bluuebunny/crossref_metadata_2025 huggingface dataset:
Specific HER2 Exon 20 Gly776 Deletion-Insertions in Non-Small Cell Lung Cancer: Structural Analysis and Sensitivity to HER2-Targeted Tyrosine Kinase Inhibitors
Authors: Yang Guangjian , Xu Haiyan , Hu Jiaqi , Liu Runze , Hu Peizeng , Yang Yaning , Li Weihua , Hao Xuezhi , Zhang Shuyang , Xu Fei , Ai Xin , Li Junling , Wang Yan
Published: March 2022

Background:HER2 exon 20 insertions remain a subset heterogeneous alterations in lung cancer, with currently unmet need for precision targeted therapy. G776delinsVC, a typical HER2 exon 20 deletion-insertion at codon Gly776, was reported to respond discrepantly to afatinib compared with the predominant insertion A775_G776insYVMA (YVMA). However, it lacks structural evidence to illustrate the possible mechanism and predict the binding activities of its similar variants over YVMA insertion to HER2-targered tyrosine kinase inhibitors (TKIs).

Methods: Real-world cohort study was performed to investigate clinical outcomes with HER2-targeted TKI afatinib and pyrotinib, and structural analysis for exon 20 Gly776 deletion-insertions G776delinsVC, G776delinsLC and G776delinsVV, and YVMA by molecular dynamics simulation and cellular kinase inhibition assay were provided for full exploration.

Results: Afatinib revealed low objective response rate (ORR) of 0–9.5% and short median progression-free survival (mPFS) of 2.8–3.2 months for YVMA, but with higher ORR of 20–28.6% and longer mPFS of 4.3–7.1 months for G776delinsVC. Pyrotinib presented significantly improved PFS benefit than afatinib for G776delinsVC and YVMA as first-line (median, 6.8 vs. 3.4 months, p = 0.010) or second-line therapy (median, 5.8 vs. 2.8 months, p < 0.001). No significant difference was observed on drug binding pocket and TKI binding activity between G776delinsVC, G776delinsLC and G776delinsVV, and both afatinib and pyrotinib showed favorable binding activity. YVMA insertion significantly affected the loop region with altering HER2 protein secondary structure and forming steric hindrance to binding of afatinib. Pyrotinib showed the best selectivity to HER2, with more favorable activity to YVMA than afatinib indicated by cellular inhibition assay.

Conclusion: Both afatinib and pyrotinib showed favorable activity for NSCLC patients with HER2 exon 20 Gly776 deletion-insertions. Pyrotinib revealed more potent activity to A775_G776insYVMA insertion than afatinib due to the steric binding hindrance induced by YVMA.
Effectiveness and Economic Evaluation of Polyene Phosphatidyl Choline in Patients With Liver Diseases Based on Real-World Research
Authors: Fan Jian-Gao , Li Ying , Yu Ze , Luo Xing-Xian , Zheng Ping , Hao Xin , Wang Ze-Yuan , Gao Fei , Zhang Guo-Qing , Feng Wan-Yu
Published: March 2022

Aims: Liver disease has high prevalence, number, and disease burden in China, and polyene phosphatidyl choline (PPC) is a widely used liver protective drug. We aim to explore the effectiveness and economy of PPC in patients with liver diseases based on real-world research and compare with other hepatoprotective drugs.

Methods: This is a “three-phase” study from three medical centers, including descriptive study of patients using PPC injection, self-control case study of patients using PPC injection, and specific-disease cohort study of patients using PPC injection or control drugs. The major measurements of liver function for effectiveness analysis were the alanine transaminase (ALT) level changes and recovery rate. The main statistical methods were Wilcoxon signed rank test, χ2 test, and Mann–Whitney U test. Propensity score matching was applied to reduce bias. Cost-effectiveness analysis, cost minimization analysis, and sensitivity analysis were used for economic evaluation.

Results: PPC alone or in combination with glutathione and magnesium isoglycyrrhizinate shows less total hospitalization cost (p < 0.05) and smaller cost-effectiveness ratio and was effective in protecting liver function, especially in patients with liver transplantation or postoperation of nontumor liver disease (ALT decreased significantly after PPC treatment; p < 0.05). Glutathione and magnesium isoglycyrrhizinate combined with PPC could enhance the protective function of liver.

Conclusion: PPC was an effective and economic liver protective drug in patients with specific liver diseases, and PPC could enhance the liver protective function of glutathione and magnesium isoglycyrrhizinate.
Dehydrocostus Lactone Suppresses Dextran Sulfate Sodium-Induced Colitis by Targeting the IKKα/β-NF-κB and Keap1-Nrf2 Signalling Pathways
Authors: Yuan Yun , Hu Qiongying , Liu Lu , Xie Fan , Yang Luyao , Li Yuchen , Zhang Chuantao , Chen Hongqing , Tang Jianyuan , Shen Xiaofei
Published: March 2022

