bluuebunny/crossref_metadata_2025 huggingface dataset:
Hard flaccid syndrome: state of current knowledge
Authors: Abdessater Maher , Kanbar Anthony , Akakpo William , Beley Sebastien
Published: June 2020

Introduction

Hard-flaccid syndrome is gaining increased interest among male sexual dysfunctions in the last years. It is poorly understood and defined. Most of the information comes from online forums. This paper is a review of current knowledge on the clinical presentation, diagnosis, pathophysiological mechanisms and treatments of this newly recognized condition.

Material and methods

A literature review was conducted on MEDLINE, CENTRAL, PASCAL databases and google scholar, using the terms: hard, flaccid, syndrome. The research identified 16 articles published between 2018 and February 2019. After reference lists review and duplicates removal, 7 full text references were eligible and useful for our review that follows PRISMA guidelines.

Results

The condition is acquired, chronic and painful. It is characterized by a constantly semi-rigid penis at the flaccid state and a loss in erectile rigidity. Patients have penile sensory changes, urinary symptoms, erectile dysfunction, pelvic floor muscles contraction and psychological distress. Symptoms are worse in standing position. The majority of the cases aged between their second and third decades. A traumatic injury at the base of an erect penis is the initial event. Neurovascular structures damage and subsequent sensory, muscular and vascular changes follow. Initial symptoms trigger emotional distress and reactional sympathetic stimulation that worsen symptoms. Diagnosis is based on patient’s history. Imaging and blood tests are normal. Differential diagnosis includes high-flow priapism and non-erecting erections. A multimodal treatment has been so far the most beneficial strategy, consisting of behavioral modifications to reduce stress and decrease pelvic floor muscles contraction, evaluation and treatment of the associated psychological conditions, and medical therapy for pain control and the treatment of the associated erectile dysfunction.

Conclusion

Hard-flaccid syndrome is poorly recognized in the daily clinical experience and not well defined. A multimodal approach seems so far the most efficient strategy for treatment. Additional evidence based studies with better quality are needed to define the exact pathophysiological mechanisms and subsequently more efficient therapeutic strategies.
Prejudices against the unemployed—empirical evidence from Germany
Authors: Gross Christiane , Gurr Thomas , Jungbauer-Gans Monika , Lang Sebastian
Published: June 2020

Prejudices against the unemployed pose an enormous threat to their self-confidence and can make it difficult for them to re-enter the labour market, resulting in further long-term unemployment. Given these high costs for the unemployed and for society as a whole, our knowledge of prejudices against the unemployed is surprisingly scarce. We focus on the question of what determines the strength of prejudice among employees. By applying social identity theory, we assume that people who are disadvantaged in the labour market in general, also hold stronger prejudices. In addition, we assume that social status mediates this association and that self-efficacy moderates it. We use data from the German panel study “Labour Market and Social Security” (PASS) and show that some groups of people who are themselves disadvantaged in the labour market (women and first-generation immigrants) have more prejudices against the unemployed; however, people with poor mental health have even fewer prejudices. Low social status (in terms of educational background, income, and job status) is associated with strong prejudices; however, social status does work as mediator to a minor degree only. People with low self-efficacy in general (main “effect”) and first-generation immigrants in particular (moderating “effect”) have stronger prejudices. These results can be a starting point for developing measures to reduce prejudice and for the onset of a debate about the origins of prejudices against the unemployed.
Correction to: On the utility of RNA sample pooling to optimize cost and statistical power in RNA sequencing experiments
Authors: Assefa Alemu Takele , Vandesompele Jo , Thas Olivier
Published: June 2020

An amendment to this paper has been published and can be accessed via the original article.
The MYB transcription factor CiMYB42 regulates limonoids biosynthesis in citrus
Authors: Zhang Pan , Liu Xiaofeng , Yu Xin , Wang Fusheng , Long Junhong , Shen Wanxia , Jiang Dong , Zhao Xiaochun
Published: June 2020

Background

Limonoids are major bioactive compounds that are produced by the triterpenoid metabolic pathway. The detailed biochemical process of limonoid biosynthesis and the mechanism of its molecular regulation remain elusive. The identification of transcription factors that regulate limonoid biosynthetic pathways is very important for understanding the underlying regulatory mechanisms. This information could also provide tools for manipulating biosynthesis genes to modulate limonoid production.

Results

In this study, the CiMYB42 transcription factor was isolated to identify its role in limonoid biosynthesis. Multiple alignment analysis and phylogenetic analysis demonstrated that CiMYB42 is a typical R2R3MYB transcription factor that shares high similarity of its amino acid sequence with AtMYB42. Limonoids contents were higher in Citrus sinensis and Citrus grandis than in other species. Limonoid accumulation during leaf development also showed diverse trends in different genotypes. The expression of CiMYB42 was significantly related to the limonoid content and the expression of CiOSC in some citrus accessions. The overexpression of CiMYB42 in sweet orange resulted in significant accumulation of limonin, whereas the downregulation of CiMYB42 by RNAi resulted in a dwarf phenotype and less nomilin accumulation. Furthermore, the results of a yeast one-hybrid assay and EMSA indicated that CiMYB42 binds exclusively to the TTGTTG sequence (type II MYB core) in the promoter of CiOSC. Together, these results suggest that CiMYB42 positively regulates limonoid biosynthesis by regulating the expression of CiOSC by binding to the TTGTTG sequence (type II MYB core) of its promoter.

