bluuebunny/crossref_metadata_2025 huggingface dataset:
Management of penicillin allergy in primary care: a qualitative study with patients and primary care physicians
Authors: Wanat Marta , Anthierens Sibyl , Butler Christopher C. , Savic Louise , Savic Sinisa , Pavitt Sue H. , Sandoe Jonathan A. T. , Tonkin-Crine Sarah
Published: June 2021

Background

Six percent of patients are allergic to penicillin according to their medical records. While this designation protects a small number of truly allergic patients from serious reactions, those who are incorrectly labelled may be denied access to recommended first line treatment for many infections. Removal of incorrect penicillin allergy may have positive health consequences for the individual and the general population.

We aimed to explore primary care physicians’ (PCPs) and patients’ views and understanding of penicillin allergy with a focus on clinical management of infections in the face of a penicillin allergy record.

Methods

We conducted an interview study with 31 patients with a penicillin allergy record, and 19 PCPs in the North of England. Data were analysed thematically.

Results

Patients made sense of their allergy status by considering the timing and severity of symptoms. Diagnosis of penicillin allergy was reported to be ‘imperfect’ with PCPs relying on patient reports and incomplete medical records. PCPs and patients often suspected that an allergy record was incorrect, but PCPs were reluctant to change records. PCPs had limited knowledge of allergy services. PCPs often prescribed alternative antibiotics which were easy to identify. Both patients and PCPs differed in the extent to which they were aware of the negative consequences of incorrect penicillin allergy records, their relevance and importance to their lives, and management of penicillin allergy.

Conclusions

PCPs and patients appear insufficiently aware of potential harms associated with incorrect penicillin allergy records. Some of the problems experienced by PCPs could be reduced by ensuring the details of newly diagnosed reactions to antibiotics are clearly documented. In order for PCPs to overturn more incorrect penicillin records through appropriate use of allergy services, more information and training about these services will be needed.
Is therapeutic inertia present in hyperglycaemia, hypertension and hypercholesterolaemia management among adults with type 2 diabetes in three health clinics in Malaysia? a retrospective cohort study
Authors: Chew Boon-How , Hussain Husni , Supian Ziti Akthar
Published: June 2021

Background

Good-quality evidence has shown that early glycaemic, blood pressure and LDL-cholesterol control in people with type 2 diabetes (T2D) leads to better outcomes. In spite of that, diseases control have been inadequate globally, and therapeutic inertia could be one of the main cause. Evidence on therapeutic inertia has been lacking at primary care setting. This retrospective cohort study aimed to determine the proportions of therapeutic inertia when treatment targets of HbA1c, blood pressure and LDL-cholesterol were not achieved in adults with T2D at three public health clinics in Malaysia.

Methods

The index prescriptions were those that when the annual blood tests were reviewed. Prescriptions of medication were verified, compared to the preceding prescriptions and classified as 1) no change, 2) stepping up and 3) stepping down. The treatment targets were HbA1c < 7.0% (53 mmol/mol), blood pressure (BP) < 140/90 mmHg and LDL-cholesterol < 2.6 mmol/L. Therapeutic inertia was defined as no change in the medication use in the present of not reaching the treatment targets. Descriptive, univariable, multivariable logistic regression and sensitive analyses were conducted.

Results

A total of 552 cohorts were available for the assessment of therapeutic inertia (78.9% completion rate). The mean (SD) age and diabetes duration were 60.0 (9.9) years and 5.0 (6.0) years, respectively. High therapeutic inertia were observed in oral anti-diabetic (61–72%), anti-hypertensive (34–65%) and lipid-lowering therapies (56–77%), and lesser in insulin (34–52%). Insulin therapeutic inertia was more likely among those with shorter diabetes duration (adjusted OR 0.9, 95% CI 0.87, 0.98). Those who did not achieve treatment targets were less likely to experience therapeutic inertia: HbA1c ≥ 7.0%: adjusted OR 0.10 (0.04, 0.24); BP ≥ 140/90 mmHg: 0.28 (0.16, 0.50); LDL-cholesterol ≥ 2.6 mmol/L: 0.37 (0.22, 0.64).

Conclusions

Although therapeutic intensifications were more likely in the presence of non-achieved treatment targets but the proportions of therapeutic inertia were high. Possible causes of therapeutic inertia were less of the physician behaviours but might be more of patient-related non-adherence or non-availability of the oral medications. These observations require urgent identification and rectification to improve disease control, avoiding detrimental health implications and costly consequences.

Trial registration

Number NCT02730754, April 6, 2016.
Efficacy and safety analysis of dexamethasone-lipiodol emulsion in prevention of post-embolization syndrome after TACE: a retrospective analysis
Authors: Lu Haohao , Zheng Chuansheng , Liang Bin , Xiong Bin
Published: June 2021

Background

To investigate the efficacy and safety of dexamethasone-lipiodol emulsion in the prevention of post-embolization syndrome after TACE.

Method

The data of 255 patients who underwent TACE in the interventional department from June 2017 to June 2020 were collected. This is a retrospective assessment of patients who were non-randomly treated with dexamethasone in TACE. The patients were divided into two groups: TACE using lipiodol + chemotherapeutic emulsion group (TACE group, N = 133); TACE using lipiodol + dexamethasone + chemotherapeutic emulsion group (TACE + dexamethasone group, N = 122). Primary study endpoint: incidence of abdominal pain, fever, nausea and vomiting 0–72 h after TACE in both groups. Secondary study endpoints: incidence of infection after TACE in both groups.

