bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential transcriptomics in sarcoidosis lung and lymph node granulomas with comparisons to pathogen-specific granulomas
Authors: Casanova Nancy G. , Gonzalez-Garay Manuel L. , Sun Belinda , Bime Christian , Sun Xiaoguang , Knox Kenneth S. , Crouser Elliott D. , Sammani Nora , Gonzales Taylor , Natt Bhupinder , Chaudhary Sachin , Lussier Yves , Garcia Joe G. N. 
Published: December 2020

Abstract
Rationale
Despite the availability of multi-“omics” strategies, insights into the etiology and pathogenesis of sarcoidosis have been elusive. This is partly due to the lack of reliable preclinical models and a paucity of validated biomarkers. As granulomas are a key feature of sarcoidosis, we speculate that direct genomic interrogation of sarcoid tissues, may lead to identification of dysregulated gene pathways or biomarker signatures.

Objective
To facilitate the development sarcoidosis genomic biomarkers by gene expression profiling of sarcoidosis granulomas in lung and lymph node tissues (most commonly affected organs) and comparison to infectious granulomas (coccidiodomycosis and tuberculosis).

Methods
Transcriptomic profiles of immune-related gene from micro-dissected sarcoidosis granulomas within lung and mediastinal lymph node tissues and compared to infectious granulomas from paraffin-embedded blocks. Differentially-expressed genes (DEGs) were profiled, compared among the three granulomatous diseases and analyzed for functional enrichment pathways.

Results
Despite histologic similarities, DEGs and pathway enrichment markedly differed in sarcoidosis granulomas from lymph nodes and lung. Lymph nodes showed a clear immunological response, whereas a structural regenerative response was observed in lung. Sarcoidosis granuloma gene expression data corroborated previously reported genomic biomarkers (STAB1, HBEGF, and NOTCH4), excluded others and identified new genomic markers present in lung and lymph nodes, ADAMTS1, NPR1 and CXCL2. Comparisons between sarcoidosis and pathogen granulomas identified pathway divergences and commonalities at gene expression level.

Conclusion
These findings suggest the importance of tissue and disease-specificity evaluation when exploring sarcoidosis genomic markers. This relevant translational information in sarcoidosis and other two histopathological similar infections provides meaningful specific genomic-derived biomarkers for sarcoidosis diagnosis and prognosis.
Proline-rich protein 11 overexpression is associated with a more aggressive phenotype and poor overall survival in ovarian cancer patients
Authors: Zhan Yu , Wu Xueyuan , Zheng Gang , Jin Jingjing , Li Chaofu , Yu Guanzhen , Li Wenfeng 
Published: December 2020

AbstractBackgroundThe proline-rich protein 11 (PRR11) is a newly identified oncogene associated with a poor prognosis in several human cancers. Nonetheless, research on its role in ovarian cancer (OC) remains largely understudied. Therefore, this study aims to evaluate the expression levels of PRR11 protein and its role in human ovarian cancer.MethodsImmunohistochemistry analysis was used to evaluate the expression levels of PRR11 protein in human samples obtained from 49 patients diagnosed with OC and subjected to curative surgery in the First Affiliated Hospital of Wenzhou Medical University between 2007 and 2015.ResultsIn total, 57.1% of the primary OC tumor tissue evaluated demonstrated overexpression of PRR11. Meanwhile, the survival analysis showed that the overall survival (OS) of patients presenting overexpression of PRR11 was significantly lower than the OS of the patients with negative PRR11. In subsequent experiments, it was found that silencing the expression of PRR11 expression inhibited the proliferation of tumor cells and the migration of cells in vitro. Further, cells subjected to PRR11 knockdown exhibited a decrease in tumor growth in vivo. The downregulation of PRR11 was coupled with a decrease in N-cadherin and downregulation in the expression of early growth response protein 1 (EGR1).ConclusionsThe findings suggest that PRR11 might be considered as a potential target for prognostic assessment and gene therapy strategies for patients diagnosed with OC.
Chiropractic conservatism among chiropractic students in Denmark: prevalence and consequences
Authors: Nim Casper Glissmann , Lauridsen Henrik Hein , O’Neill Søren , Goncalves Guillaume , Jensen Rikke K. , Leboeuf-Yde Charlotte 
Published: December 2020

