bluuebunny/crossref_metadata_2025_split huggingface dataset:
X chromosome escapee genes are involved in ischemic sexual dimorphism through epigenetic modification of inflammatory signals
Authors: Qi Shaohua , Al Mamun Abdullah , Ngwa Conelius , Romana Sharmeen , Ritzel Rodney , Arnold Arthur P. , McCullough Louise D. , Liu Fudong 
Published: March 2021

Abstract
Background
Stroke is a sexually dimorphic disease. Previous studies have found that young females are protected against ischemia compared to males, partially due to the protective effect of ovarian hormones, particularly estrogen (E2). However, there are also genetic and epigenetic effects of X chromosome dosage that contribute to stroke sensitivity and neuroinflammation after injury, especially in the aged. Genes that escape from X chromosome inactivation (XCI) contribute to sex-specific phenotypes in many disorders. Kdm5c and kdm6a are X escapee genes that demethylate H3K4me3 and H3K27me3, respectively. We hypothesized that the two demethylases play critical roles in mediating the stroke sensitivity.

Methods
To identify the X escapee genes involved in stroke, we performed RNA-seq in flow-sorted microglia from aged male and female wild type (WT) mice subjected to middle cerebral artery occlusion (MCAO). The expression of these genes (kdm5c/kdm6a) were confirmed in four core genotypes (FCG) mice and in post-mortem human stroke brains by immunohistochemistry (IHC), Western blot, and RT-PCR. Chromatin immunoprecipitation (ChIP) assays were conducted to detect DNA levels of inflammatory interferon regulatory factor (IRF) 4/5 precipitated by histone H3K4 and H3K27 antibodies. Manipulation of kdm5c/kdm6a expression with siRNA or lentivirus was performed in microglial culture, to determine downstream pathways and examine the regulatory roles in inflammatory cytokine production.

Results
Kdm5c and kdm6a mRNA levels were significantly higher in aged WT female vs. male microglia, and the sex difference also existed in ischemic brains from FCG mice and human stroke patients. The ChIP assay showed the IRF 4/5 had higher binding levels to demethylated H3K4 or H3K27, respectively, in female vs. male ischemic microglia. Knockdown or over expression of kdm5c/kdm6a with siRNA or lentivirus altered the methylation of H3K4 or H3K27 at the IRF4/5 genes, which in turn, impacted the production of inflammatory cytokines.

Conclusions
The KDM-Histone-IRF pathways are suggested to mediate sex differences in cerebral ischemia. Epigenetic modification of stroke-related genes constitutes an important mechanism underlying the ischemic sexual dimorphism.
1,25-Dihydroxyvitamin D3 modulates adipogenesis of human adipose-derived mesenchymal stem cells dose-dependently
Authors: Salehpour Amin , Hedayati Mehdi , Shidfar Farzad , Neshatbini Tehrani Asal , Farshad Ali Asghar , Mohammadi Saeed 
Published: March 2021

Abstract
Purpose
1,25-dihydroxyvitamin D3 may regulate adipogenesis in adipocytes in-vitro, but little is known about possible molecular mechanisms related to the inhibitory effect of 1,25-dihydroxyvitamin D3 on adipogenesis in humans҆ adipose tissue.

Methodology
In this study, human adipose-derived mesenchymal stem cells (hASCs) were cultured for 14 days in adipogenic differentiation media containing concentrations of 1,25-dihydroxyvitamin D3 (10−10–10−8 M). The extent of adipogenic differentiation in ASCs was assessed by Oil Red O staining and quantitative polymerase chain reaction (PCR) to determine expression levels of key adipogenic markers.

Results
Our results showed that vitamin D receptor (VDR), as a mediator of most actions of 1,25-dihydroxyvitamin D3, glucose trasporter-4 (GLUT4),and fatty acid binding protein-4 (FABP4) was expressed in vitamin D-treated hASCs. However, the protein level of these markers was lower than the control group. Treatment of human preadipocytes with 1,25-dihydroxyvitamin D3 significantly altered expression of adipogenic markers and triglyceride accumulation in a dose-dependent manner. 1,25-dihydroxyvitamin D3 at concentration of 10−8 M enhanced expression of sterol regulatory element-binding protein-1c (SREBP1c), CCAAT-enhancer-binding protein-β (C/EBPβ), a mitotic clonal expansion, peroxisome proliferator-activated receptor-gamma (PPARγ), fatty acid synthase (FASN), a marker of de novo lipogenesis,and lipoprotein lipase (LPL).

