bluuebunny/crossref_metadata_2025_split huggingface dataset:
The in-vivo dynamics of Plasmodium falciparum HRP2: implications for the use of rapid diagnostic tests in malaria elimination
Authors: Marquart Louise , Webb Lachlan , O’Rourke Peter , Gatton Michelle L. , Hsiang Michelle S. , Kalnoky Michael , Jang Ihn Kyung , Ntuku Henry , Mumbengegwi Davis R. , Domingo Gonzalo J. , McCarthy James S. , Britton Sumudu 
Published: August 2022

Abstract
Background
Rapid diagnostic tests (RDTs) that rely on the detection of Plasmodium falciparum histidine-rich protein 2 (PfHRP2) have become key tools for diagnosing P. falciparum infection. The utility of RDTs can be limited by PfHRP2 persistence, however it can be a potential benefit in low transmission settings where detection of persistent PfHRP2 using newer ultra-sensitive PfHRP2 based RDTs can serve as a surveillance tool to identify recent exposure. Better understanding of the dynamics of PfHRP2 over the course of a malaria infection can inform optimal use of RDTs.

Methods
A previously published mathematical model was refined to mimic the production and decay of PfHRP2 during a malaria infection. Data from 15 individuals from volunteer infection studies were used to update the original model and estimate key model parameters. The refined model was applied to a cohort of patients from Namibia who received treatment for clinical malaria infection for whom longitudinal PfHRP2 concentrations were measured.

Results
The refinement of the PfHRP2 dynamic model indicated that in malaria naïve hosts, P. falciparum parasites of the 3D7 strain produce 33.6 × 10−15 g (95% CI 25.0–42.1 × 10−15 g) of PfHRP2 in vivo per parasite replication cycle, with an elimination half-life of 1.67 days (95% CI 1.11–3.40 days). The refined model included these updated parameters and incorporated individualized body fluid volume calculations, which improved predictive accuracy when compared to the original model. The performance of the model in predicting clearance of PfHRP2 post treatment in clinical samples from six adults with P. falciparum infection in Namibia improved when using a longer elimination half-life of 4.5 days, with 14% to 67% of observations for each individual within the predicted range.

Conclusions
The updated mathematical model can predict the growth and clearance of PfHRP2 during the production and decay of a mono-infection with P. falciparum, increasing the understanding of PfHRP2 antigen dynamics. This model can guide the optimal use of PfHRP2-based RDTs for reliable diagnosis of P. falciparum infection and re-infection in endemic settings, but also for malaria surveillance and elimination programmes in low transmission areas.
Sustainable kidney care delivery and climate change – a call to action
Authors: Yeo See Cheng , Ooi Xi Yan , Tan Tracy Suet Mun 
Published: August 2022

AbstractThe delivery of kidney care, particularly haemodialysis treatment, can result in substantial environmental impact through greenhouse emissions, natural resources depletion and waste generation. However, strategies exist to mitigate this impact and improve long term environmental sustainability for the provision of haemodialysis treatment. The nephrology community has begun taking actions to improve the environmental sustainability of dialysis, but much work remains to be done by healthcare professionals, dialysis providers and professional organisations.
Incidence and risk factors of preoperative deep vein thrombosis in patients with intertrochanteric fractures: a retrospective study
Authors: Song Kai , Zhu Bowen , Yao Yao , Jiang Qing , Xiong Jin , Shi Hongfei 
Published: August 2022

Abstract
Background
The risk of perioperative complications remains high in patients with intertrochanteric fractures. Immobilization after injury may predispose these patients to deep vein thrombosis (DVT) while waiting for surgery. The aims of this study were to determine the incidence of preoperative DVT in patients with intertrochanteric fractures and identify independent risk factors.

Methods
This retrospective study included patients with intertrochanteric fractures waiting for surgical interventions at our institution from June 2018 to December 2020. All patients received pharmacologic thromboprophylaxis after admission and ultrasound screening for DVT in both lower limbs before surgery. Demographic, clinical and laboratory data of these patients were collected to perform univariate analysis first. Subsequently, factors with a significant difference in univariate analysis were introduced into the multivariate logistic regression analysis to determine the independent risk factors for preoperative DVT.

