Miracle-dz/UniFAR-FTUs huggingface dataset:
The complete mitochondrial genome of the Megalobrama pellegrini (Teleostei: Cyprinidae)

Abstract The complete mitochondrial genome of Megalobrama pellegrini was determined by using a PCR-based sequencing method. The mitochondrial was 16,620 bp in length, including 13 protein genes, two ribosomal RNA (rRNA) genes, 22 transfer RNA (tRNA) genes, and one control region. All genes were encoded on the heavy strain except for ND6 and eight tRNA genes. The gene arrangement of M. pellegrini was similar to those found in the other Megalobrama species. Base composition of the heavy strain was A (31.19%), T (24.69%), C (46.37%), G (16.22%) and with A + T bias of 55.88%.
Exploring RGB+Depth Fusion for Real-Time Object Detection

In this paper, we investigate whether fusing depth information on top of normal RGB data for camera-based object detection can help to increase the performance of current state-of-the-art single-shot detection networks. Indeed, depth sensing is easily acquired using depth cameras such as a Kinect or stereo setups. We investigate the optimal manner to perform this sensor fusion with a special focus on lightweight single-pass convolutional neural network (CNN) architectures, enabling real-time processing on limited hardware. For this, we implement a network architecture allowing us to parameterize at which network layer both information sources are fused together. We performed exhaustive experiments to determine the optimal fusion point in the network, from which we can conclude that fusing towards the mid to late layers provides the best results. Our best fusion models significantly outperform the baseline RGB network in both accuracy and localization of the detections.
A multiscale analysis in CD38−/− mice unveils major prefrontal cortex dysfunctions

Autism spectrum disorder (ASD) is characterized by early onset of behavioral and cognitive alterations. Low plasma levels of oxytocin (OT) have also been found in ASD patients; recently, a critical role for the enzyme CD38 in the regulation of OT release was demonstrated. CD38 is important in regulating several Ca2+‐dependent pathways, but beyond its role in regulating OT secretion, it is not known whether a deficit in CD38 expression leads to functional modifications of the prefrontal cortex (PFC), a structure involved in social behavior. Here, we report that CD38−/− male mice show an abnormal cortex development, an excitation‐inhibition balance shifted toward a higher excitation, and impaired synaptic plasticity in the PFC such as those observed in various mouse models of ASD. We also show that a lack of CD38 alters social behavior and emotional responses. Finally, examining neuromodulators known to control behavioral flexibility, we found elevated monoamine levels in the PFC of CD38−/− adult mice. Overall, our study unveiled major changes in PFC physiologic mechanisms and provides new evidence that the CD38−/− mouse could be a relevant model to study pathophysiological brain mechanisms of mental disorders such as ASD. —Martucci, L. L. , Amar, M. , Chaussenot, R. , Benet, G. , Bauer, O. , de Zélicourt, A. , Nosjean, A. , Launay, J.‐M. , Callebert, J., Sebrié, C. , Galione, A. , Edeline, J.‐M. , de la Porte, S. , Fossier, P., Granon, S. , Vaillend, C. , Cancela, J.‐M. , A multiscale analysis in CD38‐/‐ mice unveils major prefrontal cortex dysfunctions. FASEB J. 33, 5823–5835 (2019). www.fasebj. org
Angiotensin II–Induced Oxidative Stress Resets the Ca2+ Dependence of Ca2+–Calmodulin Protein Kinase II and Promotes a Death Pathway Conserved Across Different Species

