Miracle-dz/UniFAR-FTUs huggingface dataset:
Convalescent patient-derived monoclonal antibodies targeting different epitopes of E protein confer protection against Zika virus in a neonatal mouse model

ABSTRACT The Zika virus (ZIKV) outbreak and its link to microcephaly triggered a public health concern. To examine antibody response in a patient infected with ZIKV, we used single-cell PCR to clone 31 heavy and light chain-paired monoclonal antibodies (mAbs) that bind to ZIKV envelope (E) proteins isolated from memory B cells of a ZIKV-infected patient. Three mAbs (7B3, 1C11, and 6A6) that showed the most potent and broad neutralization activities against the African, Asian, and American strains were selected for further analysis. mAb 7B3 showed an IC50 value of 11.6 ng/mL against the circulating American strain GZ02. Epitope mapping revealed that mAbs 7B3 and 1C11 targeted residue K394 of the lateral ridge (LR) epitope of the EDIII domain, but 7B3 has a broader LR epitope footprint and recognizes residues T335, G337, E370, and N371 as well. mAb 6A6 recognized residues D67, K118, and K251 of the EDII domain. Interestingly, although the patient was seronegative for DENV infection, mAb 1C11, originating from the VH3-23 and VK1-5 germline pair, neutralized both ZIKV and DENV1. Administration of the mAbs 7B3, 1C11, and 6A6 protected neonatal SCID mice infected with a lethal dose of ZIKV. This study provides potential therapeutic antibody candidates and insights into the antibody response after ZIKV infection.
A diagnosis of rheumatoid arthritis, endometriosis or IBD is associated with later onset of fibromyalgia and chronic widespread pain

Widespread pain is a common comorbidity in several chronic diseases and is suspected to be caused by pain resulting from the underlying disease that has provoked a state of central sensitization. However, this argument is currently limited by evidence that has insufficiently captured the temporal nature of the relationship between diagnosis of the underlying disease and onset of widespread pain. The aim of this study was to investigate if patients with rheumatoid arthritis (RA), endometriosis or inflammatory bowel disease (IBD), have a higher risk of developing widespread pain (fibromyalgia or chronic widespread pain [CWP]).
A Nationwide Assessment of the “July Effect” and Predictors of Post-Endoscopic Retrograde Cholangiopancreatography Sepsis at Urban Teaching Hospitals in the United States

Background/Aims To analyze the incidence of post-endoscopic retrograde cholangiopancreatography (ERCP) sepsis in the early (July to September) and later (October to June) academic months to assess the “July effect”. Methods The National Inpatient Sample (2010–2014) was used to identify ERCP-related adult hospitalizations at urban teaching hospitals by applying relevant procedure codes from the International Classification of Diseases, 9th revision, Clinical Modification. Post-ERCP outcomes were compared between the early and later academic months. A multivariate analysis was performed to evaluate the odds of post-ERCP sepsis and its predictors. Results Of 481,193 ERCP procedures carried out at urban teaching hospitals, 124,934 were performed during the early academic months. The demographics were comparable for ERCP procedures performed during the early and later academic months. A higher incidence (9.4% vs. 8.8%, p<0.001) and odds (odds ratio [OR], 1.07) of post-ERCP sepsis were observed in ERCP performed during the early academic months. The in-hospital mortality rate (7% vs. 7.5%, p=0.072), length of stay, and total hospital charges in patients with post-ERCP sepsis were also equivalent between the 2 time points. Pre-ERCP cholangitis (OR, 3.20) and post-ERCP complications such as cholangitis (OR, 6.27), perforation (OR, 3.93), and hemorrhage (OR, 1.42) were significant predictors of higher post-ERCP sepsis in procedures performed during the early academic months. Conclusions The July effect was present in the incidence of post-ERCP sepsis, and academic programs should take into consideration the predictors of post-ERCP sepsis to lower health-care burden.
Does enhanced nutrient availability increase volatile emissions in cranberry?

