bluuebunny/crossref_metadata_2025_split huggingface dataset:
Temporal evolution of the resistance genotypes of Plasmodium falciparum in isolates from Equatorial Guinea during 20 years (1999 to 2019)
Authors: Berzosa Pedro , Molina de la Fuente Irene , Ta-Tang Thuy-Huong , González Vicenta , García Luz , Rodríguez-Galet Ana , Díaz-Regañón Ramón , Galán Rosario , Cerrada-Gálvez Laura , Ncogo Policarpo , Riloha Matilde , Benito Agustin 
Published: December 2021

Abstract
Background
Malaria is one of the deadliest diseases in the world, particularly in Africa. As such, resistance to anti-malarial drugs is one of the most important problems in terms of global malaria control. This study assesses the evolution of the different resistance markers over time and the possible influence of interventions and treatment changes that have been made in Equatorial Guinea.

Methods
A total of 1223 biological samples obtained in the period 1999 to 2019 were included in the study. Screening for mutations in the pfdhfr, pfdhps, pfmdr1, and pfcrt genes was carried out by nested PCR and restriction-fragment length polymorphisms (RFLPs), and the study of pfk13 genes was carried out by nested PCR, followed by sequencing to determine the presence of mutations.

Results
The partially and fully resistant haplotypes (pfdhfr + pfdhps) were found to increase over time. Moreover, in 2019, the fully resistant haplotype was found to be increasing, although its super-resistant counterpart remains much less prevalent. A continued decline in pfmdr1 and pfcrt gene mutations over time was also found. The number of mutations detected in pfk13 has increased since 2008, when artemisinin-based combination therapy (ACT) were first introduced, with more mutations being observed in 2019, with two synonymous and five non-synonymous mutations being detected, although these are not related to resistance to ACT. In addition, the non-synonymous A578S mutation, which is the most frequent on the African continent, was detected in 2013, although not in the following years.

Conclusions
Withdrawal of the use of chloroquine (CQ) as a treatment in Equatorial Guinea has been shown to be effective over time, as wild-type parasite populations outnumber mutant populations. The upward trend observed in sulfadoxine-pyrimethamine (SP) resistance markers suggest its misuse, either alone or in combination with artesunate (AS) or amodiaquine (AQ), in some areas of the country, as was found in a previous study conducted by this group, which allows selective pressure from SP to continue. Single nucleotide polymorphisms (SNPs) 540E and 581G do not exceed the limit of 50 and 10%, respectively, thus meaning that SP is still effective as an intermittent preventive treatment (IPT) in this country. As for the pfk13 gene, no mutations have been detected in relation to resistance to ACT. However, in 2019 there is a greater accumulation of non-synonymous mutations compared to years prior to 2008.

Graphical Abstract
Insecticidal effect of ethnobotanical plant extracts against Anopheles arabiensis under laboratory conditions
Authors: Ejeta Desta , Asme Ansha , Asefa Animut 
Published: December 2021

Abstract
Background
The emergence and spread of resistant strains of malaria vectors to chemical insecticides are becoming major problems for malaria vector management. Natural plant products have a vital role to play in the current challenge of malaria control. The current study was conducted to evaluate insecticidal effect of ethnobotanical plant extracts against the primary malaria vector, Anopheles arabiensis in northwestern Ethiopia.

Methods
Primarily, ethnobotanical plants used for Anopheles mosquito control were surveyed in Dangur district, northwestern Ethiopia. Insecticide-susceptible strains of Anopheles arabiensis mosquito were reared in the insectary of the Tropical and Infectious Diseases Research Centre, Assosa University. After surveying plants used for mosquito control in local people, four frequently used plants were identified for extraction. The larvicidal and adulticidal potential of frequently used plant extracts against susceptible strains of the laboratory colony were evaluated.

