bluuebunny/crossref_metadata_2025 huggingface dataset:
Effectiveness of naltrexone treatment for alcohol use disorders in HIV: a systematic review
Authors: Farhadian Negin , Moradi Sajad , Zamanian Mohammad Hossein , Farnia Vahid , Rezaeian Shahab , Farhadian Maryam , Shahlaei Mohsen
Published: March 2020

Background

Because alcohol use disorders (AUDs) in patients living with HIV/AIDS are associated with a reduction in therapeutic outcomes and increases the risk of morbidity/mortality, finding an appropriate pharmacotherapy treatment for this disorder is necessary.

Objectives

This systematic review contains studies that examine the effects of pharmacological intervention (oral naltrexone (NTX) or injectable extended-release naltrexone (XR-NTX)) on the persons living with HIV and AUDs.

Methods

A systematic literature search using three electronic databases including Pubmed Medline, Scopus and the Cochrane Library and Google Scholar was conducted and includes articles published from 1995 to 2019. Records were collected by searching relevant keywords and those that meet the inclusion/exclusion criteria are included.

Results

Overall, in this systematic review, the results of 7 relevant studies including pilot and randomized controlled/clinical trials were summarized and reviewed. Among selected records 2 of these assessed the efficacy of NTX and 5 tested the XR-NTX effectiveness in treating AUDs among persons living with HIV (PLH). In summary, with some expectations, NTX and XR-NTX administration in persons living with HIV and AUDs led to reduced alcohol use, improved viral suppression, unchanged ART adherence and has no significant adverse events.

Conclusion

The findings of this systematic review suggest the beneficial effects and safety of the NTX and XR-NTX for treating AUDs in PLH. Further studies are needed in the future to focus on the treatment of AUDs in people living with HIV.
The potential drug for treatment in pancreatic adenocarcinoma: a bioinformatical study based on distinct drug databases
Authors: Liu Han , Zhou Qi , Wei Wenjuan , Qi Bing , Zeng Fen , Bao Nabuqi , Li Qian , Guo Fangyue , Xia Shilin
Published: March 2020

Background

The prediction of drug-target interaction from chemical and biological data can advance our search for potential drug, contributing to a therapeutic strategy for pancreatic adenocarcinoma (PAAD). We aim to identify hub genes of PAAD and search for potential drugs from distinct databases. The docking simulation is adopted to validate our findings from computable perspective.

Methods

Differently expressed genes (DEGs) of PAAD were performed based on TCGA. With two Cytoscape plugins of CentiScaPe and MCODE, hub genes were analyzed and visualized by STRING analysis of Protein–protein Interaction (PPI). The hub genes were further selected with significant prognostic values. In addition, we examined the correlation between hub genes and immune infiltration in PAAD. Subsequently, we searched for the hub gene-targeted drugs in Connectivity map (Cmap) and cBioportal, which provided a large body of candidate drugs. The hub gene, which was covered in the above two databases, was estimated in Traditional Chinese Medicine Systems Pharmacology (TCMSP) and Herbal Ingredients’ Targets (HIT) database, which collected natural herbs and related ingredients. After obtaining molecular structures, the potential ingredient from TCMSP was applied for a docking simulation. We finalized a network connectivity of ingredient and its targets.

Results

A total of 2616 DEGs of PAAD were identified, then we further determined and visualized 24 hub genes by a connectivity analysis of PPI. Based on prognostic value, we identified 5 hub genes including AURKA (p = 0.0059), CCNA2 (p = 0.0047), CXCL10 (p = 0.0044), ADAM10 (p = 0.00043), and BUB1 (p = 0.0033). We then estimated tumor immune correlation of these 5 hub genes, because the immune effector process was one major result of GO analysis. Subsequently, we continued to search for candidate drugs from Cmap and cBioportal database. BUB1, not covered in the above two databases, was estimated in TCMSP and HIT databases. Our results revealed that genistein was a potential drug of BUB1. Next, we generated two docking modes to validate drug-target interaction based on their 3D structures. We eventually constructed a network connectivity of BUB1 and its targets.

Conclusions

All 5 hub genes that predicted poor prognosis had their potential drugs, especially our findings showed that genistein was predicted to target BUB1 based on TCMSP and docking simulation. This study provided a reasonable approach to extensively retrieve and initially validate putative therapeutic agents for PAAD. In future, these drug-target results should be investigated with solid data from practical experiments.
A recurrent ABCC2 p.G693R mutation resulting in loss of function of MRP2 and hyperbilirubinemia in Dubin-Johnson syndrome in China
Authors: Wu Lina , Li Yanmeng , Song Yi , Zhou Donghu , Jia Siyu , Xu Anjian , Zhang Wei , You Hong , Jia Jidong , Huang Jian , Ou Xiaojuan
Published: March 2020

Background

Dubin-Johnson syndrome (DJS) is a rare autosomal recessive disorder characterized by predominantly conjugated hyperbilirubinemia that is caused by pathogenic mutations in the adenosine triphosphate-binding cassette subfamily C member 2 (ABCC2) gene, which encodes multidrug resistance-associated protein 2 (MRP2). However, little is known about the causative mutation of DJS in China. Recently, we have reported ABCC2 p.G693R mutation in two unrelated cases. In the present study, we investigated the pathogenicity of the ABCC2 p.G693R mutation in DJS in China.

