Miracle-dz/UniFAR-FTUs huggingface dataset:
Increased Prevalence of Alloimmunization in Sickle Cell Disease? Should We Restore Blood Donation in French Guiana?

Patients with sickle cell disease often undergo frequent blood transfusions. This increases their exposure to red blood cell alloantigens of donor units, thus making it more likely that they produce alloantibodies. This cross-sectional study aimed to describe the prevalence of allo-immunization in patients with sickle cell disease who were monitored at Cayenne Hospital in 2016. Of the 451 patients recruited during the study period, 238 (52.8%) were female. There were 262 (58.1%) homozygous sickle cell and 151 (33.5%) compound heterozygous sickle cell patients. The median age of the participants was 23.09 years (range, 0.5–68). We noted different red blood cell extended phenotypes: -in the Duffy system, the Fya- Fyb–profile was found in 299 patients (66%);—for the Kidd system, the most represented profile was Jka+ Jkb-, with 213 patients (47%). The Jka antigen was present in 355 patients;—in the MNS system, the S-s+ profile was found in 297 patients (66%);—the Lea antigen of the Lewis system was absent in 319 patients. The most frequent Rh phenotype in our patients was D+ C- E- c+ e+ K-, representing 51% of the patients. A total of 6,834 transfused packed red blood cell units were recorded. Sixty-eight patients (23%; 95% confidence interval, 20–25%) had detectable RBC alloantibodies. In multivariate logistic regression, only the mean number of single transfusions was statistically higher for the alloimmunized patients (p < 0.04). Thirteen (19%) of the patients with alloimmunization developed a delayed hemolytic transfusion reaction, thus representing 4.4% of the total number of transfused patients. Whether differences between donors from France vs. recipients from French Guiana could explain this high prevalence of alloimmunization to be examined. In conclusion, careful transfusion strategies for patients with RBC alloantibodies should allow further reduction of the rate of alloimmunization.
Early Deformation of Deep Brain Stimulation Electrodes Following Surgical Implantation: Intracranial, Brain, and Electrode Mechanics

Introduction Although deep brain stimulation is nowadays performed worldwide, the biomechanical aspects of electrode implantation received little attention, mainly as physicians focused on the medical aspects, such as the optimal indication of the surgical procedure, the positive and adverse effects, and the long-term follow-up. We aimed to describe electrode deformations and brain shift immediately after implantation, as it may highlight our comprehension of intracranial and intracerebral mechanics. Materials and Methods Sixty electrodes of 30 patients suffering from severe symptoms of Parkinson’s disease and essential tremor were studied. They consisted of 30 non-directional electrodes and 30 directional electrodes, implanted 42 times in the subthalamus and 18 times in the ventrolateral thalamus. We computed the x (transversal), y (anteroposterior), z (depth), torsion, and curvature deformations, along the electrodes from the entrance point in the braincase. The electrodes were modelized from the immediate postoperative CT scan using automatic voxel thresholding segmentation, manual subtraction of artifacts, and automatic skeletonization. The deformation parameters were computed from the curve of electrodes using a third-order polynomial regression. We studied these deformations according to the type of electrodes, the clinical parameters, the surgical-related accuracy, the brain shift, the hemisphere and three tissue layers, the gyration layer, the white matter stem layer, and the deep brain layer (type I error set at 5%). Results We found that the implanted first hemisphere coupled to the brain shift and the stiffness of the type of electrode impacted on the electrode deformations. The deformations were also different according to the tissue layers, to the electrode type, and to the first-hemisphere-brain-shift effect. Conclusion Our findings provide information on the intracranial and brain biomechanics and should help further developments on intracerebral electrode design and surgical issues.
Unraveling the Regulatory Mechanism of Color Diversity in Camellia japonica Petals by Integrative Transcriptome and Metabolome Analysis

