bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dose adjustment of follicle-stimulating hormone (FSH) during ovarian stimulation as part of medically-assisted reproduction in clinical studies: a systematic review covering 10 years (2007–2017)
Authors: Fatemi Human , Bilger Wilma , Denis Deborah , Griesinger Georg , La Marca Antonio , Longobardi Salvatore , Mahony Mary , Yin Xiaoyan , D’Hooghe Thomas 
Published: May 2021

Abstract
Background
Individualization of the follicle-stimulating hormone (FSH) starting dose is considered standard clinical practice during controlled ovarian stimulation (COS) in patients undergoing assisted reproductive technology (ART) treatment. Furthermore, the gonadotropin dose is regularly adjusted during COS to avoid hyper- or hypo-ovarian response, but limited data are currently available to characterize such adjustments. This review describes the frequency and direction (increase/decrease) of recombinant-human FSH (r-hFSH) dose adjustment reported in clinical trials.

Methods
We evaluated the proportion of patients undergoing ART treatment who received ≥ 1 r-hFSH dose adjustments. The inclusion criteria included studies (published Sept 2007 to Sept 2017) in women receiving ART treatment that allowed dose adjustment within the study protocol and that reported ≥ 1 dose adjustments of r-hFSH; studies not allowing/reporting dose adjustment were excluded. Data on study design, dose adjustment and patient characteristics were extracted. Point-incidence estimates were calculated per study and overall based on pooled number of cycles with dose adjustment across studies. The Clopper–Pearson method was used to calculate 95% confidence intervals (CI) for incidence where adjustment occurred in < 10% of patients; otherwise, a normal approximation method was used.

Results
Initially, 1409 publications were identified, of which 318 were excluded during initial screening and 1073 were excluded after full text review for not meeting the inclusion criteria. Eighteen studies (6630 cycles) reported dose adjustment: 5/18 studies (1359 cycles) reported data for an unspecified dose adjustment (direction not defined), in 10/18 studies (3952 cycles) dose increases were reported, and in 11/18 studies (5123 cycles) dose decreases were reported. The studies were performed in women with poor, normal and high response, with one study reporting in oocyte donors and one in obese women. The median day that dose adjustment was permitted was Day 6 after the start of treatment. The point estimates for incidence (95% CI) for unspecified dose adjustment, dose increases, and dose decreases were 45.3% (42.7, 48.0), 19.2% (18.0, 20.5), and 9.5% (8.7, 10.3), respectively.

Conclusions
This systematic review highlights that, in studies in which dose adjustment was allowed and reported, the estimated incidence of r-hFSH dose adjustments during ovarian stimulation was up to 45%.
Extracellular vesicle-derived miRNA as a novel regulatory system for bi-directional communication in gut-brain-microbiota axis
Authors: Zhao Liang , Ye Yingze , Gu Lijuan , Jian Zhihong , Stary Creed M. , Xiong Xiaoxing 
Published: May 2021

AbstractThe gut-brain-microbiota axis (GBMAx) coordinates bidirectional communication between the gut and brain, and is increasingly recognized as playing a central role in physiology and disease. MicroRNAs are important intracellular components secreted by extracellular vesicles (EVs), which act as vital mediators of intercellular and interspecies communication. This review will present current advances in EV-derived microRNAs and their potential functional link with GBMAx. We propose that EV-derived microRNAs comprise a novel regulatory system for GBMAx, and a potential novel therapeutic target for modifying GBMAx in clinical therapy.
Capsazepine decreases corneal pain syndrome in severe dry eye disease
Authors: Fakih Darine , Guerrero-Moreno Adrian , Baudouin Christophe , Réaux-Le Goazigo Annabelle , Parsadaniantz Stéphane Mélik 
Published: May 2021

Abstract
Background
Dry eye disease (DED) is a multifactorial disease of the ocular surface accompanied by neurosensory abnormalities. Here, we evaluated the effectiveness of transient receptor potential vanilloid-1 (TRPV1) blockade to alleviate ocular pain, neuroinflammation, and anxiety-like behavior associated with severe DED.

