed , Abdalla Abualgasim Elgaili , Mohamed Magdi Awadalla
Published: June 2020

Background:

Tuberculosis (TB) is one of the infectious diseases associated with high rate of
morbidity and mortality and still remains one of the top-ten leading causes of human death in the world.
The development of new anti-TB drugs is mandatory due to the existence of latent infection as well as
the expansion of the resistant Mycobacterium tuberculosis (MBT) strains. Xanthones encompass a wide
range of structurally diverse bioactive compounds, obtained either naturally or through chemical synthesis.
There is a growing body of literature that recognizes the antitubercular activity of xanthone derivatives.

Objective:

The objective of this review is to highlight the main natural sources along with the critical
design elements, structure-activity relationships (SARs), modes of action and pharmacokinetic profiles
of xanthone-based anti-TB compounds.

Methods:

In the present review, the anti-TB activity of xanthones reported in the literature from 1972 to
date is presented and discussed.

Results:

Exploration of xanthone scaffold led to the identification of several members of this class having
superior activity against both sensitive and resistant MBT strains with distinctive mycobacterial
membrane disrupting properties. However, studies regarding their modes of action, pharmacokinetic
properties and safety are limited.

Conclusion:

Comprehendible data and information are afforded by this review and it would certainly
provide scientists with new thoughts and means which will be conducive to design and develop new
drugs with excellent anti-TB activity through exploration of xanthone scaffold.
Multi-objective Genetic Algorithm for De Novo Drug Design (MoGADdrug)
Authors: Devi R. Vasundhara , Sathya S. Siva , Coumar Mohane S.
Published: June 2020

Background:

A multi-objective genetic algorithm for De novo drug design
(MoGADdrug) has been proposed in this paper for the design of novel drug-like molecules similar
to some reference molecules. The algorithm developed accepts a set of fragments extracted from
approved drugs and available in fragment libraries and combines them according to specified rules
to discover new drugs through the in-silico method.

Method:

For this process, a genetic algorithm has been used, which encodes the fragments as
genes of variable length chromosomes and applies various genetic operators throughout the generations.
A weighted sum approach is used to simultaneously optimize the structural similarity of the
new drug to a reference molecule as well as its drug-likeness property.

Results:

Five reference molecules namely Lidocaine, Furano-pyrimidine derivative, Imatinib,
Atorvastatin and Glipizide have been chosen for the performance evaluation of the algorithm.

Conclusion:

Also, the newly designed molecules were analyzed using ZINC, PubChem databases
and docking investigations.
Characterization of Flavonoid Constituents in Stems of Lithocarpus litseifolius (Hance) Chun by UHPLC-Q-Exactive Orbitrap MS
Authors: Liu Liang-Hong , Peng Jie , Shi Si-lin , Li Kai-Lin , Xiong Pei , Cai Wei
Published: June 2020

Background:

Lithocarpus litseifolius (Hance) Chun (L. litseifolius) has been used for
treating diabetes, allergic and inflammatory diseases, and hyperlipidemia in folk medicine. Previous
studies have shown that the main active ingredients of its leaves are flavonoids. However, to the best
of our knowledge, the stem of L. litseifolius has not been investigated for its constituents yet. The
stems of the decaying plants fall every year. It is considered as a waste due to limited knowledge of
the benefits of these stems, which is a sheer waste of the plant resource. Therefore, it is necessary to
investigate the chemical constituents of the stem, which will be beneficial for the treatment of many
diseases and help utilize the stem in a better way instead of wasting the plant resource.

Methods:

In this study, the dry twigs of L. litseifolius were collected, powdered, and extracted. Then,
the extracted sample was subjected to UHPLC-Q-Exactive Orbitrap MS in negative mode combined
with Parallel reaction monitoring scanning to gain the high-resolution mass spectrum, which was
processed by the Compound Discover version 3.0 using high resolution extracted ion chromatography
to predict the constituent compounds.

