bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effects of family based care program on the health status of hemiplegic patients with stroke: A Randomized Control Trial
Authors: Naderipor Arsalan , Faramarzi Hadith , Jalali Amir , Salari Nader , Rezaei Jahangir 
Published: February 2020

Abstract
Background Stroke is a chronic disease requiring continuous and prolonged rehabilitation. A family-based care program can be an effective approach to rehabilitate the patients. This study aimed at determining the effects of family-based care program on the health status of hemiplegic patients with stroke. Methods In this clinical trial, 40 hemiplegic stroke patients were randomly selected through convenience sampling and allocated to experiment and control groups. The patients’ care providers in the experiment group received the home-based care program for four consecutive sessions (50-60min) in addition to the routine care at the time of discharge. The trainings were then performed by care givers at home for four weeks. The patients in the control group received routine cares during the discharge. The health status of patients in the both groups was evaluated using a health status questionnaire before and one months after implementing the program. The collected data was analyzed using SPSS V.21. Results The results indicated that the difference between the mean scores of the health status of the two groups was not significant before the experiment; however, it was significant after the experiment (P< 0.05). The mean scores after the experiment were significantly higher in the experiment group compared to those of the pre-intervention; this difference was not significant in the control group. Conclusion Providing home care education programs to family members and allowing them to contribute to patient care programs can increase self-care of the patients and improve their health status.
Tumor-derived exosomes induced M2 macrophage polarization and promoted the metastasis of osteosarcoma cells through Tim-3
Authors: Cheng Zhonghua , Wang Liqin , Wu Chenhuan , Huang Lin , Ruan Yuan , Xue Wei 
Published: February 2020

Abstract
Background: Osteosarcomas, the second most prevalent primary malignancy of the bone, are often presented with high-grade subclinical metastatic disease that metastasizes at very early stages. Exosomes, as molecular information carriers, may play a potent role in the occurrence and development of tumors through oncogenic molecular reprogramming of tumor-associated macrophage (TAM). In this study, we will investigate the effect of osteosarcoma-derived exosomes on the polarization of TAM and decipher its underlying molecular mechanism. Material and Methods: Osteosarcoma-derived exosomes from MG63 cells were isolated and characterized by transmission electron microscopy, and nano-particle size analysis. Double fluorescence staining was performed to confirm the macrophages phagocytosis of exosomes. Western blot, qRT-PCR, and transwell assays were conducted to assess the effect of exosomes on migration, invasion, and macrophage differentiation. The mouse model of osteosarcoma was established to evaluate the effects of exosomes on lung metastasis in vivo. Results: MG63 exosomes were successfully isolated and verified to be phagocytized by macrophages through fluorescence confocal microscopy. The results revealed that osteosarcoma cells could induce M2 type differentiation of macrophages largely through Tim-3 mediated by exosomes, which in turn could promote the migration, invasion, EMT, and lung metastasis of osteosarcoma cells through the secretion of cytokines including IL-10, TGFβ, and VEGF. Conclusions: Our results demonstrated that osteosarcoma-derived exosomes induced M2 polarization of macrophages and promoted the invasion and metastasis of tumors through Tim-3; besides, the study also suggests a novel therapeutic target for future studies.
Abnormal Regional and Global Connectivity Measures in Subjective Cognitive Decline Depending on Cerebral Amyloid Status
Authors: Li Shumei , Daamen Marcel , Scheef Lukas , Gaertner Florian C. , Buchert Ralph , Buchmann Martina , Buerger Katharina , Catak Cihan , Dobisch Laura , Drzezga Alexander , Ertl-Wagner Birgit , Essler Markus , Fliessbach Klaus , Haynes John Dylan , Incesoy Enise Irem , Kilimann Ingo , Krause Bernd J. , Lange Catharina , Laske Christoph , Priller Josef , Ramirez Alfredo , Reimold Matthias , Rominger Axel , Roy Nina , Scheffler Klaus , Schmitt Angelika , Schneider Anja , Spottke Annika , Spruth Eike Jakob , Teipel Stefan J. , Tscheuschler Maike , Wagner Michael , Wolfsgruber Steffen , Düzel Emrah , Jessen Frank , Peters Oliver , Boecker Henning 
Published: February 2020

