Miracle-dz/UniFAR-FTUs huggingface dataset:
Improved empirical models describing hormesis

During the past two decades, the phenomenon of hormesis has gained increased recognition. To promote research in hormesis, a soudund statistical quantification of important parameters, such as the level and significance of the increase in response and the range of concentration where it occurs, is strongly needed. Here, we present an improved statistical model to describe hormetic dose—response curves and test for the presence of hormesis. Using the delta method and freely available software, any percentage effect dose or concentration can be derived with its associated standard errors. Likewise, the maximal response can be extracted and the growth stimulation calculated. The new model was tested on macrophyte data from multiple‐species experiments and on laboratory data of Lemna minor. For the 51 curves tested, significant hormesis was detected in 18 curves, and for another 17 curves, the hormesis model described that data better than the logistic model did. The increase in response ranged from 5 to 109%. The growth stimulation occurred at an average dose somewhere between zero and concentrations corresponding to approximately 20 to 25% of the median effective concentration (EC50). Testing the same data with the hormesis model proposed by Brain and Cousens in 1989, we found no significant hormesis. Consequently, the new model is shown to be far more robust than previous models, both in terms of variation in data and in terms of describing hormetic effects ranging from small effects of a 10% increase in response up to effects of an almost 100% increase in response.
Overview and assessment of the suicidal child

A comprehensive evaluation and assessment of the suicidal child is important to target those at risk. This article identifies risk factors for suicide in children and adolescents and provides a step‐by‐step interview scheme that captures all relevant information that is obtained when assessing these children and adolescents. Depression and Anxiety 14:157–163, 2001. © 2001 Wiley‐Liss, Inc.
Perinatal outcome in singleton pregnancies complicated with preeclampsia and eclampsia in Ecuador

Preeclampsia in Ecuador is an understudied subject since available epidemiological data are scarce. The aim of this study was to describe perinatal outcomes among singleton pregnancies complicated with preeclampsia and eclampsia in a sample of low-income Ecuadorian women. Pregnant women complicated with preeclampsia (mild and severe) and eclampsia (defined according to criteria of the ACOG) delivering at the Enrique C. Sotomayor Obstetrics and Gynecology Hospital, Guayaquil, Ecuador were surveyed with a structured questionnaire containing maternal (socio-demographic) and neonatal data. Perinatal outcomes were compared according to severity of clinical presentation. A total of 163 women with preeclampsia [mild (23.9%), severe (68.7%) and eclampsia (7.4%)] were surveyed. Perinatal mortality and stillbirth rate was similar among studied groups (mild vs. severe preeclampsia/eclampsia cases). However, severe cases displayed higher rates of adverse perinatal outcomes: lower birth Apgar scores, more preterm births, and more low birth weight and small for gestational age infants. Caesarean-section rate and the number of admissions to intensive or intermediate neonatal care were higher in severe cases. A similar trend was found when analysis excluded preterm gestations. In conclusion, in this specific low-income Ecuadorian population perinatal outcome was adverse in pregnancies complicated with severe preeclampsia/eclampsia.
Roles, responsibilities and characteristics of lay community health workers involved in diabetes prevention programmes: A systematic review

Aim To examine the characteristics of community health workers (CHWs) involved in diabetes prevention programmes (DPPs) and their contributions to expected outcomes. Methods Electronic databases including PubMed-MEDLINE, EBSCOHost, and SCOPUS/EMBASE were searched for studies published between January 2000 and March 2016. All studies that used CHWs to implement DPP in ≥18-year-old participants without diabetes but at high risk for developing the condition, irrespective of the study design, setting or outcomes measured, were included. Results were synthesized narratively. Results Forty papers of 30 studies were identified. Studies were mainly community-based and conducted in minority populations in USA. Sample sizes ranged from 20 participants in a single community to 2369 participants in 46 communities. Although CHWs were generally from the local community, their qualifications, work experience and training received differed across studies. Overall the training was culturally sensitive and/or appropriate, covering topics such as the importance of good nutrition and the benefits of increased physical activity, communication and leadership. CHWs delivered a variety of interventions and also screened or recruited participants. The shared culture and language between CHWs and participants likely contributed to better programme implementation and successful outcomes. Conclusions The complexity of DPPs and the diverse CHW roles preclude attributing specific outcomes to CHW involvement. Nevertheless, documenting potential CHW roles and the relevant training required may optimise CHW contributions and facilitate their involvement in DPPs in the future.
ENVIRONMEN TAL HEALTH PER SPEC T I VES ehp Parabens and Human Epidermal Growth Factor Receptor Ligands Cross-Talk in Breast Cancer Cells

