bluuebunny/crossref_metadata_2025_split huggingface dataset:
Correlation of the severity of anemia in patients undergoing total joint arthroplasty with preoperative deep vein thrombosis: a retrospective cohort study
Authors: Xiong Xiaojuan , Xu Shenglian , Li Ting , Cheng Bo 
Published: December 2022

Abstract
Background
To explore the correlation of the severity of preoperative anemia with deep vein thrombosis (DVT) in patients undergoing total joint arthroplasty (TJA).

Methods
A total of 2461 TJA patients were classified into anemia and non-anemia groups or DVT and non-DVT groups. A logistic regression model was established using propensity score matching (PSM) analysis with preoperative anemia of TJA patients as a dependent variable and DVT-related variables as covariates. The caliper value was set as 0.01, and the anemia and non-anemia groups were matched based on the ratio of 1:1 (835 pairs). Finally, data of all patients were analyzed by binary logistic regression.

Results
Preoperative anemia was observed in 872 cases (35.43%) and DVT in 170 cases (6.91%). Binary logistic regression after PSM revealed that the DVT risk of patients with preoperative, moderate and severe anemia increased by 1.82 [P = 0.00, 95% confidence interval (95% CI) (1.32–2.48)], 2.77 [P = 0.00, 95% CI (1.72–4.45)], and 8.26 [P = 0.00, 95% CI (3.22–21.16)] times, respectively. The risks of blood transfusion in the perioperative period in patients with anemia, mild anemia, moderate anemia, and severe anemia increased by 3.52 times [P = 0.00, 95% CI (2.78–4.47)], 2.13 [P = 0.00, 95% CI (1.63–2.79)], 7.22 [P = 0.00, 95% CI (5.30–9.83)], and 61.37 [P = 0.00, 95% CI (14.21–265.04)] times, respectively.

Conclusion
Preoperative anemia is an independent risk factor for preoperative DVT and blood transfusion in the perioperative period for TJA patients. The more severe the preoperative anemia, the greater the risk of preoperative DVT and perioperative blood transfusion in TJA patients. Therefore, patients with preoperative anemia, especially with moderate and severe anemia, should be screened for DVT formation before undergoing TJA.
Trial registration ChiCRT2100054844.
SMAD9-MYCN positive feedback loop represents a unique dependency for MYCN-amplified neuroblastoma
Authors: Tan Kezhe , Mo Jialin , Li Meng , Dong Yu , Han Yujie , Sun Xi , Ma Yingxuan , Zhu Kai , Wu Wei , Lu Li , Liu Jiangbin , Zhao Kewen , Zhang Lei , Tang Yujie , Lv Zhibao 
Published: December 2022

Abstract
Background
Neuroblastoma (NB) is the most common extracranial solid tumor occurring during childhood and high-risk NB patients have a poor prognosis. The amplified MYCN gene serves as an important determinant of a high risk of NB.

Methods
We performed an integrative screen using public NB tissue and cell line data, and identified that SMAD9 played an important role in high-risk NB. An investigation of the super-enhancers database (SEdb) and chromatin immunoprecipitation sequencing (ChIP-seq) dataset along with biological experiments of incorporating gene knockdown and CRISPR interference (CRISPRi) were performed to identify upstream regulatory mechanism of SMAD9. Gene knockdown and rescue, quantitative real-time PCR (Q-RT-PCR), cell titer Glo assays, colony formation assays, a subcutaneous xenograft model and immunohistochemistry were used to determine the functional role of SMAD9 in NB. An integrative analysis of ChIP-seq data with the validation of CRISPRi and dual-luciferase reporter assays and RNA sequencing (RNA-seq) data with Q-RT-PCR validation was conducted to analyze the downstream regulatory mechanism of SMAD9.

Results
High expression of SMAD9 was specifically induced by the transcription factors including MYCN, PHOX2B, GATA3 and HAND2 at the enhancer region. Genetic suppression of SMAD9 inhibited MYCN-amplified NB cell proliferation and tumorigenicity both in vitro and in vivo. Further studies revealed that SMAD9 bound to the MYCN promoter and transcriptionally regulate MYCN expression, with MYCN reciprocally binding to the SMAD9 enhancer and transactivating SMAD9, thus forming a positive feedback loop along with the MYCN-associated cancer cell cycle.