Results
A total of 15 plants were identified as ethnobotanical plants that help local people with mosquito control. Azadirachta indica, Ocimum lamiifolium, Ocimum americanum, Moringa olifeira leaf, and Moringa olifeira seed species of local plants were found to be frequently used to kill and/or repel mosquitoes in the study district. All the plant extracts were found to have potential larvicidal activity against fourth instar larvae of An. arabiensis and only ethanol and methanol extract of Azadirachta indica and Ocimum lamiifolium were found to have potential adulticidal effect against adult of An. arabiensis. The highest larvicidal activity was observed in ethanol extract of Azadirachta indica with 95% larval mortality and lowest Lethal Concentration 50 (LC 50) of 40.73parts per million (ppm) and LC90 of 186.66 ppm. The highest adulticidal activity was observed in methanol extract of Azadirachta indica with 75% adult mortality at 300 ppm and lowest LC50 of 106.65 ppm and LC90 of 1,293 ppm. The lowest larvicidal and adulticidal activity was observed in methanol extracts of Ocimum lamiifolium with 63.35% larval mortality and leaf extract of Moringa olifeira with 50% adult mortality at 300 ppm, respectively.

Conclusion
Ethanol extract of Azadirachta indica exerted a remarkable larvicidal effect against An. arabiensis and thus it can be used for botanical mosquito insecticide development. Since the current finding is based on susceptible strain of An. arabiensis, further work on wild mosquitoes is recommended.
Spatiotemporal regulation of angiogenesis/osteogenesis emulating natural bone healing cascade for vascularized bone formation
Authors: Zhou Xingzhi , Chen Jiayu , Sun Hangxiang , Wang Fangqian , Wang Yikai , Zhang Zengjie , Teng Wangsiyuan , Ye Yuxiao , Huang Donghua , Zhang Wei , Mo Xianan , Liu An , Lin Peng , Wu Yan , Tao Huimin , Yu Xiaohua , Ye Zhaoming 
Published: December 2021

AbstractEngineering approaches for growth factor delivery have been considerably advanced for tissue regeneration, yet most of them fail to provide a complex combination of signals emulating a natural healing cascade, which substantially limits their clinical successes. Herein, we aimed to emulate the natural bone healing cascades by coupling the processes of angiogenesis and osteogenesis with a hybrid dual growth factor delivery system to achieve vascularized bone formation. Basic fibroblast growth factor (bFGF) was loaded into methacrylate gelatin (GelMA) to mimic angiogenic signalling during the inflammation and soft callus phases of the bone healing process, while bone morphogenetic protein-2 (BMP-2) was bound onto mineral coated microparticles (MCM) to mimics osteogenic signalling in the hard callus and bone remodelling phases. An Initial high concentration of bFGF accompanied by a sustainable release of BMP-2 and inorganic ions was realized to orchestrate well-coupled osteogenic and angiogenic effects for bone regeneration. In vitro experiments indicated that the hybrid hydrogel markedly enhanced the formation of vasculature in human umbilical vein endothelial cells (HUVECs), as well as the osteogenic differentiation of mesenchymal stem cells (BMSCs). In vivo results confirmed the optimal osteogenic performance of our F/G-B/M hydrogel, which was primarily attributed to the FGF-induced vascularization. This research presents a facile and potent alternative for treating bone defects by emulating natural cascades of bone healing.
Graphical Abstract
Assessing the relative importance of key quality of life dimensions for people with and without a disability: an empirical ranking comparison study
Authors: Crocker Matthew , Hutchinson Claire , Mpundu-Kaambwa Christine , Walker Ruth , Chen Gang , Ratcliffe Julie 
Published: December 2021

Abstract
Background
In economic evaluation, the quality of life of people with a disability has traditionally been assessed using preference-based instruments designed to measure and value quality of life. To provide robust measurement of the effectiveness of programs designed to improve the quality of life of people living with a disability, preference-based measures need to be sufficiently sensitive to detect incremental changes in the quality of life dimensions that are most important to people who have a disability. This study sought to explore whether there was a difference in the ranked order of importance of quality of life dimensions between people with a disability and people without a disability.

Methods
An online survey was developed and administered Australia wide. The first sample (n = 410) comprised adults (aged ≥ 18 years) with a disability (n = 208) and family carers of person/s with a disability who were asked to respond on behalf of the person with a disability (n = 202). The second sample included adults without disability (n = 443). Respondents were asked to rank the importance of 12 quality of life dimensions extracted from the content of established preference-based quality of life measures (EQ-5D, AQoL and ASCOT).

