Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification of Enteropathogens by Multiplex PCR among Rural and Urban Guatemalan Children with Acute Diarrhea.

Multiplex PCR platforms have enhanced understanding of intestinal pathogens in low- and middle-income countries (LMICs). However, few such studies have been performed in Latin America, where poverty, poor sanitation, and undernutrition persist. Multiplex PCR (BioFire, Salt Lake City, UT) was used to identify viral, bacterial, and parasitic pathogens in stool collected on day 1 and 31 from children aged 6 to 35 months with acute, non-bloody diarrhea in two locations (rural and urban) in Guatemala. We analyzed correlation between pathogens and clinical, demographic, and socioeconomic variables; described patterns of pathogen acquisition, persistence, and clearance over the 30-day period; and calculated population attributable fractions (PAFs) for diarrheal causation for individual pathogens. We analyzed 316 subjects (144 urban; 172 rural) enrolled between March 2015 and January 2016. Rural subjects had significantly more malnutrition, animal exposure, and unimproved water/sanitation infrastructure. The majority of subjects had multiple pathogens/sample (4.8 rural and 2.7 urban). Few meaningful correlates were identified between individual pathogens and clinical, demographic, or environmental variables. Escherichia coli pathotypes, Shigella, Campylobacter, and Giardia had high rates of persistence between initial and 30-day follow-up. Statistically significant adjusted PAFs were identified for Campylobacter (14.9%, 95% CI: 3.2-23.1), norovirus (10.2%, 95% CI: 0.4-17.1), sapovirus (7.6%, 95% CI: 2.3-10.9), and adenovirus 40/41 (5.6%, 95% CI: 0.3-8.7). These observations further characterize the diversity and complexity of enteric pathogens in children in LMICs. Patterns of chronic symptomatic and asymptomatic infection among Latin American children are similar to those observed in other LMIC regions. Findings have direct implications for practitioners treating individuals with acute infectious diarrhea and should inform regional public health strategies.
Osteostatin Inhibits Collagen-Induced Arthritis by Regulation of Immune Activation, Pro-Inflammatory Cytokines, and Osteoclastogenesis

In chronic inflammatory joint diseases, such as rheumatoid arthritis, there is an important bone loss. Parathyroid hormone-related protein (PTHrP) and related peptides have shown osteoinductive properties in bone regeneration models, but there are no data on inflammatory joint destruction. We have investigated whether the PTHrP (107-111) C-terminal peptide (osteostatin) could control the development of collagen-induced arthritis in mice. Administration of osteostatin (80 or 120 μg/kg s.c.) after the onset of disease decreased the severity of arthritis as well as cartilage and bone degradation. This peptide reduced serum IgG2a levels as well as T cell activation, with the downregulation of RORγt+CD4+ T cells and upregulation of FoxP3+CD8+ T cells in lymph nodes. The levels of key cytokines, such as interleukin(IL)-1β, IL-2, IL-6, IL-17, and tumor necrosis factor-α in mice paws were decreased by osteostatin treatment, whereas IL-10 was enhanced. Bone protection was related to reductions in receptor activator of nuclear factor-κB ligand, Dickkopf-related protein 1, and joint osteoclast area. Osteostatin improves arthritis and controls bone loss by inhibiting immune activation, pro-inflammatory cytokines, and osteoclastogenesis. Our results support the interest of osteostatin for the treatment of inflammatory joint conditions.
Efficacy of a Bispecific Antibody Co-Targeting VEGFA and Ang-2 in Combination with Chemotherapy in a Chemoresistant Colorectal Carcinoma Xenograft Model