Results
A total of 266 patients were enrolled in this study. Seventy-one patients (26.7%) developed DVTs before surgery. The majority of DVTs were distal types (91.5%). There were 40 patients with DVTs only in the affected limb, 7 patients with DVTs only in the unaffected limb, and 24 patients with DVTs in both lower limbs. Advanced age, female, prolonged period from injury to admission, combined cranial trauma, shorter thrombin time, increased level of D-dimer and lower level of albumin proved to be the independent risk factors for preoperative DVT.

Conclusions
We observed a high incidence of preoperative DVT in patients with intertrochanteric fractures. Identification of patients at high risk may improve the prevention and treatment of preoperative DVT in this population.
The effects of synbiotic and/or vitamin D supplementation on gut-muscle axis in overweight and obese women: a study protocol for a double-blind, randomized, placebo-controlled trial
Authors: Jamshidi Sanaz , Masoumi Seyed Jalil , Abiri Behnaz , Vafa Mohammadreza 
Published: August 2022

Abstract
Background
Sarcopenia refers to an age-related loss of skeletal muscle content, strength, and function, leading to a decrease in mobility. Obesity may exacerbate age-related complications such as sarcopenia through inflammatory pathways. In addition, intestinal dysbiosis has been proposed as an emerging contributor to sarcopenia due to the stimulation of the immune system and elevated barrier permeability of the intestine. Targeting microbiome with synbiotic and vitamin D supplementation may modulate the microbiome followed by the enhancement of sarcopenia indices. Thus, the present study aims to evaluate the effect of synbiotic supplementation with or without vitamin D on the intestinal microbiome and its relationship with strength, muscle function, and body composition in middle-aged overweight and obese women.

Methods
This multi-factorial, double-blind, randomized controlled trial will be conducted on 88 participants in eight weeks. The participants will be allocated into four groups receiving vitamin D placebo (weekly) and synbiotic placebo (daily), vitamin D and synbiotic placebo, vitamin D placebo and symbiotic, and vitamin D and synbiotic. Intestinal microbiome assessment will be done by DNA isolation and real-time polymerase chain reaction (PCR). In addition, anthropometric indices, body composition, muscle strength, and physical performance will be evaluated by standard methods. All measurements will be made at the beginning and end of the study.

Discussion
The previous studies showed that probiotics were involved in reducing inflammation, insulin sensitivity, modulation of atrophy markers such as atherogen-1, and decreasing reactive oxygen indices. In addition, vitamin D was found to improve the intestinal microbiome and facilitate muscle anabolism. The present protocol is novel as it aims to investigate the impact of the co-supplementation of synbiotic and vitamin D on the gut microbiome and sarcopenia indices.

Trial registration
This trial has been registered in the Iranian Registry of Clinical Trials (IRCT20090822002365N25, date of registration: March 2021).
Inflammatory plasma biomarkers in subjects with preclinical Alzheimer’s disease
Authors: Prins Samantha , de Kam Marieke L. , Teunissen Charlotte E. , Groeneveld Geert Jan 
Published: August 2022