Conclusion
This study delineates that SMAD9 forms a positive transcriptional feedback loop with MYCN and represents a unique tumor-dependency for MYCN-amplified neuroblastoma.
Association of ABO blood groups with ovarian reserve: a retrospective cohort study in Chinese Han women younger than 40 years with infertility
Authors: Sun Xingyu , Sun Chenyu , Meng Muzi , Liu Ling 
Published: December 2022

Abstract
Background
Ovarian reserve reflects both the quantity and quality of oocytes available for procreation and is affected by many known and unknown factors. ABO blood type is related to several infertility processes, but it is unclear whether and how ABO blood type affects ovarian reserve.

Objective
The purpose of the study was to explore the correlation between ABO blood types and ovarian reserve in infertile Chinese Han women under 40 years of age undergoing the in vitro fertilization (IVF)/ intracytoplasmic sperm injection (ICSI)-embryo transfer (IVF/ICSI-ET) treatment.

Methods
Women aged < 40 years who underwent IVF/ICSI-ET at our institution and had a documented ABO blood type were eligible for this study. In this study, patients were divided into two groups according to the diminished ovarian reserve (DOR) group (AMH < 1.1 ng/mL, AFC < 6) and the non-diminished ovarian reserve (non-DOR) group (AMH ≥ 1.1 ng/mL, AFC ≥ 6). The relationship between ovarian reserve and ABO blood group was determined by correlation analysis.

Results
In this retrospective cohort study, clinical data were collected from 1690 Chinese Han women treated with IVF/ ICSI-ET in hospital records between April 2019 and March 2020 in the affiliated hospital of Southwest Medical University, located in Luzhou, China. The differences in age, duration of infertility, BMI, FSH, FSH / LH, and p (DOR vs non-DOR) for each parameter (DOR vs non-DOR) were statistically significant, and the differences in LH and E2 were not statistically significant. ABO blood groups were most prevalent in the DOR group with O (143, 34.8%) and A (122, 29.7%) and in the non-DOR group with A (428, 33.5%) and O (419, 32.8%). ABO blood groups were most prevalent in the DOR group with O (n = 57, 30.5%) and A (n = 54, 28.9%) and in the non-DOR group with A (n = 335, 34.0%) and O (n = 323, 32.8%) were the most frequent in the non-DOR group.

Conclusions
In this retrospective cohort study, we confirmed the lack of a significant association between ABO blood type and ovarian reserve. Further studies are needed to clarify whether there is any prognostic correlation between ABO blood group and ovarian reserve in women undergoing IVF/ICSI-ET.
Definition of a novel breast tumor-specific classifier based on secretome analysis
Authors: Sirven Philémon , Faucheux Lilith , Grandclaudon Maximilien , Michea Paula , Vincent-Salomon Anne , Mechta-Grigoriou Fatima , Scholer-Dahirel Alix , Guillot-Delost Maude , Soumelis Vassili 
Published: December 2022

Abstract
Background
During cancer development, the normal tissue microenvironment is shaped by tumorigenic events. Inflammatory mediators and immune cells play a key role during this process. However, which molecular features most specifically characterize the malignant tissue remains poorly explored.

Methods
Within our institutional tumor microenvironment global analysis (T-MEGA) program, we set a prospective cohort of 422 untreated breast cancer patients. We established a dedicated pipeline to generate supernatants from tumor and juxta-tumor tissue explants and quantify 55 soluble molecules using Luminex or MSD. Those analytes belonged to five molecular families: chemokines, cytokines, growth factors, metalloproteinases, and adipokines.

Results
When looking at tissue specificity, our dataset revealed some breast tumor-specific characteristics, as IL-16, as well as some juxta-tumor-specific secreted molecules, as IL-33. Unsupervised clustering analysis identified groups of molecules that were specific to the breast tumor tissue and displayed a similar secretion behavior. We identified a tumor-specific cluster composed of nine molecules that were secreted fourteen times more in the tumor supernatants than the corresponding juxta-tumor supernatants. This cluster contained, among others, CCL17, CCL22, and CXCL9 and TGF-β1, 2, and 3. The systematic comparison of tumor and juxta-tumor secretome data allowed us to mathematically formalize a novel breast cancer signature composed of 14 molecules that segregated tumors from juxta-tumors, with a sensitivity of 96.8% and a specificity of 96%.

