Miracle-dz/UniFAR-FTUs huggingface dataset:
Administration of GDF3 Into Septic Mice Improves Survival via Enhancing LXRα-Mediated Macrophage Phagocytosis

The defective eradication of invading pathogens is a major cause of death in sepsis. As professional phagocytic cells, macrophages actively engulf/kill microorganisms and play essential roles in innate immune response against pathogens. Growth differentiation factor 3 (GDF3) was previously implicated as an important modulator of inflammatory response upon acute sterile injury. In this study, administration of recombinant GDF3 protein (rGDF3) either before or after CLP surgery remarkably improved mouse survival, along with significant reductions in bacterial load, plasma pro-inflammatory cytokine levels, and organ damage. Notably, our in vitro experiments revealed that rGDF3 treatment substantially promoted macrophage phagocytosis and intracellular killing of bacteria in a dose-dependent manner. Mechanistically, RNA-seq analysis results showed that CD5L, known to be regulated by liver X receptor α (LXRα), was the most significantly upregulated gene in rGDF3-treated macrophages. Furthermore, we observed that rGDF3 could promote LXRα nuclear translocation and thereby, augmented phagocytosis activity in macrophages, which was similar as LXRα agonist GW3965 did. By contrast, pre-treating macrophages with LXRα antagonist GSK2033 abolished beneficial effects of rGDF3 in macrophages. In addition, rGDF3 treatment failed to enhance bacteria uptake and killing in LXRα-knockout (KO) macrophages. Taken together, these results uncover that GDF3 may represent a novel mediator for controlling bacterial infection.
Bile Duct Injury During Cholecystectomy: Necessity to Learn How to Do and Interpret Intraoperative Cholangiography

Introduction: Biliary duct injury (BDI) is a serious complication during cholecystectomy. Perioperative cholangiography (POC) has recently been generating interest in order to prevent BDI. However, the current literature (including randomized controlled trials) cannot conclude whether POC is protective or not against the risk of BDI. The aim of our study was to investigate whether POC could demonstrate earlier BDI and which criteria are required to make that diagnosis. Methods: We performed a retrospective study between 2005 and 2018 in our French tertiary referral center, which included all patients who had presented following BDI during cholecystectomy. Results: Twenty-two patients were included. Nine patients had POC, whereas 13 did not. When executed, POC was interpreted as normal for three patients and abnormal for six. In this latter group, only two cases had a BDI diagnosed intraoperatively. In other cases, the interpretation was not adequate. Conclusion: BDIs are rare but may reduce patients' quality of life. Our study highlights the surgeon's responsibility to learn how to perform and interpret POC in order to diagnose and manage BDIs and potentially avoid catastrophic consequences.
Fatigue-Related Changes in Spatiotemporal Parameters, Joint Kinematics and Leg Stiffness in Expert Runners During a Middle-Distance Run

Fatigue with its underlying mechanisms and effects is a broadly discussed topic and an important phenomenon, particularly in endurance sports. Although several studies have already shown a variety of changes in running kinematics with fatigue, few of them have analyzed competitive runners and even fewer have focused on middle-distance running. Furthermore, the studies investigating fatigue-related changes have mostly reported the results in terms of discrete parameters [e.g., range of motion (RoM)] in the frontal or sagittal plane, and therefore potentially overlooked effects occurring in subphases of the gait cycle or in the transverse plane. On this basis, the goal of the present study was to analyze the effects of exhaustive middle-distance running on expert runners by means of both discrete parameters and time series analysis in 3D. In this study, 13 runners ran on a treadmill to voluntary exhaustion at their individually determined fatigue speeds which was held constant during the measurements. Kinematic data were collected by means of a 3D motion capture system. Spatiotemporal and stiffness parameters as well as the RoM of joints and of center of mass (CoM) within the stance and flight phases were calculated. Independent t-tests were performed to investigate any changes in means and coefficients of variation (CV) of these parameters between the rested (PRE) and fatigued (POST) state. Statistical parametric mapping method was applied on the time series data of the joints and the CoM. Results from this exploratory study revealed that during a middle-distance run, expert runners change their stance time, rather than their step frequency or step length in order to maintain the constant running speed as long as possible. Increased upper body movements occurred to counteract the increased angular moment of the lower body possibly due to longer stance times. These findings provide insights into adaptation strategies of expert runners during a fatiguing middle-distance run and may serve a valuable information particularly for comparisons with other group of runners (e.g., females or non-athletes) as well with other conditions (e.g., non-constant speed or interval training), and might be useful for the definition of training goals (e.g., functional core training).
Molecular Characterization of blaIMP–4-Carrying Enterobacterales in Henan Province of China

