bluuebunny/crossref_metadata_2025_split huggingface dataset:
The lnc-CTSLP8 upregulates CTSL1 as a competitive endogenous RNA and promotes ovarian cancer metastasis
Authors: Wang Xinjing , Li Xiaoduan , Lin Feikai , Sun Huizhen , Lin Yingying , Wang Ziliang , Wang Xipeng 
Published: May 2021

Abstract
Background
Ovarian cancer is highly lethal and has a poor prognosis due to metastasis. Long non-coding RNAs (lncRNAs) are key regulators of tumor development, but their role in ovarian cancer metastasis remains unclear.

Methods
The expression of lnc-CTSLP8 in ovarian cancer was analyzed in public databases (TCGA and GEO) and validated via qRT-PCR. Lnc-CTSLP8 overexpression and knockout cell lines were constructed using a lentiviral vector and the CRISP/Cas9 system. Cell proliferation, colony formation, migration, and invasion were analyzed. An ovarian orthotopic tumor mouse model was used for the in vivo study. Changes in autophagosomes, autolysosomes, and mitochondria in ovarian cancer cells were observed via transmission electron microscopy. EMT markers were detected by immunoblotting and immunofluorescence assays. RNA immunoprecipitation, RNA pull-down, and dual luciferase reporter assays were performed to confirm the interaction between lnc-CTSLP8 and miR-199a-5p.

Results
A novel pseudogene, lnc-CTSLP8, was identified in ovarian cancer, with significantly elevated expression in metastatic tumor tissues compared to primary ovarian tumors. When overexpressed, lnc-CTSLP8 promoted ovarian cancer in vitro and in vivo by acting as a sponge for miR-199a-5p. Autophagy and EMT in ovarian cancer were also enhanced by lnc-CTSLP8. Mechanistically, lnc-CTSLP8 upregulated CTSL1 as a competitive endogenous RNA and exhibited oncogenic effects. Moreover, CTSL1 inhibitor treatment and miR-199a-5p overexpression abrogated the effects of lnc-CTSLP8 overexpression.

Conclusions
lnc-CTSLP8 acts as a ceRNA in ovarian cancer and represents a potential therapeutic target for metastatic ovarian cancer.
Machine learning approach to support taxonomic species discrimination based on helminth collections data
Authors: Borba Victor Hugo , Martin Coralie , Machado-Silva José Roberto , Xavier Samanta C. C. , de Mello Flávio L. , Iñiguez Alena Mayo 
Published: May 2021

Abstract
Background
There are more than 300 species of capillariids that parasitize various vertebrate groups worldwide. Species identification is hindered because of the few taxonomically informative structures available, making the task laborious and genus definition controversial. Thus, its taxonomy is one of the most complex among Nematoda. Eggs are the parasitic structures most viewed in coprological analysis in both modern and ancient samples; consequently, their presence is indicative of positive diagnosis for infection. The structure of the egg could play a role in genera or species discrimination. Institutional biological collections are taxonomic repositories of specimens described and strictly identified by systematics specialists.

Methods
The present work aims to characterize eggs of capillariid species deposited in institutional helminth collections and to process the morphological, morphometric and ecological data using machine learning (ML) as a new approach for taxonomic identification. Specimens of 28 species and 8 genera deposited at Coleção Helmintológica do Instituto Oswaldo Cruz (CHIOC, IOC/FIOCRUZ/Brazil) and Collection de Nématodes Zooparasites du Muséum National d’Histoire Naturelle de Paris (MNHN/France) were examined under light microscopy. In the morphological and morphometric analyses (MM), the total length and width of eggs as well as plugs and shell thickness were considered. In addition, eggshell ornamentations and ecological parameters of the geographical location (GL) and host (H) were included.

Results
The performance of the logistic model tree (LMT) algorithm showed the highest values in all metrics compared with the other algorithms. Algorithm J48 produced the most reliable decision tree for species identification alongside REPTree. The Majority Voting algorithm showed high metric values, but the combined classifiers did not attenuate the errors revealed in each algorithm alone. The statistical evaluation of the dataset indicated a significant difference between trees, with GL + H + MM and MM only with the best scores.

