bluuebunny/crossref_metadata_2025 huggingface dataset:
Intestinal Microbiota—A Promising Target for Antiviral Therapy?
Authors: Yang Mengling , Yang Yang , He Qingnan , Zhu Ping , Liu Mengqi , Xu Jiahao , Zhao Mingyi
Published: May 2021

The intestinal microbiota is thought to be an important biological barrier against enteric pathogens. Its depletion, however, also has curative effects against some viral infections, suggesting that different components of the intestinal microbiota can play both promoting and inhibitory roles depending on the type of viral infection. The two primary mechanisms by which the microbiota facilitates or inhibits viral invasion involve participation in the innate and adaptive immune responses and direct or indirect interaction with the virus, during which the abundance and composition of the intestinal microbiota might be changed by the virus. Oral administration of probiotics, faecal microbiota transplantation (FMT), and antibiotics are major therapeutic strategies for regulating intestinal microbiota balance. However, these three methods have shown limited curative effects in clinical trials. Therefore, the intestinal microbiota might represent a new and promising supplementary antiviral therapeutic target, and more efficient and safer methods for regulating the microbiota require deeper investigation. This review summarizes the latest research on the relationship among the intestinal microbiota, anti-viral immunity and viruses and the most commonly used methods for regulating the intestinal microbiota with the goal of providing new insight into the antiviral effects of the gut microbiota.
Acute Hemolysis and Heme Suppress Anti-CD40 Antibody-Induced Necro-Inflammatory Liver Disease
Authors: Pfefferlé Marc , Ingoglia Giada , Schaer Christian A. , Hansen Kerstin , Schulthess Nadja , Humar Rok , Schaer Dominik J. , Vallelian Florence
Published: May 2021

Clearance of red blood cells and hemoproteins is a key metabolic function of macrophages during hemolytic disorders and following tissue injury. Through this archetypical phagocytic function, heme is detoxified and iron is recycled to support erythropoiesis. Reciprocal interaction of heme metabolism and inflammatory macrophage functions may modify disease outcomes in a broad range of clinical conditions. We hypothesized that acute hemolysis and heme induce acute anti-inflammatory signals in liver macrophages. Using a macrophage-driven model of sterile liver inflammation, we showed that phenylhydrazine (PHZ)-mediated acute erythrophagocytosis blocked the anti-CD40 antibody-induced pathway of macrophage activation. This process attenuated the inflammatory cytokine release syndrome and necrotizing hepatitis induced by anti-CD40 antibody treatment of mice. We further established that administration of heme-albumin complexes specifically delivered heme to liver macrophages and replicated the anti-inflammatory effect of hemolysis. The anti-inflammatory heme-signal was induced in macrophages by an increased intracellular concentration of the porphyrin independently of iron. Overall, our work suggests that induction of heme-signaling strongly suppresses inflammatory macrophage function, providing protection against sterile liver inflammation.
Murine Factor H Co-Produced in Yeast With Protein Disulfide Isomerase Ameliorated C3 Dysregulation in Factor H-Deficient Mice
Authors: Kerr Heather , Herbert Andrew P. , Makou Elisavet , Abramczyk Dariusz , Malik Talat H. , Lomax-Browne Hannah , Yang Yi , Pappworth Isabel Y. , Denton Harriet , Richards Anna , Marchbank Kevin J. , Pickering Matthew C. , Barlow Paul N.
Published: May 2021

Recombinant human factor H (hFH) has potential for treating diseases linked to aberrant complement regulation including C3 glomerulopathy (C3G) and dry age-related macular degeneration. Murine FH (mFH), produced in the same host, is useful for pre-clinical investigations in mouse models of disease. An abundance of FH in plasma suggests high doses, and hence microbial production, will be needed. Previously,Pichia pastorisproduced useful but modest quantities of hFH. Herein, a similar strategy yielded miniscule quantities of mFH. Since FH has 40 disulfide bonds, we created aP. pastorisstrain containing a methanol-inducible codon-modified gene for protein-disulfide isomerase (PDI) and transformed this with codon-modified DNA encoding mFH under the same promoter. What had been barely detectable yields of mFH became multiple 10s of mg/L. Our PDI-overexpressing strain also boosted hFH overproduction, by about tenfold. These enhancements exceeded PDI-related production gains reported for other proteins, all of which contain fewer disulfide-stabilized domains. We optimized fermentation conditions, purified recombinant mFH, enzymatically trimmed down its (non-human) N-glycans, characterised its functionsin vitroand administered it to mice. In FH-knockout mice, our de-glycosylated recombinant mFH had a shorter half-life and induced more anti-mFH antibodies than mouse serum-derived, natively glycosylated, mFH. Even sequential daily injections of recombinant mFH failed to restore wild-type levels of FH and C3 in mouse plasma beyond 24 hours after the first injection. Nevertheless, mFH functionality appeared to persist in the glomerular basement membrane because C3-fragment deposition here, a hallmark of C3G, remained significantly reduced throughout and beyond the ten-day dosing regimen.
Aging and Options to Halt Declining Immunity to Virus Infections
Authors: Palacios-Pedrero Miguel Ángel , Osterhaus Albert D. M. E. , Becker Tanja , Elbahesh Husni , Rimmelzwaan Guus F. , Saletti Giulietta
Published: May 2021