Carbapenem-resistant Enterobacterales (CRE) pose a serious threat to clinical management and public health. We investigated the molecular characteristics of 12 IMP-4 metallo-β-lactamase-producing strains, namely, 5 Enterobacter cloacae, 3 Escherichia coli, 2 Klebsiella pneumoniae, and 2 Citrobacter freundii. These strains were collected from a tertiary teaching hospital in Zhengzhou from 2013 to 2015. The minimum inhibitory concentration (MIC) results showed that each blaIMP–4-positive isolate was multidrug-resistant (MDR) but susceptible to colistin. All of the E. coli belonged to ST167, two C. freundii isolates belonged to ST396, and diverse ST types were identified in E. cloacae and K. pneumoniae. S1-PFGE, Southern blotting, and PCR-based replicon typing assays showed that the blaIMP–4-carrying plasmids ranged from ∼52 to ∼360 kb and belonged to FII, FIB, HI2/HI2A, and N types. N plasmids were the predominant type (8/12, 66.7%). Plasmid stability testing indicated that the blaIMP–4-carrying N-type plasmid is more stable than the other types of plasmids. Conjugative assays revealed that three of the blaIMP–4-carrying N plasmids were transferrable. Complete sequence analysis of a representative N type (pIMP-ECL14–57) revealed that it was nearly identical to pIMP-FJ1503 (KU051710) (99% nucleotide identity and query coverage), an N-type blaIMP–4-carrying epidemic plasmid in a C. freundii strain. PCR mapping indicated that a transposon-like structure [IS6100-mobC-intron (K1.pn.I3)-blaIMP–4-IntI1-IS26] was highly conserved in all of the N plasmids. IS26 involved recombination events that resulted in variable structures of this transposon-like module in FII and FIB plasmids. The blaIMP–4 gene was captured by a sul1-type integron In1589 on HI2/HI2A plasmid pIMP-ECL-13–46.
Presence of the Weakly Pathogenic Fusarium poae in the Fusarium Head Blight Disease Complex Hampers Biocontrol and Chemical Control of the Virulent Fusarium graminearum Pathogen

Fusarium head blight (FHB) in wheat (Triticum aestivum L.) is caused by a consortium of mutually interacting Fusarium species. In the field, the weakly pathogenic F. poae often thrives on the infection sites of the virulent F. graminearum. In this ecological context, we investigated the efficacy of chemical and biocontrol agents against F. graminearum in wheat ears. For this purpose, one fungicide comprising prothioconazole + spiroxamine and two bacterial biocontrol strains, Streptomyces rimosus LMG 19352 and Rhodococcus sp. R-43120 were tested for their efficacy to reduce FHB symptoms and mycotoxin (deoxynivalenol, DON) production by F. graminearum in presence or absence of F. poae. Results showed that the fungicide and both actinobacterial strains reduced FHB symptoms and concomitant DON levels in wheat ears inoculated with F. graminearum. Where Streptomyces rimosus appeared to have direct antagonistic effects, Rhodococcus and the fungicide mediated suppression of F. graminearum was linked to the archetypal salicylic acid and jasmonic acid defense pathways that involve the activation of LOX1, LOX2 and ICS. Remarkably, this chemical- and biocontrol efficacy was significantly reduced when F. poae was co-inoculated with F. graminearum. This reduced efficacy was linked to a suppression of the plant’s intrinsic defense system and increased levels of DON. In conclusion, our study shows that control strategies against the virulent F. graminearum in the disease complex causing FHB are hampered by the presence of the weakly pathogenic F. poae. This study provides generic insights in the complexity of control strategies against plant diseases caused by multiple pathogens.
A Comparative Psycholinguistic Study on the Subjective Feelings of Well-Being Outcomes of Foreign Language Learning in Older Adults From the Czech Republic and Poland