Rationale: Angiotensin (Ang) II–induced apoptosis was reported to be mediated by different signaling molecules. Whether these molecules are either interconnected in a single pathway or constitute different and alternative cascades by which Ang II exerts its apoptotic action, is not known. Objective: To investigate in cultured myocytes from adult cat and rat, 2 species in which Ang II has opposite inotropic effects, the signaling cascade involved in Ang II–induced apoptosis. Methods and Results: Ang II (1 &mgr;mol/L) reduced cat/rat myocytes viability by ≈40%, in part, because of apoptosis (TUNEL/caspase-3 activity). In both species, apoptosis was associated with reactive oxygen species (ROS) production, Ca2+/calmodulin–dependent protein kinase (CaMK)II, and p38 mitogen-activated protein kinase (p38MAPK) activation and was prevented by the ROS scavenger MPG (2-mercaptopropionylglycine) or the NADPH oxidase inhibitor DPI (diphenyleneiodonium) by CaMKII inhibitors (KN-93 and AIP [autocamtide 2-related inhibitory peptide]) or in transgenic mice expressing a CaMKII inhibitory peptide and by the p38MAPK inhibitor, SB202190. Furthermore, p38MAPK overexpression exacerbated Ang II–induced cell mortality. Moreover, although KN-93 did not affect Ang II–induced ROS production, it prevented p38MAPK activation. Results further show that CaMKII can be activated by Ang II or H2O2, even in the presence of the Ca2+ chelator BAPTA-AM, in myocytes and in EGTA-Ca2+–free solutions in the presence of the calmodulin inhibitor W-7 in in vitro experiments. Conclusions: (1) The Ang II–induced apoptotic cascade converges in both species, in a common pathway mediated by ROS-dependent CaMKII activation which results in p38MAPK activation and apoptosis. (2) In the presence of Ang II or ROS, CaMKII may be activated at subdiastolic Ca2+ concentrations, suggesting a new mechanism by which ROS reset the Ca2+ dependence of CaMKII to extremely low Ca2+ levels.
Neutropenia and docetaxel exposure in metastatic castration‐resistant prostate cancer patients: A meta‐analysis and evaluation of a clinical cohort

The incidence of neutropenia in metastatic castration‐resistant prostate cancer (mCRPC) patients treated with docetaxel has been reported to be lower compared to patients with other solid tumors treated with a similar dose. It is suggested that this is due to increased clearance of docetaxel in mCRPC patients, resulting in decreased exposure. The aims of this study were to (1) determine if exposure in mCRPC patients is lower vs patients with other solid tumors by conducting a meta‐analysis, (2) evaluate the incidence of neutropenia in patients with mCRPC vs other solid tumors in a clinical cohort, and (3) discuss potential clinical consequences. A meta‐analysis was conducted of studies which reported areas under the plasma concentration‐time curves (AUCs) of docetaxel and variability. In addition, grade 3/4 neutropenia was evaluated using logistic regression in a cohort of patients treated with docetaxel. The meta‐analysis included 36 cohorts from 26 trials (n = 1150 patients), and showed that patients with mCRPC had a significantly lower mean AUC vs patients with other solid tumors (fold change [95% confidence interval (CI)]: 1.8 [1.5‐2.2]), with corresponding AUCs of 1.82 and 3.30 mg∙h/L, respectively. Logistic regression, including 812 patient, demonstrated that patients with mCRPC had a 2.2‐fold lower odds of developing grade 3/4 neutropenia compared to patients with other solid tumors (odds ratio [95%CI]: 0.46 [0.31‐0.90]). These findings indicate that mCRPC patients have a lower risk of experiencing severe neutropenia, possibly attributable to lower systemic exposure to docetaxel.
Red Blood Cells Are the Major Source of Alpha-Synuclein in Blood

Background: α-Synuclein has been directly linked to Parkinson’s disease etiology by mutations in and multiplication of its gene that result in a familial form of Parkinson’s disease. α-Synuclein has been detected in blood, and was found to be elevated in the blood of those individuals with the α-synuclein gene multiplication. Objective: A complete analysis of the level of α-synuclein in blood has not been performed. In this report, we determine the quantitative distribution of α-synuclein in the plasma and different cellular fractions of human blood. The levels of α-synuclein in human and mouse blood are compared. Methods: α-Synuclein levels in the different fractions of blood were quantified by a sandwich ELISA with purified recombinant α-synuclein as an assay standard. Samples were further characterized by Western immunoblot analysis. Results: More than 99% of the α-synuclein resides in the red blood cells (RBCs) with less than 1% of the total detected in the plasma, platelets and peripheral blood mononuclear cells. Conclusions: More than 99% of the α-synuclein in human blood is present in the peripheral blood cells, with the remainder in plasma. Fractionation of peripheral blood cells from human blood and quantification of α-synuclein revealed that only a very small amount of the total α-synuclein is present in peripheral blood mononuclear cells, and platelets, with the majority of α-synuclein in blood being present in RBCs. Considering the abundance and fragility of RBCs, α-synuclein levels in these other blood fractions or other bodily fluids such as cerebrospinal fluid may be artificially elevated by contamination with intact or lysed RBCs.
The stress granule protein G3BP1 binds viral dsRNA and RIG-I to enhance interferon-β response