Immunosenescence is a process associated with aging that leads to dysregulation of cells of innate and adaptive immunity, which may become dysfunctional. Consequently, older adults show increased severity of viral and bacterial infections and impaired responses to vaccinations. A better understanding of the process of immunosenescence will aid the development of novel strategies to boost the immune system in older adults. In this review, we focus on major alterations of the immune system triggered by aging, and address the effect of chronic viral infections, effectiveness of vaccination of older adults and strategies to improve immune function in this vulnerable age group.
Expanding the Scope of Non-invasive Prenatal Testing to Detect Fetal Chromosomal Copy Number Variations
Authors: Chen Songchang , Zhang Lanlan , Gao Jiong , Li Shuyuan , Chang Chunxin , Chen Yiyao , Fei Hongjun , Zhang Junyu , Wang Yanlin , Huang Hefeng , Xu Chenming , Lu Daru
Published: May 2021

Non-invasive prenatal testing (NIPT) for common fetal trisomies is effective. However, the usefulness of cell-free DNA testing to detect other chromosomal abnormalities is poorly understood. We analyzed the positive rate at different read depths in next-generation sequencing (NGS) and identified a strategy for fetal copy number variant (CNV) detection in NIPT. Pregnant women who underwent NIPT by NGS at read depths of 4–6 M and fetuses with suspected CNVs were analyzed by amniocentesis and chromosomal microarray analysis (CMA). These fetus samples were re-sequenced at a read depth of 25 M and the positive detection rate was determined. With the increase in read depth, the positive CNV detection rate increased. The positive CNV detection rates at 25 M with small fragments were higher by NGS than by karyotype analysis. Increasing read depth in NGS improves the positive CNV detection rate while lowering the false positive detection rate. NIPT by NGS may be an accurate method of fetal chromosome analysis and reduce the rate of birth defects.
Strategies for Targeting Retroviral Integration for Safer Gene Therapy: Advances and Challenges
Authors: Yoder Kristine E. , Rabe Anthony J. , Fishel Richard , Larue Ross C.
Published: May 2021

Retroviruses are obligate intracellular parasites that must integrate a copy of the viral genome into the host DNA. The integration reaction is performed by the viral enzyme integrase in complex with the two ends of the viral cDNA genome and yields an integrated provirus. Retroviral vector particles are attractive gene therapy delivery tools due to their stable integration. However, some retroviral integration events may dysregulate host oncogenes leading to cancer in gene therapy patients. Multiple strategies to target retroviral integration, particularly to genetic safe harbors, have been tested with limited success. Attempts to target integration may be limited by the multimerization of integrase or the presence of host co-factors for integration. Several retroviral integration complexes have evolved a mechanism of tethering to chromatin via a host protein. Integration host co-factors bind chromatin, anchoring the complex and allowing integration. The tethering factor allows for both close proximity to the target DNA and specificity of targeting. Each retrovirus appears to have distinct preferences for DNA sequence and chromatin features at the integration site. Tethering factors determine the preference for chromatin features, but do not affect the subtle sequence preference at the integration site. The sequence preference is likely intrinsic to the integrase protein. New developments may uncouple the requirement for a tethering factor and increase the ability to redirect retroviral integration.
Moderately Transparent Chitosan-PVA Blended Membrane for Strong Mechanical Stiffness and as a Robust Bio-Material Energy Harvester Through Contact-Separation Mode TENG
Authors: Cheedarala Ravi Kumar , Song Jung Il
Published: May 2021

The detection of sustainable materials from naturally available resources using a simple fabrication process is highly important for novel research. Here, we used chitosan-PVA (Chs-PVA) blend films via layer-by-layer casting technologies for generating power through mechanical induction through triboelectric nanogenerators. The proposed Chs-PVA biodegradable film (i.e., thickness of 60 ± 5 μm) is facile, ecofriendly, highly flexible, mechanically strong, cost-effective, and easy to scale up. FT-IR analysis of the ChS-PVA blend membrane showed the strong interactions between the amines of ChS and hydroxyl groups of PVA through chemical cross-linking by hydrogen bonding. More importantly, the triboelectric nanogenerators (TENG) values of ChS-PVA films were 3–4 orders of magnitude lower than chitosan films reported before. Layer-on-layer cast films in particular exhibited high tensile strength (15.8 ± 1 MPa) and were more than three times stronger than other polyelectrolyte multilayer films. Both types of films remained stable in an acidic environment. Furthermore, the layer-on-layer-assembled films presented greater open circuit voltage (Voc) and short circuit current (Isc) values compared to pure ChS and PVA films. The ChS-PVA membrane can be used as a functional layer to produce charges by collecting get-up-and-go through vertical contact and separation mode TENG counters to the PVDF membrane. The enhancement of Voc and Isc of ChS-PVA TENG were 244 and 1,080% from ChS TENG. Where in the case of PVA TENG, the enhancement of Voc and Isc were increased by 633 and 2,888%, respectively due to the availability of free loan pair on the -NH2 and -OH functional groups. The novel ChS-PVA TENG is a potential candidate for satisfying the tight requirement of an optimized energy harvesting device as an alternate bio-material option for contact-separation mode TENGs.
Severe Psychopathology and Substance Use Disorder Modify the Association Between Housing Trajectories and Food Security Among Homeless Adults
Authors: Lachaud James , Mejia-Lancheros Cilia , Liu Michael , Wang Ri , Nisenbaum Rosane , Stergiopoulos Vicky , Hwang Stephen W. , O'Campo Patricia
Published: May 2021

Purpose: We examined the housing trajectories of homeless people with mental illness over a follow-up period of 6 years and the association of these trajectories with food security. We then examined the modifying role of psychopathology and alcohol and substance use disorders in this association.