Conclusions
The present research proposed a novel procedure for taxonomic species identification, integrating data from centenary biological collections and the logic of artificial intelligence techniques. This study will support future research on taxonomic identification and diagnosis of both modern and archaeological capillariids.

Graphical abstract
Proteome study of cutaneous lupus erythematosus (CLE) and dermatomyositis skin lesions reveals IL-16 is differentially upregulated in CLE
Authors: Niewold Timothy B. , Meves Alexander , Lehman Julia S. , Popovic-Silwerfeldt Karin , Häyry Aliisa , Söderlund-Matell Therese , Charlesworth Cristine M. , Madden Benjamin , Lundberg Ingrid E. , Wahren-Herlenius Marie , Svenungsson Elisabet , Oke Vilija 
Published: April 2021

Abstract
Background
The objective of the study was to explore the disease pathways activated in the inflammatory foci of skin lesions in cutaneous lupus erythematosus (CLE) and dermatomyositis (DM).

Methods
Skin biopsies acquired from active CLE and DM lesions, patient (PC), and also healthy controls (HC) were investigated. Biopsy sections were examined by a pathologist, inflammatory foci were laser micro-dissected and captured, and proteins within captured tissue were detected in an unbiased manner by mass spectrometry. Protein pathway analysis was performed by the string-db.org platform. Findings of interest were confirmed by immunohistochemistry (IHC).

Results
Proteome investigation identified abundant expression of interferon-regulated proteins (IRP) as a common feature of CLE and DM. Interleukin (IL)-16 was the only abundant cytokine differentially expressed in CLE compared to DM. Caspase-3, an enzyme that cleaves IL-16 into its active form, was detected in low levels. Significantly higher proportion of IL-16- and caspase-3-positive cells was identified in CLE lesions in comparison with DM, PC, and HC. Proteomic results indicate more abundant complement deposition in CLE skin lesions.

Conclusions
Using unbiased mass spectrometry investigation of CLE and DM inflammatory infiltrates, we confirmed that high IRP expression is a common feature of both CLE and DM, while IL-16 is the only differentially expressed cytokine in CLE. IHC confirmed high expression of IL-16 and caspase-3 in CLE. Our novel molecular findings indicate that IL-16 detection could be useful in differential diagnostics between the two conditions that can display similar histopathological appearance. IL-16 could be of interest as a future therapeutic target for CLE.
Increased serum asprosin is correlated with diabetic nephropathy
Authors: Wang Rui , Lin Peng , Sun Huibo , Hu Wenchao 
Published: May 2021

Abstract
Objective
The adipokine asprosin, which was recently discovered, facilitates hepatic glucose production. The aim of this study is to see whether serum asprosin concentrations are linked to diabetic nephropathy (DN).

Methods
We performed this investigation in a group of 212 type 2 diabetes (T2DM) patients. These patients were classified into three subgroups: DN0 group (normal to mildly increased), DN1 group (moderately increased), and DN2 group (severely increased) on the basis of urine albumin-to-creatinine ratio (ACR).

Results
When compared to the controls, T2DM patients had higher serum asprosin levels. The DN2 group had significantly higher serum asprosin than the DN0 and DN1 groups. Furthermore, the DN1 group had higher serum asprosin than the DN0 group. Serum asprosin was linked to a higher risk of T2DM and DN in a logistic regression analysis. Serum asprosin was found to be positively related with disease duration, systolic blood pressure, blood urea nitrogen, creatinine, uric acid, ACR, calcium channel blockers, and angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker therapy, but negatively related with glomerular filtration rate, metformin, and acarbose therapy.

Conclusion
Serum asprosin increase with the progression of DN. Serum asprosin is correlated with renal function and ACR.
Epigenetic landscape of testis specific histone H2B variant and its influence on sperm function
Authors: Patankar Aniket , Gajbhiye Rahul , Surve Suchitra , Parte Priyanka 
Published: May 2021

Abstract
Background
Biological relevance of the major testis specific histone H2B variant (TH2B) in sperm is not fully understood. Studies in TH2A/TH2B double knockout male mice indicate its role in chromatin compaction and male fertility. Additionally, the presence of TH2B and TH2A reportedly generates more dynamic nucleosomes, leading to an open chromatin structure characteristic of transcriptionally active genome. Given that mature human sperm are transcriptionally and translationally inactive, the presence of TH2B in mature sperm is intriguing. To address its role in sperm, we investigated the genome-wide localization of TH2B in sperm of fertile men.

