Miracle-dz/UniFAR-FTUs huggingface dataset:
A pathologic two‐way street: how innate immunity impacts lung fibrosis and fibrosis impacts lung immunity

Lung fibrosis is characterised by the accumulation of extracellular matrix within the lung and is secondary to both known and unknown aetiologies. This accumulation of scar tissue limits gas exchange causing respiratory insufficiency. The pathogenesis of lung fibrosis is poorly understood, but immunologic‐based treatments have been largely ineffective. Despite this, accumulating evidence suggests that innate immune cells and receptors play important modulatory roles in the initiation and propagation of the disease. Paradoxically, while innate immune signalling may be important for the pathogenesis of fibrosis, there is also evidence to suggest that innate immune function against pathogens may be impaired, leading to dysregulated and/or impaired host defence. This review summarises the evidence for this pathologic two‐way street, highlights new concepts of pathogenesis and recommends future directions for research emphasis.
Association of the TP53 rs1042522 C>G polymorphism and hepatoblastoma risk in Chinese children

The TP53 gene encodes an important class of cell cycle and tumor-suppressing factors that play critical roles in maintaining genomic stability. The TP53 Arg72Pro (rs1042522 C>G) polymorphism has been reported to be associated with the risk of several types of adult cancers; however, its risk for pediatric cancers remains unclear. Here, we analyzed the association of the TP53 gene rs1042522 C>G polymorphism with hepatoblastoma (HB) susceptibility in a hospital-based study among Chinese children. A total of 213 HB patients and 958 healthy controls were enrolled in the study. Genotypes were determined by a TaqMan assay, and the strength of the association was assessed by the odds ratios and 95% confidence intervals generated from logistic regression models, adjusted for age, gender, and clinical stage. No significant association between the TP53 rs1042522 C>G polymorphism and HB susceptibility was detected in the main analysis or in stratification analyses of age, gender, and clinical stages. Overall, the TP53 gene rs1042522 C>G polymorphism is not associated with HB susceptibility in the Chinese population, other polymorphisms alone or in combination should be investigated to further clarify HB susceptibility.
Validation of modified albumin-bilirubin-TNM score as a prognostic model to evaluate patients with hepatocellular carcinoma

BACKGROUND An ideal staging system for hepatocellular carcinoma (HCC) should rely on the hepatic reserve function and tumor burden. With the improvement in diagnostic and treatment strategies for HCC, in addition to recent treatment of viral hepatitis, finding a suitable assessment tool for hepatic reserve has become mandatory. AIM To validate a recently proposed modified albumin-bilirubin-TNM (mALBI-T) grade as a prognostic model for patients with HCC in Egypt. METHODS For patients diagnosed with HCC, Child-Turcotte-Pugh (CTP) score, Barcelona Clinic Liver Cancer (BCLC) stage, albumin-bilirubin (ALBI), plateltet-albumin–bilirubin (PALBI), ALBI-based BCLC, ALBI-T and mALBI-T grades were estimated. Patients were followed from time of diagnosis to date of death or date of data collection if they remained alive. Overall survival and received treatments were determined. Survival data were analyzed. RESULTS A total of 1910 patients were included (mean age, 57 years; 1575 males). At presentation, 50.6% had CTP A, 36.1% had CTP B and 13.4 % had CTP C; 12% had ALBI grade 1, 62.3% had ALBI grade 2 and 24.7% had ALBI grade 3. Overall median survival was 13 mo; survival was better in patients with ALBI 1 than in those with ALBI 2 and 3 (28.6 vs 14 and 5.8 mo, respectively, P < 0.001). Patients with ALBI-T grades 0 and 1 had better survival than those with ALBI-T grades 2, 3, 4 and 5 (P < 0.001). The modified ALBI-T showed better stratification and significant improvement in prediction of survival. CONCLUSION ALBI-T grade is a superior prognostic tool that selects patients with HCC who have better liver reservoir and tumor stage. mALBI-T is a better prognostic model in patients with HCC.
Human spermatozoa anti-proprotein convertase subtilisin/kexin type 4 synthesis using New Zealand rabbit for novel immunocontraception in males

