bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of cell-free hemoglobin and haptoglobin in acute kidney injury in critically ill adults with ARDS and therapy with VV ECMO
Authors: Graw Jan A. , Hildebrandt Philip , Krannich Alexander , Balzer Felix , Spies Claudia , Francis Roland C. , Kuebler Wolfgang M. , Weber-Carstens Steffen , Menk Mario , Hunsicker Oliver 
Published: February 2022

Abstract
Background
Increased plasma concentrations of circulating cell-free hemoglobin (CFH) are supposed to contribute to the multifactorial etiology of acute kidney injury (AKI) in critically ill patients while the CFH-scavenger haptoglobin might play a protective role. We evaluated the association of CFH and haptoglobin with AKI in patients with an acute respiratory distress syndrome (ARDS) requiring therapy with VV ECMO.

Methods
Patients with CFH and haptoglobin measurements before initiation of ECMO therapy were identified from a cohort of 1044 ARDS patients and grouped into three CFH concentration groups using a risk stratification. The primary objective was to assess the association of CFH and haptoglobin with KDIGO stage 3 AKI. Further objectives included the identification of a target haptoglobin concentration to protect from CFH-associated AKI.

Measurements and main results
Two hundred seventy-three patients fulfilled the inclusion criteria. Of those, 154 patients (56.4%) had AKI at ECMO initiation. The incidence of AKI increased stepwise with increasing concentrations of CFH reaching a plateau at 15 mg/dl. Compared to patients with low [< 5 mg/dl] CFH concentrations, patients with moderate [5–14 mg/dl] and high [≥ 15 mg/dl] CFH concentrations had a three- and five-fold increased risk for AKI (adjusted odds ratio [OR] moderate vs. low, 2.69 [95% CI, 1.25–5.95], P = 0.012; and OR high vs. low, 5.47 [2.00–15.9], P = 0.001). Among patients with increased CFH concentrations, haptoglobin plasma levels were lower in patients with AKI compared to patients without AKI. A haptoglobin concentration greater than 2.7 g/l in the moderate and 2.4 g/l in the high CFH group was identified as clinical cutoff value to protect from CFH-associated AKI (sensitivity 89.5% [95% CI, 83–96] and 90.2% [80–97], respectively).

Conclusions
In critically ill patients with ARDS requiring therapy with VV ECMO, an increased plasma concentration of CFH was identified as independent risk factor for AKI. Among patients with increased CFH concentrations, higher plasma haptoglobin concentrations might protect from CFH-associated AKI and should be subject of future research.
Susceptibility to hormone-mediated cancer is reflected by different tick rates of the epithelial and general epigenetic clock
Authors: Barrett James E. , Herzog Chiara , Kim Yoo-Na , Bartlett Thomas E. , Jones Allison , Evans Iona , Cibula David , Zikan Michal , Bjørge Line , Harbeck Nadia , Colombo Nicoletta , Howell Sacha J. , Rådestad Angelique Flöter , Gemzell-Danielsson Kristina , Widschwendter Martin 
Published: February 2022

Abstract
Background
A variety of epigenetic clocks utilizing DNA methylation changes have been developed; these clocks are either tissue-independent or designed to predict chronological age based on blood or saliva samples. Whether discordant tick rates between tissue-specific and general epigenetic clocks play a role in health and disease has not yet been explored.

Results
Here we analyze 1941 cervical cytology samples, which contain a mixture of hormone-sensitive cervical epithelial cells and immune cells, and develop the WID general clock (Women’s IDentification of risk), an epigenetic clock that is shared by epithelial and immune cells and optimized for cervical samples. We then develop the WID epithelial clock and WID immune clock, which define epithelial- and immune-specific clocks, respectively. We find that the WID-relative-epithelial-age (WID-REA), defined as the difference between the epithelial and general clocks, is significantly reduced in cervical samples from pre-menopausal women with breast cancer (OR 2.7, 95% CI 1.28-5.72). We find the same effect in normal breast tissue samples from pre-menopausal women at high risk of breast cancer and show that potential risk reducing anti-progesterone drugs can reverse this. In post-menopausal women, this directionality is reversed. Hormone replacement therapy consistently leads to a significantly lower WID-REA in cancer-free women, but not in post-menopausal women with breast or ovarian cancer.