Conclusions

CiMYB42 is an important transcription activator involved in limonoid biosynthesis that regulates the expression of CiOSC by binding to the TTGTTG sequence (type II MYB core).
Diagnostic and prognostic nomograms for bone metastasis in hepatocellular carcinoma
Authors: Hu Chuan , Yang Jiaxin , Huang Zhangheng , Liu Chuan , Lin Yijun , Tong Yuexin , Fan Zhiyi , Chen Bo , Wang Cailin , Zhao Cheng-Liang
Published: June 2020

Background

Bone metastasis (BM) is one of the common sites of hepatocellular carcinoma (HCC), and the prognosis of BM patients is worse than patients without it. Our study aimed to identify predictors and prognostic factors of BM in HCC patients and develop two nomograms to quantify the risk of BM and the prognosis of HCC patients with BM.

Methods

We retrospectively reviewed the data of patients who were diagnosed as HCC between 2010 and 2015 in the Surveillance, Epidemiology, and End Results (SEER) database. Independent predictors for BM from HCC patients were determined by the univariate and multivariate logistic regression analysis. Independent prognostic factors for HCC patients with BM were identified by univariate and multivariate Cox regression analysis. Two nomograms were established and evaluated by calibration curves, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA).

Results

Nine thousand and forty-seven patients were included. The independent risk factors of BM in newly diagnosed HCC patients are sex, grade, T stage, and N stage. The independent prognostic factors for HCC patients with BM are radiotherapy, chemotherapy, and lung metastasis. The AUC of diagnostic nomogram were 0.726 in the training set and 0.629 in the testing set. For the prognostic nomogram, the AUCs of 6-, 9-, and 12-months were 0.753, 0.799, and 0.732 in the training set and 0.698, 0.770, and 0.823 in the validation set. The calibration curve and DCA indicated the good performance of the nomogram.

Conclusions

Two nomograms were established to predict the incidence of BM in HCC patients and the prognosis of HCC patients with BM, respectively. Both nomograms have satisfactory accuracy, and clinical utility may benefit for clinical decision-making.
The findings of corneal specular microscopy in patients with type-2 diabetes mellitus
Authors: Taşlı Nurdan Gamze , Icel Erel , Karakurt Yücel , Ucak Turgay , Ugurlu Adem , Yilmaz Hayati , Akbas Emin Murat
Published: June 2020

Background

We aimed to compare the morphological characteristics of corneal endothelial cells in type 2 diabetic patients and age-matched healthy subjects by specular microscopy.

We also aimed to determine the association of corneal morphological features with the general characteristics and laboratory data of diabetic patients, including disease duration, haemoglobin A1c (HbA1c) levels and urine albumin creatinine ratio.

Methods

A total of 195 diabetic patients and 100 healthy controls were enrolled in the study. All participants underwent a complete ophthalmological examination. Corneal endothelial measurements were performed using a noncontact specular microscopy. Laboratory data including serum fasting glucose, haemoglobin A1c levels, creatinine levels, and the urinary albumin-to-creatinine ratio were recorded. Diabetic patients were further subdivided into 3 groups according to the presence and stage of diabetic retinopathy. Specular microscopy findings and central corneal thickness of all patients were compared.

Results

The ECD and hexagonal cell ratio were significantly lower, while the average cell size, CV%, and central corneal thickness were determined to be significantly higher in diabetic patients than in healthy controls (p = 0.001). With the presence and advancement of diabetic retinopathy, the ECD and hexagonal cell ratio decreased, while the average cell size, CV%, and central corneal thickness increased. When correlation analysis was performed between corneal morphological features and laboratory data of diabetic patients, ECD showed a significant negative correlation with diabetes duration (p = 0.028). HbA1c levels, urinary albumin-creatinine ratio (p = 0.041), average cell size and CV showed a positive correlation with these parameters.

Conclusion

In conclusion, keratopathy is an important complication of type 2 diabetes. With an increase in the stage of diabetic retinopathy, alterations in corneal findings also increased. In that respect, we can suggest that keratopathy should be evaluated more cautiously in diabetic patients.
Access to health care for people with disabilities in rural Malawi: what are the barriers?
Authors: Harrison Josephine A. K. , Thomson Rachael , Banda Hastings T. , Mbera Grace B. , Gregorius Stefanie , Stenberg Berthe , Marshall Tim
Published: June 2020

Background

People with disabilities experience significant health inequalities. In Malawi, where most individuals live in low-income rural settings, many of these inequalities are exacerbated by restricted access to health care services. This qualitative study explores the barriers to health care access experienced by individuals with a mobility or sensory impairment, or both, living in rural villages in Dowa district, central Malawi. In addition, the impact of a chronic lung condition, alongside a mobility or sensory impairment, on health care accessibility is explored.

Methods

Using data from survey responses obtained through the Research for Equity And Community Health (REACH) Trust’s randomised control trial in Malawi, 12 adult participants, with scores of either 3 or 4 in the Washington Group Short Set (WGSS) questions, were recruited. The WGSS questions concern a person’s ability in core functional domains (including seeing, hearing and moving), and a score of 3 indicates ‘a lot of difficulty’ whilst 4 means ‘cannot do at all’. People with cognitive impairments were not included in this study. All who were selected for the study participated in an individual in-depth interview and full recordings of these were then transcribed and translated.

