bluuebunny/crossref_metadata_2025_split huggingface dataset:
A CRISPR RNA-binding protein screen reveals regulators of RUNX1 isoform generation
Authors: Davis Amanda G. , Einstein Jaclyn M. , Zheng Dinghai , Jayne Nathan D. , Fu Xiang-Dong , Tian Bin , Yeo Gene W. , Zhang Dong-Er 
Published: March 2021

Abstract
The proper balance of hematopoietic stem cell (HSC) self-renewal and differentiation is critical for normal hematopoiesis and is disrupted in hematologic malignancy. Among regulators of HSC fate, transcription factors have a well-defined central role, and mutations promote malignant transformation. More recently, studies have illuminated the importance of posttranscriptional regulation by RNA-binding proteins (RBPs) in hematopoiesis and leukemia development. However, the RBPs involved and the breadth of regulation are only beginning to be elucidated. Furthermore, the intersection between posttranscriptional regulation and hematopoietic transcription factor function is poorly understood. Here, we studied the posttranscriptional regulation of RUNX1, a key hematopoietic transcription factor. Alternative polyadenylation (APA) of RUNX1 produces functionally antagonistic protein isoforms (RUNX1a vs RUNX1b/c) that mediate HSC self-renewal vs differentiation, an RNA-processing event that is dysregulated in malignancy. Consequently, RBPs that regulate this event directly contribute to healthy and aberrant hematopoiesis. We modeled RUNX1 APA using a split GFP minigene reporter and confirmed the sensitivity of our model to detect changes in RNA processing. We used this reporter in a clustered regularly interspaced short palindromic repeats (CRISPR) screen consisting of single guide RNAs exclusively targeting RBPs and uncovered HNRNPA1 and KHDRBS1 as antagonistic regulators of RUNX1a isoform generation. Overall, our study provides mechanistic insight into the posttranscriptional regulation of a key hematopoietic transcription factor and identifies RBPs that may have widespread and important functions in hematopoiesis.
Fetal sex modulates placental microRNA expression, potential microRNA-mRNA interactions, and levels of amino acid transporter expression and substrates: INFAT study subpopulation analysis of n-3 LCPUFA intervention during pregnancy and associations with offspring body composition
Authors: Sedlmeier Eva-Maria , Meyer Dorothy M. , Stecher Lynne , Sailer Manuela , Daniel Hannelore , Hauner Hans , Bader Bernhard L. 
Published: March 2021

AbstractBackgroundPreviously, we revealed sexually dimorphic mRNA expression and responsiveness to maternal dietary supplementation with n-3 long-chain polyunsaturated fatty acids (LCPUFA) in placentas from a defined INFAT study subpopulation. Here, we extended these analyses and explored the respective placental microRNA expression, putative microRNA-mRNA interactions, and downstream target processes as well as their associations with INFAT offspring body composition.ResultsWe performed explorative placental microRNA profiling, predicted microRNA-mRNA interactions by bioinformatics, validated placental target microRNAs and their putative targets by RT-qPCR and western blotting, and measured amino acid levels in maternal and offspring cord blood plasma and placenta. microRNA, mRNA, protein, and amino acid levels were associated with each other and with offspring body composition from birth to 5 years of age. Forty-six differentially regulated microRNAs were found. Validations identified differential expression formicroRNA-99a(miR-99a) and its predicted target genesmTOR,SLC7A5, encoding L-type amino acid transporter 1 (LAT1), andSLC6A6, encoding taurine transporter (TauT), and their prevailing significant sexually dimorphic regulation. Target mRNA levels were mostly higher in placentas from control male than from female offspring, whereas respective n-3 LCPUFA responsive target upregulation was predominantly found in female placentas, explaining the rather balanced expression levels between the sexes present only in the intervention group. LAT1 and TauT substrates tryptophan and taurine, respectively, were significantly altered in both maternal plasma at 32 weeks’ gestation and cord plasma following intervention, but not in the placenta. Several significant associations were observed formiR-99a, mTORmRNA,SLC7A5mRNA, and taurine and tryptophan in maternal and cord plasma with offspring body composition at birth, 1 year, 3 and 5 years of age.ConclusionsOur data suggest that the analyzed targets may be part of a sexually dimorphic molecular regulatory network in the placenta, possibly modulating gene expression per se and/or counteracting n-3 LCPUFA responsive changes, and thereby stabilizing respective placental and fetal amino acid levels. Our data propose placentalmiR-99,SLC7A5mRNA, and taurine and tryptophan levels in maternal and fetal plasma as potentially predictive biomarkers for offspring body composition.
Trophic specialisation reflected by radular tooth material properties in an “ancient” Lake Tanganyikan gastropod species flock
Authors: Krings Wencke , Neiber Marco T. , Kovalev Alexander , Gorb Stanislav N. , Glaubrecht Matthias 
Published: March 2021