Vascular endothelial growth factor (VEGF) inhibition by the addition of bevacizumab to the chemotherapy regimen of metastatic colorectal cancer leads to an improved outcome. However, anti-angiogenic tumor therapy targeting a single factor may be limited by complementary mechanisms. Angiopoietin-2 (Ang-2, ANGPT2) is another important factor that cooperates with VEGF to drive tumor angiogenesis. It was shown that high Ang-2 levels are associated with a poor clinical outcome of colorectal cancer patients treated with bevacizumab-containing therapy. Therefore, combined inhibition of VEGF and Ang-2 was supposed to improve anti-angiogenic therapy. Here, we evaluated the efficacy of a bispecific antibody (CrossMab) co-targeting VEGF and Ang-2 in combination with chemotherapy in a chemoresistant colorectal carcinoma model. Antitumor activity was evaluated in athymic nude mice bearing subcutaneous DLD1 xenograft tumors and treated with anti-VEGF (B20), anti-Ang-2 (LC06) and anti-VEGF/Ang-2 (CrossMab) antibodies. Chemotherapy consisted of 5-FU and irinotecan. Resected tumors were analyzed immunohistochemically. First, an impact of targeting each single factor but also a clear advantage of co-targeting both factors could be demonstrated. Accordingly, tumor tissue showed strong staining for VEGF and Ang-2. Chemotherapy alone was less effective. Efficient tumor growth inhibition could be achieved by treatment with anti-VEGF/chemotherapy, single CrossMab and CrossMab/chemotherapy, which resulted in 3 out of 10, 6 out of 10 and 10 out of 10 complete responses, respectively, during seven weeks. Complete retarded tumors were characterized by massive intratumoral necrosis surrounded by layers of vital tumor cells and connective tissue with CD31-positive vessels at the periphery. In some cases, a distinct feature known as vessel co-option could be observed. In conclusion, the data from this model clearly support the strategy of co-targeting VEGF and Ang-2 and further demonstrate the beneficial impact of co-treatment with chemotherapy. The clear superiority of the CrossMab-containing regimen compared to clinical standard anti-VEGF/chemotherapy warrants further analyses in other models.
Biomechanical Effect of Foot Orthoses on Rearfoot Motions and Joint Moment Parameters in Patients with Flexible Flatfoot

Background The effect of foot orthoses in terms of kinematics and kinetics during walking could be affected on different geometrical designs. Therefore, the purpose of this study was to compare the biomechanical and clinical effects of 3 different insoles on rearfoot motion (RFM) and ankle joint moment parameters. Material/Methods Twenty eight university students with flexible flatfoot were recruited for this study, and each participant was asked to wear 3 different insoles: normal insole without arch support function, type A insole with only arch support function, and type B insole with both arch support and cushion pads for shock absorbing functions. Three-dimensional motion analysis was performed to compute the ranges and peak orientation angles of RFM and ankle joint moment parameters. Results The type A and type B insoles exhibited significantly smaller peak everted position and evertor moment than the normal insole. Also, the type A insole showed significantly smaller range of rearfoot motion in the longitudinal axis and the length of MA (moment arm) in the mediolateral axis than the normal insole. Conclusions The use of the type A insole using arch support function was induced to promote a cautious gait pattern associated with a relatively lower potential risk compared to the normal insole. The type A and type B insoles could be important to positively reduce the possibility of injury. Also, the smaller length of MA in the type A insole might have a contribution to the decrease of ankle joint evertor moment.
High rates of primary production in structurally complex forests.

Structure-function relationships are central to many ecological paradigms. Chief among these is the linkage of net primary production (NPP) with species diversity and canopy structure. Using the National Ecological Observatory Network (NEON) as a subcontinental-scale research platform, we examined how temperate forest NPP relates to several measures of site-level canopy structure and tree species diversity. Novel multi-dimensional canopy traits describing structural complexity, most notably canopy rugosity, were more strongly related to site NPP than were species diversity measures and other commonly characterized canopy structural features. The amount of variation in site-level NPP explained by canopy rugosity alone was 83%, which was substantially greater than that explained individually by vegetation area index (31%) or Shannon's Index of species diversity (30%). Forests that were more structurally complex, had higher vegetation area indices, or were more diverse absorbed more light and used light more efficiently to power biomass production, but these relationships were most strongly tied to structural complexity. Implications for ecosystem modeling and management are wide-ranging, suggesting structural complexity traits are broad, mechanistically-robust indicators of NPP that, in application, could improve the prediction and management of temperate forest carbon sequestration. This article is protected by copyright. All rights reserved.
Large 10  ×  10 single cell grid networks of human hNT astrocytes on raised parylene-C/SiO2 substrates