Results

Incidence of post-embolization syndrome after TACE (TACE group vs TACE + dexamethasone group): abdominal pain, 55.6% versus 36.1% (P value 0.002); fever, 37.6% versus 13.1% (P value 0.000); nausea, 60.9% versus 41.0% (P value 0.001); vomiting, 48.1% versus 21.3% (P value 0.000). Incidence of infection after TACE (TACE group vs TACE + dexamethasone group): 1.5% versus 2.5% (P value 0.583).

Conclusion

The lipiodol + dexamethasone emulsion can significantly reduce the incidence rate of post-embolization syndrome after TACE, with exact effect and high safety.
Inequities in childhood immunisation coverage associated with socioeconomic, geographic, maternal, child, and place of birth characteristics in Kenya
Authors: Allan Simon , Adetifa Ifedayo M. O. , Abbas Kaja
Published: June 2021

Background

The global Immunisation Agenda 2030 highlights coverage and equity as a strategic priority goal to reach high equitable immunisation coverage at national levels and in all districts. We estimated inequities in full immunisation coverage associated with socioeconomic, geographic, maternal, child, and place of birth characteristics among children aged 12–23 months in Kenya.

Methods

We analysed full immunisation coverage (1-dose BCG, 3-dose DTP-HepB-Hib (diphtheria, tetanus, pertussis, hepatitis B and Haemophilus influenzae type B), 3-dose polio, 1-dose measles, and 3-dose pneumococcal vaccines) of 3943 children aged 12–23 months from the 2014 Kenya Demographic and Health Survey. We disaggregated mean coverage by socioeconomic (household wealth, religion, ethnicity), geographic (place of residence, province), maternal (maternal age at birth, maternal education, maternal marital status, maternal household head status), child (sex of child, birth order), and place of birth characteristics, and estimated inequities in full immunisation coverage using bivariate and multivariate logistic regression.

Results

Immunisation coverage ranged from 82% [81–84] for the third dose of polio to 97.4% [96.7–98.2] for the first dose of DTP-HepB-Hib, while full immunisation coverage was 68% [66–71] in 2014. After controlling for other background characteristics through multivariate logistic regression, children of mothers with primary school education or higher have at least 54% higher odds of being fully immunised compared to children of mothers with no education. Children born in clinical settings had 41% higher odds of being fully immunised compared to children born in home settings. Children in the Coast, Western, Central, and Eastern regions had at least 74% higher odds of being fully immunised compared to children in the North Eastern region, while children in urban areas had 26% lower odds of full immunisation compared to children in rural areas. Children in the middle and richer wealth quintile households were 43–57% more likely to have full immunisation coverage compared to children in the poorest wealth quintile households. Children who were sixth born or higher had 37% lower odds of full immunisation compared to first-born children.

Conclusions

Children of mothers with no education, born in home settings, in regions with limited health infrastructure, living in poorer households, and of higher birth order are associated with lower rates of full immunisation. Targeted programmes to reach under-immunised children in these subpopulations will lower the inequities in childhood immunisation coverage in Kenya.
Age related gene DST represents an independent prognostic factor for MYCN non-amplified neuroblastoma
Authors: Wang Haiwei , Wang Xinrui , Xu Liangpu , Zhang Ji , Cao Hua
Published: June 2021

Background

MYCN amplification and age are two critical prognostic factors of pediatric neuroblastoma. Previously, we had revealed the prognosis of MYCN target genes. However, the prognostic effects of age related genes in neuroblastoma are unclear.

Methods

The prognostic significance of age and MYCN amplification was determined through multivariate cox regression and Kaplan-Meier survival analysis. Genes differentially expressed in MYCN non-amplified younger neuroblastoma patients were identified using Therapeutically Applicable Research to Generate Effective Treatments (TARGET) and Gene Expression Omnibus (GEO) datasets. The prognostic effects of age related genes ALCAM, CACNA2D3, DST, EPB41L4A and KIF1B in pediatric neuroblastoma patients were determined by Kaplan-Meier survival.

Results

In a pediatric pan-cancer analysis, age was associated with the overall survival of pediatric B-lineage acute lymphoblastic leukemia, neuroblastoma and wilms tumor in TARGET dataset. Moreover, the prognostic effects of age in neuroblastoma were validated using two independent neuroblastoma cohorts. Furthermore, age and MYCN amplification were independent prognostic factors in pediatric neuroblastoma. Compared with MYCN non-amplified older neuroblastoma patients, MYCN non-amplified younger neuroblastoma patients had better clinical outcomes. ALCAM, CACNA2D3, DST, EPB41L4A and KIF1B were highly expressed in MYCN non-amplified younger neuroblastoma patients. And the higher expression levels of ALCAM, CACNA2D3, DST, EPB41L4A or KIF1B were associated with better prognosis of MYCN non-amplified neuroblastoma patients. DST was an independent prognostic factor in MYCN non-amplified neuroblastoma patients and MYCN non-amplified neuroblastoma younger patients with higher DST expression levels had the best clinical overall survival.