Methods

Clinical and genetic analysis was conducted for the two patients with the ABCC2 p.G693R mutation. Whole exome sequencing for mutations in other known hyperbilirubinemia-related genes was conducted for the cases with ABCC2 p.G693R. Expression and cellular localization of the mutant MRP2 p.G693R were analyzed by Western blotting and immunofluorescence assay, respectively. Organic anion transport activity was evaluated by the analysis of glutathione-conjugated-monochlorobimane.

Results

The two DJS patients with ABCC2 p.G693R mutation, which was conserved among different species, showed typical hyperbilirubinemia phenotype. No pathogenic mutation was identified in the other known hyperbilirubinemia related genes. Functional studies in three cell lines showed that the expression, localization and the organic anion transport activity were significantly compromised by MRP2 p.G693R mutation compared with wild-type MRP2.

Conclusions

The recurrent ABCC2 p.G693R mutation is associated with loss of function of the MRP2 protein and may result in hyperbilirubinemia in DJS in China.
Dynamic LTR retrotransposon transcriptome landscape in septic shock patients
Authors:   MIPrea Study Group, Mommert Marine ,   REALISM Study Group, Tabone Olivier , Guichard Audrey , Oriol Guy , Cerrato Elisabeth , Denizot Mélanie , Cheynet Valérie , Pachot Alexandre , Lepape Alain , Monneret Guillaume , Venet Fabienne , Brengel-Pesce Karen , Textoris Julien , Mallet François
Published: March 2020

Background

Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. Numerous studies have explored the complex and dynamic transcriptome modulations observed in sepsis patients, but a large fraction of the transcriptome remains unexplored. This fraction could provide information to better understand sepsis pathophysiology. Multiple levels of interaction between human endogenous retroviruses (HERV) and the immune response have led us to hypothesize that sepsis is associated with HERV transcription and that HERVs may contribute to a signature among septic patients allowing stratification and personalized management.

Methods

We used a high-density microarray and RT-qPCR to evaluate the HERV and Mammalian Apparent Long Terminal Repeat retrotransposons (MaLR) transcriptome in a pilot study that included 20 selected septic shock patients, stratified on mHLA-DR expression, with samples collected on day 1 and day 3 after inclusion. We validated the results in an unselected, independent cohort that included 100 septic shock patients on day 3 after inclusion. We compared septic shock patients, according to their immune status, to describe the transcriptional HERV/MaLR and conventional gene expression. For differential expression analyses, moderated t tests were performed and Wilcoxon signed-rank tests were used to analyze RT-qPCR results.

Results

We showed that 6.9% of the HERV/MaLR repertoire was transcribed in the whole blood, and septic shock was associated with an early modulation of a few thousand of these loci, in comparison to healthy volunteers. We provided evidence that a subset of HERV/MaLR and conventional genes were differentially expressed in septic shock patients, according to their immune status, using monocyte HLA-DR (mHLA-DR) expression as a proxy. A group of 193 differentially expressed HERV/MaLR probesets, tested in an independent septic shock cohort, identified two groups of patients with different immune status and severity features.

Conclusion

We demonstrated that a large, unexplored part of our genome, which codes for HERV/MaLR, may be linked to the host immune response. The identified set of HERV/MaLR probesets should be evaluated on a large scale to assess the relevance of these loci in the stratification of septic shock patients. This may help to address the heterogeneity of these patients.
High hepatocyte growth factor expression in primary tumor predicts better overall survival in male breast cancer
Authors: Qiu Si-Qi , van Rooijen Johan , Nienhuis Hilde H. , van der Vegt Bert , Timmer-Bosscha Hetty , van Leeuwen-Stok Elise , Walenkamp Annemiek M. E. , van Deurzen Carolien H. M. , de Bock Geertruida H. , de Vries Elisabeth G. E. , Schröder Carolien P.
Published: March 2020

Background

Breast cancer is rare in men, but management is focused on tumor characteristics commonly found in female breast cancer. The tumor microenvironment of male breast cancer is less well understood, and insight may improve male breast cancer management. The hepatocyte growth factor (HGF)/c-MET axis and the stromal cell-derived factor-1 (CXCL12)/C-X-C chemokine receptor type 4 (CXCR4) axis are prognostic in women with breast cancer. We aimed to investigate these factors in male breast cancer and correlate them with patient survival.

Methods

From 841 Dutch males with breast cancer who were enrolled in the EORTC 10085/TBCRC/BIG/NABCG International Male Breast Cancer Program (NCT01101425) and diagnosed between 1990 and 2010, archival primary tumor samples were collected. Tissue microarrays were constructed with 3 cores per sample and used for immunohistochemical analysis of HGF, c-MET, CXCL12, and CXCR4. Overall survival (OS) of the patients without metastases (M0) was analyzed using the Kaplan-Meier method. The value of the markers regarding OS was determined using univariable and multivariable Cox regression analyses, providing hazard ratios (HRs) and 95% confidence intervals (95% CIs).