Results:

A total of 35 flavonoids including flavone, flavonol, dihydroflavone, isoflavone, and dihydrochalcone
were putatively identified based on their accurate mass measurement, chromatographic
retention, MSn spectra, and bibliography data.

Conclusion:

In this study, a total of 35 flavonoids were identified in the stem of L. litseifolius,
among which 5 flavonoids were the first to be reported from this plant, which will be very helpful for
the development of medicines for the treatment of many diseases and utilization of the stem of L.
litseifolius.
Herbal Based Polymeric Nanoparticles as a Therapeutic Remedy for Breast Cancer
Authors: Mughees Mohd , Wajid Saima
Published: June 2020

Background:

The currently available anti breast cancer agents as well as conventional drug delivery
methods have some limitations.

Objective:

In view of these limitations, researchers used phytochemicals/herbal extracts as anti-breast cancer
agents together with the polymeric nanoparticles to provide an effective way of targeted drug delivery with
lesser /no side effects.

Methods:

The literature for this review was searched during the year 2015 to 2019, using the keywords, ‘ ‘breast
cancer’, ‘breast cancer and its current treatments’, ‘plants against the breast cancer’, ‘polymeric nanoparticles’,
‘herbal based polymeric nanoparticles’. The databases i.e., PubMed, Science Direct, and Google Scholar, were
used for collecting the information.

Results:

In the present review, an attempt was made to summarize the potential of herbal-based nanoformulation
as a specific and high efficacy therapeutic strategy in order to pave the way for future research involving screening
and use of herbal nanoparticles for the treatment of breast cancer.

Conclusion:

The encapsulation of the herbal extract in the polymeric nanoparticles is the prominent, effective,
and emerging way of targeted drug delivery for cancer. It may serve as a safer way of targeted drug delivery and
maybe the answer to the complications related to the currently available anti-breast cancer agents as well as
limitations of the conventional method of drug delivery.
Encapsulation of Imatinib in Targeted KIT-5 Nanoparticles for Reducing its Cardiotoxicity and Hepatotoxicity
Authors: Varshosaz Jaleh , Fardshouraki Saeedeh , Mirian Mina , Safaeian Leila , Jandaghian Setareh , Taymouri Somayeh
Published: June 2020

Background:

Using imatinib, a tyrosine kinase inhibitor drug used in lymphoblastic leukemia, has
always had limitations due to its cardiotoxicity and hepatotoxicity side effects. The objective of this study is to
develop a target-oriented drug carrier to minimize these adverse effects by the controlled release of the drug.

Methods:

KIT-5 nanoparticles were functionalized with 3-aminopropyltriethoxysilane and conjugated to rituximab
as the targeting agent for the CD20 positive receptors of the B-cells. Then they were loaded with imatinib
and their physical properties were characterized. The cell cytotoxicity of the nanoparticles was studied by MTT
assay in Ramos (CD20 positive) and Jurkat cell lines (CD20 negative) and their cellular uptake was shown by
fluorescence microscope. Wistar rats received an intraperitoneal injection of 50 mg/kg of the free drug or targeted
nanoparticles for 21 days. Then the level of aspartate Aminotransferase (AST), alanine Aminotransferase
(ALT), Alkaline Phosphatase (ALP) and Lactate Dehydrogenase (LDH) were measured in serum of animals. The
cardiotoxicity and hepatotoxicity of the drug were also studied by hematoxylin and eosin staining of the tissues.

Results:

The targeted nanoparticles of imatinib showed to be more cytotoxic to Ramos cells rather than Jurkat
cells. The results of the biochemical analysis displayed a significant reduction in AST, ALT, ALP, and LDH
levels in animals treated with targeted nanoparticles, compared to the free drug group. By comparison with the
free imatinib, histopathological results represented less cardiotoxicity and hepatotoxicity in the animals, which
received the drug through the current designed delivery system.