Objective. The ‘Astrocytic Network’ is an emerging research field for researchers in cell biology. Culturing astrocytes in organised networks is a novel method for permitting controlled studies and investigations into the calcium transients of such networks. Recent research has photolithographically patterned hNT astrocytes on parylene-C inlayed SiO2 trench grid networks. However, it was observed that the trench networks could not specifically immobilise the astrocyte cell bodies to the nodes of the networks. Approach. In this study, for the first time, we demonstrate how it is possible to establish grid networks of human hNT astrocytes on raised parylene-C structures where the cell bodies are specifically organised down to the single-cell level on nodes of the grid and connected throughout. Main results. Here, we report these to be the largest patterned single-cell grid network of astrocytes of their kind consisting of 100 cells in a 10 × 10 grid arrangement to an 80% efficiency. We quantify the level of patterning through six cell patterning assessment indices: the parylene adhesion index (PAI); SiO2 attraction index (SAI); node index (NI) and connectivity interval (χI), number of components (k) and fielder value (λss) and report that the best connected network is obtained with 65 µm node size, 90 µm node spacing, and 5 µm interconnecting track width (PAI = 0.77 ± 0.040, SAI = 0.12 ± 0.049, NI = 0.81 ± 0.066, χI = 0.25 ± 0.064, k = 2.33 ± 1.528, λss = 0.0249 ± 0.0018). We finally demonstrate, through delivery of ATP, that the networks are functional on the raised parylene-C grid structures. Significance. The significance of this study is that it determines the optimal dimensions to obtain highly organised, large, interlinked, single-cell networks which provide an effective platform to investigate calcium communication within astrocytic networks in an accurate, controlled and repeatable manner.
Trolox‐induced cardiac differentiation is mediated by the inhibition of Wnt/β‐catenin signaling in human embryonic stem cells

Cardiac differentiation of human pluripotent stem cells may be induced under chemically defined conditions, wherein the regulation of Wnt/β‐catenin pathway is often desirable. Here, we examined the effect of trolox, a vitamin E analog, on the cardiac differentiation of human embryonic stem cells (hESCs). 6‐Hydroxy‐2,5,7,8‐tetramethylchromane‐2‐carboxylic acid (Trolox) significantly enhanced cardiac differentiation in a time‐ and dose‐dependent manner after the mesodermal differentiation of hESCs. Trolox promoted hESC cardiac differentiation through its inhibitory activity against the Wnt/β‐catenin pathway. This study demonstrates an efficient cardiac differentiation method and reveals a novel Wnt/β‐catenin regulator.
Incretins in obesity and diabetes

Incretins are hormones secreted from enteroendocrine cells after nutrient intake that stimulate insulin secretion from β cells in a glucose‐dependent manner. Glucose‐dependent insulinotropic polypeptide (GIP) and glucagon‐like peptide‐1 (GLP‐1) are the only two known incretins. Dysregulation of incretin secretion and actions are noted in diseases such as obesity and diabetes. In this review, we first summarize our traditional understanding of the physiology of GIP and GLP‐1, and our current knowledge of the relationships between GIP and GLP‐1 and obesity and diabetes. Next, we present the results from major randomized controlled trials on the use of GLP‐1 receptor agonists for managing type 2 diabetes, and emerging data on treating obesity and prediabetes. We conclude with a glimpse of the future with possible complex interactions between nutrients, gut microbiota, the endocannabinoid system, and enteroendocrine cells.
Diffusion tensor imaging of the abdominal organs: Influence of oriented intravoxel flow compartments

Water flow in partially oriented intravoxel compartments mimics an anisotropic fast‐diffusion regime, which contributes to the signal attenuation in diffusion‐weighted images. In the abdominal organs, this flow may reflect physiological fluid movements (eg, tubular urine flow in kidneys, or bile flow through the liver) and have a clinical relevance. This study investigated the influence of anisotropic intravoxel water flow on diffusion tensor imaging (DTI) of the abdominal organs.
Botanicals Against Tetranychus urticae Koch Under Laboratory Conditions: A Survey of Alternatives for Controlling Pest Mites