Purpose Proprotein convertase subtilisin/kexin type 4 (PCSK4, a 54-kDa protease) is expressed in the plasma membrane of the acrosome in human spermatozoa. It plays a critical role in penetrating the zona pellucida. Synthesis of human anti-PCSK4 might be important for novel male immunocontraception. Materials and Methods We used semen from adult males as the source of antigen (acrosomal PCSK4). Isolation and antigen characterization were done by immunohistochemistry followed by electrophoresis. Purification of PCSK4 was done by the electroelution method, followed by immunization with an animal model (Oryctolagus cuniculus). Antibody was collected, purified, and tested by using Western blot and dot blot. Antibody in vitro potential testing was performed on human spermatozoa by laser scanning microscopy with rhodamine stain under a light microscope and on rat spermatozoa. Results Human anti-PCSK4 bound with PCSK4 on the head of human spermatozoa and could interfere with rat spermatozoa activity to penetrate the oocyte. Conclusions The result of this study can be used as a basis to develop new immunocontraceptives targeted towards males. This study shows that antibodies from induction of PCSK4 from spermatozoa may hinder fertilization.
Incomplete neutralization and maintenance of phonological contrasts in varieties of Standard German

We investigated the perceptibility of stop voicing in a domain-final neutralizing context in German that according to various phonological models is completely neutralized in favour of the voiceless category but that according to various empirical studies is distinguishable phonetically. A primary aim was to determine whether acoustic cues that were available for the stop voicing distinction were perceptible in a neutralizing context. A secondary aim was to assess whether voicing perception was influenced by phonotactic frequency and the potential for resyllabification. Nineteen listeners of a Standard German speaking variety made forcedchoice judgments to synthetic stimuli spanning a voiced-voiceless continuum containing domain-final alveolar and velar stops in various neutralizing contexts that differed in terms of phonotactic probability and the potential for resyllabification. Our results showed that voicing information could be distinguished but that the perceptibility of this distinction also depended on statistical properties of phoneme sequences and whether a domain-final stop could potentially be perceptually resyllabified as domain-initial. Our general conclusion is that a categorical neutralization model is insufficient to account for stop voicing perception in German in a domain-final context: instead, voicing perceptibility in these contexts depends on an interaction between acoustic information and phonological knowledge which emerges as a generalization across the lexicon. * A version of this chapter was published in the Journal of Phonetics, 38 (Kleber, John, & Harrington, 2010).
Stabilisation of time delay systems with nonlinear disturbances using sliding mode control

This paper focuses on a class of control systems with delayed states and nonlinear disturbances using sliding mode techniques. Both matched and mismatched uncertainties are considered which are assumed to be bounded by known nonlinear functions. The bounds are used in the control design and analysis to reduce conservatism. A sliding function is designed and a set of sufficient conditions is derived to guarantee the asymptotic stability of the corresponding sliding motion by using the Lyapunov-Razumikhin approach which allows large time-varying delay with fast changing rate. A delay dependent sliding mode control is synthesised to drive the system to the sliding surface in finite time and maintain a sliding motion thereafter. Effectiveness of the proposed method is demonstrated via a case study on a continuous stirred tank reactor system.
Julia's Efficient Algorithm for Subtyping Unions and Covariant Tuples (Pearl)

9 The Julia programming language supports multiple dispatch and provides a rich type annotation 10 language to specify method applicability. When multiple methods are applicable for a given call, 11 Julia relies on subtyping between method signatures to pick the correct method to invoke. Julia’s 12 subtyping algorithm is surprisingly complex, and determining whether it is correct remains an open 13 question. In this paper, we focus on one piece of this problem: the interaction between union 14 types and covariant tuples. Previous work normalized unions inside tuples to disjunctive normal 15 form. However, this strategy has two drawbacks: complex type signatures induce space explosion, 16 and interference between normalization and other features of Julia’s type system. In this paper, 17 we describe the algorithm that Julia uses to compute subtyping between tuples and unions—an 18 algorithm that is immune to space explosion and plays well with other features of the language. We 19 prove this algorithm correct and complete against a semantic-subtyping denotational model in Coq. 20 2012 ACM Subject Classiﬁcation Theory of computation → Type theory 21
What Message Characteristics Make Social Engineering Successful on Facebook: The Role of Central Route, Peripheral Route, and Perceived Risk

