bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recruitment And Retention Of Participants From Socioeconomically Deprived Communities: Lessons From The Awareness And Beliefs About Cancer (ABACus3) Randomised Controlled Trial.
Authors: Kolovou Vasiliki , Moriarty Yvonne , Gilbert Stephanie , Quinn-Scoggins Harriet , Townson Julia , Padgett Louise , Owen Sioned , Buckle Peter , Edwards Adrian , Hepburn Julie , Lau Mandy , Matthews Maura , Mitchell Caroline , Neal Richard , Playle Rebecca , Robling Michael , Smits Stephanie , Trubey Robert , Wood Fiona , Brain Kate 
Published: October 2020

Abstract
Background: Recruitment of research participants poses challenges in socioeconomically deprived areas. The Awareness and Beliefs About Cancer (ABACus) phase 3 Randomised Control Trial recruited adult participants from socioeconomically deprived areas using a combined healthcare/community engagement model. We report the strategies used to successfully recruit and retain our trial participant sample.Methods: Community and healthcare settings in areas of high socioeconomic deprivation were identified by lay advisors who recruited participants opportunistically or by appointment. Follow-up was done by telephone or post at 2-weeks and 6-months after recruitment, and all participants were offered financial incentives. Qualitative interviews were conducted with lay advisors regarding their experience and reflections.Results: The lay advisors identified and contacted 107 potential recruitment venues across South and West Yorkshire and South East Wales of which 41.1% (n= 42) were opened for recruitment. A total of 234 participants were recruited, with 91% (n= 212) retention at 2-weeks and 85% (n= 199) at 6-months. Community settings yielded 75% (n= 176) of participants. Participants had a mean age of 61.3 years and 63.3% (n= 148) were female, with 66% (n= 154) resident in the most deprived geographical areas. Lay advisors described recruitment as intensive, although engaging participants was easier in community settings.Conclusions: The ABACus3 trial achieved recruitment and high retention with a population that is often “hard to reach” or entirely missed in health research. Strategies were specifically tailored to engage the venues and adult residents of highly deprived areas. Future studies recruiting adults living in the most deprived areas might benefit from community recruitment and from collaborating with local gatekeepers who are key to engagement.This study adheres to CONSORT guidelines.Trial RegistrationRetrospectively registered with ISRCTN (http://www.isrctn.com/ISRCTN16872545) on 12.01.2018.
Disruption of Plasmodium falciparum histidine-rich protein II may affect haem metabolism in the blood stage
Authors: Yang Yingchao , Tang Tongke , Feng Bo , Li Shanshan , Hou Nan , Ma Xiao , Jiang Lubin , Xin Xiaofang , Chen Qijun 
Published: October 2020

Abstract
Background. Haem is a key metabolic factor in the life cycle of the malaria parasite. In the blood stage, the parasite acquires host haemoglobin to generate amino acids for protein synthesis and the by-product haem for metabolic use. The malaria parasite can also synthesize haem de novo by itself. Plasmodium falciparum-specific histidine-rich protein 2 (PfHRP2) has a haem-binding site to mediate the formation of haemozoin, a biocrystallized form of haem aggregates. Notably, the gene regulates the mechanism of haemoglobin-derived haem metabolism and the de novo haem biosynthetic pathway in the Pfhrp2-disrupted parasite line during the intraerythrocytic stages. Methods. The CRISPR/Cas9 system was used to disrupt the gene locus of Pfhrp2. DNA was extracted from the transgenic parasite, and polymerase chain reaction (PCR), Southern blotting and Western blotting were used to confirm the establishment of transgenic parasites. RNA-Seq and comparative transcriptome analysis were performed to identify differences in gene expression between 3D7 and Pfhrp2- 3D7 parasites.Results. Pfhrp2- transgenic parasites were successfully established by the CRISPR/Cas9 system. A total of 964, 1261, 3138, 1064, 2512, and 1778 differentially expressed genes (DEGs) were identified in the six comparison groups, and a total of 373, 520, 1499, 353, 1253, and 742 of the DEGs were upregulated, and 591, 741, 1639, 711, 1259, and 1036 of the DEGs were downregulated, respectively. Five DEGs related to haem metabolism and synthesis were identified in the comparison groups of six time points (0, 8, 16, 24, 32, and 40 h after merozoite invasion). The genes encoding ALAS and FC, related to haem biosynthesis, were found to be significantly upregulated in the comparison groups, and the HO, SPP, and PBGD genes were found to be significantly downregulated. No GO terms were significantly enriched in haem-related processes (Q value=1).Conclusion: In this study, our findings revealed changes in the transcriptome expression profile of the Pfhrp2-3D7 parasite during the intraerythrocytic stages. The results suggested that disruption of Pfhrp2 alters the parasite’s haem metabolic and biosynthesis pathways at the gene transcript level. A cooperative mechanism exists between the haem biosynthesis and metabolic pathways for parasite growth and survival in the blood stage. It is difficult to treat malaria patients by inhibiting only one pathway with traditional antimalarial drugs. The above findings provide insight at the gene transcript level for further research and development of anti-malaria drugs.
Real-time PCR on skin biopsies for super-spreaders’ detection in bovine besnoitiosis.
Authors: Grisez Christelle , Bottari Leslie , Prévot Françoise , Alzieu Jean-Pierre , Liénard Emmanuel , Corbière Fabien , Rameil Marie , Desclaux Xavier , Lacz Christophe , Boulon Christian , Petermann Julie , Mével Jeanne Le , Vilardell Carine , Jacquiet Philippe 
Published: October 2020