Results

Of 720 out of 841 patients, sufficient tissue was available for analysis; 487 out of 720 patients had M0 disease. Patients with high HGF expression and high CXCL12 expression had a superior OS (low vs high expression of both markers, 7.5 vs 13.0 years, hazard ratio [HR] 0.64, 95% CI 0.49–0.84, P = 0.001 [HGF]; 9.1 vs 15.3 years, HR 0.63, 95% CI 0.45–0.87, P = 0.005 [CXCL12]). Multivariate analysis identified HGF as an independent predictor for OS (HR 0.64, 95% CI 0.47–0.88, P = 0.001).

Conclusions

HGF and CXCL12 tumor expression appear to identify male breast cancer patients with a relatively good prognosis. Possibly, this could support male breast cancer-specific management strategies in the future.
Standardized patients in psychotherapy training and clinical supervision: study protocol for a randomized controlled trial
Authors: Kühne Franziska , Heinze Peter Eric , Weck Florian
Published: March 2020

Background

Psychotherapy is highly effective and widely acknowledged for treating various mental disorders. Nevertheless, in terms of methods for teaching effective psychotherapeutic approaches and competencies, there has been a lack of investigation. Training and supervision are the main strategies for teaching therapist competencies, and standardized role-plays with simulated patients (i.e., trained individuals playing someone with a mental disorder) seem useful for evaluating training approaches. In medical education, this procedure is now internationally established. However, so far, little use has been made of standardized role-playing to evaluate training and supervision in the area of clinical psychology and psychotherapy.

Methods

In this study, standardized role-plays are used to evaluate methods for training and supervision. Central cognitive behavioral approaches for treating depression are taught in the training. The first experiment compares an active training approach (i.e., model learning) with a passive one (i.e., reading manual-based instructions). The second experiment compares a direct supervision technique (i.e., supervision based on video analysis) with an indirect one (i.e., supervision based on verbal reporting). In each experiment, 68 bachelor’s and master’s students of psychology will be randomly assigned to the experimental and control groups. Each student takes part in three role-plays (baseline, post and 3-month follow-up), which are all videotaped. Two independent raters assess therapist competencies in each role-play on the basis of a standardized competence scale.

Discussion

The research project aims to contribute to the development of specific training and supervision methods in order to improve psychotherapy training and patient care.

Trial registration

ISRCTN Registry, ISRCTN19173895. Registered on 10 December 2019.
Protocol for a randomized control trial of the caregiver support intervention with Syrian refugees in Lebanon
Authors: Miller Kenneth E. , Arnous Maguy , Tossyeh Fadila , Chen Alexandra , Bakolis Ioannis , Koppenol-Gonzalez Gabriela V. , Nahas Nayla , Jordans Mark J. D.
Published: March 2020

Background

There is evidence that chronic stress negatively impacts parenting among refugees and other war-affected communities. Persistent parental stress and distress may lead to unresponsive, anxious, or overly harsh parenting and a corresponding increase in emotional and behavior problems among children. Most parenting interventions emphasize the acquisition of knowledge and skills; however, this overlooks the deleterious effects of chronic stress on parenting. The Caregiver Support Intervention (CSI) aims to strengthen quality of parenting skills by lowering stress and improving psychosocial wellbeing among refugee caregivers of children aged 3–12 years, while also increasing knowledge and skills related to positive parenting. The CSI is a nine-session psychosocial group intervention delivered by non-specialist providers. It is intended for all adult primary caregivers of children in high-adversity communities, rather than specifically targeting caregivers already showing signs of elevated distress.

Methods/design

The primary objective of this study is to assess the effectiveness of the CSI through a parallel group randomized controlled study with Syrian refugee families in North Lebanon. Participants will be primary caregivers of children aged 3–12 years, with one index child per family. Families will be randomized to the CSI or a waitlist control group.

A total of 240 families (480 caregivers) will be recruited into the study. Randomization will be at the family level, and CSI groups will be held separately for women and men. The study will be implemented in two waves. Outcomes for both arms will be assessed at baseline, post-intervention, and at a 3-month follow-up. The primary outcome is quality of parenting skills. Secondary outcomes include parental warmth and sensitivity, harsh parenting, parenting knowledge, and child psychosocial wellbeing. Putative mediators of the CSI on parenting are caregiver stress, distress, psychosocial wellbeing, and stress management.

Discussion

This trial may establish the CSI as an effective intervention for strengthening parenting in families living in settings of high adversity, particularly refugee communities.

Trial registration

International Society for the Registration of Clinical Trials, ISRCTN22321773. Registered on 5 August 2019
Ginger in patients with active ulcerative colitis: a study protocol for a randomized controlled trial
Authors: Shayesteh Forough , Haidari Fatemeh , Shayesteh Ali Akbar , Mohammadi-Asl Javad , Ahmadi-Angali Kambiz
Published: March 2020

Background

As a lifetime disorder, ulcerative colitis (UC) is an inflammatory bowel disease (IBD) that affects quality of life and also demands long-term interventions. In spite of considerable side effects and sometimes restricted uses, efficient medications are available for UC treatment. Some in vitro and in vivo examinations have correspondingly introduced ginger and its active components with antioxidant, anti-inflammatory, and anti-ulcerative properties. Therefore, this trial aims to evaluate the effect of ginger supplementation on patients with active UC.