AbstractBackgroundThis study investigated plasma biomarkers for neuroinflammation associated with Alzheimer’s disease (AD) in subjects with preclinical AD compared to healthy elderly. How these biomarkers behave in patients with AD, compared to healthy elderly is well known, but determining these in subjects with preclinical AD is not and will add information related to the onset of AD. When found to be different in preclinical AD, these inflammatory biomarkers may be used to select preclinical AD subjects who are most likely to develop AD, to participate in clinical trials with new disease-modifying drugs.MethodsHealthy elderly (n= 50; age 71.9; MMSE >24) and subjects with preclinical AD (n=50; age 73.4; MMSE >24) defined by CSF Aβ1-42 levels < 1000 pg/mL were included. Four neuroinflammatory biomarkers were determined in plasma, GFAP, YKL-40, MCP-1, and eotaxin-1. Differences in biomarker outcomes were compared using ANCOVA. Subject characteristics age, gender, and APOE ε4 status were reported per group and were covariates in the ANCOVA. Least square means were calculated for all 4 inflammatory biomarkers using both the Aβ+/Aβ− cutoff and Ptau/Aβ1-42 ratio.ResultsThe mean (standard deviation, SD) age of the subjects (n=100) was 72.6 (4.6) years old with 62 male and 38 female subjects. Mean (SD) overall MMSE score was 28.7 (0.49) and 32 subjects were APOE ε4 carriers. The number of subjects in the different APOE ε4 status categories differed significantly between the Aβ+ and Aβ− groups. Plasma GFAP concentration was significantly higher in the Aβ+ group compared to the Aβ− group with significant covariates age and sex, variables that also correlated significantly with GFAP.ConclusionGFAP was significantly higher in subjects with preclinical AD compared to healthy elderly which agrees with previous studies. When defining preclinical AD based on the Ptau181/Aβ1-42 ratio, YKL-40 was also significantly different between groups. This could indicate that GFAP and YKL-40 are more sensitive markers of the inflammatory process in response to the Aβ misfolding and aggregation that is ongoing as indicated by the lowered Aβ1-42 levels in the CSF. Characterizing subjects with preclinical AD using neuroinflammatory biomarkers is important for subject selection in new disease-modifying clinical trials.Trial registrationISRCTN.orgidentifier: ISRCTN79036545 (retrospectively registered).
Downregulation of DNA methyltransferase-3a ameliorates the osteogenic differentiation ability of adipose-derived stem cells in diabetic osteoporosis via Wnt/β-catenin signaling pathway
Authors: Zhang Maorui , Gao Yujin , Li Qing , Cao Huayue , Yang Jianghua , Cai Xiaoxiao , Xiao Jingang 
Published: August 2022

Abstract
Background
Diabetes-related osteoporosis (DOP) is a chronic disease caused by the high glucose environment that induces a metabolic disorder of osteocytes and osteoblast-associated mesenchymal stem cells. The processes of bone defect repair and regeneration become extremely difficult with DOP. Adipose-derived stem cells (ASCs), as seed cells in bone tissue engineering technology, provide a promising therapeutic approach for bone regeneration in DOP patients. The osteogenic ability of ASCs is lower in a DOP model than that of control ASCs. DNA methylation, as a mechanism of epigenetic regulation, may be involved in DNA methylation of various genes, thereby participating in biological behaviors of various cells. Emerging evidence suggests that increased DNA methylation levels are associated with activation of Wnt/β-catenin signaling pathway. The purpose of this study was to investigate the influence of the diabetic environment on the osteogenic potential of ASCs, to explore the role of DNA methylation on osteogenic differentiation of DOP-ASCs via Wnt/β-catenin signaling pathway, and to improve the osteogenic differentiation ability of ASCs with DOP.

Methods
DOP-ASCs and control ASCs were isolated from DOP C57BL/6 and control mice, respectively. The multipotency of DOP-ASCs was confirmed by Alizarin Red-S, Oil Red-O, and Alcian blue staining. Real-time polymerase chain reaction (RT-PCR), immunofluorescence, and western blotting were used to analyze changes in markers of osteogenic differentiation, DNA methylation, and Wnt/β-catenin signaling. Alizarin Red-S staining was also used to confirm changes in the osteogenic ability. DNMT small interfering RNA (siRNA), shRNA-Dnmt3a, and LVRNA-Dnmt3a were used to assess the role of Dnmt3a in osteogenic differentiation of control ASCs and DOP-ASCs. Micro-computed tomography, hematoxylin and eosin staining, and Masson staining were used to analyze changes in the osteogenic capability while downregulating Dnmt3a with lentivirus in DOP mice in vivo.

Results
The proliferative ability of DOP-ASCs was lower than that of control ASCs. DOP-ASCs showed a decrease in osteogenic differentiation capacity, lower Wnt/β-catenin signaling pathway activity, and a higher level of Dnmt3a than control ASCs. When Dnmt3a was downregulated by siRNA and shRNA, osteogenic-related factors Runt-related transcription factor 2 and osteopontin, and activity of Wnt/β-catenin signaling pathway were increased, which rescued the poor osteogenic potential of DOP-ASCs. When Dnmt3a was upregulated by LVRNA-Dnmt3a, the osteogenic ability was inhibited. The same results were obtained in vivo.