ABSTRACT Nutrient availability impacts plant indirect defenses, such as emissions of herbivore-induced plant volatiles (HIPVs) that attract natural enemies of herbivores. However, the effects are variable depending on the cropping system, and emissions may increase, decrease, or be not affected by nutrient availability. Here, we evaluated the effects of different fertilizer regimes, which varied nitrogen (N), phosphorus (P), and potassium (K) availability, on HIPV emissions in cranberry, Vaccinium macrocarpon Ait. Plants included six cranberry varieties that were subjected to four different fertilizer regimes and either noninduced or induced with methyl jasmonate (MeJA), an elicitor of HIPVs, in a 6 × 4 × 2 factorial design. Results show that enhanced NPK fertilizer applications increased total HIPV emissions in MeJA-treated cranberries, regardless of variety. This effect was due to an increase in plant fresh weight. Although the ecological effects of increased HIPV emissions need to be investigated, these findings may have implications for natural enemy manipulation in agro-ecosystems.
Disentangling the Effects of Exposure to Maternal Substance Misuse and Physical Abuse and Neglect on Child Behavioral Problems

There is inconsistent evidence on the association between prenatal substance exposure and child behavioral problems. Children affected by maternal substance misuse are vulnerable to physical abuse and neglect. Few studies have examined factors contributing to internalizing and externalizing problems in these children. This study, with a focus on children with prenatal substance exposure, investigated whether family characteristics (the duration of maternal substance misuse postpartum or the existence of a sibling) moderated the association between adverse exposure (physical abuse or neglect) and behavior (internalizing or externalizing problems). We recruited 54 Hong Kong Chinese mothers with registered records of substance misuse during pregnancy and their children (2-9 years). Mothers completed questionnaires on drug use patterns during pregnancy and postpartum, abusive and neglectful parenting behaviors in the preceding year, and children’s current behavioral problems. Moderated regression analyses tested whether abusive and neglectful parenting behavior interacted with family characteristics to affect child behavioral problems. The existence of a sibling moderated the relationship between neglect experience and internalizing problems, with a positive relationship observed only among single children (adjusted B [95% confidence interval] = 3.70 [0.98, 6.41], p = .012). The duration of maternal substance misuse postpartum moderated the relationship between physical abuse experience and externalizing problems, with a positive relationship observed only among children of mothers abusing substances beyond the child’s infancy period (adjusted B [95% confidence interval] = 6.86 [2.34, 11.38], p = .008). The results show that the impact of physical abuse and neglect experiences depend on the type of behavior assessed and family and child characteristics. Positive sibling relationship and early detoxification in the mother can foster healthy behavioral development for children exposed prenatally to maternal substance misuse.
Clinical practice update on heart failure 2019: pharmacotherapy, procedures, devices and patient management. An expert consensus meeting report of the Heart Failure Association of the European Society of Cardiology

The European Society of Cardiology (ESC) has published a series of guidelines on heart failure (HF) over the last 25 years, most recently in 2016. Given the amount of new information that has become available since then, the Heart Failure Association (HFA) of the ESC recognized the need to review and summarise recent developments in a consensus document. Here we report from the HFA workshop that was held in January 2019 in Frankfurt, Germany. This expert consensus report is neither a guideline update nor a position statement, but rather a summary and consensus view in the form of consensus recommendations. The report describes how these guidance statements are supported by evidence, it makes some practical comments, and it highlights new research areas and how progress might change the clinical management of HF. We have avoided re‐interpretation of information already considered in the 2016 ESC/HFA guidelines.
Pharmacokinetics of golimumab in moderate to severe ulcerative colitis: the GO-KINETIC study