Conclusions

Age related gene DST was an independent prognostic factor in MYCN non-amplified neuroblastoma. MYCN non-amplified younger neuroblastoma patients with higher DST expression levels had the best clinical overall survival.
Clinical efficacy and therapeutic value of delayed surgery in patients with symptomatic old thoracolumbar fractures
Authors: Li Pan , Huang Yunfei , Liang Zhuowen , Gan Lu , Wei Bin , Ye Zhengxu , Li Mo , Luo Zhuojing
Published: June 2021

Background

To investigate the clinical efficacy and therapeutic value of posterior decompression reduction, bone grafting fusion, and internal fixation for treatment of symptomatic old thoracolumbar fractures.

Method

Retrospective analysis was conducted for 14 patients (9 men, 5 women; average age 40.1 years) with old thoracolumbar fractures who underwent posterior operation. American Spinal Injury Association (ASIA) scores were used to evaluate neurologic function. Vertebral body height, Cobb angle in the sagittal plane, spinal canal volume ratio (%) and bone graft fusion were analyzed by radiography and computed tomography on different follow-up times.

Results

Mean follow-up was 27.1 months (23–36 months). Of three patients with ASIA grade A, 2 had improved postoperative urination and defecation, although no classification change. Preoperative ASIA score for eight patients with incomplete injury was grade B; four patients recovered to grade C at final follow-up. Preoperative ASIA score was C in three patients, increased to D in two patients and returned to normal E in one patient. Preoperative results showed average injured vertebra height loss rate decreased from 50.4 to 8.9%; average Cobb angle on the sagittal plane recovered from 39.6 to 6.9°; and the average spinal canal volume ratio recovered from 33.8 to 5.9%. Bony fusion was achieved; local lumbago and leg pain were relieved to some extent. No patients exhibited loosening of the fracture treated by internal fixation, pseudoarthrosis, or other related serious complications.

Conclusion

Treatment of old thoracolumbar fractures by posterior decompression reduction, bone grafting fusion, and internal fixation can relieve spinal cord compression, improve neurologic function of some patients (ASIA grades B–C), effectively relieve pain, correct deformity, restore biomechanical stability, and significantly improve quality of life.
CCDC114, DNAI2 and TOP2A involves in the effects of tibolone treatment on postmenopausal endometrium
Authors: Lv Yanhua , Liu Yanqing , Wang Yueqiang , Kong Fanrong , Pang Qiuxiang , Hu Guirong
Published: June 2021

Background

This study aimed to explore the molecular mechanisms of tibolone treatment in postmenopausal women.

Methods

The gene set enrichment profile, GSE12446, which includes 9 human endometrial samples from postmenopausal women treated with tibolone (tibolone group) and 9 control samples (control group), was downloaded from GEO database for analysis. Differentially expressed genes (DEGs) in tibolone vs. control groups were identified and then used for function and pathway enrichment analysis. Protein–protein interaction (PPI) network and module analyses were also performed. Finally, drug–target interaction was predicted for genes in modules, and then were validated in Pubmed.

Results

A total of 238 up-regulated DEGs and 72 down-regulated DEGs were identified. These DEGs were mainly enriched in various biological processed and pathways, such as cilium movement (e.g., CCDC114 and DNAI2), calcium ion homeostasis, regulation of hormone levels and complement/coagulation cascades. PPI network contained 368 interactions and 166 genes, of which IGF1, DNALI1, CCDC114, TOP2A, DNAH5 and DNAI2 were the hue genes. A total of 96 drug–gene interactions were obtained, including 94 drugs and eight genes. TOP2A and HTR2B were found to be targets of 28 drugs and 38 drugs, respectively. Among the 94 obtained drugs, only 12 drugs were reported in studies, of which 7 drugs (e.g., epirubicin) were found to target TOP2A.

Conclusions

CCDC114 and DNAI2 might play important roles in tibolone-treated postmenopausal women via cilium movement function. TOP2A might be a crucial target of tibolone in endometrium of postmenopausal women.
Different clinical parameters inform epicardial fat thickness in pre- and post-menopausal women with obstructive sleep apnea
Authors: Zhang Yong , Wang Jian , Shui Wen , Zhang Zhenxia , Li Juan , Ma Jin
Published: June 2021

Background

Obstructive sleep apnea (OSA) is a sleep-related disorder with breathing difficulties. Previous studies revealed that epicardial fat thickness (EFT) correlates with OSA severity. Interestingly, female patients display a stronger EFT-OSA correlation than males. The purpose of this study is to investigate the relationship between EFT and different clinical characteristics in pre- and post-menopausal women diagnosed with OSA.

Methods

Patients diagnosed with OSA were divided into pre/early peri-menopausal (Group 1) and post/late peri-menopausal (Group 2) according to the menopause status. EFT was obtained from parasternal long-axis echocardiographic images. We also collected general clinical characteristics of patients involved in this study, and performed spearman correlation analysis to explore the correlations between EFT and the general clinical characteristics. We further applied Multiple stepwise linear regression analysis to explore the predictors for EFT in both groups.

Results

A total number of 23 and 59 patients were enrolled in Group 1 and Group 2 respectively. EFT in Group 2 was significantly higher than that of Group 1. In both groups, EFT was positively correlated with apnea–hypopnea index (AHI), percentage of total sleep time when blood oxygen saturation was less than 90% (T90), oxygen desaturation index (ODI) and glucose; while EFT was negatively correlated with mean and lowest SaO2 (oxygen saturation) levels. However, EFT was positively correlated with total cholesterol (TC) only in Group 1 and body mass index (BMI) only in Group2, respectively. Multiple stepwise linear regression analysis showed that AHI was independently associated with EFT in Group 1. However, both AHI and BMI were independent predictors of EFT in Group 2.

