bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oral toxicity of titanium dioxide P25 at repeated dose 28-day and 90-day in rats
Authors: Heo Min Beom , Kwak Minjeong , An Kyu Sup , Kim Hye Jin , Ryu Hyeon Yeol , Lee So Min , Song Kyung Seuk , Kim In Young , Kwon Ji-Hwan , Lee Tae Geol 
Published: July 2020

Abstract
Background
Nanotechnology is indispensable to many different applications. Although nanoparticles have been widely used in, for example, cosmetics, sunscreen, food packaging, and medications, they may pose human safety risks associated with nanotoxicity. Thus, toxicity testing of nanoparticles is essential to assess the relative health risks associated with consumer exposure.

Methods
In this study, we identified the NOAEL (no observed adverse effect level) of the agglomerated/aggregated TiO2 P25 (approximately 180 nm) administered at repeated doses to Sprague-Dawley (SD) rats for 28 and 90 days. Ten of the 15 animals were necropsied for toxicity evaluation after the repeated-dose 90-day study, and the remaining five animals were allowed to recover for 28 days. The agglomerated/aggregated TiO2 P25 dose levels used included 250 mg kg− 1 d− 1 (low), 500 mg kg− 1 d− 1 (medium), and 1000 mg kg− 1 d− 1 (high), and their effects were compared with those of the vehicle control. During the treatment period, the animals were observed for mortality, clinical signs (detailed daily and weekly clinical observations), functional observation battery, weekly body weight, and food and water consumption and were also subjected to ophthalmological examination and urinalysis. After termination of the repeated-dose 28-day, 90-day, and recovery studies, clinical pathology (hematology, blood coagulation time, and serum biochemistry), necropsy (organ weights and gross findings), and histopathological examinations were performed.

Results
No systemic toxicological effects were associated with the agglomerated/aggregated TiO2 P25 during the repeated-dose 28-day, 90-day, and recovery studies in SD rats. Therefore, the NOAEL of the agglomerated/aggregated TiO2 P25 was identified as 1000 mg kg− 1 d− 1, and the substance was not detected in the target organs.

Conclusion
Subacute and subchronic oral administration of the agglomerated/aggregated TiO2 P25 was unlikely to cause side effects or toxic reactions in rats.
Intermittent kangaroo mother care and the practice of breastfeeding late preterm infants: results from four hospitals in different provinces of China
Authors: Zhang Bo , Duan Zhiying , Zhao Yingxi , Williams Sarah , Wall Stephen , Huang Limin , Zhang Xiaoqin , Wu Wenli , Yue Jieya , Zhang Lin , Liu Jun , Zhao Gengli 
Published: July 2020

Abstract
Background
China has an extremely low exclusive breastfeeding rate. Kangaroo mother care (KMC) has been shown to increase the exclusive breastfeeding rate among infants born extremely or very preterm. However, there is limited evidence surrounding intermittent KMC and exclusive breastfeeding in late preterm infants. In our study we investigated the association between the provision of intermittent KMC and breastfeeding practice for late preterm infants in four hospitals in different provinces of China.

Methods
Intermittent KMC was recommended to the mothers of all preterm infants admitted to the postnatal wards of participating hospitals between March 2018 and March 2019. Those who agreed to practice KMC were enrolled in the “KMC group”, those who did not were enrolled in the “No KMC group”. Basic maternal socio-demographic information was collected, feeding practice; outcome and method, were recorded daily whilst in hospital. A follow-up survey of feeding practice was conducted 42 days after discharge. Calculations for feeding practice were performed separately for both groups. Logistics regression was used to analyze the association between KMC and feeding outcome and method, adjusting for socio-demographic covariates.

Results
Among the 844 mothers participating in the study, 627 (74.3%) chose to perform KMC. More of the mothers who provided KMC were exclusively breast milk feeding their infants in the 24 h before hospital discharge (54.6%) and at follow-up (57.3%), compared to mothers who did not provide KMC (34.6% at discharge and 33.2% at follow-up,). Mothers in the KMC group were more likely to be breastfeeding (method) than mothers in the No KMC group (65.3% vs. 52.1% at discharge, and 83.1% vs. 67.3% at follow up). Logistic regression indicated that compared with the No KMC group, mothers who provided KMC were twice as likely to be exclusively breast milk feeding their infants at discharge (OR = 2.15 (95% CI 1.53, 3.02)), use breastfeeding method at discharge as opposed to other means such as bottle or cup feeding (OR = 1.61 (95% CI 1.15, 2.25)), be exclusive breast milk feeding at follow-up (OR = 2.55 (95% CI 1.81, 3.61)), and use breastfeeding method at follow-up (OR = 2.09 (95% CI 1.44, 3.02)).