Abstract Background: Golimumab (GLM) is approved for the treatment of moderate to severe ulcerative colitis (UC). Higher serum concentrations of anti-tumor necrosis factor (TNF) agents are associated with improved clinical and endoscopic outcomes. Correlations between GLM serum concentrations and clinical and endoscopic outcomes were investigated during induction and maintenance treatment. In addition, a population pharmacokinetic model was developed to identify factors associated with the pharmacokinetics of GLM in UC. Methods: A prospective observational trial (GO-KINETIC) was conducted in patients with moderate to severe UC receiving induction and maintenance treatment with GLM. Clinical and endoscopic outcomes were evaluated, fecal GLM concentrations were measured and pharmacokinetic data were analyzed. Results: A total of 20 patients were enrolled. At week 8 (after induction treatment), 12 out of 20 patients (60%) showed an endoscopic response (≥1 point reduction in endoscopic Mayo score). Patients with endoscopic response at week 8 had numerically higher median GLM serum concentrations at week 2 compared to endoscopic non-responders: 9.1 µg/ml [5.9–12.3] vs. 7.1 µg/mL [5.2–9.0]; p = . 384, respectively. At week 52, 3/20 patients (15%) achieved endoscopic remission (endoscopic Mayo score ≤1) and continued GLM treatment. Population pharmacokinetic analysis showed an inverse association between albumin concentrations and GLM clearance. GLM concentrations were undetectable in fecal samples. Conclusions: After induction therapy, 60% of the patients showed endoscopic response. During maintenance therapy, about one third of patients discontinued GLM treatment because of loss of response. These patients might benefit from dose optimization.
FGF Gradient Controls Boundary Position Between Proliferating and Differentiating Cells and Regulates Lacrimal Gland Growth Dynamics

Fibroblast growth factor (FGF) signaling plays an important role in controlling cell proliferation, survival, and cell movements during branching morphogenesis of many organs. In mammals branching morphogenesis is primarily regulated by members of the FGF7-subfamily (FGF7 and FGF10), which are expressed in the mesenchyme, and signal to the epithelial cells through the “b” isoform of fibroblast growth factor receptor-2 (FGFR2). Our previous work demonstrated that FGF7 and FGF10 form different gradients in the extracellular matrix (ECM) and induce distinct cellular responses and gene expression profiles in the lacrimal and submandibular glands. The last finding was the most surprising since both FGF7 and FGF10 bind signal most strongly through the same fibroblast growth factor receptor-2b isoform (FGFR2b). Here we revisit this question to gain an explanation of how the different FGFs regulate gene expression. For this purpose, we employed our ex vivo epithelial explant migration assay in which isolated epithelial explants are grown near the FGF loaded beads. We demonstrate that the graded distribution of FGF induces activation of ERK1/2 MAP kinases that define the position of the boundary between proliferating “bud” and differentiating “stalk” cells of growing lacrimal gland epithelium. Moreover, we showed that gene expression profiles of the epithelial explants exposed to distinct FGFs strictly depend on the ratio between “bud” and “stalk” area. Our data also suggests that differentiation of “stalk” and “bud” regions within the epithelial explants is necessary for directional and persistent epithelial migration. Gaining a better understanding of FGF functions is important for development of new approaches to enhance tissue regeneration.
Adoption of Secure Pork Supply Plan Biosecurity by U.S. Swine Producers

There is mounting concern about the negative animal health and supply chain consequences of animal disease outbreaks in the United States. Recent disease outbreaks have drawn attention to the need for additional understanding of biosecurity efforts to reduce disease frequency, spread, and impact. Biosecurity is a key component of the Secure Pork Supply (SPS) Plan designed to provide business continuity in the event of a foreign animal disease outbreak as well as help protect operations from endemic diseases. Core biosecurity recommendations outlined in the SPS Plan are a written site-specific biosecurity plan and implementation of a perimeter buffer area and a line of separation. To-date, no benchmarking of SPS Plan biosecurity implementation has been done. Utilizing data from a 2017 survey of U.S. swine producers, this study shows that SPS Plan biosecurity adoption varies and is affected by how feasible producers believe implementation of each biosecurity practice is on their operation. Furthermore, binomial logit regression analyses indicate producer and operation demographics and producer risk attitudes and perceptions affect biosecurity adoption. Conditional probabilities reveal that adoption of biosecurity practices is overwhelmingly complementary, suggesting that one biosecurity practice likely increases marginal efficacy of another biosecurity practice. The insights this study provides regarding the complexities of biosecurity adoption are vitally important to both educators and policy makers.
CT Texture Analysis—Correlations With Histopathology Parameters in Head and Neck Squamous Cell Carcinomas