Results

Through thematic analysis of the transcripts, three main barriers to timely and adequate health care were identified: 1) Cost of transport, drugs and services, 2) Insufficient health care resources, and 3) Dependence on others. Attitudinal factors were explored and, whilst unfavourable health seeking behaviour was found to act as an access barrier for some participants, community and health care workers’ attitudes towards disability were not reported to influence health care accessibility in this study.

Conclusions

This study finds that health care access for people with disabilities in rural Malawi is hindered by closely interconnected financial, practical and social barriers. There is a clear requirement for policy makers to consider the challenges identified here, and in similar studies, and to address them through improved social security systems and health system infrastructure, including outreach services, in a drive for equitable health care access and provision.
Influence of gender in monocrotaline and chronic hypoxia induced pulmonary hypertension in obese rats and mice
Authors: Neupane Balram , Sydykov Akylbek , Pradhan Kabita , Vroom Christina , Herden Christiane , Karnati Srikanth , Ghofrani Hossein Ardeschir , Avdeev Sergey , Ergün Süleyman , Schermuly Ralph Theo , Kosanovic Djuro
Published: June 2020

Background

Obesity and pulmonary hypertension (PH) share common characteristics, such as augmented inflammation and oxidative stress. However, the exact role of obesity in the pathology of PH is largely uninvestigated. Therefore, we have hypothesized that in the context of obesity the gender difference may have influence on development of PH in animal models of this disease.

Methods

Animal experiments were conducted in monocrotaline (MCT) and chronic hypoxia (HOX) models of PH. Lean and obese Zucker rats or B6 mice of both genders were used for MCT or HOX models, respectively. Echocardiography, hemodynamic measurements, histology and immuno-histochemistry were performed to analyze various parameters, such as right ventricular function and hypertrophy, hemodynamics, pulmonary vascular remodeling and lung inflammation.

Results

Both lean and obese male and female Zucker rats developed PH after a single MCT injection. However, negligible differences were seen between lean and obese male rats in terms of PH severity at the end stage of disease. Conversely, a more prominent and severe PH was observed in obese female rats compared to their lean counterparts. In contrast, HOX induced PH in lean and obese, male and female mice did not show any apparent differences.

Conclusion

Gender influences PH severity in obese MCT-injected rats. It is also an important factor associated with altered inflammation. However, further research is necessary to investigate and reveal the underlying mechanisms.
Local expression profiles of vitamin D-related genes in airways of COPD patients
Authors: Mathyssen Carolien , Aelbrecht Celine , Serré Jef , Everaerts Stephanie , Maes Karen , Gayan-Ramirez Ghislaine , Vanaudenaerde Bart , Janssens Wim
Published: June 2020

Treatment of Chronic Obstructive Pulmonary Disease (COPD) is based on bronchodilation, with inhaled corticosteroids or azithromycin associated when frequent exacerbations occur. Despite the proven benefits of current treatment regimens, the need for new interventions in delineated subgroups remains. There is convincing evidence for oral vitamin D supplementation in reducing exacerbations in COPD patients severely deficient for circulating vitamin D. However, little is known about local vitamin D metabolism in the airways and studies examining expression of the vitamin D receptor (VDR), the activating enzyme (CYP27B1) and inactivating enzyme (CYP24A1) of vitamin D in lung tissue of COPD patients are lacking. Therefore, the expression and localization of key enzymes and the receptor of the vitamin D pathway were examined in tissue of 10 unused donor lungs and 10 COPD explant lungs. No differences in the expression of CYP27B1 and CYP24A1 were found. Although protein expression of VDR was significantly lower in COPD explant tissue, there was no difference in downstream expression of the antimicrobial peptide cathelicidin. Whereas CYP27B1 and CYP24A1 were present in all layers of the bronchial epithelium, VDR was only expressed at the apical layer of a fully differentiated bronchial epithelium with no expression in vascular endothelial cells. By contrast, CYP24A1 expression was highly present in lung endothelial cells suggesting that systemic vitamin D can be inactivated before reaching the epithelial compartment and the tissue immune cells. These data support the idea of exploring the role of vitamin D inhalation in patients with COPD.
Using force data to self-pace an instrumented treadmill and measure self-selected walking speed
Authors: Song Seungmoon , Choi Hojung , Collins Steven H.
Published: June 2020

Background

Self-selected speed is an important functional index of walking. A self-pacing controller that reliably matches walking speed without additional hardware can be useful for measuring self-selected speed in a treadmill-based laboratory.

Methods

We adapted a previously proposed self-pacing controller for force-instrumented treadmills and validated its use for measuring self-selected speeds. We first evaluated the controller’s estimation of subject speed and position from the force-plates by comparing it to those from motion capture data. We then compared five tests of self-selected speed. Ten healthy adults completed a standard 10-meter walk test, a 150-meter walk test, a commonly used manual treadmill speed selection test, a two-minute self-paced treadmill test, and a 150-meter self-paced treadmill test. In each case, subjects were instructed to walk at or select their comfortable speed. We also assessed the time taken for a trial and a survey on comfort and ease of choosing a speed in all the tests.