Abstract
Background: Bovine besnoitiosis, an emerging disease in Europe that can be transmitted by vectors, is caused by the apicomplexan Besnoitia besnoiti. Bovine besnoitiosis is difficult to control due to the complexity of its diagnosis in the acute stage of the disease, poor treatment success and chronically asymptomatic cattle acting as parasite reservoirs. When serological prevalence is low, detection and specific culling of seropositive cattle is feasible; however, economic considerations preclude this approach when serological prevalence is high. The aims of this study were to evaluate the accuracy of detection of super-spreaders in highly infected herds and to test their selective elimination as a new control strategy for bovine besnoitiosis. Methods: Previous real-time PCR analyses performed on skin tissues from 160 asymptomatic animals sampled at slaughterhouses showed that the tail base was the best location to evaluate the dermal parasite DNA load. All seropositive animals (n = 518) from eight dairy or beef cattle farms facing a high serological prevalence of besnoitiosis were sampled at the tail base and their skin sample analysed by real-time PCR. A recommendation of rapid and selective culling of super-spreaders was formulated and provided to the cattle breeders. Subsequent serological monitoring of naïve animals was used to evaluate the interest of this control strategy over time.Results: Among the 518 seropositive animals, a low proportion of individuals (14.5%) showed Cq values below 36, 17.8% had doubtful results (36 < Cq ≤ 40) and 67.8% had negative PCR results. These proportions were grossly similar on the eight farms, regardless of their production type (beef or dairy cattle), size, geographical location or history of besnoitiosis. Within two weeks of the biopsy, the rapid culling of super-spreaders was implemented on only three farms. The numbers of newly infected animals were lower on these farms compared to those where super-spreaders were maintained in the herd. Conclusions: Real-time PCR analyses performed on skin biopsies of seropositive cattle showed huge individual variabilities in parasite DNA load. The rapid culling of individuals considered as super-spreaders seems to be a new and encouraging strategy for bovine besnoitiosis control.
Association of PICK1 and BDNF variations with increased risk of methamphetamine dependence among Iranian population; a case-control study
Authors: Tajbakhsh Amir , Alimardani Maliheh , Asghari Mahla , Abedini Soheila , Khadem Sohrab Saghafi , Bajestani Abolfazl Nesaei , Alipoor Forough , Alidoust Maryam , Savardashtaki Amir , Hashemian Peyman , Pasdar Alireza 
Published: October 2020

