bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using bioprinting and spheroid culture to create a skin model with sweat glands and hair follicles
Authors: Zhang Yijie , Enhejirigala  , Yao Bin , Li Zhao , Song Wei , Li Jianjun , Zhu Dongzhen , Wang Yuzhen , Duan Xianlan , Yuan Xingyu , Huang Sha , Fu Xiaobing 
Published: May 2021

Abstract

Background
Sweat glands (SGs) and hair follicles (HFs) are two important cutaneous appendages that play crucial roles in homeostatic maintenance and thermoregulation, and their interaction is involved in wound healing. SGs can be regenerated from mesenchymal stem cell-laden 3D bioprinted scaffolds, based on our previous studies, whereas regeneration of HFs could not be achieved in the same model. Due to the lack of an in vitro model, the underlying molecular mechanism of the interaction between SGs and HFs in regeneration could not be fully understood. The purpose of the present study was to establish an in vitro model of skin constructs with SGs and HFs and explore the interaction between these two appendages in regeneration.

Methods
To investigate the interaction effects between SGs and HFs during their regeneration processes, a combined model was created by seeding HF spheroids on 3D printed SG scaffolds. The interaction between SG scaffolds and HF spheroids was detected using RNA expression and immunofluorescence staining. The effects of microenvironmental cues on SG and HF regeneration were analysed by altering seed cell types and plantar dermis homogenate in the scaffold.

Results
According to this model, we overcame the difficulties in simultaneously inducing SG and HF regeneration and explored the interaction effects between SG scaffolds and HF spheroids. Surprisingly, HF spheroids promoted both SG and HF differentiation in SG scaffolds, while SG scaffolds promoted SG differentiation but had little effect on HF potency in HF spheroids. Specifically, microenvironmental factors (plantar dermis homogenate) in SG scaffolds effectively promoted SG and HF genesis in HF spheroids, no matter what the seed cell type in SG scaffolds was, and the promotion effects were persistent.

Conclusions
Our approach elucidated a new model for SG and HF formation in vitro and provided an applicable platform to investigate the interaction between SGs and HFs in vitro. This platform might facilitate 3D skin constructs with multiple appendages and unveil the spatiotemporal molecular program of multiple appendage regeneration.
Conducting correlation analysis: important limitations and pitfalls
Authors: Janse Roemer J , Hoekstra Tiny , Jager Kitty J , Zoccali Carmine , Tripepi Giovanni , Dekker Friedo W , van Diepen Merel 
Published: May 2021

Abstract
The correlation coefficient is a statistical measure often used in studies to show an association between variables or to look at the agreement between two methods. In this paper, we will discuss not only the basics of the correlation coefficient, such as its assumptions and how it is interpreted, but also important limitations when using the correlation coefficient, such as its assumption of a linear association and its sensitivity to the range of observations. We will also discuss why the coefficient is invalid when used to assess agreement of two methods aiming to measure a certain value, and discuss better alternatives, such as the intraclass coefficient and Bland–Altman’s limits of agreement. The concepts discussed in this paper are supported with examples from literature in the field of nephrology.
Cybersecurity of consumer products against the background of the EU model of cyberspace protection
Authors: Banasiński Cezary , Rojszczak Marcin 
Published: May 2021

Abstract
The entry into force of Regulation 2019/881 heralded a new stage in the construction of the EU cybersecurity model. At present, at the level of both EU institutions and individual Member States, preparatory work is underway to create the first ICT certification programmes relating to the area of cybersecurity. To date, the role of national competition and consumer protection authorities in helping to build a coherent cybersecurity model has not been sufficiently highlighted. The problem of the cybersecurity of products intended for the consumer market is a pressing issue. Furthermore, its significance is growing due in no small part to the increasing number of so-called smart connected consumer products and the mass expansion of the IoT market. As a result, threats to security or privacy increasingly stem not from cyberattacks on leading providers of online services but from the exploitation of vulnerabilities in commonly-used consumer products. This article aims to discuss the possible role of competition and consumer protection authorities in shaping a future model of EU cybersecurity. We discuss the existing mechanisms in EU law that allow supervisory authorities to shape the consumer product safety market and consider whether these measures can also be considered adequate for cybersecurity purposes. Particular attention is paid to identifying what legislative steps would be necessary to effectively synthesize the new EU cybersecurity regulations (including the planned cybersecurity certification framework) with existing consumer product safety laws.
Safety and acute efficacy of cryoballoon ablation for atrial fibrillation at community hospitals
Authors: Hoffmann Rainer , Parade Ulli , Bauerle Hansjörg , Winter Klaus-Dieter , Rauschenbach Ulrich , Mischke Karl , Schaefer Carl , Gutleben Klaus-Jürgen , Rana Obaida R , Willich Tobias , Schlößer Marc , Rötzer Alfons , Breithardt Ole A , Middendorf Stefan , Waldecker Berndt , Grove Rainer , Mosa Jörg , Krug Joachim , Imnadze Guram , Saygili Erol , Michaelsen Jochen 
Published: May 2021