Methods

This study will be a 12-week, double-blind, parallel-group, randomized, controlled trial (RCT) in which 44 patients will be allocated to ginger and placebo groups receiving basic routine treatments plus ginger or placebo capsules, respectively. The primary outcomes are inflammatory markers (TNF-α and hs-CRP) and total antioxidant capacity.

Discussion

The findings of this trial will provide evidence on the effect of ginger on patients with active UC.

Trial registration

Iranian Registry of Clinical Trials, IRCT20190129042552N1. Registered on 21 June 2019.
Multiplex PCRs for the specific identification of marsupial and deer species from faecal samples as a basis for non-invasive epidemiological studies of parasites
Authors: Koehler Anson V. , Zhang Yan , Wang Tao , Haydon Shane R. , Gasser Robin B.
Published: March 2020

Background

The specific identification of animals through the analysis of faecal DNA is important in many areas of scientific endeavour, particularly in the field of parasitology.

Methods

Here, we designed and assessed two multiplex PCR assays using genetic markers in a mitochondrial cytochrome b (cytb) gene region for the unequivocal identification and discrimination of animal species based on the specific amplification of DNA from faecal samples collected from water catchment areas in Victoria, Australia. One of these assays differentiates three marsupial species (eastern grey kangaroo, swamp wallaby and common wombat) and the other distinguishes three deer species (fallow, red and sambar deer). We tested these two assays using a total of 669 faecal samples, collected as part of an ongoing programme to monitor parasites and microorganisms in these animals.

Results

These two PCR assays are entirely specific for these animal species and achieve analytical sensitivities of 0.1–1.0 picogram (pg). We tested 669 faecal samples and found that some previous inferences of species based on faecal morphology were erroneous. We were able to molecularly authenticate all of the 669 samples.

Conclusions

We have established PCR assays that accurately distinguish the faecal samples of some of the prominent large mammalian herbivores found within a water catchment system in the state of Victoria, Australia. The multiplex assays for marsupials and deer produce amplicons that are easily differentiable based on their size on an agarose gel, and can be readily sequenced for definitive species authentication. Although established for marsupials and deer, the methodology used here can be applied to other host-parasite study systems to ensure data integrity.
Detection of enteric parasite DNA in household and bed dust samples: potential for infection transmission
Authors: Mejia Rojelio , Seco-Hidalgo Victor , Garcia-Ramon Diana , Calderón Evelyn , Lopez Andrea , Cooper Philip J.
Published: March 2020

Background

Enteric parasites are transmitted in households but few studies have sampled inside households for parasites and none have used sensitive molecular methods.

Methods

We collected bed and living room dust samples from households of children participating in a clinical trial of anthelmintic treatment in rural coastal Ecuador. Dust was examined for presence of DNA specific for 11 enteric parasites (Ascaris lumbricoides, Trichuris trichiura, Ancylostoma duodenale, Necator americanus, Strongyloides stercoralis, Toxocara canis and T. cati, Giardia lamblia, Blastocystis hominis, Cryptosporidium spp., and Entamoeba histolytica) by quantitative PCR (qPCR).

Results

Of the 38 households sampled, 37 had positive dust for at least one parasite and up to 8 parasites were detected in single samples. Positivity was greatest for B. hominis (79% of household samples) indicating a high level of environmental fecal contamination. Dust positivity rates for individual pathogens were: S. stercoralis (52%), A. lumbricoides (39%), G. lamblia (39%), Toxocara spp. (42%), hookworm (18%) and T. trichiura (8%). DNA for Cryptosporidium spp. and E. histolytica was not detected. Bed dust was more frequently positive than floor samples for all parasites detected. Positivity for A. lumbricoides DNA in bed (adjusted OR: 10.0, 95% CI: 2.0–50.1) but not floor dust (adjusted OR: 3.6, 95% CI: 0.3–37.9) was significantly associated with active infections in children.

Conclusions

To our knowledge, this is the first use of qPCR on environmental samples to detect a wide range of enteric pathogen DNA. Our results indicate widespread contamination of households with parasite DNA and raise the possibility that beds, under conditions of overcrowding in a humid tropical setting, may be a source of transmission.
How much of skin improvement over time in systemic sclerosis is due to normal ageing? A prospective study with shear-wave elastography
Authors: Santiago T. , Santiago M. , Coutinho M. , Salvador M. J. , Da Silva J. A. P.
Published: March 2020

Background

Measurement of skin involvement is essential for the diagnosis and assessment of prognosis and disease progression in systemic sclerosis (SSc). The modified Rodnan skin score (mRSS) is the gold standard measure of skin thickness, but it has been criticised for the lack of objectivity, poor inter-observer reproducibility and lack of sensitivity to change. Recently, shear-wave elastography (SWE) emerged as a promising tool for the objective and quantitative assessment of the skin in SSc patients. However, no studies have evaluated its sensitivity to change over time.

Objective

To assess changes in skin stiffness in SSc patients using SWE during a 5-year follow-up.

Methods

Skin stiffness [i.e. shear-wave velocity values (SWV) in metres per second] was assessed by SWE ultrasound (using virtual touch image quantification) at the 17 sites of the mRSS, in each participant, at baseline and follow-up. mRSS was performed at both time points. Differences between groups were analysed using the related-samples Wilcoxon signed-rank test and the Mann–Whitney U test.