Abstract
Background: Genetic factors play an important role in susceptibility to methamphetamine dependency. In this line, protein that interact with C-kinase-1 (PICK1) and brain-derived neurotrophic factor (BDNF) genes are linked to methamphetamine dependence (substance use disorder). Thus, in a case-control study, we investigated the association between polymorphisms of PICK1 and BDNF genes and methamphetamine dependence in an Iranian population.Methods: Total of 235 cases and 204 controls were recruited in a period between 2015 to 2018. The PICK1-rs713729, -rs2076369 and BDNF-rs6265 genotypes were determined via ARMS-PCR assay. Statistical analysis was performed, using SPSS 20.0, PHASE 2.1.1 program as well as SNP Analyzer 2.0.Results: In the present study, two polymorphisms including PICK1-rs713729 (OR: 1.38 (CI: 1.08-1.52; P-value: 0.004) in multiplicative and dominant models, and PICK1-rs2076369 (OR: 1.31 (CI: 1.10-1.56; P-value: 0.002) in multiplicative, dominant and co-dominant models were associated with the risk of methamphetamine abuse. Moreover, haplotype analysis showed a significant association of haplotype AG (OR: 2.50 (CI: 1.50-4.16; P-value: 0.0002) in dominant, recessive and co-dominant models, and haplotype TT (OR: 0.67 (CI: 0.50-0.91; P-value: 0.009) in dominant and co-dominant models with the risk of methamphetamine abuse. None of the polymorphisms in this study had a high level of linkage disequilibrium. Conclusion: Our findings indicate that the PICK1 gene polymorphism might affect the risk of methamphetamine dependency in our population.
Mutation Analysis of GARS and Genotype-Phenotype Correlation in CMT2D/HMN5A in Chinese Patients
Authors: Sun Bo , He Zhengqing , Li Yanran , Wang Hongfen , Yang Fei , Cui Fang , Huang Xu-Sheng 
Published: October 2020

Abstract
BackgroundCMT2D is a rare subtype of axonal CMT, caused by a variant of the glycyl-tRNA synthetase (GARS) gene which is also a disease-causing gene of distal spinal muscular atrophy type V (dSMA-V) or hereditary motor neuropathy 5A (HMN5A). There were only several cases reported in China, all lacking an epidemiological study of CMT2D/ HMN5A.Methods206 patients of Chinese Han descent, clinically diagnosed with inherited peripheral neuropathy (IPN), were recruited in this study from December 20, 2012 to July 31, 2019. All patients underwent a detailed medical history screening, a neurological examination, a laboratory examination, several electrophysiological studies, and genetic testing.ResultsA total of 206 unrelated patients underwent genetic analysis. Four variants of GARS from four different families were found, including c.794C > T (p.S265F), c.374A > G (p.E125G), c.1000A > T (p.I334F), and c.781T > G (p.Y261D), with the first three being considered pathogenic. For the three pathogenic variant carriers, one was diagnosed with CMT2D, while the two others were diagnosed with HMN5A.ConclusionGARS mutation is a rare outcome of inherited peripheral neuropathy and the phenotype tends to be CMT2D or HMN5A.
ChemSpectra: A web-based spectra editor for analytical data
Authors: Huang Yu-Chieh , Tremouilhac Pierre , Nguyen An , Jung Nicole , Bräse Stefan 
Published: October 2020

Abstract
ChemSpectra, a web-based software to visualize and analyze spectroscopic data, integrating solutions for IR (infrared spectroscopy), MS (mass spectrometry), and one-dimensional 1 H and 13 C NMR (proton and carbon nuclear magnetic resonance) spectroscopy, is described. ChemSpectra serves as web-based tool for the analysis of the most often used types of one-dimensional spectroscopic data in synthetic (organic) chemistry research. It was developed to support in particular processes for the use of open file formats which enable the work according to the FAIR data principles. The software can deal with the open file formats JCAMP-DX (IR, MS, NMR) and mzML (MS) proposing these data file types to gain interoperable data. ChemSpectra can be extended to read also other formats as exemplified by selected proprietary mass spectrometry data files of type RAW and NMR spectra files of type FID. The JavaScript-based editor can be integrated with other software, as demonstrated by integration into the Chemotion electronic lab notebook (ELN) and Chemotion repository, demonstrating the implementation into a digital work environment that offers additional functionality and sustainable research data management options. ChemSpectra supports different functions for working with spectroscopic data such as zoom functions, peak picking and automatic peak detection according to a default or manually defined threshold. NMR specific functions include the definition of a reference signal, the integration of signals, coupling constant calculation and multiplicity assignment. Embedded into a web application such as an ELN or a repository, the editor can also be used to generate an association of spectra to a sample and a file management. The file management supports the storage of the original spectra along with the last edited version and an automatically generated image of the spectra in png format. To maximize the benefit of the spectra editor for e.g. ELN users, an automated procedure for the transfer of the detected or manually chosen signals to the ELN was implemented. ChemSpectra is released under the AGPL license to encourage its re-use and further developments by the community.
Use of the ankle-brachial index combined with the percentage of mean arterial pressure at the ankle to improve prediction of all-cause mortality in type 2 diabetes mellitus: An observational study
Authors: Li Yu-Hsuan , Sheu Wayne Huey-Herng , Lee I-Te 
Published: October 2020

