bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multi-factor regulatory network and different clusters in hypertrophic obstructive cardiomyopathy
Authors: Qin Xianyu , Huang Lei , Chen Sicheng , Chen Shaoxian , Wen Pengju , Wu Yueheng , Zhuang Jian 
Published: August 2021

AbstractBackgroundPractical biosignatures and thorough understanding of regulatory processes of hypertrophic obstructive cardiomyopathy (HOCM) are still lacking.MethodsFirstly, public data from GSE36961 and GSE89714 datasets of Gene Expression Omnibus (GEO), Gene database of NCBI (National Center of Biotechnology Information) and Online Mendelian Inheritance in Man (OMIM) database were merged into a candidate gene set of HOCM. Secondly, weighted gene co-expression network analysis (WGCNA) for the candidate gene set was carried out to determine premier co-expressed genes. Thirdly, significant regulators were found out by virtue of a multi-factor regulatory network of long non-coding RNAs (lncRNAs), messenger RNAs (mRNAs), microRNAs (miRNAs) and transcription factors (TFs) with molecule interreactions from starBase v2.0 database and TRRUST v2 database. Ultimately, HOCM unsupervised clustering and “tsne” dimensionality reduction was employed to gain hub genes, whose classification performance was evaluated by a multinomial model of lasso logistic regression analysis binded with receiver operating characteristic (ROC) curve.ResultsTwo HOCM remarkably-interrelated modules were from WGCNA, followed by the recognition of 32 crucial co-expressed genes. The multi-factor regulatory network disclosed 7 primary regulatory agents, containing lncRNAs (XIST, MALAT1, and H19), TFs (SPI1 and SP1) and miRNAs (hsa-miR-29b-39 and has-miR-29a-3p). Four clusters of HOCM and 4 hub genes (COMP, FMOD, AEBP1 and SULF1) significantly expressing in preceding four subtypes were obtained, while ROC curve demonstrated satisfactory performance of clustering and 4 genes.ConclusionsOur consequences furnish valuable resource which may bring about prospective mechanistic and therapeutic anatomization in HOCM.
Exertional intolerance and dyspnea with preserved lung function: an emerging long COVID phenotype?
Authors: Lam Grace Y. , Befus A. Dean , Damant Ronald W. , Ferrara Giovanni , Fuhr Desi P. , Stickland Michael K. , Varughese Rhea A. , Wong Eric Y. , Smith Maeve P. 
Published: August 2021

AbstractThe COVID-19 pandemic has resulted in significant acute morbidity and mortality worldwide. There is now a growing recognition of the longer-term sequelae of this infection, termed “long COVID”. However, little is known about this condition. Here, we describe a distinct phenotype seen in a subset of patients with long COVID who have reduced exercise tolerance as measured by the 6 min walk test. They are associated with significant exertional dyspnea, reduced health-related quality of life and poor functional status. However, surprisingly, they do not appear to have any major pulmonary function abnormalities or increased burden of neurologic, musculoskeletal or fatigue symptoms.
Sexualized drug injection among men who have sex with men in Madrid and Barcelona as the first episode of drug injecting
Authors: Guerras Juan-Miguel , García de Olalla Patricia , Belza María José , de la Fuente Luis , Palma David , del Romero Jorge , García-Pérez Jorge-Néstor , Hoyos Juan ,   the Methysos Project Group, Donat Marta , del Carmen Burgos María , Romero César Pérez , Bueno José Antonio San Juan , Urrestarazu Francisca Román , Ospina Jesus E , Gutiérrez Miguel Alarcón , Ayerdi Oskar , Rodríguez Carmen , del Corral Del Campo Sonsoles , Zamora Natividad Jerez , Fernández Marta Ruiz , Polo Montserrat González , Gracia María Jesús Barbera , Pérez Luis López , Cortes Claudia Broto , Martin Julio Morais 
Published: August 2021

Abstract
Background
We estimate the prevalence of drug injection, the variables associated with having ever injected and the proportion of ever injectors whose first drug injection was for having sex; we describe the first drug injection episode, analyze the drugs most frequently injected and estimate the prevalence of risky injecting behaviors.

Methods
The participants were 3387 MSM without a previous HIV diagnosis attending four HIV/STI diagnosis services in Madrid and Barcelona. Lifetime prevalence and prevalence ratios (PRs) by different factors were calculated using Poisson regression models with robust variance. We compared the characteristics of first drug injection episode, lifetime injection and risky injecting behaviors of those whose first injection was for sex (FIS) with those whose was not (non-FIS).