AbstractBackgroundLake Tanganyika belongs to the East African Great Lakes and is well known for harbouring a high proportion of endemic and morphologically distinct genera, in cichlids but also in paludomid gastropods. With about 50 species these snails form a flock of high interest because of its diversity, the question of its origin and the evolutionary processes that might have resulted in its elevated amount of taxa. While earlier debates centred on these paludomids to be a result of an intralacustrine adaptive radiation, there are strong indications for the existence of several lineages before the lake formation. To evaluate hypotheses on the evolution and radiation the detection of actual adaptations is however crucial. Since the Tanganyikan gastropods show distinct radular tooth morphologies hypotheses about potential trophic specializations are at hand.ResultsHere, based on a phylogenetic tree of the paludomid species from Lake Tanganyika and adjacent river systems, the mechanical properties of their teeth were evaluated by nanoindentation, a method measuring the hardness and elasticity of a structure, and related with the gastropods’ specific feeding substrate (soft, solid, mixed). Results identify mechanical adaptations in the tooth cusps to the substrate and, with reference to the tooth morphology, assign distinct functions (scratching or gathering) to tooth types. Analysing pure tooth morphology does not consistently reflect ecological specializations, but the mechanical properties allow the determination of eco-morphotypes.ConclusionIn almost every lineage we discovered adaptations to different substrates, leading to the hypothesis that one main engine of the flock’s evolution is trophic specialization, establishing distinct ecological niches and allowing the coexistence of taxa.
Three-year clinical and radiological results of a cruciate-retaining type of the knee prosthesis with anatomical geometry developed in Japan
Authors: Nakajima Arata , Yamada Manabu , Sonobe Masato , Akatsu Yorikazu , Saito Masahiko , Yamamoto Keiichiro , Saito Junya , Norimoto Masaki , Koyama Keita , Takahashi Hiroshi , Aoki Yasuchika , Suguro Toru , Nakagawa Koichi 
Published: March 2021

AbstractBackgroundThe FINE total knee was developed in Japan and clinical use began in 2001. It has unique design features, including an oblique 3ofemorotibial joint line that reproduces anatomical geometry. Although 20 years have passed since the FINE knee was clinically used for the first time in Japan, a formal clinical evaluation including patient-reported and radiographic outcomes has not been undertaken.MethodsA total of 175 consecutive primary cruciate-retaining (CR)-FINE total knee arthroplasties (TKAs) at our hospital between February 2015 and March 2017 were included in this study. Three years postoperatively, range of motion (ROM), Knee Society Score (KSS), Knee Injury and Osteoarthritis Outcome Score (KOOS) and Forgotten Joint Score (FJS) were recorded and compared with preoperative scores. Radiographic analyses including mechanical alignment, component alignment, and incidence of radiolucent lines also were undertaken based on the radiographs 3 years postoperatively.ResultsOne-hundred twenty-two knees (70%) were available for 3-year follow-up data using KOOS, except for the sports subscale. Postoperative KOOS-symptom, −pain and -ADL were > 85 points, but KOOS-sports, −QOL and FJS were less satisfactory. ROM, KSS and all the subscales of KOOS were significantly improved compared with preoperative scores. Postoperative mean FJS was 66 and was significantly correlated with all the subscales of KOOS, but not with postoperative ROM. Radiolucent lines ≧1 mm wide were detected in five knees (4.1%). There were no major complications needing revision surgeries.ConclusionsPatient-reported outcomes (PROs) for symptoms, pain and ADL after the CR-FINE TKA were generally improved, but those for sports, QOL and FJS were improved less. The incidence of radiolucent lines was rare but detected around the femoral components. With the mid- to long-term follow-up, improvements of surgical technique will be necessary to achieve better PROs from patients receiving the FINE knee.
Smart city lifestyle sensing, big data, geo-analytics and intelligence for smarter public health decision-making in overweight, obesity and type 2 diabetes prevention: the research we should be doing
Authors: Kamel Boulos Maged N. , Koh Keumseok 
Published: March 2021

