bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of glyphosate-based herbicides and their active ingredients on earthworms, water infiltration and glyphosate leaching are influenced by soil properties
Authors: Zaller Johann G. , Weber Maureen , Maderthaner Michael , Gruber Edith , Takács Eszter , Mörtl Mária , Klátyik Szandra , Győri János , Römbke Jörg , Leisch Friedrich , Spangl Bernhard , Székács András
Published: April 2021

Background

Glyphosate-based herbicides (GBHs) are among the most often used pesticides. The hundreds of GBHs used worldwide consist of the active ingredient (AI) glyphosate in form of different salts, possibly other AIs, and various mostly undisclosed co-formulants. Pesticide risk assessments are commonly performed using single AIs or GBHs at standard soil conditions without vegetation. In a greenhouse experiment, we established a weed population with common amaranth (Amaranthus retroflexus)to examine the effects of three GBHs (Roundup LB Plus, Roundup PowerFlex, Touchdown Quattro) and their corresponding AIs (salts of glyphosate isopropylammonium, potassium, diammonium) on the activity and physiological biomarkers (glutathione S-transferase, GST; acetylcholine esterase, AChE) of an ecologically relevant earthworm species (Lumbricus terrestris). GBHs and AIs were applied at recommended doses; hand weeding served as control. Experiments were established with two soil types differing in organic matter content (SOM; 3.0% vs. 4.1%) and other properties.

Results

Earthworm activity (casting and movement activity) decreased after application of glyphosate formulations or active ingredients compared to hand weeding. We found no consistent pattern that formulations had either higher or lower effects on earthworm activity than their active ingredients; rather, differences were substance-specific. Earthworm activity was little affected by soil organic matter levels. Biomarkers remained unaffected by weed control types; GST but not AChE was decreased under high SOM. Water infiltration after a simulated heavy rainfall was interactively affected by weed control types and SOM. Leachate amount was higher after application of formulations than active ingredients and was higher under low SOM. Glyphosate concentrations in soil and leachate were strongly affected by application of formulations or active ingredients and varied with SOM (significant weed control type x SOM interaction).

Conclusions

We found that both commercial formulations and pure active ingredients can influence earthworms with consequences on important soil functions. Glyphosate products showed increased, reduced or similar effects than pure glyphosate on particular soil functions; soil properties can substantially alter this. Especially at lower SOM, heavy rainfalls could lead to more glyphosate leaching into water bodies. A full disclosure of co-formulants would be necessary to further decipher their specific contributions to these inconsistent effects.
Constructing and analysing dynamic models with modelbase v1.2.3: a software update
Authors: van Aalst Marvin , Ebenhöh Oliver , Matuszyńska Anna
Published: April 2021

Background

Computational mathematical models of biological and biomedical systems have been successfully applied to advance our understanding of various regulatory processes, metabolic fluxes, effects of drug therapies, and disease evolution and transmission. Unfortunately, despite community efforts leading to the development of SBML and the BioModels database, many published models have not been fully exploited, largely due to a lack of proper documentation or the dependence on proprietary software. To facilitate the reuse and further development of systems biology and systems medicine models, an open-source toolbox that makes the overall process of model construction more consistent, understandable, transparent, and reproducible is desired.

Results and discussion

We provide an update on the development of , a free, expandable Python package for constructing and analysing ordinary differential equation-based mathematical models of dynamic systems. It provides intuitive and unified methods to construct and solve these systems. Significantly expanded visualisation methods allow for convenient analysis of the structural and dynamic properties of models. After specifying reaction stoichiometries and rate equations modelbase can automatically assemble the associated system of differential equations. A newly provided library of common kinetic rate laws reduces the repetitiveness of the computer programming code.  is also fully compatible with SBML. Previous versions provided functions for the automatic construction of networks for isotope labelling studies. Now, using user-provided label maps,  v1.2.3 streamlines the expansion of classic models to their isotope-specific versions. Finally, the library of previously published models implemented in  is growing continuously. Ranging from photosynthesis to tumour cell growth to viral infection evolution, all these models are now available in a transparent, reusable and unified format through .

Conclusion

With this new Python software package, which is written in currently one of the most popular programming languages, the user can develop new models and actively profit from the work of others.  enables reproducing and replicating models in a consistent, tractable and expandable manner. Moreover, the expansion of models to their isotopic label-specific versions enables simulating label propagation, thus providing quantitative information regarding network topology and metabolic fluxes.
A cohort study of membranous nephropathy, primary or secondary
Authors: Arghiani Maryam , Zamani Boshra Hasan , Nazemian Fatemeh , Samadi Sara , Afsharian Malihe Saber , Habibzadeh Mahmoud , Eslami Saeid , Sabbagh Mahin Ghorban
Published: April 2021

Background

Although IgG4 deposit against phospholipase A2 receptor (anti-PLA2R) is predominantly presented in the renal biopsy of patients with primary membranous nephropathy (MN), its diagnostic value of this immune complex has not been fully established.