Background: Xenoestrogens are synthetic compounds that mimic endogenous estrogens by binding to and activating estrogen receptors. Exposure to estrogens and some xenoestrogens has been associated with cell proliferation and increased risk of breast cancer. Despite evidence of estrogenicity, parabens are among the most widely used xenoestrogens in cosmetics and personal care products, and generally considered safe. However, previous cell based studies with parabens do not take into account the signaling cross-talk between estrogen receptor (ER α ) and the human epidermal growth factor receptor (HER) family. Objectives: We investigated the hypothesis that the potency of parabens can be increased with HER ligands, such as heregulin (HRG). Methods: The effects of HER ligands on paraben activation of c-Myc expression and cell proliferation were determined by real-time PCR, western blots, flow cytometry and chromatin immunoprecipitation assays in ER α - and HER2-positive human BT-474 breast cancer cells. Results: Butylparaben (BP) and HRG produced a synergistic increase in c-Myc mRNA and protein levels in BT-474 cells. Estrogen receptor antagonists blocked the synergistic increase in c-Myc protein levels. The combination of BP and HRG also stimulated proliferation of BT-474 cells compared to BP alone. HRG decreased the dose required for BP-mediated stimulation of c-Myc mRNA expression and cell proliferation. HRG caused the phosphorylation of serine 167 in ER α . BP and HRG produced a synergistic increase in ER α recruitment to the c-Myc gene. Conclusion: Our studies demonstrate that HER ligands enhance the potency of BP to stimulate oncogene expression and breast cancer cell proliferation in vitro via ER α , suggesting that parabens might be active at exposure levels not previously considered toxicologically relevant from studies testing their effects in isolation.
Localization of small leucine‐rich proteoglycans and transforming growth factor‐β in human oral mucosal wound healing

Wound healing in oral mucosa is fast and results in little scar formation as compared with skin. The biological mechanisms underlying this property are poorly understood but may provide valuable information about the factors that promote wound regeneration. Small leucine‐rich proteoglycans (SLRPs) decorin, biglycan, fibromodulin and lumican are extracellular matrix molecules that regulate collagen fibrillogenesis, inhibit transforming growth factor‐β (TGF‐β) activity and reduce scarring. In the present study, we analyzed accumulation of SLRPs and TGF‐β during non‐scarring human oral mucosal wound healing. Biopsies were collected from healthy volunteers from unwounded tissue and from standardized experimental wounds 3–60 days postwounding. Localization of SLRPs, TGF‐β1 and TGF‐β3 was analyzed by immunohistochemical staining and quantitated by image analysis. Double immunostaining was used to study localization of SLRPs or active TGF‐β in distinct cells. Decorin, biglycan, fibromodulin, and TGF‐β isoforms showed significantly increased accumulation in the wound extracellular matrix and distinct wound cells while the abundance of lumican in the extracellular matrix was strongly reduced during wound healing. Localization and abundance of fibromodulin, lumican, and TGF‐β isoforms was also spatiotemporally regulated in the wound epithelium. The findings suggest that SLRPs regulate wound reepithelialization and connective tissue regeneration during oral mucosal wound healing.
Matrix-induced autologous chondrocyte implantation addressing focal chondral defect in adolescent knee.