AbstractThe public health burden caused by overweight, obesity (OO) and type-2 diabetes (T2D) is very significant and continues to rise worldwide. The causation of OO and T2D is complex and highly multifactorial rather than a mere energy intake (food) and expenditure (exercise) imbalance. But previous research into food and physical activity (PA) neighbourhood environments has mainly focused on associating body mass index (BMI) with proximity to stores selling fresh fruits and vegetables or fast food restaurants and takeaways, or with neighbourhood walkability factors and access to green spaces or public gym facilities, making largely naive, crude and inconsistent assumptions and conclusions that are far from the spirit of 'precision and accuracy public health'. Different people and population groups respond differently to the same food and PA environments, due to a myriad of unique individual and population group factors (genetic/epigenetic, metabolic, dietary and lifestyle habits, health literacy profiles, screen viewing times, stress levels, sleep patterns, environmental air and noise pollution levels, etc.) and their complex interplays with each other and with local food and PA settings. Furthermore, the same food store or fast food outlet can often sell or serve both healthy and non-healthy options/portions, so a simple binary classification into 'good' or 'bad' store/outlet should be avoided. Moreover, appropriate physical exercise, whilst essential for good health and disease prevention, is not very effective for weight maintenance or loss (especially when solely relied upon), and cannot offset the effects of a bad diet. The research we should be doing in the third decade of the twenty-first century should use a systems thinking approach, helped by recent advances in sensors, big data and related technologies, to investigate and consider all these factors in our quest to design better targeted and more effective public health interventions for OO and T2D control and prevention.
Comprehensive evaluation of the metabolic effects of porcine CRTC3 overexpression on subcutaneous adipocytes with metabolomic and transcriptomic analyses
Authors: Liu Jiaqi , Li Jie , Chen Wentao , Xie Xintao , Chu Xingang , Valencak Teresa G. , Wang Yizhen , Shan Tizhong 
Published: March 2021

Abstract
Background
Meat quality is largely driven by fat deposition, which is regulated by several genes and signaling pathways. The cyclic adenosine monophosphate (cAMP) -regulated transcriptional coactivator 3 (CRTC3) is a coactivator of cAMP response element binding protein (CREB) that mediates the function of protein kinase A (PKA) signaling pathway and is involved in various biological processes including lipid and energy metabolism. However, the effects of CRTC3 on the metabolome and transcriptome of porcine subcutaneous adipocytes have not been studied yet. Here, we tested whether porcine CRTC3 expression would be related to fat deposition in Heigai pigs (a local fatty breed in China) and Duroc×Landrace×Yorkshire (DLY, a lean breed) pigs in vivo. The effects of adenovirus-induced CRTC3 overexpression on the metabolomic and transcriptomic profiles of subcutaneous adipocytes were also determined in vitro by performing mass spectrometry-based metabolomics combined with RNA sequencing (RNA-seq).

Results
Porcine CRTC3 expression is associated with fat deposition in vivo. In addition, CRTC3 overexpression increased lipid accumulation and the expression of mature adipocyte-related genes in cultured porcine subcutaneous adipocytes. According to the metabolomic analysis, CRTC3 overexpression induced significant changes in adipocyte lipid, amino acid and nucleotide metabolites in vitro. The RNA-seq analysis suggested that CRTC3 overexpression alters the expression of genes and pathways involved in adipogenesis, fatty acid metabolism and glycerophospholipid metabolism in vitro.

Conclusions
We identified significant alterations in the metabolite composition and the expression of genes and pathways involved in lipid metabolism in CRTC3-overexpressing adipocytes. Our results suggest that CRTC3 might play an important regulatory role in lipid metabolism and thus affects lipid accumulation in porcine subcutaneous adipocytes.
Accurate and sensitive detection of microbial eukaryotes from whole metagenome shotgun sequencing
Authors: Lind Abigail L. , Pollard Katherine S. 
Published: March 2021

Abstract
Background
Microbial eukaryotes are found alongside bacteria and archaea in natural microbial systems, including host-associated microbiomes. While microbial eukaryotes are critical to these communities, they are challenging to study with shotgun sequencing techniques and are therefore often excluded.

