bluuebunny/crossref_metadata_2025 huggingface dataset:
First identification and genotyping of Enterocytozoon bieneusi and Encephalitozoon spp. in pet rabbits in China
Authors: Deng Lei , Chai Yijun , Xiang Leiqiong , Wang Wuyou , Zhou Ziyao , Liu Haifeng , Zhong Zhijun , Fu Hualin , Peng Guangneng
Published: June 2020

Background

Microsporidia are common opportunistic parasites in humans and animals, including rabbits. However, only limited epidemiology data concern about the prevalence and molecular characterization of Enterocytozoon bieneusi and Encephalitozoon spp. in rabbits. This study is the first detection and genotyping of Microsporidia in pet rabbits in China.

Results

A total of 584 faecal specimens were collected from rabbits in pet shops from four cities in Sichuan province, China. The overall prevalence of microsporidia infection was 24.8% by nested PCR targeting the internal transcribed spacer (ITS) region of E. bieneusi and Encephalitozoon spp. respectively. E. bieneusi was the most common species (n = 90, 15.4%), followed by Encephalitozoon cuniculi (n = 34, 5.8%) and Encephalitozoon intestinalis (n = 16, 2.7%). Mixed infections (E. bieneusi and E. cuniculi) were detected in five another rabbits (0.9%). Statistically significant differences in the prevalence of microsporidia were observed among different cities (χ2 = 38.376, df = 3, P < 0.01) and the rabbits older than 1 year were more likely to harbour microsporidia infections (χ2 = 9.018, df = 2, P < 0.05). Eleven distinct genotypes of E. bieneusi were obtained, including five known (SC02, I, N, J, CHY1) and six novel genotypes (SCR01, SCR02, SCR04 to SCR07). SC02 was the most prevalent genotype in all tested cities (43.3%, 39/90). Phylogenetic analysis showed that these genotypes were clustered into group 1–3 and group 10. Meanwhile, two genotypes (I and II) were identified by sequence analysis of the ITS region of E. cuniculi.

Conclusion

To the best of our knowledge, this is the first report of microsporidia infection in pet rabbits in China. Genotype SC02 and four novel genotypes were classified into potential zoonotic group 1, suggesting that pet rabbits may cause microsporidiosis in humans through zoonotic transmissions. These findings provide preliminary reference data for monitoring microsporidia infections in pet rabbits and humans.
Predictive factors of severe coronavirus disease 2019 in previously healthy young adults: a single-center, retrospective study
Authors: Zhou Changzhi , Huang Zhe , Tan Weijun , Li Xueying , Yin Wen , Xiao Yang , Tao Zhaowu , Geng Shuang , Hu Yi
Published: June 2020

Background

Several previously healthy young adults have developed Coronavirus Disease 2019 (COVID-19), and a few of them progressed to the severe stage. However, the factors are not yet determined.

Method

We retrospectively analyzed 123 previously healthy young adults diagnosed with COVID-19 from January to March 2020 in a tertiary hospital in Wuhan. Patients were classified as having mild or severe COVID-19 based on their respiratory rate, SpO2, and PaO2/FiO2 levels. Patients’ symptoms, computer tomography (CT) images, preadmission drugs received, and the serum biochemical examination on admission were compared between the mild and severe groups. Significant variables were enrolled into logistic regression model to predict the factors affecting disease severity. A receiver operating characteristic (ROC) curve was applied to validate the predictive value of predictors.

Result

Age; temperature; anorexia; and white blood cell count, neutrophil percentage, platelet count, lymphocyte count, C-reactive protein, aspartate transaminase, creatine kinase, albumin, and fibrinogen values were significantly different between patients with mild and severe COVID-19 (P < 0.05). Logistic regression analysis confirmed that lymphopenia (P = 0.010) indicated severe prognosis in previously healthy young adults with COVID-19, with the area under the curve (AUC) was 0.791(95% Confidence Interval (CI) 0.704–0.877)(P < 0.001).

Conclusion

For previously healthy young adults with COVID-19, lymphopenia on admission can predict severe prognosis.
Indirect comparison of glucagon like peptide-1 receptor agonists regarding cardiovascular safety and mortality in patients with type 2 diabetes mellitus: network meta-analysis
Authors: Alfayez Osamah M. , Almohammed Omar A. , Alkhezi Omar S. , Almutairi Abdulaali R. , Al Yami Majed S.
Published: June 2020

Background

The cardiovascular outcome trials (CVOTs) have shown that glucagon like peptide-1 receptor agonists (GLP1RAs) have varying degrees of cardiovascular (CV) safety in patients with type 2 diabetes mellitus (T2DM.) The lack of any head-to-head comparative trials among GLP1RAs urged the need for an indirect comparison of these agents. Therefore, this study was conducted to indirectly compare the CV safety and mortality effects among different GLP1RAs in patients with T2DM using network meta-analysis (NMA).

Methods

Medline was searched to identify GLP1RA CVOTs to date. The outcomes of interest were CV death, myocardial infarction (IM), stroke, and death from any cause. An NMA with binomial likelihood logit link model was used for the binary outcomes. We conducted both fixed effects and random effects models for each outcome, and selected the best model based on the deviance information and the average posterior residual deviance. This NMA was reported in accordance with the preferred reporting items for systematic reviews and meta-analyses (PRISMA-NMA).