Results

The self-pacing algorithm estimated subject speed and position accurately, with root mean square differences compared to motion capture of 0.023 m s −1 and 0.014 m, respectively. Self-selected speeds from both self-paced treadmill tests correlated well with those from the 10-meter walk test (R>0.93,p<1×10−13). Subjects walked slower on average in the self-paced treadmill tests (1.23±0.27 ms−1) than in the 10-meter walk test (1.32±0.18 ms−1) but the speed differences within subjects were consistent. These correlations and walking speeds are comparable to those from the manual treadmill speed selection test (R=0.89,p=3×10−11;1.18±0.24 ms−1). Comfort and ease of speed selection were similar in the self-paced tests and the manual speed selection test, but the self-paced tests required only about a third of the time to complete. Our results demonstrate that these self-paced treadmill tests can be a strong alternative to the commonly used manual treadmill speed selection test.

Conclusions

The self-paced force-instrumented treadmill well adapts to subject walking speed and reliably measures self-selected walking speeds. We provide the self-pacing software to facilitate use by gait researchers and clinicians.
Prevention of tumor risk associated with the reprogramming of human pluripotent stem cells
Authors: Wuputra Kenly , Ku Chia-Chen , Wu Deng-Chyang , Lin Ying-Chu , Saito Shigeo , Yokoyama Kazunari K.
Published: June 2020

Human pluripotent embryonic stem cells have two special features: self-renewal and pluripotency. It is important to understand the properties of pluripotent stem cells and reprogrammed stem cells. One of the major problems is the risk of reprogrammed stem cells developing into tumors. To understand the process of differentiation through which stem cells develop into cancer cells, investigators have attempted to identify the key factors that generate tumors in humans. The most effective method for the prevention of tumorigenesis is the exclusion of cancer cells during cell reprogramming. The risk of cancer formation is dependent on mutations of oncogenes and tumor suppressor genes during the conversion of stem cells to cancer cells and on the environmental effects of pluripotent stem cells. Dissecting the processes of epigenetic regulation and chromatin regulation may be helpful for achieving correct cell reprogramming without inducing tumor formation and for developing new drugs for cancer treatment. This review focuses on the risk of tumor formation by human pluripotent stem cells, and on the possible treatment options if it occurs. Potential new techniques that target epigenetic processes and chromatin regulation provide opportunities for human cancer modeling and clinical applications of regenerative medicine.
Podiatrists' views of assessment and management of pain in diabetes‐related foot ulcers: a focus group study
Authors: Frescos Nicoletta , Copnell Bev
Published: June 2020

Background

Contrary to the belief that patients with diabetes‐related foot ulcers (DRFU) do not experience wound related pain due to the presence of peripheral neuropathy there is increasing evidence that pain can be present. Subsequently, wound‐related pain is often underestimated and undertreated. The aim of this study is to describe what influences pain assessment of DRFU.

Methods

A qualitative exploratory study was conducted with podiatrists who managed DRFU. Eight podiatrists were recruited through a professional organisation to participate in a focus group. A thematic analysis was conducted to identify themes that explored the barriers and enablers to pain assessment and management of DRFU.

Results

Three themes emerged. Observational and non‐verbal cues were the preferred approaches used to assess wound pain. Assumptions and value judgments of the pain patients experienced and the relationships between podiatrists, patients and other health care practitioners were important influencers on the assessment and management of pain.

Conclusion

The perceived barriers to the assessment and management of wound related pain in DRFU were attitudes and beliefs about pain, lack of DRFU‐specific validated assessment tools and lack of knowledge and skills to manage the pain.
Oral vitamin A supplementation for ROP prevention in VLBW preterm infants
Authors: Garofoli Francesca , Barillà Donatella , Angelini Micol , Mazzucchelli Iolanda , De Silvestri Annalisa , Guagliano Rosanna , Decembrino Lidia , Tzialla Chryssoula
Published: June 2020

Vitamin A administration may decrease any stage of retinopathy of prematurity (ROP) in preterm infants. To evaluate whether vitamin A oral supplementation could be preventive in ROP incidence and severity in VLBW infants, we compared results from 31 preterm infants, (< 1500 g or < 32 weeks) who, during a previous investigation, prospectively received 3000 UI/kg/die oral retinol palmitate drops, for 28 days, with 31 matching preterm newborns hospitalized in our NICU the same period, as control group. Although ROP incidence was similar, in the supplemented group, we had 9 cases of ROP grade 1, no ROP grade ≥ 2, in the un-supplemented group, 4 cases of ROP grade 1 and 6 ROP grade ≥ 2 (p = 0.018). The percentage of babies requiring treatment for ROP was 0 in treated and 16.6 in the un-treated group (p = 0.020). Moreover, Vitamin A administration showed a protective effect with an 88% risk reduction of developing severe ROP. Since vitamin A parenteral/IM administration presents some awareness, the results of this investigation may be important to plan further trials to confirm the usefulness of oral administration in mitigating the ROP severity of VLBW infants.

ClinicalTrials.gov NCT02102711; may 03/06/2014.
Evaluating the efficacy and safety of GKT137831 in adults with type 1 diabetes and persistently elevated urinary albumin excretion: a statistical analysis plan
Authors: De Livera Alysha M. , Reutens Anne , Cooper Mark , Thomas Merlin , Jandeleit-Dahm Karin , Shaw Jonathan E. , Salim Agus
Published: June 2020

Background

The investigational medicinal product GKT137831 is a selective inhibitor of NOX 1 and 4 isoforms of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase family of enzymes, which has the potential to ameliorate diabetic kidney disease. An investigator-initiated, double-blind, randomised, placebo-controlled, multicentre phase 2 clinical trial started recruitment in December 2017, with the aim of evaluating the efficacy and safety of GKT13783, in adults with type 1 diabetes mellitus and persistently elevated urinary albumin excretion over a period of 48 weeks.

