bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrating Whole Blood Transcriptomic Collection Procedures Into the Current Anti-Doping Testing System, Including Long-Term Storage and Re-Testing of Anti-Doping Samples
Authors: Lima Giscard , Kolliari-Turner Alexander , Malinsky Fernanda Rossell , Guppy Fergus M. , Martin Renan Paulo , Wang Guan , Voss Sven Christian , Georgakopoulos Costas , Borrione Paolo , Pigozzi Fabio , Pitsiladis Yannis 
Published: October 2021

Introduction: Recombinant human erythropoietin (rHuEPO) administration studies involving transcriptomic approaches have demonstrated a gene expression signature that could aid blood doping detection. However, current anti-doping testing does not involve collecting whole blood into tubes with RNA preservative. This study investigated if whole blood in long-term storage and whole blood left over from standard hematological testing in short-term storage could be used for transcriptomic analysis despite lacking RNA preservation.Methods: Whole blood samples were collected from twelve and fourteen healthy nonathletic males, for long-term and short-term storage experiments. Long-term storage involved whole blood collected into Tempus™ tubes and K2EDTA tubes and subjected to long-term (i.e., ‒80°C) storage and RNA extracted. Short-term storage involved whole blood collected into K2EDTA tubes and stored at 4°C for 6‒48 h and then incubated at room temperature for 1 and 2 h prior to addition of RNA preservative. RNA quantity, purity, and integrity were analyzed in addition to RNA-Seq using the MGI DNBSEQ-G400 on RNA from both the short- and long-term storage studies. Genes presenting a fold change (FC) of &gt;1.1 or &lt; ‒1.1 with p ≤ 0.05 for each comparison were considered differentially expressed. Microarray analysis using the Affymetrix GeneChip® Human Transcriptome 2.0 Array was additionally conducted on RNA from the short-term study with a false discovery ratio (FDR) of ≤0.05 and an FC of &gt;1.1 or &lt; ‒1.1 applied to identify differentially expressed genes.Results: RNA quantity, purity, and integrity from whole blood subjected to short- and long-term storage were sufficient for gene expression analysis. Long-term storage: when comparing blood tubes with and without RNA preservation 4,058 transcripts (6% of coding and non-coding transcripts) were differentially expressed using microarray and 658 genes (3.4% of mapped genes) were differentially expressed using RNA-Seq. Short-term storage: mean RNA integrity and yield were not significantly different at any of the time points. RNA-Seq analysis revealed a very small number of differentially expressed genes (70 or 1.37% of mapped genes) when comparing samples stored between 6 and 48 h without RNA preservative. None of the genes previously identified in rHuEPO administration studies were differently expressed in either long- or short-term storage experiments.Conclusion: RNA quantity, purity, and integrity were not significantly compromised from short- or long-term storage in blood storage tubes lacking RNA stabilization, indicating that transcriptomic analysis could be conducted using anti-doping samples collected or biobanked without RNA preservation.
C-Reactive Protein Levels and Gadolinium-Enhancing Lesions Are Associated With the Degree of Depressive Symptoms in Newly Diagnosed Multiple Sclerosis
Authors: Yalachkov Yavor , Anschuetz Victoria , Jakob Jasmin , Schaller-Paule Martin A. , Schaefer Jan Hendrik , Reilaender Annemarie , Friedauer Lucie , Behrens Marion , Foerch Christian 
Published: October 2021

Background: Inflammation is essential for the pathogenesis of multiple sclerosis (MS). While the immune system contribution to the development of neurological symptoms has been intensively studied, inflammatory biomarkers for mental symptoms such as depression are poorly understood in the context of MS. Here, we test if depression correlates with peripheral and central inflammation markers in MS patients as soon as the diagnosis is established.Methods: Forty-four patients were newly diagnosed with relapsing-remitting MS, primary progressive MS or clinically isolated syndrome. Age, gender, EDSS, C-reactive protein (CRP), albumin, white blood cells count in cerebrospinal fluid (CSF WBC), presence of gadolinium enhanced lesions (GE) on T1-weighted images and total number of typical MS lesion locations were included in linear regression models to predict Beck Depression Inventory (BDI) score and the depression dimension of the Symptoms Checklist 90-Revised (SCL90RD).Results: CRP elevation and GE predicted significantly BDI (CRP: p = 0.007; GE: p = 0.019) and SCL90RD (CRP: p = 0.004; GE: p = 0.049). The combination of both factors resulted in more pronounced depressive symptoms (p = 0.04). CSF WBC and EDSS as well as the other variables were not correlated with depressive symptoms.Conclusions: CRP elevation and GE are associated with depressive symptoms in newly diagnosed MS patients. These markers can be used to identify MS patients exhibiting a high risk for the development of depressive symptoms in early phases of the disease.
Association of Decreased Serum BDNF With Restless Legs Syndrome in Parkinson's Disease Patients
Authors: Huang Yi-xian , Zhang Qi-lin , Huang Cai-li , Wu Wen-qi , Sun Jia-wei 
Published: October 2021