Results
Here, we present EukDetect, a bioinformatics method to identify eukaryotes in shotgun metagenomic sequencing data. Our approach uses a database of 521,824 universal marker genes from 241 conserved gene families, which we curated from 3713 fungal, protist, non-vertebrate metazoan, and non-streptophyte archaeplastida genomes and transcriptomes. EukDetect has a broad taxonomic coverage of microbial eukaryotes, performs well on low-abundance and closely related species, and is resilient against bacterial contamination in eukaryotic genomes. Using EukDetect, we describe the spatial distribution of eukaryotes along the human gastrointestinal tract, showing that fungi and protists are present in the lumen and mucosa throughout the large intestine. We discover that there is a succession of eukaryotes that colonize the human gut during the first years of life, mirroring patterns of developmental succession observed in gut bacteria. By comparing DNA and RNA sequencing of paired samples from human stool, we find that many eukaryotes continue active transcription after passage through the gut, though some do not, suggesting they are dormant or nonviable. We analyze metagenomic data from the Baltic Sea and find that eukaryotes differ across locations and salinity gradients. Finally, we observe eukaryotes in Arabidopsis leaf samples, many of which are not identifiable from public protein databases.

Conclusions
EukDetect provides an automated and reliable way to characterize eukaryotes in shotgun sequencing datasets from diverse microbiomes. We demonstrate that it enables discoveries that would be missed or clouded by false positives with standard shotgun sequence analysis. EukDetect will greatly advance our understanding of how microbial eukaryotes contribute to microbiomes.
A rare case of extensive placenta accreta in twin pregnancy after GnRH agonist treatment of adenomyosis
Authors: Agrawala Shilpi , Patil Jeevitha , Campbell Sukhkamal , Woodard Terri Lynn 
Published: March 2021

Abstract
Background
Adenomyosis remains an enigma for the reproductive endocrinologist. It is thought to contribute to sub-fertility, and its only curative treatment is hysterectomy. However, studies have documented increased live birth rates in women with adenomyosis who were treated with gonadotropin releasing hormone agonist (GnRHa).

Case
Here we present a case of a 52-year-old woman with adenomyosis who had three failed frozen embryo transfers (FETs) prior to initiating a 6-month trial of GnRHa. GnRHa therapy resulted in a decrease in uterine size from 11.5 × 7.9 × 7.0 cm to 7.8 × 6.2 × 5.9 cm and a decrease in the junctional zone (JZ) thickness from 19 to 9 mm. Subsequently, she underwent her fourth FET, which resulted in live birth of twins. The delivery was complicated by expansive accretas of both placentas requiring cesarean hysterectomy. The final pathology of the placentas demonstrated an extensive lack of decidualized endometrium that was even absent outside the basal plate.

Conclusions
GnRHa therapy in patients with adenomyosis may improve implantation rates after FET. Previous molecular studies indicate that genetic variance in the expression of the gonadotropin releasing hormone receptor (GnRHR) could explain the expansive lack of decidualized endometrium after GnRHa therapy. Further investigations are needed to determine if GnRHa therapy contributes to the pathologic process of placenta accreta.
Splenic vein stenting for recurrent chylous ascites in sinistral portal hypertension: a case report
Authors: Covello Brian , Miller Jacob , Fourzali Roberto 
Published: March 2021

Abstract
Background
Sinistral portal hypertension results from obstruction or stenosis of the splenic vein and is characterized by normal portal vein pressures and liver function tests. Gastrointestinal bleeding is the most common presentation and indication for treatment. Although sinistral portal hypertension-related chylous ascites is rare, several cases have described successful treatment with portal venous, rather than splenic venous, recanalization. Splenectomy is effective in the treatment of sinistral portal hypertension-related bleeding, although recent studies have evaluated splenic vein stenting and splenic arterial embolization as minimally-invasive treatment alternatives. Splenic vein stenting may be a viable option for other presentations of sinistral portal hypertension.