Conclusions
Our findings imply that there are multiple epigenetic clocks, many of which are tissue-specific, and that the differential tick rate between these clocks may be an informative surrogate measure of disease risk.
Evolutionary adaptation of the Polycomb repressive complex 2
Authors: Fischer Sabrina , Weber Lisa Marie , Liefke Robert 
Published: February 2022

AbstractThe Polycomb repressive complex 2 (PRC2) is an essential chromatin regulatory complex involved in repressing the transcription of diverse developmental genes. PRC2 consists of a core complex; possessing H3K27 methyltransferase activity and various associated factors that are important to modulate its function. During evolution, the composition of PRC2 and the functionality of PRC2 components have changed considerably. Here, we compare the PRC2 complex members of Drosophila and mammals and describe their adaptation to altered biological needs. We also highlight how the PRC2.1 subcomplex has gained multiple novel functions and discuss the implications of these changes for the function of PRC2 in chromatin regulation.
The correlation between point-of-care ultrasound and digital tomosynthesis when used with suspected COVID-19 pneumonia patients in primary care
Authors: Fabuel Ortega Pablo , Almendros Lafuente Noelia , Cánovas García Sandra , Martínez Gálvez Laura , González-Vidal Aurora 
Published: February 2022

Abstract
Background
The use of lung ultrasound (LU) with COVID-19 pneumonia patients should be validated in the field of primary care (PC). Our study aims to evaluate the correlation between LU and radiographic imaging in PC patients with suspected COVID-19 pneumonia.

Methods
This observational, prospective and multicentre study was carried out with patients from a PC health area whose tests for COVID-19 and suspected pneumonia had been positive and who then underwent LU and a digital tomosynthesis (DT). Four PC physicians obtained data regarding the patients’ symptoms, examination, medical history and ultrasound data for 12 lung fields: the total amount of B lines (zero to four per field), the irregularity of the pleural line, subpleural consolidation, lung consolidation and pleural effusion. These data were subsequently correlated with the presence of pneumonia by means of DT, the need for hospital admission and a consultation in the hospital emergency department in the following 15 days.

Results
The study was carried out between November 2020 and January 2021 with 70 patients (40 of whom had pneumonia, confirmed by means of DT). Those with pneumonia were older, had a higher proportion of arterial hypertension and lower oxygen saturation (sO2). The number of B lines was higher in patients with pneumonia (16.53 vs. 4.3, p < 0.001). The area under the curve for LU was 0.87 (95% CI 0.78–0.96, p < 0.001), and when establishing a cut-off point of six B lines or more, the sensitivity was 0.875 (95% CI 0.77–0.98, p < 0.05), the specificity was 0.833 (95% CI 0.692–0.975, p < 0.05), the positive-likelihood ratio was 5.25 (95% CI 2.34–11.79, p < 0.05) and the negative-likelihood ratio was 0.15 (95% CI 0.07–0.34, p < 0.05). An age of ≥ 55 and a higher number of B lines were associated with admission. Patients who required admission (n = 7) met at least one of the following criteria: ≥ 55 years of age, sO2 ≤ 95%, presence of at least one subpleural consolidation or ≥ 21 B lines.

Conclusions
LU has great sensitivity and specificity for the diagnosis of COVID-19 pneumonia in PC. Clinical ultrasound findings, along with age and saturation, could, therefore, improve decision-making in this field.
Virulence genes expression profiling of different Shigella flexneri serotypes in response to sub-inhibitory concentrations of azithromycin and ciprofloxacin
Authors: Sadredinamin Mehrzad , Shabani Mahdi , Karimi Abdollah , Sohrabi Mohammad-Reza , Karimi-Yazdi Mohammadmahdi , Ghalavand Zohreh , Alebouyeh Masoud 
Published: February 2022

Abstract
Background
Shigellosis is a self-limiting disease that antibiotic therapy could decrease its complications and duration. However, sublethal levels of antibiotics, may lead to alteration in disease state, besides its role in the emergence of resistant variants. To understand this link, we investigated diversity of Shigella serogroups in children with diarrhea, diversity of S. flexneri serotypes, cytotoxic potential, resistance patterns to antibiotics, and alteration in transcriptional expression of main virulence genes in response to sub-inhibitory concentrations of azithromycin and ciprofloxacin.

Results
The most frequently isolated serogroups were S. sonnei (70.3%), followed by S. flexneri (29.1%) and S. boydii (0.6%). Ten serotypes were characterized among the S. flexneri isolates, including 2b, 1b, 2a, 1c, 4a, 3a, 3b, 6 and X and/or Xv. Antimicrobial susceptibility testing showed low frequency of multi-drug resistance phenotype among S. flexneri isolates with minimum inhibitory concentrations (MIC) of 0.5–64 and 0.25–8 µg/mL for azithromycin and ciprofloxacin, respectively. Gene expression analysis showed upregulation of icsA in serotype 4a after exposure with azithromycin, whereas other genes in the VirF pathway were downregulated, and downregulation of virB in serotypes 2a and 3a after exposure with ciprofloxacin, while upregulation of noted genes was detected.