Methods/design

The trial is currently recruiting in Australia and New Zealand, with recruitment expected to end on 30 June 2020. The primary outcome measure of the trial is the urinary albumin excretion level measured at 48 weeks of treatment. This statistical analysis plan presents an update to the published trial protocol and provides a comprehensive description of the statistical methods that will be used for the analysis of the data from this trial. In doing so, we follow the “Guidelines for the content of statistical analysis plans in clinical trials” to support transparency and reproducibility of the trial findings.

Discussion

With the use of this prior statistical analysis plan, we aim to minimise bias in the reporting of the findings of this trial, which evaluates the investigational medicinal product GKT137831. The results of the trial are expected to be published in 2022.

Trial registration

ANZCTR registry:ACTRN12617001187336. Registered on 14 July 2017.

Universal Trial Number: U1111-1187-2609; Protocol number: T1DGKT137831; Genkyotex trial number: GSN000241.
LAMPS: an analysis pipeline for sequence-specific ligation-mediated amplification reads
Authors: Cameron Christopher J. F. , Wang Xue Q. D. , Dostie Josée , Blanchette Mathieu
Published: June 2020

Objective

Ligation-Mediated Amplification (LMA) is a versatile biochemical tool for amplifying selected DNA sequences. LMA has increased in popularity due to its integration within chromosome conformation capture (5C) and chromatin immunoprecipitation (2C-ChIP) methodologies. The output of either 5C or 2C-ChIP protocols is a single-read sequencing library of ligated primer pairs that may or may not be multiplexed. While many computational tools currently exist for read mapping and analysis, these tools neither fully support multiplexed libraries nor provide qualitative reporting on the LMA primers involved. Typically, the task of library demultiplexing or primer analysis is offloaded on to the user. Our aim was to develop an easy-to-use pipeline for processing (multiplexed) single-read sequencing data produced by sequence-specific LMA.

Results

Here, we describe the Ligation-mediated Amplified, Multiplexed Primer-pair Sequence (LAMPS) analysis pipeline. LAMPS facilitates the analysis of multiplexed LMA sequencing data and provides a thorough assessment of a library’s reads for a variety of experimental parameters (e.g., primer-pair efficiency). The standardized output of LAMPS allows for easy integration with downstream analyses, such as data track visualization on a genome browser. LAMPS is made publicly available on GitHub: https://github.com/BlanchetteLab/LAMPS
Prevalence of self-harm among lesbian, gay, bisexual, and transgender adolescents: a comparison of personal and social adversity with a heterosexual sample in Ghana
Authors: Quarshie Emmanuel N.-B. , Waterman Mitch G. , House Allan O.
Published: June 2020

Objectives

We sought to estimate the prevalence of self-reported self-harm among adolescents identifying as lesbian, gay, bisexual, and transgender (LGBT) in Ghana, and compare self-reported personal and social adversities related to self-harm in this group to those in a random sample of heterosexual adolescents from the same locality.

Results

A total of 444 adolescents aged 13-21 years, comprising 74 LGBT adolescents and 370 heterosexual adolescents, provided data. The lifetime prevalence estimate of self-harm was higher in the LGBT group (47%) than the heterosexual group (23%). The LGBT group reported a higher rate of self-harm during the previous 12 months (45%), compared to the heterosexual group (18%). LGBT adolescents reported more alcohol and substance use and more personal social adversities, including various forms of victimisation, than heterosexual adolescents. They were no more likely to report difficulty in making and keeping friends or schoolwork problems than were heterosexual adolescents.
Cell density alters bacterial community structure in culture-enriched 16S rRNA gene microbiota profiling
Authors: Adhikari Bishnu , Kwon Young Min
Published: June 2020

Objective

Microbial community profiling using 16S rRNA gene has provided invaluable insights into diverse microbial communities. Recently a few studies have attempted to use 16S rRNA gene microbiota profiling in combination with the conventional culture methods to explore bacterial communities. In this “culture-enriched microbiota profiling” approach, microbes in a sample are cultured on solid media, and the resulting colonies are combined and subjected to 16S rRNA gene microbiota profiling. Here we investigated the effect of cell densities as determined by varying levels of sample dilution on the culture-enriched microbiota profiles using De Man, Rogosa and Sharpe (MRS) agar medium as a model system.

Results

Cecal samples collected from 10 healthy chickens were serially diluted to 102 fold (M-LOW), 104 fold (M-MEDIUM), and 106 fold (M-HIGH), and the dilutions were plated on MRS agar. 16S rRNA gene profiling showed that the relative abundance of certain genera showed gradual increase (Pediococcus and Enterococcus) or decrease (Lactobacillus and Turicibacter) with higher dilutions, though it was significant only for Pediococcus (p < 0.05). The result indicates that the dilution levels of the samples can alter the resulting microbiota profiles via unknown density-dependent mechanisms and thus should be considered for designing experiments using culture-enriched microbiota profiling.
Dentoskeletal and tooth-size differences between Syrian and Hungarian adolescents with Class II division 1 malocclusion: a retrospective study
Authors: Al Ayoubi Alaa , Khandan Dezfully Alireza , Madléna Melinda
Published: June 2020

Objectives

Malocclusion features differ across various populations and ethnicities. At this time, no data are available regarding the dentofacial differences between Syrian and European adolescents with Class II division 1 malocclusion, which is one of the most frequently treated pathologies in orthodontic practice. The present combined cephalometric and tooth-size study aimed to compare the dentoskeletal and tooth-size characteristics of Syrian and Hungarian adolescents with Class II division 1 malocclusion.