Results

A total of seven GLP1RA CVOTs were included having 56,004 patients. The NMA results showed that oral semaglutide was statistically better than exenatide (OR 0.47, 95% CI 0.21–0.99), dulaglutide (OR 0.46, 95% CI 0.20–0.97), albiglutide (OR 0.45, 95% CI 0.19–0.97), lixisenatide (OR 0.43, 95% CI 0.19–0.92) in reducing CV death events. No significant differences were detected between most of the treatments regarding reducing death from any cause, MI and stroke events. The ranking results showed that oral semaglutide had the highest probability to be ranked first (> 90%) in reducing CV death and death from any cause. Moreover, once weekly semaglutide had the highest probability to be ranked first in reducing MI and stroke events.

Conclusion

The GLP1RAs have shown significant benefits in terms of CV safety. The indirect comparison and ranking probability results have shown that one weekly semaglutide and oral semaglutide seems to be the preferred option in patients with T2DM and established or at high risk of CVD. This result can aid health care providers, pharmacy and therapeutics committees in hospitals, and insurance companies when deciding which GLP1RA to start or add to their formulary.
CircRNA DONSON contributes to cisplatin resistance in gastric cancer cells by regulating miR-802/BMI1 axis
Authors: Liu Yong , Xu Jianzhong , Jiang Min , Ni Lingna , Ling Yang
Published: June 2020

Background

Circular RNA downstream neighbor of SON (circDONSON) has been revealed to promote gastric cancer (GC) growth and invasion, while the role and molecular mechanism underlying circDONSON in GC cisplatin (DDP) resistance remain unclear.

Methods

Levels of circDONSON, microRNA (miR)-802, and B lymphoma Mo-MLV insertion region 1 (BMI1) mRNA were detected using quantitative real-time polymerase chain reaction. Cell viability and apoptosis were measured by cell counting kit-8 assay, colony formation assay and flow cytometry, respectively. Protein levels of BMI1, Cyclin D1, p27, Caspase-3 Cleavage and Caspase-9 Cleavage were determined by western blot. The interaction between miR-802 and circDONSON or BMI1 was confirmed by dual-luciferase reporter assay. In vivo experiments were conducted via the murine xenograft model.

Results

CircDONSON was elevated in GC tissues and cell lines, especially in DDP-resistant GC tissues and cells. Knockdown of circDONSON sensitized GC cells to DDP by inhibiting cell viability and promoting cell apoptosis in vitro. Further mechanism-related investigations suggested that circDONSON functioned as “sponge” by competing for miR-802 binding to modulate its target BMI1. Silencing miR-802 reversed the inhibition of DDP-resistance in GC cells induced by circDONSON down-regulation. Besides, miR-802 alleviated DDP resistance in GC cells by targeting BMI1. Functionally, circDONSON knockdown enhanced the cytotoxicity of DDP in GC in vivo.

Conclusion

Our findings demonstrated circDONSON promoted cisplatin resistance in gastric cancer cells by regulating miR-802/BMI1 axis, shedding light on the development of a novel therapeutic strategy to overcome chemoresistance in gastric cancer patients.
Patterns of human exposure to malaria vectors in Zanzibar and implications for malaria elimination efforts
Authors: Monroe April , Msaky Dickson , Kiware Samson , Tarimo Brian B. , Moore Sarah , Haji Khamis , Koenker Hannah , Harvey Steven , Finda Marceline , Ngowo Halfan , Mihayo Kimberly , Greer George , Ali Abdullah , Okumu Fredros
Published: June 2020

Background

Zanzibar provides a good case study for malaria elimination. The islands have experienced a dramatic reduction in malaria burden since the introduction of effective vector control interventions and case management. Malaria prevalence has now been maintained below 1% for the past decade and the islands can feasibly aim for elimination.

Methods

To better understand factors that may contribute to remaining low-level malaria transmission in Zanzibar, layered human behavioural and entomological research was conducted between December 2016 and December 2017 in 135 randomly selected households across six administrative wards. The study included: (1) household surveys, (2) structured household observations of nighttime activity and sleeping patterns, and (3) paired indoor and outdoor mosquito collections. Entomological and human behavioural data were integrated to provide weighted estimates of exposure to vector bites, accounting for proportions of people indoors or outdoors, and protected by insecticide-treated nets (ITNs) each hour of the night.

Results

Overall, 92% of female Anopheles mosquitoes were caught in the rainy season compared to 8% in the dry season and 72% were caught outdoors compared to 28% indoors. For individual ITN users, ITNs prevented an estimated two-thirds (66%) of exposure to vector bites and nearly three quarters (73%) of residual exposure was estimated to occur outdoors. Based on observed levels of ITN use in the study sites, the population-wide mean personal protection provided by ITNs was 42%.

Discussion/conclusions

This study identified gaps in malaria prevention in Zanzibar with results directly applicable for improving ongoing programme activities. While overall biting risk was low, the most notable finding was that current levels of ITN use are estimated to prevent less than half of exposure to malaria vector bites. Variation in ITN use across sites and seasons suggests that additional gains could be made through targeted social and behaviour change interventions. However, even for ITN users, gaps in protection remain, with a majority of exposure to vector bites occurring outdoors before going to sleep. Supplemental interventions targeting outdoor exposure to malaria vectors, and groups that may be at increased risk of exposure to malaria vectors, should be explored.
Coverage of community case management for malaria through CHWs: a quantitative assessment using primary household surveys of high-burden areas in Chhattisgarh state of India
Authors: Garg Samir , Gurung Preeti , Dewangan Mukesh , Nanda Prabodh
Published: June 2020

Background

Community Case Management of Malaria (CCMM) has been implemented through community health workers (CHWs) in many countries. Existing studies have shown that CHWs can be viable means of implementing CCMM. However, not many studies have examined the coverage under large-scale CCMM programmes. India is a big contributor to global malaria burden. Chhattisgarh is a leading state in India in terms of malaria incidence and mortality. CCMM was implemented on a large scale through the ‘mitanin’ CHWs in rural Chhattisgarh from 2015. Under CCMM, 37,696 CHWs in 84 high-burden administrative blocks of the state were trained and equipped with rapid diagnostic tests (RDT), artemisinin-based combination therapy (ACT) and chloroquine.