Conclusions
Alteration in transcription of key virulence genes of S. flexneri serotypes was shown in response to sublethal concentration of antibiotics. The detected incongruency in the extent of gene transcription proposed that diverse regulatory pathways are possibly mediating response to sub-MIC concentrations of antibiotics in S. flexneri.
Nutritional prospects of jackfruit and its potential for improving dietary diversity in Uganda
Authors: Nantongo Judith S. , Odoi Juventine B. , Agaba Hillary , Gwali Samson 
Published: February 2022

AbstractObjectiveA sustainable way of providing essential nutrients from crops for the poor and undernourished is biofortification, through plant breeding. This study characterised the intraspecific variation of selected nutritional elements in the flakes and seeds of Ugandan jackfruit (Artocarpus heterophyllus) plus the phytochemical composition of leaves. The overall aim was to explore possibilities of selecting for varieties that are higher in selected essential nutrients. Selecting for nutrient dense crops has been mostly done for annual agricultural crops, and rarely for perennial fruit trees.ResultsUganda’s Jackfruit has high macronutrients, especially magnesium and calcium. This study revealed that the amounts of these macronutrients were higher than those found in commonly consumed fruits, giving jackfruit a nutritional advantage with respect to these nutrients. The varieties sampled also differed significantly (p < 0.01) for some nutrients such as vitamin C, crude fat, crude fibre, total soluble solids and juice yield, highlighting the potential for selection for targeted nutritional gains. The seeds however, had less amounts of most of the quantified nutrients that also differed among the varieties. Significant intraspecific variation of the leaf total phenolics was also observed. With regard to the quantified nutritional elements in the flakes, the ethno-varieties were separated in space along PC1 (p < 0.001), PC2 (p < 0.001) and PC3 (p < 0.01) indicating their distinctness.
A fluorometric assay to determine the protective effect of glucose-6-phosphate dehydrogenase (G6PD) against a Plasmodium spp. infection in females heterozygous for the G6PD gene: proof of concept in Plasmodium falciparum
Authors: Rumaseb Angela , Marfurt Jutta , Kho Steven , Kahn Maria , Price Ric N. , Ley Benedikt 
Published: February 2022

Abstract
Objective
Glucose-6-phosphate dehydrogenase (G6PD) deficiency offers some protection against malaria; however, the degree of protection is poorly described and likely to vary with G6PD genotype and Plasmodium species. We present a novel approach to quantify the differential invasion rates of P. falciparum between G6PD deficient and normal red blood cells (RBCs) in an ex vivo model. A flow-cytometry based assay was developed to distinguish G6PD deficient and normal, parasitized and non-parasitized RBCs within the same sample. Venous blood collected from a G6PD heterozygous female was infected and cultured ex vivo with a laboratory strain of P. falciparum (FC27).

Results
Aliquots of infected blood were assayed at schizont and subsequent synchronized ring stages. At schizont stage, 84.9% of RBCs were G6PD deficient of which 0.4% were parasitized compared to 2.0% of normal RBCs. In the subsequent ring stage, 90.4% of RBCs were deficient and 0.2% of deficient and 0.9% of normal cells respectively were parasitized. The pooled Odds Ratio for a deficient RBC to be parasitized was 0.2 (95% confidence interval: 0.18–0.22, p < 0.001) compared to a normal cell. Further studies are warranted to explore preferential parasitization with different G6PD variants and Plasmodium species.
A research note: effect of pH on meat iridescence in precooked cured pork
Authors: Ruedt Chiara , Gibis Monika , Weiss Jochen 
Published: February 2022

Abstract
Objective
The objective of this study was to investigate the effect of pH change of cooked cured pork M. longissimus thoracis et lumborum on iridescence intensity and extent (= percentage of iridescent area) since interaction with light may be related to pH-induced alterations in microstructure. Muscles were injected with brines of different pH values, cooked, sliced perpendicular to muscle fiber direction, and visually evaluated by a panel of 20 experienced panelists.