Camellia japonica petals are colorful, rich in anthocyanins, and possess important ornamental, edible, and medicinal value. However, the regulatory mechanism of anthocyanin accumulation in C. japonica is still unclear. In this study, an integrative analysis of the metabolome and transcriptome was conducted in five C. japonica cultivars with different petal colors. Overall, a total of 187 flavonoids were identified (including 25 anthocyanins), and 11 anthocyanins were markedly differentially accumulated among these petals, contributing to the different petal colors in C. japonica. Moreover, cyanidin-3-O-(6″-O-malonyl) glucoside was confirmed as the main contributor to the red petal phenotype, while cyanidin-3-O-rutinoside, peonidin-3-O-glucoside, cyanidin-3-O-glucoside, and pelargonidin-3-O-glucoside were responsible for the deep coloration of the C. japonica petals. Furthermore, a total of 12,531 differentially expressed genes (DEGs) and overlapping DEGs (634 DEGs) were identified by RNA sequencing, and the correlation between the expression level of the DEGs and the anthocyanin content was explored. The candidate genes regulating anthocyanin accumulation in the C. japonica petals were identified and included 37 structural genes (especially CjANS and Cj4CL), 18 keys differentially expressed transcription factors (such as GATA, MYB, bHLH, WRKY, and NAC), and 16 other regulators (mainly including transporter proteins, zinc-finger proteins, and others). Our results provide new insights for elucidating the function of anthocyanins in C. japonica petal color expression.
Cardiac Dysfunction in a Mouse Vascular Dementia Model of Bilateral Common Carotid Artery Stenosis

Background: Cardiac function is associated with cognitive function. Previously, we found that stroke and traumatic brain injury evoke cardiac dysfunction in mice. In this study, we investigate whether bilateral common carotid artery stenosis (BCAS), a model that induces vascular dementia (VaD) in mice, induces cardiac dysfunction. Methods: Late-adult (6–8 months) C57BL/6J mice were subjected to sham surgery (n = 6) or BCAS (n = 8). BCAS was performed by applying microcoils (0.16 mm internal diameter) around both common carotid arteries. Cerebral blood flow and cognitive function tests were performed 21–28 days post-BCAS. Echocardiography was conducted in conscious mice 29 days after BCAS. Mice were sacrificed 30 days after BCAS. Heart tissues were isolated for immunohistochemical evaluation and real-time PCR assay. Results: Compared to sham mice, BCAS in mice significantly induced cerebral hypoperfusion and cognitive dysfunction, increased cardiac hypertrophy, as indicated by the increased heart weight and the ratio of heart weight/body weight, and induced cardiac dysfunction and left ventricular (LV) enlargement, indicated by a decreased LV ejection fraction (LVEF) and LV fractional shortening (LVFS), increased LV dimension (LVD), and increased LV mass. Cognitive deficits significantly correlated with cardiac deficits. BCAS mice also exhibited significantly increased cardiac fibrosis, increased oxidative stress, as indicated by 4-hydroxynonenal and NADPH oxidase-2, increased leukocyte and macrophage infiltration into the heart, and increased cardiac interleukin-6 and thrombin gene expression. Conclusions: BCAS in mice without primary cardiac disease provokes cardiac dysfunction, which, in part, may be mediated by increased inflammation and oxidative stress.
Virulence Gene Expression of Staphylococcus aureus in Human Skin

Staphylococcus aureus is the main cause of human skin and soft tissue infections. However, S. aureus pathogenicity within the skin is not fully characterized. Here, we implemented an S. aureus cutaneous infection model using human skin explants and performed a time-course infection to study the gene expression profile of a large panel of virulence-related factors of S. aureus USA300 LAC strain, by high-throughput RT-PCR. We pinpointed the genes that were differentially regulated by the bacteria in the skin tissues and identified 12 virulence factors that were upregulated at all time points assessed. Finally, using confocal microscopy, we show that the expression of alpha-hemolysin by S. aureus varies dependent on the skin niche and that the bacteria preferentially accumulates inside sweat glands and ducts. Taken together, our study gives insights about the pathogenic lifestyle of S. aureus within human skin tissues, which may contribute for the development of anti-S. aureus therapeutic strategies.
The Prognostic Value of Preoperative Serum Tumor Markers in Non-Small Cell Lung Cancer Varies With Radiological Features and Histological Types

