bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interest on the internet for systemic lupus erythematosus: Analysis of Google Trends in Latin American countries
Authors: Tejada-Llacsa Paul J , Villacorta-Landeo Pamela , Aguilar-Buitrón Eder , Alarcón Graciela S , Ugarte-Gil Manuel F 
Published: April 2021

Background/Objective Information available on the internet about Systemic Lupus Erythematosus (SLE) can influence the doctor-patient relationship. Therefore, the aim of this study was to identify the terms used for SLE on the internet. Methods We analyzed the data downloaded from Google Trends, considering the term “Lupus” in a six-year web-based research. The frequency of the terms for each Pan-American country was obtained automatically from Google Trends, which reports relative search volumes or RSV (on a scale from 0 to 100) across regions. Results We obtained a total of 67 registered terms in 18 countries. The terms were distributed into five categories. The categories with interest in all countries were “definition” and “symptoms”. Conclusions Google Trends allows us to find useful information about SLE on the internet; once the accuracy of this information is validated, it can be used by patients, health institutions, rheumatologists and other health professionals.
Mental health literacy websites for children of parents with a mental illness
Authors: Cavanaugh Daniel L , Riebschleger Joanne , Tanis Jennifer M 
Published: April 2021

Objective: This review of online mental health resources was conducted to evaluate and document the availability of mental health resources pertinent to the needs of children of parents with a mental illness (COPMI). This review identified available websites and analyzed the appropriateness of content and readability. Methods: We conducted an extensive 6-month review of websites with available mental health literacy content that may be found by COPMI searching for information. Web content was evaluated and described with qualitative thematic analysis techniques. Web content was also evaluated for reading levels using the Flesch-Kincaid readability analysis tool. Results: The researchers described 7 descriptive themes, 10 content areas, and described what information was available across websites and where gaps existed. They also concluded the average reading level of the websites was 9.7, which was substantially higher than current web development recommendations. Conclusions: Websites can be a valuable tool for COPMI without access to direct services. To improve current web resources, developers should strive to offer content specific to the identified needs of COPMI. Additionally, web content should be developed at a level that is accessible to teens and parents.
Comparison of mothership versus drip-and-ship models in treating patients with acute ischemic stroke: A systematic review and meta-analysis
Authors: Mohamed Ahmed , Fatima Nida , Shuaib Ashfaq , Saqqur Maher 
Published: April 2021

Introduction There is controversy if direct to comprehensive center “mothership” or stopping at primary center for thrombolysis before transfer to comprehensive center “drip-and-ship” are best models of treatment of acute stroke. In this study, we compare mothership and drip-and-ship models to evaluate the best option of functional outcome. Methods Studies between 1990 and 2020 were extracted from online electronic databases. Clinical outcomes, critical time measurements, functional independence, and mortality were then compared. Results A total of 7824 patients’ data were retrieved from 13 publications (3 randomized control trials and 10 retrospective ones). In addition, 4639 (59.3%) patients were treated under mothership model, and 3185 (40.7%) followed the drip-and-ship model with mean age of 70.01 ± 3.58 versus 69.03 ± 3.36; p < 0.001, respectively. The National Institute Health Stroke Scale was 15.57 ± 3.83 for the mothership and 15.72 ± 2.99 for the drip-and-ship model (p ≤ 0.001). The mean symptoms onset-to-puncture time was significantly shorter in the mothership group compared to the drip-and-ship (159.69 min vs. 223.89 min; p ≤ 0.001, respectively). Moreover, the collected data indicated no significant difference between symptom’s onset to intravenous thrombolysis time and stroke onset-to-successful recanalization time (p = 0.205 and p ≤ 0.001, respectively). Patients had significantly worse functional outcome (modified Rankin score) (3–6) at 90 days in the drip-and-ship model (odds ratio (OR): 1.47, 95% confidence interval (CI): 1.13–1.92, p < 0.004) and 1.49-folds higher likelihood of symptomatic intracerebral hemorrhage (OR: 1.49, 95% CI: 1.22–1.81, p < 0.0001) compared to mothership. However, there were no statistically significant difference in terms of mortality (OR: 1.16, 95% CI: 0.87–1.55, p = 0.32) and successful recanalization (OR: 1.12, 95% CI: 0.76–1.65, p = 0.56) between the two models of care. Conclusion Patients in the mothership model have significantly improved functional independence and recovery. Further studies are needed as the data from prospectively randomized studies are not of sufficient quality to make definite recommendations.
Implications of extreme serum neurofilament light chain levels for the management of patients with relapsing multiple sclerosis
Authors: Engel Sinah , Protopapa Maria , Steffen Falk , Papanastasiou Vakis , Nicolaou Christoforos , Protopapas Michalis , Zipp Frauke , Bittner Stefan , Luessi Felix 
Published: April 2021