Conclusions
Our study provides the first breast tumor-specific classifier computed on breast tissue-derived secretome data. Moreover, our T-MEGA cohort dataset is a freely accessible resource to the biomedical community to help advancing scientific knowledge on breast cancer.
Techno-economic analysis of an integrated biorefinery to convert poplar into jet fuel, xylitol, and formic acid
Authors: Seufitelli Gabriel V. S. , El-Husseini Hisham , Pascoli Danielle U. , Bura Renata , Gustafson Richard 
Published: December 2022

Abstract
Background
The overall goal of the present study is to investigate the economics of an integrated biorefinery converting hybrid poplar into jet fuel, xylitol, and formic acid. The process employs a combination of integrated biological, thermochemical, and electrochemical conversion pathways to convert the carbohydrates in poplar into jet fuel, xylitol, and formic acid production. The C5-sugars are converted into xylitol via hydrogenation. The C6-sugars are converted into jet fuel via fermentation into ethanol, followed by dehydration, oligomerization, and hydrogenation into jet fuel. CO2 produced during fermentation is converted into formic acid via electrolysis, thus, avoiding emissions and improving the process’s overall carbon conversion.

Results
Three different biorefinery scales are considered: small, intermediate, and large, assuming feedstock supplies of 150, 250, and 760 dry ktonne of poplar/year, respectively. For the intermediate-scale biorefinery, a minimum jet fuel selling price of $3.13/gallon was obtained at a discount rate of 15%. In a favorable scenario where the xylitol price is 25% higher than its current market value, a jet fuel selling price of $0.64/gallon was obtained. Co-locating the biorefinery with a power plant reduces the jet fuel selling price from $3.13 to $1.03 per gallon.

Conclusion
A unique integrated biorefinery to produce jet fuel was successfully modeled. Analysis of the biorefinery scales shows that the minimum jet fuel selling price for profitability decreases with increasing biorefinery scale, and for all scales, the biorefinery presents favorable economics, leading to a minimum jet fuel selling price lower than the current price for sustainable aviation fuel (SAF). The amount of xylitol and formic produced in a large-scale facility corresponds to 43% and 25%, respectively, of the global market volume of these products. These volumes will saturate the markets, making them infeasible scenarios. In contrast, the small and intermediate-scale biorefineries have product volumes that would not saturate current markets, does not present a feedstock availability problem, and produce jet fuel at a favorable price given the current SAF policy support. It is shown that the price of co-products greatly influences the minimum selling price of jet fuel, and co-location can further reduce the price of jet fuel.
Characterization of glutamate carboxypeptidase 2 orthologs in trematodes
Authors: Jedlickova Lucie , Peterkova Kristyna , Boateng Enoch Mensah , Ulrychova Lenka , Vacek Vojtech , Kutil Zsofia , Jiang Zhenze , Novakova Zora , Snajdr Ivan , Kim Juan , O’Donoghue Anthony J. , Barinka Cyril , Dvorak Jan 
Published: December 2022

AbstractBackgroundGlutamate carboxypeptidase 2 (GCP2) belongs to the M28B metalloprotease subfamily encompassing a variety of zinc-dependent exopeptidases that can be found in many eukaryotes, including unicellular organisms. Limited information exists on the physiological functions of GCP2 orthologs in mammalian tissues outside of the brain and intestine, and such data are completely absent for non-mammalian species. Here, we investigate GCP2 orthologs found in trematodes, not only as putative instrumental molecules for defining their basal function(s) but also as drug targets.MethodsIdentified genes encoding M28B proteasesSchistosoma mansoniandFasciola hepaticagenomes were analyzed and annotated. Homology modeling was used to create three-dimensional models of SmM28B and FhM28B proteins using published X-ray structures as the template. ForS. mansoni, RT-qPCR was used to evaluate gene expression profiles, and, by RNAi, we exploited the possible impact of knockdown on the viability of worms. Enzymes from both parasite species were cloned for recombinant expression. Polyclonal antibodies raised against purified recombinant enzymes and RNA probes were used for localization studies in both parasite species.ResultsSingle genes encoding M28B metalloproteases were identified in the genomes ofS. mansoniandF. hepatica. Homology models revealed the conserved three-dimensional fold as well as the organization of the di-zinc active site. Putative peptidase activities of purified recombinant proteins were assayed using peptidic libraries, yet no specific substrate was identified, pointing towards the likely stringent substrate specificity of the enzymes. The orthologs were found to be localized in reproductive, digestive, nervous, and sensory organs as well as parenchymal cells. Knockdown of gene expression by RNAi silencing revealed that the genes studied were non-essential for trematode survival under laboratory conditions, reflecting similar findings for GCP2 KO mice.ConclusionsOur study offers the first insight to our knowledge into M28B protease orthologs found in trematodes. Conservation of their three-dimensional structure, as well as tissue expression pattern, suggests that trematode GCP2 orthologs may have functions similar to their mammalian counterparts and can thus serve as valuable models for future studies aimed at clarifying the physiological role(s) of GCP2 and related subfamily proteases.Graphical Abstract
Post-vaccine epidemiology of serotype 3 pneumococci identifies transformation inhibition through prophage-driven alteration of a non-coding RNA
Authors: Kwun Min Jung , Ion Alexandru V. , Cheng Hsueh-Chien , D’Aeth Joshua C. , Dougan Sam , Oggioni Marco R. , Goulding David A. , Bentley Stephen D. , Croucher Nicholas J. 
Published: December 2022