Conclusion

EFT was notably correlated with menopausal status in women with OSA. AHI was the independent predictor of EFT in women with OSA. BMI was the independent predictor of EFT in post/late peri-menopausal women with OSA.
Evaluation of a Mentor training program for midwives in two hospitals in Warsaw, Poland - a qualitative descriptive study
Authors: Stefaniak Małgorzata , Dmoch-Gajzlerska Ewa
Published: June 2021

Background

Mentoring is a recognized, but still underutilized strategy for effective clinical training of midwifery students. The success of formally recognized course-embedded mentoring depends on adequate preparation of clinical teacher to act as mentors and effective developing of their mentoring skills. The aim of this study was to evaluate a Mentor Training Program for midwives, the first of its kind in Poland.

Methods

Twenty-one midwives who completed a dedicated Mentor Training Program organized by the Medical University of Warsaw (12–14 June 2017) participated in this study. In Stage 1, 7 days prior to the training course, the participants completed an online questionnaire that identified their motivations and expectations. In Stage 2, they assessed the training program they had completed as well as described any perceived needs of further mentor training. Subsequently a qualitative study of the data was performed using content analysis.

Results

In Stage 1, the participants expressed their interest in the Mentor Training Program mostly expecting to develop skills allowing them to implement mentoring in clinical training of student midwives. They were aware of the potential benefits of mentoring for hands-on instruction on the wards and wanted to gain knowledge of this strategy. In Stage 2, the overall satisfaction with the program was high, but the participants assessed their preparedness to act as midwifery mentors as inadequate. The results suggest that the Mentor Training Program should be further refined and expanded while the outcomes need to be evaluated in more detail by both new mentors and their trainers over a longer period of time, possibly after the participants have gained actual experience of mentoring in the clinical setting.

Conclusion

The participants described the Mentor Training Program as innovative, valuable and largely meeting their expectations. They gained knowledge of the concept of mentoring and its potential application in clinical training of midwifery students in Poland. Future mentor training programs should be expanded with a greater focus on developing, strengthening and applying mentoring skills in the clinical setting.
Impact of the COVID-19 pandemic on UK medical school widening access schemes: disruption, support and a virtual student led initiative
Authors: Bligh Emily R , Courtney Ellie , Stirling Rebecca , Rajananthanan Asveny ,   Sheffield Neuroscience Society, Altaher Hibatallah , Thomas Joshua , Anim-Boadu Rebecca , Basiouni Doha , Kurz Julian , Floare Mara-Luciana , Nyamali Immanuelle O , Chan Young , Hussein Kawthar A , Whitfield Andrew , Nezhad Helia Ghahremani
Published: June 2021

Background

COVID-19 has disrupted medical education in the United Kingdom (UK). The pandemic may result in a long-term disproportionate negative impact to students applying to Medical School from a low-socioeconomic background. In addition, the upsurge in Medical School applications increases the likelihood of stricter University entry criteria over the coming years. There is no current research to determine how widening participation of Medicine to students from low-socioeconomic backgrounds can be improved virtually. The aim of this study is to establish the impact of COVID-19 on students enrolled in UK widening access schemes and the role of virtual student led initiatives in widening participation.

Methods

A voluntary online survey was distributed to UK Sixth Form students (N = 31) enrolled in a widening access scheme who attended Sheffield Neuroscience Society International Virtual Conference in February 2021. The event was free to attend. The five-domain survey consisted of questions determining demographics, career aspirations, impact of COVID-19, academic skillsets and an educational manipulation check.

Results

There were 30 pre-conference and 26 post-conference responses. 76.7 % had work experience cancelled due to COVID-19. A total of 36.7 % of participants reported participating in virtual work experience. ‘Observe GP’ and ‘Medic Mentor’ were each specified as attended virtual opportunities in 20 % of answers. Post conference, students felt significantly more confident in applying to Medical School (p = 0.008) and more prepared to undertake a presentation (p = 0.002). Educational manipulation check scores increased significantly (p = 0.003). 100 % of students felt inspired to do further CV building activities.

Conclusions

COVID-19 has negatively impacted pupils enrolled in UK Medical School widening access schemes. Virtual student led initiatives can instill confidence in delegates from low socio-economic backgrounds, increase their career knowledge and inspire them to take part in further CV building exercises. Both Medical Schools and medical students play a key role in widening participation. This study recommends Medical Schools promote access to virtual events, urge private and state schools to declare offered opportunities and act mindfully when determining student’s academic potential in the context of their socioeconomic and/or educational background.
The impact of guidelines on sterility precautions during indwelling urethral catheterization at two acute-care hospitals in Sweden - a descriptive survey
Authors: Kulbay Aysel , Joelsson-Alm Eva , Tammelin Ann
Published: June 2021

Background

To support a uniform and evidence-based practice for indwelling urinary catheterization in adults The European association of Urology Nurses (EAUN) published guidelines for this procedure in 2012. The Swedish national guidelines are based on the sterility precautions advocated by EAUN. Some hospitals have local guidelines with other requirements concerning sterility and leave to staff to decide how to perform the catheterization. The aim of this descriptive survey was to investigate the nurses´ self-reported sterility precautions during indwelling urethral catheterization at two acute-care hospitals, where the local guidelines differ in their sterility requirements. The study also aimed to analyze factors affecting conformity with sterility precautions in the EAUN-guidelines.