Tetranychus urticae Koch is a phytophagous mite capable of altering the physiological processes of plants, causing damages estimated at USD$ 4500 per hectare, corresponding to approximately 30% of the total cost of pesticides used in some important crops. Several tools are used in the management of this pest, with chemical control being the most frequently exploited. Nevertheless, the use of chemically synthesized acaricides brings a number of disadvantages, such as the development of resistance by the pest, hormolygosis, incompatibility with natural predators, phytotoxicity, environmental pollution, and risks to human health. In that sense, the continuous search for botanical pesticides arises as a complementary alternative in the control of T. urticae Koch. Although a lot of information is unknown about its mechanisms of action and composition, there are multiple experiments in lab conditions that have been performed to determine the toxic effects of botanicals on this mite. Among the most studied botanical families for this purpose are plants from the Lamiaceae, the Asteraceae, the Myrtaceae, and the Apiaceae taxons. These are particularly abundant and exhibit several results at different levels; therefore, many of them can be considered as promising elements to be included into integrated pest management for controlling T. urticae.
Categorising the broad impacts of continuing professional development: a scoping review

A number of systematic reviews have evaluated the impacts of continuing professional development (CPD). These reviews, due to their focused nature, may fail to capture the full range of impacts of CPD. This scoping review aims to explore the broader impacts of CPD with the intention of developing a categorisation of the types of impact of CPD.
Calibrated fMRI for dynamic mapping of CMRO2 responses using MR-based measurements of whole-brain venous oxygen saturation

Functional MRI (fMRI) can identify active foci in response to stimuli through BOLD signal fluctuations, which represent a complex interplay between blood flow and cerebral metabolic rate of oxygen (CMRO2) changes. Calibrated fMRI can disentangle the underlying contributions, allowing quantification of the CMRO2 response. Here, whole-brain venous oxygen saturation (Y v ) was computed alongside ASL-measured CBF and BOLD-weighted data to derive the calibration constant, M, using the proposed Y v -based calibration. Data were collected from 10 subjects at 3T with a three-part interleaved sequence comprising background-suppressed 3D-pCASL, 2D BOLD-weighted, and single-slice dual-echo GRE (to measure Y v via susceptometry-based oximetry) acquisitions while subjects breathed normocapnic/normoxic, hyperoxic, and hypercapnic gases, and during a motor task. M was computed via Y v -based calibration from both hypercapnia and hyperoxia stimulus data, and results were compared to conventional hypercapnia or hyperoxia calibration methods. Mean M in gray matter did not significantly differ between calibration methods, ranging from 8.5 ± 2.8% (conventional hyperoxia calibration) to 11.7 ± 4.5% (Yv-based calibration in response to hyperoxia), with hypercapnia-based M values between (p = 0.56). Relative CMRO2 changes from finger tapping were computed from each M map. CMRO2 increased by ∼20% in the motor cortex, and good agreement was observed between the conventional and proposed calibration methods.
Biomass Characteristics and Their Effect on Membrane Bioreactor Fouling

Biomass characteristics are regarded as particularly influential for fouling in Membrane Bio-Reactors (MBRs). They primarily include the Mixed Liquor Suspended Solids (MLSS), the colloids and the Extracellular Polymeric Substances (EPS). Among them, the soluble part of EPS, which is also known as Soluble Microbial Products (SMP), is the most significant foulant, i.e., it is principally responsible for membrane fouling and affects all fundamental fouling indices, such as the Trans-Membrane Pressure (TMP) and the membrane resistance and permeability. Recent research in the field of MBRs, tends to consider the carbohydrate fraction of SMP (SMPc) the most important characteristic for fouling, mainly due to the hydrophilic and gelling properties, which are exhibited by polysaccharides and allow them to be easily attached on the membrane surface. Other wastewater and biomass characteristics, which affect indirectly membrane fouling, include temperature, viscosity, dissolved oxygen (DO), foaming, hydrophobicity and surface charge. The main methods employed for the characterization and assessment of biomass quality, in terms of filterability and fouling potential, can be divided into direct (such as FDT, SFI, TTF100, MFI, DFCM) or indirect (such as CST, TOC, PSA, RH) methods, and they are shortly presented in this review.
Interactions of Behavioral Changes in Smoking, High-risk Drinking, and Weight Gain in a Population of 7.2 Million in Korea