Conclusions
Intermittent KMC was associated with a nearly doubled increase in exclusive breast milk feeding (outcome) and breastfeeding (method) at both discharge and 42 days after discharge for late preterm infants. This is especially important in China where exclusive breastfeeding rates are low, intermittent KMC provides a feasible means to increase the likelihood of these vulnerable infants receiving the benefits of exclusive breastmilk.
The relationship between perceived milk supply and exclusive breastfeeding during the first six months postpartum: a cross-sectional study
Authors: Sandhi Ayyu , Lee Gabrielle T. , Chipojola Roselyn , Huda Mega Hasanul , Kuo Shu-Yu 
Published: July 2020

Abstract
Background
Perceived milk supply is an important modifiable factor for optimal breastfeeding. However, little is known about maternal perception of milk supply or how it impacts breastfeeding practices. The aim of this study was to examine relationships of perceived milk supply, maternal breastfeeding self-efficacy, and skin-to-skin contact with early initiation and exclusive breastfeeding among mothers of infants less than 6 months of age in Indonesia.

Methods
This was a cross-sectional study conducted in Yogyakarta City, Indonesia between August and October 2015. Maternal perception of milk supply was assessed using the Hill and Humenick Lactation Scale. Data on breastfeeding practices, and maternal and infant factors were collected using a structured questionnaire. Multiple regression and multivariate logistic regression analyses were performed to obtain estimates of associations.

Results
Thirty four percent of mothers had initiated breastfeeding within an hour after birth, and 62.4% of mothers were exclusively breastfeeding. High levels of perceived breast milk supply were reported in mothers who practiced skin-to-skin contact or rooming-in with their infants, experienced positive infant sucking behavior, or had high breastfeeding self-efficacy (p < 0.05). Mothers with a higher level of perceived milk production (Odds Ratio [OR] 3.20; 95% Confidence Interval [CI] 1.76, 5.83) or practicing skin-to-skin contact (OR 2.36; 95% CI 1.13, 4.91) were more likely to exclusively breastfeed, while employed mothers were less likely to breastfeed their infants exclusively (OR 0.47; 95% CI 0.24, 0.93).

Conclusions
In this study, skin-to-skin contact and breastfeeding self-efficacy are important determinants of perceived milk supply. Higher perception of milk supply was positively linked with exclusive breastfeeding. Our study highlights the importance of the assessment for mother’s perception of milk supply, maternal breastfeeding self-efficacy, and skin-to-skin contact in achieving optimal breastfeeding outcomes.
Clubfoot treatment with Ponseti method—parental distress during plaster casting
Authors: Walter Christian , Sachsenmaier Saskia , Wünschel Markus , Teufel Martin , Götze Marco 
Published: July 2020

AbstractBackgroundClubfoot is one of the most prevalent musculoskeletal congenital defects. Gold standard treatment of idiopathic clubfoot is the conservative Ponseti method, including the reduction of deformity with weekly serial plaster casting and percutaneous Achilles tenotomy. It is well known that parents of children with severe and chronic illnesses are mentally stressed, but in recent studies regarding clubfoot treatment, parents were only asked about their satisfaction with the treatment. Largely unknown is parental distress before and during plaster casting in clubfoot.Therefore, we want to determinate first, how pronounced the parents’ worries are before treatment and if they decrease during the therapy. Second, we hypothesized that parents faced with an extreme deformity (high Pirani score), reveal more distress, than parents whose children have a less pronounced deformity (low Pirani score). Therefore, we wanted to investigate whether the Pirani score correlates with the parents’ mental resilience in relation to the therapy of the child as a global distress parameter.MethodsTo answer this question, we developed a questionnaire with the following emphases: Physical capacity, mental resilience, motion score, parents score, and child score with point scores 1 (not affected) to 6 (high affected). Subsequently, we interviewed 20 parents whose children were treated with clubfeet and determined the Pirani score of the infants at the beginning (T0) and at the end (TE) of the treatment with plaster casting.ResultsHigh values were obtained in child score (Mean (M) = 3.11), motion score (M= 2.63), and mental resilience (M= 2.25). During treatment, mental resilience improved (p= 0.015) significantly. Spearman correlation coefficient between Pirani score (T0) and mental resilience (T0) is 0.21, so the initial hypothesis had to be rejected.ConclusionThe issues of the children are in the focus of parental worries concerning clubfoot treatment, especially the assumed future motion and the assumed ability to play with other children. Particular emphasis should be placed on educating parents about the excellent long-term results in the function of the treated feet especially as this topic shows the greatest parental distress.
Overexpression of programmed cell death ligand 1 in patients with CIN and its correlation with human papillomavirus infection and CIN persistence
Authors: Sancakli Usta Ceyda , Altun Eren , Afsar Selim , Bulbul Cagla Bahar , Usta Akin , Adalı Ertan 
Published: July 2020