Results
Muscles with lowest pH (5.38) showed the lowest iridescence score of 4.63 (p < 0.05). Iridescence was greatest in muscles with normal (5.78) and high pH (6.03, respectively 6.59), but did not differ significantly (p > 0.05). Iridescence was positively correlated (p < 0.01) with pH and water content, and negatively correlated (p < 0.01) with cooking loss. Hence, hydration state and light scattering from microstructure may be important factors that determine the degree of iridescence in cooked meat products.
Mesenchymal Mycn participates in odontoblastic lineage commitment by regulating Krüppel-like Factor 4 (Klf4) in mice
Authors: Huang Zhuo , Yang Ruihuan , Li Ruyi , Zuo Yining , Gu Fan , He Miao , Bian Zhuan 
Published: February 2022

Abstract
Background
Commitment of mouse dental papilla cells (mDPCs) to the odontoblast lineage is critical for dentin formation, and this biological process is regulated by a complex transcription factor network. The transcription factor Mycn is a proto-oncogene that plays an important role in tumorigenesis and normal embryonic development. An early study revealed that Mycn is exclusively expressed in dental mesenchymal cells at E15.5, which implies a potential role of Mycn in dentinogenesis. However, the role of Mycn in dentin formation remains elusive. Thus, it is of considerable interest to elucidate the role of Mycn in dentin formation.

Methods
Mycnfl/fl; Osr2IresCre (MycnOsr2) and Mycnfl/fl; K14Cre (MycnK14) transgenic mice were generated, and micro-CT scans were performed to quantitatively analyse the volumetric differences in the molars and incisors of the mutants and their littermates. Mycn was also knocked down in vitro, and alkaline phosphatase (ALP) and alizarin red staining (ARS) were conducted. Cleavage under targets and tagmentation (CUT&Tag) analysis and dual luciferase assays were performed to identify direct downstream targets of Mycn. Immunofluorescence and immunochemistry staining and western blotting (WB) were performed to analyse the expression levels of potential targets. Quantitative PCR, WB, ALP and ARS were performed to test the rescue efficiency.

Results
Mesenchymal ablation of Mycn (MycnOsr2) led to defective dentin formation, while epithelial deletion (MycnK14) had no obvious effects on tooth development. ALP and ARS staining revealed that the commitment capacity of mDPCs to the odontoblast lineage was compromised in MycnOsr2 mice. CUT&Tag analysis identified Klf4 as a potential direct target of Mycn, and a dual luciferase reporter assay verified that Mycn could bind to the promotor region of Klf4 and directly activate its transcription. Reciprocally, forced expression of Klf4 partially recovered the odontoblastic differentiation capacity of mDPCs with Mycn knockdown.

Conclusions
Our results elucidated that mesenchymal Mycn modulates the odontoblastic commitment of dental papilla cells by directly regulating Klf4. Our study illustrated the role of Mycn in dentin development and furthers our general comprehension of the transcription factor networks involved in the dentinogenesis process. Thus, these results may provide new insight into dentin hypoplasia and bioengineered dentin regeneration.
Extending electronic medical records vector models with knowledge graphs to improve hospitalization prediction
Authors: Gazzotti Raphaël , Faron Catherine , Gandon Fabien , Lacroix-Hugues Virginie , Darmon David 
Published: February 2022

AbstractBackgroundArtificial intelligence methods applied to electronic medical records (EMRs) hold the potential to help physicians save time by sharpening their analysis and decisions, thereby improving the health of patients. On the one hand, machine learning algorithms have proven their effectiveness in extracting information and exploiting knowledge extracted from data. On the other hand, knowledge graphs capture human knowledge by relying on conceptual schemas and formalization and supporting reasoning. Leveraging knowledge graphs that are legion in the medical field, it is possible to pre-process and enrich data representation used by machine learning algorithms. Medical data standardization is an opportunity to jointly exploit the richness of knowledge graphs and the capabilities of machine learning algorithms.MethodsWe propose to address the problem of hospitalization prediction for patients with an approach that enriches vector representation of EMRs with information extracted from different knowledge graphs before learning and predicting. In addition, we performed an automatic selection of features resulting from knowledge graphs to distinguish noisy ones from those that can benefit the decision making. We report the results of our experiments on the PRIMEGE PACA database that contains more than 600,000 consultations carried out by 17 general practitioners (GPs).ResultsA statistical evaluation shows that our proposed approach improves hospitalization prediction. More precisely, injecting features extracted from cross-domain knowledge graphs in the vector representation of EMRs given as input to the prediction algorithm significantly increases the F1 score of the prediction.ConclusionsBy injecting knowledge from recognized reference sources into the representation of EMRs, it is possible to significantly improve the prediction of medical events. Future work would be to evaluate the impact of a feature selection step coupled with a combination of features extracted from several knowledge graphs. A possible avenue is to study more hierarchical levels and properties related to concepts, as well as to integrate more semantic annotators to exploit unstructured data.
Introduction and expression of PIK3CAE545K in a papillary thyroid cancer BRAFV600E cell line leads to a dedifferentiated aggressive phenotype
Authors: Pinto Nicole , Ruicci Kara M. , Khan Mohammed Imran , Shaikh Mushfiq Hassan , Zeng Yu Fan Peter , Yoo John , Fung Kevin , MacNeil S. Danielle , Mendez Adrian , Mymryk Joe S. , Barrett John W. , Boutros Paul C. , Nichols Anthony C. 
Published: February 2022