Results
People with a disability placed relatively higher importance on broader quality of life dimensions (e.g. Control, Independence, Self-care) relative to health status focused dimensions (e.g. Vision, Hearing, Physical mobility). This distinction was less differentiable for those ‘without a disability’. The biggest differences in ranked importance of dimensions were in: Vision (‘with disability’ = 10th, ‘without disability’ = 4th), Self-care (‘with disability’ = 3rd, ‘without disability’ = 7th) and Mental well-being (‘with disability’ = 6th, ‘without disability’ = 2nd).

Conclusions
The relative importance of quality of life dimensions for people with a disability differs to people without a disability. Quality of life is a key outcome for economic evaluation and for assessing the impact of disability care policy and practice in Australia and internationally. It is important that the effectiveness of interventions is measured and valued in ways which are fully reflective of the quality of life preferences of people with a disability.
Changes of antithrombotic prescription in atrial fibrillation patients with acute coronary syndrome or percutaneous coronary intervention and the subsequent impact on long-term outcomes: a longitudinal cohort study
Authors: Lee Chiao-Chin , Chang Chiao-Hsiang , Hung Yuan , Lin Chin-Sheng , Yang Shih-Ping , Cheng Shu-Meng , Yu Fan-Han , Lin Wei-Shiang , Lin Wen-Yu 
Published: December 2021

Abstract
Objectives
The choice of optimal antithrombotic therapy in atrial fibrillation (AF) patients with acute coronary syndrome (ACS) or percutaneous coronary intervention (PCI) remains controversial. The aim of this longitudinal cohort study is to investigate the prescribing pattern of antithrombotic regimen in different cohorts and its subsequent impact.

Setting and design
Longitudinal data from the Tri-Service General Hospital-Coronary Heart Disease (TSGH-CHD) registry, between January 2016 and August 2018 was screened.

Participants and method
Patients with prior history of nonvalvular AF, who had ACS presentation or underwent PCI were selected, and these patients were divided into cohort 1 and cohort 2, according to the index date of antithrombotic prescription before and after the PIONEER AF-PCI study.

Primary and secondary outcomes
The primary safety endpoints were composites of major bleeding and/or clinically relevant non-major bleeding. The secondary efficacy endpoints included the occurrence of all-cause mortality, stroke/systemic embolization, nonfatal myocardial infarction (MI), and >30-days coronary revascularization.

Results
A total of 121 patients were included into analysis (cohort 1=35; cohort 2=86). Comparing with cohort 1, the prescription rate of triple antithrombotic therapy (TAT) increased from 17.1 to 38.4%, especially the regimen with dual antiplatelet therapy (DAPT) plus low-dose non-vitamin-K dependent oral anticoagulation (NOAC). However, the prescription rate of dual antithrombotic therapy (DAT) decreased (14.3–10.5%), as well as the prescription rate of DAPT (68.6–51.2%). These changes of antithrombotic prescription across different cohorts were not associated with risk of adverse safety (HR= 0.87; 95% CI, 0.42-1.80, p=0.710) and efficacy outcomes (HR=0.96; 95% CI, 0.40-2.32, p=0.930).

Conclusions
Entering the NOAC era, the prescription of TAT increased alongside the decrease in DAT. As the prescription rate of DAPT without anticoagulation remained high, future efforts are mandatory to improve the implementation of guidelines and clinical practice.
Flavivirus replication kinetics in early-term placental cell lines with different differentiation pathways
Authors: Carrera Julio , Trenerry Alice M. , Simmons Cameron P. , Mackenzie Jason M. 
Published: December 2021

AbstractBackgroundThe uncontrollable spread of Zika virus (ZIKV) in the Americas during 2015–2017, and its causal link to microcephaly in newborns and Guillain-Barré syndrome in adults, led the World Health Organisation to declare it a global public health emergency. One of the most notable features of ZIKV pathogenesis was the ability of the virus to pass the placental barrier to infect the growing foetus. This pathogenic trait had not been observed previously for medically important flaviviruses, including dengue and yellow fever viruses.MethodsIn this study we evaluated the replication kinetics of ZIKV and the related encephalitic flavivirus West Nile strain Kunjin virus (WNVKUN) in early-term placental cell lines.ResultsWe have observed that WNVKUNin fact replicates with a greater rate and to higher titres that ZIKV in these cell lines.ConclusionsThese results would indicate the potential for all flaviviruses to replicate in placental tissue but it is the ability to cross the placenta itself that is the restrictive factor in the clinical progression and presentation of congenital Zika syndrome.
Exposure to combustion derived particulate matter exacerbates influenza infection in neonatal mice by inhibiting IL22 production
Authors: Kumar Avinash , Patel Vivek S. , Harding Jeffrey N. , You Dahui , Cormier Stephania A. 
Published: December 2021