Past research suggests that the human ability to detect social engineering deception is very limited, and it is even more limited in the virtual environment of social networking sites (SNS) such as Facebook. At the organizational level, research suggests that social engineers could succeed even among those organizations that identify themselves as being aware of social engineering techniques. This may be partly due to the complexity of human behaviors in failing to recognize social engineering tricks in SNSs. Due to the vital role that persuasion and perception play on users’ decision to accept or reject social engineering tricks, this paper aims to investigate the impact of message characteristics on users’ susceptibility to social engineering victimization on Facebook. In doing so, we investigate the role of the central route of persuasion, peripheral route of persuasion, and perceived risk on susceptibility to social engineering on Facebook. In addition, we investigate the mediation effects between the explored factors, and whether there is any relationship between the effectiveness of them and users’ demographics.
Expression of target genes in cumulus cells derived from human oocytes with and without blastocyst formation

Objective: The transcriptional profile of cumulus cells (CCs) during oocyte maturation provides information for predicting oocyte developmental competence. Our previous study using a mouse model indicated that there were nine different genes related to oocyte development potential expressed in CCs during oocyte maturation. The purpose of this study was to elucidate whether gene expression levels of CCs during oocyte maturation are associated with oocyte developmental competence. Methods: The human CCs collected from each oocyte were divided into two groups after tracking depending on whether or not they developed to the blastocyst stage: (1) the oocytes were developed to blastocyst stage after fertilization (B+) and (2) the oocytes were not developed to blastocyst stage after fertilization (B−). The expression levels of the nine selected genes (ARRB1, ATP2C1, CDH5, CNTNAP1, LGR4, MKLN1, RHOBTB1, SIX2, and SMC2) were examined. CCs were obtained from 29 women who were undergoing intracytoplasmic sperm injection treatment cycles. Quantitative reverse transcriptase-polymerase chain reaction analysis was performed on cumulus masses collected before insemination. Each sample was run three times. Statistically significant differences in mRNA expression of the target genes in independent samples were evaluated by two-tailed Student's t-test, and P < 0.05 was considered significantly different. Results: There were significant differences in the mRNA expression levels of ARRB1 (P = 0.016), LGR4 (P = 0.025), and SMC2 (P = 0.013) between the groups B+ and B−. Gene expression of ARRB1, LGR4, and SMC2 in CCs is related to blastocyst development. Conclusions: Analysis of expression of ARRB1, LGR4, and SMC2 genes in CCs as biomarkers may provide predictive information on oocyte developmental competence before insemination and fertilization.
Contralateral C7 transfer combined with acellular nerve allografts seeded with differentiated adipose stem cells for repairing upper brachial plexus injury in rats

Nerve grafting has always been necessary when the contralateral C7 nerve root is transferred to treat brachial plexus injury. Acellular nerve allograft is a promising alternative for the treatment of nerve defects, and results were improved by grafts laden with differentiated adipose stem cells. However, use of these tissue-engineered nerve grafts has not been reported for the treatment of brachial plexus injury. The aim of the present study was to evaluate the outcome of acellular nerve allografts seeded with differentiated adipose stem cells to improve nerve regeneration in a rat model in which the contralateral C7 nerve was transferred to repair an upper brachial plexus injury. Differentiated adipose stem cells were obtained from Sprague-Dawley rats and transdifferentiated into a Schwann cell-like phenotype. Acellular nerve allografts were prepared from 15-mm bilateral sections of rat sciatic nerves. Rats were randomly divided into three groups: acellular nerve allograft, acellular nerve allograft + differentiated adipose stem cells, and autograft. The upper brachial plexus injury model was established by traction applied away from the intervertebral foramen with micro-hemostat forceps. Acellular nerve allografts with or without seeded cells were used to bridge the gap between the contralateral C7 nerve root and C5–6 nerve. Histological staining, electrophysiology, and neurological function tests were used to evaluate the effect of nerve repair 16 weeks after surgery. Results showed that the onset of discernible functional recovery occurred earlier in the autograft group first, followed by the acellular nerve allograft + differentiated adipose stem cells group, and then the acellular nerve allograft group; moreover, there was a significant difference between autograft and acellular nerve allograft groups. Compared with the acellular nerve allograft group, compound muscle action potential, motor conduction velocity, positivity for neurofilament and S100, diameter of regenerating axons, myelin sheath thickness, and density of myelinated fibers were remarkably increased in autograft and acellular nerve allograft + differentiated adipose stem cells groups. These findings confirm that acellular nerve allografts seeded with differentiated adipose stem cells effectively promoted nerve repair after brachial plexus injuries, and the effect was better than that of acellular nerve repair alone. This study was approved by the Animal Ethics Committee of the First Affiliated Hospital of Sun Yat-sen University of China (approval No. 2016-150) in June 2016.
Inducing α-synuclein compaction: a new strategy for inhibiting α-synuclein aggregation?

