bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of long-distance transportation on blood constituents and composition of the nasal microbiota in healthy donkeys
Authors: Zhao Fuwei , Jiang Guimiao , Ji Chuanliang , Zhang Zhiping , Gao Weiping , Feng Peixiang , Li Haijing , Li Min , Liu Haibing , Liu Guiqin , Magalhaes Humberto B. , Li Jianji 
Published: September 2020

AbstractBackgroundThis study aims to determine the effects of transportation on the nasal microbiota of healthy donkeys using 16S rRNA sequencing.ResultsDeep nasal swabs and blood were sampled from 14 donkeys before and after 21 hours’ long-distance transportation. The values of the plasma hormone (cortisol (Cor), adrenocorticotrophic hormone (ACTH)), biochemical indicators (total protein (TP), albumin (ALB), creatinine (CREA), lactic dehydrogenase (LDH), aspartate transaminase (AST), creatine kinase (CK), blood urea (UREA), plasma glucose (GLU)) and blood routine indices (white blood cell (WBC), lymphocyte (LYM), neutrophil (NEU), red blood cell (RBC), hemoglobin (HGB)) were measured. 16S rRNA sequencing was used to assess the nasal microbiota, including alpha diversity, beta diversity, and phylogenetic structures. Results showed that levels of Cor, ACTH, and heat-shock protein 90 (HSP90) were significantly increased (p < 0.05) after long-distance transportation. Several biochemical indicators (AST, CK) and blood routine indices (Neu, RBC, and HGB) increased markedly (p < 0.05), but the LYM decreased significantly (p < 0.05). Nine families and eight genera had a mean relative abundance over 1%. The predominant phyla in nasal microbiota after and before transportation wereProteobacteria,Firmicutes,Actinobacteria, andBacteroidetes. Transportation stress induced significant changes in terms of nasal microbiota structure compared with those before transportation based on principal coordinate analysis (PCoA) coupled with analysis of similarities (ANOSIM) (p < 0.05). Among these changes, a notably gain inProteobacteriaand loss inFirmicutesat the phylum level was observed.ConclusionsThese results suggest transportation can cause stress to donkeys and change the richness and diversity of nasal microbiota. Further studies are required to understand the potential effect of these microbiota changes on the development of donkey respiratory diseases.
Geographic and host distribution of haemosporidian parasite lineages from birds of the family Turdidae
Authors: Harl Josef , Himmel Tanja , Valkiūnas Gediminas , Ilgūnas Mikas , Bakonyi Támas , Weissenböck Herbert 
Published: September 2020

AbstractBackgroundHaemosporidians (Apicomplexa, Protista) are obligate heteroxenous parasites of vertebrates and blood-sucking dipteran insects. Avian haemosporidians comprise more than 250 species traditionally classified into four genera,Plasmodium,Haemoproteus,Leucocytozoon, andFallisia. However, analyses of the mitochondrialCytBgene revealed a vast variety of lineages not yet linked to morphospecies. This study aimed to analyse and discuss the data of haemosporidian lineages isolated from birds of the family Turdidae, to visualise host and geographic distribution using DNA haplotype networks and to suggest directions for taxonomy research on parasite species.MethodsHaemosporidianCytBsequence data from 350 thrushes were analysed for the present study and complemented withCytBdata of avian haemosporidians gathered from Genbank and MalAvi database. Maximum Likelihood trees were calculated to identify clades featuring lineages isolated from Turdidae species. For each clade, DNA haplotype networks were calculated and provided with information on host and geographic distribution.ResultsIn species of the Turdidae, this study identified 82Plasmodium, 37Haemoproteus, and 119Leucocytozoonlineages, 68, 28, and 112 of which are mainly found in this host group. Most of these lineages cluster in the clades, which are shown as DNA haplotype networks. The lineages of theLeucocytozoonclades were almost exclusively isolated from thrushes and usually were restricted to one host genus, whereas thePlasmodiumandHaemoproteusnetworks featured multiple lineages also recovered from other passeriform and non-passeriform birds.ConclusionThis study represents the first attempt to summarise information on the haemosporidian parasite lineages of a whole bird family. The analyses allowed the identification of numerous groups of related lineages, which have not been linked to morphologically defined species yet, and they revealed several cases in whichCytBlineages were probably assigned to the wrong morphospecies. These taxonomic issues are addressed by comparing distributional patterns of theCytBlineages with data from the original species descriptions and further literature. The authors also discuss the availability of sequence data and emphasise that MalAvi database should be considered an extremely valuable addition to GenBank, but not a replacement.
Diabetes is associated with familial idiopathic normal pressure hydrocephalus: a case–control comparison with family members
Authors: Räsänen Joel , Huovinen Joel , Korhonen Ville E. , Junkkari Antti , Kastinen Sami , Komulainen Simo , Oinas Minna , Avellan Cecilia , Frantzen Janek , Rinne Jaakko , Ronkainen Antti , Kauppinen Mikko , Lönnrot Kimmo , Perola Markus , Koivisto Anne M. , Remes Anne M. , Soininen Hilkka , Hiltunen Mikko , Helisalmi Seppo , Kurki Mitja I. , Jääskeläinen Juha E. , Leinonen Ville 
Published: September 2020