Dehydrocostus lactone (DCL) is a major sesquiterpene lactone isolated from Aucklandia lappa Decne, a traditional Chinese herbal medicine that used to treat gastrointestinal diseases. This study aimed to examine the therapeutic effects of DCL on dextran sulfate sodium (DSS)-induced colitis with a focus on identifying the molecular mechanisms involved in DCL-mediated anti-inflammatory activity in macrophages. First, oral administration of DCL (5–15 mg/kg) not only ameliorated symptoms of colitis and colonic barrier injury, but also inhibited the expression of proinflammatory cytokines and myeloperoxidase in colon tissues in DSS-challenged mice. Furthermore, DCL also exhibited significant anti-inflammatory activity in LPS/IFNγ-stimulated RAW264.7 macrophages. Importantly, DCL significantly suppressed the phosphorylation and degradation of IκBα and subsequent NF-κB nuclear translocation, and enhanced the nuclear accumulation of Nrf2 in LPS/IFNγ-treated RAW264.7 cells. Mechanistically, DCL could directly interact with IKKα/β and Keap1, thereby leading to the inhibition of NF-κB signalling and the activation of Nrf2 pathway. Furthermore, DCL-mediated actions were abolished by dithiothreitol, suggesting a thiol-mediated covalent linkage between DCL and IKKα/β or Keap1. These findings demonstrated that DCL ameliorates colitis by targeting NF-κB and Nrf2 signalling, suggesting that DCL may be a promising candidate in the clinical treatment of colitis.
Baohuoside I Inhibits Tumor Angiogenesis in Multiple Myeloma via the Peroxisome Proliferator–Activated Receptor γ/Vascular Endothelial Growth Factor Signaling Pathway
Authors: Chen Ying , Zhang Lina , Zang Xiaoyan , Shen Xuxing , Li Jianyong , Chen Lijuan
Published: March 2022

Angiogenesis plays an important role in the development of multiple myeloma (MM). Baohuoside I (BI) is a core flavonoid monomer with anticancer property. However, the mechanism of BI on MM-stimulated angiogenesis has not been revealed. In this study, we demonstrated that BI inhibits MM-induced angiogenesis in vitro and angiogenesis in a xenograft mouse model in vivo. We further showed that peroxisome proliferator–activated receptor γ (PPARγ) transcriptional activity was mediated by a direct physical association between BI and PPARγ. Meanwhile, inhibition of PPARγ using lentivirus transfection of shRNA in human myeloma cell lines showed that the facilitation of PPARγ blocked angiogenesis and PPARγ repressed vascular endothelial growth factor (VEGF) transcription. Furthermore, BI treatment decreased VEGF expression, whereas VEGF expression remained unchanged after PPARγ knockdown when exposed to BI. Overall, our study is the first to reveal that BI inhibits MM angiogenesis by the PPARγ–VEGF signaling axis.
Intravitreal Administration of rhNGF Enhances Regenerative Processes in a Zebrafish Model of Retinal Degeneration
Authors: Cocchiaro Pasquale , Di Donato Vincenzo , Rubbini Davide , Mastropasqua Rodolfo , Allegretti Marcello , Mantelli Flavio , Aramini Andrea , Brandolini Laura
Published: March 2022

Nerve growth factor (NGF) is the best characterized neurotrophin, and it is known to play an important role in ocular homeostasis. Here, we demonstrated the expression of NGF receptors in adult zebrafish retina and optimized a light-induced retina degeneration (LID) zebrafish model that mimics human cone-rod disorders, demonstrating that intravitreal (IV) administration of rhNGF can boost zebrafish retinal regeneration in this model. Adult zebrafish retinae exposed to 60 h of light irradiation (60 h LID) displayed evident reduction of outer nuclear layer (ONL) thickness and cell number with presence of apoptotic cells. Retinal histologic evaluation at different time points showed that IV therapeutic injection of rhNGF resulted in an increase of ONL thickness and cell number at late time points after damage (14 and 21 days post injury), ultimately accelerating retinal tissue recovery by driving retinal cell proliferation. At a molecular level, rhNGF activated the ERK1/2 pathway and enhanced the regenerative potential of Müller glia gfap- and vim-expressing cells by stimulating at early time points the expression of the photoreceptor regeneration factor Drgal1-L2. Our results demonstrate the highly conserved nature of NGF canonical pathway in zebrafish and thus support the use of zebrafish models for testing new compounds with potential retinal regenerative properties. Moreover, the pro-regenerative effects of IV-injected NGF that we observed pave the way to further studies aimed at evaluating its effects also in mammals, in order to expedite the development of novel rhNGF-based therapeutic approaches for ophthalmological disorders.
Gut Microbiota-Mediated Elevated Production of Secondary Bile Acids in Chronic Unpredictable Mild Stress
Authors: Qu Yuchen , Su Cunjin , Zhao Qinhong , Shi Aiming , Zhao Fenglun , Tang Liuxing , Xu Delai , Xiang Zheng , Wang Yang , Wang Yueyuan , Pan Jie , Yu Yunli
Published: March 2022

A growing body of evidence suggests that gut microbiota could participate in the progression of depression via the microbiota–gut–brain axis. However, the detailed microbial metabolic profile changes in the progression of depression is still not fully elucidated. In this study, a liquid chromatography coupled to mass spectrometry-based untargeted serum high-throughput metabolomics method was first performed to screen for potential biomarkers in a depressive-like state in a chronic unpredictable mild stress (CUMS)-induced mouse model. Our results identified that the bile acid and energy metabolism pathways were significantly affected in CUMS progression. The detailed bile acid profiles were subsequently quantified in the serum, liver, and feces. The results showed that CUMS significantly promoted the deconjugation of conjugated bile acid and secondary bile acid biosynthesis. Furthermore, 16S rRNA gene sequencing revealed that the increased secondary bile acid levels in the feces positively correlated with Ruminococcaceae_UCG-010, Ruminococcus, and Clostridia_UCG-014 abundance. Taken together, our study suggested that changes in family Ruminococcaceae abundance following chronic stress increased biosynthesis of deoxycholic acid (DCA), a unconjugated secondary bile acid in the intestine. Aberrant activation of secondary bile acid biosynthesis pathway thereby increased the hydrophobicity of the bile acid pool, which might, in turn, promoted metabolic disturbances and disease progression in CUMS mice.
Efficacy and Safety of Neostigmine Adjunctive Therapy in Patients With Sepsis or Septic Shock: A Randomized Controlled Trial
Authors: El-Tamalawy Mona M. , Soliman Moetaza M. , Omara Amany F. , Rashad Amal , Ibrahim Osama M. , El-Shishtawy Mamdouh M.
Published: March 2022

