bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reproductive health at conflict borders: a cross-sectional survey of human rights violations and perinatal outcomes at the Thai-Myanmar border
Authors: Koning Stephanie M. , Scott Kaylee , Conway James H. , Palta Mari 
Published: March 2021

Abstract
Background
Human rights violations (HRVs) are common in conflict and displacement contexts. Women are especially vulnerable to HRVs in these contexts, and perinatal health is acutely sensitive to related stressors and health care barriers. However, how HRVs affect immediate and long-term perinatal health in chronic displacement settings has not been closely investigated. Furthermore, it remains unclear whether and how HRVs in these contexts are tied directly to displacement circumstances or other marginalizing factors affecting local migrant and minority populations generally.

Methods
We investigated these questions using novel survey data from 577 women at the northern Thai-Myanmar border, where thousands of people have fled conflict in Shan State, Myanmar, for refuge in a range of precarious settings in Thailand, including unofficial refugee camps, villages, and worksites. We compared HRV exposures by ethnicity, country of birth, legal documentation, and residential setting. We then analyzed perinatal outcomes associated with HRV frequency, timing, and type.

Results
Birth in Myanmar, and ethnic minority and precarious legal status more broadly, predicted higher HRV prevalence. HRV frequency significantly predicted unmet antenatal care and lower birth weight, along with HRVs related to labor exploitation and violence or conflict. HRVs timed closer to pregnancies were more adversely associated with perinatal outcomes. Resource/property deprivation was the strongest predictor of pregnancy complications.

Conclusions
Human rights must be urgently attended to, through expanded HRV screenings and responsive care, and policy changes to further protect migrant workers, displaced persons, and others in precarious legal status situations.
FGF19/FGFR4 signaling axis confines and switches the role of melatonin in head and neck cancer metastasis
Authors: Lang Liwei , Xiong Yuanping , Prieto-Dominguez Nestor , Loveless Reid , Jensen Caleb , Shay Chloe , Teng Yong 
Published: March 2021

Abstract
Background
There is no consensus about the effective dosages of melatonin in cancer management, thus, it is imperative to fully understand the dose-dependent responsiveness of cancer cells to melatonin and the underlying mechanisms.

Methods
Head and neck squamous cell carcinoma (HNSCC) cells with or without melatonin treatment were used as a research platform. Gene depletion was achieved by short hairpin RNA, small interfering RNA, and CRISPR/Cas9. Molecular changes and regulations were assessed by Western blotting, quantitative RT-PCR (qRT-PCR), immunohistochemistry, and chromatin Immunoprecipitation coupled with qPCR (ChIP-qPCR). The therapeutic efficacy of FGF19/FGFR4 inhibition in melatonin-mediated tumor growth and metastasis was evaluated in orthotopic tongue tumor mice.

Results
The effect of melatonin on controlling cell motility and metastasis varies in HNSCC cells, which is dose-dependent. Mechanistically, high-dose melatonin facilitates the upregulation of FGF19 expression through activating endoplasmic stress (ER)-associated protein kinase RNA-like endoplasmic reticulum kinase (PERK)-Eukaryotic initiation factor 2 alpha (eIF2α)-activating transcription factor 4 (ATF4) pathway, which in turn promotes FGFR4-Vimentin invasive signaling and attenuates the role of melatonin in repressing metastasis. Intriguingly, following long-term exposure to high-dose melatonin, epithelial HNSCC cells revert the process towards mesenchymal transition and turn more aggressive, which is enabled by FGF19/FGFR4 upregulation and alleviated by genetic depletion of the FGF19 and FGFR4 genes or the treatment of FGFR4 inhibitor H3B-6527.

Conclusions
Our study gains novel mechanistic insights into melatonin-mediated modulation of FGF19/FGFR4 signaling in HNSCC, demonstrating that activating this molecular node confines the role of melatonin in suppressing metastasis and even triggers the switch of its function from anti-metastasis to metastasis promotion. The blockade of FGF19/FGFR4 signaling would have great potential in improving the efficacy of melatonin supplements in cancer treatment.
RETRACTED ARTICLE: Downregulation of lncRNA ZNF582-AS1 due to DNA hypermethylation promotes clear cell renal cell carcinoma growth and metastasis by regulating the N(6)-methyladenosine modification of MT-RNR1
Authors: Yang Wuping , Zhang Kenan , Li Lei , Xu Yawei , Ma Kaifang , Xie Haibiao , Zhou Jingcheng , Cai Lin , Gong Yanqing , Gong Kan 
Published: March 2021

Abstract
Background
Emerging evidence confirms that lncRNAs (long non-coding RNAs) are potential biomarkers that play vital roles in tumors. ZNF582-AS1 is a novel lncRNA that serves as a potential prognostic marker of cancers. However, the specific clinical significance and molecular mechanism of ZNF582-AS1 in ccRCC (clear cell renal cell carcinoma) are unclear.