Background: Serum neurofilament light chain (sNfL) is a promising biomarker to complement the decision-making process in multiple sclerosis (MS) patients. However, although sNfL levels are able to detect disease activity and to predict future disability, the growing evidence has not yet been translated into practicable recommendations for an implementation into clinical routine. Methods: The observation of a patient with extensive inflammatory activity in magnetic resonance imaging (MRI) along with an extremely high sNfL level in the absence of any clinical symptoms prompted us to investigate common characteristics of our MS patients with the highest sNfL levels in a retrospective cohort study. The 97.5th percentile was chosen as a cut-off value because the mean sNfL level of the resulting extreme neurofilament light chain (NfL) cohort corresponded well to the sNfL level of the presented case. Patient characterization included clinical and MRI assessment with a focus on disease activity markers. sNfL levels were determined by single molecule array. Results: The 97.5th percentile of our MS cohort (958 sNfL measurements in 455 patients) corresponded to a threshold value of 46.1 pg/ml. The mean sNfL level of the extreme sNfL cohort ( n = 24) was 95.6 pg/ml (standard deviation 68.4). Interestingly, only 15 patients suffered from a relapse at the time point of sample collection, whereas nine patients showed no signs of clinical disease activity. sNfL levels of patients with and without relapse did not differ [median 81.3 pg/ml (interquartile range [IQR] 48.0–128) versus 80.2 pg/ml (IQR 46.4–97.6), p = 0.815]. The proportion of patients with contrast-enhancing lesions was high and also did not differ between patients with and without relapse (92.9% versus 87.5%, p = 0.538); 78.9% of the patients not receiving a high-efficacious therapy had ongoing disease activity during a 2-year follow-up. Conclusion: Extremely high sNfL levels are indicative of subclinical disease activity and might complement treatment decisions in ambiguous cases.
Platelet-Rich Plasma Releasate Promotes Early Healing in Tendon After Acute Injury
Authors: Yu Tung-Yang , Pang Jong-Hwei S. , Lin Li-Ping , Cheng Ju-Wen , Liu Shih-Jung , Tsai Wen-Chung 
Published: April 2021

Background: Acute tendon injury can limit motion and thereby inhibit tendon healing. Positive results have been found after the use of platelet-rich plasma (PRP) to treat tendon injury; however, the early effects of PRP on tendon regeneration are not known. Purpose/Hypothesis: The purpose of this study was to evaluate the effects of PRP releasate (PRPr) on the early stages of tendon healing in a rat partial tenotomy model. It was hypothesized that PRPr can promote early healing of an Achilles tendon in rats. Study Design: Controlled laboratory study. Methods: PRP was prepared by a 2-step method of manual platelet concentration from 10 rats. PRPr was isolated from the clotted preparation after activation by thrombin and was applied to an Achilles tendon on 1 side of 30 rats on the second day after partial tenotomy, with normal saline used as the control on the other side. Achilles tendon samples were harvested 5 and 10 days after tenotomy. At each time point, 15 Achilles tendon samples were obtained, of which 5 samples were evaluated by Masson trichrome staining, apoptosis, and cell proliferation, while the other 10 samples were tested for tensile strength using a material testing machine. Results: Compared with saline-treated control tendons, the PRPr-treated tendons showed increased collagen synthesis near the cut edge and fewer apoptotic cells ( P = .01). An immunohistochemical analysis revealed more Ki-67–positive cells but fewer cluster of differentiation (CD) 68+ (ED1+) macrophages in PRPr tendons compared with saline-treated tendons ( P < .01). Tendons treated with PRPr also showed higher ultimate tensile strength than those treated with saline ( P = .03). Conclusion: PRPr treatment promotes tissue recovery in the early phase of tendon healing by stimulating tendon cell proliferation and collagen production while inhibiting cell apoptosis and CD68+ (ED1+) macrophage infiltration. Clinical Relevance: These findings suggest that with PRPr treatment, higher loads can be applied to the healing tendon at an earlier time, which can help the patient resume activity earlier.
Low-dose decitabine modulates T-cell homeostasis and restores immune tolerance in immune thrombocytopenia
Authors: Han Panpan , Hou Yu , Zhao Yajing , Liu Yang , Yu Tianshu , Sun Yunqi , Wang Haoyi , Xu Pengcheng , Li Guosheng , Sun Tao , Hu Xiang , Liu Xinguang , Li Lizhen , Peng Jun , Zhou Hai , Hou Ming 
Published: April 2021