Background: Neostigmine has been found to improve survival in animal models of sepsis. However, its feasibility, efficacy, and safety in patients with sepsis or septic shock have not been investigated.

Aim: This parallel randomized controlled double-blinded design aimed to investigate the efficacy and safety of neostigmine as an adjunctive therapy in patients with sepsis or septic shock.

Patients and Methods: A total of 167 adult patients with sepsis or septic shock were assessed for eligibility; 50 patients were randomized to receive a continuous infusion of neostigmine (0.2 mg/h for 120 h; neostigmine arm) or 0.9% saline (control arm) in addition to standard therapy. The primary outcome was the change in Sequential Organ Failure Assessment (SOFA) scores 120 h after therapy initiation. Secondary outcomes included mortality rates and changes in procalcitonin level.

Results: The median (interquartile range) change in SOFA scores improved significantly in the neostigmine arm [−2 (−5, 1)] as compared with the control arm [1.5 (0, 2.8); p = 0.007]. Progression from sepsis to septic shock was more frequent in the control arm (p = 0.01). The incidence of shock reversal in patients with septic shock was significantly lower in the control arm than in the neostigmine arm (p = 0.04). Differences in 28-days mortality rates did not reach statistical significance between the control and neostigmine arms (p = 0.36). Percentage change in procalcitonin levels was similar in both arms (p = 0.74).

Conclusion: Neostigmine adjunctive therapy may be safe and effective when administered in patients with sepsis or septic shock.

Clinical Trial Registration: NCT04130230.
Promising Antioxidative Effect of Berberine in Cardiovascular Diseases
Authors: An Na , Zhang Guoxia , Li Yingjian , Yuan Chao , Yang Fan , Zhang Lijing , Gao Yonghong , Xing Yanwei
Published: March 2022

Berberine (BBR), an important quaternary benzylisoquinoline alkaloid, has been used in Chinese traditional medicine for over 3,000 years. BBR has been shown in both traditional and modern medicine to have a wide range of pharmacological actions, including hypoglycemic, hypolipidemic, anti-obesity, hepatoprotective, anti-inflammatory, and antioxidant activities. The unregulated reaction chain induced by oxidative stress as a crucial mechanism result in myocardial damage, which is involved in the pathogenesis and progression of many cardiovascular diseases (CVDs). Numerous researches have established that BBR protects myocardium and may be beneficial in the treatment of CVDs. Given that the pivotal role of oxidative stress in CVDs, the pharmacological effects of BBR in the treatment and/or management of CVDs have strongly attracted the attention of scholars. Therefore, this review sums up the prevention and treatment mechanisms of BBR in CVDs from in vitro, in vivo, and finally to the clinical field trials timely. We summarized the antioxidant stress of BBR in the management of coronary atherosclerosis and myocardial ischemia/reperfusion; it also analyzes the pathogenesis of oxidative stress in arrhythmia and heart failure and the therapeutic effects of BBR. In short, BBR is a hopeful drug candidate for the treatment of CVDs, which can intervene in the process of CVDs from multiple angles and different aspects. Therefore, if we want to apply it to the clinic on a large scale, more comprehensive, intensive, and detailed researches are needed to be carried out to clarify the molecular mechanism and targets of BBR.
Effects of Induced Moisture Loss in Chicken Embryos at Embryonic Day 18 and Post-hatch Immune Response During Salmonella enteritidis Lipopolysaccharide Challenge in Broilers
Authors: Gregorich Jenna L. , Lilburn Michael S. , Shanmugasundaram Revathi
Published: March 2022