Objectives To assess the association between common-used serum tumor markers and recurrence of lung adenocarcinoma and squamous cell carcinoma separately and determine the prognostic value of serum tumor markers in lung adenocarcinoma featured as ground glass opacities. Methods A total of 2,654 non-small cell lung cancer patients undergoing surgical resection between January 2008 and September 2014 were analyzed. The serum levels of carcinoma embryonic antigen (CEA), cytokeratin 19 fragment (CYFRA21-1), neuron-specific enolase (NSE), carbohydrate antigen 125 (CA125), carbohydrate antigen 153 (CA153) and carbohydrate antigen 199 (CA199) were tested preoperatively. Survival analyses were performed with COX proportional hazard regression. Results Among patients with lung adenocarcinoma, elevated preoperative serum CEA(HR=1.246, 95%CI:1.043-1.488, P=0.015), CYFRA21-1(HR=1.209, 95%CI:1.015-1.441, P=0.034) and CA125(HR=1.361, 95%CI:1.053-1.757, P=0.018) were significantly associated with poorer recurrence free survival (RFS). Elevated preoperative serum CA199 predicted worse RFS in patients diagnosed with lung squamous cell carcinoma (HR=1.833, 95%CI: 1.216-2.762, P=0.004). Preoperative serum CYFRA21-1(HR=1.256, 95%CI:1.044-1.512, P=0.016) and CA125(HR=1.373, 95%CI: 1.050-1.795, P=0.020) were independent prognostic factors for patients with adenocarcinoma presenting as solid nodules while serum CEA (HR=2.160,95%CI:1.311-3.558, P=0.003) and CA125(HR=2.475,95%CI:1.163-5.266, P=0.019) were independent prognostic factors for patients with adenocarcinoma featured as ground glass opacities. Conclusions The prognostic significances of preoperative serum tumor markers in non-small cell lung cancer were associated with radiological features and histological types.
P23 Acts as Functional RBP in the Macrophage Inflammation Response

Macrophages exert the primary cellular immune response. Pathogen components like bacterial lipopolysaccharides (LPS) stimulate macrophage migration, phagocytotic activity and cytokine expression. Previously, we identified the poly(A)+ RNA interactome of RAW 264.7 macrophages. Of the 402 RNA-binding proteins (RBPs), 32 were classified as unique in macrophages, including nineteen not reported to interact with nucleic acids before. Remarkably, P23 a HSP90 co-chaperone, also known as cytosolic prostaglandin E2 synthase (PTGES3), exhibited differential poly(A)+ RNA binding in untreated and LPS-induced macrophages. To identify mRNAs bound by P23 and to elucidate potential regulatory RBP functions in macrophages, we immunoprecipitated P23 from cytoplasmic extracts of cross-linked untreated and LPS-induced cells. RNAseq revealed that enrichment of 44 mRNAs was reduced in response to LPS. Kif15 mRNA, which encodes kinesin family member 15 (KIF15), a motor protein implicated in cytoskeletal reorganization and cell mobility was selected for further analysis. Noteworthy, phagocytic activity of LPS-induced macrophages was enhanced by P23 depletion. Specifically, in untreated RAW 264.7 macrophages, decreased P23 results in Kif15 mRNA destabilization, diminished KIF15 expression and accelerated macrophage migration. We show that the unexpected RBP function of P23 contributes to the regulation of macrophage phagocytotic activity and migration.
An Improved Detection of Circulating Tumor DNA in Extracellular Vesicles-Depleted Plasma

