bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti-dengue activity of super critical extract and isolated oleanolic acid of Leucas cephalotes using in vitro and in silico approach
Authors: Kaushik Sulochana , Dar Lalit , Kaushik Samander , Yadav Jaya Parkash 
Published: September 2021

Abstract
Backgrounds
Leucas cephalotes is a common ethnomedicinal plant widely used by traditional healers for the treatment of Malaria and other types of fever. Oleanolic acid and its derivatives have been reported for various types of pharmacological activities, such as anti-inflammatory, antioxidant, anticancer, hepatoprotective, anti-HIV and anti-HCV activity.

Methods
L.cephalotes plant extracts were prepared by supercritical fluid extraction (SFE) method and oleanolic acid was isolated by preparatory thin-layer chromatography. The compound was identified and characterize by using ultraviolet-visible spectroscopy (UV-VIS), Fourier transform infra-Red spectroscopy (FT-IR) and high-performance thin-layer chromatography (HPTLC). The structure of the compound was elucidated by proton nuclear magnetic resonance (1HNMR) and carbon nuclear magnetic resonance (1CNMR) and the purity checked by differential scanning calorimetry (DSC). The MTT assay was used to determine the toxicity of plant extract and oleanolic acid using a microplate reader at 595 nm. The anti-dengue activity of plant extract and oleanolic acid was tested in vitro and in silico using real-time RT-PCR.

Results
The optimum yield of the extract was obtained at 40 °C temperature and 15Mpa pressure. The maximum non-toxic dose (MNTD) of plant extract and oleanolic acid were found as 46.87 μg/ml and 93.75 μg/ml, respectively in C6/36 cell lines. UV spectrophotometer curve of the isolated compound was overlapped with standard oleanolic acid at 232 nm. Superimposed FT-IR structure of the isolated compound was indicated the same spectra at 3433, 2939, 2871, 1690, 1500,1463, 1387, 1250, 1209, 1137 and 656 position as per marker compound. HPTLC analysis showed the retention factor of L. cephalotes extract was 0.19 + 0.06 as similar to the standard oleanolic acid chromatogram. The NMR structure of the isolated compound was identified as similar to the marker oleanolic acid structure. DSC analysis revealed the purity of isolated oleanolic acid was 98.27% with a melting point of 311.16 °C. Real-time RT PCR results revealed that L. cephalotes supercritical extract and isolated oleanolic acid showed 100 and 99.17% inhibition against the dengue − 2 virus when treated with MNTD value of plant extract (46.87 μg/ml) and the test compound (93.75 μg/ml), respectively. The molecular study demonstrated the binding energy of oleanolic acid with NS1and NS5 (non-structural protein) were − 9.42 & -8.32Kcal/mol, respectively.

Conclusions
The SFE extract L. cephalotes and its active compound, oleanolic acid inhibiting the activity of dengue-2 serotype in the in vitro and in silico assays. Thus, the L.cephalotes plant could be an excellent source for drug design for the treatment of dengue infection.
The ethics of explantation
Authors: Hansson Sven Ove 
Published: September 2021

Abstract
Background
With the increased use of implanted medical devices follows a large number of explantations. Implants are removed for a wide range of reasons, including manufacturing defects, recovery making the device unnecessary, battery depletion, availability of new and better models, and patients asking for a removal. Explantation gives rise to a wide range of ethical issues, but the discussion of these problems is scattered over many clinical disciplines.

Methods
Information from multiple clinical disciplines was synthesized and analysed in order to provide a comprehensive approach to the ethical issues involved in the explantation of medical implants.

Results
Discussions and recommendations are offered on pre-implantation information about a possible future explantation, risk–benefit assessments of explantation, elective explantations demanded by the patient, explantation of implants inserted for a clinical trial, patient registers, quality assurance, routines for investigating explanted implants, and demands on manufacturers to prioritize increased service time in battery-driven implants and to market fewer but more thoroughly tested models of implants.