Two experiments were conducted to investigate the effects of induced moisture loss on embryonic development and the immune response following an inflammatory challenge immediately post-hatch. In Experiment I, fertile leghorn eggs (n = 100) and commercial broiler eggs (n = 300) were set at 37.5°C and moisture loss was induced in one-half of the Leghorn and broiler eggs by drilling two, 1.5 mm diameter holes. The Control eggs had 0 holes. At embryonic day (ED)18, layer and broiler eggs in the 2-holes treatment had a significant (P < 0.01) increase in moisture loss compared to the control treatment (10.1% vs. 8.2%). Similarly, at ED18, the broiler eggs with 2-holes had a significant increase (P < 0.01) in moisture loss compared with control eggs (9.9% vs. 8.4%). Thymocytes from both the leghorn (104%) and broiler (62%) embryos in the 2-holes treatment had significantly increased in vitro proliferation compared with the control embryos (P ≤ 0.05). At ED18, layer and broiler embryos in the 2-holes treatment had an approximate twofold increase in the splenic CD8+/CD4+ ratio (P ≤ 0.05) and CD4+CD25+ cells percentage in both the thymus and spleen (P ≤ 0.05). At ED18, both layer and broiler embryos from the 2-holes treatment had a significant increase in splenic IL1-β, IL-6, IL-10, and TLR-4 mRNA transcription compared to the control group (P ≤ 0.05). Experiment II was repeated with 300 fertile broiler eggs. On the day of hatch, chicks were randomly distributed into one of four treatments in a 2 (0, 2 holes) × 2 (0, 500 μg lipopolysaccharide, LPS) factorial arrangement of treatments. Chicks in the LPS groups were injected intraperitoneally with 500 μg/kg BW LPS. At 24 and 48 h post-hatch, chicks hatched from eggs with 2-holes and challenged with LPS had a significant increase (P ≤ 0.05) in thymocyte proliferation at 24 h (42%) and 48 h (37%) when compared with chicks hatched from the control (0-hole; 0 μg LPS) treatment. Chicks hatched from the 2-holes treatment and challenged with the LPS had an approximately twofold higher splenic CD8+/CD4+ ratio and 1.5 fold increase in CD4+CD25+ percentage compared to control chicks (P ≤ 0.05). In chicks hatched from the 2-holes treatment, MUC2 mRNA transcription was comparable to control chicks at 24 and 48 h in response to the LPS challenge. Our data suggest that the 2-holes treatment reprograms gene transcription to facilitate cell survival via proliferation and differentiation during an LPS inflammatory challenge.
Kam Sweet Rice (Oryza sativa L.) Is a Special Ecotypic Rice in Southeast Guizhou, China as Revealed by Genetic Diversity Analysis
Authors: Liu Chunhui , Cui Di , Jiao Aixia , Ma Xiaoding , Li Xiaobing , Han Bing , Chen Huicha , Ruan Renchao , Wang Yanjie , Han Longzhi
Published: March 2022

Kam Sweet Rice (KSR) is a special kind of rice landrace that has been domesticated for thousands of years by the local Dong people in southeast Guizhou province, China. KSR has many distinguishing characteristics including strong fragrance; high resistance to diseases, pests, and adverse abiotic conditions; difficulty of threshing; and glutinous texture. There is a lack of systematic research on its genetic diversity. In this study, we analyzed the levels and patterns of genetic diversity and nucleotide variation in 1,481 rice germplasm using simple sequence repeat (SSR) markers and single nucleotide polymorphism (SNP) haplotype analysis of six unlinked nuclear loci. The accessions included 315 KSR resources from southeast Guizhou, 578 rice landraces from six rice-growing ecological zones in Guizhou, 546 rice landraces from nine provinces around Guizhou, and 42 wild rice sources. Genetic diversity and heterozygosity of KSR were both low, and thus KSR might be close to a pure rice line. Population structure analysis showed that KSR was isolated into a single type of rice, which had a large genetic distance and a unique genetic background compared to the local varieties in Guizhou province, indicating that KSR is a special rice ecotype. Haplotype analysis of the target genes showed that the population of KSR was rich in haplotypes for resistance to bacterial blight (Xa23) and rice blast (Pid3), and identified unique haplotypes that were different from those of the six rice ecotypes in Guizhou. This study shows that KSR is an excellent rice germplasm resource, provides important information for the improvement and utilization of rice landraces, and serves as a reference for formulating effective rice conservation measures.
DNA Methylation Correlates With Responses of Experimental Hydrocotyle vulgaris Populations to Different Flood Regimes
Authors: Wang Mo-Zhu , Li Hong-Li , Tang Min , Yu Fei-Hai
Published: March 2022

Epigenetic mechanisms such as DNA methylation are considered as an important pathway responsible for phenotypic responses and rapid acclimation of plants to different environments. To search for empirical evidence that DNA methylation is implicated in stress-responses of non-model species, we exposed genetically uniform, experimental populations of the wetland clonal plantHydrocotyle vulgaristo two manipulated flood regimes, i.e., semi-submergence vs. submergence, measured phenotypic traits, and quantified different types of DNA methylation using MSAP (methylation-sensitive amplified polymorphism). We found different epi-phenotypes and significant epigenetic differentiation between semi-submerged and submerged populations. Compared to subepiloci (denoting DNA methylation conditions) for the CG-methylated state, unmethylation and CHG-hemimethylation subepiloci types contribute more prominently to the epigenetic structure of experimental populations. Moreover, we detected some epimarker outliers potentially facilitate population divergence between two flood regimes. Some phenotypic variation was associated with flood-induced DNA methylation variation through different types of subepiloci. Our study provides the indication that DNA methylation might be involved in plant responses to environmental variation without altering DNA sequences.
Parent-of-Origin Effects on Seed Size Modify Heterosis Responses in Arabidopsis thaliana
Authors: Castillo-Bravo Rosa , Fort Antoine , Cashell Ronan , Brychkova Galina , McKeown Peter C. , Spillane Charles
Published: March 2022