Positive psychology has recently seen unprecedented rise and has reached vast achievements in the area of quality of life (QoL) improvement. The purpose of this study is to show that there are different aspects of well-being that make healthy older people motivated to learn a foreign language at a later age. The research was conducted in the Czech Republic and Poland in two groups of learners aged 55 years and more. The experimental group consisted of 105 Czech respondents who were targeted with an online questionnaire with the aim to determine the level of FLL outcomes connected to QoL in healthy older adults in their L2 acquisition. The second experimental group (n = 100) was established of Polish seniors who attended similar language courses. The findings of the research clearly show that FLL has an irreplaceable role as one of several non-pharmacological strategies utilized to improve the aging process and reduce drawbacks of aging. The results indicate that seniors' overall satisfaction and subjective feelings of well-being are enormously high when attending foreign language classes at older age. FLL, therefore, creates an environment that can enhance QoL of older adults that can be supplemented by other means such as well-balanced diet, other social activities, sport and physical activity, music, or computer games. All these intervention methods can significantly improve QoL of older adults and the parties engaged and/or responsible for taking care of older generation should take it into serious consideration.
The Effects of Selective Inhibition of Histone Deacetylase 1 and 3 in Huntington’s Disease Mice

Huntington’s disease (HD) is an autosomal dominant neurodegenerative disease characterized by a late clinical onset of psychiatric, cognitive, and motor symptoms. Transcriptional dysregulation is an early and central disease mechanism which is accompanied by epigenetic alterations in HD. Previous studies demonstrated that targeting transcriptional changes by inhibition of histone deacetylases (HDACs), especially the class I HDACs, provides therapeutic effects. Yet, their exact mechanisms of action and the features of HD pathology, on which these inhibitors act remain to be elucidated. Here, using transcriptional profiling, we found that selective inhibition of HDAC1 and HDAC3 by RGFP109 alleviated transcriptional dysregulation of a number of genes, including the transcription factor genes Neurod2 and Nr4a2, and gene sets and programs, especially those that are associated to insulin-like growth factor pathway, in the striatum of R6/1 mice. RGFP109 treatment led to a modest improvement of the motor skill learning and coordination deficit on the RotaRod test, while it did not alter the locomotor and anxiety-like phenotypes in R6/1 animals. We also found, by volumetric MRI, a widespread brain atrophy in the R6/1 mice at the symptomatic disease stage, on which RGFP109 showed no significant effects. Collectively, our combined work suggests that specific HDAC1 and HDAC3 inhibition may offer benefits for alleviating the motor phenotypic deficits and transcriptional dysregulation in HD.
Phonological Underspecification: An Explanation for How a Rake Can Become Awake