Methods

This descriptive quantitative study assesses coverage of CCMM in detection and treatment of Malaria over three rounds of household surveys—2015, 2016 and 2018. Household-interviews covered more than 15,000 individuals in each round, using multi-stage random sampling across the 84 blocks. The main objectives were to find out the coverage in identification and treatment of malaria and the share of CHWs in them. A 15-days recall was used to find out cases of fever and healthcare sought by them.

Results

In 2018, 62% of febrile cases in rural population contacted CHWs. RDT, ACT and chloroquine were available with 96%, 80% and 95% of CHWs, respectively. From 2015 to 2018, the share of CHWs in testing of febrile cases increased from 34 to 70%, while it increased from 28 to 69% in treatment of malaria cases. CHWs performed better than other providers in treatment-completion and administered medication under direct observation to 72% of cases they treated.

Conclusion

This study adds to one of the most crucial but relatively less reported area of CCMM programmes, i.e. the extent of coverage of the total febrile population by CHWs, which subsequently determines the actual coverage of case-management in malaria. Mitanin-CHWs achieved high coverage and treatment-completion rates that were rarely reported in context of large-scale CCMM elsewhere. Close to community, well-trained CHWs with sufficient supplies of rapid tests and anti-malarial drugs can play a key role in achieving the desired coverage in malaria-management.
A tale of two cities: the cost, price-differential and affordability of current and healthy diets in Sydney and Canberra, Australia
Authors: Lee Amanda J. , Kane Sarah , Herron Lisa-Maree , Matsuyama Misa , Lewis Meron
Published: June 2020

Background

The perception that healthy foods are more expensive than unhealthy foods has been reported widely to be a key barrier to healthy eating. However, assessment of the relative cost of healthy and unhealthy foods and diets is fraught methodologically. Standardised approaches to produce reliable data on the cost of total diets and different dietary patterns, rather than selected foods, are lacking globally to inform policy and practice.

Methods

This paper reports the first application, in randomly selected statistical areas stratified by socio-economic status in two Australian cities, of the Healthy Diets Australian Standardized Affordability and Pricing (ASAP) method protocols: diet pricing tools based on national nutrition survey data and dietary guidelines; store sampling and location; determination of household incomes; food price data collection; and analysis and reporting. The methods were developed by the International Network on Food and Obesity/NCD Research, Monitoring and Action Support (INFORMAS) as a prototype of an optimum approach to assess, compare and monitor the cost and affordability of diets across different geographical and socio-economic settings and times.

Results

Under current tax policy in Australia, healthy diets would be 15–17% less expensive than current (unhealthy) diets in all locations assessed. Nevertheless, healthy diets are likely to be unaffordable for low income households, costing more than 30% of disposable income in both cities surveyed. Households spent around 58% of their food budget on unhealthy food and drinks. Food costs were on average 4% higher in Canberra than Sydney, and tended to be higher in high socioeconomic locations.

Conclusions

Health and fiscal policy actions to increase affordability of healthy diets for low income households are required urgently. Also, there is a need to counter perceptions that current, unhealthy diets must be less expensive than healthy diets. The Healthy Diets ASAP methods could be adapted to assess the cost and affordability of healthy and unhealthy diets elsewhere.
MicroRNA-181a as novel liquid biopsy marker of central nervous system involvement in pediatric acute lymphoblastic leukemia
Authors: Egyed Bálint , Kutszegi Nóra , Sági Judit C. , Gézsi András , Rzepiel Andrea , Visnovitz Tamás , Lőrincz Péter , Müller Judit , Zombori Marianna , Szalai Csaba , Erdélyi Dániel J. , Kovács Gábor T. , Semsei Ágnes F.
Published: June 2020

Background

Refractory central nervous system (CNS) involvement is among the major causes of therapy failure in childhood acute leukemia. Applying contemporary diagnostic methods, CNS disease is often underdiagnosed. To explore more sensitive and less invasive CNS status indicators, we examined microRNA (miR) expressions and extracellular vesicle (EV) characteristics.

Methods

In an acute lymphoblastic leukemia (ALL) discovery cohort, 47 miRs were screened using Custom TaqMan Advanced Low-Density Array gene expression cards. As a validation step, a candidate miR family was further scrutinized with TaqMan Advanced miRNA Assays on serial cerebrospinal fluid (CSF), bone marrow (BM) and peripheral blood samples with different acute leukemia subtypes. Furthermore, small EV-rich fractions were isolated from CSF and the samples were processed for immunoelectron microscopy with anti-CD63 and anti-CD81 antibodies, simultaneously.

Results

Regarding the discovery study, principal component analysis identified the role of miR-181-family (miR-181a-5p, miR-181b-5p, miR-181c-5p) in clustering CNS-positive (CNS+) and CNS-negative (CNS‒) CSF samples. We were able to validate miR-181a expression differences: it was about 52 times higher in CSF samples of CNS+ ALL patients compared to CNS‒ cases (n = 8 vs. n = 10, ΔFC = 52.30, p = 1.5E−4), and CNS+ precursor B cell subgroup also had ninefold higher miR-181a levels in their BM (p = 0.04). The sensitivity of CSF miR-181a measurement in ALL highly exceeded those of conventional cytospin in the initial diagnosis of CNS leukemia (90% vs. 54.5%). Pellet resulting from ultracentrifugation of CNS+ CSF samples of ALL patients showed atypical CD63−/CD81− small EVs in high density by immunoelectron microscopy.