Abstract
Background
The pathophysiological basis of idiopathic normal pressure hydrocephalus (iNPH) is still unclear. Previous studies have shown a familial aggregation and a potential heritability when it comes to iNPH. Our aim was to conduct a novel case-controlled comparison between familial iNPH (fNPH) patients and their elderly relatives, involving multiple different families.

Methods
Questionnaires and phone interviews were used for collecting the data and categorising the iNPH patients into the familial (fNPH) and the sporadic groups. Identical questionnaires were sent to the relatives of the potential fNPH patients. Venous blood samples were collected for genetic studies. The disease histories of the probable fNPH patients (n = 60) were compared with their ≥ 60-year-old relatives with no iNPH (n = 49). A modified Charlson Comorbidity Index (CCI) was used to measure the overall disease burden. Fisher’s exact test (two-tailed), the Mann–Whitney U test (two-tailed) and a multivariate binary logistic regression analysis were used to perform the statistical analyses.

Results
Diabetes (32% vs. 14%, p = 0.043), arterial hypertension (65.0% vs. 43%, p = 0.033), cardiac insufficiency (16% vs. 2%, p = 0.020) and depressive symptoms (32% vs. 8%, p = 0.004) were overrepresented among the probable fNPH patients compared to their non-iNPH relatives. In the age-adjusted multivariate logistic regression analysis, diabetes remained independently associated with fNPH (OR = 3.8, 95% CI 1.1–12.9, p = 0.030).

Conclusions
Diabetes is associated with fNPH and a possible risk factor for fNPH. Diabetes could contribute to the pathogenesis of iNPH/fNPH, which motivates to further prospective and gene-environmental studies to decipher the disease modelling of iNPH/fNPH.
Application of dose-volume histogram prediction in biologically related models for nasopharyngeal carcinomas treatment planning
Authors: Cao Wufei , Zhuang Yongdong , Chen Lixin , Liu Xiaowei 
Published: September 2020

Abstract
Purpose
In this study, we employed a gated recurrent unit (GRU)-based recurrent neural network (RNN) using dosimetric information induced by individual beam to predict the dose-volume histogram (DVH) and investigated the feasibility and usefulness of this method in biologically related models for nasopharyngeal carcinomas (NPC) treatment planning.

Methods and materials
One hundred patients with NPC undergoing volumetric modulated arc therapy (VMAT) between 2018 and 2019 were randomly selected for this study. All the VMAT plans were created using the Monaco treatment planning system (Elekta, Sweden) and clinically approved: > 98% of PGTVnx received the prescribed doses of 70 Gy, > 98% of PGTVnd received the prescribed doses of 66 Gy and > 98% of PCTV received 60 Gy. Of these, the data from 80 patients were used to train the GRU-RNN, and the data from the other 20 patients were used for testing. For each NPC patient, the DVHs of different organs at risk were predicted by a trained GRU-based RNN using the information given by individual conformal beams. Based on the predicted DVHs, the equivalent uniform doses (EUD) were calculated and applied as dose constraints during treatment planning optimization. The regenerated VMAT experimental plans (EPs) were evaluated by comparing them with the clinical plans (CPs).

