bluuebunny/crossref_metadata_2025_split huggingface dataset:
LINE retrotransposons characterize mammalian tissue-specific and evolutionarily dynamic regulatory regions
Authors: Roller Maša , Stamper Ericca , Villar Diego , Izuogu Osagie , Martin Fergal , Redmond Aisling M. , Ramachanderan Raghavendra , Harewood Louise , Odom Duncan T. , Flicek Paul 
Published: February 2021

Abstract
Background
To investigate the mechanisms driving regulatory evolution across tissues, we experimentally mapped promoters, enhancers, and gene expression in the liver, brain, muscle, and testis from ten diverse mammals.

Results
The regulatory landscape around genes included both tissue-shared and tissue-specific regulatory regions, where tissue-specific promoters and enhancers evolved most rapidly. Genomic regions switching between promoters and enhancers were more common across species, and less common across tissues within a single species. Long Interspersed Nuclear Elements (LINEs) played recurrent evolutionary roles: LINE L1s were associated with tissue-specific regulatory regions, whereas more ancient LINE L2s were associated with tissue-shared regulatory regions and with those switching between promoter and enhancer signatures across species.

Conclusions
Our analyses of the tissue-specificity and evolutionary stability among promoters and enhancers reveal how specific LINE families have helped shape the dynamic mammalian regulome.
Sympathetic Nervous System and Exercise Affects Cognition in Youth (SNEACY): study protocol for a randomized crossover trial
Authors: Raine Lauren B. , McDonald Katherine , Shigeta Tatsuya T. , Hsieh Shu-Shih , Hunt Jennifer , Chiarlitti Nathan A. , Lim Michelle , Gebhardt Kristen , Collins Nina , De Lisio Michael , Mullen Sean P. , Kramer Arthur F. , Hillman Charles 
Published: February 2021

Abstract
Background
There is an increasing prevalence of physical inactivity during childhood, which is associated with a variety of health problems. However, the mechanisms by which acute exercise benefits cognition in childhood remains unknown. Here we describe the protocol for a randomized crossover trial called SNEACY (Sympathetic Nervous System & Exercise Affects Cognition in Youth), a study designed to better understand mechanisms linking acute exercise and cognition in 9–10-year-old healthy, cognitively normal children.

Methods
Children from the Greater Boston, MA region will be recruited to participate in this single center study. A randomized crossover design will be utilized, such that participants will act as their own controls, through initial randomization to condition assignment and condition counterbalancing across participants. One hundred three children will participate in three randomized acute interventions: moderate intensity treadmill exercise (20 min, 70–75% of their maximal heart rate), seated rest (20 min), and a Trier Social Stress Test for Children (14 min). These visits will occur on 3 three separate days, approximately 5–8 days apart. Before and after each intervention, children complete a variety of cognitive tasks measuring attentional inhibition while their neuroelectric activity is recorded. Variables of interest include EEG data, accuracy and reaction time, academic achievement, and salivary alpha amylase. Academic achievement is also assessed following interventions. In addition, children provide passive drool samples throughout the interventions to measure various biomarkers that may explain the acute exercise benefit on cognition.

Discussion
The results from this study could influence educational and public health recommendations to enhance cognition and learning in pre-adolescent children.

Trial registration
ClinicalTrials.gov NCT03592238. Registered on 19 July 2018
Utility of Abdominal Drain in Gastrectomy (ADiGe) Trial: study protocol for a multicenter non-inferiority randomized trial
Authors:   on behalf of the Italian Research Group for Gastric Cancer (GIRCG), Weindelmayer J. , Mengardo V. , Veltri A. , Baiocchi G. L. , Giacopuzzi S. , Verlato G. , de Manzoni G. 
Published: February 2021

Abstract
Background
Prophylactic use of abdominal drain in gastrectomy has been questioned in the last 15 years, and a 2015 Cochrane meta-analysis on four RCTs concluded that there was no convincing evidence to the routine drain placement in gastrectomy. Nevertheless, the authors evidenced the moderate/low quality of the included studies and highlighted how 3 out of 4 came from Eastern countries. After 2015, only retrospective studies have been published, all with inconsistent results.