Conclusion
Special emphasis is given to the issue of control or ownership over implants, which underlies many of the ethical problems concerning explantation. It is proposed that just like transplants, implants that fulfil functions normally carried out by biological organs should be counted as supplemented body parts. This means that the patient has a strong and inalienable right to the implant, but upon explantation it loses that status.
Exploring experiences of implementing standardized cancer patient pathways within investigatory units – a qualitative study
Authors: Winterling Jeanette , Delilovic Sara , Dervish Jessica , Gunarsson Malin , Åhström Mårten , Hasson Henna 
Published: September 2021

Abstract
Background
In the implementation of standardized cancer patient pathways (CPPs), the investigatory units, endoscopy, radiology and pathology, are crucial to ensure an eventual cancer diagnosis. However, when evaluating the implementation of CPPs, little attention has been paid to the healthcare professionals working in these units. The aim of this study was to explore experiences of the implementation of CPPs among health professionals in investigatory units.

Methods
This descriptive qualitative study included 55 health professionals working in investigatory units. Participants were interviewed in 2017–2018, and data were analysed using thematic analysis.

Results
The health professionals reported benefits, facilitators and challenges when describing their experiences of implementing CPPs. Benefits included that CPP improved collaboration and increased focus on the patients. Facilitators in the implementation process included pre-existing well-functioning work processes and having supportive functions (e.g. coordinators). Challenges included the lack of staff and clinical equipment, as well as unjustified time-slots and incorrect referrals.

Conclusions
The findings show that most health professionals working in investigatory units’ experience benefits with the implementation of CPP, but the lack of resources was especially hard to overcome.
Construction of à la carte QconCAT protein standards for multiplexed quantification of user-specified target proteins
Authors: Johnson James , Harman Victoria M. , Franco Catarina , Emmott Edward , Rockliffe Nichola , Sun Yaqi , Liu Lu-Ning , Takemori Ayako , Takemori Nobuaki , Beynon Robert J. 
Published: September 2021

Abstract
Background
QconCATs are quantitative concatamers for proteomic applications that yield stoichiometric quantities of sets of stable isotope-labelled internal standards. However, changing a QconCAT design, for example, to replace poorly performing peptide standards has been a protracted process.

Results
We report a new approach to the assembly and construction of QconCATs, based on synthetic biology precepts of biobricks, making use of loop assembly to construct larger entities from individual biobricks. The basic building block (a Qbrick) is a segment of DNA that encodes two or more quantification peptides for a single protein, readily held in a repository as a library resource. These Qbricks are then assembled in a one tube ligation reaction that enforces the order of assembly, to yield short QconCATs that are useable for small quantification products. However, the DNA context of the short construct also allows a second cycle of loop assembly such that five different short QconCATs can be assembled into a longer QconCAT in a second, single tube ligation. From a library of Qbricks, a bespoke QconCAT can be assembled quickly and efficiently in a form suitable for expression and labelling in vivo or in vitro.

Conclusions
We refer to this approach as the ALACAT strategy as it permits à la carte design of quantification standards. ALACAT methodology is a major gain in flexibility of QconCAT implementation as it supports rapid editing and improvement of QconCATs and permits, for example, substitution of one peptide by another.
A missense variant rs2585405 in clock gene PER1 is associated with the increased risk of noise-induced hearing loss in a Chinese occupational population
Authors: Chen Hao , Ding Xuexue , Ding Enmin , Chen Mengyao , Wang Huimin , Yang Guangzhi , Zhu Baoli 
Published: September 2021

Abstract
Objective
To investigate the potential association of cochlear clock genes (CRY1, CRY2, PER1, and PER2), the DNF gene (brain-derived neurotrophic factor), and the NTF3 gene (neurotrophin3) with susceptivity to noise-induced hearing loss (NIHL) among Chinese noise-exposed workers.

Methods
A nested case–control study was performed with 2056 noise-exposed workers from a chemical fiber factory and an energy company who underwent occupational health examinations in 2019 as study subjects. Propensity score matching was conducted to screen cases and controls by matching sex, age, and the consumption of tobacco and alcohol. A total of 1269 participants were enrolled. Then, general information and noise exposure of the study subjects were obtained through a questionnaire survey and on-site noise detection. According to the results of audiological evaluations, the participants were divided into the case group (n = 432, high-frequency threshold shift > 25 dB) and the matched control group (n = 837, high-frequency threshold shift ≤ 25 dB) by propensity score matching. Genotyping for PER1 rs2253820 and rs2585405; PER2 rs56386336 and rs934945; CRY1 rs1056560 and rs3809236; CRY2 rs2292910 and rs6798; BDNF rs11030099, rs7124442 and rs6265; and NTF3 rs1805149 was conducted using the TaqMan-PCR technique.