Results
For the 20 test patients, the regenerated EPs guided by the GRU-RNN predictive model achieved good consistency relative to the CPs. The EPs showed better consistency in PTV dose distribution and better dose sparing for many organs at risk, and significant differences were found in the maximum/mean doses to the brainstem, brainstem PRV, spinal cord, lenses, temporal lobes, parotid glands and larynx with P-values < 0.05. On average, compared with the CPs, the maximum/mean doses to these OARs were altered by − 3.44 Gy, − 1.94 Gy, − 1.88 Gy, 0.44 Gy, 1.98 Gy, − 1.82 Gy and 2.27 Gy, respectively. In addition, significant differences were also found in brainstem and spinal cord for the dose received by 1 cc volume with 4.11 and 1.67 Gy dose reduction in EPs on average.

Conclusion
The GRU-RNN-based DVH prediction method was capable of accurate DVH prediction. The regenerated plans guided by the predicted EUDs were not inferior to the manual plans, had better consistency in PTVs and better dose sparing in critical OARs, indicating the usefulness and effectiveness of biologically related model in knowledge-based planning.
Long-term results after thoracoscopic anterior spondylodesis with or without posterior stabilization of unstable incomplete burst fractures of the thoracolumbar junction: a prospective cohort study
Authors: Hoffmann Christof , Spiegl Ulrich Josef , Paetzold Robert , Devitt Brian , Hauck Stefan , Weiss Thomas , Bühren Volker , Gonschorek Oliver 
Published: September 2020

Abstract
Background
Minimally invasive, thoracoscopic anterior spondylodesis (MIAS) is an established treatment for burst fractures of the thoracolumbar spine. Good restoration of the local sagittal alignment and good functional results have been reported. The aim of this study was to evaluate long-term results of MIAS in patients with incomplete burst fractures and to analyze the influence on global sagittal alignment, clinical outcomes, and adjacent segment degeneration.

Methods
From 2002 to 2003, 18 patients were treated with MIAS for incomplete thoracolumbar burst fractures. Mono-segmental spondylodesis was performed with an iliac crest bone graft and bisegmental spondylodesis with a titanium cage. In this single-center prospective cohort study, 15 patients were available for follow-up (FU) after an average of 12.9 years (12.1–14.4). Seven patients were treated with a combined anterior and posterior instrumentation and eight patients with anterior spondylodesis only. The primary clinical outcome parameter was the Oswestry Disability Index (ODI); secondary parameters were the Short Form 36 (SF36) and the visual analog scale (VAS spine). Full spine radiographs were assessed for bisegmental Cobb angle, alignment parameters, and signs of adjacent segment degeneration (ASD).

Results
ODI evaluation showed a mean impairment of 11.7% with minimal limitations in 13 patients. Neither a significant deterioration over time nor significant differences between both therapy strategies were found in the clinical scores at the latest follow-up. The mean bisegmental increase of regional malalignment of reduction was 8.8° (± 7.3°) with no significant correlation to any clinical outcome scores. The majority of patients had no signs of adjacent segment degeneration. Two patients showed minor radiologic changes. All patients had a balanced sagittal spine profile.

Conclusions
In conclusion, MIAS leads to good clinical results with—in majority—minimal spine-related impairment at the latest follow-up. No significant deterioration at 12-year FU was detectable compared to the 6-year results for the SF36 and VAS spine scores. There was no association between sagittal alignment, clinical outcome scores, and ASD.

Trial registration
The study was retrospectively registered in the German Clinical Trials Register (Nr.00015656).
Comparing the efficacy of syngeneic iliac and femoral allografts with iliac crest autograft in a rat model of lumbar spinal fusion
Authors: Holmes Christina , Elder Benjamin D. , Ishida Wataru , Perdomo-Pantoja Alexander , Locke John , Cottrill Ethan , Lo Sheng-Fu L. , Witham Timothy F. 
Published: September 2020

Abstract
Background
Despite widespread use of femoral-sourced allografts in clinical spinal fusion procedures and the increasing interest in using femoral reamer–irrigator–aspirator (RIA) autograft in clinical bone grafting, few studies have examined the efficacy of femoral grafts compared to iliac crest grafts in spinal fusion. The objective of this study was to directly compare the use of autologous iliac crest with syngeneic femoral and iliac allograft bone in the rat model of lumbar spinal fusion.