Conclusion
Our findings revealed that 1,25-dihydroxyvitamin D3 may provoke adipocyte development in critical periods of adipogenesis at concentration of 10−8 M, thereby leading to a greater risk of obesity in adulthood and an augmented risk of obesity-related diseases including diabetes, cardiovascular diseases, and some cancers.
Clinical outcomes after mini-hook plate fixation for small avulsion fractures around the interphalangeal or metacarpophalangeal joints of the hand
Authors: Lee Jung Il , Park Ki-Chul , So Hyun Soo , Lee Duk Hee 
Published: March 2021

Abstract
Background
Mini-hook plate has been described for the treatment of various small avulsion fragments in the hand. This retrospective study aimed to evaluate clinical outcomes after mini-hook plate fixation in patients with an avulsion fracture around the interphalangeal or metacarpophalangeal joints of the hand.

Methods
Nineteen patients with avulsion fractures around the interphalangeal or metacarpophalangeal joints of the hand were included in this study. Seven patients had a mallet fracture, and 12 patients had other phalangeal avulsion fractures including central slip, collateral ligament, volar plate, and flexor avulsion fractures. The osseous union and functional outcomes, including finger joint motion, joint stability, pinching strength, and the disabilities of the arm, shoulder, and hand score, were evaluated.

Results
The mean duration of follow-up was 33.8 months. All patients in mallet and other phalangeal avulsion fractures achieved osseous union between the avulsion fragment and phalangeal bone, and there was no joint subluxation. There were no significant differences in the disabilities of the arm, shoulder, and hand scores. However, the patients with mallet fracture have lower mean percentage values of the total active range of motion and pinching strength than other phalangeal avulsion fractures. We abandoned this procedure in mallet fractures because the early results after mini-hook plate fixation in mallet fractures appeared unfavorable.

Conclusion
These results suggest that the mini-hook plate fixation can provide sufficient stability and good clinical outcomes in those with phalangeal avulsion fractures. However, the outcomes for mallet fractures were not as good as those for other phalangeal avulsion fractures.
Determination of the optimal dose of ephedrine in the treatment of arterial hypotension due to general anesthesia in neonates and infants below 6 months old: the ephedrine study protocol for a randomized, open-label, controlled, dose escalation trial
Authors: Szostek A. S. , Boucher P. , Subtil F. , Zerzaihi O. , Saunier C. , de Queiroz Siqueira M. , Merquiol F. , Martin P. , Granier M. , Gerst A. , Lambert A. , Storme T. , Chassard D. , Nony P. , Kassai B. , Gaillard S. 
Published: March 2021

Abstract
Background
Arterial hypotension induced by general anesthesia is commonly identified as a risk factor of morbidity, especially neurological, after cardiac or noncardiac surgery in adults and children. Intraoperative hypotension is observed with sevoflurane anesthesia in children, in particular in neonates, infants younger than 6 months, and preterm babies. Ephedrine is commonly used to treat intraoperative hypotension. It is an attractive therapeutic, due to its dual action on receptors alpha and beta and its possible peripheral intravenous infusion. There are few data in the literature on the use of ephedrine in the context of pediatric anesthesia. The actual recommended dose of ephedrine (0.1 to 0.2 mg/Kg) frequently leads to a therapeutic failure in neonates and infants up to 6 months of age. The use of higher doses would probably lead to a better correction of hypotension in this population.
The objective of our project is to determine the optimal dose of ephedrine for the treatment of hypotension after induction of general anesthesia with sevoflurane, in neonates and infants up to 6 months of age.