Abstract
Background
The chiropractic profession is split between those practicing evidence-based and those whose practice is honed by vitalism. The latter has been coined ‘chiropractic conservatism’. In Denmark, the chiropractic education program is university-based in close collaboration with a medical faculty. We wanted to investigate if such conservative attitudes were present in this environment.
Our objectives were to i) determine the level of chiropractic conservatism, ii) investigate if this was linked to academic year of study, iii) determine the level of clinical appropriateness, and iv) to investigate if this was affected by the level of conservatism among students in a chiropractic program, where the students are taught alongside medical students at the University of Southern Denmark (SDU).

Methods
A cross-sectional survey of 146 (response-rate 76%) 3rd to 5th year pre-graduate students and 1st year postgraduate clinical interns from the chiropractic degree course at the University of Southern Denmark was conducted during autumn of 2019. The students’ levels of conservatism were dichotomized into appropriate/inappropriate, summed up, and used in a linear regression model to determine the association with academic year of study. Thereafter, the conservatism score was categorized into four groups (from low -1- to high -4-). Conservatism groups were cross-tabulated with the ability to answer appropriately on nine cases concerning i) contra-indications, ii) non-indications, and iii) indications for spinal manipulation and analyzed using logistic regression.

Results
Generally, the Danish chiropractic students had low conservatism scores, decreasing with increasing academic year of study. Seventy percent of the students were placed in the two lowest conservative groups. The level of conservatism (categories 1–3) was moderately (but not statistically significantly) associated with an inability to recognize non-indications to treatment. Three outliers (category 4), however, revealed a highly inappropriate handling of the clinical cases.

Conclusions
Chiropractic students enrolled at a university-based course closely integrated with a medical teaching environment are not immune to chiropractic conservatism. However, the course appears to attenuate it and limit its effect on clinical decision-making compared to other educational institutions.
A systematic review of the “promising zone” design
Authors: Edwards Julia M. , Walters Stephen J. , Kunz Cornelia , Julious Steven A. 
Published: December 2020

Abstract
Introduction
Sample size calculations require assumptions regarding treatment response and variability. Incorrect assumptions can result in under- or overpowered trials, posing ethical concerns. Sample size re-estimation (SSR) methods investigate the validity of these assumptions and increase the sample size if necessary. The “promising zone” (Mehta and Pocock, Stat Med 30:3267–3284, 2011) concept is appealing to researchers for its design simplicity. However, it is still relatively new in the application and has been a source of controversy.

Objectives
This research aims to synthesise current approaches and practical implementation of the promising zone design.

Methods
This systematic review comprehensively identifies the reporting of methodological research and of clinical trials using promising zone. Databases were searched according to a pre-specified search strategy, and pearl growing techniques implemented.

Results
The combined search methods resulted in 270 unique records identified; 171 were included in the review, of which 30 were trials. The median time to the interim analysis was 60% of the original target sample size (IQR 41–73%). Of the 15 completed trials, 7 increased their sample size. Only 21 studies reported the maximum sample size that would be considered, for which the median increase was 50% (IQR 35–100%).