Results

Class II division 1 malocclusion in Hungarian adolescents was a sagittal discrepancy, while in Syrian adolescents, it was a result of excessive vertical development. Syrian adolescents had a significantly excessive vertical development when compared with Hungarian adolescents, regardless of sex(p < 0.01). Hungarian boys had significantly more protruded maxillae(p < 0.001)and less retruded mandibles (p < 0.01)when compared with Syrian boys, while Hungarian girls had significantly shorter mandibles relative to those of Syrian girls (p < 0.01). Syrian girls had significantly more protrusive lower incisors (p < 0.001), accompanied by significantly larger anterior tooth-size ratios when compared to Hungarian girls (p < 0.001). In conclusion, these findings underscore the importance of considering ethnic differences during orthodontic diagnosis and may have implications for optimizing orthodontic treatments in Syrian and Hungarian adolescents with Class II division 1 malocclusion.
DNA methylation loci in placenta associated with birthweight and expression of genes relevant for early development and adult diseases
Authors: Tekola-Ayele Fasil , Zeng Xuehuo , Ouidir Marion , Workalemahu Tsegaselassie , Zhang Cuilin , Delahaye Fabien , Wapner Ronald
Published: June 2020

Background

Birthweight marks an important milestone of health across the lifespan, including cardiometabolic disease risk in later life. The placenta, a transient organ at the maternal-fetal interface, regulates fetal growth. Identifying genetic loci where DNA methylation in placenta is associated with birthweight can unravel genomic pathways that are dysregulated in aberrant fetal growth and cardiometabolic diseases in later life.

Results

We performed placental epigenome-wide association study (EWAS) of birthweight in an ethnic diverse cohort of pregnant women (n = 301). Methylation at 15 cytosine-(phosphate)-guanine sites (CpGs) was associated with birthweight (false discovery rate (FDR) < 0.05). Methylation at four (26.7%) CpG sites was associated with placental transcript levels of 15 genes (FDR < 0.05), including genes known to be associated with adult lipid traits, inflammation and oxidative stress. Increased methylation at cg06155341 was associated with higher birthweight and lower FOSL1 expression, and lower FOSL1 expression was correlated with higher birthweight. Given the role of the FOSL1 transcription factor in regulating developmental processes at the maternal-fetal interface, epigenetic mechanisms at this locus may regulate fetal development. We demonstrated trans-tissue portability of methylation at four genes (MLLT1, PDE9A, ASAP2, and SLC20A2) implicated in birthweight by a previous study in cord blood. We also found that methylation changes known to be related to maternal underweight, preeclampsia and adult type 2 diabetes were associated with lower birthweight in placenta.

Conclusion

We identified novel placental DNA methylation changes associated with birthweight. Placental epigenetic mechanisms may underlie dysregulated fetal development and early origins of adult cardiometabolic diseases.

Clinical trial registration

ClinicalTrials.gov, NCT00912132
SHP2 mutations induce precocious gliogenesis of Noonan syndrome-derived iPSCs during neural development in vitro
Authors: Ju Younghee , Park Jun Sung , Kim Daejeong , Kim Bumsoo , Lee Jeong Ho , Nam Yoonkey , Yoo Han-Wook , Lee Beom Hee , Han Yong-Mahn
Published: June 2020

Background

Noonan syndrome (NS) is a developmental disorder caused by mutations of Src homology 2 domain-containing protein tyrosine phosphatase 2 (SHP2). Although NS patients have diverse neurological manifestations, the mechanisms underlying the involvement of SHP2 mutations in neurological dysfunction remain elusive.

Methods

Induced pluripotent stem cells generated from dermal fibroblasts of three NS-patients (NS-iPSCs) differentiated to the neural cells by using two different culture systems, 2D- and 3D-cultured systems in vitro.

Results

Here we represent that SHP2 mutations cause aberrant neural development. The NS-iPSCs exhibited impaired development of EBs in which BMP and TGF-β signalings were activated. Defective early neuroectodermal development of NS-iPSCs recovered by inhibition of both signalings and further differentiated into NPCs. Intriguingly, neural cells developed from NS-NPCs exhibited abundancy of the glial cells, neurites of neuronal cells, and low electrophysiological property. Those aberrant phenotypes were also detected in NS-cerebral organoids. SHP2 inhibition in the NS-NPCs and NS-cerebral organoids ameliorated those anomalies such as biased glial differentiation and low neural activity.

Conclusion

Our findings demonstrate that SHP2 mutations contribute to precocious gliogenesis in NS-iPSCs during neural development in vitro.
Expression dynamics of integrin α2, α3, and αV upon osteogenic differentiation of human mesenchymal stem cells
Authors: Lee Hyun Min , Seo Se-Ri , Kim Jeeseung , Kim Min Kyu , Seo Hyosun , Kim Kyoung Soo , Jang Young-Joo , Ryu Chun Jeih
Published: June 2020

Background

The differentiation of human mesenchymal stem cells (hMSCs) into osteoblasts (OBs) is a prerequisite for bone formation. However, little is known about the definitive surface markers for OBs during osteogenesis.