Abstract
Backround
HPV causes specific cell-mediated immunity in the cervix. Mononuclear cells such as helper T cells (CD4+), cytotoxic T cells (CD8+), and dendritic cells play a critical role in the initiation of the HPV-specific immune response and destruction of virus-infected cervical epithelial cells. The programmed cell death ligand 1 (PD-L1) gene encodes an immune inhibitory receptor ligand and overexpression of PD-L1 inhibits T-cell activation and cytokine production. The aim of this study was to investigate the expression of PD-L1 in cervical tissue and its correlation with clinicopathological findings.

Methods
In this cross-sectional study, a total of 94 women who were referred for colposcopy due to abnormal Papanicolaou (PAP) test results and/or HPV positivity were evaluated. The presence of HR-HPV–DNA was analyzed using type- and gene-specific primers along with commercial real-time polymerase chain reaction. The cervical examination was done with a colposcope. Cervical biopsies were obtained from the areas that were evaluated as abnormal during the colposcopy. Histopathological result of cervical biopsies were defined as no intraepithelial neoplasia (CIN 0), mild CIN (CIN I), and moderate-to-high CIN (CIN II-III). All women were classified into four groups based on their HR-HPV positivity and cervical biopsy results: Group I (controls; n = 29), HR-HPV (−) CIN 0; Group II (n = 21), HR-HPV (+) CIN 0; Group III (n = 20), HR-HPV (+) CIN I; and Group IV (n = 24), HR-HPV (+) CIN II-III. A semi-quantitative scoring system was used to evaluate the degree of Ki-67, p16, and PD-L1 immunoreactivity in the cervical tissue samples.

Results
We found that PD-L1 expression in both mononuclear cells and in cervical epithelial cells gradually increases from the HR-HPV (−), CIN 0 group to the HR-HPV (+), CIN II-III group (p = 0.0003 and p = 0.0394, respectively) and mononuclear PD-L1 expression was correlated with HPV type, initial Pap test results, HPV persistence, and CIN persistence or recurrence (p = 0.0180, p = 0.0109, p = 0.0042, and p = 0.0189, respectively). Moreover, mononuclear PD-L1 expression was also correlated with Ki-67 and p16 immunoreactivity (p = 0.0432 and p = 0.0166, respectively). Epithelial PD-L1 expression was only correlated with HPV type and the presence of HPV persistence (p = 0.0122 and p = 0.0292, respectively).

Conclusion
During the initial evaluation of the cervical histology results, the assessment of PD-L1 expression—especially in mononuclear cells in cervical tissue samples—may provide more information on the progression of HR-HPV infection and its persistence.
Fasciola gigantica excretory-secretory products (FgESPs) modulate the differentiation and immune functions of buffalo dendritic cells through a mechanism involving DNMT1 and TET1
Authors: Mei Xuefang , Shi Wei , Zhao Wenping , Luo Honglin , Zhang Yaoyao , Wang Yurui , Sheng Zhaoan , Wang Dongying , Zhu Xing-Quan , Huang Weiyi 
Published: July 2020

Abstract
Background
Fasciola gigantica infection threatens the health of both humans and animals in the world. The excretory/secretory products (ESPs) of this fluke has been reported to impair the activation and maturation of immune cells. We have previously shown the influence of F. gigantica ESPs (FgESPs) on the maturation of buffalo dendritic cells (DCs). However, the underlying mechanisms remain unclear. The objective of this study was to investigate the potency of FgESPs in shifting the differentiation and immune functions of buffalo DCs.