Conclusions
Promising zone is being implemented in a range of trials worldwide, albeit in low numbers. Identifying trials using promising zone was difficult due to the lack of reporting of SSR methodology. Even when SSR methodology was reported, some had key interim analysis details missing, and only eight papers provided promising zone ranges.
Derivation and internal validation of a multi-biomarker-based cardiovascular disease risk prediction score for rheumatoid arthritis patients
Authors: Curtis Jeffrey R. , Xie Fenglong , Crowson Cynthia S. , Sasso Eric H. , Hitraya Elena , Chin Cheryl L. , Bamford Richard D. , Ben-Shachar Rotem , Gutin Alexander , Flake Darl D. , Mabey Brent , Lanchbury Jerry S. 
Published: December 2020

AbstractBackgroundRheumatoid arthritis (RA) patients have increased risk for cardiovascular disease (CVD). Accurate CVD risk prediction could improve care for RA patients. Our goal is to develop and validate a biomarker-based model for predicting CVD risk in RA patients.MethodsMedicare claims data were linked to multi-biomarker disease activity (MBDA) test results to create an RA patient cohort with age ≥ 40 years that was split 2:1 for training and internal validation. Clinical and RA-related variables, MBDA score, and its 12 biomarkers were evaluated as predictors of a composite CVD outcome: myocardial infarction (MI), stroke, or fatal CVD within 3 years. Model building used Cox proportional hazard regression with backward elimination. The final MBDA-based CVD risk score was internally validated and compared to four clinical CVD risk prediction models.Results30,751 RA patients (904 CVD events) were analyzed. Covariates in the final MBDA-based CVD risk score were age, diabetes, hypertension, tobacco use, history of CVD (excluding MI/stroke), MBDA score, leptin, MMP-3 and TNF-R1. In internal validation, the MBDA-based CVD risk score was a strong predictor of 3-year risk for a CVD event, with hazard ratio (95% CI) of 2.89 (2.46–3.41). The predicted 3-year CVD risk was low for 9.4% of patients, borderline for 10.2%, intermediate for 52.2%, and high for 28.2%.Model fit was good, with mean predicted versus observed 3-year CVD risks of 4.5% versus 4.4%. The MBDA-based CVD risk score significantly improved risk discrimination by the likelihood ratio test, compared to four clinical models. The risk score also improved prediction, reclassifying 42% of patients versus the simplest clinical model (age + sex), with a net reclassification index (NRI) (95% CI) of 0.19 (0.10–0.27); and 28% of patients versus the most comprehensive clinical model (age + sex + diabetes + hypertension + tobacco use + history of CVD + CRP), with an NRI of 0.07 (0.001–0.13). C-index was 0.715 versus 0.661 to 0.696 for the four clinical models.ConclusionA prognostic score has been developed to predict 3-year CVD risk for RA patients by using clinical data, three serum biomarkers and the MBDA score. In internal validation, it had good accuracy and outperformed clinical models with and without CRP. The MBDA-based CVD risk prediction score may improve RA patient care by offering a risk stratification tool that incorporates the effect of RA inflammation.
Treatment of pseudobulbar affect (PBA) in a patient with a history of traumatic brain injury, partial brain resection, and brainstem stroke: a case report
Authors: Young Fletcher Graham , Nguyen Diep 
Published: December 2020

Abstract
Background
Pseudobulbar affect is a very distressing and underdiagnosed neuropsychiatric disorder that causes contextually inappropriate episodes of laughing and crying and general emotional incontinence. Although many proposed etiologies exist, the most widely accepted theory espouses the disruption of a corticopontine–cerebellar circuit that governs the modulation of emotional response. Pseudobulbar affect is commonly diagnosed secondary to primary neurological disorders such as amyotrophic lateral sclerosis, multiple sclerosis, and traumatic brain injury. Traditional pharmacological treatment of pseudobulbar affect is largely comprised of antidepressant therapy, including tricyclic antidepressants such as amitriptyline and selective serotonin reuptake inhibitors such as fluvoxamine. However, neither of these medication classes has been studied for the treatment of pseudobulbar affect in controlled trials, and their utility remains questionable.

Case presentation
We describe a case of a 62-year-old Caucasian man with history of traumatic brain injury, ischemic brainstem stroke, and depression who developed intractable pseudobulbar affect. This patient’s intensely distressing symptoms were not alleviated by amitriptyline. However, after being placed on fixed-dose 20 mg/10 mg dextromethorphan/quinidine (Nuedexta), our patient experienced complete resolution of his symptoms. He has experienced no deleterious side effects.