Abstract
Our previous clinical study showed that low-dose decitabine exhibited sustained responses in nearly half of patients with refractory immune thrombocytopenia (ITP). The long-term efficacy of decitabine in ITP is not likely due to its simple role in increasing platelet production. Whether decitabine has the potential to restore immune tolerance in ITP is unknown. In this study, we analyzed the effect of decitabine on T-cell subpopulations in ITP in vitro and in vivo. We found that low-dose decitabine promoted the generation and differentiation of regulatory T (Treg) cells and augmented their immunosuppressive function. Splenocytes from CD61 knockout mice immunized with CD61+ platelets were transferred into severe combined immunodeficient mouse recipients to induce a murine model of ITP. Low-dose decitabine alleviated thrombocytopenia and restored the balance between Treg and helper T (Th) cells in active ITP mice. Treg deletion and depletion offset the effect of decitabine in restoring CD4+ T-cell subpopulations in ITP mice. For patients who received low-dose decitabine, the quantity and function of Treg cells were substantially improved, whereas Th1 and Th17 cells were suppressed compared with the pretreatment levels. Next-generation RNA-sequencing and cytokine analysis showed that low-dose decitabine rebalanced T-cell homeostasis, decreased proinflammatory cytokines, and downregulated phosphorylated STAT3 in patients with ITP. STAT3 inhibition analysis suggested that low-dose decitabine might restore Treg cells by inhibiting STAT3 activation. In conclusion, our data indicate that the immunomodulatory effect of decitabine provides one possible mechanistic explanation for the sustained response achieved by low-dose decitabine in ITP.
A comprehensive transcriptome signature of murine hematopoietic stem cell aging
Authors: Flohr Svendsen Arthur , Yang Daozheng , Kim KyungMok , Lazare Seka , Skinder Natalia , Zwart Erik , Mura-Meszaros Anna , Ausema Albertina , von Eyss Björn , de Haan Gerald , Bystrykh Leonid 
Published: April 2021

Abstract
We surveyed 16 published and unpublished data sets to determine whether a consistent pattern of transcriptional deregulation in aging murine hematopoietic stem cells (HSC) exists. Despite substantial heterogeneity between individual studies, we uncovered a core and robust HSC aging signature. We detected increased transcriptional activation in aged HSCs, further confirmed by chromatin accessibility analysis. Unexpectedly, using 2 independent computational approaches, we established that deregulated aging genes consist largely of membrane-associated transcripts, including many cell surface molecules previously not associated with HSC biology. We show that Selp (P-selectin), the most consistent deregulated gene, is not merely a marker for aged HSCs but is associated with HSC functional decline. Additionally, single-cell transcriptomics analysis revealed increased heterogeneity of the aged HSC pool. We identify the presence of transcriptionally “young-like” HSCs in aged bone marrow. We share our results as an online resource and demonstrate its utility by confirming that exposure to sympathomimetics or deletion of Dnmt3a/b molecularly resembles HSC rejuvenation or aging, respectively.
What’s new in the pathogenesis and treatment of therapy-related myeloid neoplasms
Authors: Voso Maria Teresa , Falconi Giulia , Fabiani Emiliano 
Published: April 2021