Conclusions

After validating in extensive cohorts, quantification of miR-181a or a specific EV subtype might provide novel tools to monitor CNS disease course and further adjust CNS-directed therapy in pediatric ALL.
Involvement of glutathione peroxidases in the occurrence and development of breast cancers
Authors: Zhang Man-Li , Wu Hua-Tao , Chen Wen-Jia , Xu Ya , Ye Qian-Qian , Shen Jia-Xin , Liu Jing
Published: June 2020

Glutathione peroxidases (GPxs) belong to a family of enzymes that is important in organisms; these enzymes promote hydrogen peroxide metabolism and protect cell membrane structure and function from oxidative damage. Based on the establishment and development of the theory of the pathological roles of free radicals, the role of GPxs has gradually attracted researchers’ attention, and the involvement of GPxs in the occurrence and development of malignant tumors has been shown. On the other hand, the incidence of breast cancer in increasing, and breast cancer has become the leading cause of cancer-related death in females worldwide; breast cancer is thought to be related to the increased production of reactive oxygen species, indicating the involvement of GPxs in these processes. Therefore, this article focused on the molecular mechanism and function of GPxs in the occurrence and development of breast cancer to understand their role in breast cancer and to provide a new theoretical basis for the treatment of breast cancer.
Modelling HIV disease process and progression in seroconversion among South Africa women: using transition-specific parametric multi-state model
Authors: Dessie Zelalem G. , Zewotir Temesgen , Mwambi Henry , North Delia
Published: June 2020

Background

HIV infected patients may experience many intermediate events including between-event transition throughout their follow up. Through modelling these transitions, we can gain a deeper understanding of HIV disease process and progression and of factors that influence the disease process and progression pathway. In this work, we present transition-specific parametric multi-state models to describe HIV disease process and progression.

Methods

The data is from an ongoing prospective cohort study conducted amongst adult women who were HIV-infected in KwaZulu-Natal, South Africa. Participants were enrolled during the acute HIV infection phase and then followed up during chronic infection, up to ART initiation.

Results

Transition specific distributions for multi-state models, including a variety of accelerated failure time (AFT) models and proportional hazards (PH) models, were presented and compared in this study. The analysis revealed that women enrolling with a CD4 count less than 350 cells/mm3(severe and advanced disease stages) had a far lower chance of immune recovery, and a considerably higher chance of immune deterioration, compared to women enrolling with a CD4 count of 350 cells/mm3or more (normal and mild disease stages). Our analyses also showed that older age, higher educational levels, higher scores for red blood cell counts, higher mononuclear scores, higher granulocytes scores, and higher physical health scores, all had a significant effect on a shortened time to immunological recovery, while women with many sex partners, higher viral load and larger family size had a significant effect on accelerating time to immune deterioration.

Conclusion

Multi-state modelling of transition-specific distributions offers a flexible tool for the study of demographic and clinical characteristics’ effects on the entire disease progression pathway. It is hoped that the article will help applied researchers to familiarize themselves with the models, including interpretation of results.
Comparison of pathological clotting using haematological, functional and morphological investigations in HIV-positive and HIV-negative patients with deep vein thrombosis
Authors: Jackson Brandon S. , Nunes Goncalves Julien , Pretorius Etheresia
Published: June 2020

Background

Patients infected with the human immunodeficiency virus (HIV) are more prone to systemic inflammation and pathological clotting, and many may develop deep vein thrombosis (DVT) as a result of this dysregulated inflammatory profile. Coagulation tests are not routinely performed unless there is a specific reason.

Methods

We recruited ten healthy control subjects, 35 HIV negative patients with deep vein thrombosis (HIV negative-DVT), and 13 HIV patients with DVT (HIV positive-DVT) on the primary antiretroviral therapy (ARV) regimen-emtricitabine, tenofovir and efavirenz. Serum inflammatory markers, haematological results, viscoelastic properties using thromboelastography (TEG) and scanning electron microscopy (SEM) of whole blood (WB) were used to compare the groups.

Results

The DVT patients (HIV positive and HIV negative) had raised inflammatory markers. The HIV positive-DVT group had anaemia in keeping with anaemia of chronic disorders. DVT patients had a hypercoagulable profile on the TEG but no significant difference between HIV negative-DVT and HIV positive-DVT groups. The TEG analysis compared well and supported our ultrastructural results. Scanning electron microscopy of DVT patient’s red blood cells (RBCs) and platelets demonstrated inflammatory changes including abnormal cell shapes, irregular membranes and microparticle formation. All the ultrastructural changes were more prominent in the HIV positive-DVT patients.

Conclusions

Although there were trends that HIV-positive patients were more hypercoagulable on functional tests (viscoelastic profile) compared to HIV-negative patients, there were no significant differences between the 2 groups. The sample size was, however, small in number. Morphologically there were inflammatory changes in patients with DVT. These ultrastructural changes, specifically with regard to platelets, appear more pronounced in HIV-positive patients which may contribute to increased risk for hypercoagulability and deep vein thrombosis.
Food insecurity and the risk of depression in people living with HIV/AIDS: a systematic review and meta-analysis
Authors: Ayano Getinet , Tsegay Light , Solomon Melat
Published: June 2020

Background

The link between food insecurity and depression in people living with HIV/AIDS (PLWHA) has been explored in numerous studies; however, the existing evidence is inconclusive due to inconsistent results. Therefore, the objective of this systematic review and meta-analysis is to examine the relationship between food insecurity and depression in PLWHA.