Case presentation
A 59-year-old gentleman with a history of necrotizing gallstone pancreatitis was referred to interventional radiology for management of recurrent chylous ascites. Analysis of ascites demonstrated a triglyceride level of 1294 mg/dL. Computed tomography revealed splenic and superior mesenteric venous stricture. The patient elected to undergo minimally invasive transhepatic portal venography, which confirmed the presence of splenic vein and superior mesenteric vein stenosis. Venography of the splenic vein showed reversal of portal venous flow, multiple collaterals, and a pressure gradient of 14 mmHg. Two 10 mm × 40 mm Cordis stents were placed, which decreased the pressure gradient to 7 mmHg and resolved the portosystemic collaterals. At 6 months follow-up, the patient had no recurrent episodes of ascites.

Conclusion
The current case highlights the successful treatment of sinistral portal hypertension-related intractable chylous ascites treated with transhepatic splenic vein stenting. Splenic venous stent patency rates of 92.9% at 12 months have been reported. Rebleeding rates of 7.1% for splenic vein stenting, 16% for splenectomy, and 47.8% for splenic arterial embolization have been reported in the treatment of sinistral portal hypertension-related gastrointestinal bleeding. The literature regarding splenic vein stenting for sinistral portal hypertension-related ascites is less robust. Technical and clinical success in the current case suggests that splenic vein recanalization may be a safe and viable option in other sinistral portal hypertension-related symptomatology.
Level of Evidence: Level 4, Case Report.
Development, optimization and characterization of flurbiprofen matrix transdermal drug delivery system using Box–Behnken statistical design
Authors: Joshi Ramakant , Garud Navneet 
Published: March 2021

Abstract
Background
Present investigation for research was to develop matrix-type transdermal drug delivery system of flurbiprofen (FBP) with the various ratio of matrix polymers (hydrophilic and hydrophobic), the concentration of plasticizer and natural penetration enhancer by Box–Behnken statistical design to investigate the combined outcome of selected independent variables for effective management of rheumatoid arthritis.
The influence of a binary mixture of polymers, plasticizer and penetration enhancer on physicochemical considerations including thickness, tensile strength, percent elongation, weight variation, percent moisture content, percent moisture uptake, water vapour transmission rate, folding endurance, drug content, in vitro drug dissolution study and then ex vivo drug permeation study was evaluated.

Results
The study demonstrated that the tensile strength of films improved by matrix polymer ratio and to a slighter gradation in the rise of plasticizer and natural penetration enhancer. Ex vivo drug permeation study was accompanied via excised porcine skin as a permeation barrier in Franz diffusion cell. Ex vivo drug permeation study indicated that matrix polymer ratio (HPMC K15M:ERL100) at 3:1 and natural penetration enhancer (d-limonene) at highest concentration 7.5% w/w containing formulation FBPT7 delivered maximum flux and supplementary improved the permeation of drug. The result of the skin irritation test revealed that the developed formulation is free from any type of skin irritation effects like erythema and oedema.

Conclusion
Based on the findings of this research, it can be established that a well-controlled release and very effective skin penetration of the drug was accomplished by the film FBPT7 in the existence of permeation enhancers for prolonged periods.
Analysis of clinical efficacy of Si Miao decoction combine with acupuncture and cupping treatment for gout: a systematic review and meta-analysis
Authors: Kim Yun Jin , Aslam Muhammad Shahzad 
Published: March 2021

This systematic review has been aimed to evaluate the clinical efficacy of the Si Miao decoction combined with acupuncture and cupping treatment for Gout. Three English and Chinese databases were searched for articles related to the effect of the Si Miao decoction combine with acupuncture and cupping therapy on CRP, UA, and ESR in Gout. The time period was limited from 01 January 2010 till 31 August 2019. Meta- analysis was performed using both the random and fixed effects model, and I2 was used to evaluate the heterogeneity. Identification was made through database searching of 238 publications. Three articles were eligible. Following the Si Miao Decoction combined with acupuncture and cupping therapy there was a significant reduction in the clinical parameters (SMD: −0.91, 95% CI: −1.081, −0.741, p = 0.000) (OR: −1.652, 95% CI: −1.960, −1.344, p = 0.000). High heterogeneity tests were indicated (Q=146.548, P = 0.00, I2 = 94.54%). This systematic review and meta-analysis indicated that the Si Miao decoction combined with acupuncture and cupping therapy significantly reduced the circulating levels of UA, ESR, and CRP. There is a need to improve the methodologies of clinical trials on modified Si Miao decoction combined with Acupuncture and Cupping treatment.