RIG-I senses viral RNA in the cytosol and initiates host innate immune response by triggering the production of type 1 interferon. A recent RNAi knockdown screen yielded close to hundred host genes whose products affected viral RNA-induced IFN-β production and highlighted the complexity of the antiviral response. The stress granule protein G3BP1, known to arrest mRNA translation, was identified as a regulator of RIG-I–induced IFN-β production. How G3BP1 functions in RIG-I signaling is not known, however. Here, we overexpress G3BP1 with RIG-I in HEK293T cells and found that G3BP1 significantly enhances RIG-I–induced ifn-b mRNA synthesis. More importantly, we demonstrate that G3BP1 binds RIG-I and that this interaction involves the C-terminal RGG domain of G3BP1. Confocal microscopy studies also show G3BP1 co-localization with RIG-I and with infecting vesicular stomatitis virus in Cos-7 cells. Interestingly, immunoprecipitation studies using biotin-labeled viral dsRNA or poly(I·C) and cell lysate–derived or in vitro translated G3BP1 indicated that G3BP1 could directly bind these substrates and again via its RGG domain. Computational modeling further revealed a juxtaposed interaction between G3BP1 RGG and RIG-I RNA-binding domains. Together, our data reveal G3BP1 as a critical component of RIG-I signaling and possibly acting as a co-sensor to promote RIG-I recognition of pathogenic RNA.
Preemptive Morphine During Therapeutic Hypothermia After Neonatal Encephalopathy: A Secondary Analysis.

Although therapeutic hypothermia (TH) improves outcomes after neonatal encephalopathy (NE), the safety and efficacy of preemptive opioid sedation during cooling therapy is unclear. We performed a secondary analysis of the data from a large multicountry prospective observational study (Magnetic Resonance Biomarkers in Neonatal Encephalopathy [MARBLE]) to examine the association of preemptive morphine infusion during TH on brain injury and neurodevelopmental outcomes after NE. All recruited infants had 3.0 Tesla magnetic resonance imaging and spectroscopy at 1 week, and neurodevelopmental outcome assessments at 22 months. Of 223 babies recruited to the MARBLE study, the data on sedation were available from 169 babies with moderate (n = 150) or severe NE (n = 19). Although the baseline characteristics and admission status were similar, the babies who received morphine infusion (n = 141) were more hypotensive (49% vs. 25%, p = 0.02) and had a significantly longer hospital stay (12 days vs. 9 days, p = 0.009) than those who did not (n = 28). Basal ganglia/thalamic injury (score ≥1) and cortical injury (score ≥1) was seen in 34/141 (24%) and 37/141 (26%), respectively, of the morphine group and 4/28 (14%) and 3/28 (11%) of the nonmorphine group (p > 0.05). On regression modeling adjusted for potential confounders, preemptive morphine was not associated with mean (standard deviation [SD]) thalamic N-acetylaspartate (NAA) concentration (6.9 ± 0.9 vs. 6.5 ± 1.5; p = 0.97), and median (interquartile range) lactate/NAA peak area ratios (0.16 [0.12-0.21] vs. 0.13 [0.11-0.18]; p = 0.20) at 1 week, and mean (SD) Bayley-III composite motor (92 ± 23 vs. 94 ± 10; p = 0.98), language (89 ± 22 vs. 93 ± 8; p = 0.53), and cognitive scores (95 ± 21 vs. 99 ± 13; p = 0.56) at 22 months. Adverse neurodevelopmental outcome (adjusted for severity of encephalopathy) was seen in 26 (18%) of the morphine group, and none of the nonmorphine group (p = 0.11). Preemptive morphine sedation during TH does not offer any neuroprotective benefits and may be associated with increased hospital stay. Optimal sedation during induced hypothermia requires further evaluation in clinical trials.
Subjective, but not objective, cognitive complaints impact long-term quality of life in cancer patients