Methods

A structured questionnaire with questions concerning the participant, working conditions and performance of indwelling urethral catheterization was left to 931 nurses in two acute care hospitals. Chi-square test, Fisher’s exact test and Mann-Whitney U-test were used for descriptive statistics. Logistic regression was used to analyze variables associated with practicing the sterility precautions in the EAUN-guidelines.

Results

Answers were obtained from 852 persons (91.5%). Most of the participants called their insertion technique “non-sterile”. Regardless of designation of the technique the participants said that the indwelling urinary catheter (IUC) should be kept sterile during procedure. Despite that not everyone used sterile equipment to maintain sterility of the catheter. The nurses´ conformity with all the sterility precautions in the EAUN-guidelines were associated with working at departments for surgery and cardiology (OR 2.35, 95% CI 1.69–3.27), use of sterile set for catheterization (OR 2.06, 95% CI 1.42–2.97), use of sterile drapes for dressing on insertion area (OR 1.91, 95% CI 1.24–2.96) and using the term “sterile technique” for indwelling urethral catheterization (OR 1.64, 95% CI 1.11–2.43).

Conclusions

Only 55–74% of the nurses practiced one or more precautions that secured sterility of the IUC thus demonstrating a gap between the EAUN-guidelines and the actual performance. Adherence to the guidelines was associated with factors that facilitated an aseptic performance such as using a sterile set and sterile drapes.

Healthcare-settings should ensure education and skill training including measures to ensure that the IUC is kept sterile during insertion.
Registered nurses’ role experiences of caring for older stroke patients: a qualitative study
Authors: Cheng Wei , Tu Jiong , Shen Xiaoyan
Published: June 2021

Background

With China’s population ageing rapidly, stroke is becoming one of the major public health problems. Nurses are indispensable for caring for older patients with acute and convalescent stroke, and their working experiences are directly linked to the quality of care provided. The study aims to investigate registered nurses’ experiences of caring for older stroke patients.

Methods

A qualitative descriptive design was adopted. Data were collected via semi-structured interviews with 26 registered nurses about their lived experiences of caring for older stroke patients. Thematic analysis was used to analyze the data.

Results

Two main themes were identified. First, the nurses identified an obvious gap between their ideal role in elderly care and their actual practice. The unsatisfactory reality was linked to the practical difficulties they encountered in their working environment. Second, the nurses expressed conflicting feelings about caring for older stroke patients, displaying a sense of accomplishment, indifference, annoyance, and sympathy. Caring for older stroke patients also affects nurses psychologically and physically. The nurses were clear about their own roles and tried their best to meet the elderly people’s needs, yet they lack time and knowledge about caring for older stroke patients. The factors influencing their working experiences extend beyond the personal domain and are linked to the wider working environment.

Conclusions

Sustaining the nursing workforce and improving their working experiences are essential to meet the care needs of older people. Understanding nurses’ lived working experiences is the first step. At the individual level, nurse mangers should promote empathy, relieve anxiety about aging, and improve the job satisfaction and morale of nurses. At the institutional level, policymakers should make efforts to improve the nursing clinical practice environment, increase the geriatric nursing education and training, achieve a proper skill mix of the health workforce, and overall attract, prepare and sustain nurses regarding caring for older people in a rapidly aging society.
Functional differentiation related to decomposing complex carbohydrates of intestinal microbes between two wild zokor species based on 16SrRNA sequences
Authors: Zou Yao , Liang Nannan , Zhang Xuxin , Han Chongxuan , Nan Xiaoning
Published: June 2021

Background

The intestinal microbes in mammals play a key role in host metabolism and adaptation. As a subterranean rodent, zokor digs tunnels for foraging and mating. These digging activities of zokors increase the energy expenditure relative to their aboveground counterparts. However, relatively little is known regarding intestinal microbes of zokor and how they make full use of limited food resources underground for high energy requirements.

Results

Eospalax cansus and Eospalax rothschildi had distinct intestinal microbes. Although the composition of intestinal microbes is similar in two species, the proportion of bacterium are distinctly different between them. At phylum level, 11 phyla were shared between two species. Firmicutes and Bacteroidota were two dominant microbes in both of two species, while Eospalax cansus have a significantly high proportion of Firmicutes/Bacteroidota than that of Eospalax rothschildi. At genus level, norank_f_Muribaculaceae were dominant microbes in both of two zokor species. The relative abundance of 12 genera were significantly different between two species. Some bacterium including unclassified_f__Lachnospiraceae, Lachnospiraceae_NK4A136_group, Ruminococcus and Eubacterium_siraeum_group associated with cellulose degradation were significantly enriched in Eospalax cansus. Although alpha diversity was with no significant differences between Eospalax cansus and Eospalax rothschildi, the intestinal microbes between them are significant distinct in PCoA analysis. We have found that trapping location affected the alpha diversity values, while sex and body measurements had no effect on alpha diversity values. PICRUSt metagenome predictions revealed significant enrichment of microbial genes involved in carbohydrate metabolism in Eospalax cansus rather than Eospalax rothschildi.