Abstract
Therapy-related myeloid neoplasms (t-MNs) include diseases onsetting in patients treated with chemo- and/or radiotherapy for a primary cancer, or an autoimmune disorder. Genomic variants, in particular, in familial cancer genes, may play a predisposing role. Recent advances in deep sequencing techniques have shed light on the pathogenesis of t-MNs, identifying clonal hematopoiesis of indeterminate potential (CHIP) as a frequent first step in the multihit model of t-MNs. CHIP is often detectable prior to any cytotoxic treatment, probably setting the fertile genomic background for secondary leukemogenesis. The evolution pattern toward t-MNs is then a complex process, shaped by the type of cancer therapy, the aging process, and the individual exposures, that favor additional hits, such as the acquisition of TP53 mutations and unfavorable karyotype abnormalities. The pathogenesis of t-MNs differs from MN associated with environmental exposure. Indeed, the genetic aberration patterns of MN developing in atomic bomb survivors show few mutations in classical DNA methylation genes, and a high prevalence of 11q and ATM alterations, together with TP53 mutations. Survival in t-MNs is poor. In addition to the biology of t-MNs, the patient’s previous disease history and the remission status at t-MN diagnosis are significant factors contributing to unfavorable outcome. New drugs active in secondary leukemias include CPX-351, or venetoclax in combination with hypomethylating agents, monoclonal antibodies as magrolimab, or targeted drugs against pathogenic mutations. Allogeneic stem cell transplantation remains the best currently available therapeutic option with curative intent for fit patients with unfavorable genetic profiles.
RETRACTED ARTICLE: Restored microRNA-326-5p Inhibits Neuronal Apoptosis and Attenuates Mitochondrial Damage via Suppressing STAT3 in Cerebral Ischemia/Reperfusion Injury
Authors: Huang Yumin , Wang Yingge , Duan Zuowei , Liang Jingyan , Xu Yijun , Zhang Shuai , Tang Tieyu 
Published: April 2021

AbstractStudies have greatly explored the role of microRNAs (miRNAs) in cerebral ischemia/reperfusion injury (CI/RI). But the specific mechanism of miR-326-5p in CI/RI is still elusive. Hence, this study was to unmask the mechanism of miR-326-5p/signal transducer and activator of transcription-3 (STAT3) axis in CI/RI. Two models (oxygen and glucose deprivation [OGD] in primary rat cortical neurons and middle cerebral artery occlusion [MCAO] in Sprague–Dawley rats) were established to mimic CI/RI in vitro and in vivo, respectively. Loss- and gain-of function assays were performed with OGD-treated neurons and with MCAO rats. Afterward, viability, apoptosis, oxidative stress and mitochondrial membrane potential in OGD-treated neurons were tested, as well as pathological changes, apoptosis and mitochondrial membrane potential in brain tissues of MCAO rats. Mitofusin-2 (Mfn2), miR-326-5p and STAT3 expression in OGD-treated neurons and in brain tissues of MCAO rats were detected. Mfn2 and miR-326-5p were reduced, and STAT3 was elevated in OGD-treated neurons and brain tissues of MCAO rats. miR-326-5p targeted and negatively regulated STAT3 expression. Restoring miR-326-5p or reducing STAT3 reinforced viability, inhibited apoptosis and oxidative stress, increased mitochondrial membrane potential and increased Mfn2 expression in OGD-treated neurons. Up-regulating miR-326-5p or down-regulating STAT3 relieved pathological changes, inhibited apoptosis and elevated mitochondrial membrane potential and Mfn2 expression in brain tissues of rats with MCAO. This study elucidates that up-regulated miR-326-5p or down-regulated STAT3 protects against CI/RI by elevating Mfn2 expression.
Open-loop analysis on sympathetically mediated arterial pressure and urine output responses in spontaneously hypertensive rats: effect of renal denervation
Authors: Kawada Toru , Nishikawa Takuya , Suehara Satoru , Sawada Satoshi , Tanaka Tetsuo , Uenohara Minako , Yamamoto Hiromi , Sugimachi Masaru 
Published: April 2021