Results
Lifetime prevalence of injection was 2.1% (CI 1.7–2.7). In the multivariate analysis, it was strongly associated with having been penetrated by more than five men in the last 12 months (aPR = 10.4; CI 2.5–43.4) and having met most of their partners at private parties (aPR = 7.5; CI 4.5–12.3), and less strongly with other factors. Of those who had ever injected drugs, 81.9% injected for sex the first time they injected drugs (FIS). At first injection, FIS participants had a mean age of 31 years, 62.7% used mephedrone and 32.2% methamphetamine on that occasion. Of this FIS group 39.0% had ever shared drugs or equipment and 82.6% had always shared for sex. Some 30.8% of non-FIS reported having also injected drugs for sex later on.

Conclusions
Only two out of a hundred had ever injected, most to have sex and with frequent drug or injecting equipment sharing. Injecting for sex is the most common first episode of drug injection and is the most efficient risky behavior for the transmission of HIV, hepatitis B or C and other blood-borne infections. MSM participating in private parties should be considered a priority group for prevention policies.
miR-381-3p suppresses breast cancer progression by inhibition of epithelial–mesenchymal transition
Authors: Yu Yong-Zheng , Mu Qiang , Ren Qian , Xie Li-Juan , Wang Qi-Tang , Wang Cui-Ping 
Published: August 2021

Abstract
Background
Accumulating evidence indicates that miRNAs are involved in multiple cellular functions and participate in various cancer development and progression, including breast cancer.

Methods
We aimed to investigate the role of miR-381-3p in breast cancer. The expression level of miR-381-3p and EMT transcription factors was examined by quantitative real-time PCR (qRT-PCR). The effects of miR-381-3p on breast cancer proliferation and invasion were determined by Cell Counting Kit-8 (CCK-8), colony formation, and transwell assays. The regulation of miR-381-3p on its targets was determined by dual-luciferase analysis, qRT-PCR, and western blot.

Results
We found that the expression of miR-381-3p was significantly decreased in breast cancer tissues and cell lines. Overexpression of miR-381-3p inhibited breast cancer proliferation and invasion, whereas knockdown of miR-381-3p promoted cell proliferation and invasion in MDA-MB-231 and SKBR3 cells. Mechanistically, overexpression of miR-381-3p inhibited breast cancer epithelial–mesenchymal transition (EMT). Both Sox4 and Twist1 were confirmed as targets of miR-381-3p. Moreover, transforming growth factor-β (TGF-β) could reverse the effects of miR-381-3p on breast cancer progression.

Conclusions
Our observation suggests that miR-381-3p inhibits breast cancer progression and EMT by regulating the TGF-β signaling via targeting Sox4 and Twist1.
DEAD-box helicase 27 enhances stem cell-like properties with poor prognosis in breast cancer
Authors: Li Shan , Ma Jinfei , Zheng Ang , Song Xinyue , Chen Si , Jin Feng 
Published: August 2021

AbstractBackgroundAlthough the rapid development of diagnosis and treatment has improved prognosis in early breast cancer, challenges from different therapeutic response remain due to breast cancer heterogeneity. DEAD-box helicase 27 (DDX27) had been proved to influence ribosome biogenesis and identified as a promoter in gastric and colorectal cancer associated with stem cell-like properties, while the impact of DDX27 on breast cancer prognosis and biological functions is unclear. We aimed to explore the influence of DDX27 on stem cell-like properties and prognosis in breast cancer.MethodsThe expression of DDX27 was evaluated in 24 pairs of fresh breast cancer and normal tissue by western blot. We conducted Immunohistochemical (IHC) staining in paraffin sections of 165 breast cancer patients to analyze the expression of DDX27 and its correlation to stemness biomarker. The Cancer Genome Atlas-Breast Cancer (TCGA-BRCA) database and the Clinical Proteomic Tumor Analysis Consortium (CPTAC) database were used to analyze the expression of DDX27 in breast cancer. Kaplan–Meier survival analysis were used to investigate the implication of DDX27 on breast cancer prognosis. Western blot, CCK-8 assay, Transwell assay and wound-healing assay were carried out to clarify the regulation of DDX27 on stem cell-like properties in breast cancer cells. Gene Set Enrichment Analysis (GSEA) was performed to analyze the potential molecular mechanisms of DDX27 in breast cancer.ResultsDDX27 was significantly high expressed in breast cancer compared with normal tissue. High expression of DDX27 was related to larger tumor size (p = 0.0005), positive lymph nodes (p = 0.0008), higher histological grade (p = 0.0040), higher ki-67 (p = 0.0063) and later TNM stage (p < 0.0001). Patients with high DDX27 expression turned out a worse prognosis on overall survival (OS,p = 0.0087) and disease-free survival (DFS,p = 0.0235). Overexpression of DDX27 could enhance the expression of biomarkers related to stemness and promote stem cell-like activities such as proliferation and migration in breast cancer cells.ConclusionDDX27 can enhance stem cell-like properties and cause poor prognosis in breast cancer, also may be expected to become a potential biomarker for breast cancer therapy.
Sarcoidosis presenting as bilateral lacrimal gland swelling: a pediatric case report
Authors: Powell Margaret S. , Cross Ashley W. , Tallo Jared , Cheeseman Edward W. , Gilbert Mileka R. 
Published: August 2021