Objectives To identify simultaneous behavioral changes in alcohol consumption, smoking, and weight using a fixed-effect model and to characterize their associations with disease status. Methods This study included 7 000 529 individuals who participated in the national biennial health-screening program every 2 years from 2009 to 2016 and were aged 40 or more. We reconstructed the data into an individual-level panel dataset with 4 waves. We used a fixed-effect model for smoking, heavy alcohol drinking, and overweight. The independent variables were sex, age, lifestyle factors, insurance contribution, employment status, and disease status. Results Becoming a high-risk drinker and losing weight were associated with initiation or resumption of smoking. Initiation or resumption of smoking and weight gain were associated with non-high-risk drinkers becoming high-risk drinkers. Smoking cessation and becoming a high-risk drinker were associated with normal-weight participants becoming overweight. Participants with newly acquired diabetes mellitus, ischemic heart disease, stroke, and cancer tended to stop smoking, discontinue high-risk drinking, and return to a normal weight. Conclusions These results obtained using a large-scale population-based database documented interactions among lifestyle factors over time.
Suboptimal Use of Inpatient Palliative Care Consultation May Lead to Higher Readmissions and Costs in End-Stage Liver Disease.

Background/Aims: Patients with end-stage liver disease (ESLD) have a high risk for readmission. We studied the role of palliative care consultation (PCC) in ESLD-related readmissions with a focus on health care resource utilization in the United States. Methods: We performed a retrospective longitudinal analysis on patients surviving hospitalizations with ESLD from January 2010 to September 2014 utilizing the Nationwide Readmissions Database with a 90-day follow-up after discharge. We analyzed annual trends in PCC among patients with ESLD. We matched PCC to no-PCC (1:1) using propensity scores to create a pseudorandomized clinical study. We estimated the impact of PCC on readmission rates (30- and 90-day), and length of stay (LOS) and cost during subsequent readmissions. Results: Of the 67,480 hospitalizations with ESLD, 3485 (5.3%) received PCC, with an annual increase from 3.6% to 6.7% (p for trend <0.01). The average 30- and 90-day annual readmission rates were 36.2% and 54.6%, respectively. PCC resulted in a lower risk for 30- and 90-day readmissions (hazard ratio: 0.42, 95% confidence interval [CI]: 0.38-0.47 and 0.38, 95% CI: 0.34-0.42, respectively). On subsequent 30- and 90-day readmissions, PCC was associated with decreased LOS (5.6- vs. 7.4 days and 5.7- vs. 6.9 days, p < 0.01) and cost (US $48,752 vs. US $75,810 and US $48,582 vs. US $69,035, p < 0.01). Conclusion: Inpatient utilization of PCC for ESLD is increasing annually, yet still remains low in the United States. More importantly, PCC was associated with a decline in readmission rates resulting in a lower burden on health care resource utilization and improvement in cost savings during subsequent readmissions.
Sympathetic‐Parasympathetic Interaction and Externalizing Problems in Children with Autism Spectrum Disorder

Children with autism spectrum disorder (ASD) exhibit significant difficulties with emotion regulation and reactivity, which may be linked to underlying psychophysiology. The present study examined associations between autonomic nervous system activity and individual differences in externalizing behavior problems in children with ASD. A multisystem approach was adopted to consider the interplay between markers of sympathetic (electrodermal reactivity—EDA‐R) and parasympathetic reactivity (respiratory sinus arrhythmia reactivity—RSA‐R) in relation to behavioral challenges. Fifty‐two children with ASD ages 6–10 years contributed complete psychophysiological data. Measures of EDA‐R and RSA‐R (RSA withdrawal) were obtained in response to a laboratory challenge task and parents reported on child externalizing behavior problems using a standardized questionnaire and a structured clinical interview. An equifinality model was supported, with two distinct psychophysiological pathways linked to heightened externalizing behavior problems. Greater RSA‐R was associated with more externalizing problems in the context of higher levels of EDA‐R, and lower EDA‐R was associated with increased externalizing problems at lower levels of RSA‐R. Findings underscore the importance of considering the role of psychophysiology in the unfolding of comorbid externalizing problems in children with ASD. Potential implications for tailoring coregulatory supports are discussed. Autism Res 2019, 12: 1805–1816. © 2019 International Society for Autism Research, Wiley Periodicals, Inc.