Conclusions

Our results demonstrate that Eospalax cansus harbor a stronger ability of fermentation for dietary plants than Eospalax rothschildi. The stronger ability of fermentation and degradation of cellulose of intestinal microbes of Eospalax cansus may be a long-time adaptation to limited food resources underground.
The emerging role of circular RNAs in common solid malignant tumors in children
Authors: Yu Jiabin , Yang Li , Lu Hongting
Published: June 2021

Malignant tumors are one of the fatal diseases that threaten children’s physical and mental health and affect their development. Research has shown that the occurrence and development of malignant tumors are associated with the abnormal expression and regulation of genes. Circular RNAs (circRNAs) are noncoding RNAs that have a closed circular structure, with a relatively stable expression, and do not undergo exonuclease-mediated degradation readily. Recent studies have shown that circRNA plays an important role in the occurrence, metastasis, and invasion of solid malignant tumors (SMTs) in children. Thus, circRNA is being considered as a breakthrough in the treatment of SMTs in children. In this review, we describe the functions and mechanisms of circRNAs involved in SMTs in children oncogenesis, and summarize the roles of circRNAs in regulating cell proliferation, cell apoptotic death, the cell cycle, cell migrative and invasive ability, epithelial-mesenchymal transition (EMT), cancer stem cells and drug resistance in SMTs in children. In addition, we also discuss the role of circRNAs in the early diagnosis, pathological grading, targeted therapy, and prognosis evaluation of common SMTs in children. CircRNAs are likely to provide a novel direction in therapy in SMTs of children.
Type I IFN signaling limits hemorrhage-like disease after infection with Japanese encephalitis virus through modulating a prerequisite infection of CD11b+Ly-6C+ monocytes
Authors: Patil Ajit Mahadev , Choi Jin Young , Park Seong Ok , Uyangaa Erdenebelig , Kim Bumseok , Kim Koanhoi , Eo Seong Kug
Published: June 2021

Background

The crucial role of type I interferon (IFN-I, IFN-α/β) is well known to control central nervous system (CNS) neuroinflammation caused by neurotrophic flaviviruses such as Japanese encephalitis virus (JEV) and West Nile virus. However, an in-depth analysis of IFN-I signal-dependent cellular factors that govern CNS-restricted tropism in JEV infection in vivo remains to be elucidated.

Methods

Viral dissemination, tissue tropism, and cytokine production were examined in IFN-I signal-competent and -incompetent mice after JEV inoculation in tissues distal from the CNS such as the footpad. Bone marrow (BM) chimeric models were used for defining hematopoietic and tissue-resident cells in viral dissemination and tissue tropism.

Results

The paradoxical and interesting finding was that IFN-I signaling was essentially required for CNS neuroinflammation following JEV inoculation in distal footpad tissue. IFN-I signal-competent mice died after a prolonged neurological illness, but IFN-I signal-incompetent mice all succumbed without neurological signs. Rather, IFN-I signal-incompetent mice developed hemorrhage-like disease as evidenced by thrombocytopenia, functional injury of the liver and kidney, increased vascular leakage, and excessive cytokine production. This hemorrhage-like disease was closely associated with quick viral dissemination and impaired IFN-I innate responses before invasion of JEV into the CNS. Using bone marrow (BM) chimeric models, we found that intrinsic IFN-I signaling in tissue-resident cells in peripheral organs played a major role in inducing the hemorrhage-like disease because IFN-I signal-incompetent recipients of BM cells from IFN-I signal-competent mice showed enhanced viral dissemination, uncontrolled cytokine production, and increased vascular leakage. IFN-I signal-deficient hepatocytes and enterocytes were permissive to JEV replication with impaired induction of antiviral IFN-stimulated genes, and neuron cells derived from both IFN-I signal-competent and -incompetent mice were vulnerable to JEV replication. Finally, circulating CD11b+Ly-6C+ monocytes infiltrated into the distal tissues inoculated by JEV participated in quick viral dissemination to peripheral organs of IFN-I signal-incompetent mice at an early stage.

Conclusion

An IFN-I signal-dependent model is proposed to demonstrate how CD11b+Ly-6C+ monocytes are involved in restricting the tissue tropism of JEV to the CNS.
Cordycepin confers long-term neuroprotection via inhibiting neutrophil infiltration and neuroinflammation after traumatic brain injury
Authors: Wei Pengju , Wang Ke , Luo Chen , Huang Yichen , Misilimu Dilidaer , Wen Huimei , Jin Peng , Li Chuhua , Gong Ye , Gao Yanqin
Published: June 2021

Background

The secondary injury caused by traumatic brain injury (TBI), especially white matter injury (WMI), is highly sensitive to neuroinflammation, which further leads to unfavored long-term outcomes. Although the cross-talk between the three active events, immune cell infiltration, BBB breakdown, and proinflammatory microglial/macrophage polarization, plays a role in the vicious cycle, its mechanisms are not fully understood. It has been reported that cordycepin, an extract fromCordyceps militaris, can inhibit TBI-induced neuroinflammation although the long-term effects of cordycepin remain unknown. Here, we report our investigation of cordycepin’s long-term neuroprotective function and its underlying immunological mechanism.