Abstract
Background
Particulate matter (PM) containing environmentally persistent free radicals (EPFRs) are formed during various combustion processes, including the thermal remediation of hazardous wastes. Exposure to PM adversely affects respiratory health in infants and is associated with increased morbidity and mortality due to acute lower respiratory tract infections. We previously reported that early-life exposure to PM damages the lung epithelium and suppresses immune responses to influenza virus (Flu) infection, thereby enhancing Flu severity. Interleukin 22 (IL22) is important in resolving lung injury following Flu infection. In the current study, we determined the effects of PM exposure on pulmonary IL22 responses using our neonatal mouse model of Flu infection.

Results
Exposure to PM resulted in an immediate (0.5–1-day post-exposure; dpe) increase in IL22 expression in the lungs of C57BL/6 neonatal mice; however, this IL22 expression was not maintained and failed to increase with either continued exposure to PM or subsequent Flu infection of PM-exposed mice. This contrasts with increased IL22 expression in age-matched mice exposed to vehicle and Flu infected. Activation of the aryl hydrocarbon receptor (AhR), which mediates the induction and release of IL22 from immune cells, was also transiently increased with PM exposure. The microbiome plays a major role in maintaining epithelial integrity and immune responses by producing various metabolites that act as ligands for AhR. Exposure to PM induced lung microbiota dysbiosis and altered the levels of indole, a microbial metabolite. Treatment with recombinant IL22 or indole-3-carboxaldehyde (I3A) prevented PM associated lung injury. In addition, I3A treatment also protected against increased mortality in Flu-infected mice exposed to PMs.

Conclusions
Together, these data suggest that exposure to PMs results in failure to sustain IL22 levels and an inability to induce IL22 upon Flu infection. Insufficient levels of IL22 may be responsible for aberrant epithelial repair and immune responses, leading to increased Flu severity in areas of high PM.
Clinical application of anterior ring internal fixator system combined with sacroiliac screw fixation in Tile C pelvic fracture treatment
Authors: Liu Lin , Fan Shicai , Zeng Donggui , Chen Yuhui , Song Hui , Zeng Letian , Jin Dadi 
Published: December 2021

Abstract
Background
How to perform minimally invasive surgery for Tile C pelvic fracture is a major problem in clinical practice. We performed minimally invasive surgery for Tile C pelvic fracture using anterior ring internal fixator systems combined with sacroiliac screw fixation.

Objective
To investigate the advantages and efficacy of anterior ring internal fixator systems combined with sacroiliac screw fixation in the treatment of Tile C pelvic fracture.

Methods
From May 2017 to May 2020, 27 patients with Tile C pelvic fracture who underwent anterior ring internal fixator system combined with sacroiliac screw fixation (group A) and 21 patients with Tile C pelvic fracture who underwent plate-screw system combined with sacroiliac screw fixation (group B) were retrospectively analyzed.

Results
All 48 patients were followed up for more than 12 months, all fractures healed within 3–6 months. The operative time, intraoperative bleeding volume, blood transfusion volume, incision length, hospital stay, complication rate and Majeed score were 63.5 ± 10.7 min, 48.3 ± 27.9 ml, 0 ml, 4.5 ± 0.8 cm, 10.2 ± 2.7 d, 3.7% and 89.7 ± 4.6 points, respectively, in group A and 114.8 ± 19.1 min, 375 ± 315.8 ml, 266.7 ± 326.6 ml, 9.2 ± 3.9 cm, 20.9 ± 5.7 d, 23.8% and 88.7 ± 4.9 points, respectively, in group B. Combined excellent and good rates of the Matta evaluation and Majeed score were 100% in both groups. There were no significant differences in the Matta evaluation or Majeed score between the two groups (both P > 0.05), whereas the operative time, intraoperative bleeding volume, blood transfusion volume, incision length and hospital stay were significantly less in group A (all P < 0.05).