Abstract Objectives: Cognitive complaints, of objective or subjective nature, may negatively impact cancer patients’ quality of life (QoL). Further, the early detection of cognitive alterations may lead to an improved QoL. However, the content of such screening is yet unclear. This paper presents long-term QoL data of cancer patients treated with curative intent and its relation with objective and subjective cognitive complaints, and patient-reported outcome measures (PROMs). Methods: QoL data, measured by the EORTC QLQ C-30, were obtained at baseline, 6 (T1), 12 (T2), and 24 months (T3) after treatment start, and compared between patients with and without objective and subjective cognitive complaints. The predictive value of PROMs was also examined. Results: QoL data at baseline was collected in 125 patients. Response rates at T1, T2, and T3 were 84.7%, 81.5%, and 83.1%, respectively. Eighty-nine patients returned their QoL questionnaires at all times. Baseline subjective cognitive complaints had a stronger association with worse scores on patients’ overall QoL and QoL subscale scores than objective cognitive complaints. An exploratory analysis into the value of PROMs in predicting long-term QoL at T3 revealed a significant effect for the Hospital Anxiety and Depression Scale-Depression and FACIT Fatigue scale. Conclusions: Self-perceived cognitive alterations are negatively associated with patients’ overall QoL. As these troubles may already be present at baseline, oncology nurses should screen for the early signs of subjective cognitive complaints by use of PROMs, in order to refer the patient to proper intervention programs which may lead to an improved long-term QoL and faster reintegration into society.
Pressure Overload–Induced Alterations in Fibrillar Collagen Content and Myocardial Diastolic Function: Role of Secreted Protein Acidic and Rich in Cysteine (SPARC) in Post–Synthetic Procollagen Processing

Background— Chronic pressure overload causes myocardial hypertrophy, increased fibrillar collagen content, and abnormal diastolic function. We hypothesized that one determinant of these pressure overload–induced changes is the extracellular processing of newly synthesized procollagen into mature collagen fibrils. We further hypothesized that secreted protein acidic and rich in cysteine (SPARC) plays a key role in post–synthetic procollagen processing in normal and pressure-overloaded myocardium. Methods and Results— To determine whether pressure overload–induced changes in collagen content and diastolic function are affected by the absence of SPARC, age-matched wild-type (WT) and SPARC-null mice underwent either transverse aortic constriction (TAC) for 4 weeks or served as nonoperated controls. Left ventricular (LV) collagen content was measured histologically by collagen volume fraction, collagen composition was measured by hydroxyproline assay as soluble collagen (1 mol/L NaCl extractable) versus insoluble collagen (mature cross-linked collagen), and collagen morphological structure was examined by scanning electron microscopy. SPARC expression was measured by immunoblot. LV, myocardial, and cardiomyocyte structure and function were assessed by echocardiographic, papillary muscle, and isolated cardiomyocyte studies. In WT mice, TAC increased LV mass, SPARC expression, myocardial diastolic stiffness, fibrillar collagen content, and soluble and insoluble collagen. In SPARC-null mice, TAC increased LV mass to an extent similar to WT mice. In addition, in SPARC-null mice, TAC increased fibrillar collagen content, albeit significantly less than that seen in WT TAC mice. Furthermore, the proportion of LV collagen that was insoluble was less in the SPARC-null TAC mice (86±2%) than in WT TAC mice (99±2%, P<0.05), and the proportion of collagen that was soluble was greater in the SPARC-null TAC mice (14±2%) than in WT TAC mice (1±2%, P<0.05) As a result, myocardial diastolic stiffness was lower in SPARC-null TAC mice (0.075±0.005) than in WT TAC mice (0.045±0.005, P<0.05). Conclusions— The absence of SPARC reduced pressure overload–induced alterations in extracellular matrix fibrillar collagen and diastolic function. These data support the hypothesis that SPARC plays a key role in post–synthetic procollagen processing and the development of mature cross-linked collagen fibrils in normal and pressure-overloaded myocardium.
Patterns of fluctuating asymmetry in the limbs of anurans