Results

We included 21 patients [85.7% females; mean age 56.3 (10.4) years at baseline, 57.1% with limited SSc] and 15 healthy controls [73.3% females; mean age 53.6 (14.1) years)]. The median follow-up was 4.9 (0.4) years.

Skin stiffness decreased significantly at all Rodnan sites (p ≤ 0.001) (except in the fingers), in SSc patients, over time. The same phenomenon occurred in controls, but to a lesser degree, in terms of percentage change.

The percentage reduction in skin stiffness varied in the different Rodnan sites and in different phases of the disease. In addition, SWV values also decreased significantly in 15/16 skin sites with local normal Rodnan at baseline, whereas local Rodnan skin score only changed significantly in the upper arm (p = 0.046) and forearm (p = 0.026).

Conclusion

This study provides first-time evidence suggesting that skin SWV values are more sensitive to change over time than mRSS and reduce significantly over time in SSc and normal controls.
Breast milk vitamin B12 concentration and incidence of diarrhea and respiratory infections among infants in urban Tanzania: a prospective cohort study
Authors: Lweno Omar N. , Sudfeld Christopher R. , Hertzmark Ellen , Manji Karim P. , Darling Anne Marie , Fawzi Wafaie W.
Published: March 2020

Objective

A recent trial of vitamin B12 supplementation among Indian children 6–30 months found no effect on the incidence of diarrhea and respiratory infections. These results differ with studies in adults that showed improvement of the immune response following treatment with vitamin B12. We sought to determine how the adequacy of vitamin B12 concentrations in breast milk could act as immune modulator and protect against the incidence of diarrhea and respiratory infections of children up to 18 months in urban Tanzania.

Results

A prospective cohort study was undertaken to determine the association of breast milk vitamin B12 concentration with the incidence of acute respiratory infection and diarrhea among infants in urban Tanzania. A random sample of 491 women enrolled in a trial of multivitamins provided milk for B12 analysis at or around 6 weeks postpartum. Of 491 women, 345 had breast milk vitamin B12 inadequacy (< 310 pmol/L). Using generalized estimating equations, we found no overall association of milk vitamin B12 concentration with incident diarrhea and acute respiratory infections in infants. Studies measuring longitudinal changes of breast milk B12 concentration over time are needed to clarify the role of breast milk vitamin B12 in childhood infections.
Effects of oxytocin administration on salivary sex hormone levels in autistic and neurotypical women
Authors: Procyshyn Tanya L. , Lombardo Michael V. , Lai Meng-Chuan , Auyeung Bonnie , Crockford Sarah K. , Deakin J , Soubramanian S. , Sule A , Baron-Cohen Simon , Bethlehem Richard A. I.
Published: March 2020

Background

Oxytocin administration, which may be of therapeutic value for individuals with social difficulties, is likely to affect endogenous levels of other socially relevant hormones. However, to date, the effects of oxytocin administration on endogenous hormones have only been examined in neurotypical individuals. The need to consider multi-hormone interactions is particularly warranted in oxytocin trials for autism due to evidence of irregularities in both oxytocin and sex steroid systems.

Methods

In this double-blind cross-over study, saliva samples were collected from 16 autistic and 29 neurotypical women before and after intranasal administration of 24 IU oxytocin or placebo. Oestradiol, testosterone, and oxytocin levels were quantified in saliva samples. Participants also completed the Autism-Spectrum Quotient (AQ) and Empathy Quotient (EQ) questionnaires.

Results

Distinct patterns of change in testosterone and oestradiol levels pre- to-post-administration were observed in autistic relative to neurotypical women (ANCOVA, p < 0.05 main effect of Group), controlling for sample collection time. The mean percent change oestradiol was + 8.8% for the autism group and − 13.0% for the neurotypical group (t = 1.81, p = 0.08), while the mean percent change testosterone was + 1.1% in the autism group and − 12.6% in the neurotypical group (t = 1.26, p = 0.22). In the oxytocin condition, the mean percent change oestradiol was + 12.6% in the autism group and − 6.9% in the neurotypical group (t = 1.78, p = 0.08), while the mean percent change testosterone was + 14.4% in the autism group and − 15.2% in the neurotypical group (t = 3.00, p = 0.006). Robust regression confirmed that group differences in percent change hormone levels were not driven by a small number of influential individuals. Baseline hormone levels did not differ between groups when considered individually. However, baseline testosterone relative to oestradiol (T:E2 ratio) was higher in autistic women (p = 0.023, Cohen’s d = 0.63), and this ratio correlated positively and negatively with AQ and EQ scores, respectively, in the combined sample.

Limitations

Further studies with larger and more diverse autistic sample are warranted to confirm these effects.