Abstract

Aims
Pulmonary vein isolation (PVI) using cryoballoon ablation (CBA) is an established procedure for treating symptomatic paroxysmal and persistent atrial fibrillation (AF). The safety and efficacy of PVI performed at community hospitals are unknown. We aimed to determine the safety and acute efficacy of PVI using CBA performed at community hospitals with limited annual case numbers.

Methods and results
This registry study included 1004 consecutive patients who had PVI performed for symptomatic paroxysmal (n = 563) or persistent AF (n = 441) from January 2019 to September 2020 at 20 hospitals. Each hospital performed fewer than 100 CBA–PVI procedures/year according to local standards. Procedural data, efficacy, and complication rates were determined. The mean number of CBA procedures performed/year at each centre was 59 ± 25. The average procedure time was 90.1 ± 31.6 min and the average fluoroscopy time was 19.2 ± 11.4 min. Isolation of all pulmonary veins was documented in 97.9% of patients. The most frequent reason for not achieving complete isolation was development of phrenic nerve palsy. No hospital deaths were observed. Two patients (0.2%) suffered a clinical stroke. Pericardial effusion occurred in six patients (0.6%), two of whom (0.2%) required pericardial drainage. Vascular complications occurred in 24 patients (2.4%), two of whom (0.2%) required vascular surgery. Phrenic nerve palsy occurred in 48 patients (4.8%) and persisted up to hospital discharge in six patients (0.6%).

Conclusion
Pulmonary vein isolation procedures for paroxysmal or persistent AF using CBA can be performed at community hospitals with high acute efficacy and low complication rates.
shrunken4 is a mutant allele of ZmYSL2 that affects aleurone development and starch synthesis in maize
Authors: He Yonghui , Yang Qing , Yang Jun , Wang Yong-Fei , Sun Xiaoliang , Wang Shu , Qi Weiwei , Ma Zeyang , Song Rentao 
Published: May 2021

Abstract
Minerals are stored in the aleurone layer and embryo during maize seed development, but how they affect endosperm development and activity is unclear. Here, we cloned the gene underlying the classic maize kernel mutant shrunken4 (sh4) and found that it encodes the YELLOW STRIPE-LIKE oligopeptide metal transporter ZmYSL2. sh4 kernels had a shrunken phenotype with developmental defects in the aleurone layer and starchy endosperm cells. ZmYSL2 showed iron and zinc transporter activity in Xenopus laevis oocytes. Analysis using a specific antibody indicated that ZmYSL2 predominately accumulated in the aleurone and sub-aleurone layers in endosperm and the scutellum in embryos. Specific iron deposition was observed in the aleurone layer in wild-type kernels. In sh4, however, the outermost monolayer of endosperm cells failed to accumulate iron and lost aleurone cell characteristics, indicating that proper functioning of ZmYSL2 and iron accumulation are essential for aleurone cell development. Transcriptome analysis of sh4 endosperm revealed that loss of ZmYSL2 function affects the expression of genes involved in starch synthesis and degradation processes, which is consistent with the delayed development and premature degradation of starch grains in sh4 kernels. Therefore, ZmYSL2 is critical for aleurone cell development and starchy endosperm cell activity during maize seed development.
Adding Nuance to Our Understanding of Dog–Wildlife Interactions and the Need for Management
Authors: Gompper Matthew E 
Published: May 2021