Conclusion:

The obtained results confirmed that the rituximab targeted KIT-5 nanoparticles are promising in
the controlled release of imatinib and could decrease its cardiotoxicity and hepatotoxicity side effects.
New Insight into Triple-Negative Breast Cancer Therapy: The Potential Roles of Endoplasmic Reticulum Stress and Autophagy Mechanisms
Authors: Ashrafizadeh Milad , Mohammadinejad Reza , Tavakol Shima , Ahmadi Zahra , Sahebkar Amirhossein
Published: June 2020

Background:

Breast cancer is accounted as the fifth leading cause of mortality among the other cancers.
Notwithstanding, Triple Negative Breast Cancer (TNBC) is responsible for 15-20% of breast cancer mortality.
Despite many investigations, it remains incurable in part due to insufficient understanding of its exact
mechanisms.

Methods:

A literature search was performed in PubMed, SCOPUS and Web of Science databases using the
keywords autophagy, Endoplasmic Reticulum (ER) stress, apoptosis, TNBC and the combinations of these
keywords.

Results:

It was found that autophagy plays a dual role in cancer, so that it may decrease the viability of tumor
cells or act as a cytoprotective mechanism. It then appears that using compounds having modulatory effects on
autophagy is of importance in terms of induction of autophagic cell death and diminishing the proliferation and
metastasis of tumor cells. Also, ER stress can be modulated in order to stimulate apoptotic and autophagic cell
death in tumor cells.

Conclusion:

Perturbation in the signaling pathways related to cell survival leads to the initiation and progression
of cancer. Regarding the advancement in the cancer pathology, it seems that modulation of autophagy and ER
stress are promising.
Smart Nanocarriers for Targeted Cancer Therapy
Authors: Martinelli Chiara
Published: June 2020

:

Cancer is considered one of the most threatening diseases worldwide. Although many therapeutic approaches have been developed and optimized for ameliorating patient’s conditions and life expectancy, however, it frequently remains an incurable pathology. Notably, conventional treatments may reveal inefficient in the presence of metastasis development, multidrug resistance and inability to achieve targeted drug delivery.

:

In the last decades, nanomedicine has gained a prominent role, due to many properties ascribable to nanomaterials. It is worth mentioning their small size, their ability to be loaded with small drugs and bioactive molecules and the possibility to be functionalized for tumor targeting. Natural vehicles have been exploited, such as exosomes, and designed, such as liposomes. Biomimetic nanomaterials have been engineered, by modification with biological membrane coating. Several nanoparticles have already entered clinical trials and some liposomal formulations have been approved for therapeutic applications. In this review, natural and synthetic nanocarriers functionalized for actively targeting cancer cells will be described, focusing on their advantages with respect to conventional treatments. Recent innovations related to biomimetic nanoparticles camouflaged with membranes isolated from different types of cells will be reported, together with their promising applications. Finally, a short overview on the latest advances in carrier-free nanomaterials will be provided.
Night-time Noise Levels and Patients’ Sleep Experiences in a Medical Assessment Unit in Northern England
Authors: Astin Felicity , Stephenson John , Wakefield Jonathan , Evans Ben , Rob Priyanka , Joanna Garside , Harris Emma
Published: June 2020

Background:

Hospital in-patients need sleep so that restorative process and healing can take place. However, over one third of in-patients experience sleep disturbance, often caused by noise. This can compromise patients’ perceptions of care quality and cause physical and psychological ill health.

Aims:

To assess 1) in-patients sleep quality, quantity, reported sources of sleep disturbance and their suggestions for improvement 2) objectively measure decibel levels recorded at night.

Methods:

This descriptive study conducted in a Medical Assessment Unit used multi-methods; a semi-structured ‘sleep experience’ questionnaire administered to a purposive sample of in-patients; recording of night-time noise levels, on 52 consecutive nights, using two calibrated Casella sound level meters.