Parent-of-origin effects arise when a phenotype depends on whether it is inherited maternally or paternally. Parent-of-origin effects can exert a strong influence on F1 seed size in flowering plants, an important agronomic and life-history trait that can contribute to biomass heterosis. Here we investigate the natural variation in the relative contributions of the maternal and paternal genomes to F1 seed size across 71 reciprocal pairs of F1 hybrid diploids and the parental effect on F1 seed size heterosis. We demonstrate that the paternally derived genome influences F1 seed size more significantly than previously appreciated. We further demonstrate (by disruption of parental genome dosage balance in F1 triploid seeds) that hybridity acts as an enhancer of genome dosage effects on F1 seed size, beyond that observed from hybridity or genome dosage effects on their own. Our findings indicate that interactions between genetic hybridity and parental genome dosage can enhance heterosis effects in plants, opening new avenues for boosting heterosis breeding in crop plants.
Maize Endosperm Development: Tissues, Cells, Molecular Regulation and Grain Quality Improvement
Authors: Wu Hao , Becraft Philip W. , Dannenhoffer Joanne M.
Published: March 2022

Maize endosperm plays important roles in human diet, animal feed and industrial applications. Knowing the mechanisms that regulate maize endosperm development could facilitate the improvement of grain quality. This review provides a detailed account of maize endosperm development at the cellular and histological levels. It features the stages of early development as well as developmental patterns of the various individual tissues and cell types. It then covers molecular genetics, gene expression networks, and current understanding of key regulators as they affect the development of each tissue. The article then briefly considers key changes that have occurred in endosperm development during maize domestication. Finally, it considers prospects for how knowledge of the regulation of endosperm development could be utilized to enhance maize grain quality to improve agronomic performance, nutrition and economic value.
The Connection and Development of Unpredictability and Sensitivity in Maternal Care Across Early Childhood
Authors: Holmberg Eeva , Kataja Eeva-Leena , Davis Elysia Poggi , Pajulo Marjukka , Nolvi Saara , Hakanen Hetti , Karlsson Linnea , Karlsson Hasse , Korja Riikka
Published: March 2022

Both patterns of maternal sensory signals and sensitive care have shown to be crucial elements shaping child development. However, research concerning these aspects of maternal care has focused mainly on maternal sensitivity with fewer studies evaluating the impact of patterns of maternal behaviors and changes in these indices across infancy and childhood. The aims of this study were to explore how maternal unpredictability of sensory signals and sensitivity develop and associate with each other from infancy to toddlerhood and whether elevated maternal depressive and anxiety symptoms relate to maternal unpredictable signals and sensitivity in toddlerhood. The study population consisted of 356 mother–child dyads assessed at 30 months; a subset of 103 mother–child dyads additionally participated in 8 months assessment. Maternal unpredictability and sensitivity were assessed from video-recorded free-play episodes at 8 and 30 months. Maternal depressive and anxiety symptoms were assessed with questionnaires at gestational weeks 14, 24, 34 and 3, 6, 12, and 24 months. Mean level of mothers’ unpredictability decreased on average whereas sensitivity did not change between infancy and toddlerhood. Both maternal unpredictability and sensitivity showed moderate level of individual stability from infancy to toddlerhood and these two measures were modestly correlated within each age. Elevated maternal depressive and anxiety symptoms were not related to unpredictability but related to lower maternal sensitivity in toddlerhood. These results identify unpredictable sensory signals as a characteristic of parental care that is independent of standard quality measures and suggest that it may be less influenced by maternal depressive and anxiety symptoms.
Intergenerational Educational Inequality and Its Transmission in China’s Elite Universities
Authors: Wei Jianwen , Li Shuanglong , Han Yang , Fu Wangqian
Published: March 2022

China is experiencing high social inequality accompanying influential education reforms. The Independent Freshmen Admission (IFA) policy was one of the multiple strategies in higher education reforms in China against the social context of high social inequality and the expansion of higher education. By comparing students admitted through IFA with those admitted by the National College Entrance Examination (NCEE), we examined how family advantages contributed to higher education inequality in terms of educational opportunity, process, and results. Using data from an elite university in Beijing, we found that: (1) Family advantages improved a student’s likelihood of being admitted through IFA, exhibiting opportunity inequality. (2) No significant difference in academic grades existed between the students admitted through IFA and NCEE. In comprehensive quality, however, those recruited through IFA performed significantly better than those admitted through NCEE. (3) Family social capital not only increased the likelihood of students being admitted through IFA but also, through direct and indirect effects, increased their comprehensive quality performance in terms of receiving student association and social practice awards.
“A Group of Fellow Travellers Who Understand”: Interviews With Autistic People About Post-diagnostic Peer Support in Adulthood
Authors: Crompton Catherine J. , Hallett Sonny , McAuliffe Christine , Stanfield Andrew C. , Fletcher-Watson Sue
Published: March 2022

Receiving a diagnosis of autism in adulthood can be a life changing event, impacting identity, relationships, and mental health. A lack of post-diagnostic support has been highlighted by autistic adults, their allies, clinicians, and service providers. It can be a source of distress for autistic adults, reinforcing feelings of social isolation and rejection. Peer support could be a cost-effective, flexible, and sustainable model to provide community-based support for autistic adults. However, there is little research on the value of peer support, despite calls from the autistic community. This qualitative study explored autistic experiences and needs post-diagnosis, identifying specific ways that peer support may benefit them, and exploring the limitations of peer support. Twelve autistic adults who had all received an autism diagnosis in adulthood completed a semi-structured interview focussing on the diagnostic experience, post-diagnostic support needed and provided, engagement with the autistic community, and post-diagnostic peer support. Thematic analysis of interview transcripts resulted in four themes: (1) Mismatch in support needed and provided; (2) Community connection; (3) Flexible and personalised support; and (4) Sustainability. Participants indicated that peer support may be a useful mechanism to support autistic adults’ post-diagnosis and offers unique opportunities not available through other support channels. Though informal peer support exists, it could be more sustainable and effective if well-supported and funded.
Pathways of Parental Education on Children's and Adolescent's Body Mass Index: The Mediating Roles of Behavioral and Psychological Factors
Authors: Seum Teresa , Meyrose Ann-Katrin , Rabel Matthias , Schienkiewitz Anja , Ravens-Sieberer Ulrike
Published: March 2022