Conclusions

This study provides the first evidence that oxytocin influences endogenous testosterone levels in autistic individuals, with autistic women showing increases similar to previous reports of neurotypical men. These findings highlight the need to consider sex steroid hormones as a variable in future oxytocin trials.
COVER: conformational oversampling as data augmentation for molecules
Authors: Hemmerich Jennifer , Asilar Ece , Ecker Gerhard F.
Published: March 2020

Training neural networks with small and imbalanced datasets often leads to overfitting and disregard of the minority class. For predictive toxicology, however, models with a good balance between sensitivity and specificity are needed. In this paper we introduce conformational oversampling as a means to balance and oversample datasets for prediction of toxicity. Conformational oversampling enhances a dataset by generation of multiple conformations of a molecule. These conformations can be used to balance, as well as oversample a dataset, thereby increasing the dataset size without the need of artificial samples. We show that conformational oversampling facilitates training of neural networks and provides state-of-the-art results on the Tox21 dataset.
Transformer-CNN: Swiss knife for QSAR modeling and interpretation
Authors: Karpov Pavel , Godin Guillaume , Tetko Igor V.
Published: March 2020

We present SMILES-embeddings derived from the internal encoder state of a Transformer [1] model trained to canonize SMILES as a Seq2Seq problem. Using a CharNN [2] architecture upon the embeddings results in higher quality interpretable QSAR/QSPR models on diverse benchmark datasets including regression and classification tasks. The proposed Transformer-CNN method uses SMILES augmentation for training and inference, and thus the prognosis is based on an internal consensus. That both the augmentation and transfer learning are based on embeddings allows the method to provide good results for small datasets. We discuss the reasons for such effectiveness and draft future directions for the development of the method. The source code and the embeddings needed to train a QSAR model are available on https://github.com/bigchem/transformer-cnn. The repository also has a standalone program for QSAR prognosis which calculates individual atoms contributions, thus interpreting the model’s result. OCHEM [3] environment (https://ochem.eu) hosts the on-line implementation of the method proposed.
Clinical significance of miR-19b-3p in patients with sepsis and its regulatory role in the LPS-induced inflammatory response
Authors: Xu Huimin , Liu Xiuwu , Ni Huaijun
Published: March 2020

Background

MicroRNAs (miRNAs) play important roles in the development and progression of sepsis. This study investigated the clinical value of miR-19b-3p in sepsis patients, and explored its role in regulating inflammatory responses in HUVECs cells.

Methods

103 patients with sepsis and 98 healthy individuals were recruited. qRT-PCR was used for the measurement of miR-19b-3p level. Cell viability was evaluated using CCK-8. The protein levels of TNF-α and IL-6 were measured using ELISA. Receiver operating characteristic (ROC) curve and logistic regression analysis were constructed to evaluate the diagnostic and prognostic values of miR-19b-3p in sepsis patients.

Results

MiR-19b-3p level was significantly reduced in the serum from patients with sepsis compared with healthy controls (P < 0.001). Sepsis patients in the survival group had significantly high miR-19b-3p levels compared with the non-survival group (P < 0.001). MiR-19b-3p was of a good value in predicting sepsis risk, and was an independent prognostic factor for 28-day survival in sepsis patients (OR = 3.226, 95% CI 1.076–9.670, P = 0.037). MiR-19b-3p level was negatively associated with serum levels of IL-6 (r = − 0.852, P < 0.001) and TNF-α (r = − 0.761, P < 0.001). Overexpression of miR-19b-3p alleviated LPS-induced inflammatory response of HUVECs, which was reflected by the decrease of the levels of IL-6 and TNF-α induced by LPS treatment (P < 0.001).

Conclusion

MiR-19b-3p might be a potential biomarker for the early diagnosis and prognosis of sepsis patients. Overexpression of miR-19b-3p alleviated sepsis-induced inflammatory responses.
Cities and migration: generative urban policies through contextual vulnerability
Authors: Monno Valeria , Serreli Silvia
Published: March 2020

This paper deals with the relationships between urban policies for the integration of migrants and the construction of new spaces of coexistence in the contemporary city. It discusses the limits of the current conceptual framework of integration and shows how it works in a way that seperates space and people from each other. This creates marginalisation and segregation in already unjust and uneven cities. By contrast, the paper proposes a different perspective toward the construction of coexistence between local populations and migrants. It places a particular emphasis on contextual vulnerability and on its role in generative planning experiments that are aimed at creating inclusive cities. It also reflects on some of these experiences by considering their potential to reconnect local people, migrants and places, and shows how a focus on a relational and embodied understanding of vulnerability can give rise to supportive, less disciplining forms of coexistence in the contemporary city.
Linear feature extraction from point cloud using color information
Authors: Alshawabkeh Yahya
Published: March 2020

LiDAR is considered as an effective technology for digitizing the real scene at a very high-resolution and in a short time. However, the resolution of the LiDAR is not sufficient to identify and evaluate the façade surface features like edges and cracks. Generally, photographs provide a better interpretation of the linear characteristics. The complementary benefits of each allow exploring valuable spatial information with different surface detail levels. The paper introduces a flexible image-based approach for linear feature extraction from LiDAR point cloud. Initially, the algorithm converts the point clouds into a structured depth image to reduce the complexity and computation time. Using transformation matrix and camera calibration parameters, the visible point clouds are perceptively projected into color image space using co-linearity equations. The result depth channel is sampled with the interpolation process and added to the color channels to compute (RGBD) layers. The edges and linear features of the surface are initially extracted using the optical 2D imagery and subsequently, each pixel of the linear features can be projected directly into 3D space. Due to the various acquisition positions of the laser and color images, the issue of occlusion is resolved using the visibility algorithm. Applying the methodology, experimental results from the Treasury Monument of Jordan’s ancient Petra City, indicate that the developed approach provides adequate contour points for better interpretation and quantification of weathering processes and dangerous cracking. 3D Modeling these features can also reduce data size, facilitating surface inspection and analysis with simpler models.
Deficiency of vitamin B12 and its relation with neurological disorders: a critical review
Authors: Nawaz Ammara , Khattak Noor Nasir , Khan Muhammad Saleem , Nangyal Hasnain , Sabri Sabeen , Shakir Muhammad
Published: March 2020