Methods

We systematically searched PubMed, EMBASE, and Scopus to identify relevant studies. A random-effect model was used for conducting the meta-analysis. We assessed the risk of publication bias by funnel plot and Egger’s regression asymmetry test.

Results

In this review, seven studies were included in the final analysis. Our meta-analysis revealed that food insecurity significantly increased the risk of depression in PLWHA [RR 2.28 (95% CI 1.56–3.32)]. This association remained significant after adjusting for the confounding effects of drug use [RR 1.63 (95% CI 1.27–2.10)], social support [RR 2.21 (95% CI 1.18–4.16)] as well as ART drugs [RR 1.96 (95% CI 1.17–3.28)]. Our subgroup and sensitivity confirmed the robustness of the main analysis.

Conclusion

This systematic review and meta-analysis suggest a significant association between food insecurity and increased risk of depression PLWHA. Therefore, early screening and management of food insecurity in PLWHA seem to be necessary.
Association of LIN28B polymorphisms with chronic hepatitis B virus infection
Authors: Han Qunying , Sang Jiao , Fan Xiude , Wang Xiaoyun , Zeng Lu , Zhang Xiaoge , Zhang Kun , Li Na , Lv Yi , Liu Zhengwen
Published: June 2020

Background

LIN28B is involved in multiple cellular developmental processes, tissue inflammatory response and tumourigenesis. The association of LIN28B polymorphisms with hepatitis B virus (HBV) infection remains unknown.

Methods

This study investigated the association of LIN28B rs314277, rs314280, rs369065 and rs7759938 polymorphisms in patients with chronic HBV infection, a major cause of liver disease including hepatocellular carcinoma (HCC). A total of 781 individuals including 515 cases of chronic HBV infection (91 asymptomatic carrier status, 128 chronic hepatitis, 127 cirrhosis and 169 HCC), 97 HBV infection resolvers and 169 healthy controls were investigated.

Results

LIN28 rs314280 genotypes GA + AA were higher in resolver and controls than patients (P = 0.011). Patients had significantly lower rs314280 allele A than resolvers (P = 0.031, OR 0.689, 95%CI 0.491–0.969) or controls (P = 0.034, OR 0.741, 95%CI 0.561–0.978). In dominant model, patients had significantly lower rs314280 genotypes AA+GA than controls (P = 0.008, OR 0.623, 95%CI 0.439–0.884). LIN28 rs7759938 genotypes TC + CC were higher in resolvers and controls than patients (P = 0.015). Patients had significantly lower rs7759938 allele C than resolvers (P = 0.048, OR 0.708, 95%CI 0.503–0.999). In dominant model, patients had significantly lower rs7759938 genotypes TC + CC than controls (P = 0.010, OR 0.632, 95%CI 0.445–0.897). Chronic hepatitis patients had lower frequency of rs369065 genotype TC than asymptomatic carriers, cirrhosis and HCC (P = 0.019).

Conclusions

These results suggest that LIN28 rs314280 and rs7759938 may be related to the susceptibility of chronic HBV infection. Further studies are warranted to examine the association of LIN28B polymorphisms with HBV-related diseases, especially HCC.
Outcomes in patients with lacrimal gland carcinoma treated with definitive radiotherapy or eye-sparing surgery followed by adjuvant radiotherapy
Authors: Lin Yun-Hsuan , Huang Shih-Ming , Yap Wing-Keen , Yang Ju-Wen , Yeung Ling , Tsan Din-Li , Chang Joseph Tung-Chieh , Chen Lung-Chien
Published: June 2020

Background

The optimal treatment for lacrimal gland cancer remains unclear. Eye-preserving surgery, as opposed to exenteration, followed by adjuvant radiotherapy (RT), has recently been reported to deliver satisfactory outcomes, but evidence is sparse. The aim of the present study was to evaluate outcomes in patients with lacrimal gland cancer treated at two tertiary medical centers.

Methods

We retrospectively examined data from patients with lacrimal gland cancer who had received eye-preserving surgical treatment followed by adjuvant RT with or without chemotherapy, or (if the tumor was inoperable) needle biopsy with definitive RT with or without chemotherapy. Baseline clinical and pathological characteristics were considered. Outcomes of interest included post-treatment complications, overall survival (OS), locoregional progression-free survival (LPFS), and distant metastasis-free survival (DMFS).

Results

Eighteen patients were included. Two-year OS, LPFS, and DMFS rates were 69.0, 76.7, and 71.4%, respectively. Patients with early-stage (T1–T2) lacrimal gland cancer had significantly better outcomes than those with advanced-stage disease (T3–T4). Two-year OS, LPFS, and DMFS rates were each 100% in patients with disease stages T1–T2, and 37.5, 50, and 37.5%, respectively, in those with disease stages T3–T4 (P < 0.05). Orbital complications were well tolerated.

Conclusions

Eye-sparing surgery with adjuvant RT can achieve satisfactory results in patients with T1–T2 lacrimal gland carcinoma. Disease stage T3 and above was associated with poor outcomes even with post-operative RT, likely due to distant metastasis. Adding neoadjuvant chemotherapy or adjuvant chemotherapy to current treatment strategies might be a suitable choice for this group of patients.
The utility of 18F-FDG PET and PET/CT in the diagnosis and staging of chondrosarcoma: a meta-analysis
Authors: Zhang Qingyu , Xi Yongming , Li Dong , Yuan Zenong , Dong Jun
Published: June 2020

Objective

Chondrosarcoma is the second most common primary bone sarcoma; however, unlike other tumors, the biopsy cannot easily make a definite diagnosis or predict the histological grade. This meta-analysis was performed to evaluate the utility of 18F-FDG PET and PET/CT to differentiate chondrosarcoma from benign cartilaginous lesions and to predict the histopathological grade of chondrosarcoma.