Methods
Buffalo DCs were incubated with FgESPs directly or further co-cultured with lymphocytes in vitro. qRT-PCR was employed to determine the gene expression profile of DCs or the mixed cells, and an ELISA was used to measure cytokine levels in the supernatants. Hoechst and Giemsa staining assays, transmission electron microscopy, caspase-3/7 activity test and histone methylation test were performed to determine DC phenotyping, apoptosis and methylation. To investigate the mechanism involved with DNA methylation, a Co-IP assay and immunofluorescent staining assay were performed to observe if there was any direct interaction between FgESPs and DNMT1/TET1 in buffalo DCs, while RNAi technology was employed to knockdown DNMT1 and TET1 in order to evaluate any different influence of FgESPs on DCs when these genes were absent.

Results
qRT-PCR and ELISA data together demonstrated the upregulation of DC2 and Th2/Treg markers in DCs alone and DCs with a mixed lymphocyte reaction (MLR), suggesting a bias of DC2 that potentially directed Th2 differentiation in vitro. DC apoptosis was also found and evidenced morphologically and biochemically, which might be a source of tolerogenic DCs that led to Treg differentiation. In addition, FgESPs induced methylation level changes of histones H3K4 and H3K9, which correlate with DNA methylation. Co-IP and immunofluorescent subcellular localization assays showed no direct interaction between the FgESPs and DNMT1/TET1 in buffalo DCs. The productions of IL-6 and IL-12 were found separately altered by the knockdown of DNMT1 and TET1 in DCs after FgESPs treatment.

Conclusions
FgESPs may induce the DC2 phenotype or the apoptosis of buffalo DCs to induce the downstream Th2/Treg response of T cells, possibly through a DNMT1- or TET1-dependent manner(s).
Histone N-alpha terminal modifications: genome regulation at the tip of the tail
Authors: Demetriadou Christina , Koufaris Costas , Kirmizis Antonis 
Published: July 2020

AbstractHistone proteins are decorated with numerous post-(PTMs) or co-(CTMs) translational modifications mainly on their unstructured tails, but also on their globular domain. For many decades research on histone modifications has been focused almost solely on the biological role of modifications occurring at the side-chain of internal amino acid residues. In contrast, modifications on the terminal N-alpha amino group of histones—despite being highly abundant and evolutionarily conserved—have been largely overlooked. This oversight has been due to the fact that these marks were being considered inert until recently, serving no regulatory functions. However, during the past few years accumulating evidence has drawn attention towards the importance of chemical marks added at the very N-terminal tip of histones and unveiled their role in key biological processes including aging and carcinogenesis. Further elucidation of the molecular mechanisms through which these modifications are regulated and by which they act to influence chromatin dynamics and DNA-based processes like transcription is expected to enlighten our understanding of their emerging role in controlling cellular physiology and contribution to human disease. In this review, we clarify the difference between N-alpha terminal (Nt) and internal (In) histone modifications; provide an overview of the different types of known histone Nt-marks and the associated histone N-terminal transferases (NTTs); and explore how they function to shape gene expression, chromatin architecture and cellular phenotypes.
New generalized fractional versions of Hadamard and Fejér inequalities for harmonically convex functions
Authors: Qiang Xiaoli , Farid Ghulam , Yussouf Muhammad , Khan Khuram Ali , Rahman Atiq Ur 
Published: July 2020

AbstractThe aim of this paper is to establish new generalized fractional versions of the Hadamard and the Fejér–Hadamard integral inequalities for harmonically convex functions. Fractional integral operators involving an extended generalized Mittag-Leffler function which are further generalized via a monotone increasing function are utilized to get these generalized fractional versions. The results of this paper give several consequent fractional inequalities for harmonically convex functions for known fractional integral operators deducible from utilized generalized fractional integral operators.
Molecular analysis of methicillin-resistant Staphylococcus aureus isolates from four teaching hospitals in Iran: the emergence of novel MRSA clones
Authors: Firoozeh Farzaneh , Omidi Mitra , Saffari Mahmood , Sedaghat Hossein , Zibaei Mohammad 
Published: July 2020

Abstract
Background
The global spread of methicillin-resistant Staphylococcus aureus (MRSA) infections necessitates the use of validated methods for the identification and typing of this bacterium. This study aimed to determine the distribution of main molecular types of MRSA strain circulating among hospitalized patients in teaching hospitals in Isfahan and Kashan.