Conclusion
An anterior ring internal fixator system combined with sacroiliac screw fixation can effectively treat Tile C pelvic fracture, and has advantages, including minimal invasiveness, simple operation, short operative time, safe and reliable features, fewer complications, short hospital stay and a good curative effect.
Flavonoids kaempferol and quercetin are nuclear receptor 4A1 (NR4A1, Nur77) ligands and inhibit rhabdomyosarcoma cell and tumor growth
Authors: Shrestha Rupesh , Mohankumar Kumaravel , Martin Greg , Hailemariam Amanuel , Lee Syng-ook , Jin Un-ho , Burghardt Robert , Safe Stephen 
Published: December 2021

Abstract
Background
Flavonoids exhibit both chemopreventive and chemotherapeutic activity for multiple tumor types, however, their mechanisms of action are not well defined. Based on some of their functional and gene modifying activities as anticancer agents, we hypothesized that kaempferol and quercetin were nuclear receptor 4A1 (NR4A1, Nur77) ligands and confirmed that both compounds directly bound NR4A1 with KD values of 3.1 and 0.93 μM, respectively.

Methods
The activities of kaempferol and quercetin were determined in direct binding to NR4A1 protein and in NR4A1-dependent transactivation assays in Rh30 and Rh41 rhabdomyosarcoma (RMS) cells. Flavonoid-dependent effects as inhibitors of cell growth, survival and invasion were determined in XTT and Boyden chamber assays respectively and changes in protein levels were determined by western blots. Tumor growth inhibition studies were carried out in athymic nude mice bearing Rh30 cells as xenografts.

Results
Kaempferol and quercetin bind NR4A1 protein and inhibit NR4A1-dependent transactivation in RMS cells. NR4A1 also regulates RMS cell growth, survival, mTOR signaling and invasion. The pro-oncogenic PAX3-FOXO1 and G9a genes are also regulated by NR4A1 and, these pathways and genes are all inhibited by kaempferol and quercetin. Moreover, at a dose of 50 mg/kg/d kaempferol and quercetin inhibited tumor growth in an athymic nude mouse xenograft model bearing Rh30 cells.

Conclusion
These results demonstrate the clinical potential for repurposing kaempferol and quercetin for clinical applications as precision medicine for treating RMS patients that express NR4A1 in order to increase the efficacy and decrease dosages of currently used cytotoxic drugs.
A guide to enteral nutrition in intensive care units: 10 expert tips for the daily practice
Authors: Preiser Jean-Charles , Arabi Yaseen M. , Berger Mette M. , Casaer Michael , McClave Stephen , Montejo-González Juan C. , Peake Sandra , Reintam Blaser Annika , Van den Berghe Greet , van Zanten Arthur , Wernerman Jan , Wischmeyer Paul 
Published: December 2021

AbstractThe preferential use of the oral/enteral route in critically ill patients over gut rest is uniformly recommended and applied. This article provides practical guidance on enteral nutrition in compliance with recent American and European guidelines. Low-dose enteral nutrition can be safely started within 48 h after admission, even during treatment with small or moderate doses of vasopressor agents. A percutaneous access should be used when enteral nutrition is anticipated for ≥ 4 weeks. Energy delivery should not be calculated to match energy expenditure before day 4–7, and the use of energy-dense formulas can be restricted to cases of inability to tolerate full-volume isocaloric enteral nutrition or to patients who require fluid restriction. Low-dose protein (max 0.8 g/kg/day) can be provided during the early phase of critical illness, while a protein target of > 1.2 g/kg/day could be considered during the rehabilitation phase. The occurrence of refeeding syndrome should be assessed by daily measurement of plasma phosphate, and a phosphate drop of 30% should be managed by reduction of enteral feeding rate and high-dose thiamine. Vomiting and increased gastric residual volume may indicate gastric intolerance, while sudden abdominal pain, distension, gastrointestinal paralysis, or rising abdominal pressure may indicate lower gastrointestinal intolerance.