Results
We have identified the genomic loci associated with TH2B in fertile human sperm by ChIP-seq analysis. Bioinformatic analysis revealed ~ 5% sperm genome and 5527 genes to be associated with TH2B. Out of these 105 (1.9%) and 144 (2.6%) genes showed direct involvement in sperm function and early embryogenesis, respectively. Chromosome wide analysis for TH2B distribution indicated its least distribution on X and Y chromosomes and varied distribution on autosomes. TH2B showed relatively higher percentage of gene association on chromosome 4, 18, 3 and 2. TH2B enrichment was more in promoter and gene body region. Gene Ontology (GO) analysis revealed signal transduction and associated kinase activity as the most enriched biological and molecular function, respectively. We also observed the enrichment of TH2B at developmentally important loci, such as HOXA and HOXD and on genes required for normal sperm function, few of which were validated by ChIP-qPCR. The relative expression of these genes was altered in particular subgroup of infertile men showing abnormal chromatin packaging. Chromatin compaction positively correlated with sperm- motility, concentration, viability and with transcript levels of PRKAG2 and CATSPER B.

Conclusion
ChIP-seq analysis of TH2B revealed a putative role of TH2B in sperm function and embryo development. Altered expression of TH2B associated genes in infertile individuals with sperm chromatin compaction defects indicates involvement of TH2B in transcriptional regulation of these genes in post meiotic male germ cells. This altered transcriptome may be a consequence or cause of abnormal nuclear remodeling during spermiogenesis.
Artificial intelligence-based computational framework for drug-target prioritization and inference of novel repositionable drugs for Alzheimer’s disease
Authors: Tsuji Shingo , Hase Takeshi , Yachie-Kinoshita Ayako , Nishino Taiko , Ghosh Samik , Kikuchi Masataka , Shimokawa Kazuro , Aburatani Hiroyuki , Kitano Hiroaki , Tanaka Hiroshi 
Published: May 2021

Abstract
Background
Identifying novel therapeutic targets is crucial for the successful development of drugs. However, the cost to experimentally identify therapeutic targets is huge and only approximately 400 genes are targets for FDA-approved drugs. As a result, it is inevitable to develop powerful computational tools that can identify potential novel therapeutic targets. Fortunately, the human protein-protein interaction network (PIN) could be a useful resource to achieve this objective.

Methods
In this study, we developed a deep learning-based computational framework that extracts low-dimensional representations of high-dimensional PIN data. Our computational framework uses latent features and state-of-the-art machine learning techniques to infer potential drug target genes.

Results
We applied our computational framework to prioritize novel putative target genes for Alzheimer’s disease and successfully identified key genes that may serve as novel therapeutic targets (e.g., DLG4, EGFR, RAC1, SYK, PTK2B, SOCS1). Furthermore, based on these putative targets, we could infer repositionable candidate-compounds for the disease (e.g., tamoxifen, bosutinib, and dasatinib).

Conclusions
Our deep learning-based computational framework could be a powerful tool to efficiently prioritize new therapeutic targets and enhance the drug repositioning strategy.
Interaction between early-life pet exposure and methylation pattern of ADAM33 on allergic rhinitis among children aged 3–6 years in China
Authors: Zhang Yu , Tan Meiyu , Qian Xiaoqiong , Li Cong , Yue Lei , Liu Yuehong , Shi Song 
Published: May 2021

Abstract
Background
Recent research has pointed out the important roles of epigenetic modifications in the development and persistence of allergic rhinitis (AR), especially in relation to DNA methylation of disease-associated genes. We investigated whether AR susceptibility genes were epigenetically regulated, and whether methylation modulation of these genes in response to early-life environment could be a molecular mechanism underlying the risk for AR onset in a cohort of children aged 3–6 years in China.

Methods
Peripheral blood mononuclear cell (PBMC) samples were collected from 130 children patients, aged 3–6 years and diagnosed with AR; and 154 matched controls to detect promoter methylation in 25 AR susceptibility genes with the MethylTarget approach. Methylation levels were compared for each CpG site, each amplified region, and each gene. In addition, the relationship among DNA methylation, early-life environmental risk factors and AR onset were assessed.