Conclusions
This case provides anecdotal evidence for the efficacy of dextromethorphan/quinidine in the treatment of pseudobulbar affect with remarkably swift and complete cessation of symptoms. As a secondary point, it is worth noting that our patient had experienced two devastating neurological traumas, both in anatomical areas that have been implicated in the corticopontine–cerebellar circuit thought to be responsible for pseudobulbar affect. However, only the second trauma, an acute left pontine infarction, produced symptoms of emotional disinhibition. The authors hope that reporting this case will provide both context for physicians managing this condition and hope for patients with this socially and psychiatrically damaging disease.
The ‘migratory connectivity’ concept, and its applicability to insect migrants
Authors: Gao Boya , Hedlund Johanna , Reynolds Don R. , Zhai Baoping , Hu Gao , Chapman Jason W. 
Published: December 2020

AbstractMigratory connectivity describes the degree of linkage between different parts of an animal’s migratory range due to the movement trajectories of individuals. High connectivity occurs when individuals from one particular part of the migratory range move almost exclusively to another localized part of the migratory range with little mixing with individuals from other regions. Conversely, low migratory connectivity describes the situation where individuals spread over a wide area during migration and experience a large degree of mixing with individuals from elsewhere. The migratory connectivity concept is frequently applied to vertebrate migrants (especially birds), and it is highly relevant to conservation and management of populations. However, it is rarely employed in the insect migration literature, largely because much less is known about the migration circuits of most migratory insects than is known about birds. In this review, we discuss the applicability of the migratory connectivity concept to long-range insect migrations. In contrast to birds, insect migration circuits typically comprise multigenerational movements of geographically unstructured (non-discrete) populations between broad latitudinal zones. Also, compared to the faster-flying birds, the lower degree of control over movement directions would also tend to reduce connectivity in many insect migrants. Nonetheless, after taking account of these differences, we argue that the migratory connectivity framework can still be applied to insects, and we go on to consider postulated levels of connectivity in some of the most intensively studied insect migrants. We conclude that a greater understanding of insect migratory connectivity would be of value for conserving threatened species and managing pests.
An unusual homing behavior found in the Sichuan Partridge during the early brooding period
Authors: Fu Yiqiang , Wang Shufang , Chen Benping , Dowell Simon , Zhang Zhengwang 
Published: December 2020

AbstractIn this study, we report an unusual homing behavior of the Sichuan Partridge (Arborophila rufipectus) at the Laojunshan National Nature Reserve, Sichuan Province, China. Hen Sichuan Partridges led the chicks back to the nests where they hatched in the evening and roosted there over night. This behavior lasted 6.7 ± 4.3 nights (range = 1–15; n = 13) after the chicks hatched. At this stage, the hens became very vigilant to predators and human disturbance. If disturbed, they often abandoned the nests immediately and no longer returned thereafter. The ambient temperature at night during the early brooding period of Sichuan Partridge at our study site was ~ 12.4 °C. Our findings suggest that hen Sichuan Partridges may make trade-offs between nest predation risks versus the thermoregulatory needs of their young.
Nanoparticle technology and its implications in endodontics: a review
Authors: Raura Natasha , Garg Anirudh , Arora Arpit , Roma M. 
Published: December 2020

Abstract

Background
The era of Nanomaterials has had a long lasting impression in the field of medical science. It’s excellent use in medicine has led to its application in dental science. Serious concerns regarding the eradication of microbial biofilms from the root canal system still exists in the field of endodontics. Nanoparticles have proven to be much more efficient with good bonding capabilities and surface chemistry as compared to the conventional materials. The practical applications of nanotechnology in endodontics has led to future prospects in research in this field.