Synopsis
The interactions of dogs and wildlife are receiving increasing attention across the globe. Evidence suggests that dogs can negatively affect wildlife in a variety of ways, including through the risk of predation, by hybridizing with other Canis species, by acting as a reservoir or vector of pathogens, and by competing with wildlife for resources. A multitude of observations and case studies for each of these interactions has led to calls to prioritize increased management of dogs, for instance, through population reduction, vaccination, movement restrictions, and enhanced care of the dogs themselves. Here, I argue that while the risks that dogs present to wildlife are real, they vary in their importance across the globe. Furthermore, often the approaches used to address these risks are championed without a full understanding of the likelihood of success given the necessary spatial scale of management, the availability of alternative management approaches, and the role dogs play in societies. For instance, culling, vaccination, and animal husbandry approaches in reducing the impacts of dogs on wildlife sometimes fail to recognize that local human populations actively recruit replacement dogs, that vaccination often fails to reach levels necessary for herd immunity, and that enhanced dog husbandry may have indirect impacts on wildlife by requiring environmentally impactful activities. I suggest there is a need for attention not only to identify the impacts of dogs but also to determine where and when such interactions with wildlife are problematic and the likelihood of success for any proposed management approach. The impacts of dogs should be mediated in a context-specific manner that accounts for factors such as the local density of dogs, the susceptibility of local wildlife populations to the risks that dog populations may represent, and the local societal norms that underpin how dogs might be managed.
Estimating location parameters in sample-heterogeneous distributions
Authors: Pensia Ankit , Jog Varun , Loh Po-Ling 
Published: May 2021

Abstract
Estimating the mean of a probability distribution using i.i.d. samples is a classical problem in statistics, wherein finite-sample optimal estimators are sought under various distributional assumptions. In this paper, we consider the problem of mean estimation when independent samples are drawn from $d$-dimensional non-identical distributions possessing a common mean. When the distributions are radially symmetric and unimodal, we propose a novel estimator, which is a hybrid of the modal interval, shorth and median estimators and whose performance adapts to the level of heterogeneity in the data. We show that our estimator is near optimal when data are i.i.d. and when the fraction of ‘low-noise’ distributions is as small as $\varOmega \left (\frac{d \log n}{n}\right )$, where $n$ is the number of samples. We also derive minimax lower bounds on the expected error of any estimator that is agnostic to the scales of individual data points. Finally, we extend our theory to linear regression. In both the mean estimation and regression settings, we present computationally feasible versions of our estimators that run in time polynomial in the number of data points.
Global epidemiology of Giardia duodenalis infection in cancer patients: a systematic review and meta-analysis
Authors: Mahdavi Farzad , Sadrebazzaz Alireza , Chahardehi Amir Modarresi , Badali Roya , Omidian Mostafa , Hassanipour Soheil , Asghari Ali 
Published: May 2021

Abstract

Background
Application of chemotherapeutics in cancer patients may provide an immunosuppressive milieu, favourable for parasitic infections. Giardia duodenalis is an important zoonotic intestinal parasite responsible for diarrhoea in humans worldwide.

Methods
The present systematic review and meta-analysis was conducted to estimate the prevalence of G. duodenalis and respective odds ratios (ORs) in cancer patients around the globe. Four online databases—PubMed, Scopus, Web of Science and Google Scholar—were carefully explored for relevant literature without time limitation until 28 November 2020. Meta-analysis was done based on a random effects model to pool the estimations and define 95% confidence intervals (CIs).

Results
The overall weighted prevalence of G. duodenalis infection in cancer patients was calculated to be 6.9% (95% CI 0.5 to 9.3) globally, based on data from 32 studies. Although not statistically significant, eight case–control studies revealed that cancer patients were 1.24 times (95% CI 0.66 to 2.31; p=0.501) more exposed to G. duodenalis infection than healthy controls. Moreover, the prevalence of infection was not significantly associated with quantitative variables, including publication year (regression coefficient −0.0135, p=0.578), sample size (regression coefficient −0.0007, p=0.074) and human development index (regression coefficient −1.6263, p=0.419). Also, subgroup analysis of the pooled G. duodenalis infection was performed for publication year, World Health Organization regions, countries, continents, cancer types and country income.