Abstract
Background
To describe a case of pediatric sarcoidosis which initially presented as papillary conjunctivitis before manifesting as bilateral lacrimal gland swelling without other known systemic involvement.

Case presentation
A 10-year-old female presented to the pediatric ophthalmology clinic with complaints of bilateral eyelid swelling, tearing and itching for approximately 1 month. Her history and exam were most consistent with allergic conjunctivitis, for which she was started on a standard topical regimen. Despite initial improvement, she re-presented with significantly worsened eyelid swelling and minimal allergic symptoms. Enlargement of the lacrimal glands were palpable at this time. Lacrimal gland biopsy was obtained which demonstrated noncaseating granulomas. Systemic workup did not reveal evidence of disease involvement elsewhere.

Conclusions
Sarcoidosis in the pediatric population may present in a myriad of ways and is well-known to mimic other disease entities. We present a case of pediatric sarcoidosis which presented initially as papillary conjunctivitis before manifesting as bilateral lacrimal gland swelling without systemic involvement.
Normalization of HE-stained histological images using cycle consistent generative adversarial networks
Authors: Runz Marlen , Rusche Daniel , Schmidt Stefan , Weihrauch Martin R. , Hesser Jürgen , Weis Cleo-Aron 
Published: August 2021

Abstract
Background
Histological images show strong variance (e.g. illumination, color, staining quality) due to differences in image acquisition, tissue processing, staining, etc. This can impede downstream image analysis such as staining intensity evaluation or classification. Methods to reduce these variances are called image normalization techniques.

Methods
In this paper, we investigate the potential of CycleGAN (cycle consistent Generative Adversarial Network) for color normalization in hematoxylin-eosin stained histological images using daily clinical data with consideration of the variability of internal staining protocol variations. The network consists of a generator network GB that learns to map an image X from a source domain A to a target domain B, i.e. GB:XA→XB. In addition, a discriminator network DB is trained to distinguish whether an image from domain B is real or generated. The same process is applied to another generator-discriminator pair (GA,DA), for the inverse mapping GA:XB→XA. Cycle consistency ensures that a generated image is close to its original when being mapped backwards (GA(GB(XA))≈XA and vice versa). We validate the CycleGAN approach on a breast cancer challenge and a follicular thyroid carcinoma data set for various stain variations. We evaluate the quality of the generated images compared to the original images using similarity measures. In addition, we apply stain normalization on pathological lymph node data from our institute and test the gain from normalization on a ResNet classifier pre-trained on the Camelyon16 data set.

Results
Qualitative results of the images generated by our network are compared to original color distributions. Our evaluation indicates that by mapping images to a target domain, the similarity training images from that domain improves up to 96%. We also achieve a high cycle consistency for the generator networks by obtaining similarity indices greater than 0.9. When applying the CycleGAN normalization to HE-stain images from our institute the kappa-value of the ResNet-model that is only trained on Camelyon16 data is increased more than 50%.