Materials and Methods: We followed 487 homeless adults with mental illness at the Toronto site of the At Home/Chez-Soi project—a randomized trial of Housing First. Food security data were collected seven times during the follow-up period. Psychopathology (Colorado Symptom Index score) and alcohol and substance use disorders were assessed at baseline. Housing trajectories were identified using group-based trajectory modeling. Logistic regression was used to estimate the association between housing trajectory groups and food security.

Results: Three housing trajectory groups were identified: rapid move to consistent stable housing (34.7%), slow and inconsistent housing (52.1%), and never moved to stable housing (13.2%). Individuals included in the rapid move to consistent housing trajectory group had higher odds of remaining food secure compared with those in the never moved to stable housing trajectory group over the follow-up period [AOR 2.9, 95% CI: 1.3–6.6, P-value: 0.009]. However, when interactions were considered, this association was significant among those with moderate psychopathology but not severe psychopathology. Individuals with substance use disorder and in the never moved to stable housing group had the lowest food security status.

Discussion: Severe psychopathology and substance use disorders modified the association between housing trajectories and food security.

International Standard Randomized Control Trial Number Register (ISRCTN42520374).
Prognostic and Clinicopathological Value of Human Leukocyte Antigen G in Gastrointestinal Cancers: A Meta-Analysis
Authors: Peng Yongjia , Xiao Jian , Li Wenyun , Li Shuna , Xie Binbin , He Jiang , Liu Chaoqun
Published: May 2021

Background

The prognostic value of human leukocyte antigen G (HLA-G) expression in gastrointestinal (GI) cancers remains controversial. Thus, this meta-analysis aimed to summarize available evidence from case-control or cohort studies that evaluated this association.

Methods

The PubMed, EMBASE, Cochrane Library, and Web of Science databases were searched to identify relevant studies written in English published up to April 1, 2021, and with no initial date. Furthermore, the Google Scholar and Google databases were also searched manually for gray literature. The protocol for this meta-analysis was registered at PROSPERO (CRD42020213411). Pooled hazard ratios (HRs) or odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for end points using fixed- and random-effects statistical models to account for heterogeneity. Publication bias was evaluated using a funnel plot, Begg’s and Egger’s tests, and the “trim and fill” method.

Results

A total of 30 eligible articles with 5737 unique patients, including 12 studies on colorectal cancer (CRC), 6 on gastric cancer (GC), 5 on esophageal cancer (ESCC), 5 on hepatocellular carcinoma (HCC), and 2 on pancreatic adenocarcinoma (PC), were retrieved. Both univariate (HR = 2.01, 95% CI: 1.48 ~ 2.72) and multivariate (HR = 2.69, 95% CI: 2.03 ~ 3.55) analyses revealed that HLA-G expression was significantly correlated with poor overall survival (OS), regardless of the cancer type or antibody used. Subgroup analysis stratified by antibody showed that the 4H84 (I2 = 45.8%, P = 0.101) antibodies could be trustworthy and reliable for detecting HLA-G expression in GI cancers. In addition, HLA-G expression was found to be correlated with adverse clinicopathological parameters such as clinical stage, nodal status, metastasis, and histological grade but not tumor status.

Conclusion

Elevated HLA-G expression indicates a poor prognosis for GI cancer patients, and screening for this marker could allow for the early diagnosis and treatment of GI cancers to improve survival rates.
Calcium Channel Protein ORAI1 Mediates TGF-β Induced Epithelial-to-Mesenchymal Transition in Colorectal Cancer Cells
Authors: Kang Qingjie , Peng Xudong , Li Xiangshu , Hu Denghua , Wen Guangxu , Wei Zhengqiang , Yuan Baohong
Published: May 2021