Methods
Single-level bilateral posterolateral intertransverse process lumbar spinal fusion surgery was performed on Lewis rats divided into three experimental groups: iliac crest autograft, syngeneic iliac crest allograft, and syngeneic femoral allograft bone. Eight weeks postoperatively, fusion was evaluated via microCT analysis, manual palpation, and histology. In vitro analysis of the colony-forming and osteogenic capacity of bone marrow cells derived from rat femurs and hips was also performed to determine whether there was a correlation with the fusion efficacy of these graft sources.

Results
Although no differences were observed between groups in CT fusion mass volumes, iliac allografts displayed an increased number of radiographically fused fusion masses and a higher rate of bilateral fusion via manual palpation. Histologically, hip-derived grafts showed better integration with host bone than femur derived ones, likely associated with the higher concentration of osteogenic progenitor cells observed in hip-derived bone marrow.

Conclusions
This study demonstrates the feasibility of using syngeneic allograft bone in place of autograft bone within inbred rat fusion models and highlights the need for further study of femoral-derived grafts in fusion.
CDK4/6 inhibitors: a novel strategy for tumor radiosensitization
Authors: Yang Yilan , Luo Jurui , Chen Xingxing , Yang Zhaozhi , Mei Xin , Ma Jinli , Zhang Zhen , Guo Xiaomao , Yu Xiaoli 
Published: September 2020

AbstractRecently, the focus of enhancing tumor radiosensitivity has shifted from chemotherapeutics to targeted therapies. Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors are a novel class of selective cell cycle therapeutics that target the cyclin D-CDK4/6 complex and induce G1 phase arrest. These agents have demonstrated favorable effects when used as monotherapy or combined with endocrine therapy and targeted inhibitors, stimulating further explorations of other combination strategies. Multiple preclinical studies have indicated that CDK4/6 inhibitors exhibit a synergistic effect with radiotherapy both in vitro and in vivo. The principal mechanisms of radiosensitization effects include inhibition of DNA damage repair, enhancement of apoptosis, and blockade of cell cycle progression, which provide the rationale for clinical use. CDK4/6 inhibitors also induce cellular senescence and promote anti-tumor immunity, which might represent potential mechanisms for radiosensitization. Several small sample clinical studies have preliminarily indicated that the combination of CDK4/6 inhibitors and radiotherapy exhibited well-tolerated toxicity and promising efficacy. However, most clinical trials in combined therapy remain in the recruitment stage. Further work is required to seek optimal radiotherapy-drug combinations. In this review, we describe the effects and underlying mechanisms of CDK4/6 inhibitors as a radiosensitizer and discuss previous clinical studies to evaluate the prospects and challenges of this combination.
Failure of target attainment of beta-lactam antibiotics in critically ill patients and associated risk factors: a two-center prospective study (EXPAT)
Authors: Abdulla Alan , Dijkstra Annemieke , Hunfeld Nicole G. M. , Endeman Henrik , Bahmany Soma , Ewoldt Tim M. J. , Muller Anouk E. , van Gelder Teun , Gommers Diederik , Koch Birgit C. P. 
Published: September 2020

Abstract
Background
Early and appropriate antibiotic dosing is associated with improved clinical outcomes in critically ill patients, yet target attainment remains a challenge. Traditional antibiotic dosing is not suitable in critically ill patients, since these patients undergo physiological alterations that strongly affect antibiotic exposure. For beta-lactam antibiotics, the unbound plasma concentrations above at least one to four times the minimal inhibitory concentration (MIC) for 100% of the dosing interval (100%ƒT > 1–4×MIC) have been proposed as pharmacodynamic targets (PDTs) to maximize bacteriological and clinical responses. The objectives of this study are to describe the PDT attainment in critically ill patients and to identify risk factors for target non-attainment.