Results
Maternal allergic history (P = 0.0390) and pet exposure (P = 0.0339) were significantly associated with increased AR risk. Differential methylation analyses were successfully performed for 507 CpG sites, 34 amplified regions and 17 genes and significant hypomethylation was observed in the promoter region of ADAM33 in AR patients [multiple test-corrected (FDR) P-value < 0.05]. Spearman correlation analysis revealed that the hypomethylation of ADAM33 was significantly associated with higher eosinophil counts (Spearman’s ρ: − 0.187, P-value = 0.037). According to the results of the multiple regression analysis, after adjusting for cofounders, the interaction of early-life pet exposure with methylation level of ADAM33 increased the risk for AR onset 1.423 times more in children (95% CI = 0.0290–4.109, P-value = 0.005).

Conclusion
This study provides evidence that early-life pet exposure and low methylation level of ADAM33 increase AR risk in children, and the interaction between pet exposure and methylation level of ADAM33 may play an important role in the development of AR.
CT facilitates improved diagnosis of adult intestinal malrotation: a 7-year retrospective study based on 332 cases
Authors: Xiong Ziman , Shen Yaqi , Morelli John N. , Li Zhen , Hu Xuemei , Hu Daoyu 
Published: April 2021

Abstract
Objective
To classify adult intestinal malrotation by CT.

Methods
This retrospective study enrolled adults diagnosed with intestinal malrotation who underwent abdominal CT at our institution between June 1, 2013, and August 30, 2020. All patients’ clinical information was recorded. Patients were divided into groups undergoing surgical and conservative management. The duodenum (nonrotation, partial rotation, and malrotation), jejunum, cecum, and the superior mesenteric artery/superior mesenteric vein relationship were reviewed on the CT images of each patient, and classification criteria developed based on the first three items. For each patient, each item was assessed separately by three radiologists. Consensus was required from at least two of them.

Results
A total of 332 eligible patients (218 men and 114 women; mean age 51.0 ± 15.3 years) were ultimately included and classified into ten types of malrotation. Duodenal partial rotation was present in most (73.2%, 243/332) with only 25% (83/332) demonstrating nonrotation. The jejunum was located in the right abdomen in 98.2% (326/332) of cases, and an ectopic cecum was found in only 12% (40/332, 29 cases with a left cecum, 7 pelvic, and 4 at midline). Asymptomatic patients comprised 56.6% (188/332) of cases, much higher than that in previous studies (17%, n = 82, p < .001), comprised mainly of patients with duodenal partial rotation (80.3%, 151/188). In 91 patients with detailed clinical data available (12 managed surgically and 79 conservatively), a significant difference in malrotation CT categorization was identified (p = .016).

Conclusions
CT enables greater detection of asymptomatic intestinal malrotation, enabling classification into multiple potentially clinically relevant subtypes.
Severe COVID-19 in the intensive care unit: a case series
Authors: Hariyanto Hori , Yahya Corry Quando , Aritonang Ronald Christian Agustinus 
Published: May 2021

Abstract
Background
Coronavirus disease 2019 (COVID-19) was first identified in Indonesia in March 2020, and the number of infections has grown exponentially. The situation is at its worst, overwhelming intensive care unit (ICU) resources and capacity.

Case presentation
This is a single-center observational case study of 21 confirmed COVID-19 patients admitted to the ICU from March 20, 2020, to April 31, 2020. Demographics, baseline comorbidities, clinical symptoms, laboratory tests, electrocardiogram (ECG) and chest imaging were obtained consecutively during patient care. We identified 21 patients with confirmed COVID-19 severe infection in our ICU. The mean (± standard deviation) age of the patients was 54 ± 10 years; 95% were men, with shortness of breath (90.6%) the most common symptom. Hypertension was identified as a comorbidity in 28.6% of patients. The most common reason for admission to the ICU was hypoxemic respiratory failure, with 80% (17 patients) requiring mechanical ventilation. Half of the patients (10) died between day 1 and day 18, with septic shock as the primary cause of death. Of the 11 surviving patients, five were discharged home, while six were discharged from the ICU but remained in the hospital ward. Even then, the median length of ICU stay amongst survivors was 18 days.