B12 is an essential vitamin for human body which reduces the chances of neurological diseases, birth defects, and chronic disorders. It is a vital micro-nutrient for maintaining the brain health. This review sorts out some causes of vitamin B12 (B12) deficiency and develops its link with neurological disorders. The portals include PubMed, Google Scholar, Directory of Open Access Journals (DOAJ), Pak MediNet, and Science Direct were search for literature retrieval. Study of literature revealed that deficiency of this vitamin occurs primarily due to insufficient dietary intake which results in a group of neurological symptoms in adults as well as infants. These neurological disorders include apathy, anorexia, irritability, growth retardation, and developmental regression. It may also involve in delayed myelination or demyelination of neurons. It was concluded that B12 is vital micro-nutrient for healthy brain in children, younger, and elders. Various conditions are responsible for deficiency of B12. A timely and proper supplementation is necessary if it is dietary deficiency.
Towards more-than-human heritage: arboreal habitats as a challenge for heritage preservation
Authors: Roudavski Stanislav , Rutten Julian
Published: March 2020

Trees belong to humanity’s heritage, but they are more than that. Their loss, through catastrophic fires or under business-as-usual, is devastating to many forms of life. Moved by this fact, we begin with an assertion that heritage can have an active role in the design of future places. Written from within the field of architecture, this article focuses on structures that house life. Habitat features of trees and artificial replacement habitats for arboreal wildlife serve as concrete examples. Designs of such habitats need to reflect behaviours, traditions and cultures of birds, bats, and other animals. Our narrative highlights the nonhuman aspect of heritage, seeking to understand how nonhuman stakeholders can act as users and consumers of heritage and not only as its constituents. Our working definition states that more-than-human heritage encompasses tangible and intangible outcomes of historical processes that are of value to human as well as nonhuman stakeholders. From this basis, the article asks how the established notions of heritage can extend to include nonhuman concerns, artefacts, behaviours and cultures. As a possible answer to this question, the hypothesis tested here is that digital information can (1) contribute to the preservation of more-than-human heritage; and (2) illuminate its characteristics for future study and use. This article assesses the potential of three imaging technologies and considers the resulting data within the conceptual framework of more-than-human heritage, illuminating some of its concrete aspects and challenges.
Patients With APECED Have Increased Early Mortality Due to Endocrine Causes, Malignancies and infections
Authors: Borchers Joonatan , Pukkala Eero , Mäkitie Outi , Laakso Saila
Published: March 2020

Context

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is an autoimmune endocrinopathy with severe and unpredictable course. The impact of APECED on mortality has not been determined.

Objective

To assess overall and cause-specific mortality of patients with APECED.

Design and Setting

A follow-up study of Finnish patients with APECED from 1971 to 2018. Causes and dates of death were collected from Finnish registries.

Patients

Ninety-one patients with APECED.

Main Outcome Measure

Overall and cause-specific standardized mortality ratios (SMRs) determined by comparing the observed numbers of death and those expected on the basis of respective population death rates in Finland.

Results

The overall disease mortality was significantly increased (29 deaths, SMR 11; 95% confidence interval [CI] 7.2-16; P < 0.001). The relative risk (SMR) was highest in the youngest age groups but the absolute excess risk was similar (about 10 per 10 000 person-years) in all age categories. The highest SMRs were seen for endocrine and metabolic diseases (SMR 570; 95% CI, 270-1000; P < 0.001) and for oral and esophageal malignancies (SMR 170; 95% CI, 68-360; P < 0.001). Mortality was also increased for infections, diseases of digestive system, alcohol-related deaths, and for accidents. Due to the small number of cases we were unable to evaluate whether mortality was affected by disease severity.

Conclusions

Patients with APECED have significantly increased mortality in all age groups. Highest SMRs are found for causes that are directly related to APECED but also for infections. Increased alcohol- and accident-related deaths may be influenced by psychosocial factors.
Ten Years Later: Reflections on Critics' Worst-Case Scenarios for the Affordable Care Act
Authors: McMorrow Stacey , Blumberg Linda J. , Holahan John
Published: March 2020

The primary goals of the Affordable Care Act (ACA) were to increase the availability and affordability of health insurance coverage and thereby improve access to needed health care services. Numerous studies have overwhelmingly confirmed that the law has reduced uninsurance and improved affordability of coverage and care for millions of Americans. Not everyone believed that the ACA would lead to positive outcomes, however. Critics raised numerous concerns in the years leading up to the law's passage and full implementation, including about its consequences for national health spending, labor supply, employer health insurance markets, provider capacity, and overall population health. This article considers five frequently heard worst-case scenarios related to the ACA and provides research evidence that these fears did not come to pass.
The Secretary Shall . . . : Implementing the Affordable Care Act's Private Insurance Expansions
Authors: Glied Sherry , Khalid Aryana , Tavenner Marilyn B.
Published: March 2020