Abstract
Background: While cerebral beta-amyloid accumulation was found in many studies to alter precuneus-based functional connectivity (FC) in mild cognitive impairment and demented Alzheimer’s disease (AD) patients, its impact is less well understood in subjective cognitive decline (SCD), which in the presence of underlying AD pathologic change corresponds to a progression to stage 2 of the clinical Alzheimer’s continuum in the 2018 National Institute on Aging and Alzheimer’s Association research framework, and represents the earliest clinical manifestation of AD. Methods: From the DELCODE (DZNE – Longitudinal Cognitive Impairment and Dementia Study) cohort, two groups of 24 age- and gender-matched amyloid-positive SCD (SCDAβ+) and amyloid-negative SCD (SCDAβ-) patients were selected according to visual [18F]-Florbetaben PET readings, and studied with resting-state BOLD fMRI. Local (regional homogeneity (ReHo), amplitude of low-frequency fluctuation (ALFF) and fractional ALFF (fALFF)) and global (degree centrality (DC), precuneus seed-based FC maps) measures were calculated and compared between both groups. Furthermore, follow-up correlation analyses probed linear relationships of observed group differences with global as well as precuneal amyloid load measured by Florbetaben standard uptake value ratios (SUVRFBB). Results: For the local measures, ReHo was significantly higher in the bilateral precuneus for the SCDAβ+ group, whereas ALFF and fALFF measures were not altered between groups. For the global measures, relatively higher precuneus-based FC with occipital areas (but no altered DC) was observed in the SCDAβ+ group. Moreover, the FC differences between precuneus and occipital areas were positively correlated with global (SCDAβ+) and local precuneus SUVRFBB (both groups). Conclusions: While confounding influences due to a higher ratio of APOE e4 carriers in the SCDAβ+ group cannot be excluded, results indicate functional alterations in the precuneus hub region that were linearly related to beta-amyloid load, highlighting incipient pathology and possible compensatory mechanisms in stage 2 of the AD continuum.
Study on the migration and transformation characteristics of arsenic and antimony in the rhizosphere of plants grown in zinc smelting waste residue
Authors: sun hang , Li Xinlong , Wu Yonggui 
Published: February 2020

Abstract
Background: In this paper, the physical and chemical characteristics of the rhizospheres of Broussonetia papyrifera, Cryptomeria fortunei, Arundo donax, Robinia pseudoacacia, Photinia serrulata and Lolium perenne grown in indigenous Zn-smelting waste residue were studied, and the effects of the rhizosphere on the migration and transformation of arsenic and antimony in waste residue were investigated. Results: The results showed that compared with the control waste residue, the pH and Eh of the waste residues from the rhizospheres of the six plants decreased significantly (P<0.05), and the dissolved organic carbon (DOC) content increased significantly (P<0.05). The peak strength of hydroxyl groups, aliphatic groups, aromatic groups, calcite and quartz in the rhizosphere waste residue decreased to different degrees compared with that of the control waste residue, and the peak strength of carbohydrates/organosilicates increased. Overall, the contents of arsenic and antimony in the rhizosphere waste residues of the 6 plants were lower than those of the control waste residue, and the contents of arsenic(III) and antimony(III) were significantly higher than those of arsenic(V) and antimony(V), respectively (P<0.05). The proportions of residual arsenic and antimony in the rhizosphere waste residues were the highest, and the proportion was significantly higher than that of control waste residue, and the proportions of exchangeable state, the aluminum-bound state and the calcium-bound state were lower than that in the control waste residue. The contents of arsenic and antimony in the tissues of the six plants followed the order of roots > leaves > stems, and the enrichment coefficients of arsenic and antimony in different plants were low. Conclusion: After 7 years of phytoremediation, the content and bioavailability of arsenic and antimony in the waste residue were significantly reduced, and the enrichment of arsenic and antimony in plant tissue was also low. It is speculated that the migration of arsenic and antimony in waste residue may increase in the early stage of phytoremediation and gradually stabilize in the later stage.
A retrospective study of prevalence and antibiotic resistance of bacteria isolated from the cerebrospinal fluid of neurosurgical patients in a Shanghai tertiary hospital
Authors: Liu Min , Zhu Yunxia , Zhou Yin , Xu Siyi , Ma Jing , Zhang Tao , Xu Li , Wu Wenjuan , Zhong Chunlong 
Published: February 2020