Abstract
Background
The respiratory pathogen Streptococcus pneumoniae (the pneumococcus) is a genetically diverse bacterium associated with over 101 immunologically distinct polysaccharide capsules (serotypes). Polysaccharide conjugate vaccines (PCVs) have successfully eliminated multiple targeted serotypes, yet the mucoid serotype 3 has persisted despite its inclusion in PCV13. This capsule type is predominantly associated with a single globally disseminated strain, GPSC12 (clonal complex 180).

Methods
A genomic epidemiology study combined previous surveillance datasets of serotype 3 pneumococci to analyse the population structure, dynamics, and differences in rates of diversification within GPSC12 during the period of PCV introductions. Transcriptomic analyses, whole genome sequencing, mutagenesis, and electron microscopy were used to characterise the phenotypic impact of loci hypothesised to affect this strain’s evolution.

Results
GPSC12 was split into clades by a genomic analysis. Clade I, the most common, rarely underwent transformation, but was typically infected with the prophage ϕOXC141. Prior to the introduction of PCV13, this clade’s composition shifted towards a ϕOXC141-negative subpopulation in a systematically sampled UK collection. In the post-PCV13 era, more rapidly recombining non-Clade I isolates, also ϕOXC141-negative, have risen in prevalence. The low in vitro transformation efficiency of a Clade I isolate could not be fully explained by the ~100-fold reduction attributable to the serotype 3 capsule. Accordingly, prophage ϕOXC141 was found to modify csRNA3, a non-coding RNA that inhibits the induction of transformation. This alteration was identified in ~30% of all pneumococci and was particularly common in the unusually clonal serotype 1 GPSC2 strain. RNA-seq and quantitative reverse transcriptase PCR experiments using a genetically tractable pneumococcus demonstrated the altered csRNA3 was more effective at inhibiting production of the competence-stimulating peptide pheromone. This resulted in a reduction in the induction of competence for transformation.

Conclusion
This interference with the quorum sensing needed to induce competence reduces the risk of the prophage being deleted by homologous recombination. Hence the selfish prophage-driven alteration of a regulatory RNA limits cell-cell communication and horizontal gene transfer, complicating the interpretation of post-vaccine population dynamics.
Prediction of the Ki-67 marker index in hepatocellular carcinoma based on Dynamic Contrast-Enhanced Ultrasonography with Sonazoid
Authors: Huang Zhe , Zhou PingPing , Li ShanShan , Li Kaiyan 
Published: December 2022

Abstract
Background
Ki-67 is widely used as a proliferative and prognostic factor in HCC. This study aimed to analyze the relationship between dynamic contrast-enhanced ultrasonography (DCE-US) parameters and Ki-67 expression.

Methods
One hundred and twenty patients with histopathologically confirmed HCC who underwent DCE-US were included in this prospective study. Patients were classified according to the Ki-67 marker index into low Ki-67 (< 10%) (n = 84) and high Ki-67 (≥ 10%) groups (n = 36). Quantitative perfusion parameters were obtained and analyzed.

Results
Clinicopathological features (pathological grade and microvascular invasion) were significantly different between the high and low Ki-67 expression groups (p = 0.029 and p = 0.020, respectively). In the high Ki-67 expression group, the peak energy (PE) in the arterial phase and fall time (FT) were significantly different between the HCC lesions and distal liver parenchyma (p = 0.016 and p = 0.025, respectively). PE in the Kupffer phase was significantly different between the HCC lesions and the distal liver parenchyma in the low Ki-67 expression group (p = 0.029). The difference in PE in the Kupffer phase between HCC lesions and distal liver parenchyma was significantly different between the high and low Ki-67 expression groups (p = 0.045). The difference in PE in the Kupffer phase between HCC lesions and distal liver parenchyma < − 4.0 × 107 a.u. may contribute to a more accurate diagnosis of the high Ki-67 expression group, and the sensitivity and specificity were 82.9% and 38.7%, respectively.