Results:

Patient ratings of ‘in-hospital’ sleep quantity (3.25; 2.72 SD) and quality (2.91; 2.56 SD) was poorer compared to ‘home’ sleep quantity (5.07; 2.81 SD) and quality (5.52; 2.79 SD). The difference in sleep quality (p<0.001) and quantity (p<0.001) ratings whilst in hospital, compared to at home, was statistically significant. Care processes, noise from other patients and the built environment were common sources of sleep disturbance. Participants’ suggestions for improvement were similar to interventions identified in current research. The constant noise level ranged from 38-57 decibels (equivalent to an office environment), whilst peak levels reached a maximum of 116 decibels, (equivalent to banging a car door one metre away).

Conclusion:

The self-rated patient sleep experience was significantly poorer in hospital, compared to home. Noise at night contributed to sleep disturbance. Decibel levels were equivalent to those reported in other international studies. Data informed the development of a ‘Sleep Smart’ toolkit designed to improve the in-patient sleep experience.
Tetanus Toxoid Immunization Status and Associated Factors among Mothers in Hawzen, Eastern Zone of Tigray, Ethiopia, 2019
Authors: Mengesha Meresa Berwo , Weldegeorges Desta Abraha , Assefa Natnael Etsay , Gebremeskel Senait Gebreslasie , Hidru Hagos Degefa , Teame Hirut , Hailesilassie Yared
Published: June 2020

Background:

Neonatal tetanus remains a significant avertable cause of morbidity and mortality in neonates. Adequate vaccination strategies, including at least two doses of tetanus toxoid for reproductive age women, can decrease neonatal mortality. In Ethiopia, a few numbers of neonates were protected at birth through this proactive intervention. Therefore, this study aimed to determine factors associated with the low coverage of tetanus toxoid immunization.

Objective:

This study aimed to determine the status of Tetanus Toxoid immunization coverage and factors associated with it.

Methods:

Community-based cross-sectional study design was implemented among 515 mothers in Hawzen, Eastern zone of Tigray. The data were entered into Epi data manager version 3.5.1 and exported to Statistical Package for Social Science version 20 software for analysis. Bivariate and multivariate logistic regression was used to identify factors significantly associated with tetanus toxoid immunization coverage.

Results:

Two hundred and seven (40.2%) mothers were protected against tetanus at last birth. Mothers whose age was less than 20 years [AOR 0.19(0.10, 0.32), had no future plan for fertility [AOR 0.30(0.17, 0.53)], mothers attended once for antenatal care visits [AOR 0.38(0.18, 0.82)] and who got information from media [AOR 4.49(1.82, 11.07] were independent predictors of tetanus toxoid immunization status of mothers.

Conclusion:

More than half of the mothers were not protected against tetanus at the time of last birth. This study found the age of mothers, future fertility plans, numbers of antenatal care visits and mothers who got information from media; these were significant factors associated with the likelihood of tetanus toxoid immunization of mothers.
A Blended Physiotherapy Intervention for Persons With Hemophilic Arthropathy: Development Study (Preprint)
Authors: Timmer Merel A , Kloek Corelien J J , de Kleijn Piet , Kuijlaars Isolde A R , Schutgens Roger E G , Veenhof Cindy , Pisters Martijn F
Published: June 2020

BACKGROUND

Joint bleeds are the hallmark of hemophilia, leading to a painful arthritic condition called as hemophilic arthropathy (HA). Exercise programs are frequently used to improve the physical functioning in persons with HA. As hemophilia is a rare disease, there are not many physiotherapists who are experienced in the field of hemophilia, and regular physiotherapy sessions with an experienced physiotherapist in the field of hemophilia are not feasible for persons with HA. Blended care is an innovative intervention that can support persons with HA at home to perform the advised physical activities and exercises and provide self-management information.

OBJECTIVE

The aim of this study was to develop a blended physiotherapy intervention for persons with HA.

METHODS

The blended physiotherapy intervention, namely, e-Exercise HA was developed by cocreation with physiotherapists, persons with HA, software developers, and researchers. The content of e-Exercise HA was compiled using the first 3 steps of the Center for eHealth Research roadmap model (ie, contextual inquiry, value specification, and design), including people with experience in the development of previous blended physiotherapy interventions, a literature search, and focus groups.