Circulating tumor DNA (ctDNA) in plasma has been used as a biomarker for cancer detection and outcome prediction. In this study, we collected the five precipitates (fractions 1–5) and leftover supernatant plasma component (fraction 6) by a sequential centrifugation in plasma samples from nine small cell lung cancer (SCLC) patients. The fractions 3, 5 and 6 were large vesicles, exosomes and extracellular vesicles (EVs)-depleted plasma, respectively. Fragment size analysis using DNAs from these fractions showed dramatical differences from a peak of 7–10 kb in fraction 1 to 140–160 bp in fraction 6. To determine ctDNA content, we performed whole genome sequencing and applied copy number-based algorithm to calculate ctDNA percentage. This analysis showed the highest ctDNA content in EV-depleted plasma (average = 27.22%), followed by exosomes (average = 22.09%) and large vesicles (average = 19.70%). Comparatively, whole plasma, which has been used in most ctDNA studies, showed an average of 23.84% ctDNA content in the same group of patients. To further demonstrate higher ctDNA content in fraction 6, we performed mutational analysis in the plasma samples from 22 non-small cell lung cancer (NSCLC) patients with known EGFR mutations. This analysis confirmed higher mutation detection rates in fraction 6 (14/22) than whole plasma (10/22). This study provides a new insight into potential application of using fractionated plasma for an improved ctDNA detection.
New Insights Into Microbiota Modulation-Based Nutritional Interventions for Neurodevelopmental Outcomes in Preterm Infants

Gut microbiota and the central nervous system have parallel developmental windows during pre and post-natal life. Increasing evidences suggest that intestinal dysbiosis in preterm infants predisposes the neonate to adverse neurological outcomes later in life. Understanding the link between gut microbiota colonization and brain development to tailor therapies aimed at optimizing initial colonization and microbiota development are promising strategies to warrant adequate brain development and enhance neurological outcomes in preterm infants. Breast-feeding has been associated with both adequate cognitive development and healthy microbiota in preterms. Infant formula are industrially produced substitutes for infant nutrition that do not completely recapitulate breast-feeding benefices and could be largely improved by the understanding of the role of breast milk components upon gut microbiota. In this review, we will first discuss the nutritional and bioactive component information on breast milk composition and its contribution to the assembly of the neonatal gut microbiota in preterms. We will then discuss the emerging pathways connecting the gut microbiota and brain development. Finally, we will discuss the promising microbiota modulation-based nutritional interventions (including probiotic and prebiotic supplementation of infant formula and maternal nutrition) for improving neurodevelopmental outcomes.
IL-33 Gene Polymorphisms as Potential Biomarkers of Disease Susceptibility and Response to TNF Inhibitors in Rheumatoid Arthritis, Ankylosing Spondylitis, and Psoriatic Arthritis Patients

Objective Rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA) belong to inflammatory rheumatic diseases, the group of conditions of unknown etiology. However, a strong genetic component in their pathogenesis has been well established. A dysregulation of cytokine networks plays an important role in the development of inflammatory arthritis. Interleukin 33 (IL-33) is a recently identified member of the IL-1 family. To date, the significance of IL-33 in inflammatory arthritis has been poorly studied. This research aimed to investigate the potential of IL-33 gene polymorphisms to serve as biomarkers for disease susceptibility and TNF inhibitor response in RA, AS, and PsA patients. Materials and Methods In total, 735 patients diagnosed with RA, AS, and PsA and 229 healthy individuals were enrolled in the study. Genotyping for three single nucleotide polymorphisms (SNPs) within the IL-33 gene, namely, rs16924159 (A/G), rs10975519 (T/C), and rs7044343 (C/T), was performed using polymerase chain reaction amplification employing LightSNiP assays. Results In the present study, the IL-33 rs10975519 CC genotype was associated with a decreased risk of developing RA in females, while the IL-33 rs16924159 polymorphism was associated with the efficacy of anti-TNF therapy and clinical parameters for RA and AS patients. The IL-33 rs16924159 AA genotype correlated with higher disease activity and worse clinical outcomes in RA patients treated with TNF inhibitors, and AS patients carrying the IL-33 rs16924159 AA genotype had higher disease activity and a worse response to anti-TNF therapy. That indicates a deleterious role of the IL-33 rs16924159 AA genotype in the context of RA, as well as AS. Conclusions The obtained results suggest that IL-33 gene polymorphisms might be potential candidate biomarkers of disease susceptibility and anti-TNF treatment response in patients with inflammatory rheumatic diseases.
Development and Validation of a Score for Screening Suicide of Patients With Neuroendocrine Neoplasms