Methods
Expression level and clinical significance of ZNF582-AS1 were determined by TCGA-KIRC data and qRT-PCR results of 62 ccRCCs. DNA methylation status of ZNF582-AS1 promoter was examined by MSP, MassARRAY methylation and demethylation analysis. Gain-of-function experiments were conducted to investigate the biological roles of ZNF582-AS1 in the phenotype of ccRCC. The subcellular localization of ZNF582-AS1 was detected by RNA FISH. iTRAQ, RNA pull-down and RIP-qRT-PCR were used to identify the downstream targets of ZNF582-AS1. rRNA MeRIP-seq and MeRIP-qRT-PCR were utilized to examine the N(6)-methyladenosine modification status. Western blot and immunohistochemistry assays were used to determine the protein expression level.

Results
ZNF582-AS1 was downregulated in ccRCC, and decreased ZNF582-AS1 expression was significantly correlated with advanced tumor stage, higher pathological stage, distant metastasis and poor prognosis. Decreased ZNF582-AS1 expression was caused by DNA methylation at the CpG islands within its promoter. ZNF582-AS1 overexpression inhibited cell proliferative, migratory and invasive ability, and increased cell apoptotic rate in vitro and in vivo. Mechanistically, we found that ZNF582-AS1 overexpression suppressed the N(6)-methyladenosine modification of MT-RNR1 by reducing rRNA adenine N(6)-methyltransferase A8K0B9 protein level, resulting in the decrease of MT-RNR1 expression, followed by the inhibition of MT-CO2 protein expression. Furthermore, MT-RNR1 overexpression reversed the decreased MT-CO2 expression and phenotype inhibition of ccRCC induced by increased ZNF582-AS1 expression.

Conclusions
This study demonstrates for the first time that ZNF582-AS1 functions as a tumor suppressor gene in ccRCC and ZNF582-AS1 may serve as a potential biomarker and therapeutic target of ccRCC.
Young child with painful edema and purpura: a case report
Authors: Contorno Sarah , Cozzi Giorgio , Berti Irene , Barbi Egidio , Taddio Andrea 
Published: March 2021

Abstract
Background
We reported the case of a two-old-year boy with a painful acute hemorrhagic edema. This is a self-limited benign condition: usually, affected children are well appearing and this strongly support the diagnosis. In the opposite, in our case, we observed a painful presentation of the edema. Therefore, we demonstrated that rarely, this condition could have also a painful presentation.

Conclusions
This case report helps clinician to know that also acute hemorrhagic edema could have a painful presentation, so we must considered it in the differential diagnosis with sepsis, sickle cell crisis and child abuse. We believe that these findings will be of interest to pediatricians.
Failure to thrive in infant and toddlers: a practical flowchart-based approach in a hospital setting
Authors: Franceschi Roberto , Rizzardi Caterina , Maines Evelina , Liguori Alice , Soffiati Massimo , Tornese Gianluca 
Published: March 2021

AbstractBackgroundFailure to thrive is a common reason for referral to paediatric services. Malnutrition or inadequate caloric intake is the most common cause, while organic form is unlikely in children who are asymptomatic and healthy on examination. By this study we evaluate the application of a cost-effective flow chart that helps the clinician in a hospital setting discern accurately organic and non-organic failure to thrive.MethodsConduct a prospective single-center study in children up to 2 years of age with growth faltering. The pediatricians used a practical flow chart, took the medical history, created a growth chart, performed clinical examinations, and requested blood test and consultations in a step by step approach.ResultsAmong the 74 subjects included in the study, the diagnosis of organic failure to thrive was reached by 42%. Gastrointestinal and genetic diagnoses were the most frequent. Patients with organic failure to thrive had significantly lower gestational age and birth weight. Age at diagnosis and Z-score weight were lower in organic than in non-organic forms. Most patients with non-organic forms (88%) did not undergo in-depth blood test or specialist advice.ConclusionThe flow chart we presented was accurate for diagnosing children with failure to thrive in a hospital setting and distinct organic and non-organic forms. It was cost-effective to avoid unnecessary blood test or consultations in most non-organic diagnoses.
The NF-κB signalling pathway and TM7SF3 contribute to liver fibrosis caused by secreted phospholipase A2 of Clonorchis sinensis
Authors: Wu Yin-Juan , He Qing , Shang Mei , Yin Ying-Xuan , Li Ye , Du Xue , Li Xue-Rong 
Published: March 2021