Methods

To study the surface markers on OBs, we generated and used monoclonal antibodies (MAbs) against surface molecules on transforming growth factor-β1 (TGF-β1)-treated cancer cells. The generated MAbs were further selected toward expression changes on hMSCs cultured with TGF-β1/bone morphogenetic protein-2 (BMP-2) or osteogenic differentiation medium (ODM) by flow cytometry. Immunoprecipitation and mass spectrometry were performed to identify target antigens of selected MAbs. Expression changes of the target antigens were evaluated in hMSCs, human periodontal ligament cells (hPDLCs), and human dental pulp cells (hDPCs) during osteogenic and adipogenic differentiation by quantitative polymerase chain reaction (qPCR) and flow cytometry. hMSCs were also sorted by the MAbs using magnetic-activated cell sorting system, and osteogenic potential of sorted cells was evaluated via Alizarin Red S (ARS) staining and qPCR.

Results

The binding reactivity of MR14-E5, one of the MAbs, was downregulated in hMSCs with ODM while the binding reactivity of ER7-A7, ER7-A8, and MR1-B1 MAbs was upregulated. Mass spectrometry and overexpression identified that MR14-E5, ER7-A7/ER7-A8, and MR1-B1 recognized integrin α2, α3, and αV, respectively. Upon osteogenic differentiation of hMSCs, the expression of integrin α2 was drastically downregulated, but the expression of integrin α3 and αV was upregulated in accordance with upregulation of osteogenic markers. Expression of integrin α3 and αV was also upregulated in hPDLCs and hDPCs during osteogenic differentiation. Cell sorting showed that integrin αV-high hMSCs have a greater osteogenic potential than integrin αV-low hMSCs upon the osteogenic differentiation of hMSCs. Cell sorting further revealed that the surface expression of integrin αV is more dramatically induced even in integrin αV-low hMSCs.

Conclusion

These findings suggest that integrin α3 and αV induction is a good indicator of OB differentiation. These findings also shed insight into the expression dynamics of integrins upon osteogenic differentiation of hMSCs and provide the reason why different integrin ligands are required for OB differentiation of hMSCs.
Efficacy of mesenchymal stem cell therapy for sepsis: a meta-analysis of preclinical studies
Authors: Sun Xue-Yi , Ding Xian-Fei , Liang Huo-Yan , Zhang Xiao-Juan , Liu Shao-Hua , Bing-Han  , Duan Xiao-Guang , Sun Tong-Wen
Published: June 2020

Background

Multiple studies have reported that mesenchymal stem cell (MSC) therapy has beneficial effects in experimental models of sepsis. However, this finding remains inconclusive. This study was performed to systematically determine the connection between MSC therapy and mortality in sepsis animal models by pooling and analyzing data from newly published studies.

Methods

A detailed search of related studies from 2009 to 2019 was conducted in four databases, including MEDLINE, EMBASE, Cochrane Library, and Web of Science. After browsing and filtering out articles that met the inclusion criteria for statistical analysis, the inverse variance method of the fixed effects model was used to calculate the pooled odds ratios (ORs) and their 95% confidence intervals (CIs).

Results

Twenty-nine animal studies, including 1266 animals, were identified. None of the studies was judged to have a low risk of bias. The meta-analysis demonstrated that MSC therapy was related to a significantly lower mortality rate (OR 0.29, 95% CI 0.22–0.38, P < 0.001). Subgroup analyses performed based on the MSC injection dose (< 1.0 × 106 cells, OR = 0.33, 95% CI 0.20–0.56, P < 0.001; 1.0 × 106 cells, OR = 0.24, 95% CI 0.16–0.35, P < 0.001) and injection time (< 1 h, OR = 0.24, 95% CI 0.13–0.45, P < 0.001; 1 h, OR = 0.28, 95% CI 0.17–0.46, P < 0.001) demonstrated that treatment with MSCs significantly reduced the mortality rate of animals with sepsis.

Conclusion

This up-to-date meta-analysis showed a connection between MSC therapy and lower mortality in sepsis animal models, supporting the potential therapeutic effect of MSC treatment in future clinical trials. The results in this study contradict a previous meta-analysis with regards to the ideal dose of MSC therapy. Thus, further research is required to support these findings.
Low-intensity pulsed ultrasound upregulates osteogenesis under inflammatory conditions in periodontal ligament stem cells through unfolded protein response
Authors: Li Han , Deng Yuejia , Tan Minmin , Feng Ge , Kuang Yunchun , Li Jie , Song Jinlin
Published: June 2020

Background

In periodontal tissue engineering, periodontal ligament stem cells derived from patients with periodontitis (P-PDLSCs) are among the most promising and accessible stem cells for repairing disrupted alveolar bone and other connective tissues around the teeth. However, the inflammatory environment influences the osteogenic differentiation ability of P-PDLSCs. We examined low-intensity pulsed ultrasound (LIPUS) in P-PDLSCs in vitro and in rats with experimental periodontitis to determine whether LIPUS can enhance the osteogenic differentiation of stem cells.

Materials and methods

P-PDLSCs were harvested and isolated from the periodontal tissues around the teeth of periodontitis patients, and healthy PDLSCs (H-PDLSCs) were obtained from tissues around healthy teeth. After validation by flow cytometry analysis, the P-PDLSCs were cultured in osteogenic medium either pretreated with the endoplasmic reticulum stress (ERS) inhibitor 4-phenyl butyric acid (4-PBA) or not pretreated and then treated with or without LIPUS (90 mW/cm2, 1.5 MHz) for 30 min per day. Cell viability, ERS marker expression, and osteogenic potential were determined between the different treatment groups. LPS-induced H-PDLSCs were used to mimic the inflammatory environment. In addition, we established a model of experimental periodontitis in rats and used LIPUS and 4-PBA as treatment methods. Then, the maxillary bone was collected, and micro-CT and histology staining methods were used to detect the absorption of alveolar bone.