Anaplastic thyroid cancer (ATC) is a rare, aggressive form of undifferentiated thyroid cancer, which exhibits rapid progression and is almost universally fatal. At least a subset of ATC is thought to arise from pre-existing well-differentiated thyroid cancer, most frequently papillary thyroid cancer (PTC). While PIK3CA mutations are rare in PTC, they are common in ATC and tend to co-occur with BRAF mutations. This provided the rationale for our study to identify the potential role of PIK3CA mutations in the progression from well-differentiated to undifferentiated thyroid cancer. We introduced PIK3CAE545K into the LAM1 PTC cell line, which carries a BRAFV600E mutation. In culture, the engineered cell line (LAM1: PIK3CAE545K) proliferated faster and demonstrated increased clonogenic potential relative to the parental line carrying an empty vector (LAM1EV). Both the LAM1EV and LAM1: PIK3CAE545K edited lines were implanted into hind flanks of athymic nude mice for in vivo determination of disease progression. While tumour weights and volumes were not significantly higher in LAM1: PIK3CAE545K mice, there was a decrease in expression of thyroid differentiation markers TTF-1, thyroglobulin, PAX8 and B-catenin, suggesting that introduction of PIK3CAE545K led to dedifferentiation in vivo. Collectively, this study provides evidence of a role for PIK3CAE545K in driving disease progression from a well-differentiated to an undifferentiated thyroid cancer; however, over-expression was not a determinant of an accelerated growth phenotype in ATC. Graphical Abstract
Dynamic deformation and fault locking of the Xianshuihe Fault Zone, Southeastern Tibetan Plateau: implications for seismic hazards
Authors: Li Layue , Wu Yanqiang , Li Yujiang , Zhan Wei , Liu Xinzhong 
Published: February 2022

AbstractThe Xianshuihe Fault Zone is one of the most historically seismically active regions in mainland China. However, the seismicity along this fault zone has been quiescent for the past 40 years, since the Daofu M6.9 earthquake in 1981. Understanding its current deformation patterns and fault coupling characteristics is of great significance to estimate the potential risk of strong earthquakes. In this study, we analyzed the dynamic deformation and fault coupling characteristics along the Xianshuihe Fault Zone using Global Navigation Satellite System (GNSS) data for 1999–2007 and 2016–2020. The results show that the deformation pattern of the Xianshuihe fault zone underwent a dynamic adjustment after the 2008 Wenchuan Mw7.9 and 2013 Lushan Mw6.6 earthquakes, i.e., the maximum shear strain accumulation rates of the Luhuo and Daofu sections significantly decreased from 6.0 × 10–8/a to 3.2 × 10–8/a, while that of the southeastern segment (i.e., Kangding and Moxi sections) increased from 4.5 × 10–8/a to 6.2 × 10–8/a. Additionally, the slip rate and deformation width of the Xianshuihe Fault Zone also changed during these two periods. Combined with the near-field cross-fault observation data, we suggest that the surrounding strong earthquakes Wenchuan and Lushan had evident differential impacts on the deformation pattern of the Xianshuihe Fault Zone. The fault-coupling inversion results show that the locking degree of the Xianshuihe Fault Zone continued to increase after the Wenchuan and Lushan earthquakes, especially the Qianning and Moxi sections increased significantly, with an average coupling coefficient of greater than 0.9 and left-lateral slip-rate deficits of ~ 5 mm/a and ~ 8 mm/a, respectively. In contrast, the locking degree of the Kangding section decreased with almost no slip-rate deficit, which is in a state of creeping status. The analysis of the recent rupture history and strain accumulation characteristics of the Xianshuihe Fault Zone indicates that both the Qianning and Moxi sections have a high seismic potential for the next strong earthquake in the Xianshuihe Fault Zone.
Graphical Abstract