Conclusions
Altogether, the epidemiology of G. duodenalis infection and its associated risk factors in immunocompromised individuals, especially cancer patients, is still open to question and deserves comprehensive investigations.
Safety and efficacy of abiraterone acetate plus prednisolone in patients with castration-resistant prostate cancer: a prospective, observational, post-marketing surveillance study
Authors: Koroki Yosuke , Imanaka Keiichiro , Yasuda Yukiko , Harada Sayuri , Fujino Akiko 
Published: May 2021

Abstract

Background
Abiraterone acetate plus prednisolone is approved to treat patients with castration-resistant prostate cancer. This study evaluated the safety and efficacy of abiraterone acetate plus prednisolone in castration-resistant prostate cancer patients with or without previous chemotherapy in a real-world setting in Japan.

Methods
This study was an observational, prospective, post-marketing surveillance. Castration-resistant prostate cancer patients, who initiated abiraterone acetate after its approval in Japan, were enrolled. Data were collected during an observation period of 12 months and a follow-up period of another 12 months. Adverse events and adverse drug reactions were evaluated for safety. Prostate-specific antigen levels and overall survival were evaluated for efficacy.

Results
From 141 participating institutions, 497 patients were registered: 492 patients including 180 chemotherapy-naïve, 311 chemotherapy-experienced and one off-label-use patient received abiraterone and were evaluated for safety. Adverse events were observed in 225/492 patients (45.7%), adverse drug reactions in 131/492 patients (26.6%) and serious adverse drug reactions in 61/492 patients (12.4%). The most commonly observed adverse drug reaction was abnormal hepatic function (6.5%), followed by hypokalemia (3.0%) and decreased appetite (2.0%). At week 12, 110/432 patients (25.5%) achieved ≥50% decrease from baseline in prostate-specific antigen, and the proportion was higher in chemotherapy-naïve patients (56/161 patients; 34.8%) compared with chemotherapy-experienced patients (54/271 patients; 19.9%, P &lt; 0.001). Survival rates at 24 months were 68.3% (295/432 patients), 73.9% (119/161 chemotherapy-naïve patients) and 64.9% (176/271 chemotherapy-experienced patients).

Conclusions
This large-scale, real-world, post-marketing surveillance study confirmed the safety and efficacy of abiraterone acetate plus prednisolone in Japanese castration-resistant prostate cancer patients with or without previous chemotherapy.
The RNA content of human sperm reflects prior events in spermatogenesis and potential post-fertilization effects
Authors: Corral-Vazquez C , Blanco J , Aiese Cigliano R , Sarrate Z , Rivera-Egea R , Vidal F , Garrido N , Daub C , Anton E 
Published: May 2021

AbstractTranscriptome analyses using high-throughput methodologies allow a deeper understanding of biological functions in different cell types/tissues. The present study provides an RNA-seq profiling of human sperm mRNAs and lncRNAs (messenger and long non-coding RNAs) in a well-characterized population of fertile individuals. Sperm RNA was extracted from twelve ejaculate samples under strict quality controls. Poly(A)-transcripts were sequenced and aligned to the human genome. mRNAs and lncRNAs were classified according to their mean expression values (FPKM: Fragments Per Kilobase of transcript per Million mapped reads) and integrity. Gene Ontology analysis of the Expressed and Highly Expressed mRNAs showed an involvement in diverse reproduction processes, while the Ubiquitously Expressed and Highly Stable mRNAs were mainly involved in spermatogenesis. Transcription factor enrichment analyses revealed that the Highly Expressed and Ubiquitously Expressed sperm mRNAs were primarily regulated by zinc-fingers and spermatogenesis-related proteins. Regarding the Expressed lncRNAs, only one-third of their potential targets corresponded to Expressed mRNAs and were enriched in cell-cycle regulation processes. The remaining two-thirds were absent in sperm and were enriched in embryogenesis-related processes. A significant amount of post-testicular sperm mRNAs and lncRNAs was also detected. Even though our study is solely directed to the poly-A fraction of sperm transcripts, results indicate that both sperm mRNAs and lncRNAs constitute a footprint of previous spermatogenesis events and are configured to affect the first stages of embryo development.
Mergeomics 2.0: a web server for multi-omics data integration to elucidate disease networks and predict therapeutics
Authors: Ding Jessica , Blencowe Montgomery , Nghiem Thien , Ha Sung-min , Chen Yen-Wei , Li Gaoyan , Yang Xia 
Published: May 2021