Results

Our data showed that the P-PDLSCs derived from periodontitis tissues were in a more pronounced ERS state than were the H-PDLSCs, which resulted in the former being associated with increased inflammation and decreased osteogenic ability. LIPUS can alleviate ERS and inflammation while increasing the bone formation capacity of P-PDLSCs in vivo and in vitro.

Conclusions

LIPUS may be an effective method to enhance the outcome of periodontal tissue engineering treatments of periodontitis by suppressing inflammation and increasing the osteogenic differentiation of P-PDLSCs through the unfolded protein response pathway, and more detailed studies are needed in the future.
Characterization of deltamethrin degradation and metabolic pathway by co-culture of Acinetobacter junii LH-1-1 and Klebsiella pneumoniae BPBA052
Authors: Tang Jie , Hu Qiong , Lei Dan , Wu Min , Zeng Chaoyi , Zhang Qing
Published: June 2020

Deltamethrin and its major metabolite 3‐phenoxybenzoic acid (3‐PBA) have caused serious threat to the environment as well as human health, yet little is known about their degradation pathways by bacterial co-cultures. In this study, the growth and degradation kinetics of Acinetobacter junii LH-1-1 and Klebsiella pneumoniae BPBA052 during deltamethrin and 3-PBA degradation were established, respectively. When the inoculum proportion of the strains LH-1-1 and BPBA052 was 7.5:2.5, and LH-1-1 was inoculated 24 h before inoculation of strain BPBA052, 94.25% deltamethrin was degraded and 9.16 mg/L of 3-PBA remained within 72 h, which was 20.36% higher and 10.25 mg/L lesser than that in monoculture of LH-1-1, respectively. And the half-life of deltamethrin was shortened from 38.40 h to 24.58 h. Based on gas chromatography–mass spectrometry, 3-phenoxybenzaldehyde, 1,2-benzenedicarboxylic butyl dacyl ester, and phenol were identified as metabolites during deltamethrin degradation in co-culture. This is the first time that a co-culture degradation pathway of deltamethrin has been proposed based on these identified metabolites. Bioremediation of deltamethrin-contaminated soils with co-culture of strains LH-1-1 and BPBA052 significantly enhanced deltamethrin degradation and 3-PBA removal. This study provides a platform for further studies on deltamethrin and 3-PBA biodegradation mechanism in co-culture, and it also proposes a promising approach for efficient bioremediation of environment contaminated by pyrethroid pesticides and their associated metabolites.
Mapping evidence of young people’s experiences of sexual aggression in the United Kingdom: A systematic scoping review protocol
Authors: Mulqueeny Delarise Maud , Roberts Jennifer , Nkabini Senzelokuhle Mpumelelo
Published: June 2020

Background

According to the UK’s Office for National Statistics, England and Wales reported a 2.9% increase in sexual aggression cases (3.4 million females and 631,000 males) between 2009 and 2019. In Scotland, sexual aggression cases increased by 66%, with 40% of these sexual violations being perpetrated on individuals under the age of 18 years, while incidents relating to sexual misconduct in Northern Ireland increased by 21.0%, with only 41.2% of those cases being prosecuted. Acts of sexual aggression can have physical, emotional and mental consequences which predispose young people to subsequent short- and long-term mental and social disorders and comorbidities. Such consequences include feelings of guilt, shame, anger, experiencing post-traumatic stress disorders, antisocial behaviour, alcohol and drug misuse and dependency, confusion surrounding sexuality and sexually transmitted illnesses including the human immuno-deficiency virus. However, despite the societal, health, economic and educational implications for young people in the UK and increasing statistics, few studies address this scourge. Hence, the objective is to systematically map evidence of young people’s experiences of sexual aggression in the UK and identify literature gaps that could inform future research.

Methods

The included literature for this scoping review is published peer-reviewed articles of all research designs; grey literature including governmental reports, policy statements, conference and media reports; and unpublished theses. Electronic searches of databases and search engines such as Embase, Google, Google Scholar, EBSCOhost, CINAHL, PubMed, Education Resources Information Centre (ERIC), PsycInfo, World Health Organization (WHO), media organizations, governmental and education departments and higher learning websites for published literature. Additional searches will include screening citations in reference lists of articles and perusing “Cited by” logs. All retrieved literature will be exported to an Endnote X9.2 library. Duplicate documents will be deleted prior to title screening commencing. An adapted Mixed Method Appraisal Tool (MMAT) will be independently used by two reviewers to ensure a rigorous study and quality assessment of all included studies.

Discussion

This scoping review employs a mixed-method approach to map and select relevant literature and summarize and report on young people’s experiences of sexual aggression in the UK. Once the data is summarized, it could inform planning and policy pertaining to a safe and effective sexual health curriculum for all young people, assist with the development of effective strategies to reduce sexual aggression and guide future research.
Correction to: Social determinants of overweight and obesity in the mother-child binomial: evidences from Mexico
Authors: Arredondo Armando , Torres Christian , Orozco Emanuel , Resendiz Oscar
Published: June 2020

An amendment to this paper has been published and can be accessed via the original article.