Aim

The increasing body mass index (BMI) often followed by overweight and obesity is a global health problem of the 21st century. Children and adolescents with lower socioeconomic status are more affected than their counterparts. The mechanisms behind these differences must be well understood to develop effective prevention strategies. This analysis aims at examining the association of parental education as an indicator of the socioeconomic status on children's and adolescent's body mass index and the role of behavioral and psychological risk factors for a higher BMI longitudinally.

Methods

The analysis was based on a nationwide sample of N = 460 children and adolescents, aged 11 to 17 at baseline (2009–2012), who took part in the representative BELLA study, the mental health module of the German National Health Interview and Examination Survey among Children and Adolescents (KiGGS). A follow-up was conducted 5 years later. Using mediation analyses, the mediating effects of breakfast consumption, consumption of sugar-sweetened beverages, screen time, physical activity, mental health problems (Strengths and Difficulties Questionnaire), and health-related quality of life (KIDSCREEN-10) on the association of parent's years of education on their children's BMI were investigated.

Results

A lower level of parental education was significantly associated with a higher BMI in children and adolescents 5 years later. The association was partially mediated by breakfast consumption and total screen time, with breakfast consumption mediating 16.7% and total screen time 27.8% of the association. After controlling for age, gender, and migration status, only breakfast consumption remained a partial mediator (8.5%). Other included variables had no mediating effects.

Conclusions

Preventive measures should be mainly targeted at children and adolescents of parents with lower educational levels. Tailored strategies to prevent the development of overweight and obesity in this population among children and adolescents should promote daily breakfast consumption at home and reducing screen time.
The Impact of Limited Prosthetic Socket Documentation: A Researcher Perspective
Authors: Olsen Jennifer , Turner Shruti , Chadwell Alix , Dickinson Alex , Ostler Chantel , Armitage Lucy , McGregor Alison H. , Dupan Sigrid , Day Sarah
Published: March 2022

The majority of limb prostheses are socket mounted. For these devices, the socket is essential for adequate prosthetic suspension, comfort, and control. The socket is unique among prosthetic components as it is not usually mass-produced and must instead be custom-made for individual residual limbs by a prosthetist. The knowledge of what constitutes “good” socket fit is gained by expert prosthetists and technicians over years of experience, and rarely documented. The reliance on tacit knowledge makes it difficult to standardize the criteria for a well-fitting socket, leading to difficulties understanding the impact of socket fit. Despite its importance, the workflow for socket fitting is often overlooked in literature. Due to the customized nature of sockets, if information is provided in literature, generally only the type of socket and suspension mechanism is noted, with information regarding the fitting and manufacturing processes omitted. In this article, the concerns, issues and consequences arising from lack of upper and lower limb socket documentation are discussed from a researcher perspective, supported by healthcare professionals and socket fabrication specialists. Key changes are proposed to the way socket manufacturing and evaluation are documented to assist future research.
Gingival Transcriptome of Innate Antimicrobial Factors and the Oral Microbiome With Aging and Periodontitis
Authors: Ebersole Jeffrey L. , Kirakodu Sreenatha , Nguyen Linh , Gonzalez Octavio A.
Published: March 2022

The epithelial barrier at mucosal sites comprises an important mechanical protective feature of innate immunity, and is intimately involved in communicating signals of infection/tissue damage to inflammatory and immune cells in these local environments. A wide array of antimicrobial factors (AMF) exist at mucosal sites and in secretions that contribute to this innate immunity. A non-human primate model of ligature-induced periodontitis was used to explore characteristics of the antimicrobial factor transcriptome (n= 114 genes) of gingival biopsies in health, initiation and progression of periodontal lesions, and in samples with clinical resolution. Age effects and relationship of AMF to the dominant members of the oral microbiome were also evaluated. AMF could be stratified into 4 groups with high (n= 22), intermediate (n= 29), low (n= 18) and very low (n= 45) expression in healthy adult tissues. A subset of AMF were altered in healthy young, adolescent and aged samples compared with adults (e.g., APP, CCL28, DEFB113, DEFB126, FLG2, PRH1) and were affected across multiple age groups. With disease, a greater number of the AMF genes were affected in the adult and aged samples with skewing toward decreased expression, for example WDC12, PGLYRP3, FLG2, DEFB128, and DEF4A/B, with multiple age groups. Few of the AMF genes showed a >2-fold increase with disease in any age group. Selected AMF exhibited significant positive correlations across the array of AMF that varied in health and disease. In contrast, a rather limited number of the AMF significantly correlated with members of the microbiome; most prominent in healthy samples. These correlated microbes were different in younger and older samples and differed in health, disease and resolution samples. The findings supported effects of age on the expression of AMF genes in healthy gingival tissues showing a relationship to members of the oral microbiome. Furthermore, a dynamic expression of AMF genes was related to the disease process and showed similarities across the age groups, except for low/very low expressed genes that were unaffected in young samples. Targeted assessment of AMF members from this large array may provide insight into differences in disease risk and biomolecules that provide some discernment of early transition to disease.
Sexually Transmitted Infections and Associated Risk Factors Among Male Clients of Sex Workers: A Cross-Sectional Pilot Project in Antwerp, Belgium
Authors: Platteau Tom , De Baetselier Irith , Van Mieghem Heleen , Tsoumanis Achilleas , Keersmaekers Kris , Ooms Lieselot , Cuylaerts Vicky , Florence Eric
Published: March 2022