Methods
ADiGe (Abdominal Drain in Gastrectomy) Trial is a multicenter prospective randomized non-inferiority trial with a parallel design. It aimed to verify whether avoiding routine use of abdominal drain is burdened with complications, particularly an increase in postoperative invasive procedures. Patients with gastric cancer, scheduled for subtotal or total gastrectomy with curative intent, are eligible for inclusion, irrespective of previous oncological treatment.
The primary composite endpoint is reoperation or percutaneous drainage procedures within 30 postoperative days. The primary analysis will verify whether the incidence of the primary composite endpoint is higher in the experimental arm, avoiding routine drain placement, than control arm, undergoing prophylactic drain placement, in order to falsify or support the null hypothesis of inferiority. Secondary endpoints assessed for superiority are overall morbidity and mortality, Comprehensive Complications Index, incidence and time for diagnosis of anastomotic and duodenal leaks, length of hospital stay, and readmission rate.
Assuming one-sided alpha of 5%, and cumulative incidence of the primary composite endpoint of 6.4% in the control arm and 4.2% in the experimental one, 364 patients allow to achieve 80% power to detect a non-inferiority margin difference between the arm proportions of 3.6%. Considering a 10% drop-out rate, 404 patients are needed. In order to have a balanced percentage between total and subtotal gastrectomy, recruitment will end at 202 patients for each type of gastrectomy. The surgeon and the patient are blinded until the end of the operation, while postoperative course is not blinded to the patient and caregivers.

Discussion
ADiGe Trial could contribute to critically re-evaluate the role of prophylactic drain in gastrectomy, a still widely used procedure.

Trial registration
Prospectively registered (last updated on 29 October 2020) at ClinicalTrials.gov with the identifier NCT04227951.
Sheep nemabiome diversity and its response to anthelmintic treatment in Swedish sheep herds
Authors: Halvarsson Peter , Höglund Johan 
Published: February 2021

Abstract
Background
A novel way to study the species composition and diversity of nematode parasites in livestock is to perform deep sequencing on composite samples containing a mixture of different species. Herein we describe for the first time the nematode community structures (nemabiomes) inhabiting Swedish sheep and how these are/were affected by host age and recent anthelmintic treatments.

Methods
A total of 158 fecal samples were collected (n = 35 in 2007 and n = 123 in 2013–2016) and cultured from groups of sheep on 61 commercial farms in the south-central part of the country where most animals are grazed. Among the samples, 2 × 44 (56%) were paired collections from the same groups pre- and post-treatment with anthelmintics such as macrocyclic lactones, benzimidazoles or levamisole. Samples were analyzed for their nemabiome using the PacBio platform followed by bioinformatic sequence analysis with SCATA. Species richness and diversity were calculated and analyzed in R.

Results
Nematode ITS2 sequences were found in all larval culture samples except two, even though the fecal egg counts were below the McMaster threshold in 20 samples. Sequencing yielded, on average, 1008 sequences per sample. In total, 16 operational taxonomical units (OTU), all with ≥ 98 % identity to sequences in the NCBI database, were recognized. The OTUs found represented nematode species of which ten are commonly associated with sheep. Multiple species were identified in all pre-anthelmintic treatment larval culture samples. No effects on nematode diversity were found in relation to host age. On the other hand, recent anthelmintic treatment lowered species richness, especially after use of ivermectin and albendazole. Interestingly, despite zero egg counts after use of levamisole, these samples still contained nematode DNA and especially H. contortus.

Conclusions
Our findings provide evidence that nemabiome analysis combined with diversity index analysis provides an objective methodology in the study of the efficacy of anthelmintic treatment as both high and low abundant species were detected.

Graphical Abstract
Curcumin and its analog alleviate diabetes-induced damages by regulating inflammation and oxidative stress in brain of diabetic rats
Authors: Miao Chengfeng , Chen Hanbin , Li Yulian , Guo Ying , Xu Feifei , Chen Qi , Zhang Yanyan , Hu Mengjun , Chen Guorong 
Published: February 2021

Abstract
Background
Diabetic encephalopathy is a severe diabetes complication with cognitive dysfunction and neuropsychiatric disability. The mechanisms underlying diabetic encephalopathy is believed to be relevant with oxidative stress, vascular amylin deposition, immune receptors, inflammation, etc. This study wanted to evaluate the ability of curcumin and its analog A13 to alleviate oxidative stress and inflammation in diabetes-induced damages in brain.