Abstract
Background: Peripheral artery disease (PAD) in the lower extremities is a common complication of type 2 diabetes and has been shown to be associated with mortality. The ankle-brachial index (ABI) is a simple noninvasive method to screen PAD, but this method has limited sensitivity. We hypothesized that using the percentage of mean arterial pressure (%MAP) in combination with the ABI would improve the prediction of mortality.Methods: We retrospectively collected data from patients with type 2 diabetes who had undergone ABI and %MAP measurements at our hospital. We separated the cohort into four groups according to their ABI and %MAP values, and we examined whether these indices were associated with mortality.Results: A total of 5569 patients (mean age, 65 ± 11 years) were enrolled. During the follow-up period (median, 22.9 months), 266 (4.8%) of the enrolled patients died. The combination of ABI and %MAP was significantly more effective than ABI alone for predicting mortality (C index of 0.62, 95% confidence interval [CI] of 0.57 to 0.65 vs. C index of 0.57, 95% CI of 0.53 to 0.62; P = 0.038). In multivariate analysis (with a reference group defined by ABI >0.90 and %MAP ≤45%), the highest risk of mortality was seen in patients with ABI ≤0.90 and %MAP >45% (hazard ratio = 2.045 [95% CI: 1.420, 2.945], P < 0.001).Conclusions: The use of %MAP alongside ABI appears to significantly improve the prediction of all-cause mortality in patients with type 2 diabetes.
Complex foot deformities associated with lower limb deformities: a new therapeutic strategy for simultaneous correction using Ilizarov procedure together with osteotomy and soft tissue release
Authors: Boquan Qin , Yi Ren , Tingjiang Gan , Xi Liu , Hui Zhang 
Published: October 2020

Abstract
Aim The aim of the current study is to introduce a new therapeutic strategy for simultaneous correction of complex foot deformities (CFD) and the associated lower limb deformities (LLD) by using Ilizarov technique with osteotomy and soft tissue procedure and to report its early clinical results.Methods A retrospective review of CFD associated with LLD simultaneous correction utilizing Ilizarov procedure together with osteotomy and soft tissue balance from 2015 to 2019 was conducted.Results Thirty-two patients were followed for an average of 42.8 months. The mean external fixation time (EFT) was 6.5 months. The mean healing index (HI) was 1.7 months/cm. At the time of fixator removal, plantigrade feet were achieved in all patient and lower limb deformities were corrected. No recurrence of the deformities occurred. The mean LLRS AIM score was improved from 7.5 to 0.3. At the final follow-up, ASAMI-Paley score was graded as excellent in all limbs in the aspect of bone results, and functional results were defined as excellent in 29 (90.6%) limbs and good in 3 (9.4%) limbs. The mean Modified Dimeglio score was significantly improved from 7.2 to 1.3. No deep infection of the osteotomy site or nonunion was noted in the current study.Conclusion The therapeutic strategy by using Ilizarov procedure together with osteotomy and soft tissue balance is a safe and effective way to simultaneously correct CFD and LLD.Level of Evidence Level IV, retrospective case series
The Phlebotomus papatasi systemic transcriptional response to trypanosomatid-contaminated blood does not differ from the non-infected blood meal
Authors: Sloan Megan A. , Sadlova Jovana , Lestinova Tereza , Sanders Mandy J. , Cotton James A. , Volf Petr , Ligoxygakis Petros 
Published: October 2020

Abstract
Background Leishmaniasis, caused by parasites of the genus Leishmania, is a disease that effects up to 8 million people worldwide. Parasites are transmitted to human and animal hosts through the bite of an infected sand fly. Novel strategies for disease control, require a better understanding of the key step for transmission namely, the establishment of infection inside the fly. Methods In this work we wanted to identify fly systemic transcriptomic signatures associated with Leishmania infection. We used next generation sequencing to describe the transcriptome of whole Phlebotomus papatasi sand flies when fed with blood alone (control) or with blood containing one of three trypanosomatids: Leishmania major, Leishmania donovani and Herpetomonas muscarum: a parasite not transmitted to humans. Results Of these, only L. major is able to successfully establish an infection in P. papatasi. However, the transcriptional signatures observed after each parasite-contaminated blood meal were not specific to success or failure of a specific infection and were not different from each other. They were also indistinguishable from non-contaminated blood. Conclusions This implies that sand flies perceive Leishmania as just one feature of their microbiome landscape and that any strategy to tackle transmission should focus on the response towards the blood meal rather than parasite establishment. Alternatively, Leishmania could suppress host responses. These results will generate new thinking around the concept of stopping transmission by controlling the parasite inside the insect.
Structure-based discovery of potential inhibitors targeting sodium-bile acid co-transporter of carcinogenic liver fluke Clonorchis sinensis
Authors: Yoo Won Gi , Dai Fuhong , Pak Jhang Ho , Hong Sung-Jong 
Published: October 2020