Neural markers, such as the mismatch negativity (MMN), have been used to examine the phonological underspecification of English feature contrasts using the Featurally Underspecified Lexicon (FUL) model. However, neural indices have not been examined within the approximant phoneme class, even though there is evidence suggesting processing asymmetries between liquid (e.g., /ɹ/) and glide (e.g., /w/) phonemes. The goal of this study was to determine whether glide phonemes elicit electrophysiological asymmetries related to [consonantal] underspecification when contrasted with liquid phonemes in adult English speakers. Specifically, /ɹɑ/ is categorized as [+consonantal] while /wɑ/ is not specified [i.e., (–consonantal)]. Following the FUL framework, if /w/ is less specified than /ɹ/, the former phoneme should elicit a larger MMN response than the latter phoneme. Fifteen English-speaking adults were presented with two syllables, /ɹɑ/ and /wɑ/, in an event-related potential (ERP) oddball paradigm in which both syllables served as the standard and deviant stimulus in opposite stimulus sets. Three types of analyses were used: (1) traditional mean amplitude measurements; (2) cluster-based permutation analyses; and (3) event-related spectral perturbation (ERSP) analyses. The less specified /wɑ/ elicited a large MMN, while a much smaller MMN was elicited by the more specified /ɹɑ/. In the standard and deviant ERP waveforms, /wɑ/ elicited a significantly larger negative response than did /ɹɑ/. Theta activity elicited by /ɹɑ/ was significantly greater than that elicited by /wɑ/ in the 100–300 ms time window. Also, low gamma activation was significantly lower for /ɹɑ/ vs. /wɑ/ deviants over the left hemisphere, as compared to the right, in the 100–150 ms window. These outcomes suggest that the [consonantal] feature follows the underspecification predictions of FUL previously tested with the place of articulation and voicing features. Thus, this study provides new evidence for phonological underspecification. Moreover, as neural oscillation patterns have not previously been discussed in the underspecification literature, the ERSP analyses identified potential new indices of phonological underspecification.
The Small GTPase Cdc42 Negatively Regulates the Formation of Neutrophil Extracellular Traps by Engaging Mitochondria

Neutrophil granulocytes represent the first line of defense against invading pathogens. In addition to the production of Reactive Oxygen Species, degranulation, and phagocytosis, these specialized cells are able to extrude Neutrophil Extracellular Traps. Extensive work was done to elucidate the mechanism of this special form of cell death. However, the exact mechanisms are still not fully uncovered. Here we demonstrate that the small GTPase Cdc42 is a negative regulator of NET formation in primary human and murine neutrophils. We present a functional role for Cdc42 activity in NET formation that differs from the already described NETosis pathways. We show that Cdc42 deficiency induces NETs independent of the NADPH-oxidase but dependent on protein kinase C. Furthermore, we demonstrate that Cdc42 deficiency induces NETosis through activation of SK-channels and that mitochondria play a crucial role in this process. Our data therefore suggests a mechanistic role for Cdc42 activity in primary human neutrophils, and identify Cdc42 activity as a target to modulate the formation of Neutrophil Extracellular Traps.
Expression, Characterization and Its Deinking Potential of a Thermostable Xylanase From Planomicrobium glaciei CHR43

Genome mining is more and more widely used in identifying new enzymes from database. In the present study, we reported a putative xylanase, Pg-Xyn (WP_053166147.1), which originated from a psychrotolerant strain Planomicrobium glaciei CHR 43, and was identified from Genbank by genome mining. Sequence analysis and homology modeling showed that Pg-Xyn belongs to glycosyl hydrolase family 10. On the basis of heterologous expression in E. coli and biochemical characterization, we found Pg-Xyn was most active at pH 9.0 and 80°C and exhibited good stability from pH 5.0 to 12.0 and below 90°C. Pg-Xyn was slightly activated in the presence of Ca2+ and Mg2+, while it was strongly inhibited by Mn2+. The analysis of hydrolysis products showed that Pg-Xyn was an endo-β-1,4-xylanase. In addition, Pg-Xyn performed good deinking ability in a paper deinking test. In consideration of its unique properties, Pg-Xyn might be a promising candidate for application in the paper and pulp industries.
Hypoxic Characteristic in the Immunosuppressive Microenvironment of Hepatocellular Carcinoma