AbstractPrimary acute sympathetic activation (PASA) causes a subsequent arterial pressure (AP) elevation. In this case, an antidiuretic effect via the renal innervation and pressure diuresis can act antagonistically on the kidneys. We examined the effect of PASA on urine output in spontaneously hypertensive rats (SHR) 4–7 days after unilateral renal denervation (RDN) (n = 9). The slope of the plot of urine flow versus AP was positive (0.120 ± 0.031 μL min−1 kg−1 mmHg−1) on the intact side, but it was less than 1/3 of the slope observed previously in normotensive Wistar–Kyoto rats (WKY). RDN did not normalize the slope of urine flow versus AP (0.179 ± 0.025 μL min−1 kg−1 mmHg−1, P = 0.098 versus the intact side). The urine flow at the operating point of the AP tended to be greater on the denervated than the intact side (29.0 ± 1.8 vs. 25.3 ± 1.9 μL min−1 kg−1, P = 0.055). The percent increase (17.2 ± 7.2%) was not different from that observed previously in WKY. Although high-resting sympathetic nerve activity is prerequisite for maintaining hypertension in SHR, the effect of sympathetic innervation on the urine output function was not greater than that in WKY.
FINDER: an automated software package to annotate eukaryotic genes from RNA-Seq data and associated protein sequences
Authors: Banerjee Sagnik , Bhandary Priyanka , Woodhouse Margaret , Sen Taner Z. , Wise Roger P. , Andorf Carson M. 
Published: April 2021

Abstract
Background
Gene annotation in eukaryotes is a non-trivial task that requires meticulous analysis of accumulated transcript data. Challenges include transcriptionally active regions of the genome that contain overlapping genes, genes that produce numerous transcripts, transposable elements and numerous diverse sequence repeats. Currently available gene annotation software applications depend on pre-constructed full-length gene sequence assemblies which are not guaranteed to be error-free. The origins of these sequences are often uncertain, making it difficult to identify and rectify errors in them. This hinders the creation of an accurate and holistic representation of the transcriptomic landscape across multiple tissue types and experimental conditions. Therefore, to gauge the extent of diversity in gene structures, a comprehensive analysis of genome-wide expression data is imperative.

Results
We present FINDER, a fully automated computational tool that optimizes the entire process of annotating genes and transcript structures. Unlike current state-of-the-art pipelines, FINDER automates the RNA-Seq pre-processing step by working directly with raw sequence reads and optimizes gene prediction from BRAKER2 by supplementing these reads with associated proteins. The FINDER pipeline (1) reports transcripts and recognizes genes that are expressed under specific conditions, (2) generates all possible alternatively spliced transcripts from expressed RNA-Seq data, (3) analyzes read coverage patterns to modify existing transcript models and create new ones, and (4) scores genes as high- or low-confidence based on the available evidence across multiple datasets. We demonstrate the ability of FINDER to automatically annotate a diverse pool of genomes from eight species.

Conclusions
FINDER takes a completely automated approach to annotate genes directly from raw expression data. It is capable of processing eukaryotic genomes of all sizes and requires no manual supervision—ideal for bench researchers with limited experience in handling computational tools.
AutoDTI++: deep unsupervised learning for DTI prediction by autoencoders
Authors: Sajadi Seyedeh Zahra , Zare Chahooki Mohammad Ali , Gharaghani Sajjad , Abbasi Karim 
Published: April 2021

AbstractBackgroundDrug–target interaction (DTI) plays a vital role in drug discovery. Identifying drug–target interactions related to wet-lab experiments are costly, laborious, and time-consuming. Therefore, computational methods to predict drug–target interactions are an essential task in the drug discovery process. Meanwhile, computational methods can reduce search space by proposing potential drugs already validated on wet-lab experiments. Recently, deep learning-based methods in drug-target interaction prediction have gotten more attention. Traditionally, DTI prediction methods' performance heavily depends on additional information, such as protein sequence and molecular structure of the drug, as well as deep supervised learning.ResultsThis paper proposes a method based on deep unsupervised learning for drug-target interaction prediction called AutoDTI++. The proposed method includes three steps. The first step is to pre-process the interaction matrix. Since the interaction matrix is sparse, we solved the sparsity of the interaction matrix with drug fingerprints. Then, in the second step, the AutoDTI approach is introduced. In the third step, we post-preprocess the output of the AutoDTI model.ConclusionsExperimental results have shown that we were able to improve the prediction performance. To this end, the proposed method has been compared to other algorithms using the same reference datasets. The proposed method indicates that the experimental results of running five repetitions of tenfold cross-validation on golden standard datasets (Nuclear Receptors, GPCRs, Ion channels, and Enzymes) achieve good performance with high accuracy.