Material and methods

A comprehensive search was performed in three electronic databases including Medline/PubMed, the Cochrane Library and Embase to retrieve diagnostic studies evaluating the role of 18F-FDG PET or PET/CT for appraising the status of chondrosarcoma. Reference lists of related articles were also scrutinized manually. Useful data were extracted to calculate the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), the summary receiver operating characteristic curve (sROC), and the area under the curve (AUC) of 18F-FDG PET or PET/CT in diagnosing chondrosarcoma, and pooled weighted mean differences (WMD) of maximum standardized uptake value (SUVmax) between different entities of cartilaginous neoplasms by using Stata 19.0.

Results

A total of twelve studies provided sufficient data for the quantitative analysis. For the diagnosis of chondrosarcoma, the pooled sensitivity, specificity, and DOR of 18F-FDG PET were 0.84 (95% confidence interval [CI] 0.46 to 0.97), 0.82 (95% CI 0.55 to 0.94), and 24.244 (95% CI 1.985 to 96.148), respectively while those of 18F-FDG PET/CT were 0.94 (95% CI 0.86 to 0.97), 0.89 (95% CI 0.82 to 0.93), and 112.999 (95% CI 41.341 to 308.866), respectively. The pooled WMD of SUVmax were − 0.89 (95% CI −1.67 to −0.10) between benign cartilaginous lesions and grade 1 (G1) chondrosarcoma, −1.94 (95% CI −2.76 to −1.12) between G1 and grade 2 (G2) chondrosarcoma, and − 2.37 (95% CI −5.79 to 1.05) between G2 and grade 3 (G3) chondrosarcoma.

Conclusions

In a word, 18F-FDG PET/CT revealed excellent accuracy in the diagnosis of chondrosarcoma and might assist in clinical decision-making. Meanwhile, although SUVmax alone showed restricted ability to differentiate benign cartilaginous lesions and G1 chondrosarcoma, as well as between G2 and G3 chondrosarcoma, it can identify intermediate/high-grade chondrosarcoma from low-grade ones.

Level of evidence

Level I evidence, a summary of meta-analysis
Fetal aortic valvuloplasty: first report of two cases from Saudi Arabia
Authors: Atiyah Merna , Kurdi Ahmed , Al Tuwaijry Osama , Al Sahari Atif , Al Rakaf Maha , Babic Inas , Al Habshan Fahad , Alhalees Zohair , Al Najashi Khalid
Published: June 2020

Background

Fetal aortic stenosis may progress to hypoplastic left heart syndrome (HLHS), which carries a poor prognosis. We report two infants with fetal aortic stenosis successfully treated with fetal aortic valvuloplasty (FAV) using balloon dilatation.

Case presentation

Of five fetuses with aortic stenosis fulfilling the FAV criteria of severe aortic stenosis with a left ventricular length Z-score of ≥ − 2, retrograde flow in the transverse aortic arch, left-to-right flow across the foramen ovale, monophasic mitral inflow, and significant left ventricular dysfunction, we obtained permission for FAV in two fetuses. FAV was performed successfully under echocardiographic guidance using balloon dilatation. Both fetuses survived to birth. During FAV, mild pericardial effusion developed when introducing the stylet needle in the second fetus, and this resolved within 48 h. No intraprocedural complications occurred in the first patient, and no maternal complications occurred. The first infant underwent the Ross procedure after birth and is currently 7 years old and doing well. The second patient underwent aortic and mitral valve repair with endocardial fibroelastosis resection approximately 2 weeks after birth, which temporarily addressed the mitral valve stenosis; high doses of inotropes were subsequently required. The infant died of sepsis at 2 months of age.

Conclusion

FAV using balloon dilatation to treat fetal aortic stenosis was successful in our two patients, with subsequent neonatal biventricular repair resulting in long-term survival in one patient and death secondary to sepsis in the second patient.
Pathologic substrate of gastropathy in Anderson-Fabry disease
Authors: Di Toro Alessandro , Narula Nupoor , Giuliani Lorenzo , Concardi Monica , Smirnova Alexandra , Favalli Valentina , Urtis Mario , Alvisi Costanza , Antoniazzi Elena , Arbustini Eloisa
Published: June 2020

In both classic and late-onset AFD, mutations of the GLA gene cause deficient activity of the alpha-galactosidase enzyme resulting in intracellular accumulation of the undigested substrate. Gastrointestinal symptoms (GI) are common but non-specific and imputed to the AFD, irrespective of the demonstration of substrate accumulation in GI cells. We demonstrate substrate accumulation in gastric epithelial, vascular, and nerve cells of patients with classic AFD and, vice versa, absence of accumulation in late-onset AFD and controls.
Novel MNX1 mutations and genotype–phenotype analysis of patients with Currarino syndrome
Authors: Han Lu , Zhang Zhen , Wang Hui , Song Hui , Gao Qing , Yan Yuchun , Tao Ran , Xiao Ping , Li Long , Jiang Qian , Li Qi
Published: June 2020

Background

Currarino syndrome (CS) is a specific complex of congenital caudal anomalies, including anorectal malformations, presacral mass and sacral anomalies. Mutations in theMNX1gene are closely related to CS and occur in almost all familial cases and less than half of sporadic patients. We investigated the spectrum ofMNX1pathogenic variants and associated clinical features in Chinese patients with CS.