BACKGROUND Matrix-induced autologous chondrocyte implantation (MACI) is the third generation tissue-engineering technique for the treatment of full-thickness articular cartilage defects. The aim of this study was to describe this new technique and the postoperative findings in adolescent knee with focal chondral defect. METHODS The MACI consists of diagnostic arthroscopy and cartilage harvest, chondrocyte culture and seeding in tissue-engineering collagenous membrane, and implantation of the scaffold. Clinical outcome at minimum 1-year follow-up was assessed in seven patients (mean age (16.6 ± 1.5) years; 14 - 19 years) with full-thickness cartilage defects, with International Knee Documentation Committee (IKDC) score, the International Cartilage Repair Society (ICRS) score and the Knee Injury and Osteoarthritis Outcome Score (KOOS). Besides, MR imaging was performed with T1 and T2-weighted imaging and three-dimensional spoiled gradient-recalled (3D-SPGR) MR imaging. RESULTS Clinical evaluation showed significant improvement and MRI analysis showed that the structure was homogeneous and the implant surface was regular and intact in six patients, but irregular in one. Of all the seven patients, the cartilage defect site was nearly totally covered by the implanted scaffold. CONCLUSIONS These results indicated that MACI technique is an option for cartilage defect in adolescent knee joint, especially large defect of over 2 cm(2). Long-term assessment is necessary to determine the true value of this technique.
Forecasting Stock Returns with Artificial Neural Networks

During the last few years there has been growing literature on applications of artificial neural networks to business and financial domains. In fact, a great deal of attention has been placed in the area of stock return forecasting. This is due to the fact that once artificial neural network applications are successful, monetary rewards will be substantial. Many studies have reported promising results in successfully applying various types of artificial neural network architectures for predicting stock returns. This chapter reviews and discusses various neural network research methodologies used in 45 journal articles that attempted to forecast stock returns. Modeling techniques and suggestions from the literature are also compiled and addressed. The results show that artificial neural networks are an emerging and promising computational technology that will continue to be a challenging tool for future research.
Genetic analysis for insulitis in NOD mice.

Non-obese diabetic (NOD) mice spontaneously develop diabetic signs akin to those of Type I diabetes in man. Insulitis, i.e., lymphocytic infiltration around and into the pancreatic islets is one of the characteristics of such mice. It is also the etiologic pathological lesion in the development of diabetes mellitus in NOD mice. Thus, we chose insulitis as a marker for genetic analysis of the development of diabetes mellitus in NOD mice and clarified the mode of its inheritance. In breeding studies between NOD and C57BL/6J mice, insulitis was not observed in the F1 and (F1 X C57BL/6J) backcross generations, but was found with incidences of 3.9% in females and 1.4% in males in the F2 generation and 23.7% in females and 12.1% in males in the (F1 X NOD) backcross generation. These incidences in the F2 and (F1 X NOD) backcross females corresponded approximately to 1/16 and 1/4 of the incidences of 89.7% in the NOD females, respectively. A similar relationship was observed between the F2 and (F1 X NOD) backcross males and the NOD males. When the gene expressivity of both sexes for a double recessive homozygote was assumed to be the incidences of insulitis in 9-week-old NOD females and males, respectively, the expected numbers of both sexes with and without insulitis in the F2 and backcross generations agreed well with the observed ones. These observations suggest that two recessive genes on independent autosomal chromosomes are necessary for the development of insulitis in NOD mice.
Subunit δ Is the Key Player for Assembly of the H+-translocating Unit of Escherichia coli FOF1 ATP Synthase*

Background: FOF1 ATP synthases are rotary nanomachines transporting protons across the membrane during catalysis. Results: Escherichia coli FOF1 is assembled from subcomplexes with subunit δ functioning as clamp to generate stable FO. Conclusion: δ guarantees that the open proton channel is concomitantly assembled within coupled FOF1. Significance: We investigate how a proton-translocating unit is assembled while simultaneously maintaining the low membrane proton permeability essential for viability. The ATP synthase (FOF1) of Escherichia coli couples the translocation of protons across the cytoplasmic membrane to the synthesis or hydrolysis of ATP. This nanomotor is composed of the rotor c10γϵ and the stator ab2α3β3δ. To study the assembly of this multimeric enzyme complex consisting of membrane-integral as well as peripheral hydrophilic subunits, we combined nearest neighbor analyses by intermolecular disulfide bond formation or purification of partially assembled FOF1 complexes by affinity chromatography with the use of mutants synthesizing different sets of FOF1 subunits. Together with a time-delayed in vivo assembly system, the results demonstrate that FOF1 is assembled in a modular way via subcomplexes, thereby preventing the formation of a functional H+-translocating unit as intermediate product. Surprisingly, during the biogenesis of FOF1, F1 subunit δ is the key player in generating stable FO. Subunit δ serves as clamp between ab2 and c10α3β3γϵ and guarantees that the open H+ channel is concomitantly assembled within coupled FOF1 to maintain the low membrane proton permeability essential for viability, a general prerequisite for the assembly of multimeric H+-translocating enzymes.
Vaccinia virus impairs directional migration and chemokine receptor switch of human dendritic cells