Methods
Sixty adult male Sprague–Dawley rats were divided into 5 groups: normal control (NC) group, diabetes mellitus (DM) group, curcumin-treated diabetes mellitus (CUR) group, high dose of A13-treated diabetes mellitus (HA) group, low dose of A13-treated diabetes mellitus (LA) group. Activation of the nuclear factor kappa-B (NF-κB p65) pathway was detected by RT-qPCR, immunohistochemical (IHC) staining and Western blot; oxidative stress was detected by biochemical detection kit; brain tissue sections were stained with hematoxylin–eosin (HE) staining and Myelin staining.

Results
RT-qPCR, IHC staining and Western blot showed that curcumin and A13 treatment could inhibit the NF-κB p65 pathway. Curcumin and A13 increased the activity of superoxide dismutase and decreased the malondialdehyde level in the brain of diabetic rats. Furthermore, HE staining and Myelin staining demonstrated that the histological lesions of the brain in diabetic rats could be significantly ameliorated by curcumin and A13.

Conclusion
Curcumin analog A13 could alleviate the damages in the brain of diabetes rats by regulating the pathways of inflammation and oxidative stress. A13 may be a new potential therapeutic agent for diabetic encephalopathy.
The application of next-generation sequence-based DNA barcoding for bloodmeal detection in host-seeking wild-caught Ixodes scapularis nymphs
Authors: Lumsden G. A. , Zakharov E. V. , Dolynskyj S. , Weese J. S. , Lindsay L. R. , Jardine C. M. 
Published: February 2021

AbstractObjectiveOur objective was to apply next-generation sequence-based DNA barcoding to identify the remnant larval bloodmeals in wild-caught host-seeking (unengorged)Ixodes scapularisnymphs (n = 216). To infer host species identification, vertebrate DNA was amplified using universal primers for cytochromecoxidase subunit I (COI) and sequenced using next-generation sequencing (NGS) for comparison against known barcode references.ResultsBloodmeal identification was unsuccessful in most samples (99% of 216 specimens) demonstrating a very low detection rate of this assay. Sequences that surpassed quality thresholds were obtained for 41.7% of nymphs (n = 90) and of those, confident species identification was obtained for 15.6% of nymphs (n = 14). Wild host identifications were only obtained from 2 specimens, where DNA from the eastern grey squirrel (Sciurus carolinensis) was identified. Human and bovine DNA was identified in remaining nymphs and considered to be contaminants. Further optimization of the technique is required to improve detection of remnant bloodmeals in host-seeking nymphs.
Data-driven FDG-PET subtypes of Alzheimer’s disease-related neurodegeneration
Authors: Levin Fedor , Ferreira Daniel , Lange Catharina , Dyrba Martin , Westman Eric , Buchert Ralph , Teipel Stefan J. , Grothe Michel J. ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: February 2021

AbstractBackgroundPrevious research has described distinct subtypes of Alzheimer’s disease (AD) based on the differences in regional patterns of brain atrophy on MRI. We conducted a data-driven exploration of distinct AD neurodegeneration subtypes using FDG-PET as a sensitive molecular imaging marker of neurodegenerative processes.MethodsHierarchical clustering of voxel-wise FDG-PET data from 177 amyloid-positive patients with AD dementia enrolled in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) was used to identify distinct hypometabolic subtypes of AD, which were then further characterized with respect to clinical and biomarker characteristics. We then classified FDG-PET scans of 217 amyloid-positive patients with mild cognitive impairment (“prodromal AD”) according to the identified subtypes and studied their domain-specific cognitive trajectories and progression to dementia over a follow-up interval of up to 72 months.ResultsThree main hypometabolic subtypes were identified: (i) “typical” (48.6%), showing a classic posterior temporo-parietal hypometabolic pattern; (ii) “limbic-predominant” (44.6%), characterized by old age and a memory-predominant cognitive profile; and (iii) a relatively rare “cortical-predominant” subtype (6.8%) characterized by younger age and more severe executive dysfunction. Subtypes classified in the prodromal AD sample demonstrated similar subtype characteristics as in the AD dementia sample and further showed differential courses of cognitive decline.ConclusionsThese findings complement recent research efforts on MRI-based identification of distinct AD atrophy subtypes and may provide a potentially more sensitive molecular imaging tool for early detection and characterization of AD-related neurodegeneration variants at prodromal disease stages.
Introduction of an assessment toolkit associated with increased rate of DLB diagnosis
Authors: Surendranathan A. , Kane J. , Bentley A. , Barker S. , McNally R. , Bamford C. , Taylor J.-P. , Thomas A. , McKeith I. , Burn D. , O’Brien J. T. 
Published: February 2021