Objective: To objective of the study was to investigate whether serum brain-derived neurotrophic factor (BDNF) levels are associated with the severity of restless legs syndrome (RLS) in Parkinson's disease (PD).Methods: A total of 249 PD patients with (n = 53) and without RLS (n = 196) and 326 age-matched controls were included in this study. All the serum BDNF levels of the participants were measured. The International Restless Legs Syndrome Study Group Rating Scale (IRLSSG-RS) was administered for the severity of RLS. The severity of PD patients were assessed by the Unified PD Rating Scale (UPDRS) and the Hoehn and Yahr (H-Y) stage.Results: The prevalence of RLS was significantly higher in PD patients (21.3%) than in the controls group (7.4%) (p &lt; 0.05). The IRLSSG-RS score in PD patients with RLS (16.25 ± 5.24) was significantly increased than in controls with RLS (12.08 ± 3.99) (p &lt; 0.01). The serum BDNF levels were significantly decreased in PD patients with RLS than in PD patients without RLS, controls without RLS, and controls with RLS (p &lt; 0.001). BDNF levels were negatively associated with IRLSSG-RS in both PD patients with RLS and controls with RLS group (both p &lt; 0.01). Multiple regression analysis confirmed that in either PD with RLS or controls with RLS group, BDNF was an independent contributor to IRLSSG-RS (both p &lt; 0.01).Conclusions: Decreased serum BDNF levels may be involved in the pathophysiology of RLS in PD, suggesting that it may serve as a potential blood biomarker of diagnostic value for RLS in PD.
Suppression of EGFR/PKC-δ/NF-κB Signaling Associated With Imipramine-Inhibited Progression of Non-Small Cell Lung Cancer
Authors: Yueh Po-Fu , Lee Yuan-Hao , Chiang I-Tsang , Chen Wei-Ting , Lan Keng-Li , Chen Cheng-Hsien , Hsu Fei-Ting 
Published: October 2021

BackgroundAnti-depressants have been reported to own anti-tumor potential types of cancers; however, the role of imipramine in non-small cell lung cancer (NSCLC) has not been elucidated. Epidermal growth factor receptor (EGFR) was known to be one of the key regulators that control NSCLC progression. Whether EGFR would be the target of imipramine for suppressing tumor signaling transduction and results in anti-tumor potential is remaining unclear.MethodsWe used CL-1-5-F4 cells and animal models to identify the underlying mechanism and therapeutic efficacy of imipramine. Cytotoxicity, apoptosis, invasion/migration, DNA damage, nuclear translocation of NF-κB, activation of NF-κB, phosphorylation of EGFR/PKC-δ/NF-κB was assayed by MTT, flow cytometry, transwell, wound healing assay, comet assay, immunofluorescence staining, NF-κB reporter gene assay and Western blotting, respectively. Tumor growth was validated by CL-1-5-F4/NF-κB-luc2 bearing animal model.ResultsImipramine effectively induces apoptosis of NSCLC cells via both intrinsic and extrinsic apoptosis signaling. DNA damage was increased, while, invasion and migration potential of NSCLC cells was suppressed by imipramine. The phosphorylation of EGFR/PKC-δ/NF-κB and their downstream proteins were all decreased by imipramine. Similar tumor growth inhibition was found in imipramine with standard therapy erlotinib (EGFR inhibitor). Non-obvious body weight loss and liver pathology change were found in imipramine treatment mice.ConclusionImipramine-triggered anti-NSCLC effects in both in vitro and in vivo model are at least partially attributed to its suppression of EGFR/PKC-δ/NF-κB pathway.
The Clinical Spectrum of Inflammatory Bowel Disease Associated With Specific Genetic Syndromes: Two Novel Pediatric Cases and a Systematic Review
Authors: Gatti Simona , Gelzoni Giulia , Catassi Giulia N. , Catassi Carlo 
Published: October 2021