It has been hypothesized that fluctuating asymmetry (FA) may provide an indication of the functional importance of structures within an organism, with structures that more strongly impact fitness being more symmetric. Based on this idea, we predicted that for tetrapods in which the forelimbs and hindlimbs play an unequal role in locomotion, the less functionally important limb set should display higher levels of FA. We conducted a multispecies test of this hypothesis in anurans (frogs and toads), whose saltatory locomotor mode is powered by the hindlimbs. We also tested whether FA in the forelimbs, which play a more important role during landing, differed between families that differ in the degree of forelimb use in locomotion (Bufonidae vs. Ranidae). We calculated FA from the lengths of humeri and femora measured from disarticulated skeletal specimens of four anuran taxa (Bufonidae: Anaxyrus americanus, Rhinella marina; Ranidae: Lithobates catesbeianus, Lithobates clamitans). Our findings were consistent with the hypothesis that natural selection for increased locomotor performance may influence patterns of FA seen in vertebrate limbs, with all species displaying lower mean FA in the hindlimbs. More subtle functional roles between the forelimbs of bufonids and ranids, however, did not elicit different levels of FA.
CRISPR/Cas9‐mediated knockout of Ms1 enables the rapid generation of male‐sterile hexaploid wheat lines for use in hybrid seed production

Summary The development and adoption of hybrid seed technology have led to dramatic increases in agricultural productivity. However, it has been a challenge to develop a commercially viable platform for the production of hybrid wheat (Triticum aestivum) seed due to wheat's strong inbreeding habit. Recently, a novel platform for commercial hybrid seed production was described. This hybridization platform utilizes nuclear male sterility to force outcrossing and has been applied to maize and rice. With the recent molecular identification of the wheat male fertility gene Ms1, it is now possible to extend the use of this novel hybridization platform to wheat. In this report, we used the CRISPR/Cas9 system to generate heritable, targeted mutations in Ms1. The introduction of biallelic frameshift mutations into Ms1 resulted in complete male sterility in wheat cultivars Fielder and Gladius, and several of the selected male‐sterile lines were potentially non‐transgenic. Our study demonstrates the utility of the CRISPR/Cas9 system for the rapid generation of male sterility in commercial wheat cultivars. This represents an important step towards capturing heterosis to improve wheat yields, through the production and use of hybrid seed on an industrial scale.
PEEK surface modification by fast ambient-temperature sulfonation for bone implant applications

We develop a simple, fast and economical surface treatment under ambient temperature to improve the hydrophilicity and osteoconductivity of polyetheretherketone (PEEK) for bone implant applications. A major challenge in bone implants is the drastic difference in stiffness between traditional implant materials (such as titanium and stainless steel) and human bone. PEEK is biocompatible with an elastic modulus closely matching that of human bone, making it a highly attractive alternative. However, its bio-inert and poorly hydrophilic surface presents a serious challenge for osseointegration. Sulfonation can improve hydrophilicity and introduce bioactive sulfonate groups, but PEEK sulfonation has traditionally been applied for fuel cells, employing elevated temperatures and long reaction times to re-cast PEEK into sulfonated films. Little research has systematically studied PEEK surface modification by short reaction time (seconds) and ambient-temperature sulfonation for biomedical applications. Here, we investigate three ambient-temperature sulfonation treatments under varying reaction times (5–90 s) and evaluate the hydrophilicity and morphology of 15 modified PEEK surfaces. We establish an optimal treatment using 30 s H2SO4 followed by 20 s rinsing, and then 20 s immersion in NaOH followed by 20 s rinsing. This 30 s ambient-temperature sulfonation is found to be more effective than conventional plasma treatments and reduced PEEK water contact angle from 78° to 37°.
Measuring the performance of the Mental Health Continuum-Short Form (MHC-SF) in a primary care youth mental health service

Objectives Mental health is regarded as more than the absence of mental health difficulties, with clinical and research focus moving towards measurement of well-being. The Mental Health Continuum-Short Form (MHC-SF) was developed to assess overall and emotional, social and psychological well-being. Little is known about the use of the MHC-SF with young people engaging with mental health services. The current pilot study sought to examine the performance of the MHC-SF in an Irish primary care youth mental health service for 12–25 year olds. Methods A sample of 229 young people (female n=143; male n=85, unknown n=1) aged 12–24 years (M=15.87, SD=2.51) who completed the MHC-SF prior to commencing their first intervention session in Jigsaw participated in this study. The psychometric properties of the MHC-SF were investigated using confirmatory factor analysis (CFA) and Cronbach’s alpha for internal consistency. Results CFA supported the three-factor structure of the MHC-SF for emotional, social, and psychological well-being, and very good internal consistency was observed. Conclusion Findings provide evidence for the psychometric properties of the MHC-SF in a primary care youth mental health setting, and suggest that the MHC-SF’s three-factor structure is valid for use in this context. Limitations and recommendations for future research are discussed.