A crucial event for the induction of an anti‐viral immune response is the coordinated, phenotype‐dependent migration of dendritic cells (DC) to sites of infection and secondary lymphoid organs. Here we show that the vaccinia virus (VV) strains Western Reserve (WR) and modified virus Ankara (MVA) inhibit directional migration of mature DC toward the lymphoid chemokines CCL19 and CXCL12 without affecting surface expression of the respective chemokine receptors or impairing undirected cellular locomotion. Instead, infection with VV results in a deficiency of extracellular signal‐regulated kinase‐1 and a disturbance of intracellular calcium mobilization, indicating a viral interference with signaling events downstream of the surface chemokine receptors. In immature DC, apart from inhibiting chemokine‐induced migration of infected DC, infection with both VV strains increases expression of the inflammatory chemokine receptors CCR1 and CXCR1 on non‐infected bystander DC, which depends on the activity of IFN‐α. Although functional, these chemokine receptors are resistant to lipopolysaccharide‐induced down‐regulation. In addition, VV‐infected and non‐infected bystander DC fail to up‐regulate the lymphoid chemokine receptor CCR7 upon activation, together pointing to a disability to undergo the chemokine receptor switch. This study shows that VV targets directional migration of professional antigen‐presenting cells at multiple functional levels, revealing a potent viral strategy of immune escape.
Face Parsing via a Fully-Convolutional Continuous CRF Neural Network

In this work, we address the face parsing task with a Fully-Convolutional continuous CRF Neural Network (FC-CNN) architecture. In contrast to previous face parsing methods that apply region-based subnetwork hundreds of times, our FC-CNN is fully convolutional with high segmentation accuracy. To achieve this goal, FC-CNN integrates three subnetworks, a unary network, a pairwise network and a continuous Conditional Random Field (C-CRF) network into a unified framework. The high-level semantic information and low-level details across different convolutional layers are captured by the convolutional and deconvolutional structures in the unary network. The semantic edge context is learnt by the pairwise network branch to construct pixel-wise affinity. Based on a differentiable superpixel pooling layer and a differentiable C-CRF layer, the unary network and pairwise network are combined via a novel continuous CRF network to achieve spatial consistency in both training and test procedure of a deep neural network. Comprehensive evaluations on LFW-PL and HELEN datasets demonstrate that FC-CNN achieves better performance over the other state-of-arts for accurate face labeling on challenging images.
Maternal tract factors contribute to paternal seminal fluid impact on metabolic phenotype in offspring