Results

Seventeen index patients from 16 families were recruited from 2015 to 2018. All patients were diagnosed with CS and treated at the Capital Institute of Pediatrics Affiliated Children’s Hospital. Genetic testing was applied to identify mutations in CS patients and their relatives by whole-exome sequencing and Sanger sequencing. Functional verification was performed for a recurrent noncanonical splice site variant inMNX1with a minigene splicing assay. In 17 CS patients, 14 were complete CS and 3 were mild CS. Nine variants inMNX1were identified in 11 patients, and these included two frameshift mutations (p.Leu223Leufs*61, p.X402Serfs*70), four nonsense mutations (p.Gly42X, p.Cys88X, p.Gln24X, p.Cys241X), one missense mutation (p.Trp288Leu), one splice region variant (c.691 + 3G > T) and one polyalanine polymorphism (p.Ala135insAlaAla). Seven of these nine variants have never been reported. PathogenicMNX1mutations were found in 100% (4/4) of familial and 46% (6/13) of sporadic patients.

Conclusion

Our study expanded the mutation spectrum ofMNX1and provided clinical and genetic analyses of seventeen CS patients from mainland China.
Inherited duplication of the pseudoautosomal region Xq28 in a subject with Gilles de la Tourette syndrome and intellectual disability: a case report
Authors: Maccarini Stefania , Cipani Annamaria , Bertini Valeria , Skripac Jelena , Salvi Alessandro , Borsani Giuseppe , Marchina Eleonora
Published: June 2020

Background

Tourette syndrome (TS) is a complex neurodevelopmental disorder (NDD) characterized by multiple chronic involuntary motor and vocal tics with onset during childhood or adolescence. Most TS patients present with additional comorbidities, typically attention deficit hyperactivity disorder (ADHD), obsessive- compulsive disorder (OCD), autism spectrum disorder (ASD) and intellectual disability (ID). Both TS and ID are genetically complex disorders that likely occur as a result of the effects of multiple genes interacting with other environmental factors. In addition to single gene mutations and chromosomal disorders, copy number variations (CNVs) are implicated across many NDDs and ID and contribute to their shared genetic etiology. Screening of CNVs using microarray-based Comparative Genomic Hybridization (aCGH) is now routinely performed in all subjects with NDD and ID.

Case presentation

We report a case of a 12-year-old girl diagnosed with Gilles de la Tourette Syndrome associated to behavior disorders and intellectual disability in particular with regard to language. Array-CGH analysis showed a CNV of a subtelomeric region Xq28 (gain of 260 kb) inherited from the healthy father. The duplication contains two genes, VAMP7 and SPRY3 of the PAR2 pseudoautosomal region. FISH analysis revealed that the duplicated segment is located on the short arm of a chromosome 13, resulting in a trisomy of the region. In the proband the expression levels of the genes evaluated in the peripheral blood sample are comparable both those of the mother and to those of female control subjects.

Conclusions

Although the trisomy of the 260 kb region from Xq28 identified in proband is also shared by the healthy father, it is tantalizing to speculate that, together with genetic risk factors inherited from the mother, it may play a role in the development of a form of Tourette syndrome with intellectual disability. This hypothesis is also supported by the fact that both genes present in the duplicated region (VAMP7 and SPRY3) are expressed in the CNS and are implicated in neurotransmission and neurite growth and branching. In addition, similar CNVs have been identified in individuals whose phenotype is associated with autism spectrum disorders or intellectual disability.
Differential expression of Cdk5-phosphorylated CRMP2 following a spared nerve injury
Authors: Moutal Aubin , Ji Yingshi , Bellampalli Shreya Sai , Khanna Rajesh
Published: June 2020

Effective treatment of high-impact pain patients is one of the major stated goals of the National Pain Strategy in the United States. Identification of new targets and mechanisms underlying neuropathic pain will be critical in developing new target-specific medications for better neuropathic pain management. We recently discovered that peripheral nerve injury-induced upregulation of an axonal guidance phosphoprotein collapsin response mediator protein 2 (CRMP2) and the N-type voltage-gated calcium (CaV2.2) as well as the NaV1.7 voltage-gated sodium channel, correlates with the development of neuropathic pain. In our previous studies, we found that interfering with the phosphorylation status of CRMP2 is sufficient to confer protection from chronic pain. Here we examined the expression of CRMP2 and CRMP2 phosphorylated by cyclin-dependent kinase 5 (Cdk5, on serine residue 522 (S522)) in sciatic nerve, nerve terminals of the glabrous skin, and in select subpopulations of DRG neurons in the SNI model of neuropathic pain. By enhancing our understanding of the phosphoregulatory status of CRMP2 within DRG subpopulations, we may be in a better position to design novel pharmacological interventions for chronic pain.
Approaches for integrating heterogeneous RNA-seq data reveal cross-talk between microbes and genes in asthmatic patients
Authors: Spakowicz Daniel , Lou Shaoke , Barron Brian , Gomez Jose L. , Li Tianxiao , Liu Qing , Grant Nicole , Yan Xiting , Hoyd Rebecca , Weinstock George , Chupp Geoffrey L. , Gerstein Mark
Published: June 2020