Accumulating evidence suggested that calcium release-activated calcium modulator 1(ORAI1), a key calcium channel pore-forming protein-mediated store-operated Ca2+ entry (SOCE), is associated with human cancer. However, its role in colorectal cancer (CRC) progression has not been well studied. Epithelial-mesenchymal transition (EMT) is a multistep process that occurs during the progression of cancers and is necessary for metastasis of epithelial cancer. Transforming growth factor-β (TGF-β) is a pleiotropic cytokine that has been shown to induce EMT. In this study, we are aimed at exploring the effects of ORAI1 on TGF-β1-induced EMT process in CRC cells. Herein, we confirmed ORAI1 expression was higher in CRC tissues than in adjacent non-cancerous tissues by using immunohistochemical staining and Western blot analysis. Higher ORAI1 expression was associated with more advanced clinical stage, higher incidence of metastasis and shorter overall survival. We compared ORAI1 expression in SW480 and SW620 cells, two CRC cell lines with the same genetic background, but different metastatic potential. We found ORAI1 expression was significantly higher in SW620 cells which exhibited higher EMT characteristics. Furthermore, knockdown of ORAI1 suppressed the EMT of SW620 Cells. After induced the EMT process in SW480 cells with TGF-β1, we found treatment of TGF-β1 showed a significant increase in cell migration along with the loss of E-cadherin and an increase in N-cadherin and Vimentin protein levels. Also, TGF-β1 treatment increased ORAI1 expression and was closely associated with the increase of SOCE. Silencing ORAI1 significantly suppressed Ca2+ entry, reversed the changes of EMT-relevant marks expression induced by TGF-β1, and inhibited TGF-β1-mediated calpain activation and cell migration. Finally, we blocked SOCE with 2-APB (2-Aminoethyl diphenylborinate), a pharmacological inhibitor. Interestingly, 2-APB and sh-ORAI1 both exhibited similar inhibition effects to the SW480 cells. In conclusion, our results demonstrated that ORAI1 could mediate TGF-β-Induced EMT by promoting Ca2+ entry and calpain activity in Colorectal Cancer Cells.
A Randomized Double-Blinded Dose-dependent Study of Metaraminol for Preventing Spinal-Induced Hypotension in Caesarean Delivery
Authors: Xiao Fei , Xu Wen-Ping , Yao Han-Qing , Fan Jia-Ming , Chen Xin-Zhong
Published: May 2021

Purpose: Prophylactic infusion of a vasopressor is preferred as a rational choice in clinical practice in Cesarean delivery. Metaraminol is one of most common vasopressors used in obstetric clinical practice. However, the dose-response of metaraminol has not been fully determined and the optimal infusion dose is unknown. Therefore, this study aimed to determine the median effective dose (ED50) and 90% effective dose (ED90) of weight-based fixed-rate metaraminol infusions for preventing spinal-anesthesia-induced hypotension in patients having combined spinal-epidural anesthesia for elective Caesarean delivery.

Methods: One hundred and seventeen patients with singleton pregnancies were enrolled and randomly allocated into one of five groups in this study. Patients received prophylactic metaraminol infusion at a fixed rate of 0, 0.25, 1.0, 1.75 or 2.5 μg/kg/min in each group immediately after induction with intrathecal 10 mg of hyperbaric bupivacaine mixed with 5 μg of sufentanil. An effective prophylactic dose was defined as no occurrence of hypotension during the period of spinal introduction and neonatal delivery. Values for ED50 and ED90 of prophylactic infusion of metaraminol were calculated using probit regression. Characteristics of spinal anesthesia and side effects were recorded.

Results: The ED50 and ED90 values of weight-based fixed rate of metaraminol infusion were 0.64 (95% CI, 0.04–1.00) μg/kg/min and 2.00 (95% CI, 1.58–2.95) μg/kg/min respectively. The incidence of hypotension decreased with an increased infusion rate of metaraminol in the five groups (test for trend, p < 0.001). The incidence of hypotension was similar between group 0 and 0.25, but significant higher than other groups; the incidence of hypotension was also similar between group 1.0 and 1.75, but higher than group 2.5. The incidence of reactive hypertension was significantly higher in group 2.5 compared to the other groups. Physician interventions were more frequent in group 0, 0.25 and 2.5 than in group 1.0 and 1.75 (adjusted p < 0.001). No difference was found in neonatal outcomes, including Apgar score and pH value of the umbilical artery.

Conclusion: In summary, we have compared four different prophylactic weight-based infusion doses of metaraminol for preventing post-spinal hypotension in Cesarean delivery. The ED50 and ED90 values of metaraminol infusion for preventing spinal anesthesia-induced hypotension were 0.64 μg/kg/min and 2.00 μg/kg/min, respectively. This finding may be helpful for guiding clinical practice and further research.
Targeted Therapeutic Strategies in the Battle Against Pathogenic Bacteria
Authors: Yang Bingqing , Fang Dan , Lv Qingyan , Wang Zhiqiang , Liu Yuan
Published: May 2021

The emergence and rapid spread of antibiotic resistance in pathogenic bacteria constitute a global threat for public health. Despite ongoing efforts to confront this crisis, the pace of finding new potent antimicrobials is far slower than the evolution of drug resistance. The abuse of broad-spectrum antibiotics not only accelerates the formation of resistance but also imposes a burden on the intestinal microbiota, which acts a critical role in human homeostasis. As such, innovative therapeutic strategies with precision are pressingly warranted and highly anticipated. Recently, target therapies have achieved some breakthroughs by the aid of modern technology. In this review, we provide an insightful illustration of current and future medical targeted strategies, including narrow-spectrum agents, engineered probiotics, nanotechnology, phage therapy, and CRISPR-Cas9 technology. We discuss the recent advances and potential hurdles of these strategies. Meanwhile, the possibilities to mitigate the spread of resistance in these approaches are also mentioned. Altogether, a better understanding of the advantages, disadvantages, and mechanisms of action of these targeted therapies will be conducive to broadening our horizons and optimizing the existing antibacterial approaches.
Transformation of Long-Lived Albino Epipremnum aureum ‘Golden Pothos’ and Restoring Chloroplast Development
Authors: Hung Chiu-Yueh , Zhang Jianhui , Bhattacharya Chayanika , Li Hua , Kittur Farooqahmed S. , Oldham Carla E. , Wei Xiangying , Burkey Kent O. , Chen Jianjun , Xie Jiahua
Published: May 2021