AbstractBackgroundThe NF-κB signalling pathway has been reported to be related to liver fibrosis, and we investigated whether the NF-κB signalling pathway is involved in liver fibrosis caused by secreted phospholipase A2 ofClonorchis sinensis(CssPLA2). Furthermore, expression of the receptor ofCssPLA2 on the cell surface of hepatic stellate cells (HSCs) may greatly contribute to liver fibrosis.MethodsCssPLA2 was administered to BALB/c mice by abdominal injection. The levels of markers of NF-κB signalling pathway activation in mouse liver tissue were measured by quantitative RT-PCR, ELISA and western blot. Additionally, HSCs were incubated withCssPLA2, and an NF-κB signalling inhibitor (BAY 11-7082) was applied to test whether the NF-κB signalling pathway plays a role in the effect ofCssPLA2. Then, the interaction betweenCssPLA2 and its receptor transmembrane 7 superfamily member 3 (TM7SF3) was confirmed by co-immunoprecipitation (co-IP) and GST pull-down. To determine how TM7SF3 influences the ability ofCssPLA2 to cause liver fibrosis, a TM7SF3 antibody was used to block TM7SF3.ResultsThe levels of the NF-ΚB signalling pathway activation markers TNF-α, IL-1β and phospho-p65 were increased byCssPLA2 in the context of liver fibrosis. In addition, the interaction between TM7SF3 andCssPLA2 was confirmed by co-IP and GST pull-down. When TM7SF3 was blocked by an antibody targeting 1–295 amino acids of TM7SF3, activation of HSCs caused byCssPLA2 was alleviated.ConclusionsThe NF-ΚB signalling pathway is involved in the activation of HSCs byCssPLA2. TM7SF3, the receptor ofCssPLA2, plays important roles in liver fibrosis caused byCssPLA2.Graphical Abstract
Hypermagnesemia in a 20-month-old healthy girl caused by the use of a laxative: a case report
Authors: Araki Kotaro , Kawashima Yuhei , Magota Miyuki , Shishida Norio 
Published: March 2021

Abstract
Background
Hypermagnesemia can be a fatal condition and should be diagnosed early on. Most reports of hypermagnesemia have been of adults with impaired renal function. We describe the case of a pediatric patient without renal dysfunction who developed severe hypermagnesemia.

Case presentation
A healthy 20-month-old Asian girl presented to our emergency department with episodes of vomiting and a reduced level of consciousness. The neurological examination showed a symmetric decrease in muscle tone, and the deep tendon reflexes were decreased. On admission, her magnesium (Mg) level was 11.0 mg/dL after receiving magnesium oxide for 4 days because of constipation. She was immediately administered calcium gluconate infusion (3.9 mEq), and then was continuously infused with it (0.23 mEq/h) as a Mg antagonist to cardiac side effects. She was kept hydrated with 0.9% sodium chloride to maintain good urine output to excrete the Mg. The level of the serum Mg decreased to 2.4 mg/dL, enabling her to regain consciousness. During 5 years of follow-up, she was neurologically well, without the recurrence of hypermagnesemia.

Conclusions
Even in the absence of significant renal dysfunction, the prescription of a laxative containing Mg for constipation can result in severe hypermagnesemia. In addition, the symptoms of hypermagnesemia are nonspecific, and early diagnosis is difficult unless it is actively suspected.
Regulation of connective tissue growth factor expression by miR-133b for the treatment of renal interstitial fibrosis in aged mice with unilateral ureteral obstruction
Authors: Cao Dan , Wang Yuan , Zhang Yingjie , Zhang Yinping , Huang Qi , Yin Zhong , Cai Guangyan , Chen Xiangmei , Sun Xuefeng 
Published: March 2021

Abstract
Introduction
Renal interstitial fibrosis, an important pathological feature of kidney aging and chronic renal failure, is regulated by mesenchymal stem cells (MSCs). We have previously demonstrated low expression of miR-133b in MSC-derived extracellular vesicles (MSC-EVs) in aged rats. However, miR-133b can mediate the inhibition of epithelial-mesenchymal transition (EMT) of renal tubules induced by transforming growth factor-β1 (TGF-β1). We investigated the effect of miR-133b for the treatment of geriatric renal interstitial fibrosis and evaluated its target genes.