Introduction

Prevalence of sexually transmitted infections (STIs) is increasing in Belgium in recent years. Clients of sex workers form a key population for acquisition of STIs, due to their sexual relations, with or without a condom, with sex workers. STI testing uptake is low among clients of sex workers, and prevalence of STIs remains to be investigated in Belgium. Therefore, we offered STI-testing to clients of sex workers during outreach sessions in Antwerp.

Methods

Time location sampling (TLS) was used to improve representativeness of the sample during ten test sessions in the red light district, Antwerp in May and September 2019 by using a passive approach. Individuals that were interested to get tested for STIs could enter the study. Participants completed an online survey and samples for STI testing were collected. Testing included HIV, syphilis, Chlamydia trachomatis (Ct) and Neisseria gonorrhoeae (Ng). Test results were communicated via a cell phone message (for negative test results) or by phone (for positive test results).

Results

In total, 154 male clients of sex workers with a median age of 38 participated. A total of eight Ct and one Ng infections were detected. TLS analysis revealed a Ct/Ng prevalence of 8.2%. No new HIV nor syphilis infections were detected. Using univariate analysis, testing positive for STI was associated with younger age and anorectal sex with a sex worker. Using multivariate analysis, an STI-positive test result was associated with being younger, having non-Belgian nationality, and being in a relationship.

Conclusion

Our study found a substantial prevalence of Ct/Ng which highlights the need for sensitization and facilitation of STI testing among clients of sex workers. It is difficult to compare results due to the lack of reference material. Moreover, our relatively small convenience sample limits generalizability of results. However, phone counseling (for positive test results) was accepted, linkage to care was provided, and partner notification was facilitated.
Distance Perception in the Oculus Quest and Oculus Quest 2
Authors: Kelly Jonathan W. , Doty Taylor A. , Ambourn Morgan , Cherep Lucia A.
Published: March 2022

Distances in virtual environments (VEs) viewed on a head-mounted display (HMD) are typically underperceived relative to the intended distance. This paper presents an experiment comparing perceived egocentric distance in a real environment with that in a matched VE presented in the Oculus Quest and Oculus Quest 2. Participants made verbal judgments and blind walking judgments to an object on the ground. Both the Quest and Quest 2 produced underperception. Verbal judgments in the VE were 82% and 75% of the object distance, in contrast with real world judgments that were 94% of the object distance. Blind walking judgments were 68% and 70% of object distance in the Quest and Quest 2, respectively, compared to 88% in the real world. This project shows that significant underperception of distance persists even in modern HMDs.
Primary Small Bowel Melanoma: A Case Report and Review of Literature
Authors: Graças Amanda M. , Souza Willy P. , Canut Ana Carolina A. , Franciss Maurice Y. , Zilberstein Bruno
Published: March 2022

Background

The present study analyzes diagnostic and therapeutic surgical aspects of primary small bowel melanoma, describing the clinical case and reviewing the literature. Malignant melanomas represent 1–3% of all malignant tumors of the gastrointestinal tract and are therefore uncommon. Only a few cases of metastatic melanoma (1–5%) are diagnosed in the early stages, while still asymptomatic. They show up as imaging exam findings and have better chance of treatment. Most of the time, the diagnosis is late and made in the presence of complications. The final diagnosis frequently depends on the surgical intervention after a serious complication.

Case report

This case report refers to a 55-year-old male patient, complaining of abdominal pain, blackened stools, and palpable tumor in the abdomen for ~30 days. A tomography scan was performed, which revealed the thickening and parietal enhancement of the small intestine loops with mesenteric adenomegaly and intermingled collection. For diagnostic confirmation, a laparoscopy was performed, which revealed a tumor at the jejunal level, and its resection was performed in the same act. The anatomopathological examination revealed that it was a primary small bowel melanoma.

Conclusion

The bibliographic research of the small bowel melanoma demonstrated that, in this situation, the lesion can be interpreted as a primary site or metastatic lesion, considering the possibility of a single primary lesion, whose diagnosis becomes more laborious. In such cases, adjuvant therapy must be considered. The expected 5-year survival is about 9–13%.
Lead Levels in a Potters Population and Its Association With the Use of Different Glazes: Cross-Sectional Evaluation of the Approved Pottery Program
Authors: Peralta Netzy , Cantoral Alejandra , Téllez-Rojo Martha María , Trejo-Valdivia Belem , Estrada-Sánchez Daniel , Richardson-L Vesta , Caravanos Jack , Fuller Richard
Published: March 2022