Significance Events at conception shape the future growth and health of offspring, to impact life course potential and disease susceptibility. The environment and experiences of both parents contribute to programming offspring phenotype through epigenetic modifications imparted before embryo implantation. How the father transmits this information remains elusive. Possible pathways include the sperm genome and epigenome, postejaculatory effects of seminal fluid on sperm, and indirect actions of seminal fluid on various female factors regulating embryo development. In this study, we provide evidence that seminal fluid acts to influence both sperm integrity and the balance of embryotrophic and embryotoxic signals in the female reproductive tract, in turn affecting embryo development and programming of future adiposity and metabolic phenotype in male offspring. Paternal characteristics and exposures influence physiology and disease risks in progeny, but the mechanisms are mostly unknown. Seminal fluid, which affects female reproductive tract gene expression as well as sperm survival and integrity, provides one potential pathway. We evaluated in mice the consequences for offspring of ablating the plasma fraction of seminal fluid by surgical excision of the seminal vesicle gland. Conception was substantially impaired and, when pregnancy did occur, placental hypertrophy was evident in late gestation. After birth, the growth trajectory and metabolic parameters of progeny were altered, most profoundly in males, which exhibited obesity, distorted metabolic hormones, reduced glucose tolerance, and hypertension. Altered offspring phenotype was partly attributable to sperm damage and partly to an effect of seminal fluid deficiency on the female tract, because increased adiposity was also evident in adult male progeny when normal two-cell embryos were transferred to females mated with seminal vesicle-excised males. Moreover, embryos developed in female tracts not exposed to seminal plasma were abnormal from the early cleavage stages, but culture in vitro partly alleviated this. Absence of seminal plasma was accompanied by down-regulation of the embryotrophic factors Lif, Csf2, Il6, and Egf and up-regulation of the apoptosis-inducing factor Trail in the oviduct. These findings show that paternal seminal fluid composition affects the growth and health of male offspring, and reveal that its impact on the periconception environment involves not only sperm protection but also indirect effects on preimplantation embryos via oviduct expression of embryotrophic cytokines.
Polymorphisms at the Paraoxonase 1 L55M and Q192R Loci Affect the Pathophysiology of Alzheimer’s Disease: Emphasis on the Cholinergic System and Beta-Amyloid Levels

Background: Paraoxonase 1 (PON1) functions to protect the cholinergic system against nerve gases and the organophosphate family of pesticides. Recent studies have shown that polymorphisms at the PON1 L55M and Q192R loci might affect individual susceptibility to experience-derived and environmental events such as the exposure to inhibitors of cholinesterase (ChEIs). Objective: ChEI therapy being the treatment of choice for mild-to-moderate Alzheimer’s disease (AD) patients, we determined whether genetic variations in the PON1 loci are associated with AD risk and whether they affect brain choline acetyltransferase (CHAT) activity, nicotinic receptor density, and β-amyloid (Aβ) levels in different regions of AD and age-matched control subjects. Methods: This pilot genetic study used a small cohort of brains from autopsy-confirmed AD patients and age-matched controls from the Douglas Hospital Brain Bank, Quebec, Canada. Results: The frequency of the M55M genotype at the PON1 L55M locus was found to be significantly increased in AD patients relative to age-matched controls (p < 0.05). Significant associations were observed between the PON1 L55M and Q192R polymorphisms and frontal cortex Aβ levels as well as CHAT activity and nicotinic receptor density in the temporal cortex. Conclusions: Our results suggest a prominent role for PON1 in the pathophysiology of common AD with a marked impact on the cholinergic system and Aβ levels in the brain.
Development and Validation of a Questionnaire to Assess Multimorbidity in Primary Care: An Indian Experience

Multimorbidity remains an underexplored domain in Indian primary care. We undertook a study to assess the prevalence, correlates, and outcomes of multimorbidity in primary care settings in India. This paper describes the process of development and validation of our data collection tool “Multimorbidity Assessment Questionnaire for Primary Care (MAQ-PC). ” An iterative process comprising desk review, chart review, and expert consultations was undertaken to generate the questionnaire. The MAQ-PC contained items on chronic conditions, health care utilization, health related quality of life, disease severity, and sociodemographics. It was first tested with twelve adults for comprehensibility followed by test-retest reliability with 103 patients from four primary care practices. For interrater reliability, two interviewers separately administered the questionnaire to sixteen patients. MAQ-PC displayed strong internal consistency (Cronbach's alpha: 0.69), interrater reliability (Cohen's Kappa: 0.78–1), and test-retest reliability (ICC: 0.970–0.741). Substantial concordance between self-report and physician diagnosis (Scott Kappa: 0.59–1.0) was observed for listed chronic conditions indicating strong concurrent validity. Nearly 54% had one chronic condition and 23.3% had multimorbidity. Our findings demonstrate MAQ-PC to be a valid and reliable measure of multimorbidity in primary care practice and suggest its potential utility in multimorbidity research in India.