Chloroplasts are organelles responsible for chlorophyll biosynthesis, photosynthesis, and biosynthesis of many metabolites, which are one of key targets for crop improvement. Elucidating and engineering genes involved in chloroplast development are important approaches for studying chloroplast functions as well as developing new crops. In this study, we report a long-lived albino mutant derived from a popular ornamental plant Epipremnum aureum ‘Golden Pothos’ which could be used as a model for analyzing the function of genes involved in chloroplast development and generating colorful plants. Albino mutant plants were isolated from regenerated populations of variegated ‘Golden Pothos’ whose albino phenotype was previously found to be due to impaired expression of EaZIP, encoding Mg-protoporphyrin IX monomethyl ester cyclase. Using petioles of the mutant plants as explants with a traceable sGFP gene, an efficient transformation system was developed. Expressing Arabidopsis CHL27 (a homolog of EaZIP) but not EaZIP in albino plants restored green color and chloroplast development. Interestingly, in addition to the occurrence of plants with solid green color, plants with variegated leaves and pale-yellow leaves were also obtained in the regenerated populations. Nevertheless, our study shows that these long-lived albino plants along with the established efficient transformation system could be used for creating colorful ornamental plants. This system could also potentially be used for investigating physiological processes associated with chlorophyll levels and chloroplast development as well as certain biological activities, which are difficult to achieve using green plants.
Resveratrol Alleviates the KCl Salinity Stress of Malus hupehensis Rhed
Authors: Li Tingting , Li Yuqi , Sun Zhijuan , Xi Xiangli , Sha Guangli , Ma Changqing , Tian Yike , Wang Caihong , Zheng Xiaodong
Published: May 2021

Applying large amounts of potash fertilizer in apple orchards for high apple quality and yield aggravates KCl stress. As a phytoalexin, resveratrol (Res) participates in plant resistance to biotic stress. However, its role in relation to KCl stress has never been reported. Herein we investigated the role of Res in KCl stress response of Malus hupehensis Rehd., a widely used apple rootstock in China which is sensitive to KCl stress. KCl-stressed apple seedlings showed significant wilting phenotype and decline in photosynthetic rate, and the application of 100 μmol Res alleviated KCl stress and maintained photosynthetic capacity. Exogenous Res can strengthen the activities of peroxidase and catalase, thus eliminating reactive oxygen species production induced by KCl stress. Moreover, exogenous Res can decrease the electrolyte leakage by accumulating proline for osmotic balance under KCl stress. Furthermore, exogenous Res application can affect K+/Na+ homeostasis in cytoplasm by enhancing K+ efflux outside the cells, inhibiting Na+ efflux and K+ absorption, and compartmentalizing K+ into vacuoles through regulating the expression of K+ and Na+ transporter genes. These findings provide a theoretical basis for the application of exogenous Res to relieve the KCl stress of apples.
A Meta-Analysis of the Effects of Mental Contrasting With Implementation Intentions on Goal Attainment
Authors: Wang Guoxia , Wang Yi , Gai Xiaosong
Published: May 2021

Mental contrasting with implementation intentions (MCII) is a self-regulation strategy that enhances goal attainment. This meta-analysis evaluated the efficacy of MCII for goal attainment and explored potential moderators. A total of 21 empirical studies with 24 independent effect sizes (15,907 participants) were included in the analysis. Results showed that MCII to be effective for goal attainment with a small to medium effect size (g = 0.336). The effect was mainly moderated by intervention style. Specifically, studies with interventions based on interactions between participants and experimenters (g = 0.465) had stronger effects than studies with interventions based on interactions between participants and documents (g = 0.277). The results revealed that MCII is a brief and effective strategy for goal attainment with a small to moderate effect; however, because of some publication bias, the actual effect sizes may be smaller. Due to small number of studies in this meta-analysis, additional studies are needed to determine the role of moderator variables.
Assessing Phonological Profiles in Children and Adolescents With Down Syndrome: The Effect of Elicitation Methods
Authors: Diez-Itza Eliseo , Vergara Patricio , Barros María , Miranda Manuela , Martínez Verónica
Published: May 2021

In the context of comparing linguistic profiles across neurodevelopmental disorders, Down syndrome (DS) has captured growing attention for its uneven profile. Although specific weaknesses in grammatical and phonological processing have been reported, research evidence on phonological development remains scarce, particularly beyond early childhood. The purpose of this study was to explore the phonological profiles of children and adolescents with Down syndrome. The profiles were based on the frequency and relative proportion of the processes observed by classes, and they were compared to those of typically developing preschool children of similar verbal age. A complementary goal was to assess the effect of two different methods of elicitation: a test of articulation and spontaneous speech sampling. Finally, intergroup and intragroup differences in full match percentages between three positions at syllable-level (complex onset, medial coda, and final coda) were assessed. The results of the present study confirmed that the frequency of phonological processes in children and adolescents with DS is atypically high and is above what is expected for lexical age and at the same level as grammatical age. Highly increased frequency of processes, consistent in all kinds of processes and positions at the syllable-level, and asynchronous with verbal age and mental age suggest atypical developmental trajectories of phonological development in the Down syndrome population.
Uncovering Prolonged Grief Reactions Subsequent to a Reproductive Loss: Implications for the Primary Care Provider
Authors: Grauerholz Kathryn R. , Berry Shandeigh N. , Capuano Rebecca M. , Early Jillian M.
Published: May 2021