Abstract
Background
Dementia with Lewy bodies (DLB) and dementia in Parkinson’s disease (PDD) are recognised to be under-recognised in clinical practice in the UK, with only one third to a half of expected cases diagnosed. We aimed to assess whether clinical diagnostic rates could be increased by the introduction of a structured assessment toolkit for clinicians.

Methods
We established baseline diagnostic rates for DLB and PDD in four memory clinics and three movement disorder/Parkinson’s disease (PD) clinics in two separate geographical regions in the UK. An assessment toolkit specifically developed to assist with the recognition and diagnosis of DLB and PDD was then introduced to the same clinical teams and diagnostic rates for DLB and PDD were reassessed.
For assessing DLB diagnosis, a total of 3820 case notes were reviewed before the introduction of the toolkit, and 2061 case notes reviewed after its introduction. For PDD diagnosis, a total of 1797 case notes were reviewed before the introduction of the toolkit and 3405 case notes after it. Mean values and proportions were analysed using Student’s t test for independent samples and χ2 test, respectively.

Results
DLB was diagnosed in 4.6% of dementia cases prior to the introduction of the toolkit, and 6.2% of dementia cases afterwards, an absolute rise of 1.6%, equal to a 35% increase in the number of DLB cases diagnosed when using the toolkit (χ2 = 4.2, P = 0.041).
The number of PD patients diagnosed with PDD was not found overall to be significantly different when using the toolkit: 9.6% of PD cases before and 8.2% of cases after its introduction (χ2 = 1.8, P = 0.18), though the ages of PD patients assessed after the toolkit’s introduction were lower (73.9 years vs 80.0 years, t = 19.2, p < 0.001).

Conclusion
Introduction of the assessment toolkit was associated with a significant increase in the rate of DLB diagnosis, suggesting that a structured means of assessing symptoms and clinical features associated with DLB can assist clinicians in recognising cases. The assessment toolkit did not alter the overall rate of PDD diagnosis, suggesting that alternate means may be required to improve the rate of diagnosis of dementia in Parkinson’s disease.
Urethral cancer managed with phallus preserving surgery: a case report
Authors: Walsh Emily , Kelly Niall , Daly Padraig , Shah Nigam , Cullen Ivor 
Published: February 2021

AbstractBackgroundPrimary urethral carcinoma (PUC) is rare and accounts for < 1% of all genito-urinary cancers. There is a male predominance of 3:1 and a peak incidence in the 7th and 8th decades. The aetiology of this cancer is similar to penile cancer, and the human papilloma virus (HPV) is thought to be an essential factor in tumorigenesis. Urethral cancer should be diagnosed and staged with a combination of tumour biopsy, MRI, and CT with treatment involving a multimodal approach. Contemporary management emphasises phallus-preserving surgery where feasible.Case presentationHere, we describe a case of distal urethral carcinoma, which presented as a metastatic groin mass and identifying the primary lesion proved challenging. Diagnostic flexible cystoscopy identified a tiny lesion in the navicular fossa, which was biopsied and confirmed to be a squamous cell carcinoma. The patient then underwent phallus preserving surgery, including distal urethrectomy with bilateral inguinal lymph node dissections. The final stage was pT1N1M0, and adjuvant chemotherapy was started. The distal urethrectomy involved the surgical creation of a hypospadic meatus in the midshaft of the penis. Normal voiding and sexual function were preserved.ConclusionsUrethral cancer is a rare malignancy and clinicians should bear in mind that early diagnosis of this disease can be very difficult depending on the anatomical location of the tumour. Treatment currently favours penis-preserving surgery.
Low-frequency electromagnetic fields combined with tissue engineering techniques accelerate intervertebral fusion
Authors: Li Weigang , Huang Chunwei , Ma Tian , Wang Jiachen , Liu Wenbin , Yan Jiyuan , Sheng Gaohong , Zhang Ruizhuo , Wu Hua , Liu Chaoxu 
Published: February 2021