Abstract
Background: Clonorchis sinensis requires bile acid transporters as this fluke inhabits bile juice-filled biliary ducts, which provide an extreme environment. C. sinensis sodium-bile acid co-transporter (CsSBAT) is indispensable for survival in the final host, as it circulates taurocholate and prevents bile toxicity in the fluke; hence, it is recognized as a useful drug target.Results: In the present study, using structure-based drug discovery approach, we presented inhibitor candidates targeting a bile acid-binding pocket of CsSBAT. CsSBAT models were built using comparative tertiary structure modeling based on a bile acid transporter template (PDB ID: 3zuy and 4n7x), and were applied into AutoDock Vina for competitive docking simulation. First, potential compounds were identified from PubChem (holding more than 100,000 compounds) by applying three criteria: i) interacting more favorably with CsSBAT than with a human homolog, ii) intimate interaction to the inward- and outward-facing conformational states, iii) binding with CsSBAT more preferably than natural bile acids. Second, two compounds were identified following Lipinski’s rule of five. Third, another two compounds of molecular weight higher than 500 Da (Mr > 500 Da) were presumed to efficiently block the transporter via a feasible rational screening strategy. These four inhibitor candidates exhibited least toxicity that may enhance drug-likeness properties.Conclusion: It is proposed that four compounds act as potential inhibitors toward CsSBAT, and further studies are warranted for drug development process against clonorchiasis.
Frailty, delirium and hospital mortality of older adults admitted to intensive care: the Delirium (Deli) in ICU study.
Authors: Sanchez David , Brennan Kathleen , Safye Masar El , Shunker Sharon-Ann , Bogdanoski Tony , Hedges Sonja , Hou Yu Chin , Lynch Joan M , Hunt Leanne , Alexandrou Evan , Saxena Manoj , Abel Simon , Lakshmanan Ramanathan , Bhonagiri Deepak , Parr Michael J. , Aneman Anders , Chroinin Danielle Ni , Hillman Kenneth M. , Frost Steven Alfred 
Published: October 2020

Abstract
Background: Clinical frailty among older adults admitted to intensive care has been proposed as an important determinant of patient outcomes. Among this group of patients an acute episode of delirium is also common, but its relationship to frailty and increased risk of mortality has not been extensively explored. Therefore, the aim of this study was to explore the relationship between clinical frailty, delirium and hospital mortality of older adults admitted to intensive care.Methods: This study is part of a Delirium in Intensive Care (Deli) study. During the initial 6-month baseline period, clinical frailty status on admission to intensive care, among adults aged 50-years or more, acute episodes of delirium, and the outcomes of intensive care and hospital stay were explored.Results: During the 6-month baseline period 997 patients, aged 50-years or more, were included in this study. The average age was 71-years (IQR, 63-79), 55% were male (n = 537). Among these patients 39.2% (95% CI 36.1 – 42.3%, n = 396) had a Clinical Frailty Score (CFS) of 5 or more, and 13.0% (n=127) had at least one acute episode of delirium. Frail patients were at greater risk of an episode of delirium (17% versus 10%, adjusted Rate Ratio (adjRR) = 1.71, 95% Confidence Interval (CI) 1.20 – 2.43, p = 0.003), had a longer hospital stay (2.6 days, 95% CI 1-7 days, p = 0.009), and higher risk of hospital mortality (19% versus 7%, adjRR = 2.54, 95% CI 1.72 – 3.75, p < 0.001), when compared to non-frail patients. Patients who were frail and experienced an acute episode of delirium in the intensive care had a 35% rate of hospital mortality, versus 10% among non-frail patients who also experienced delirium in the ICU.Conclusion: Frailty and delirium significantly increase the risk of hospital mortality. Therefore, it important to identify patients who are frail and institute measures to reduce the risk of adverse events in the ICU such as delirium. And, importantly to discuss these issues in an open and empathetic way with the patient and their families.