Introduction: Texture analysis is an emergent imaging technique to quantify heterogeneity in radiological images. It is still unclear whether this technique is capable to reflect tumor microstructure. The present study sought to correlate histopathology parameters with texture features derived from contrast-enhanced CT images in head and neck squamous cell carcinomas (HNSCC). Materials and Methods: Twenty-eight patients with histopathological proven HNSCC were retrospectively analyzed. In every case EGFR, VEGF, Hif1-alpha, Ki67, p53 expression derived from immunhistochemical specimen were semiautomatically calculated. Furthermore, mean cell count was estimated. Texture analysis was performed on contrast-enhanced CT images as a whole lesion measurement. Spearman's correlation analysis was performed, adjusted with Benjamini-Hochberg correction for multiple tests. Results: Several texture features correlated with histopathological parameters. After correction only CT texture joint entropy and CT entropy correlation with Hif1-alpha expression remained statistically significant (ρ = −0.60 and ρ = −0.50, respectively). Conclusions: CT texture joint entropy and CT entropy were associated with Hif1-alpha expression in HNSCC and might be able to reflect hypoxic areas in this entity.
Characterization of ocular and nasopharyngeal microbiome in allergic rhinoconjunctivitis

Allergic rhinoconjunctivitis (ARC) is a prevalent allergic condition in the pediatric population. Microbial dysbiosis has increasingly been recognized to influence on host immunity and allergic diseases. However, the microbial profile of ARC has not been characterized. This cross‐sectional study aims to evaluate the changes in nasal and ocular surface microbiome of children with ARC.
Linking drought legacy effects across scales: From leaves to tree rings to ecosystems

Severe drought can cause lagged effects on tree physiology that negatively impact forest functioning for years. These “drought legacy effects” have been widely documented in tree‐ring records and could have important implications for our understanding of broader scale forest carbon cycling. However, legacy effects in tree‐ring increments may be decoupled from ecosystem fluxes due to (a) postdrought alterations in carbon allocation patterns; (b) temporal asynchrony between radial growth and carbon uptake; and (c) dendrochronological sampling biases. In order to link legacy effects from tree rings to whole forests, we leveraged a rich dataset from a Midwestern US forest that was severely impacted by a drought in 2012. At this site, we compiled tree‐ring records, leaf‐level gas exchange, eddy flux measurements, dendrometer band data, and satellite remote sensing estimates of greenness and leaf area before, during, and after the 2012 drought. After accounting for the relative abundance of tree species in the stand, we estimate that legacy effects led to ~10% reductions in tree‐ring width increments in the year following the severe drought. Despite this stand‐scale reduction in radial growth, we found that leaf‐level photosynthesis, gross primary productivity (GPP), and vegetation greenness were not suppressed in the year following the 2012 drought. Neither temporal asynchrony between radial growth and carbon uptake nor sampling biases could explain our observations of legacy effects in tree rings but not in GPP. Instead, elevated leaf‐level photosynthesis co‐occurred with reduced leaf area in early 2013, indicating that resources may have been allocated away from radial growth in conjunction with postdrought upregulation of photosynthesis and repair of canopy damage. Collectively, our results indicate that tree‐ring legacy effects were not observed in other canopy processes, and that postdrought canopy allocation could be an important mechanism that decouples tree‐ring signals from GPP.
A review of concussion diagnosis and management in Australian professional sporting codes