Methods
The ephedrine study is a prospective, randomized, open-label, controlled, dose-escalation trial. The dose escalation consists of 6 successive cohorts of 20 subjects. The doses studied are 0.6, 0.8, 1, 1.2, and 1.4 mg/kg. The dose chosen as the reference is 0.1 mg/kg, the actual recommended dose. Neonates and infants younger than 6 months, males and females, including preterm babies who undergo a surgery with general anesthesia inducted with sevoflurane were eligible. Parents of the subject were informed. Then, the subjects were randomized if presenting a decrease in mean blood pressure superior to 20% of their initial mean blood pressure (before induction of anesthesia), despite a vascular filling with sodium chloride 0.9%. The primary outcome is the success of the therapy defined as an mBP superior to 80% of the baseline mBP (prior to anesthesia) within 10 min post ephedrine administration. The subjects were followed-up for 3 days postanesthesia.

Discussion
This study is the first randomized, controlled trial intending to determine the optimal dose of ephedrine to treat hypotension in neonates and infants below 6 months old.

Trial registration
ClinicalTrials.gov NCT02384876. Registered on March 2015.
The effect of crop species on DNase-producing bacteria in two soils
Authors: Kamino Leila N. , Gulden Robert H. 
Published: March 2021

Abstract
Purpose
Extracellular deoxyribonucleases (exDNases) from microbial origin contribute substantially to the restriction of extracellular DNA (exDNA) in the soil. Hence, it is imperative to understand the diversity of bacterial species capable of performing this important soil function and how crop species influence their dynamics in the soil. The present study investigates the occurrence of DNase-producing bacteria (DPB) in leachate samples obtained from soils in which the crop species of alfalfa (Medicago sativa L.), canola (Brassica napus L.), soybean (Glycine max [L.] Merr.) and wheat (Triticum aestivum L.) were raised in a growth room.

Methods
Selective media containing methyl green indicator was used to screen for DPB from leachate samples, whereas the 16S rRNA sequence analysis was employed to identify the isolates.

Results
The proportion of culturable DPB ranged between 5.72 and 40.01%; however, we did observe specific crop effects that shifted throughout the growing period. In general, higher proportions of exDNase producers were observed when the soils had lower nutrient levels. On using the 16S rRNA to classify the DPB isolates, most isolates were found to be members of the Bacillus genera, while other groups included Chryseobacterium, Fictibacillus, Flavobacterium, Microbacterium, Nubsella, Pseudomonas, Psychrobacillus, Rheinheimera, Serratia and Stenotrophomonas. Five candidate exDNase/nuclease-encoding proteins were also identified from Bacillus mycoides genomes using online databases.

Conclusion
Results from this study showed that crop species, growth stage and soil properties were important factors shaping the populations of DPB in leachate samples; however, soil properties seemed to have a greater influence on the trends observed on these bacterial populations. It may be possible to target soil indigenous bacteria that produce exDNases through management to decrease potential unintended effects of transgenes originating from genetically modified organisms (GMOs) or other introduced nucleic acid sequences in the environment.
Morusin induces osteogenic differentiation of bone marrow mesenchymal stem cells by canonical Wnt/β-catenin pathway and prevents bone loss in an ovariectomized rat model
Authors: Chen Ming , Han Hui , Zhou Siqi , Wen Yinxian , Chen Liaobin 
Published: March 2021

Abstract
Background
Osteoporosis (OP) is a metabolic bone disease due to the imbalance of osteogenesis and bone resorption, in which, bone marrow mesenchymal stem cells (BMSCs) have a significant effect as the seed cells. Recent research has shown the function of Morusin on inhibiting osteoclast differentiation in vitro. However, whether Morusin can regulate the osteogenic differentiation in addition to the proliferation of BMSCs remains unclear.

Methods
BMSCs were isolated from 4-week-old Wistar rats and then treated with different concentrations of Morusin for 3, 5, 7, and 14 days. The proliferation of BMSCs was detected by MTT assay. The effect of Morusin on osteogenic differentiation of BMSCs was detected by RT-qPCR, Western blotting, ALP, and Alizarin Red staining. The effect of Morusin on Wnt/β-catenin signaling pathway was analyzed by RT-qPCR, Western blotting, and immunofluorescence. Finally, in the ovariectomy-induced osteoporosis model, the anti-osteoporosis activity of Morusin was determined by micro-CT, HE, and immunohistochemistry.