Methods
Chronic DED was induced by unilateral excision of the Harderian and extraorbital lacrimal glands of adult male mice. Investigations were conducted at 21 days after surgery. The mRNA levels of TRPV1, transient receptor potential ankyrin-1 (TRPA1), and acid-sensing ion channels 1 and 3 (ASIC1 and ASIC3) in the trigeminal ganglion (TG) were evaluated by RNAscope in situ hybridization. Multi-unit extracellular recording of ciliary nerve fiber activity was used to monitor spontaneous and stimulated (cold, heat, and acid) corneal nerve responsiveness in ex vivo eye preparations. DED mice received topical instillations of the TRPV1 antagonist (capsazepine) twice a day for 2 weeks from d7 to d21 after surgery. The expression of genes involved in neuropathic and inflammatory pain was evaluated in the TG using a global genomic approach. Chemical and mechanical corneal nociception and spontaneous ocular pain were monitored. Finally, anxiety-like behaviors were assessed by elevated plus maze and black and white box tests.

Results
First, in situ hybridization showed DED to trigger upregulation of TRPV1, TRPA1, ASIC1, and ASIC3 mRNA in the ophthalmic branch of the TG. DED also induced overexpression of genes involved in neuropathic and inflammatory pain in the TG. Repeated instillations of capsazepine reduced corneal polymodal responsiveness to heat, cold, and acidic stimulation in ex vivo eye preparations. Consistent with these findings, chronic capsazepine instillation inhibited the upregulation of genes involved in neuropathic and inflammatory pain in the TG of DED animals and reduced the sensation of ocular pain, as well as anxiety-like behaviors associated with severe DED.

Conclusion
These data provide novel insights on the effectiveness of TRPV1 antagonist instillation in alleviating abnormal corneal neurosensory symptoms induced by severe DED, opening an avenue for the repositioning of this molecule as a potential analgesic treatment for patients suffering from chronic DED.
Birth weight and childhood obesity: effect modification by residence and household wealth
Authors: Andriani Helen 
Published: May 2021

Abstract
Background
There are both genetic and environmental factors which contribute to a child’s chances of being obese. When low birth weight (LBW) has been specifically evaluated relative to its association with childhood obesity, the results have produced conflicting findings. This study aims to describe the relationship between birth weight and childhood obesity and investigate the influence that residence and household wealth has on this relationship.

Methods
I performed a secondary analysis on the 2013 Riskesdas (or Basic Health Research), a cross-sectional, nationally representative survey of the Indonesian population. Height, weight, information regarding child’s birth weight, and basic characteristics of the study population were collected from parents with children aged 0 to 5 years (n = 63,237) in 2013. The exposure was child’s birth weight and the outcomes were child’s current weight, BMI z-score, and obesity. Data were analyzed by using multiple linear regression and multiple logistic regression.

Results
I found a significant increase in the weight, BMI z-score, and risk of childhood obesity to be associated with LBW. LBW children in rural area were associated with higher BMI z-score (mean ± standard error: 1.44 ± 0.02) and higher odds (odds ratio (95% confidence interval): 7.46 (6.77–8.23)) of obesity than those in urban area. LBW children from low class families were associated with higher BMI z-score (1.79 ± 0.04) and had higher odds (14.79 (12.47–17.54)) of obesity than those from middle class and wealthy families.

Conclusions
Effective prevention and intervention to childhood obesity as early as possible are imperative. As far as this study was concerned, efforts, policies, and targets are required to reduce the prevalence of LBW. Children born of LBW, who live in a rural area and from low income families, should be emphatically intervened as early as possible.
COVID-19 and periodontitis: reflecting on a possible association
Authors: Campisi Giuseppina , Bizzoca Maria Eleonora , Lo Muzio Lorenzo 
Published: May 2021