The federal bureaucracy played a critical role in implementing most aspects of the Affordable Care Act's private insurance coverage expansion. Through brief case studies, the authors review three dimensions of this role: the development of the Center for Consumer Information and Insurance Oversight, rulemaking in the formulation of the essential health benefits package, and the implementation of the federal website. They relate these to themes in the public administration literature. Politics—both through state decisions and through continuing congressional action (and inaction)—pervaded the implementation process. The challenges of staffing and situating the new bureaucracy effectively changed vertical boundaries within the Department of Health and Human Services, with long-lasting consequences. Finally, the complex design of the policy itself made passage of the legislation easier but implementation much more difficult. Ultimately, however, implementation was remarkably successful, achieving improvements in coverage consistent with the Congressional Budget Office's projections.
Race, Politics, and the Affordable Care Act
Authors: Michener Jamila
Published: March 2020

The political processes surrounding the Affordable Care Act (ACA) offer valuable lessons about race and politics in the United States. In particular, the ACA underscores a critical tension between politics and policy in a racialized polity: even when policies are intended to target and address racial disparities, politics can undermine the steps necessary to do so. Close scrutiny of the ACA during its first decade reveals how race intersects with politics to render public policy less equitable and more vulnerable to erosion. Ultimately, this analysis points to the ways that racialized political processes are formidable barriers to equitable material outcomes. By examining such processes and making them visible, this article elucidates the possibilities, limits, and contours of public policy as a mechanism for achieving racial justice.
What Health Reform Tells Us about American Politics
Authors: Jacobs Lawrence R. , Mettler Suzanne
Published: March 2020

The passage and initial implementation of the Affordable Care Act (ACA) were imperiled by partisan divisions, court challenges, and the quagmire of federalism. In the aftermath of Republican efforts to repeal the ACA, however, the law not only carries on but also is changing the nature of political debate as its benefits are facilitating increased support for it, creating new constituents who rely on its benefits and share intense attachments to them, and lifting the confidence of Americans in both their individual competence to participate effectively in politics and that government will respond. Critics from the Left and the Right differ on their favored remedy, but both have failed to appreciate the qualitative shifts brought on by the ACA; this myopia results from viewing reform as a fixed endpoint instead of a process of evolution over time. The result is that conservatives have been blind to the widening network of support for the ACA, while those on the left have underestimated health reform's impact in broadening recognition of medical care as a right of citizenship instead of a privilege earned in the workplace. The forces that constrained the ACA's development still rage in American politics, but they no longer dictate its survival as they did during its passage in 2010.
Leaves of Regret, Flowers of Gloom: Mourning Ghosts and Crafting a Theater of Han in the Dream Journey Narrative
Authors: Cho Sookja
Published: March 2020

This article scrutinizes the representation of gender and war experiences in seventeenth-century mongyurok (records of a dreamer’s journey), addressing in particular their contribution to a widening of the Korean literary landscape and writing practice of the time. These tales liberated the suppressed voices of war victims, weaving their individual pain and loss into a broader discourse on war, rife with trenchant criticism of those responsible. The article investigates how the dream journey records succeed in drawing such powerful public messages from personal experiences and thus evolve into a strongly critical narrative and a collective releasing of han (grudge). Focusing on female revenants and their mode of storytelling in the Kangdo mongyurok (Record of a Dreamer’s Journey to Kangdo), the article demonstrates how narrative elements, particularly the evocation of sound and the interplay of different ontological realms, foster both social criticism and individual han-releasing. The theatricality of ghostly sounds and performances in the narrative transforms a dismal (post)war reality into an auditorium for voices offering change and healing to both the dead and the living. This powerful storytelling invigorated mimetic interest and provided viable supernatural metanarratives, driving literary evolution forward.
Temporalities of Tonghak: Eschatology, Rebellion, and Civilization
Authors: Shin Seungyop
Published: March 2020

This article examines how the ideological orientations of the Tonghak religion, particularly the eschatological vision of time, empowered its practitioners and peasants to imagine a new world and act out their faith. By paying attention to the notion of kaebyŏk, I explore how different temporalities—redemptive time, now-time, and progressive time—played a significant role in the Tonghak movement from its formation through its reconfiguration as Ch’ŏndogyo. In the shifting geopolitics of East Asia at the turn of the twentieth century, Tonghak emerged as a dissonant theology whose prediction of an apocalyptic upheaval of the universe was discordant with the conceptions of time dominant in both traditional Chosŏn and modern Korea. Viewing history as cyclical, the Tonghak founders conceptualized kaebyŏk as an unexpected critical event that could happen in an abrupt, ever-present now. This unique temporal consciousness underpinned the revolutionary characteristics of Tonghak thought and laid the foundation for its followers to manifest their aspirations for social change through a massive uprising at now-time. Yet Tonghak’s theoretical agenda gradually lost its revolutionary edge during the modernization of the church. By adopting ideologies of civilization and enlightenment as well as social Darwinism, Ch’ŏndogyo focused on the self-cultivating role that kaebyŏk played within the progressive vision of time.