ABSTRACT Objectives: The recognition and management of concussion has become a major health concern across all sports. Despite recent attention, concussion assessment and return-to-play protocols appear to be highly variable between leading professional sporting bodies across Australia. Without readily available guidelines, players at all levels may be at risk of suboptimal management following in-game trauma. The purpose of this study was to explore the publicly available concussion guidelines of the major Australian sporting codes with an aim to identify potential opportunities to develop a national sporting consensus. Methods: Internet sites of the major sporting organizations within Australia were accessed between June 2018 to July 2018. Sites were reviewed for information pertaining to an available concussion protocol or guidelines including; concussion definition, player education documentation, requirement of baseline testing, standard concussion diagnostic measures, use of sideline testing and removal from play guidelines, return-to-play, minimum return-to-play intervals and the implementation of external evaluation of potential concussion cases. Results: Twelve sites were visited. There was consensus between many of the sporting organizations in terms of concussion definition, removal of play and sideline testing protocols. A step-wise return-to-play protocol was prevalent across most sports. A number of sporting sites however did not have readily available information. Conclusions: There is notable room for the development of concussion guidelines in Australian sport. Researchers and sporting organizations need to continuously amend current protocols to ensure this reflects best evidence-based practice.
Direct adaptive output tracking control using multilayered neural networks

Multilayered neural networks are used to construct nonlinear learning control systems for a class of unknown nonlinear systems in a canonical form. An adaptive output tracking architecture is proposed using the outputs of the two three-layered neutral networks which are trained to approximate the unknown nonlinear plant to any desired degree of accuracy by using the modified back-propagation technique. A weight-learning algorithm is presented using the gradient descent method with a dead-zone function, and the descent and convergence of the error index during weight learning are shown. The closed-loop system is proved to be stable, with the output tracking error converging to the neighbourhood of the origin. The effectiveness of the proposed control scheme is illustrated through simulations.
Recent Progress of Additive Manufactured Ti-6 Al-4 V by Electron Beam Melting

Electron beam melting (EBM) is one of the powder-bed fusion additive manufacturing technologies. This technology is very suitable for producing near-net-shape small to medium volume metallic parts with complex geometries. However, layer-by-layer fusion step introduces rapid thermal cycles, which results in a different microstructure as compared to their cast or wrought counterparts. Therefore, the microstructure and mechanical properties produced by EBM must be better understood and in turn to control the microstructure for requirements of some specific applications. Accordingly, in this paper, an insight will be provided on the effort of understanding the microstructure and mechanical properties from atomic scale to real complex big-sized industrial components. The spatialand geometrical-based microstructure and mechanical properties of EBM Ti-6Al-4V as well as the effect of heat treatment on them were investigated using atom probe tomography, transmission electron microscopy, scanning electron microscopy, optical microscopy, x-ray diffraction, x-ray computed tomography, nanohardness testing, microhardness testing, tensile testing and finite element simulations. The microstructure and deformation mode depend on both the build thickness and build height which are closely linked to the heat input and the cooling rate in EBM process. Furthermore, the control of microstructure by varying the process parameters and heat treatment schemes was also proposed. By using these findings, an impeller prototype with a base diameter of 100 mm, a height of 53 mm and thinnest sections of ~0.7 mm and a turbine blade prototype with dimensions of 180×70×360 mm were successfully fabricated by EBM. These components exhibited an overall improved combination of strength and ductility as compared to the counterparts fabricated by conventional methods. These results revealed that EBM is a promising method for fabricating complex-shaped industrial components with superior mechanical performance for practical application.
Investigation of Perceived Stress and Quality of Life Assessment of pharm. D. Students at Ibn Sina National College in Saudi Arabia during 2016.

Abstract: Objective The aim of present study was to investigate the perceived stress and quality of life among Pharm. D students at Ibn Sina National College (ISNC). Methods The sample was surveyed electronically through (Google document) that was sent to students through the email. Pharm D students from the last three professional years were invited to participate in our study. Results Out of 209 eligible students, 52.6 % (N = 110) completed the questionnaire. The average age of the participants was 22.3 Â± 2.5 years, 78.2 % (N = 86) of which were females and 21.8% (N = 24). Students reported that they were sometimes out of control during a month period with regards to the following (with p