AbstractRecent studies have demonstrated a relationship between the severe clinical course of COVID-19 and other chronic diseases such as: cardiovascular disease, hypertension, diabetes mellitus, obesity and chronic renal disease. It may be possible to extend this association to a common and chronic oral disease in adults: periodontitis. Alternatively, the latter could be simply related to the systemic chronic diseases cited above, as already observed in the non-COVID-19 literature. In order to provide an overview and their opinion, the authors in this perspective article will report and discuss the most recent references of interest relating to COVID-19 and periodontitis pathophysiology. Within such a narrative review, the authors will hypothesize that the association between chronic periodontitis and COVID-19 could exist via two pathways: a direct link, through the ACEII and CD147 receptors used by the virus to infect the cells, which would occur in greater numbers in cases of periodontitis (thereby favoring a SARS-CoV-2 infection); and/or an indirect pathway involving the overexpression of inflammatory molecules, especially IL-6 and IL-17. An expression of the latter has been found to play a role in periodontitis, in addition to severe cases of COVID-19, although it is still unclear if it plays a direct role in the worsening of the clinical course.
Warburg effect-promoted exosomal circ_0072083 releasing up-regulates NANGO expression through multiple pathways and enhances temozolomide resistance in glioma
Authors: Ding Chenyu , Yi Xuehan , Chen Xiangrong , Wu Zanyi , You Honghai , Chen Xiaoyong , Zhang Gaoqi , Sun Yong , Bu Xingyao , Wu Xiyue , Lin Zhangya , Gu Jianjun , Lin Yuanxiang , Kang Dezhi 
Published: May 2021

Abstract
Background
Temozolomide (TMZ) resistance limits its application in glioma. Exosome can carry circular RNAs (circRNAs) to regulate drug resistance via sponging microRNAs (miRNAs). miRNAs can control mRNA expression by regulate the interaction with 3’UTR and methylation. Nanog homeobox (NANOG) is an important biomarker for TMZ resistance. Hitherto, it is unknown about the role of exosomal hsa_circ_0072083 (circ_0072083) in TMZ resistance in glioma, and whether it is associated with NANOG via regulating miRNA sponge and methylation.

Methods
TMZ-resistant (n = 36) and sensitive (n = 33) patients were recruited. The sensitive cells and constructed resistant cells were cultured and exposed to TMZ. circ_0072083, miR-1252-5p, AlkB homolog H5 (ALKBH5) and NANOG levels were examined via quantitative reverse transcription polymerase chain reaction and western blot. The half maximal inhibitory concentration (IC50) of TMZ, cell proliferation, apoptosis, migration and invasion were analyzed via Cell Counting Kit-8, colony formation, flow cytometry, wound healing and transwell assays. The in vivo function was assessed using xenograft model. The N6-methyladenosine (m6A) level was analyzed via methylated RNA immunoprecipitation (MeRIP). Target relationship was investigated via dual-luciferase reporter assay and RNA immunoprecipitation. Warburg effect was investigated via lactate production, glucose uptake and key enzymes expression. Exosome was isolated and confirmed via transmission electron microscopy and specific protein expression.

Results
circ_0072083 expression was increased in TMZ-resistant glioma tissues and cells. circ_0072083 knockdown restrained the resistance of resistant cells via decreasing IC50 of TMZ, proliferation, migration, invasion and xenograft tumor growth and increasing apoptosis. circ_0072083 silence reduced NANOG expression via blocking ALKBH5-mediated demethylation. circ_0072083 could regulate NANOG and ALKBH5 via targeting miR-1252-5p to control TMZ resistance. Warburg effect promoted the release of exosomal circ_0072083 in resistant cells. Exosomal circ_0072083 from resistant cells increased the resistance of sensitive cells to TMZ in vitro and xenograft model. Exosomal circ_0072083 level was enhanced in resistant patients, and it had a diagnostic value and indicated a lower overall survival in glioma.

Conclusion
Exosomal circ_0072083 promoted TMZ resistance via increasing NANOG via regulating miR-1252-5p-mediated degradation and demethylation in glioma.
What are the applications of single-cell RNA sequencing in cancer research: a systematic review
Authors: Li Lvyuan , Xiong Fang , Wang Yumin , Zhang Shanshan , Gong Zhaojian , Li Xiayu , He Yi , Shi Lei , Wang Fuyan , Liao Qianjin , Xiang Bo , Zhou Ming , Li Xiaoling , Li Yong , Li Guiyuan , Zeng Zhaoyang , Xiong Wei , Guo Can 
Published: May 2021