Conclusions
Dnmt3a silencing rescues the negative effects of DOP on ASCs and provides a possible approach for bone tissue regeneration in patients with diabetic osteoporosis.
The frequency of efflux pump genes expression in Acinetobacter baumannii isolates from pulmonary secretions
Authors: Rafiei Ebrahim , Shahini Shams Abadi Milad , Zamanzad Behnam , Gholipour Abolfazl 
Published: August 2022

AbstractAcinetobacter baumannii is an important opportunistic pathogen, and the cause of nosocomial infections worldwide in recent decades. Efflux pumps are considered as the important causes of multidrug resistance of A. baumannii. The aim of this study was to determine the frequency of efflux pump genes, and evaluate the antibiotic effect of Tigecycline on the expression of adeB gene in isolates of multidrug-resistant. A. baumannii. 70 isolates of A. baumannii were collected and confirmed by biochemical and molecular tests. Antibiotic resistance (Ciprofloxacin, Trimethoprim-sulfamethoxazole, and Tigecycline) was performed based on the minimum inhibitory concentration (MIC) method. Then, the effect of Carbonyl cyanide m-chlorophenyl hydrazone inhibitor (CCCP) on isolates was investigated and the frequency of adeB, adeG, adeJ and abeM genes were examined by PCR for isolates with reduced in MIC titer. Also, the antibiotic effect of Tigecycline on adeB gene expression in A. baumannii isolates was analyzed by Real-Time PCR. The antibiotic resistance for Ciprofloxacin, Trimethoprim-sulfamethoxazole, and Tigecycline was 97.1%, 95.8% and 37.2%, respectively. Following CCCP inhibitor use, the MIC titer had a decrease in MIC titer containing CCCP inhibitor was 64.3% for Ciprofloxacin, 51.5% for Trimethoprim-sulfamethoxazole and 50% for Tigecycline. The frequencies of genes associated with adeB, adeG, adeJ and abeM efflux pump were 100%, 92.8%, 86% and 98.5%, respectively. Real-Time PCR results showed a correlation between the antibiotic effects of Tigecycline on adeB gene expression. The antibiotic resistance of the isolates was relatively high. The isolates were resistant to Ciprofloxacin and Trimethoprim-sulfamethoxazole antibiotics, while more sensitive to Tigecycline. Also, efflux pump genes, which are the antibiotic resistance factors of A. baumannii, are frequently high in the isolates but it seems that isolates use other effluxe pumps than RND family to exit tigecycline.
Graphical Abstract
Are winter rangelands enough to satisfy the nutritional requirements of late-gestation transhumant goats in Patagonia?
Authors: Caballero Verónica Jorgelina , Romero Martinez Jesús , Borrelli Laura Beatriz , Castillo Daniel Alejandro , Mikuc Juan Pablo , Villar María Laura , Villagra Edgar Sebastian 
Published: August 2022

AbstractTranshumant herds graze across two different rangeland types according to the season. Winter rangelands differ from summer rangelands in the amount and quality of available fodder, with the former being the less productive. In cold areas, winter rangeland has low forage quality where goats may suffer severe nutritional restrictions during gestation which lead to significant reproductive losses in the form of abortions and perinatal losses. In Argentinian northern Patagonia, the transhumant Criollo goat is a dual-purpose breed, producing both meat and cashmere and grazing on winter rangelands where they complete their reproductive cycle. Our objective was to evaluate to what extent the winter rangelands of northern Argentine Patagonia satisfy the nutritional requirements needed by Criollo transhumant goats during late gestating. We evaluated a study between 2010 and 2012 where we analysed the body weight and body condition score of the goats reaching the winter rangelands and before kidding. We also analysed the botanical composition of their diet, the quality forage (metabolizable energy, crude protein and digestibility) contribution offered by the species and the proportions of the nutritional requirements of the goats during the last third of gestation. Significantly, we found a decrease in body weight and body condition score in late gestation. In 2010, the goats’ diet showed a nutritional deficiency value of 0.6 Mcal/day metabolizable energy and 30.43 g/day crude protein; in 2011, a deficiency of 0.77 Mcal/day metabolizable energy and 65.48 g/day crude protein; and in 2012, a deficiency of 0.75 Mcal/day metabolizable energy and 55.41 g/day crude protein. Forage present 51, 52 and 48% digestibility in each year, respectively. We conclude that forage quality in winter rangelands in Argentinean Patagonia is not high enough to satisfy the nutritional requirements of Criollo transhumant goats during the last third of gestation. We recommend 550 g/day of an 80:20 mixture of corn:soy expeller supplementation during late gestation.
Camera traps reveal the natural corridors used by mammalian species in eastern Mexico
Authors: Huerta-Rodríguez Jonathan O. , Rosas-Rosas Octavio C. , López-Mata Lauro , Alcántara-Carbajal José L. , Tarango-Arámbula Luis A. 
Published: August 2022