Results
The results showed the function of 2.5–10 μM Morusin in the promotion of the proliferation in addition to osteogenic differentiation of BMSCs. Moreover, it also has an impact in activating the Wnt/β-catenin signaling pathway via inhibition of β-catenin phosphorylation as well as promotion of its nuclear translocation. Upon Dickkopf-related protein-1 (DKK-1, an inhibitor of the Wnt/β-catenin signaling pathway) was added to the Morusin, Morusin had a decreased stimulatory osteogenic effect on BMSCs. Finally, in the rat OP model, we found that Morusin could also exert anti-osteoporosis activity in vivo.

Conclusions
This study indicates the ability of Morusin in the promotion of osteogenic differentiation of BMSCs via the activation of Wnt/β-catenin signaling pathway and also shows the potential of Morusin to be an agent for osteoporosis treatment.
Mitochondria and metabolic transitions in cardiomyocytes: lessons from development for stem cell-derived cardiomyocytes
Authors: Garbern Jessica C. , Lee Richard T. 
Published: March 2021

AbstractCurrent methods to differentiate cardiomyocytes from human pluripotent stem cells (PSCs) inadequately recapitulate complete development and result in PSC-derived cardiomyocytes (PSC-CMs) with an immature or fetal-like phenotype. Embryonic and fetal development are highly dynamic periods during which the developing embryo or fetus is exposed to changing nutrient, oxygen, and hormone levels until birth. It is becoming increasingly apparent that these metabolic changes initiate developmental processes to mature cardiomyocytes. Mitochondria are central to these changes, responding to these metabolic changes and transitioning from small, fragmented mitochondria to large organelles capable of producing enough ATP to support the contractile function of the heart. These changes in mitochondria may not simply be a response to cardiomyocyte maturation; the metabolic signals that occur throughout development may actually be central to the maturation process in cardiomyocytes. Here, we review methods to enhance maturation of PSC-CMs and highlight evidence from development indicating the key roles that mitochondria play during cardiomyocyte maturation. We evaluate metabolic transitions that occur during development and how these affect molecular nutrient sensors, discuss how regulation of nutrient sensing pathways affect mitochondrial dynamics and function, and explore how changes in mitochondrial function can affect metabolite production, the cell cycle, and epigenetics to influence maturation of cardiomyocytes.
Value of conventional magnetic resonance imaging texture analysis in the differential diagnosis of benign and borderline/malignant phyllodes tumors of the breast
Authors: Li Xiaoguang , Jiang Nianping , Zhang Chunlai , Luo Xiangguo , Zhong Peng , Fang Jingqin 
Published: March 2021

Abstract
Background
The purpose of this study was to determine the potential value of magnetic resonance imaging (MRI) texture analysis (TA) in differentiating between benign and borderline/malignant phyllodes tumors of the breast.

Methods
The preoperative MRI data of 25 patients with benign phyllodes tumors (BPTs) and 19 patients with borderline/malignant phyllodes tumors (BMPTs) were retrospectively analyzed. A gray-level histogram and gray-level cooccurrence matrix (GLCM) were used for TA with fat-suppressed T2-weighted imaging (FS-T2WI), diffusion-weighted imaging (DWI), apparent diffusion coefficient (ADC) images, and 2- and 7-min postcontrast T1W images on dynamic contrast-enhanced MRI (DCE-T1WI2min and DCE-T1WI7min) between BPTs and BMPTs. Independent sample t-test and Mann-Whitney U test were performed for intergroup comparison. A regression model was established by using binary logistic regression analysis, and receiver operating characteristic (ROC) curve analysis was carried out to evaluate diagnostic efficiency.

Results
For ADC images, the texture parameters angular second moment (ASM), correlation, contrast, entropy and the minimum gray values of ADC images (ADCMinimum) showed significant differences between the BPT group and BMPT group (all p<0.05). The parameter entropy of FS-T2WI and the maximum gray values and kurtosis of the tumor solid region of DCE-T1WI7min also showed significant differences between these two groups. Except for ADCMinimum, angular second moment of FS-T2WI (FS-T2WIASM), and the maximum gray values of DCE-T1WI7min (DCE-T1WI7min-Maximum) of the tumor solid region, the AUC values of other positive texture parameters mentioned above were greater than 0.75. Binary logistic regression analysis demonstrated that the contrast of ADC images (ADCContrast) and entropy of FS-T2WI (FS-T2WIEntropy) could be considered independent texture variables for the differential diagnosis of BPTs and BMPTs. Combined, the AUC of these parameters was 0.891 (95% CI: 0.793–0.988), with a sensitivity of 84.2% and a specificity of up to 89.0%.