Abstract
Background
Intervertebral fusion is the most common surgery to treat lumbar degenerative disease (LDD). And the graft material used in the operation is derived from the iliac crest to promote fusion. However, autografts possess the fatal disadvantage of lack of source. Therefore, economical and practical bone substitutes are urgently needed to be developed. Sinusoidal electromagnetic fields (EMF) combined with tissue engineering techniques may be an appropriate way to promote intervertebral fusion.

Methods
In this research, porous scaffolds made of polycaprolactone (PCL) and nano-hydroxyapatite (nHA) were used as cell carriers. Then, the scaffolds loaded with bone marrow mesenchymal stem cells (BMSCs) were treated with sinusoidal electromagnetic field and the osteogenic capability of BMSCs was tested later. In addition, an intervertebral disc of the tail vertebra of the rat was removed to construct a spinal intervertebral fusion model with a cell-scaffold implanted. The intervertebral fusion was observed and analyzed by X-ray, micro-CT, and histological methods.

Results
BMSCs stimulated by EMF possess splendid osteogenic capability under an osteogenic medium (OM) in vitro. And the conditioned medium of BMSCs treated with EMF can further promote osteogenic differentiation of the primitive BMSCs. Mechanistically, EMF regulates BMSCs via BMP/Smad and mitogen-activated protein kinase (MAPK)-associated p38 signaling pathways. In vivo experiments revealed that the scaffold loaded with BMSCs stimulated by EMF accelerated intervertebral fusion successfully.

Conclusion
In summary, EMF accelerated intervertebral fusion by improving the osteogenic capacity of BMSCs seeded on scaffolds and might boost the paracrine function of BMSCs to promote osteogenic differentiation of the homing BMSCs at the injured site. EMF combined with tissue engineering techniques may become a new clinical treatment for LDD.
Rhomboid protein 2 of Eimeria maxima provided partial protection against infection by homologous species
Authors: Chen Yufeng , Tian Di , Xu Lixin , Yan Ruofeng , Li Xiangrui , Shah Muhammad Ali A. , Song Xiaokai 
Published: February 2021

AbstractRhomboid-like proteases (ROMs) are considered as new candidate antigens for developing new-generation vaccines due to their important role involved in the invasion of apicomplexan protozoa. In prior works, we obtained a ROM2 sequence ofEimeria maxima(EmROM2). This study was conducted to evaluate the immunogenicity and protective efficacy of EmROM2 recombinant protein (rEmROM2) and EmROM2 DNA (pVAX1-EmROM2) against infection byEimeria maxima(E. maxima). Firstly, Western blot assay was conducted to analyze the immunogenicity of rEmROM2. The result showed that rEmROM2 was recognized by chicken anti-E. maximaserum. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blot assay revealed apparent transcription and expression of EmROM2 at the injection site. qRT-PCR (quantitative real-time PCR), flow cytometry and indirect ELISA indicated that vaccination with rEmROM2 or EmROM2 DNA significantly upregulated the transcription level of cytokines (IFN-γ, IL-2, IL-4, IL-10, IL-17, TGF-β and TNF SF15), the proportion of CD8+and CD4+T lymphocytes and serum IgG antibody response. Ultimately, a vaccination-challenge trial was performed to evaluate the protective efficacy of rEmROM2 and pVAX1-EmROM2 againstE. maxima. The result revealed that vaccination with rEmROM2 or pVAX1-EmROM2 significantly alleviated enteric lesions, weight loss, and reduced oocyst output caused by challenge infection ofE. maxima, and provided anticoccidial index (ACI) of more than 160, indicating partial protection againstE. maxima. In summary, vaccination with rEmROM2 or pVAX1-EmROM2 activated notable humoral and cell-mediated immunity and provided partial protection againstE. maxima. These results demonstrated that EmROM2 protein and DNA are promising vaccine candidates againstE. maximainfection.