Methods

TBI mice model was established with a controlled cortical impact (CCI) method. Cordycepin was intraperitoneally administered twice daily for a week. Neurological outcomes were assessed by behavioral tests, including grid walking test, cylinder test, wire hang test, and rotarod test. Immunofluorescence staining, transmission electron microscopy, and electrophysiology recording were employed to assess histological and functional lesions. Quantitative-PCR and flow cytometry were used to detect neuroinflammation. The tracers of Sulfo-NHS-biotin and Evans blue were assessed for the blood-brain barrier (BBB) leakage. Western blot and gelatin zymography were used to analyze protein activity or expression. Neutrophil depletion in vivo was performed via using Ly6G antibody intraperitoneal injection.

Results

Cordycepin administration ameliorated long-term neurological deficits and reduced neuronal tissue loss in TBI mice. Meanwhile, the long-term integrity of white matter was also preserved, which was revealed in multiple dimensions, such as morphology, histology, ultrastructure, and electrical conductivity. Cordycepin administration inhibited microglia/macrophage pro-inflammatory polarization and promoted anti-inflammatory polarization after TBI. BBB breach was attenuated by cordycepin administration at 3 days after TBI. Cordycepin suppressed the activities of MMP-2 and MMP-9 and the neutrophil infiltration at 3 days after TBI. Moreover, neutrophil depletion provided a cordycepin-like effect, and cordycepin administration united with neutrophil depletion did not show a benefit of superposition.

Conclusions

The long-term neuroprotective function of cordycepin via suppressing neutrophil infiltration after TBI, thereby preserving BBB integrity and changing microglia/macrophage polarization. These findings provide significant clinical potentials to improve the quality of life for TBI patients.
Anti-CD20 treatment effectively attenuates cortical pathology in a rat model of widespread cortical demyelination
Authors: Haindl Michaela T. , Üçal Muammer , Klaus Benjamin , Tögl Lennart , Dohrmann Jana , Adzemovic Milena Z. , Enzinger Christian , Hochmeister Sonja
Published: June 2021

Background

Cortical demyelination represents a prominent feature of the multiple sclerosis (MS) brain, especially in (late) progressive stages. We recently developed a new rat model that reassembles critical features of cortical pathology characteristic to progressive types of MS. In persons affected by MS, B-cell depleting anti-CD20 therapy proved successful in the relapsing remitting as well as the early progressive course of MS, with respect to reducing the relapse rate and number of newly formed lesions. However, if the development of cortical pathology can be prevented or at least slowed down is still not clear. The main goal of this study was thus to increase our understanding for the mode of action of B-cells and B-cell directed therapy on cortical lesions in our rat model.

Methods

For this purpose, we set up two separate experiments, with two different induction modes of B-cell depletion. Brain tissues were analyzed thoroughly using histology.

Results

We observed a marked reduction of cortical demyelination, microglial activation, astrocytic reaction, and apoptotic cell loss in anti-CD20 antibody treated groups. At the same time, we noted increased neuronal preservation compared to control groups, indicating a favorable impact of anti-CD20 therapy.

Conclusion

These findings might pave the way for further research on the mode of action of B-cells and therefore help to improve therapeutic options for progressive MS.
The LINC00922 aggravates ovarian cancer progression via sponging miR-361-3p
Authors: Wang Liping , Ren Chenchen , Xu Yajuan , Yang Li , Chen Yannan , Zhu Yuanhang
Published: June 2021

Background

Long noncoding RNA (lncRNA) LINC00922 has been reported to promote tumorigenesis of lung and breast cancer. However, the functions and mechanisms of LINC00922 in ovarian cancer (OC) remain unclarified. The current study aims to clarify the detailed functions and underlying mechanisms of LINC00922 in the progression of OC.

Methods

LINC00922 expression in OC tissues and cells was identified by a comprehensive strategy of data miming, computational biology and quantitative real-time polymerase chain reaction (RT-qPCR) experiment. In vitro CCK-8, wound healing, transwell invasion, western blotting and in vivo tumorigenesis assays LINC00922 were conducted to evaluate the functions of LINC00992. Subsequently, bioinformatics technology and dual luciferase reporter assay were performed to confirm the between miR-361-3p and LINC00922 or CLDN1. Finally, rescue experiments were performed to confirm whether LINC00922 effect functions of OC cells through regulation of miR-361-3p.

Results

LINC00922 was significantly upregulated in OC tissues and cell lines, which is significantly positively corelated with the poor prognosis of patients with OC. LINC00922 knockdown inhibited proliferation and tumorigenesis of OC cells in vitro and vivo. In addition, LINC00922 knockdown suppressed migration, invasion, and EMT of OC cells in vitro. Mechanically, LINC00922 could competitively bind with miR-361-3p to relieve the repressive effect of miR-361-3p on its target gene CLDN1 in OC cells. In addition, silencing miR-361-3p promoted OC cell proliferation, migration, invasion, EMT and Wnt/β-catenin signaling, while LINC00922 knockdown inhibited Wnt/β-catenin signaling by upregulating miR-361-3p. Rescue experiments revealed that LINC00922 knockdown inhibited OC cell proliferation, migration, invasion and EMT by regulating miR-361-3p.

Conclusion

This study suggested that LINC00922 could competitively bind with miR-361-3p to promote the CLDN1 expression and activate Wnt/β-catenin signaling in OC progression, which providing a promising therapeutically target for OC.
Photoactivation of TGFβ/SMAD signaling pathway ameliorates adult hippocampal neurogenesis in Alzheimer’s disease model
Authors: Wu Xiaolei , Shen Qi , Zhang Zhan , Zhang Di , Gu Ying , Xing Da
Published: June 2021

Background

Adult hippocampal neurogenesis (AHN) is restricted under the pathological conditions of neurodegenerative diseases, especially in Alzheimer’s disease (AD). The drop of AHN reduces neural circuit plasticity, resulting in the decrease of the generation of newborn neurons in dentate gyrus (DG), which makes it difficult to recover from learning/memory dysfunction in AD, therefore, it is imperative to find a therapeutic strategy to promote neurogenesis and clarify its underlying mechanism involved.