AbstractSingle-cell RNA sequencing (scRNA-seq) is a tool for studying gene expression at the single-cell level that has been widely used due to its unprecedented high resolution. In the present review, we outline the preparation process and sequencing platforms for the scRNA-seq analysis of solid tumor specimens and discuss the main steps and methods used during data analysis, including quality control, batch-effect correction, normalization, cell cycle phase assignment, clustering, cell trajectory and pseudo-time reconstruction, differential expression analysis and gene set enrichment analysis, as well as gene regulatory network inference. Traditional bulk RNA sequencing does not address the heterogeneity within and between tumors, and since the development of the first scRNA-seq technique, this approach has been widely used in cancer research to better understand cancer cell biology and pathogenetic mechanisms. ScRNA-seq has been of great significance for the development of targeted therapy and immunotherapy. In the second part of this review, we focus on the application of scRNA-seq in solid tumors, and summarize the findings and achievements in tumor research afforded by its use. ScRNA-seq holds promise for improving our understanding of the molecular characteristics of cancer, and potentially contributing to improved diagnosis, prognosis, and therapeutics.
Deconvolution of cell type-specific drug responses in human tumor tissue with single-cell RNA-seq
Authors: Zhao Wenting , Dovas Athanassios , Spinazzi Eleonora Francesca , Levitin Hanna Mendes , Banu Matei Alexandru , Upadhyayula Pavan , Sudhakar Tejaswi , Marie Tamara , Otten Marc L. , Sisti Michael B. , Bruce Jeffrey N. , Canoll Peter , Sims Peter A. 
Published: May 2021

Abstract
Background
Preclinical studies require models that recapitulate the cellular diversity of human tumors and provide insight into the drug sensitivities of specific cellular populations. The ideal platform would enable rapid screening of cell type-specific drug sensitivities directly in patient tumor tissue and reveal strategies to overcome intratumoral heterogeneity.

Methods
We combine multiplexed drug perturbation in acute slice culture from freshly resected tumors with single-cell RNA sequencing (scRNA-seq) to profile transcriptome-wide drug responses in individual patients. We applied this approach to drug perturbations on slices derived from six glioblastoma (GBM) resections to identify conserved drug responses and to one additional GBM resection to identify patient-specific responses.

Results
We used scRNA-seq to demonstrate that acute slice cultures recapitulate the cellular and molecular features of the originating tumor tissue and the feasibility of drug screening from an individual tumor. Detailed investigation of etoposide, a topoisomerase poison, and the histone deacetylase (HDAC) inhibitor panobinostat in acute slice cultures revealed cell type-specific responses across multiple patients. Etoposide has a conserved impact on proliferating tumor cells, while panobinostat treatment affects both tumor and non-tumor populations, including unexpected effects on the immune microenvironment.

Conclusions
Acute slice cultures recapitulate the major cellular and molecular features of GBM at the single-cell level. In combination with scRNA-seq, this approach enables cell type-specific analysis of sensitivity to multiple drugs in individual tumors. We anticipate that this approach will facilitate pre-clinical studies that identify effective therapies for solid tumors.
Gambogic acid protects LPS-induced apoptosis and inflammation in a cell model of neonatal pneumonia through the regulation of TrkA/Akt signaling pathway
Authors: Gao Xu , Dai Jingya , Li Guifang , Dai Xinya 
Published: May 2021

Abstract
Objective
In this work, we investigated the effects of gambogic acid (GA) on lipopolysaccharide (LPS)-induced apoptosis and inflammation in a cell model of neonatal pneumonia.

Method
Human WI-38 cells were maintained in vitro and incubated with various concentrations of GA to examine WI-38 survival. GA-preincubated WI-38 cells were then treated with LPS to investigate the protective effects of GA on LPS-induced death, apoptosis and inflammation. Western blot assay was utilized to analyze the effect of GA on tropomyosin receptor kinase A (TrkA) signaling pathway in LPS-treated WI-38 cells. In addition, human AKT serine/threonine kinase 1 (Akt) gene was knocked down in WI-38 cells to further investigate the associated genetic mechanisms of GA in protecting LPS-induced inflammation and apoptosis.