Abstract
Background: Postoperative central nervous system infections (PCNSIs) are serious complications following neurosurgery. Effective management of the infections depends on the identification of causative pathogens and the antibiotic sensitivities. The aim of this study was to investigate the clinical features, causative organisms and their antimicrobial susceptibility testing results, which could help clinicians to initiate appropriate empirical antibiotic therapy.Methods: This was a retrospective study conducted over a period of 3.5 years (from January 2016 to July 2019). All in-patients admitted neurosurgery and ICU meeting the inclusion criteria of PCNSIs were included in the study. Demographic characteristics, type of neurosurgery, laboratory data, causative organisms and antimicrobial susceptibility testing results were analyzed.Results: A total of 1500 patients underwent operation during this study. Twenty-three patients with 34 isolates out of 79 patients with 157 CSF culture samples were available for data analysis. The estimated incidence and culture-positive rate of PCNSIs were approximately 1.5% and 29.1%, respectively. The predominant organism was coagulase-negative staphylococci, of which most were methicillin-resistant coagulase-negative staphylococci (MRCoNS). All were susceptible to vancomycin, linezolid, and rifampicin. Acinetobacter baumannii was the most frequent causative Gram-negative agent and was resistant to 14 out of 17 antimicrobials tested. The sensitivity rates for amikacin, sulfamethoxazole-trimethoprim and minocycline were only 44, 44, and 11%, respectively.Conclusions: The MRCoNS were the predominant organism for PCNSIs. The management of Acinetobacter baumannii could be a major clinical challenge with few effective antimicrobials in PCNSIs.
Methylation regulation of MUC6 correlates with metastasis of gastric cancer
Authors: Shi Ding , Xi Xiaoxia 
Published: February 2020

Abstract
Background: The aim of this study was to investigate the mechanism of the downregulation of MUC6 and its influence on GC metastasis.Methods: The expression of MUC6 was examined in cancer tissues and their corresponding adjacent normal tissues in 40 gastric adenocarcinoma patients. The investigation of methylation level of MUC6 promoter region in gastric cell lines and gastric specimen tissues was performed through immunohistochemistry and/or quantitative polymerase chain reaction (qPCR)s. MUC6 was knocked down in GES-1 cell lines and overexpressed in SGC7901 cell lines; the effects of MUC6 knockdown and overexpression on cell migration and invasion were examined using Transwell migration assay. The effects of demethylation and methylation on MUC6 expression were examined using Western blot, qPCR, or double luciferase report experiment.Results: The expression of MUC6 in GC tissues was significantly lower than that in normal paracancerous tissues. While the cells migration and invasion abilities were decreased significantly after overexpression of MUC6, these abilities increased significantly after the knocking down of MUC6. The methylation levels of MUC6 in GC tissues and GC cell lines (MGC803, MKN45, AGS, SGC7901, and BGC823) were significantly higher than those in paracancerous tissues and gastric epithelial cells. The promoter methylation could significantly reduce the binding of MUC6 promoter region to the related transcription factors. The expression of MUC6 increased with the concentration of demethylated drugs and the time of action.Conclusion: The expression of MUC6 was regulated by methylation of its promoter, and this methylation of MUC6 promoter may lead to significant downregulation of MUC6 in GC and promote the metastasis of GC.
Natural presence of the V179D and K103R/V179D mutations associated with resistance to nonnucleoside reverse transcriptase inhibitors in HIV-1 CRF65_cpx strains
Authors: Liu Yongjian , Zhang Yu , Li Hanping , Wang Xiaolin , Jia Lei , Han Jingwan , Li Tianyi , Li Jingyun , Li Lin 
Published: February 2020

Abstract
Background: There is increasing evidence that HIV-1 genetic diversity can have an impact on drug resistance. The aim of this study is to investigate the epidemiological situation of CRF65_cpx and the impact of natural polymorphisms of this variant on genotypic resistance.
Methods: We used the BLAST search program followed by phylogenetic analysis to identify additional CRF65_cpx pol sequences from the Los Alamos HIV Sequence Database. Maximum likelihood phylogeny was estimated to clarify the epidemiological relationship of CRF65_cpx strains. Genotypic resistance was determined by submitting sequences to the Stanford HIV Drug Resistance Database.
Results: A total of 32 CRF65_cpx pol sequences were obtained. The CRF65_cpx strains were detected in seven provinces with large geographic distance. Yunnan CRF65_cpx sequences were mainly derived from a heterosexual risk group, whereas the CRF65_cpx sequences in other provinces were almost exclusively derived from an MSM population. With one exception of V179E, the other 31 strains harbored V179D mutation. The combination of V179D and K103R, conferring intermediate resistance to EFV and NVP, was detected in seven treatment-naive MSM patients.
Conclusions: This study confirmed the expansion CRF65_cpx in China. Furthermore, we found the natural presence of the V179D and K103R/V179D mutations associated with resistance to NNRTIs in HIV-1 CRF65_cpx. Our findings highlight the contribution of polymorphic mutations to drug resistance and underscore the challenges in treating patients harboring CRF65_cpx strains.
Alkylamino Phenol Derivative Induces Apoptosis by Inhibiting EGFR Signaling Pathway in Breast Cancer Cells
Authors: Palanivel Suresh , Yli-Harja Olli , Kandhavelu Meenakshisundaram 
Published: February 2020