Methods

Amyloid precursor protein/presenilin 1 (APP/PS1) mice were treated with photobiomodulation therapy (PBMT) for 0.1 mW/mm2per day in the dark for 1 month (10 min for each day). The neural stem cells (NSCs) were isolated from hippocampus of APP/PS1 transgenic mice at E14, and the cells were treated with PBMT for 0.667 mW/mm2in the dark (5 min for each time).

Results

In this study, photobiomodulation therapy (PBMT) is found to promote AHN in APP/PS1 mice. The latent transforming growth factor-β1 (LTGFβ1) was activated in vitro and in vivo during PBMT-induced AHN, which promoted the differentiation of hippocampal APP/PS1 NSCs into newborn neurons. In particular, behavioral experiments showed that PBMT enhanced the spatial learning/memory ability of APP/PS1 mice. Mechanistically, PBMT-stimulated reactive oxygen species (ROS) activates TGFβ/Smad signaling pathway to increase the interaction of the transcription factors Smad2/3 with Smad4 and competitively reduce the association of Smad1/5/9 with Smad4, thereby significantly upregulating the expression of doublecortin (Dcx)/neuronal class-III β-tubulin (Tuj1) and downregulating the expression of glial fibrillary acidic protein (GFAP). These in vitro effects were abrogated when eliminating ROS. Furthermore, specific inhibition of TGFβ receptor I (TGFβR I) attenuates the DNA-binding efficiency of Smad2/3 to the Dcx promotor triggered by PBMT.

Conclusion

Our study demonstrates that PBMT, as a viable therapeutic strategy, directs the adult hippocampal APP/PS1 NSCs differentiate towards neurons, which has great potential value for ameliorating the drop of AHN in Alzheimer’s disease mice.
Parkinson’s disease–associated VPS35 mutant reduces mitochondrial membrane potential and impairs PINK1/Parkin-mediated mitophagy
Authors: Ma Kai Yu , Fokkens Michiel R. , Reggiori Fulvio , Mari Muriel , Verbeek Dineke S.
Published: June 2021

Background

Mitochondrial dysfunction plays a prominent role in the pathogenesis of Parkinson’s disease (PD), and several genes linked to familial PD, including PINK1 (encoding PTEN-induced putative kinase 1 [PINK1]) and PARK2 (encoding the E3 ubiquitin ligase Parkin), are directly involved in processes such as mitophagy that maintain mitochondrial health. The dominant p.D620N variant of vacuolar protein sorting 35 ortholog (VPS35) gene is also associated with familial PD but has not been functionally connected to PINK1 and PARK2.

Methods

To better mimic and study the patient situation, we used CRISPR-Cas9 to generate heterozygous human SH-SY5Y cells carrying the PD-associated D620N variant of VPS35. These cells were treated with a protonophore carbonyl cyanide m-chlorophenylhydrazone (CCCP) to induce the PINK1/Parkin-mediated mitophagy, which was assessed using biochemical and microscopy approaches.

Results

Mitochondria in the VPS35-D620N cells exhibited reduced mitochondrial membrane potential and appeared to already be damaged at steady state. As a result, the mitochondria of these cells were desensitized to the CCCP-induced collapse in mitochondrial potential, as they displayed altered fragmentation and were unable to accumulate PINK1 at their surface upon this insult. Consequently, Parkin recruitment to the cell surface was inhibited and initiation of the PINK1/Parkin-dependent mitophagy was impaired.

Conclusion

Our findings extend the pool of evidence that the p.D620N mutation of VPS35 causes mitochondrial dysfunction and suggest a converging pathogenic mechanism among VPS35, PINK1 and Parkin in PD.
Assessing the validity of an IAU General English Achievement Test through hybridizing differential item functioning and differential distractor functioning
Authors: Jamalzadeh Mehri , Lotfi Ahmad Reza , Rostami Masoud
Published: June 2021

The current study sought to examine the validity of a General English Achievement Test (GEAT), administered to university students in the fall semester of 2018–2019 academic year, by hybridizing differential information (DIF) and differential distractor function (DDF) analytical models. Using a purposive sampling method, from the target population of undergraduate students studying in different disciplines at Islamic Azad University (IAU), (Isfahan branch), a sample of 835 students taking GEAT were selected. The 60-item multiple-choice test comprised four sub-sections; namely, vocabulary, grammar, cloze test, and reading comprehension. The students’ test scores served as the targeted data and the validity of the test was examined through the application of Cochran-Mantel-Haenszel (CMH) and multinomial log-linear regression models for detecting DIF and DDF, respectively. To account for the assumption of uni-dimensionality, the test sub-sections were analyzed independently. Furthermore, the assumption of local independence was checked based on correlational analysis and no extreme values were observed. The results of the study identified five moderate-level DIF items and one DDF item signaling an adverse effect on test fairness due to the existing biased items. Notably, these findings may have important implications for both language policymakers and test developers.