Results
In the dominant model and the co-dominant model, the distribution of PER1 rs2585405 genotypes between the case group and the control group was significantly different (P = 0.03, P = 0.01). The NIHL risk of the subjects with the GC genotype was 1.41 times the risk of those carrying the GG genotype (95% confidence interval (CI) of odds ratio (OR): 1.01–1.96), and the NIHL risk of the subjects with the CC genotype was 0.93 times the risk of those carrying the GG genotype (95%CI of OR: 0.71–1.21). After the noise exposure period and noise exposure intensities were stratified, in the co-dominant model, the adjusted OR values for noise intensities of ≤ 85 was 1.23 (95%CI: 0.99–1.53). In the dominant model, the adjusted OR values for noise exposure periods of ≤ 16 years and noise intensities of ≤ 85 were 1.88 (95%CI: 1.03–3.42) and 1.64 (95%CI: 1.12–2.38), respectively.

Conclusion
The CC/CG genotype of rs2585405 in the PER1 gene was identified as a potential risk factor for NIHL in Chinese noise-exposed workers, and interaction between rs2585405 and high temperature was found to be associated with NIHL risk.
Effect of anti-diabetic drugs in dialysis patients with diabetes: a nationwide retrospective cohort study
Authors: Ou Shih-Hsiang , Chen Hsin-Yu , Fang Nai-Wen , Yin Chun-Hao , Chen Chien-Liang , Chen Jin-Shuen 
Published: September 2021

Abstract
Background
Type 2 diabetes mellitus is common in patients undergoing dialysis. However, the association between anti-diabetic drug use and survival outcomes is rarely discussed. We aimed to investigate whether continued anti-diabetic medication use affects the survival of diabetic dialysis patients and whether different hypoglycemic drug use influences prognosis.

Methods
Using a nationwide database, we enrolled patients with incident end-stage renal disease under maintenance dialysis during 2011–2015 into the pre-existing diabetes dialysis (PDD), incident diabetes after dialysis (IDD), and non-diabetic dialysis (NDD) groups. The PDD group was further subclassified into patients who continued (PDD-M) and discontinued (PDD-NM) anti-diabetic drug use after dialysis.

Results
A total of 5249 dialysis patients were examined. The PDD-NM group displayed a significantly higher mortality rate than the IDD, PDD-M, and NDD groups (log-rank test P < 0.001). The PDD-M group had a significantly lower risk of death, regardless of insulin (P < 0.001) or oral hypoglycemic agent (OHA) (P < 0.001) use. Initial insulin administration or OHA had no statistically significant effect on overall mortality in the IDD group. But OHA use had better survival trends than insulin administration for the older (P = 0.02) and male subgroups (P = 0.05).

Conclusions
For dialysis patients with diabetes, continuous administration of anti-diabetic drugs after dialysis and choice of medication may affect outcomes.
Impact of insulin therapy on the mortality of acute heart failure patients with diabetes mellitus
Authors: Jang Se Yong , Jang Jieun , Yang Dong Heon , Cho Hyun-Jai , Lim Soo , Jeon Eun-Seok , Lee Sang Eun , Kim Jae-Joong , Kang Seok-Min , Baek Sang Hong , Cho Myeong-Chan , Choi Dong-Ju , Yoo Byung-Su , Kim Kye Hun , Park Sue K. , Lee Hae-Young 
Published: September 2021

Abstract
Background
Patients with diabetes mellitus (DM) have a higher prevalence of heart failure (HF) than those without it. Approximately 40 % of HF patients have DM and they tend to have poorer outcomes than those without DM. This study evaluated the impact of insulin therapy on mortality among acute HF patients.

Methods
A total of 1740 patients from the Korean Acute Heart Failure registry with DM were included in this study. The risk of all-cause mortality according to insulin therapy was assessed using the Cox proportional hazard models with inverse probability of treatment weighting to balance the clinical characteristics (pretreatment covariates) between the groups.

Results
DM patients had been treated with either oral hypoglycemic agents (OHAs) alone (n = 620), insulin alone (n = 682), or insulin combined with OHAs (n = 438). The insulin alone group was associated with an increased mortality risk compared with the OHA alone group (HR = 1.41, 95 % CI 1.21–1.66]). Insulin therapy combined with OHAs also showed an increased mortality risk (HR = 1.29, 95 % CI 1.14–1.46) compared with the OHA alone group. Insulin therapy was consistently associated with increased mortality risk, regardless of the left ventricular ejection fraction (LVEF) or HF etiology. A significant increase in mortality was observed in patients with good glycemic control (HbA1c < 7.0 %) receiving insulin, whereas there was no significant association in patients with poor glycemic control (HbA1c ≥ 7.0%).