Methods
This prospective observational study was performed in two ICUs in the Netherlands. We enrolled adult patients treated with the following beta-lactam antibiotics: amoxicillin (with or without clavulanic acid), cefotaxime, ceftazidime, ceftriaxone, cefuroxime, and meropenem. Based on five samples within a dosing interval at day 2 of therapy, the time unbound concentrations above the epidemiological cut-off (ƒT > MICECOFF and ƒT > 4×MICECOFF) were determined. Secondary endpoints were estimated multivariate binomial and binary logistic regression models, for examining the association of PDT attainment with patient characteristics and clinical outcomes.

Results
A total of 147 patients were included, of whom 63.3% achieved PDT of 100%ƒT > MICECOFF and 36.7% achieved 100%ƒT > 4×MICECOFF. Regression analysis identified male gender, estimated glomerular filtration rate (eGFR) ≥ 90 mL/min/1.73 m2, and high body mass index (BMI) as risk factors for target non-attainment. Use of continuous renal replacement therapy (CRRT) and high serum urea significantly increased the probability of target attainment. In addition, we found a significant association between the 100%ƒT > MICECOFF target attainment and ICU length of stay (LOS), but no significant correlation was found for the 30-day survival.

Conclusions
Traditional beta-lactam dosing results in low target attainment in the majority of critically ill patients. Male gender, high BMI, and high eGFR were significant risk factors for target non-attainment. These predictors, together with therapeutic drug monitoring, may help ICU clinicians in optimizing beta-lactam dosing in critically ill patients.

Trial registration
Netherlands Trial Registry (EXPAT trial), NTR 5632. Registered on 7 December 2015.
Long-term physical activity on prescription intervention for patients with insufficient physical activity level—a randomized controlled trial
Authors: Lundqvist Stefan , Börjesson Mats , Cider Åsa , Hagberg Lars , Ottehall Camilla Bylin , Sjöström Johan , Larsson Maria E. H. 
Published: September 2020

Abstract
Background
Physical activity (PA) can be used to prevent and treat diseases. In Sweden, licensed healthcare professionals use PA on prescription (PAP) to support patients to increase their PA level. The aim of this randomized controlled trial was to evaluate a 2-year intervention of two different strategies of PAP treatment for patients with insufficient PA level, after a previous 6-month period of ordinary PAP treatment in a primary health care setting.

Methods
We included 190 patients, 27–77 years, physically inactive with metabolic risk factors where the patients were not responding to a previous 6-month PAP treatment with increased PA. The patients were randomized to either enhanced support from a physiotherapist (PT group) or continued ordinary PAP treatment at the health care centre (HCC group). The PAP treatment included an individualized dialogue; an individually dosed PA recommendation, including a written prescription; and a structured follow-up. In addition to PAP, the PT group received aerobic fitness tests and more frequent scheduled follow-ups. The patient PA level, metabolic health, and health-related quality of life (HRQOL) were measured at baseline and at 1- and 2-year follow-ups.

Results
At the 2-year follow-up, 62.9% of the PT group and 50.8% of the HCC group had increased their PA level and 31.4% vs. 38.5% achieved ≥ 150 min of moderate-intensity PA/week (difference between groups n.s.). Over 2 years, both groups displayed increased high-density lipoproteins (HDL) (p = 0.004 vs. baseline), increased mental health status (MCS) (p = 0.036), and reduced body mass index (BMI) (p = 0.001), with no difference between groups.

Conclusion
During long-term PAP interventions, the PA level, metabolic health, and HRQOL increased in patients at metabolic risk without significant differences between groups. The results indicate to be independent of any changes in pharmacological treatment. We demonstrated that the PAP treatment was feasible in ordinary primary care. Both the patients and the healthcare system benefitted from the improvement in metabolic risk factors. Future studies should elucidate effective long-term PAP-treatment strategies.

Trial registration
ClinicalTrials.gov NCT03012516. Registered on 30 December 2016—retrospectively registered.