Methods
A total of 146 Staphylococcus aureus strains were isolated from patients in four teaching hospitals in Isfahan and Kashan during June 2017 to September 2018. The antimicrobial resistance patterns of Staphylococcus aureus strains were performed by disc diffusion method. The MRSA strains were identified phenotypically and confirmed by PCR assay. The prevalence of microbial surface components recognizing adhesive matrix molecules (MSCRAMMs) genes among MRSA strains was evaluated by multiplex PCR. The genotypes of MRSA strains were determined by multilocus sequence typing and SCCmec typing.

Results
Of 146 Staphylococcus aureus isolates, 24 (16.4%) isolates were identified as MRSA strains. According to antimicrobial susceptibility testing the highest resistance rates were seen for tetracycline, erythromycin, ciprofloxacin and gentamicin. All of Staphylococcus aureus isolates were susceptible to vancomycin whereas 3 (2.1%) isolates were resistant to linezolid. Three different SCCmec types were obtained among MRSA strains including 16 (66.7%) SCCmec type V, 3 (12.5%) SCCmec type III and 5 (20.8%) SCCmec type II. Of 24 MRSA isolates 20 (83.3%) carried MSCRAMMs genes including eno (70.8%), fib (54.1%), cna (25.0%), fnbB (16.6%), ebps 5 (20.8%), and the fnbA, bbp and clfA genes were not detected in any MRSA isolate. MLST analysis revealed 11 sequence types among MRSA isolates as follows: ST239, ST291, ST22, ST861, ST889, ST8, ST59, ST343, ST772, ST6 and ST1465. Also seven MLST-based clonal complexes (CCs) were identified among MRSA strains including: CC8, CC7, CC398, CC59, CC22, CC1 and CC5.

Conclusions
A relatively high diversity was found in MRSA genotypes in Kashan and Isfahan hospitals, and seven clonal complexes were identified. Pandemic MRSA clones including CC8 and CC22 were the most prevalent clones and the novel ST types including ST1465, ST861, ST 889 and ST772 are reported for the first time in Iran in the present study. In addition the high prevalence of MSCRAMMs genes in MRSA isolates demonstrates the high potential of these strains for pathogenicity.
Plasma circulating tumor DNA assessment reveals KMT2D as a potential poor prognostic factor in extranodal NK/T-cell lymphoma
Authors: Li Qiong , Zhang Wei , Li Jiali , Xiong Jingkang , Liu Jia , Chen Ting , Wen Qin , Zeng Yunjing , Gao Li , Gao Lei , Zhang Cheng , Kong Peiyan , Peng Xiangui , Liu Yao , Zhang Xi , Rao Jun 
Published: July 2020

Abstract
Background
The early detection of tumors upon initial diagnosis or during routine surveillance is important for improving survival outcomes. Here, we investigated the feasibility and clinical significance of circulating tumor DNA (ctDNA) detection for Extranodal NK/T-cell lymphoma, nasal type (ENTKL).

Methods
The plasma ctDNA assessment was based on blood specimens collected from 65 newly diagnosed patients with ENKTL in the hematology medical center of Xinqiao Hospital. Longitudinal samples collected under chemotherapy were also included. The gene mutation spectrum of ENKTL was analyzed via next generation sequencing.

Results
We found that the most frequently mutated genes were KMT2D (23.1%), APC (12.3%), ATM (10.8%), ASXL3 (9.2%), JAK3 (9.2%), SETD2 (9.2%), TP53 (9.2%) and NOTCH1 (7.7%). The mutation allele frequencies of ATM and JAK3 were significantly correlated with the disease stage, and mutated KMT2D, ASXL3 and JAK3 were positively correlated with the metabolic tumor burden of the patients. Compared with the tumor tissue, ctDNA profiling showed good concordance (93.75%). Serial ctDNA analysis showed that treatment with chemotherapy could decrease the number and mutation allele frequencies of the genes. Compared with PET/CT, ctDNA has more advantages in tracking residual disease in patients. In addition, patients with mutated KMT2D had higher expression compared with those with wild type, and mutated KMT2D predicted poor prognosis.

Conclusion
Our results unveil the mutation spectrum of ENKTL patients’ plasma, which can be used to monitor the disease status of the patients exactly, and KMT2D is the most frequently mutated gene with prognosis prediction value. The application of ctDNA sequencing can provide precision treatment strategies for patients.

Trial registration
This study is registered with chictr.org (ChiCTR1800014813, registered 7 February, 2018-Retrospectively registered).