Conclusions
Insulin therapy was found to be associated with increased mortality compared to OHAs. The insulin therapy was harmful especially in patients with low HbA1c levels which may suggest the necessity of specific management strategies and blood sugar targets when using insulin in patients with HF.
External applicability of SGLT2 inhibitor cardiovascular outcome trials to patients with type 2 diabetes and cardiovascular disease
Authors: Smidt Lisanne C. A. , Visseren Frank L. J. , de Ranitz-Greven Wendela L. , Nathoe Hendrik M. , Kappelle L. Jaap , de Borst Gert J. , de Valk Harold W. , Westerink Jan ,   the UCC-SMART Study Group
Published: September 2021

Abstract
Background
Recent treatment guidelines support the use of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in patients with type 2 diabetes and cardiovascular disease based on the results of cardiovascular outcome trials (CVOTs). Applicability of these trials to everyday patients with type 2 diabetes and cardiovascular disease is however unknown. The aim of this study is to assess the external applicability of SGLT2i CVOTs in daily clinical practice type 2 diabetes patients with established cardiovascular disease.

Methods
Trial in- and exclusion criteria from EMPA-REG OUTCOME, CANVAS, DECLARE-TIMI 58 and VERTIS-CV were applied to 1389 type 2 diabetes patients with cardiovascular disease in the Utrecht Cardiovascular Cohort-Secondary Manifestations of ARTerial disease (UCC-SMART). To evaluate the difference in cardiovascular risk (MACE) and all-cause mortality between trial eligible and ineligible patients, age and sex-adjusted Cox-regression analyses were performed.

Results
After applying trial in- and exclusion criteria, 48% of UCC-SMART patients with type 2 diabetes and cardiovascular disease would have been eligible for DECLARE-TIMI 58, 35% for CANVAS, 29% for EMPA-REG OUTCOME and 21% for VERTIS-CV. Without the eligibility criteria of HbA1c, eligibility was 58–88%. For all trials the observed risk for cardiovascular events and all-cause mortality was similar in eligible and ineligible patients after adjustment for age and gender.

Conclusion
A large proportion of patients with type 2 diabetes and cardiovascular disease in daily clinical practice would have been eligible for participation in the SGLT2i CVOTs. Trial eligible and ineligible patients have the same risk for MACE and all-cause mortality.
Calculated identification of mutator-derived lncRNA signatures of genomic instability to predict the clinical outcome of muscle-invasive bladder cancer
Authors: Liang Yingchun , Ye Fangdie , Cheng Zhang , Ou Yuxi , Zou Lujia , Hu Yun , Hu Jimeng , Jiang Haowen 
Published: September 2021

Abstract
Background
Muscle-invasive bladder cancer (MIBC) is one of the most important type of bladder cancer, with a high morbidity and mortality rate. Studies have found that long non-coding RNA (lncRNA) plays a key role in maintaining genomic instability. However, Identification of lncRNAs related to genomic instability (GIlncRNAs) and their clinical significance in cancers have not been extensively studied yet.

Methods
Here, we downloaded the lncRNA expression profiles, somatic mutation profiles and clinical related data in MIBC patients from The Cancer Genome Atlas (TCGA) database. A lncRNA computational framework was used to find differentially expressed GIlncRNAs. Multivariate Cox regression analysis was used to construct a genomic instability-related lncRNA signature (GIlncSig). Univariate and multivariate Cox analyses were used to assess the independent prognostic for the GIlncSig and other key clinical factors.

Results
We found 43 differentially expressed GIlncRNAs and constructed the GIlncSig with 6 GIlncRNAs in the training cohort. The patients were divided into two risk groups. The overall survival of patients in the high-risk group was lower than that in the low-risk group (P < 0.001), which were further verified in the testing cohort and the entire TCGA cohort. Univariate and multivariate Cox regression showed that the GIlncSig was an independent prognostic factor. In addition, the GIlncSig correlated with the genomic mutation rate of MIBC, indicating its potential as a measure of the degree of genomic instability. The GIlncSig was able to divide FGFR3 wild- and mutant-type patients into two risk groups, and effectively enhanced the prediction effect.