Results
Pre-incubating WI-38 cells with low and medium concentrations GA protected LPS-induced cell death, apoptosis and inflammatory protein productions of IL-6 and MCP-1. Using western blot assay, it was demonstrated that GA promoted TrkA phosphorylation and Akt activation in LPS-treated WI-38 cells. Knocking down Akt gene in WI-38 cells showed that GA-associated protections against LPS-induced apoptosis and inflammation were significantly reduced.

Conclusions
GA protected LPS-induced apoptosis and inflammation, possibly through the activations of TrkA and Akt signaling pathway. This work may broaden our understanding on the molecular mechanisms of human neonatal pneumonia.
Variations in vertical mucosal thickness at edentulous ridge according to site and gender measured by cone-beam computed tomography
Authors: Munakata Motohiro , Nagata Koudai , Sanda Minoru , Kawamata Ryota , Sato Daisuke , Yamaguchi Kikue 
Published: May 2021

Abstract
Background
The vertical thickness of the peri-implant mucosa is associated with the amount of post treatment marginal bone loss. However, the variations in mucosal thickness at the different edentulous sites have been sparsely documented. The purpose of the study was to conduct a survey of the frequency distribution of variations in mucosal thickness at the different sites of the edentulous alveolar ridge and to compare them according to gender.
Our study included 125 partially edentulous patients having a total of 296 implant sites. Cone-beam computed tomography (CBCT) scans were obtained by placing a diagnostic template with a radiopaque crown indicator on the ridge to determine the mucosal thickness at the crest of the alveolar ridge.

Results
The mucosal thickness was 3.0±1.3 mm in the maxilla, which was significantly greater than the mucosal thickness of 2.0±1.0 mm in the mandible (p<0.001). In both the maxilla and the mandible, the mucosa was the thickest in the anterior region, followed by the premolar and molar regions. Sites were further classified into two groups based on whether the mucosal thickness was greater than 2 mm. In the mandible, more than half of the sites showed a mucosal thickness of 2 mm or less.

Conclusions
Although this study was a limited preoperative study, the vertical mucosal thickness at the edentulous ridge differed between the maxillary and mandibular regions. The majority of sites in the mandibular molar region had a mucosal thickness of less than 2 mm. Practitioners might be able to develop an optimal dental implant treatment plan for long-term biologic and esthetic stability by considering these factors.
Elastic FWI for orthorhombic media with lithologic constraints applied via machine learning
Authors: Singh Sagar , Tsvankin Ilya , Zabihi Naeini Ehsan 
Published: May 2021

Full-waveform inversion (FWI) of 3D wide-azimuth data for elastic orthorhombic media suffers from parameter trade-offs which cannot be overcome without constraining the model-updating procedure. We present an FWI methodology that incorporates geologic constraints to reduce the inversion nonlinearity and increase the resolution of parameter estimation for orthorhombic models. These constraints are obtained from well logs, which can provide rock-physics relationships for different geologic facies. Because the locations of the available well logs are usually sparse, a supervised machine-learning (ML) algorithm (Support Vector Machine) is employed to account for lateral heterogeneity in building the lithologic constraints. The advantages of the facies-based FWI are demonstrated on the modified SEG-EAGE 3D overthrust model, which is made orthorhombic with the symmetry planes that coincide with the Cartesian coordinate planes. We employ a velocity-based parameterization, whose suitability for FWI was studied using the radiation-pattern analysis. Application of the facies-based constraints substantially increases the resolution of the P- and S-wave vertical velocities ([Formula: see text], [Formula: see text], and [Formula: see text]) and, therefore, of the depth scale of the model. Improvements are also observed for the P-wave horizontal and normal-moveout velocities ([Formula: see text], [Formula: see text], [Formula: see text], and [Formula: see text]) and the S-wave horizontal velocity [Formula: see text]. However, the velocity [Formula: see text] that depends on Tsvankin’s parameter [Formula: see text] defined in the horizontal plane is not well recovered from the surface data. On the whole, the developed algorithm achieves a much higher spatial resolution compared to unconstrained FWI, even in the absence of recorded frequencies below 2 Hz.