Conclusions
CycleGANs have proven to efficiently normalize HE-stained images. The approach compensates for deviations resulting from image acquisition (e.g. different scanning devices) as well as from tissue staining (e.g. different staining protocols), and thus overcomes the staining variations in images from various institutions.The code is publicly available at https://github.com/m4ln/stainTransfer_CycleGAN_pytorch. The data set supporting the solutions is available at 10.11588/data/8LKEZF.
2006 to 2019 Story; percutaneously implantable aortic valve prototypes
Authors: Zervides Constantinos , Nohra Ornella , Hunduma Gabriel , Thomas Neil Wild , Samia Ramy 
Published: August 2021

Abstract
Aims
A review was conducted on the composition, advantages and limitations of available aortic valve prototypes to create an ideal valve for percutaneous implantation.
Patients
Patients with multiple comorbidities who cannot withstand the risks of open cardiac surgery.

Methodology
The search was performed using online databases and textbooks. Articles were excluded based on specific criterion.

Results
Ten prototypes created between 2006 and 2019 were found and reviewed. The prototypes had a set of advantages and limitations with their characteristics coinciding at times.

Conclusions
The ideal percutaneously implantable aortic valve should have minimum coaptation height, zero folds in the leaflets, minimum valve height, minimum leaflet flexion and three leaflets. It can be composed of biological or synthetic material, as long as it provides minimal risk of thrombosis. However, more studies are needed to ensure other ideal parameters.
Osteomyelitis variolosa, an issue inherited from the past: case report and systematic review
Authors: Tang Jinshuo , Shao Pu , Liu Te , Wen Xinggui , Wang Yeliang , Wang Chenyu , Peng Yachen , Yao Hua , Zuo Jianlin 
Published: August 2021

Abstract
Background
Osteomyelitis variolosa is a self-limiting disease triggered by variola virus that cannot be prevented or repaired. Smallpox has been eradicated for 40 years, and complications that remain after smallpox has been cured have become a remarkable diagnostic challenge for contemporary physicians. In this systematic review, we searched PubMed (MEDLINE), Web of Science, and Google Scholar for cases on complications, diagnosis, and treatment for osteomyelitis variolosa between January 1980 and February 2021.

Results
Ten papers and eleven finished cases, all patients from India, were included for comparison with the present case. In total, 100% of patients presented with bilateral elbow deformities, the ankle was the second most common site of lesion in 50%, and knee lesions accounted for 25% in this study. Flexion contracture, joint instability, secondary arthritis, and fracture are common complications of osteomyelitis variolosa, and most patients receive conservative treatment, while internal fixation has good results for combined fractures.

Conclusions
Although osteomyelitis variolosa is not a direct threat to the safety of patients, severe skeletal deformities can have a significant impact on quality of life. With advances in surgical techniques, clinicians are offering an increasing number of treatment options for patients with osteomyelitis variolosa. However, most importantly, smallpox has basically been removed from the historical arena, and for areas where smallpox was once endemic, physicians need to deepen the understanding of this disease again.
Development of an RNAi-based microalgal larvicide for the control of Aedes aegypti
Authors: Fei Xiaowen , Zhang Yang , Ding Lili , Xiao Sha , Xie Xiaoqing , Li Yajun , Deng Xiaodong 
Published: August 2021

Abstract
Background
Mosquito-borne diseases affect over half of the human population globally. Multiple studies have shown that chemical insecticides are ineffective because of resistance. Therefore, environmentally safe mosquito population control tools need to be developed. Ribonucleic acid interference (RNAi) is a reverse genetic mechanism recently introduced as a new pest control tool. This technique represents a new class of biorational technology that could combat the increased global incidence of insecticide resistance. The technique has the potential of becoming a critical component of integrated vector control programs.

Methods
A 3-hydroxykynurenine transaminase (3-HKT) RNAi expression plasmid was constructed, generated and transformed into Chlamydomonas and Chlorella algae. The transgenic algae were then used to feed Ae. aegypti mosquito larvae. The feeding experiments were conducted on a small and large scale with 10 and about 300 larvae, respectively. The mortality rate of the larvae was calculated over 30 days. In addition, histological examination of the insect tissues was performed to examine the extent of tissue damage.

Results
The integumentary system and midguts of larvae fed with transgenic Chlamydomonas were severely damaged. The mortality rate of the larvae fed with transgenic Chlamydomonas ranged from 60 to 100% in small-scale tests. The survival rate of adult mosquitoes was 0.0% in a large-scale feeding experiment when the larvae were fed with transgenic Chlamydomonas. Moreover, when the larvae were fed with transgenic Chlorella, the mortality rate ranged from 6.7% to 43% compared to that fed wild-type Chlorella.