Methods
We performed real-time polymerase chain reaction to detect miR-133b expression induced during EMT of HK2 cells by TGF-β1 at different concentrations (0, 6, 8, and 10 ng/mL) and at different time points (0, 24, 48, and 72 h). The target genes of miR-133b were validated using the dual-luciferase reporter assay. In vitro experiments were performed to evaluate mRNA and protein expression of miR-133b targets, E-cadherin, α-smooth muscle actin (SMA), fibronectin, and collagen 3A1 (Col3A1), in HK2 cells transfected with miR-133b under TGF-β1 stimulation. A 24-month-old unilateral ureteral obstruction (UUO) mouse model was established and injected with transfection reagent and miR-133b into the caudal vein. The target gene of miR-133b and other parameters mentioned above such as mRNA and protein expression levels and renal interstitial fibrosis were detected at 7 and 14 days.

Results
miR-133b expression gradually decreased with an increase in TGF-β1 concentration and treatment time, and the miR-133b mimic downregulated connective tissue growth factor (CTGF) expression. The dual-luciferase reporter assay confirmed CTGF as a direct target of miR-133b. Transfection of the miR-133b mimic inhibited TGF-β1-induced EMT of HK2 cells; this effect was reversed by CTGF overexpression. miRNA-133b expression significantly increased (approximately 70–100 times) in mouse kidney tissues after injection of the miRNA-133b overexpression complex, which significantly alleviated renal interstitial fibrosis in mice with UUO.

Conclusion
miR-133b exerted targeted inhibitory effects on CTGF expression, which consequently reduced TGF-β1-induced EMT of HK2 cells and renal interstitial fibrosis in aged mice with UUO.
Arrangements with the NHS for providing healthcare services: do they improve financial performance of private for-profit hospitals in Spain?
Authors: Ruiz-Mallorquí María Victoria , Aguiar-Díaz Inmaculada , González- López Valcárcel Beatriz 
Published: March 2021

Abstract
Background
In developed countries around the world there is a trend to enhance the public-private collaboration in healthcare. In Spain, a decentralized country with a NHS funded with taxes and universal coverage, commissioning to for-profit private hospitals the production of healthcare services to specific patients that are publicly insured is a traditional practice. Around 43% of the for-profit private hospitals in Spain have a commissioning agreement with the NHS to diagnose or treat patients on public tariffs. These revenues represent 26% of the total revenues of private for-profit hospitals. The research question of this study is if commissioning with the NHS improves the financial performance of private-for-profit hospitals in Spain.

Methods
With a long panel (2000–2017) of for-profit hospitals we estimate a model for the financial performance (return on assets) using commissioning as main explanatory variable and other variables as control (variables financial indicators and structural information). Specific models are estimated for subgroups of hospitals according to size and specialization. The models are estimated by panel regression with fixed effects and GMM as robustness.

Results
Private for-profit hospitals that have commissioning with NHS obtain higher financial performance than no-commissioning hospitals. This effect varies depending on hospital size and type (hospital specialization), the advantage being more relevant for general hospitals and particularly for hospital with at least 50 beds.

Conclusions
Commissioning with the NHS is a promising source of financial profitability for general acute private for-profit hospitals. The evidence provided by this study may orientate the NHS in the regulation and negotiation of commissioning contracts in healthcare.
Organoids: a promising new in vitro platform in livestock and veterinary research
Authors: Kar Soumya K. , Wells Jerry M. , Ellen Esther D. , te Pas Marinus F. W. , Madsen Ole , Groenen Martien A. M. , Woelders Henri 
Published: March 2021