RESULTS

A 12-week blended intervention was developed, integrating face-to-face physiotherapy sessions with a web-based app. The intervention consists of information modules for persons with HA and information modules for physiotherapists, a graded activity program using a self-chosen activity, and personalized video-supported exercises. The information modules consist of text blocks, videos, and reflective questions. The patients can receive pop-ups as reminders and give feedback on the performance of the prescribed activities.

CONCLUSIONS

In this study, we developed a blended physiotherapy intervention for persons with HA, which consists of information modules, a graded activity program, and personalized video-supported exercises.
Rethinking Language and Gender in African Fiction: Towards De-gendering and Re-gendering
Authors: Ngeh Andrew T. , Nalova Sarah M.
Published: June 2020

The recognition and acceptance of the social construction of gender and the coercive nature of gendered subjectivities has been at the centre of feminist discourse which challenges the subjugation of the woman. G.D. Nyamndi, therefore, in his Facing Meamba attempts to address these concerns and proffer feasible solutions. The representation of women in literature, the role of gender in both literary creation and literary criticism, as studied ingynocriticism, the connection between gender and various aspects of literary form in such genre and metre embody masculine values of heroism, war, and adventure. This androcentric stand has compromised the rights of the woman, resulting in her marginalization, alienation and exclusion from socio-cultural activities. She is maligned with a sense of inadequacy. The patriarchal centre prevails and dominates the woman who has been pushed to the margin of the society. In this regard, Nyamndi demonstrates that, the African woman still has a place within the postcolonial context even though the man is imbued with more powers than the woman. Informed by the postcolonial theory, this study argues that, gendering constitutes a grave danger to a harmonious existence between the two genders. The study revealed that, de-gendering and re-gendering can create harmony between the man and woman because the two concepts are basis for gender equality. To achieve this, language which constitutes a semiotic mould has been exploited to deploy themes like, gender inequality and cultural issues.
STAFFING FOR SCENARIOS OF SUSTAINABLE DEVELOPMENT OF KHARKIV REGION ECONOMIC SECTORS
Authors: Rodchenko Volodymyr , Rekun Ganna , Naidina Eugenia , Prus Yuliia , Medenets Valeriia
Published: June 2020

The article is devoted to the study of the emergence and deepening of staffing gaps that affect the development of the region under the influence of transforming production dominants in the conditions of Economy 4.0. In the course of the study, the system of factors for the emergence of staffing gaps that affect the sustainable development of the region is generalized. A matrix approach to determining staffing gaps is proposed and sectorial scenarios for preventing them in Kharkiv region economy are developed. The assumption about the perspective structure of economy sectors in Kharkiv region according to the scenarios of inertial and innovative ways of development of Ukraine is formed.
Contrato psicológico, agotamiento y cinismo del empleado: su efecto en la rotación del personal operativo en la frontera norte mexicana
Authors: Reyes Flores Griselda , Maynez-Guaderrama Aurora Irma , Cavazos Arroyo Judith , Hernández Gómez Jesús Andrés
Published: June 2020

La rotación de personal es un fenómeno costoso en términos de productividad y desempeño. La variable que mejor la predice es la intención de rotar, pero en México son escasos los trabajos empíricos sobre ella. Esta investigación tuvo por objetivo indagar si el agotamiento emocional, el cinismo organizacional y la violación del contrato psicológico, influyen sobre la intención de rotación. Para ello, se realizó una investigación cuantitativa, empírica y transversal, en una muestra de 201 empleados operativos en la industria maquiladora autopartista para la exportación, localizada en Ciudad Juárez, Chihuahua. Como técnica estadística se utilizó la modelación estructural PLS. Los resultados indican que el agotamiento emocional y el cinismo del empleado llevan a la intención de rotar, y comparativamente, es mayor la influencia del cinismo. Sin embargo, la relación predictiva entre la violación del contrato psicológico y la intención de rotar, se rechazó.