Introduction

There is a paucity of clinical guidelines for the routine assessment of maladaptive reproductive grief reactions in outpatient primary care and OB-GYN settings in the United States. Because of the disenfranchised nature of perinatal grief reactions, many clinicians may be apt to miss or dismiss a grief reaction that was not identified in the perinatal period. A significant number of those experiencing a reproductive loss exhibit signs of anxiety, depression, or post-traumatic stress disorder. Reproductive losses are typically screened for and recorded numerically as part of a woman’s well-visit intake, yet this process often fails to identify patients emotionally troubled by a prior pregnancy loss.

Materials and Methods

A summative content analysis of 164 recent website blogs from female participants who self-reported having experienced a miscarriage or abortion in their lifetime was conducted. The narratives were reviewed for details regarding the time span between the pregnancy loss and the composition of the blog post. The stories were analyzed for subsequent relationship problems and detrimental mental health conditions. Maladaptive reactions were contrasted for those that indicated a greater than 12 months’ time-lapse and those who had not.

Results

More than a third (39.6%) of the women reported in the narrative that at least one year or more had passed since experiencing the miscarriage or abortion. For those women, the median time span between the loss and composing the blog was 4 years with a range of 47 years. Mental health conditions attributed to the reproductive loss by those who reported longer bereavement times included subsequent relationship problems, substance misuse, depression, suicidal ideation, and PTSD. The percent of reported maladaptive issues was more than double (136.9% vs. 63.6%) for those who reported that a year or more had passed since the loss of the pregnancy.

Discussion

Grief reactions following the loss of a pregnancy may be prolonged or delayed for several months which can contribute to adverse biopsychosocial outcomes. Recognition and treatment of maladaptive grief reactions following a pregnancy loss are critical. Screening methods should be enhanced for clinicians in medical office settings to help identify and expedite the appropriate mental health assistance.
Impact of the Optimistic Perspective on the Intention to Create Social Enterprises: A Comparative Study Between Portugal and Spain
Authors: Margaça Clara , Hernández-Sánchez Brizeida Raquel , Cardella Giuseppina Maria , Sánchez-García José Carlos
Published: May 2021

Social entrepreneurship (SE) enables business consolidation, combined with the production of positive impact and improvements in society. Aligned with 2030 Agenda for the achievement of the United Nations Sustainable Development Goals, it is important to clarify the role of social entrepreneurs, as they are making visible the impact of their creative ideas in several areas, from civic engagement to the environment, health and learning. The main purpose of this study is to specify a model of social entrepreneurial intention (SEI) and explore it by country, based on the dimensions of the Theory of Planned Behavior and how these are mediated by spirituality and optimism. With a convenience sample of 1476 Portuguese and Spanish students, Structural Equation Modeling (SEM) was used. For a deeply understanding, variables within the model were compared by country usingt-rest, and multivariate analysis was done by each one separately. The mean comparison between countries, demonstrated that there are differences only between perceived behavioral control (PBC), Spirituality, Optimism and SEI, with Portuguese students scoring the highest values, in all variables except Optimism. A mediation path was carried out, and Spirituality mediate a significant effect between the three TPB dimensions in Portuguese students, but not in students from Spain. Finally, after discussing the results, theoretical and practical contributions are analyzed, with regard to the field of SE in Portugal and Spain, and alternatives are pointed out for a more social and sustainable entrepreneurial future.
Identifying Subgroups of Patients With Autism by Gene Expression Profiles Using Machine Learning Algorithms
Authors: Lin Ping-I , Moni Mohammad Ali , Gau Susan Shur-Fen , Eapen Valsamma
Published: May 2021

Objectives: The identification of subgroups of autism spectrum disorder (ASD) may partially remedy the problems of clinical heterogeneity to facilitate the improvement of clinical management. The current study aims to use machine learning algorithms to analyze microarray data to identify clusters with relatively homogeneous clinical features.

Methods: The whole-genome gene expression microarray data were used to predict communication quotient (SCQ) scores against all probes to select differential expression regions (DERs). Gene set enrichment analysis was performed for DERs with a fold-change >2 to identify hub pathways that play a role in the severity of social communication deficits inherent to ASD. We then used two machine learning methods, random forest classification (RF) and support vector machine (SVM), to identify two clusters using DERs. Finally, we evaluated how accurately the clusters predicted language impairment.

Results: A total of 191 DERs were initially identified, and 54 of them with a fold-change >2 were selected for the pathway analysis. Cholesterol biosynthesis and metabolisms pathways appear to act as hubs that connect other trait-associated pathways to influence the severity of social communication deficits inherent to ASD. Both RF and SVM algorithms can yield a classification accuracy level >90% when all 191 DERs were analyzed. The ASD subtypes defined by the presence of language impairment, a strong indicator for prognosis, can be predicted by transcriptomic profiles associated with social communication deficits and cholesterol biosynthesis and metabolism.