Conclusions
To date, there are no known effective antiviral agents or specific therapy to treat COVID-19. As severe systemic inflammatory response and multiple organ failure seems to be the primary cause of death, supportive care in maintaining oxygenation and hemodynamic stability remain the mainstay goals in treating critically ill COVID-19 patients.
Successful treatment of acute promyelocytic leukemia in a patient with prosthetic heart valves: a case report and review of the literature
Authors: Haghighat Shirin , Rezvani Alireza , Mokhtari Maral 
Published: May 2021

Abstract
Background
Although life-threatening hemorrhage is a usual manifestation of acute promyelocytic leukemia (APL), thrombotic events seem to be more common in APL compared to other subtypes of acute leukemia. The treatment and prophylaxis of thrombosis are controversial due to the high risk of bleeding caused by disseminated intravascular coagulation (DIC) and thrombocytopenia. To the best of our knowledge we report the first case of APL in a patient with prosthetic heart valves successfully treated with a combination of all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO). We hope this case report helps clinicians to manage different spectra of coagulopathy in APL successfully.

Case presentation
A 38-year-old Asian man presented with diagnosis of APL confirmed by bone marrow biopsy. He was on warfarin due to prosthetic mitral and aortic valves. He was at risk of both hemorrhagic events due to DIC and life-threatening valve thrombosis. Our management regimen included unfractionated heparin adjusted according to the platelet count to prevent both valve thrombosis and bleeding events. The patient tolerated treatment well without any hemorrhagic or thrombotic events, and complete molecular remission was achieved by ATRA and ATO without the need for chemotherapeutic agents.

Conclusion
Although this case is exceptional, a precise evaluation may be needed to select the appropriate dose and type of anticoagulant to treat a patient with APL.
Combined topical and systemic administration with human adipose-derived mesenchymal stem cells (hADSC) and hADSC-derived exosomes markedly promoted cutaneous wound healing and regeneration
Authors: Zhou Yang , Zhao Bo , Zhang Xin-Liao , Lu Yi-jun , Lu Shou-Tao , Cheng Jian , Fu Yu , Lin Lin , Zhang Ning-Yan , Li Pei-Xin , Zhang Jing , Zhang Jun 
Published: May 2021

Abstract
Background
Cutaneous wound healing and regeneration have become a recognized health challenge in the world, which causes severe damage to the mental and physical health of patients. Human adipose-derived mesenchymal stem cells (hADSC) play an essential role in wound healing via their paracrine function. Exosomes secreted by hADSC may contribute to this progress. In this study, we investigated the potential clinical application roles of hADSC and hADSC-derived exosomes (hADSC-Exo) in cutaneous wound healing.

Methods
hADSC-Exo was isolated from human hADSC by ultracentrifugation. Mice were subjected to a full-thickness skin biopsy experiment and treated with either control vehicle or hADSC or hADSC-Exo by smearing administration (sm) or subcutaneous administration (sc) or intravenous administration (iv). The efficacy of hADSC and hADSC-Exo on wound healing was evaluated by measuring wound closure rates, histological analysis.

Results
Combined application of local hADSC-Exo smearing and hADSC/hADSC-Exo intravenous administration offered the additional benefit of promoting wound healing, accelerating re-epithelialization, reducing scar widths, and enhancing angiogenesis and collagen synthesis. Either topical application of hADSC-Exo or systemic administration with hADSC/hADSC-Exo appeared more effective in stimulating cell proliferation, inhibiting cell apoptosis and inflammation, and promoting skin elasticity and barrier integrity, with increased genes expression of PCNA, VEGF, collagen III, Filaggrin, Loricrin, and AQP3, with decreased genes expression of TNF-alpha.

Conclusion
Our findings suggest that the combined administration of hADSC/hADSC-Exo can facilitate cutaneous wound healing and reduce scar formation. These data provide the first evidence for the feasibility of smearing of hADSC-Exo as a cell-free therapy in treating cutaneous wounds, and the potential clinical value of combined administration of hADSC/hADSC-Exo.