Background and Aims:Inflammatory bowel disease (IBD) is a typical polygenic disorder and less frequently shows a monogenic origin. Furthermore, IBD can originate in the context of specific genetic syndromes associated with a risk of autoimmune disorders. We aimed to systematically evaluate the prevalence of IBD in specific genetic syndromes and to review the clinical characteristics of the published cases.Methods:According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, studies describing patients with IBD and a genetic syndrome and/or studies indicating the prevalence or incidence of IBD in subjects with a genetic syndrome were included.Results:Forty-six studies describing a total of 67 cases of IBD in six genetic syndromes and two personally assessed unpublished cases were included in the review. The majority of cases were associated with Turner syndrome (TS) (38 cases), Down syndrome (DS) (18 cases) and neurofibromatosis type 1 (NF1) (8 cases). Sporadic cases were described in DiGeorge syndrome (2), Kabuki syndrome (2), and Williams syndrome (1). The prevalence of IBD ranged from 0.67 to 4% in TS and from 0.2 to 1.57% in DS. The incidence of IBD was increased in TS and DS compared to the general population. Eight cases of IBD in TS had a severe/lethal course, many of which described before the year 2000. Two IBD cases in DS were particularly severe.Conclusion:Evidence of a greater prevalence of IBD is accumulating in TS, DS, and NF1. Management of IBD in patients with these genetic conditions should consider the presence of comorbidities and possible drug toxicities.Systematic Review Registration: PROSPERO, identifier: CRD42021249820
Structure–Activity Relationship of Novel Second-Generation Synthetic Cathinones: Mechanism of Action, Locomotion, Reward, and Immediate-Early Genes
Authors: Nadal-Gratacós Nuria , Alberto-Silva Ana Sofia , Rodríguez-Soler Míriam , Urquizu Edurne , Espinosa-Velasco Maria , Jäntsch Kathrin , Holy Marion , Batllori Xavier , Berzosa Xavier , Pubill David , Camarasa Jordi , Sitte Harald H. , Escubedo Elena , López-Arnau Raúl 
Published: October 2021

Several new synthetic cathinones, which mimic the effect of classical psychostimulants such as cocaine or MDMA, have appeared in the global illicit drug market in the last decades. In fact, the illicit drug market is continually evolving by constantly adding small modifications to the common chemical structure of synthetic cathinones. Thus, the aim of this study was to investigate the in vitro and in vivo structure–activity relationship (SAR) of six novel synthetic cathinones currently popular as recreational drugs, pentedrone, pentylone, N-ethyl-pentedrone (NEPD), N-ethyl-pentylone (NEP), 4-methyl-pentedrone (4-MPD), and 4-methyl-ethylaminopentedrone (4-MeAP), which structurally differ in the absence or presence of different aromatic substituents and in their amino terminal group. Human embryonic kidney (HEK293) cells expressing the human isoforms of SERT and DAT were used for the uptake inhibition and release assays. Moreover, Swiss CD-1 mice were used to investigate the psychostimulant effect, rewarding properties (3, 10, and 30 mg/kg, i.p.), and the induction of immediate-early genes (IEGs), such as Arc and c-fos in the dorsal striatum (DS) and ventral striatum (VS) as well as bdnf in the medial prefrontal cortex (mPFC), of the test compounds. Our results demonstrated that all tested synthetic cathinones are potent dopamine (DA) uptake inhibitors, especially the N-ethyl analogs, while the ring-substituted cathinones tested showed higher potency as SERT inhibitors than their no ring-substituted analogs. Moreover, unlike NEP, the remaining test compounds showed clear “hybrid” properties, acting as DAT blockers but SERT substrates. Regarding the locomotion, NEP and NEPD were more efficacious (10 mg/kg) than their N-methyl analogs, which correlates with their higher potency inhibiting the DAT and an overexpression of Arc levels in the DS and VS. Furthermore, all compounds tested induced an increase in c-fos expression in the DS, except for 4-MPD, the least effective compound in inducing hyperlocomotion. Moreover, NEP induced an up-regulation of bdnf in the mPFC that correlates with its 5-HTergic properties. Finally, the present study demonstrated for the first time that NEP, 4-MPD, and 4-MeAP induce reward in mice. Altogether, this study provides valuable information about the mechanism of action and psychostimulant and rewarding properties as well as changes in the expression of IEGs related to addiction induced by novel second-generation synthetic cathinones.
Analysis of Real-World Implementation of the Biopsychosocial Approach to Healthcare: Evidence From a Combination of Qualitative and Quantitative Methods
Authors: Xiao Xiaohua , Song Haidong , Sang Tian , Wu Zhihua , Xie Ying , Yang Qian 
Published: October 2021