Conclusion: The results suggest that both RF and SVM are acceptable options for machine learning algorithms to identify AD subgroups characterized by clinical homogeneity related to prognosis.
Case Report: Treatment of a Comorbid Attention Deficit Hyperactivity Disorder and Obsessive–Compulsive Disorder With Psychostimulants
Authors: Dogan-Sander Ezgi , Strauß Maria
Published: May 2021

Introduction: Attention deficit hyperactivity disorder (ADHD) is a common disease in childhood and adolescence. In about 60% of pediatric patients, the symptoms persist into adulthood. Treatment guidelines for adult ADHD patients suggest multimodal therapy consisting of psychostimulants and psychotherapy. Many adult ADHD patients also suffer from psychiatric comorbidities, among others obsessive–compulsive disorder (OCD). The treatment of the comorbidity of ADHD and OCD remains challenging as the literature is sparse. Moreover, the impact of psychostimulants on obsessive–compulsive symptoms is still unclear.

Case Presentation: Here, we report on a 33-year-old patient with an OCD who was unable to achieve sufficient remission under long-term guideline-based treatment for OCD. The re-examination of the psychological symptoms revealed the presence of adult ADHD as a comorbid disorder. The patient has already been treated with paroxetine and quetiapine for the OCD. Due to the newly established diagnosis of ADHD, extended-release methylphenidate (ER MPH) was administered in addition to a serotonin reuptake inhibitor. After a dose of 30 mg ER MPH, the patient reported an improvement in both the ADHD and the obsessive–compulsive symptoms. After discharge, the patient reduced ER MPH without consultation with a physician due to subjectively described side effects. The discontinuation of medication led to a renewed increase in ADHD and obsessive–compulsive symptoms. The readjustment to ER MPH in combination with sertraline and quetiapine thereafter led to a significant improvement in the compulsive symptoms again.

Conclusion: The present case shows that in ADHD and comorbid obsessive–compulsive disorder, treatment with psychostimulants can improve the obsessive–compulsive symptoms in addition to the ADHD-specific symptoms. To our knowledge, this is only the second case report describing a treatment with ER MPH for an adult patient with OCD and ADHD comorbidity in the literature. Further research, especially randomized controlled trials, is needed to standardize treatment options.
Machine Learning Based Clinical Decision Support System for Early COVID-19 Mortality Prediction
Authors: Karthikeyan Akshaya , Garg Akshit , Vinod P. K. , Priyakumar U. Deva
Published: May 2021

The coronavirus disease 2019 (COVID-19), caused by the virus SARS-CoV-2, is an acute respiratory disease that has been classified as a pandemic by the World Health Organization (WHO). The sudden spike in the number of infections and high mortality rates have put immense pressure on the public healthcare systems. Hence, it is crucial to identify the key factors for mortality prediction to optimize patient treatment strategy. Different routine blood test results are widely available compared to other forms of data like X-rays, CT-scans, and ultrasounds for mortality prediction. This study proposes machine learning (ML) methods based on blood tests data to predict COVID-19 mortality risk. A powerful combination of five features: neutrophils, lymphocytes, lactate dehydrogenase (LDH), high-sensitivity C-reactive protein (hs-CRP), and age helps to predict mortality with 96% accuracy. Various ML models (neural networks, logistic regression, XGBoost, random forests, SVM, and decision trees) have been trained and performance compared to determine the model that achieves consistently high accuracy across the days that span the disease. The best performing method using XGBoost feature importance and neural network classification, predicts with an accuracy of 90% as early as 16 days before the outcome. Robust testing with three cases based on days to outcome confirms the strong predictive performance and practicality of the proposed model. A detailed analysis and identification of trends was performed using these key biomarkers to provide useful insights for intuitive application. This study provide solutions that would help accelerate the decision-making process in healthcare systems for focused medical treatments in an accurate, early, and reliable manner.
International Interprofessional Collaborative Office Rounds (iiCOR): Addressing Children's Developmental, Behavioral, and Emotional Health Using Distance Technology
Authors: Kiing Jennifer S. H. , Feldman Heidi M. , Ladish Chris , Srinivasan Roopa , Donnelly Craig L. , Chong Shang Chee , Weitzman Carol C.
Published: May 2021

Developmental, behavioral, and emotional issues are highly prevalent among children across the globe. Among children living in low- and middle-income countries, these conditions are leading contributors to the global burden of disease. A lack of skilled professionals limits developmental and mental health care services to affected children globally. Collaborative Office Rounds are interprofessional groups that meet regularly to discuss actual cases from the participants' practices using a non-hierarchical, peer-mentoring approach. In 2017, International Interprofessional Collaborative Office Rounds was launched with several goals: to improve the knowledge and skills of practicing child health professionals in high and low resourced settings regarding developmental and mental health care, to support trainees and clinicians in caring for these children, and to promote best practice in diagnosis and management of these conditions. Five nodes, each comprised of 3–4 different sites with an interprofessional team, from 8 countries in North America, Africa, Asia, and South America met monthly via videoconferencing. This report describes and evaluates the first 2 years' experience. Baseline surveys from participants (N = 141) found that 13 disciplines were represented. Qualitative analysis of 51 discussed cases, revealed that all cases were highly complex. More than half of the cases (N = 26) discussed children with autism or traits of autism and almost all (N = 49) had three or more themes discussed. Frequently occurring themes included social determinants of health (N = 31), psychiatric co-morbidity (N = 31), aggression and self-injury (N = 25), differences with the healthcare provider (N = 17), cultural variation in accepting diagnosis or treatment (N = 19), and guidance on gender and sexuality issues (N = 8). Participants generally sought recommendations on next steps in clinical care or management. A survey of participants after year 1 (N = 47) revealed that 87% (N = 41) had expectations that were completely or mostly met by the program. Our experience of regular meetings of interprofessional groups from different countries using distance-learning technology allowed participants to share on overlapping challenges, meet continuing educational needs while learning about different approaches in high- and low-resourced settings. International Interprofessional Collaborative Office Rounds may prove a useful strategy for increasing the work force capacity for addressing developmental, behavioral, and emotional conditions worldwide. More systematic studies are needed.
Endogenous Mechanisms of Craniomaxillofacial Repair: Toward Novel Regenerative Therapies
Authors: desJardins-Park Heather E. , Mascharak Shamik , Longaker Michael T. , Wan Derrick C.
Published: May 2021