Lead is one of the most harmful toxic metals to humans. In Mexico, though most potters still use a lead-based glazing process, a new lead-free glaze has been introduced to the production of pottery. The Approved Pottery Program (APP) promotes the production of lead-free pottery. As a component of the APP, we aimed to document in this pilot study the blood lead levels (BLLs) of a sample of potters and the association with the type of glaze used. A cross-sectional study was conducted based on information from 46 potters grouped by 26 workshops. We measured general sociodemographic characteristics, capillary BLLs, and the lead levels of the dirt floors of the workshops. The evaluation of associations and comparisons between glaze types was performed based on a regression model clustered by workshop. The median BLL measured was 13.6 μg/dl (IQR: 7.8–20.4 μg/dl), and 70% of the BLLs were greater than 10 μg/dl. Workshop managers presented higher BLLs compared to others working in the same workshop (median of 14.1 μg/dl (IQR: 11.6–25.3 μg/dl) versus 10.1 μg/dl (IQR: 5.2–16.7 μg/dl), respectively). The median BLLs of potters who used lead-free glaze in at least 80% of production were 8.8 μg/dl (95% CI: −17.3 to −0.3 μg/dl) lower than the BLLs of those who used lead-free glaze in less than 30% of production, adjusted by workshop role. Additionally, the lead levels were significantly lower in workshop dirt floors where lead-free glaze was used in at least 80% of the production compared to those that use less than 30% (180 versus 916 mg/kg; p < 0.05). The use of lead-free glaze in the production of pottery was associated with both lower BLLs in potters and lower soil lead levels in the workshop area.
From Causal Networks to Adverse Outcome Pathways: A Developmental Neurotoxicity Case Study
Authors: Ramšak Živa , Modic Vid , Li Roman A. , vom Berg Colette , Zupanic Anze
Published: March 2022

The last decade has seen the adverse outcome pathways (AOP) framework become one of the most powerful tools in chemical risk assessment, but the development of new AOPs remains a slow and manually intensive process. Here, we present a faster approach for AOP generation, based on manually curated causal toxicological networks. As a case study, we took a recently published zebrafish developmental neurotoxicity network, which contains causally connected molecular events leading to neuropathologies, and developed two new adverse outcome pathways: Inhibition of Fyna (Src family tyrosine kinase A) leading to increased mortality via decreased eye size (AOP 399 on AOP-Wiki) and GSK3beta (Glycogen synthase kinase 3 beta) inactivation leading to increased mortality via defects in developing inner ear (AOP 410). The approach consists of an automatic separation of the toxicological network into candidate AOPs, filtering the AOPs according to available evidence and length as well as manual development of new AOPs and weight-of-evidence evaluation. The semiautomatic approach described here provides a new opportunity for fast and straightforward AOP development based on large network resources.
An Update on African Trypanocide Pharmaceutics and Resistance
Authors: Kasozi Keneth Iceland , MacLeod Ewan Thomas , Ntulume Ibrahim , Welburn Susan Christina
Published: March 2022

African trypanosomiasis is associated with Trypanosoma evansi, T. vivax, T. congolense, and T. brucei pathogens in African animal trypanosomiasis (AAT) while T. b gambiense and T. b rhodesiense are responsible for chronic and acute human African trypanosomiasis (HAT), respectively. Suramin sodium suppresses ATP generation during the glycolytic pathway and is ineffective against T. vivax and T. congolense infections. Resistance to suramin is associated with pathogen altered transport proteins. Melarsoprol binds irreversibly with pyruvate kinase protein sulfhydryl groups and neutralizes enzymes which interrupts the trypanosome ATP generation. Melarsoprol resistance is associated with the adenine-adenosine transporter, P2, due to point mutations within this transporter. Eflornithine is used in combination with nifurtimox. Resistance to eflornithine is caused by the deletion or mutation of TbAAT6 gene which encodes the transmembrane amino acid transporter that delivers eflornithine into the cell, thus loss of transporter protein results in eflornithine resistance. Nifurtimox alone is regarded as a poor trypanocide, however, it is effective in melarsoprol-resistant gHAT patients. Resistance is associated with loss of a single copy of the genes encoding for nitroreductase enzymes. Fexinidazole is recommended for first-stage and non-severe second-stage illnesses in gHAT and resistance is associated with trypanosome bacterial nitroreductases which reduce fexinidazole. In AAT, quinapyramine sulfate interferes with DNA synthesis and suppression of cytoplasmic ribosomal activity in the mitochondria. Quinapyramine sulfate resistance is due to variations in the potential of the parasite's mitochondrial membrane. Pentamidines create cross-links between two adenines at 4–5 pairs apart in adenine-thymine-rich portions of Trypanosoma DNA. It also suppresses type II topoisomerase in the mitochondria of Trypanosoma parasites. Pentamidine resistance is due to loss of mitochondria transport proteins P2 and HAPT1. Diamidines are most effective against Trypanosome brucei group and act via the P2/TbAT1 transporters. Diminazene aceturate resistance is due to mutations that alter the activity of P2, TeDR40 (T. b. evansi). Isometamidium chloride is primarily employed in the early stages of trypanosomiasis and resistance is associated with diminazene resistance. Phenanthridine (homidium bromide, also known as ethidium bromide) acts by a breakdown of the kinetoplast network and homidium resistance is comparable to isometamidium. In humans, the development of resistance and adverse side effects against monotherapies has led to the adoption of nifurtimox-eflornithine combination therapy. Current efforts to develop new prodrug combinations of nifurtimox and eflornithine and nitroimidazole fexinidazole as well as benzoxaborole SCYX-7158 (AN5568) for HAT are in progress while little comparable progress has been done for the development of novel therapies to address trypanocide resistance in AAT.