Conclusions
The DCE-US parameters have potential as biomarkers for predicting Ki-67 expression in patients with HCC.
FOXO3a-dependent PARKIN negatively regulates cardiac hypertrophy by restoring mitophagy
Authors: Sun Teng , Han Yu , Li Jia-Lei , Jiao Xiang-Ying , Zuo Lin , Wang Jin , Wang Hai-Xiong , Yang Jun-Li , Cao Ji-Min , Wang Jian-Xun 
Published: December 2022

Abstract
Background
Sustained cardiac hypertrophy often develops maladaptive myocardial remodeling, and eventually progresses to heart failure and sudden death. Therefore, maladaptive hypertrophy is considered as a critical therapeutic target for many heart diseases. Mitophagy, a crucial mechanism in mitochondria quality control and cellular homeostasis, has been implicated in diverse cardiac disorders such as myocardial infarction, diabetic cardiomyopathy, cardiac hypertrophy and heart failure. However, what role mitophagy plays in heart diseases remains an enigma. PARKIN functions as an E3 ubiquitin protein ligase and mediates mitophagy cascades. It is still unclear whether PARKIN participates in the regulation of cardiac hypertrophy.

Results
PARKIN was downregulated in cardiomyocytes and hearts under hypertrophic stress. Enforced expression of PARKIN inhibited Ang II-induced cardiomyocyte hypertrophy. Compared to wide-type mice with Ang II-induced cardiac hypertrophy, Parkin transgenic mice subjected to Ang II administration showed attenuated cardiac hypertrophy and improved cardiac function. In addition, mitophagy machinery was impaired in response to Ang II, which was rescued by overexpression of PARKIN. PARKIN exerted the anti-hypertrophy effect through restoring mitophagy. In further exploring the underlying mechanisms, we found that PARKIN was transcriptionally activated by FOXO3a. FOXO3a promoted mitophagy and suppressed cardiac hypertrophy by targeting Parkin.

Conclusions
The present study reveals a novel cardiac hypertrophy regulating model composed of FOXO3a, PARKIN and mitophagy program. Modulation of their levels may provide a new approach for preventing cardiac hypertrophy and heart failure.

Graphical Abstract
Phosphorylation of adducin-1 by TPX2 promotes interpolar microtubule homeostasis and precise chromosome segregation in mouse oocytes
Authors: Zhang Ying , Fan Bingfeng , Li Xiaoxia , Tang Yu , Shao Jing , Liu Lixiang , Ren Yuhe , Yang Yifeng , Xu Baozeng 
Published: December 2022

AbstractBackgroundADD1 (adducin-1) and TPX2 (targeting protein for Xklp2) are centrosomal proteins and regulate mitotic spindle assembly. Mammalian oocytes that segregate homologous chromosomes in Meiosis I and sister chromatids in Meiosis II with a spindle lacking centrosomes are more prone to chromosome segregation errors than in mitosis. However, the regulatory mechanisms of oocyte spindle assembly and the functions of ADD1 and TPX2 in this process remain elusive.ResultWe found that the expression levels and localization of ADD1, S726 phosphorylated ADD1 (p-ADD1), and TPX2 proteins exhibited spindle assembly-dependent dynamic changes during mouse oocyte meiosis. Taxol treatment, which stabilizes the microtubule polymer and protects it from disassembly, made the signals of ADD1, p-ADD1, and TPX2 present in the microtubule organizing centers of small asters and spindles. Knockdown of approximately 60% of ADD1 protein levels destabilized interpolar microtubules in the meiotic spindle, resulting in aberrant chromosome alignment, reduced first polar body extrusion, and increased aneuploidy in metaphase II oocytes, but did not affect K-fiber homeostasis and the expression and localization of TPX2. Strikingly, TPX2 deficiency caused increased protein content of ADD1, but decreased expression and detachment of p-ADD1 from the spindle, thereby arresting mouse oocytes at the metaphase I stage with collapsed spindles.ConclusionPhosphorylation of ADD1 at S726 by TPX2 mediates acentriolar spindle assembly and precise chromosome segregation in mouse oocytes.