Background and Objective:
The present study was carried out to evaluate the anticancer property of
an alkylamino phenol derivative -2-((3,4-Dihydroquinolin-1(2H)-yl)(p-tolyl)methyl)phenol) (THTMP) against
human breast cancer cells. The cytotoxicity of the THTMP was assessed to know its specificity towards breast
cancer cells without affecting the normal cells.

Methods:
The THTMP was synthesized and the cytotoxicity was assessed by MTT assay, Caspases enzyme
activity, DNA fragmentation and FITC/Annexin V, AO/EtBr staining, RT-PCR and QSAR. In addition, ADME
analysis was executed to understand the mode of action of THTMP.

Results:
THTMP showed potential cytotoxic activity against the growth of MCF7 and SK-BR3 cells with the
IC50 values of 87.92μM and 172.51μM, respectively. Interestingly, THTMP found to activate caspase 3 and
caspase 9 enzymes in cancer cells, which are the key enzymes implicated in apoptosis. THTMP induced apoptosis
in which 33% of the cells entered the late apoptotic stage after 24h of treatment. The results also revealed
that the apoptotic response could be influenced by the association of THTMP with the Epidermal Growth Factor
Receptor (EGFR) mediated inhibition of the Phosphatidylinositol 3-Kinase (PI3K)/S6K1 signaling pathway. In
addition, docking was performed to study the binding mode of the THTMP, which shows better interaction with
EGFR. The structural elucidation of THTMP by Quantitative Structure-Activity Relationship model (QSAR)
and ADMET screening suggested, THTMP as an effective anticancer compound.

Conclusion:
This work strengthens the potential of a promising drug-like compound, THTMP, for the discovery
of anticancer drug against breast cancer.
Benzisothiazolone Derivatives Exhibit Cytotoxicity in Hodgkin’s Lymphoma Cells through NF-κB Inhibition and are Synergistic with Doxorubicin and Etoposide
Authors: Nandakumar Natarajan , Gopinath Pushparathinam , Gopas Jacob , Muraleedharan Kannoth M. 
Published: February 2020

Background:
The authors investigated the NF-κB inhibitory role of three Benzisothiazolone (BIT)
derivatives (1, 2 and 3) in Hodgkin’s Lymphoma cells (L428) which constitutively express activated NF-κB. All
three compounds showed dose-dependent NF-κB inhibition (78.3, 70.7 and 34.6%) in the luciferase reporter
gene assay and were found cytotoxic at IC50 values of 3.3μg/ml, 4.35μg/ml and 13.8μg/ml, respectively by the
XTT assay. BIT 1and BIT 2 (but not BIT 3) suppressed both NF-κB subunits p50 and p65 in cytoplasmic and
nuclear extracts in a concentration-dependent manner. Furthermore, BIT 1 showed a moderate synergistic effect
with the standard chemotherapy drugs etoposide and doxorubicin, whereas BIT 2 and 3 showed a moderate
additive effect to antagonistic effect. Cisplatin exhibited an antagonist effect on all the compounds tested under
various concentrations, except in the case of 1.56μg/ml of BIT 3 with 0.156μg/ml of cisplatin. The compounds
also inhibited the migration of adherent human lung adenocarcinoma cells (A549) in vitro. We conclude that
especially BIT 1 and BIT 2 have in vitro anti-inflammatory and anti-cancer activities, which can be further
investigated for future potential therapeutic use.