COMMENTS TO AUTHORS This is a very well written invited comment on the work of Carija et al (2019) that explored the inhibition of alpha synuclein aggregation using an in vitro model of double cysteine mutation that render the initial molecule more compact. The lower aggregation of this form (as compared to wt) was not only an intrinsic characteristic but may delay the aggregation of the wt form (when mixed). A complete biochemical analysis of the behaviour of this mutant form is provided and nicely summarised in this invited paper.
Development and validation of a nomogram for predicting the probability of live birth in infertile women

Objective: To develop a nomogram to predict the probability of live birth on the basis of the association of patient characteristics in subfertile individuals or couples. Methods: A retrospective study was conducted from January 2014 to December 2015. A nomogram was built from a training cohort and tested on an independent validation cohort. A total of 2,257 patients who had undergone their first nondonor cycle of in vitro fertilization (IVF) (including intracytoplasmic sperm injection) were randomly split 2:1 into training (n = 1,527) and validation (n = 730) cohorts. Results: There were no statistically significant differences in the patients' baseline and cycle characteristics between the training and validation cohorts. On multiple logistic regression analysis, female age, antral follicle count, tubal factor, anovulation, ethnicity, unexplained fertility, and male factor were significantly associated with live birth. The nomogram had a C-index of 0.700 (95% confidence interval [CI]: 0.698–0.701) in the training cohort and 0.684 (95% CI: 0.681–0.687) in the validation cohort. Conclusions: Our nomogram can predict the probability of live birth for infertile women and can be used to guide clinicians and couples to decide on an IVF treatment option.
Atsttrin reduces lipopolysaccharide-induced neuroinflammation by inhibiting the nuclear factor kappa B signaling pathway

Progranulin is closely related to neuronal survival in a neuroinflammatory mouse model and attenuates inflammatory reactions. Atsttrin is an engineered protein composed of three progranulin fragments and has been shown to have an effect similar to that of progranulin. Atsttrin has anti-inflammatory actions in multiple arthritis mouse models, and it protects against further arthritis development. However, whether Atsttrin has a role in neuroinflammation remains to be elucidated. In this study, we produced a neuroinflammatory mouse model by intracerebroventricular injection of 1 μL lipopolysaccharide (10 μg/μL). Atsttrin (2.5 mg/kg) was administered via intraperitoneal injection every 3 days over a period of 7 days before intracerebroventricular injection of 1 μL lipopolysaccharide (10 μg/μL). In addition, astrocyte cultures were treated with 0, 100 or 300 ng/mL lipopolysaccharide, with 200 ng/mL Atsttrin simultaneously. Immunohistochemistry, enzyme-linked immunosorbent assay and real-time reverse transcription-polymerase chain reaction were performed to examine the protein and mRNA levels of inflammatory mediators and to assess activation of the nuclear factor kappa B signaling pathway. Progranulin expression in the brain of wild-type mice and in astrocyte cultures was increased after lipopolysaccharide administration. The protein and mRNA expression levels of tumor necrosis factor-α, interleukin-1β and inducible nitric oxide synthase were increased in the brain of progranulin knockout mice after lipopolysaccharide administration. Atsttrin treatment reduced the lipopolysaccharide-induced increase in the protein and mRNA levels of tumor necrosis factor-α, interleukin-1β, matrix metalloproteinase-3 and inducible nitric oxide synthase in the brain of progranulin knockout mice. Atsttrin also reduced the expression of cyclooxygenase-2, inducible nitric oxide synthase and matrix metalloproteinase 3 mRNA in lipopolysaccharide-treated astrocytes in vitro, and decreased the concentration of tumor necrosis factor a and interleukin-1β in the supernatant. Furthermore, Atsttrin significantly reduced the levels of phospho-nuclear factor kappa B inhibitor a in the brain of lipopolysaccharide-treated progranulin knockout mice and astrocytes, and it decreased the expression of nuclear factor kappa B2 in astrocytes. Collectively, our findings show that the anti-neuroinflammatory effect of Atsttrin involves inhibiton of the nuclear factor kappa B signaling pathway, and they suggest that Atsttrin may have clinical potential in neuroinflammatory therapy. The study was approved by the Animal Ethics Committee of Qilu Hospital of Shandong University, China (approval No. KYLL-2015(KS)-088) on February 10, 2015.
Immunological and biochemical parameters in patients with hepatitis C virus nephropathy before and after direct hepatitis C virus antiviral agents