Sputum induction is a non-invasive method to evaluate the airway environment, particularly for asthma. RNA sequencing (RNA-seq) of sputum samples can be challenging to interpret due to the complex and heterogeneous mixtures of human cells and exogenous (microbial) material. In this study, we develop a pipeline that integrates dimensionality reduction and statistical modeling to grapple with the heterogeneity. LDA(Latent Dirichlet allocation)-link connects microbes to genes using reduced-dimensionality LDA topics. We validate our method with single-cell RNA-seq and microscopy and then apply it to the sputum of asthmatic patients to find known and novel relationships between microbes and genes.
The PRINTEMPS study: protocol of a cluster-randomized controlled trial of the local promotion of a smartphone application and associated website for the prevention of suicidal behaviors in the adult general population in France
Authors: Gandré Coralie , Le Jeannic Anaïs , Vinet Marie-Amélie , Turmaine Kathleen , Courtet Philippe , Roelandt Jean-Luc , Vaiva Guillaume , Giraudeau Bruno , Alberti Corinne , Chevreul Karine
Published: June 2020

Background

Suicide constitutes a cause of death which could be prevented by e-health programs accessible to the general population. Effective promotion has the potential to maximize the uptake of such programs. However, few e-health programs have been combined with promotion campaigns. The primary objective of this trial is to assess the effectiveness of a tailored promotion, at a local level, of a mobile application and website offering evidence-based content for suicide prevention (the StopBlues program), and to compare the effectiveness of two types of local promotion in terms of their impact on suicidal acts. Secondary objectives focus on the effectiveness of the promotion in terms of the intensity of utilization of the StopBlues program, help-seeking behaviors and the level of psychological impairment of program users.

Methods/design

This is a three-arm, parallel-group, cluster-randomized controlled trial, with before-and-after observation. Thirty-four clusters, corresponding to geographical areas sharing a common local authority in France, will be included. They will be randomly assigned to one of the following arms with a ratio of 1:1:1: a control group; a basic promotion group in which promotion of the StopBlues program will be done by local authorities; and an intensified promotion group in which basic promotion will be supplemented by an additional one in a general practitioner’s waiting room. The primary outcome measure will be the number of suicidal acts within each cluster over a 12-month period following the launch of the intervention. Baseline data will be collected for each cluster over the 12-month period prior to the trial. Secondary outcomes will include length of use of the StopBlues program, measures of help-seeking behaviors and level of psychological distress among users of the program, as well as the cost-effectiveness and budgetary impact of its promotion. A more sustained promotion by local authorities will also be implemented after 12 months in the control group and assessed using the same outcome measures.

Discussion

This research should contribute to the sparse evidence base regarding the promotion of e-health programs and will support the wider delivery of the intervention evaluated if proven effective.

Trial registration

ClinicalTrials.gov, ID: NCT03565562. Registered on 11 June 2018
Correction to: Impact of phenylalanine on cognitive, cerebral, and neurometabolic parameters in adult patients with phenylketonuria (the PICO study): a randomized, placebo-controlled, crossover, noninferiority trial
Authors: Trepp Roman , Muri Raphaela , Abgottspon Stephanie , Bosanska Lenka , Hochuli Michel , Slotboom Johannes , Rummel Christian , Kreis Roland , Everts Regula
Published: June 2020

An amendment to this paper has been published and can be accessed via the original article.
Clinical efficacy of ceramic versus resin-based composite endocrowns in Chinese adults: study protocol for a randomized controlled trial
Authors: Wang Jilei , Ling Zhiting , Zheng Ziting , Zheng Chunqing , Gai Yawen , Zeng Yuting , Zhu Xiaoxia , Chen Liya , Wu Buling , Yan Wenjuan
Published: June 2020

Background

Endocrown restoration is widely used to restore endodontically treated teeth. However, the clinical effects of different computer-aided design/computer-aided manufacturing (CAD/CAM) materials for endocrown restoration are not clear. The primary objective of this trial is to compare the clinical efficacy of resin-based bloc and ceramic endocrowns for restoring endodontically treated teeth.

Methods

The proposed resin-based bloc and ceramic endocrown assessment trial is a parallel group-designed randomized controlled trial. We will recruit 156 adults between 18 and 75 years old with a minimum of one such molar. The inclusion criteria were good oral hygiene habits, root apex of molar without evident damage, receipt of standard endodontic treatment, need for endocrown restoration, and only one endocrown restoration performed per patient. Patients participating in another study or those with systemic diseases, disabilities, or known allergies to used materials will be excluded. All patients will be randomized and restored with resin-based bloc and ceramic endocrown according to a random number table. Clinical evaluations will be performed at baseline and after treatment at 6, 12, and 24 months, in accordance with the modified Federation Dentaire Internationale (FDI) criteria, by two independent evaluators. The primary outcome is marginal adaptation; secondary outcomes include wear, tooth integrity, fracture of material and retention, marginal staining, and patient view. All data will be analyzed by an independent statistician. Signed rank-sum tests will be used for intragroup comparisons. Wilcoxon rank-sum tests will be used for intergroup comparisons. Hierarchical logistic regression will be used to adjust the baseline and other important indicators.

Discussion

This study will investigate endocrowns of two CAD/CAM materials for endodontically treated molars. The results may help clinicians choose the better CAD/CAM material option and explain to patients the advantages and disadvantages of these two materials with evidence-based support. For patients, the results may lead to improvement in long-term restoration.

Trial registration

ClinicalTrials.gov NCT04033380. Registered on 24 July 2019
Correction to: Treatment of severely ill COVID-19 patients with anti-interleukin drugs (COV-AID): A structured summary of a study protocol for a randomised controlled trial
Authors: Maes Bastiaan , Bosteels Cedric , De Leeuw Elisabeth , Declercq Jozefien , Van Damme Karel , Delporte Anja , Demeyere Bénédicte , Vermeersch Stéfanie , Vuylsteke Marnik , Willaert Joren , Bollé Laura , Vanbiervliet Yuri , Decuypere Jana , Libeer Frederick , Vandecasteele Stefaan , Peene Isabelle , Lambrecht Bart N.
Published: June 2020

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