Methods:
Inspired by the electrophilic sulfur in Nuphar alkaloids, monomeric and dimeric benzisothiazolones
were synthesized from dithiodibenzoic acid and their NF-κB inhibitory role was explored. NF-κB inhibition and
cytotoxicity of the synthesized derivatives were studied using luciferase reporter gene assay and XTTassay.
Immunocytochemistry studies were performed using L428 cells. Cell migration assay was conducted using the
A549 cell line. L428 cells were used to conduct combination studies and the results were plotted using
CompuSyn software.

Results:
Benzisothiazolone derivatives exhibited cytotoxicity in Hodgkin’s Lymphoma cells through NF-κB
inhibition. Potent compounds showed suppression of both NF-κB subunits p50 and p65 in a concentrationdependent
manner, both in cytoplasmic and nuclear extracts. Combination studies suggest that benzisothiazolone
derivatives possess a synergistic effect with etoposide and doxorubicin. Furthermore, the compounds
also inhibited the migration of A549 cells.

Conclusion:
Benzisothiazolones bearing one or two electrophilic sulfur atoms as part of the heterocyclic
framework exhibited cytotoxicity in Hodgkin’s Lymphoma cells through NF-κB inhibition. In addition, these
derivatives also exhibited a synergistic effect with etoposide and doxorubicin along with the ability to inhibit the
migration of A549 cells. Our study suggests that BIT-based new chemical entities could lead to potential anticancer
agents.
Development of A Novel System Based on Green Magnetic / Graphene Oxide / Chitosan /Allium Sativum / Quercus / Nanocomposite for Targeted Release of Doxorubicin Anti-Cancer Drug
Authors: Arjmand Omid , Ardjmand Mehdi , Amani Ali M. , Eikani Mohmmad H. 
Published: February 2020

Background:
Doxorubicin, as a strong anti-cancer agent for clinical treatment of various cancer types
along with other drugs, is widely utilized. Due to the physiology of the human body and cancerous tissues, the applicability
of doxorubicin is still limited and the targeted treatment of the different types of cancers is considered.
Also, the side effects of the conventional forms of chemotherapy medicines, damaging and stressing the normal
cells are considerable.

Objective:
This study introduces a novel and effective system for the targeted release of doxorubicin by successfully
fabricating the green magnetic graphene oxide, chitosan, allium sativum, and quercus nanocomposite.

Methods:
The in vitro release of doxorubicin loaded on the nanocomposite was evaluated and investigated at pH 7.4
and 6.5, respectively. The drug diffusivity in the plasma environment was assessed for a more accurate analysis of
the drug diffusion process. The nanocomposite loaded drug release mechanism and kinetics, as well as cytotoxicity
assay was investigated.

Results:
The efficiency of the drug encapsulation was significantly enhanced using natural extract ingredients and
consequently, the efficacy of the targeted treatment of cancerous tissues was improved. The developed nanocomposite
provided a controlled release of doxorubicin in similar acidic conditions of the normal and cancerous cells and
affirming that the fabricated system is thoroughly pH-dependent.

Conclusion:
The cytotoxicity assay confirmed that the fabricated nanocomposite at a high growth rate of cancerous
cells has an anticancer property and acts as a toxic agent against tumor cells, suggesting that in conjunction with
doxorubicin, it can be highly improved for killing cancerous cells.
Sialuria-Related Intellectual Disability in Children and Adolescent of Pakistan: Tenth Patient Described has a Novel Mutation in the GNE Gene
Authors: Ishtiaq Hina , Siddiqui Sonia , Nawaz Rukhsana , Jamali Khawar Saeed , Khan Abdul Ghani 
Published: February 2020

Background:Sialuria is a rare inborn error of metabolism caused by excessive synthesis of sialic acid due to the mutation in the binding site of the cytidine monophosphate-sialic acid of UDPGlcNAc 2-Epimerase/ManNAc Kinase (GNE/MNK).Objective:This is the first study investigating the molecular basis of neuronal disorders exhibiting sialuria in Pakistani children/adolescents.Methods:The current study genotyped GNE SNPs rs121908621, rs121908622 and rs121908623 by using PCR, RFLP, and DNA sequencing methods. Socioeconomic and clinical histories were also recorded.Results:Our data suggest that clinical symptoms and financial status play a significant role in conferring sialuria related Intellectual Disability (ID). SNP: rs121908623 showed G/A substitution (R263Q) in the GNE gene.Conclusion:We have identified one case study in Pakistan, so this makes our research a leap forward towards the identification of the 10th case study worldwide.