Conclusion
Texture analysis could be helpful in improving the diagnostic efficacy of conventional MR images in differentiating BPTs and BMPTs.
Patient Preferences for Outcomes Following DCIS Management Strategies: A Discrete Choice Experiment
Authors: Chapman Brittany M. , Yang Jui-Chen , Gonzalez Juan Marcos , Havrilesky Laura , Reed Shelby D. , Hwang E. Shelley 
Published: March 2021

PURPOSE: Ductal carcinoma in situ (DCIS), a nonobligate precursor of breast cancer, is often aggressively managed with multimodal therapy. However, there is limited research on patients' preferences for trade-offs among treatment-related outcomes such as breast appearance, side effects, and future cancer risk. We sought to investigate whether women consider treatment features aside from cancer risk when making treatment choices for ductal carcinoma in situ and if so, to what degree other features influence these decisions. METHODS: A discrete choice experiment was administered to participants in a comprehensive cancer screening mammography clinic. The experimental design was used to generate constructed health profiles resulting from different management strategies. Health profiles were defined by breast appearance, severity of infection within the first year, chronic pain, hot flashes, and risk of developing or dying from breast cancer within 10 years. RESULTS: One hundred ninety-four women without a personal history of breast cancer completed the choice task. Across 10 choice questions, 29% always selected the health profile with a lower risk of invasive breast cancer (ie, dominated on cancer risk), regardless of the effects of treatment. For nonrisk dominators, breast cancer risk remained the most important factor but was closely followed by chronic pain (24% [95% CI, 20 to 28]) and infection (22% [95% CI, 18 to 25]). Depending on treatment outcomes, the tolerable increase in breast cancer risk was as high as 3.4%. CONCLUSION: Most women were willing to make some trade-offs between invasive cancer risk and treatment-related outcomes. Our findings highlight the importance of shared decision-making weighing risks and benefits between patient and provider management of low-risk disease.
Time to Treatment Initiation for Breast Cancer During the 2020 COVID-19 Pandemic
Authors: Hawrot Kathryn , Shulman Lawrence N. , Bleiweiss Ira J. , Wilkie Elizabeth J. , Frosch Zachary A. K. , Jankowitz Rachel C. , Laughlin Amy I. 
Published: March 2021

PURPOSE: The COVID-19 pandemic has posed significant pressures on healthcare systems, raising concern that related care delays will result in excess cancer-related deaths. Because data regarding the impact on patients with breast cancer are urgently needed, we aimed to provide a preliminary estimate of the impact of COVID-19 on time to treatment initiation (TTI) for patients newly diagnosed with breast cancer cared for at a large academic center. METHODS: We conducted a retrospective study of patients with newly diagnosed early-stage breast cancer between January 1, 2020, and May 15, 2020, a time period during which care was affected by COVID-19, and an unaffected cohort diagnosed between January 1, 2018 and May 15, 2018. Outcomes included patient volume, TTI, and initial treatment modality. Adjusted TTI was compared using multivariable linear regression. RESULTS: Three hundred sixty-six patients were included. There was an 18.8% decrease in patient volume in 2020 (n = 164) versus 2018 (n = 202). There was no association between time of diagnosis (pre-COVID-19 or during COVID-19) and adjusted TTI ( P = .926). There were fewer in situ diagnoses in the 2020 cohort ( P = .040). There was increased use of preoperative systemic therapy in 2020 (43.9% overall, 20.7% chemotherapy, and 23.2% hormonal therapy) versus 2018 (16.4% overall, 12.4% chemotherapy, and 4.0% hormonal therapy) ( P < .001). CONCLUSION: TTI was maintained among patients diagnosed and treated for breast cancer during the COVID-19 pandemic at a single large academic center. There was a decrease in patient volume, specifically in patients with in situ disease and a shift in initial therapy toward the use of preoperative hormonal therapy.