Background: If the diagnosis of neuroendocrine neoplasm (NEN) increases the risk of patients to commit suicide has not been investigated so far. Identifying NEN patients at risk to commit suicide is important to increase their life quality and life expectancy. Methods and findings: Cancer cases were extracted from the Surveillance, Epidemiology, and End Results program and were divided into the NEN and the non-NEN cohorts. Subsequently, the NEN patients were randomly split into a training data set and a validation data set. Analyzing the training data set, we developed a score for assessing the risk to commit suicide for patients with NEN. In addition, we validated the score using the validation data set and evaluated, if this score could also be applied to other cancer entities by using the test data set, a non-NEN cohort. The odds ratio (OR) of suicide between NEN and non-NEN patients was determined. Moreover, the performance of a score was evaluated by the receiver operating characteristic curve and the area under the curve (AUC). Compared to non-NEN, NEN significantly increased the risk of suicide to 1.8-fold (NEN vs. non-NEN; OR, 1.832; P < 0.001). In addition, we observed that age, gender, race, marital status, tumor stage, histologic grade, surgery, and chemotherapy were associated with suicide among NEN patients; and a synthesized score based on these factors could significantly distinguish suicide individuals from non-suicide individuals in the training data set (AUC, 0.829; P < 0.001) and in the validation data set (AUC, 0.735; P < 0.001). This score also had a good performance when it was assessed by the test data set (AUC, 0.690; P < 0.001). This demonstrates that the score might also be applicable to other cancer entities. Conclusions: This population-based study suggests that NEN patients have a higher risk of suicide than non-NEN patients. In addition, this study provided a score, which can identify NEN patients at high-risk of committing suicide. Thus, this score in combination with current screening and prevention strategies for suicide may improve life quality and life expectancy of NEN patients.
Extrinsic and Existential Mortality Risk in Reproductive Decision-Making: Examining the Effects of COVID-19 Experience and Climate Change Beliefs

While the COVID-19 pandemic has presented an immediate risk to human life around the world, climate change poses an arguably greater—although less immediate—threat to our species’ survival. Within the framework of life-history theory (LHT), this pre-registered study investigated whether extrinsic risk (i.e., external factors that pose a risk to an individual’s life, e.g., COVID-19) and existential risk (i.e., risks with outcomes that threaten the existence of humans as a species, e.g., climate change) had similar or different relationships with reproductive decision-making. A UK representative sample of 325 participants between 18 and 35 years of age was asked to indicate their ideal number of children, ideal age to start having children, and whether their desire for a child had recently changed. Participants were asked about their experiences of COVID-19 and given a series of scales with which to assess their beliefs about climate change. In support of LHT, the study found evidence that knowing people who had been hospitalized with or died of COVID-19 was associated with a greater ideal number of children. Conversely, there was no clear evidence of a relationship between climate change beliefs and reproductive decision-making. The repercussions for understanding how we interpret and respond to different forms of mortality risk are discussed.
Porcine RIG-I and MDA5 Signaling CARD Domains Exert Similar Antiviral Function Against Different Viruses

The RIG-I-like receptors (RLRs) RIG-I and MDA5 play critical roles in sensing and fighting viral infections. Although RIG-I and MDA5 have similar molecular structures, these two receptors have distinct features during activation. Further, the signaling domains of the N terminal CARD domains (CARDs) in RIG-I and MDA5 share poor similarity. Therefore, we wonder whether the CARDs of RIG-I and MDA5 play similar roles in signaling and antiviral function. Here we expressed porcine RIG-I and MDA5 CARDs in 293T cells and porcine alveolar macrophages and found that MDA5 CARDs exhibit higher expression and stronger signaling activity than RIG-I CARDs. Nevertheless, both RIG-I and MDA5 CARDs exert comparable antiviral function against several viruses. Transcriptome analysis showed that MDA5 CARDs are more effective in regulating downstream genes. However, in the presence of virus, both RIG-I and MDA5 CARDs exhibit similar effects on downstream gene transcriptions, reflecting their antiviral function.