Abstract
Background
Habitat loss and fragmentation in the Sierra Madre Oriental (SMO) ecological corridor have negative impacts on the movement and distribution of mammalian species that are of great ecological and evolutionary importance. Part of the SMO ecological corridor that is located in the state of Hidalgo is less studied despite being a potential dispersal route for mammals. The objectives of this study were to evaluate the presence and activity of terrestrial mammals in the riparian and non-riparian zones of SMO.

Results
Camera traps detected 15 mammalian species (i.e., 14 native and 1 domestic) in the non-riparian zone, and 12 mammalian species in the riparian zone (i.e., 10 wild and 2 domestic). The riparian corridor was mainly used by opportunistic medium-sized carnivores, while large carnivores and their potential prey were more frequent in the non-riparian zone.

Conclusions
Our findings suggest terrestrial mammals avoid the use of natural corridors due to the presence of domestic dogs, cattle and humans and look for new dispersal routes to move through their habitat and find the resources they need to survive. Even though some species can use disturbed corridors to move and find resources, they will change their activity patterns to avoid contact with humans and potential threats like dogs. It is, therefore, crucial to identify not one, but several corridors that must be preserved to improve the connectivity of terrestrial mammals in disturbed landscapes.
Quantitative microbial population study reveals geographical differences in bacterial symbionts of Ixodes ricinus
Authors: Krawczyk Aleksandra I. , Röttjers Lisa , Fonville Manoj , Takumi Katshuisa , Takken Willem , Faust Karoline , Sprong Hein 
Published: August 2022

Abstract
Background
Ixodes ricinus ticks vector pathogens that cause serious health concerns. Like in other arthropods, the microbiome may affect the tick’s biology, with consequences for pathogen transmission. Here, we explored the bacterial communities of I. ricinus across its developmental stages and six geographic locations by the 16S rRNA amplicon sequencing, combined with quantification of the bacterial load.

Results
A wide range of bacterial loads was found. Accurate quantification of low microbial biomass samples permitted comparisons to high biomass samples, despite the presence of contaminating DNA. The bacterial communities of ticks were associated with geographical location rather than life stage, and differences in Rickettsia abundance determined this association.
Subsequently, we explored the geographical distribution of four vertically transmitted symbionts identified in the microbiome analysis. For that, we screened 16,555 nymphs from 19 forest sites for R. helvetica, Rickettsiella spp., Midichloria mitochondrii, and Spiroplasma ixodetis. Also, the infection rates and distributions of these symbionts were compared to the horizontally transmitted pathogens Borrelia burgdorferi sensu lato, Anaplasma phagocytophilum, and Neoehrlichia mikurensis.
The infection rates of all vertically transmitted symbionts differed between the study sites, and none of the symbionts was present in all tested ticks suggesting a facultative association with I. ricinus. The proportions in which symbionts occurred in populations of I. ricinus were highly variable, but geographically close study sites expressed similar proportions. These patterns were in contrast to what we observed for horizontally transmitted pathogens. Lastly, nearly 12% of tested nymphs were free of any targeted microorganisms, which is in line with the microbiome analyses.

Conclusions
Our results show that the microbiome of I. ricinus is highly variable, but changes gradually and ticks originating from geographically close forest sites express similar bacterial communities. This suggests that geography-related factors affect the infection rates of vertically transmitted symbionts in I. ricinus. Since some symbionts, such as R. helvetica can cause disease in humans, we propose that public health investigations consider geographical differences in its infection rates.