Conclusions
3HKT RNAi transgenic algae are in some scales lethal to Ae. aegypti. The findings of this study indicate that technology based on microalgae RNAi may provide a new way to control mosquito populations.

Graphical Abstract
Establishment and validation of a guinea pig model for human congenital toxoplasmosis
Authors: Grochow Thomas , Beck Britta , Rentería-Solís Zaida , Schares Gereon , Maksimov Pavlo , Strube Christina , Seeger Johannes , Raqué Lisa , Ulrich Reiner , Daugschies Arwid , Fietz Simone A. 
Published: August 2021

Abstract
Background
Toxoplasma gondii is an obligate intracellular parasite with a worldwide distribution. Congenital infection in humans and animals may lead to severe symptoms in the offspring, especially in the brain. A suitable animal model for human congenital toxoplasmosis is currently lacking. The aim of this study is to establish and validate the guinea pig as a model for human congenital toxoplasmosis by investigating the impact of the T. gondii infection dose, the duration of infection and the gestational stage at infection on the seroconversion, survival rate of dams, fate of the offspring, T. gondii DNA loads in various offspring tissues and organs and the integrity of the offspring brain.

Methods
Pregnant guinea pigs were infected with three different doses (10, 100, 500 oocysts) of T. gondii strain ME49 at three different time points during gestation (15, 30, 48 days post-conception). Serum of dams was tested for the presence of T. gondii antibodies using immunoblotting. T. gondii DNA levels in the dam and offspring were determined by qPCR. Offspring brains were examined histologically.

Results
We found the survival rate of dams and fate of the offspring to be highly dependent on the T. gondii infection dose with an inoculation of 500 oocysts ending lethally for all respective offspring. Moreover, both parameters differ depending on the gestational stage at infection with infection in the first and third trimester of gestation resulting in a high offspring mortality rate. The duration of infection was found to substantially impact the seroconversion rate of dams with the probability of seroconversion exceeding 50% after day 20 post-infection. Furthermore, the infection duration of dams influenced the T. gondii DNA loads in the offspring and the integrity of offspring brain. Highest DNA levels were found in the offspring brain of dams infected for  ≥ 34 days.

Conclusion
This study contributes to establishing the guinea pig as a suitable model for human congenital toxoplasmosis and thus lays the foundation for using the guinea pig as a suitable animal model to study scientific questions of high topicality and clinical significance, which address the pathogenesis, diagnosis, therapy and prognosis of congenital toxoplasmosis.

Graphical abstract
Technological interventions for loneliness and social isolation among older adults: a scoping review protocol
Authors: Wister Andrew , Fyffe Ian , O’Dea Eireann 
Published: August 2021

Abstract
Background
Loneliness and social isolation are prevalent public health concerns among community-dwelling older adults. One approach that is becoming an increasingly popular method of reducing levels of loneliness and social isolation among older adults is through technology-driven solutions. This protocol outlines a research trajectory whereby a scoping review will be initiated in order to illustrate and map the existing technological approaches that have been utilized to diminish levels of loneliness and social isolation among community-dwelling older adults aged 60 years or older. We will address the question: what are the most common and less used technological approaches to reduce loneliness and social isolation among community-dwelling older adults?

Methods
A scoping review of Academic Search Premier, AGEline, Global Health, MEDLINE, PsycINFO, and Web of Science databases will take place using our search terms including the following: loneliness, social isolation, older adults, elderly, Aged, Aged 80 and over, program, evaluation, trial, intervention, technology, computer, information and communication technology, internet, and robot. The initial electronic search will be supplemented by reviewing the reference lists and review articles to identify any missing studies. To meet study inclusion criteria, intervention studies had to pertain to community-dwelling adults aged 60 years or older, include technological interventions, include loneliness and/or social isolation as outcome variables, and be written in the English language. Two parallel independent assessments of study eligibility will be conducted for the title, abstract, and full-text screens. Any disagreement will be resolved by consensus and a third reviewer consulted to make a decision if consensus is not achieved initially. Finally, the amalgamation of results will be an iterative process whereby reviewers will refine the plan for presenting results after data extraction is completed so that all of the contents of the extraction may be included in the results.

Discussion
The information gleaned in this scoping review will be essential to understand the degree to which technological interventions influence social isolation and loneliness among older adults and identify gaps for further research.