Aims: The modern medical model has been transformed into a biopsychosocial model. The integration of the biopsychosocial approach in healthcare can help improve the effectiveness of diagnosis and treatment. This study explored the actual application of the biopsychosocial approach in healthcare and provides a basis for targeted interventions to promote the biopsychosocial approach in healthcare.Methods: Study 1 involved one-on-one interviews with 30 medical staff and focus group interviews with 16 recent patients. Study 2 was a cross-sectional survey of 13,105 medical staff in Hangzhou, China that analyzed the status quo implementation of the biopsychosocial approach in healthcare.Results: Study 1 found that medical staff did not welcome patients to report information unrelated to their disease, hoping patients did not express their emotions. In the treatment process, patients believed that medical staff refused to attend to or did not encourage reporting of any information other than the disease, and that patients should have reasonable expectations for medical staff. Study 2 found that medical staff had a 37.5% probability of actively paying attention to the patient's psychosocial status. Female medical staff (38.5%) were actively concerned about the patient's psychosocial status significantly more than male medical staff (34.2%) (P &lt; 0.01). The medical staff in the psychiatric department (58.4%) paid more active attention to the patient's psychosocial status than staff in the non-psychiatric departments (37.2%). Gender, department, hospital level, and professional title were the factors associated with the medical staff's attention to the patient's psychosocial status (P &lt; 0.05). The influence of age on the probability of medical staff actively paying attention to the psychosocial status of patients increased with the number of years of employment. Participants that were 31–40 years old, had an intermediate professional title, and 11–15 years of employment were the least likely to actively pay attention to patients' psychosocial status.Conclusion: Although the biopsychosocial approach has been popularized for many years, it has not been widely used in medical care. Medical staff pay more attention to patients' physical symptoms and less attention to patients' psychosocial status. It is recommended that training will be provided to medical personnel on implementing a biopsychosocial approach with particular attention to the sociodemographic characteristics of medical personnel. Additionally, we propose helping patients set reasonable expectations, and formulating guidelines for implementing the biopsychosocial approach.
ICF-Based Assessment of Functioning in Daily Clinical Practice. A Promising Direction Toward Patient-Centred Care in Patients With Low Back Pain
Authors: Ibsen Charlotte , Maribo Thomas , Nielsen Claus Vinther , Hørder Mogens , Schiøttz-Christensen Berit 
Published: October 2021

Background: Patient-centred care has received increased attention in recent years. Patient-Reported Outcomes (PROs) and shared decision-making are key components of Patient-Centred care. Low back pain (LBP) is a complex symptom affected by multiple, interacting factors. Therefore, evidence strongly recommend a biopsychosocial and patient-centred approach in the assessment and management. The International Classification of Functioning, Disability and Health (ICF) provide a biopsychosocial model for describing functioning and disability. ICF is widely acknowledged, but implementation into clinical practice is lacking. To support the use of a biopsychosocial and patient-centred approach in daily clinical practice among patients with LBP we developed a practice-friendly tool based on ICF; the LBP assessment tool.Objective: To compare an ICF-based assessment facilitated by the LBP assessment tool with standard care in terms of the use of PROs and shared decision-making in order to promote patient-centred care in patients with LBP.Methods: A non-randomized controlled design was used. Eligible patients were allocated to one of two groups: the ICF group, assessed with the LBP assessment tool or the control group, assessed with a conventional LBP assessment. Primary outcome includes use of PROs. Secondary outcomes include use of a graphical overview displaying the patient profile and shared decision-making. A patient evaluation questionnaire was used to collect data.Results: Seven hundred ten patients were assessed for eligibility of whom 531 were allocated to the ICF group (n = 299) or the control group (n = 232). A significantly higher use of PRO data (p &lt; 0.00) and the patient profile (p &lt; 0.00) was reported in favor of the ICF group. Patients in the ICF group also experienced being more involved in decision-making (p = 0.01).Conclusions: This study showed that a functioning assessment, by means of the LBP assessment tool, increased use of PROs and shared decision-making when compared to a conventional LBP assessment. Additionally, this study demonstrated that routine use of ICF-based PRO data and shared decision-making promoted patient-centred care in patients with LBP. The LBP assessment tool may be a strong candidate for a user-friendly ICF-based tool with the potential to support health professionals in a shift toward a biopsychosocial and patient-centred approach to patients with LBP.
Predictive Value of the Serum Albumin Level on Admission in Patients With Spontaneous Subarachnoid Hemorrhage
Authors: Shang Feng , Zhao Hao , Cheng Weitao , Qi Meng , Wang Ning , Qu Xin 
Published: October 2021