Background Chronic hepatitis C is associated with multiple extrahepatic manifestations that may affect the infected patients. Egypt is the country with the highest incidence of hepatitis C virus (HCV) infection in the world. Hepatitis C-induced kidney disease is a devastating complication in patients with HCV infection. The development of multiple direct-acting antivirals (DAAs) has revolutionized the HCV infection treatment. Aim The aim was to determine the changes in immunological and biochemical parameters in patients with HCV nephropathy who receive DAA. Patients and methods The study included 30 patients diagnosed with HCV nephropathy according to the inclusion criteria and were tested for the immunological (C3, C4, rheumatoid factor) and biochemical parameters (urea, creatinine, urine analysis, 24 h proteins), before receiving their direct HCV antiviral agents for 12 weeks. Then participants were followed up regarding their immunological and biochemical parameters directly after termination of treatment. Results A total of 18 (60%) patients received sofosbuvir and daclatasvir with ribavirin, whereas 12 (40%) patients were on ombitasvir, ritnoprevir, and paritaprevir with ribavirin. Levels of transaminases were significantly improved after direct HCV antiviral agents in the current study. Significant improvement in the mean levels of blood urea and creatinine after direct HCV antiviral agents post-therapy when compared with their levels before treatment (49.16 ± 15.52 and 285.11 ± 39.07 mg/dl at pretreatment versus 25.44 ± 9.37 and185.03 ± 31.07 mg/dl after treatment respectively, with P < 0.05) with significant reduction in 24-h urinary protein following the antiviral therapy. Our study showed significant improvement in C3 and C4 levels after therapy with DAA. After 12 weeks of the therapy, all patients had negative HCV RNA by PCR at follow-up. Conclusion HCV infection is a major medical burden in patients with chronic kidney disease. However, HCV infection itself can cause chronic kidney disease. Effective antiviral agents play an important role in improvement of HCV-related nephropathy and other extrahepatic manifestations.
Value of procalcitonin levels as a predictive biomarker for sepsis in pediatric patients with burn injuries

Aim: The aim of the present study was to investigate the value of serum procalcitonin (PCT) measurements for the prediction of sepsis in pediatric patients with burn injuries. Method: All pediatric patients with burn aged between 1 and 15 years who were treated at Burn Centre of Kartal Training and Research Hospital, Istanbul, Turkey between January 2014 and January 2015 were included in this study. The patients were classified into three groups according to levels of serum PCT. Groups one, two, and three consisted of patients with PCT levels lower than 0.5 ng/dl, patients with PCT levels 0.5--2.0 ng/dl, and patients with PCT levels greater than 2.0 ng/dl, respectively. Demographic data (age, gender), burn etiology, body region of burns, percentage of affected total body surface area (TBSA), antibiotic requirement, intensive care unit (ICU) requirement, hospitalization time, blood culture results, and mortality were evaluated in relation to PCT levels. Results: The mean PCT level at admittance was 2.2 ± 5.8 ng/dl. There were 52, 7, and 11 patients in group one, two, and three, respectively. Higher PCT levels were significantly associated with higher percentage TBSA (P < 0.001), positive blood cultures (P < 0.001), higher requirement of antibiotics and intensive care (P = 0.004 and P < 0.001, respectively), and longer hospitalization time (P < 0,001). Conclusion: High PCT levels may be a predictive biomarker for the development of sepsis in pediatric patients with burn injury. However, more comprehensive prospective studies may be required to validate this finding.