Abstract
The Mergeomics web server is a flexible online tool for multi-omics data integration to derive biological pathways, networks, and key drivers important to disease pathogenesis and is based on the open source Mergeomics R package. The web server takes summary statistics of multi-omics disease association studies (GWAS, EWAS, TWAS, PWAS, etc.) as input and features four functions: Marker Dependency Filtering (MDF) to correct for known dependency between omics markers, Marker Set Enrichment Analysis (MSEA) to detect disease relevant biological processes, Meta-MSEA to examine the consistency of biological processes informed by various omics datasets, and Key Driver Analysis (KDA) to identify essential regulators of disease-associated pathways and networks. The web server has been extensively updated and streamlined in version 2.0 including an overhauled user interface, improved tutorials and results interpretation for each analytical step, inclusion of numerous disease GWAS, functional genomics datasets, and molecular networks to allow for comprehensive omics integrations, increased functionality to decrease user workload, and increased flexibility to cater to user-specific needs. Finally, we have incorporated our newly developed drug repositioning pipeline PharmOmics for prediction of potential drugs targeting disease processes that were identified by Mergeomics. Mergeomics is freely accessible at http://mergeomics.research.idre.ucla.edu and does not require login.
An exceptionally well-preserved herbaceous eudicot from the Early Cretaceous (late Aptian–early Albian) of Northwest China
Authors: Du Baoxia , Zhang Mingzhen , Sun Bainian , Li Aijing , Zhang Jing , Yan Defei , Xie Sanping , Wu Jingyu 
Published: May 2021

Abstract
A fossil eudicot, Gansufructus saligna gen. et sp. nov., is reported from the Early Cretaceous (late Aptian–early Albian) of the Gansu Province, Northwest China, based on numerous well-preserved axes with attached leaves and infructescences. The leaves are alternate, short petiolate and linear-lanceolate with low rank pinnate to reticulate venation. The infructescences are loose panicles bearing fruits in different stages of maturity, each containing four partly free carpels borne in a whorled arrangement. Each carpel has three to five seeds borne along its ventral margin. The nature of the leaves and axes indicates a terrestrial, herbaceous habit. In general organization, Gansufructus is closely similar to the fruit-bearing axes of Sinocarpus decussatus from the Early Cretaceous Jehol Biota, as well as other more or less contemporaneous angiosperms from the Far East, which together provide evidence of diverse eudicot angiosperms of low stature colonizing areas close to environments of deposition.
Use of Matrix-Assisted Laser Desorption Ionization Time-of-Flight Mass Spectrometry Analysis of Serum Peptidome to Classify and Predict Coronavirus Disease 2019 Severity
Authors: Gomila Rosa M , Martorell Gabriel , Fraile-Ribot Pablo A , Doménech-Sánchez Antonio , Albertí Miguel , Oliver Antonio , García-Gasalla Mercedes , Albertí Sebastián 
Published: May 2021

Abstract

Background
Classification and early detection of severe coronavirus disease 2019 (COVID-19) patients is required to establish an effective treatment. We tested the utility of matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) to classify and predict the severity of COVID-19.

Methods
We used MALDI-TOF MS to analyze the serum peptidome from 72 patients with COVID-19 (training cohort), clinically classified as mild (28), severe (23), and critical (21), and 20 healthy controls. The resulting matrix of peak intensities was used for Machine Learning (ML) approaches to classify and predict COVID-19 severity of 22 independent patients (validation cohort). Finally, we analyzed all sera by liquid chromatography mass spectrometry (LC-MS/MS) to identify the most relevant proteins associated with disease severity.

Results
We found a clear variability of the serum peptidome profile depending on COVID-19 severity. Forty-two peaks exhibited a log fold change ≥1 and 17 were significantly different and at least 4-fold more intense in the set of critical patients than in the mild ones. The ML approach classified clinical stable patients according to their severity with 100% accuracy and correctly predicted the evolution of the nonstable patients in all cases. The LC-MS/MS identified 5 proteins that were significantly upregulated in the critical patients. They included the serum amyloid protein A2, which probably yielded the most intense peak detected by MALDI-TOF MS.

Conclusions
We demonstrate the potential of the MALDI-TOF MS as a bench to bedside technology to aid clinicians in their decision making regarding patients with COVID-19.