Objective: To determine the effect of the serum albumin level on admission in patients with spontaneous subarachnoid hemorrhage (SAH).Methods: A total of 229 patients with SAH were divided into control and hypoalbuminemia groups. The serum albumin levels were measured. The data, including age, gender, co-existing medical conditions, risk factors, Hunt-Hess (H-H) grade on admission, Glasgow coma score (GCS) on admission, complications during hospitalizations, length of hospital stay, length of intensive care unit (ICU) stay, in-hospital mortality, survival rate, outcome at discharge, and the 6-month follow-up outcome, were compared between the two groups.Results: Older age, an increased number of patients who consumed an excess of alcohol, and a lower GCS on admission were findings in the hypoalbuminemia group compared to the control group (p &lt; 0.001). The ratio of patients with H-H grade I on admission in the hypoalbuminemia group was decreased compared to the control group (p &lt; 0.05). Patients with hypoalbuminemia were more likely to be intubated, and have pneumonia and cerebral vasospasm than patients with a normal albumin level on admission (p &lt; 0.001). Furthermore, the length of hospital and ICU stays were longer in the hypoalbuminemia group than the control group (p &lt; 0.001). Hypoalbuminemia on admission significantly increased poor outcomes at discharge (p &lt; 0.001). The number of patients with severe disability was increased and the recovery rate was decreased with respect to in-hospital outcomes in the hypoalbuminemia group than the control group (p &lt; 0.001).Conclusion: Hypoalbuminemia was shown to be associated with a poor prognosis in patients with SAH.
Efficacy of Nx4 to Reduce Plasma Cortisol and Gastrin Levels in Norwegian Sled Dogs During an Exercise Induced Stress Response: A Prospective, Randomized, Double Blinded, Placebo-Controlled Cohort Study
Authors: Keller Alexandra , Conradi Jana , Weber Corinna , Failing Klaus , Wergin Melanie 
Published: October 2021

Introduction:An exercise induced stress response is commonly seen in high performance sled dogs, resulting in increased plasma cortisol. A stress induced rise of cortisol might result in increased prevalence of gastritis and gastric ulcers mediated by an increase of gastrin. Neurexan®(Nx4) is a medicinal product used for stress relief by reduction of cortisol. The aim of the study was to show that Nx4 reduces plasma cortisol and plasma gastrin in high performance sled dogs and to show tolerability of Nx4 in dogs.Material and Methods:First, a pilot study was done to validate the increase of cortisol by performance. The data from the pilot study was used for sample size estimation via an adapted power analysis as well as the identification of important variables. These were then used in the randomization procedure of the main study. Second, a prospective randomized, double blinded, placebo-controlled cohort study was conducted. The main study included 45 sled dogs, assigning 23 dogs to the Nx4 group, and 22 dogs to the placebo group, to analyze plasma cortisol and plasma gastrin at four time points: before, directly after and 30 and 120 min after performance.Results:For the main target variable, area under the curve (AUC) of plasma cortisol, a significantly lower adjusted mean value in the Nx4 group compared to the placebo group (p= 0.031) was found. Plasma gastrin was also significantly reduced in the Nx4 group 30 min after performance (p= 0.023), resulting in a significantly reduced plasma gastrin AUC in the Nx4 group compared to the placebo group (p= 0.049).Discussion:Within the limitation of the study, the results carry implications for the usefulness of Nx4 to reduce exercise induced plasma cortisol and gastrin levels. The reduction of the exercise induced stress response could help to improve the welfare of high-performance sled dogs. Since activation of the hypothalamic-pituitary-adrenal axis resulting in increased cortisol is similar for exercise induced stress and psychologic stress, the same might be true independent of the stressor, making Nx4 potentially useful in any stressful situation for dogs.