Background: Generally, hepatocellular carcinoma (HCC) exists in an immunosuppressive microenvironment that promotes tumor evasion. Hypoxia can impact intercellular crosstalk in the tumor microenvironment. This study aimed to explore and elucidate the underlying relationship between hypoxia and immunotherapy in patients with HCC. Methods: HCC genomic and clinicopathological datasets were obtained from The Cancer Genome Atlas (TCGA-LIHC), Gene Expression Omnibus databases (GSE14520) and International Cancer Genome Consortium (ICGC-LIRI). The TCGA-LIHC cases were divided into clusters based on single sample gene set enrichment analysis and hierarchical clustering. After identifying patients with immunosuppressive microenvironment with different hypoxic conditions, correlations between immunological characteristics and hypoxia clusters were investigated. Subsequently, a hypoxia-associated score was established by differential expression, univariable Cox regression, and lasso regression analyses. The score was verified by survival and receiver operating characteristic curve analyses. The GSE14520 cohort was used to validate the findings of immune cell infiltration and immune checkpoints expression, while the ICGC-LIRI cohort was employed to verify the hypoxia-associated score. Results: We identified hypoxic patients with immunosuppressive HCC. This cluster exhibited higher immune cell infiltration and immune checkpoint expression in the TCGA cohort, while similar significant differences were observed in the GEO cohort. The hypoxia-associated score was composed of five genes (ephrin A3, dihydropyrimidinase like 4, solute carrier family 2 member 5, stanniocalcin 2, and lysyl oxidase). In both two cohorts, survival analysis revealed significant differences between the high-risk and low-risk groups. In addition, compared to other clinical parameters, the established score had the highest predictive performance at both 3 and 5 years in two cohorts. Conclusion: This study provides further evidence of the link between hypoxic signals in patients and immunosuppression in HCC. Defining hypoxia-associated HCC subtypes may help reveal potential regulatory mechanisms between hypoxia and the immunosuppressive microenvironment, and our hypoxia-associated score could exhibit potential implications for future predictive models.
Completeness of Retention Data and Determinants of Attrition in Birth Cohorts of Very Preterm Infants: A Systematic Review

Background: Birth cohorts provided essential knowledge for clinical and public health decision-making. However, little is known about retention and determinants of attrition in these specific longitudinal studies, although characterizing predictors of attrition sets the path to mitigate its occurrence and to promote valid inferences. We systematically reviewed retention in follow-ups of birth cohorts of very preterm or very low birth weight infants and the determinants of attrition. PROSPERO registration number: CRD42017082672. Methods: Publications were identified through PubMed®, Scopus, Web of Science, and Cochrane Library databases from inception to December 2017. Studies were included when reporting at least one of the following: retention at follow-ups, reasons for attrition, or characteristics of non-participants. Quality assessment was conducted using the completeness of the report of participation features in the articles. Non-participant's characteristics were presented using descriptive statistics. Local polynomial regression was used to describe overall retention trends over years of follow-up. Results: We identified 57 eligible publications, reporting on 39 birth cohorts and describing 83 follow-up evaluations. The overall median retention was 87% (p25–p75:75.8–93.6), ranging from 14.6 to 100%. Overall, retention showed a downward trend with increasing child age. Completeness of retention report was considered “enough” in only 36.8% of publications. Considering the 33 (57.9%) publications providing information on participants and non-participants, and although no formal meta-analysis was performed, it was evident that participants lost to follow-up were more often male, had foreign-born, multiparous, and younger mothers, and with a lower socioeconomic status. Conclusion: This systematic review evidenced a lack of detailed data on retention, which may threaten the potential use of evidence derived from cohort studies of very preterm infants for clinical and public health purpose. It supports the requirement for a standardized presentation of retention features responding to current guidelines.
Meningococcal Vaccines: A Technological Revolution

The sneaky meningococcus is a bacterium that can cause terrible disease. Development of an effective vaccine has been extremely difficult. Meningococcal vaccines developed in the 1990s are based on the bacterial capsule, a shield that protects the bacteria and that is used to instruct our body to combat this terrible disease. These vaccines work against four types of meningococcus: A, C, W, and Y. However, they do not work against meningococcus B. Scientists had to invent a completely new way to make vaccines, reading the bacterial DNA to search for new protective components. With this new approach, named reverse vaccinology, three new bacterial components were discovered: NadA, NHBA, and fHbp. When combined with a fourth component (PorA), they form the 4CMenB vaccine. This vaccine has reduced meningococcal disease in infants by 75% in the UK. Today, 4CMenB protects children all around the world.