Main body
Nanoparticles in endodontics have shown promising results. The various nanoaprticles like graphene, silver nanoparticles, chitosan, hydroxyapaptite nanoparticles, Iron compound, zirconia, Poly (lactic) co-glycolic acid, bioactive glass, mesoporous calcium silicate, titanium dioxide nanoparticles, Magnesium, Calcium oxide and Copper oxide have been discussed. These nanoparticles have fetched and shown great results in various application in endodontics like incorporation of nanoparticles in selaers, obturating materials, irrigation, and intracanal medicament.

Conclusion
The application of nanoparticles from natural and synthetic materials is rapidly evolving in dentistry. These biomaterials have helped in treatment of oral diseases, in eradication of smear layer and biofilms, have been incorporated in various dental materials for their antimicrobial effects. Combining all their beneficial aspects, these nanoparticles will provide new paradigm shift in dentistry. This review on nanoparticles will provide the reader with the latest knowledge of these materials, their mechanism of action and its implications in endodontics.
Development of a simple method for the analysis of phenylalanine in dried blood spot using tandem mass spectrometry
Authors: Gouda Amr S. , Nazim Walaa S. 
Published: December 2020

AbstractBackgroundPhenylketonuria (PKU), inborn error of metabolism, results from phenylalanine hydroxylase deficiency. PKU leads to neurological manifestations, intellectual disability, and mental disorders. Treatment depends on phenylalanine-restricted diet.Diagnosis and follow-up of PKU depends on blood phenylalanine level. The development of bacterial inhibition assay was the first routine screening test for PKU. ELISA and amino acids analyzers methods were then developed.Tandem mass spectrometry was introduced for newborn screening from dried blood spot in the late 1990s. Since then, several methods were developed, starting from using HPLC column followed by direct injection in mass spectrometer by analyte derivatization and use of external and internal standards. Kits are available for neonatal screening without derivatization using internal standards for quantitation.Due to high PKU incidence in Egypt, it is important to continuously ameliorate the methods for neonatal diagnosis and follow-up.ResultsExternal standards as dried blood spots were prepared according to the previously described procedures. These standards were evaluated for phenylalanine concentration using ELISA kit. Analysis of samples was done with a single-step elution from dried blood spot followed by 1-min mass spectrometry analysis. Validation was done according to US FDA and other related guidelines. Fifty samples were analyzed by ELISA and another 126 samples were analyzed by mass spectrometer kit. All these samples were analyzed by the developed method and no statistically significant difference was observed.ConclusionNew simple method is developed for phenylalanine quantitation in dried blood spot using tandem mass spectrometry. This method is cost and time effective.
Impact of hemodialysis on the wellbeing of chronic kidney diseases patients: a pre-post analysis
Authors: Um-e-Kalsoom  , Khan Sabiha , Ahmad Israr 
Published: December 2020

Abstract
Background
Hemodialysis may have serious psychological impact upon patients suffering from chronic kidney diseases. The aim of the present study is to investigate the impact of hemodialysis on the wellbeing of individuals with chronic kidney diseases (CKD).

Result
A sample consists of (N = 100) CKD patients referred from neurology ward of Leady Reading Hospital Peshawar. Data was collected from both male (50%) and female (50%) in 2017. Participants were divided into two groups on the basis of pre-set criteria. In group I, individuals with 4–5 stage of CKD referred first time for dialysis treatment were recruited. Group II comprised of CKD patients with 1–3 stage. Demographic data sheet, Pakistan Anxiety and Depression, WHO Quality of Life scale, and Perceived Social support scale (PSS) were used to test the hypotheses. Paired sample t test was use to see the difference between pre- and post-analysis of depression, anxiety, QOL, and PSS in group I (experimental group). Results suggests significant difference on depression (p > .001), anxiety (p > .001), and QOL (p > .001), while no significant difference was reported on perceived social support (p <.673). Findings also indicate no significant difference between group I and group II on QOL depression, anxiety, and PSS.

Conclusion
The findings concluded that patients under hemodialysis treatment suffered from depression, anxiety, and poor quality of life.