AbstractOrganoids are self-organizing, self-renewing three-dimensional cellular structures that resemble organs in structure and function. They can be derived from adult stem cells, embryonic stem cells, or induced pluripotent stem cells. They contain most of the relevant cell types with a topology and cell-to-cell interactions resembling that of the in vivo tissue. The widespread and increasing adoption of organoid-based technologies in human biomedical research is testament to their enormous potential in basic, translational- and applied-research. In a similar fashion there appear to be ample possibilities for research applications of organoids from livestock and companion animals. Furthermore, organoids as in vitro models offer a great possibility to reduce the use of experimental animals. Here, we provide an overview of studies on organoids in livestock and companion animal species, with focus on the methods developed for organoids from a variety of tissues/organs from various animal species and on the applications in veterinary research. Current limitations, and ongoing research to address these limitations, are discussed. Further, we elaborate on a number of fields of research in animal nutrition, host-microbe interactions, animal breeding and genomics, and animal biotechnology, in which organoids may have great potential as an in vitro research tool.
Positive regulation of Type III secretion effectors and virulence by RyhB paralogs in Salmonella enterica serovar Enteritidis
Authors: Chen Binjie , Meng Xianchen , Ni Jie , He Mengping , Chen Yanfei , Xia Pengpeng , Wang Heng , Liu Siguo , Zhu Guoqiang , Meng Xia 
Published: March 2021

AbstractSmall non-coding RNA RyhB is a key regulator of iron homeostasis in bacteria by sensing iron availability in the environment. Although RyhB is known to influence bacterial virulence by interacting with iron metabolism related regulators, its interaction with virulence genes, especially the Type III secretion system (T3SS), has not been reported. Here, we demonstrate that two RyhB paralogs of Salmonella enterica serovar Enteritidis upregulate Type III secretion system (T3SS) effectors, and consequently affect Salmonella invasion into intestinal epithelial cells. Specifically, we found that RyhB-1 modulate Salmonella response to stress condition of iron deficiency and hypoxia, and stress in simulated intestinal environment (SIE). Under SIE culture conditions, both RyhB-1 and RyhB-2 are drastically induced and directly upregulate the expression of T3SS effector gene sipA by interacting with its 5′ untranslated region (5′ UTR) via an incomplete base-pairing mechanism. In addition, the RyhB paralogs upregulate the expression of T3SS effector gene sopE. By regulating the invasion-related genes, RyhBs in turn affect the ability of S. Enteritidis to adhere to and invade into intestinal epithelial cells. Our findings provide evidence that RyhBs function as critical virulence factors by directly regulating virulence-related gene expression. Thus, inhibition of RyhBs may be a potential strategy to attenuate Salmonella.
Low complexity channel estimation algorithm using paired spatial signatures for UAV 3D MIMO systems
Authors: Xie Peizhong , Wan Yingqing , Li Ting , Ju Renjie 
Published: March 2021

AbstractThis paper proposes a low complexity channel estimation algorithm for unmanned aerial vehicle three dimension multi-user multiple-input-multiple-output (3D MIMO) systems with the uniform planar array (UPA) at base station using paired spatial signatures. With the aid of antenna array theory and array signal processing, 3D channel is firstly modeled based on the angles between the direction of arrival along x- and y-axis of the UPA. And 3D MIMO channels can be projected onto the x- and y-directions, respectively. Then, channel estimation for multi-user uplinks using small amount of training resources is divided into two phases. At the first uplink preamble phase, each user is assigned the orthogonal pilot, and the paired spatial signatures and optimal rotation angle of each user through the same pilot sequence are obtained. We also propose a user grouping strategy based on three-dimension angle-division multiple access (3D-ADMA) to ensure that the user's spatial signatures do not overlap. At the second phase during several coherence times, the same pilot sequence within a group and orthogonal pilot sequences between groups are assigned, then, the channel state information of the user's x- and y-directions are recovered by the paired space signatures and optimal rotation angle of each user obtained in the preamble phase, respectively. And dynamically updating the user's paired spatial signatures and optimal rotation angle utilizes the obtained channel parameter of x- and y-directions. Finally, the channel parameter of the x- and y-directions are reconstructed by the updated user's space signatures and the optimal rotation angle, and the 3D MIMO channel estimation is obtained through the Kronecker product. Compared with the conventional channel estimation method of the 3D MIMO system under UPA using a low-rank model, the proposed methods reduce the computational complexity without degrading the estimated performance to a large extent. Furthermore, it is carried out with limited training resources, and the pilot resource overhead of the system is greatly reduced by the 3D-ADMA packet and the two-stage pilot allocation. Simulation results verified that the proposed algorithm is effective and feasible.