In the fields of oral and craniomaxillofacial surgery, regeneration of multiple tissue types—including bone, skin, teeth, and mucosal soft tissue—is often a desired outcome. However, limited endogenous capacity for regeneration, as well as predisposition of many tissues to fibrotic healing, may prevent recovery of normal form and function for patients. Recent basic science research has advanced our understanding of molecular and cellular pathways of repair in the oral/craniofacial region and how these are influenced by local microenvironment and embryonic origin. Here, we review the current state of knowledge in oral and craniomaxillofacial tissue repair/regeneration in four key areas: bone (in the context of calvarial defects and mandibular regeneration during distraction osteogenesis); skin (in the context of cleft lip/palate surgery); oral mucosa (in the context of minimally scarring repair of mucosal injuries); and teeth (in the context of dental disease/decay). These represent four distinct healing processes and outcomes. We will discuss both divergent and conserved pathways of repair in these contexts, with an eye toward fundamental mechanisms of regeneration vs. fibrosis as well as translational research directions. Ultimately, this knowledge can be leveraged to develop new cell-based and molecular treatment strategies to encourage bone and soft tissue regeneration in oral and craniomaxillofacial surgery.
Health and Welfare Outcomes for Adolescents Following Release from Prison in Queensland, Australia: A Prospective Cohort Study
Authors: Borschmann Rohan , de Andrade Dominique , Kinner Stuart A.
Published: May 2021

Background: The transition from prison to the community can be a difficult process and may present different challenges for adolescents (aged < 25 years) compared with their older peers. Methods: Using data from a prospective cohort study in Australia, we compared the health and welfare outcomes of adolescents (aged < 25 years) and adults (aged ≥ 25 years) at 1, 3, and 6 months after release from prison. Results: After one month, adolescents were less likely to be unemployed (adjusted odds ratio (aOR) 0.31; 95% CI 0.15–0.63), report low levels of social support (aOR 0.41; 95% CI 0.21–0.80), or report high psychological distress (aOR 0.50; 95% CI 0.25–0.99). After three months, adults were more likely to have visited a general practitioner (aOR 2.05; 95% CI 1.04–4.07) and adolescents remained less likely to be unemployed (aOR 0.37; 95% CI 0.19–0.74). After six months, adolescents were three times more likely to have used amphetamine-type stimulants (aOR 3.42; 95% CI 1.29–9.09). Conclusions: Adolescents experience different challenges than their older peers when transitioning from prison to the community. Age-specific, integrated support is needed for adolescents during this critical period, including strategies to promote early primary care contact, capitalise on social support networks, and discourage risky substance use.
Geographical Distribution and Risk Assessment of Volatile Organic Compounds in Tributaries of the Han River Watershed
Authors: Im Jong-Kwon , Cho Yong-Chul , Noh Hye-Ran , Yu Soon-Ju
Published: May 2021

Volatile organic compounds (VOCs), with negative impacts on the aquatic ecosystem, are increasingly released into the environment by anthropogenic activities. Water samples were collected from five areas of the Han River Watershed (HRW) tributaries, South Korea, to detect 11 VOCs, which were classified as halogenated aliphatic hydrocarbons (HAHs) and aromatic hydrocarbons (AHs). Among the 11 VOCs, 1,1-dichloroethylene, 1,1,1-trichloroethane, and vinyl chloride were undetected. The highest concentration compounds were chloroform (0.0596 ± 0.1312 µg/L), trichloroethylene (0.0253 ± 0.0781 µg/L), and toluene (0.0054 ± 0.0139 µg/L). The mean concentration (0.0234 µg/L) and detection frequency (37.0%) of HAHs were higher than those of AHs (0.0036 µg/L, 21.0%, respectively). The Imjin Hantan River area exhibited the highest mean concentration (0.2432 µg/L) and detection frequency (22.9%), because it is located near industrial complexes, thus, highlighting their role as important VOC sources. However, the detected VOCs had lower concentrations than those permitted by the EU, WHO, USA, and South Korea drinking water guidelines. Ecological risks associated with the VOCs were estimated by risk quotient (RQ); consequently, the predicted no-effect concentration was 0.0029 mg/L, and the toluene and styrene RQ values were >1 and >0.5, respectively. The findings may facilitate policymakers in designing pollution control strategies.