Conclusion
Our study introduced an important reference for further research on the role of GIlncRNAs, and provided prognostic indicators and potential biological therapy targets for MIBC.
Urban malaria in sub-Saharan Africa: dynamic of the vectorial system and the entomological inoculation rate
Authors: Doumbe-Belisse P. , Kopya E. , Ngadjeu C. S. , Sonhafouo-Chiana N. , Talipouo A. , Djamouko-Djonkam L. , Awono-Ambene H. P. , Wondji C. S. , Njiokou F. , Antonio-Nkondjio C. 
Published: September 2021

AbstractSub-Saharan Africa is registering one of the highest urban population growth across the world. It is estimated that over 75% of the population in this region will be living in urban settings by 2050. However, it is not known how this rapid urbanization will affect vector populations and disease transmission. The present study summarizes findings from studies conducted in urban settings between the 1970s and 2020 to assess the effects of urbanization on the entomological inoculation rate pattern and anopheline species distribution. Different online databases such as PubMed, ResearchGate, Google Scholar, Google were screened. A total of 90 publications were selected out of 1527. Besides, over 200 additional publications were consulted to collate information on anopheline breeding habitats and species distribution in urban settings. The study confirms high malaria transmission in rural compared to urban settings. The study also suggests that there had been an increase in malaria transmission in most cities after 2003, which could also be associated with an increase in sampling, resources and reporting. Species of theAnopheles gambiaecomplex were the predominant vectors in most urban settings. Anopheline larvae were reported to have adapted to different aquatic habitats. The study provides updated information on the distribution of the vector population and the dynamic of malaria transmission in urban settings. The study also highlights the need for implementing integrated control strategies in urban settings.
CircMYH9 drives colorectal cancer growth by regulating serine metabolism and redox homeostasis in a p53-dependent manner
Authors: Liu Xin , Liu Yunze , Liu Zhao , Lin Changwei , Meng Fanchao , Xu Lei , Zhang Xiuzhong , Zhang Chong , Zhang Penbo , Gong Shuai , Wu Nai , Ren Zeqiang , Song Jun , Zhang Yi 
Published: September 2021

Abstract
Background
Circular RNAs (circRNAs) play important roles in cancer progression and metabolism regulation. Serine/glycine metabolism supports the growth of cancer cells by contributing to their anabolic demands and epigenome as well as by regulating their redox state. However, the role of circRNA in the regulation of serine/glycine metabolism has not been well elucidated.

Methods
Microarray analysis was used to screen differentially expressed novel circRNAs. qRT-PCR and FISH were utilized to analyzed the expression of circMYH9. CCK8, colony formation and FACS were used to analyze proliferation of colorectal cancer (CRC) cells. Xenograft experiments were used to analyze tumor growth in vivo. RNA-sequencing, immunoblot and LC–MS were used to identify the downstream metabolic pathway of circMYH9. ChIRP, Mass Spectrometry, RIP and RNA pulldown were utilized to test the interaction between circMYH9, hnRNPA2B1 and p53 pre-mRNA. ChIP-qPCR was used to analyze the binding sites of HIF-1α. Chemically-induced CRC mice were generated to evaluate the role of circMYH9 in tumorigenesis.

Results
We identified an intron-derived circRNA, circMYH9, which was significantly upregulated in CRC tissues. A higher circMYH9 level correlated with shorter relapse-free survival and overall survival of CRC patients. CircMYH9 promoted serine/glycine metabolism, the NAD + /NADH ratio, and glutathione recycling and inhibited reactive oxygen species (ROS) in a p53-dependent manner, impacting tumour growth. Mechanistically, circMYH9 destabilized the pre-mRNA of p53 by recruiting hnRNPA2B1 in the nucleus. hnRNPA2B1 bound to N6-methyladenosine sites on the 3' untranslated region of p53 pre-mRNA and maintained its stability. Moreover, a lack of amino acids led to an elevated level of ROS, resulting in increased HIF1α, which promoted circMYH9 expression by binding to the promoter region. Furthermore, in vivo AAV9-mediated transfection of circMYH9 could drive chemically-induced carcinogenesis by suppressing p53 in mice.

Conclusions
The overexpression of circMYH9 promotes CRC proliferation though modulating serine/glycine metabolism and redox homeostasis in a p53-dependent manner, and targeting circMYH9 and its pathway may be an effective strategy for the treatment of CRC.