Methods

In this cohort study, 108 biopsy-proven MN patients with proteinuria were evaluated during two years follow up and were divided into primary and secondary groups. Renal biopsy specimens were pathologically assessed for IgG4 and PLA2R depositions by immunohistochemistry (IHC). Therefore, the relationships between staining severity, MN type and total proteinuria in all patients were determined.

Results

Of 108 patients, 73.1% had primary MN and 26.9% were diagnosed as secondary form. IHC staining in patients with primary MN was positive for PLA2R in 76 (96.2%) and IgG4 in 68 (86.1%). Cases with positive PLA2R expression had a significantly higher rate among patients with mild to moderate stages (P = 0.03). No significant relationship was found between intensity of PLA2R and IgG4 deposits with proteinuria and serum creatinine. Based on our data, double positivity/negativity of PLA2R and IgG4 expression adds prominent information to the clinical data and were found to be useful and robust biomarkers for detection of primary MN patients with high sensitivity and specificity (97.1 and 96.3% respectively, PPV = 98.5% and NPV = 92.9%).

Conclusions

Simultaneously expression of PLA2R and IgG4 in renal biopsy specimens of patients with MN could possibly be used as a potential diagnostic method to distinguish primary from secondary MN and also pathological severity of the disease.
A nomogram to predict lymph node metastasis risk for early esophageal squamous cell carcinoma
Authors: Duan Xiaofeng , Shang Xiaobin , Yue Jie , Ma Zhao , Chen Chuangui , Tang Peng , Jiang Hongjing , Yu Zhentao
Published: April 2021

Background

A nomogram was developed to predict lymph node metastasis (LNM) for patients with early-stage esophageal squamous cell carcinoma (ESCC).

Methods

We used the clinical data of ESCC patients with pathological T1 stage disease who underwent surgery from January 2011 to June 2018 to develop a nomogram model. Multivariable logistic regression was used to confirm the risk factors for variable selection. The risk of LNM was stratified based on the nomogram model. The nomogram was validated by an independent cohort which included early ESCC patients underwent esophagectomy between July 2018 and December 2019.

Results

Of the 223 patients, 36 (16.1%) patients had LNM. The following three variables were confirmed as LNM risk factors and were included in the nomogram model: tumor differentiation (odds ratio [OR] = 3.776, 95% confidence interval [CI] 1.515–9.360, p = 0.004), depth of tumor invasion (OR = 3.124, 95% CI 1.146–8.511, p = 0.026), and tumor size (OR = 2.420, 95% CI 1.070–5.473, p = 0.034). The C-index was 0.810 (95% CI 0.742–0.895) in the derivation cohort (223 patients) and 0.830 (95% CI 0.763–0.902) in the validation cohort (80 patients).

Conclusions

A validated nomogram can predict the risk of LNM via risk stratification. It could be used to assist in the decision-making process to determine which patients should undergo esophagectomy and for which patients with a low risk of LNM, curative endoscopic resection would be sufficient.
Comprehensive analyses of competing endogenous RNA networks reveal potential biomarkers for predicting hepatocellular carcinoma recurrence
Authors: Yan Ping , Huang Zuotian , Mou Tong , Luo Yunhai , Liu Yanyao , Zhou Baoyong , Cao Zhenrui , Wu Zhongjun
Published: April 2021

Background

Hepatocellular carcinoma (HCC) is one of the most common and deadly malignant tumors, with a high rate of recurrence worldwide. This study aimed to investigate the mechanism underlying the progression of HCC and to identify recurrence-related biomarkers.

Methods

We first analyzed 132 HCC patients with paired tumor and adjacent normal tissue samples from the Gene Expression Omnibus (GEO) database to identify differentially expressed genes (DEGs). The expression profiles and clinical information of 372 HCC patients from The Cancer Genome Atlas (TCGA) database were next analyzed to further validate the DEGs, construct competing endogenous RNA (ceRNA) networks and discover the prognostic genes associated with recurrence. Finally, several recurrence-related genes were evaluated in two external cohorts, consisting of fifty-two and forty-nine HCC patients, respectively.

Results

With the comprehensive strategies of data mining, two potential interactive ceRNA networks were constructed based on the competitive relationships of the ceRNA hypothesis. The ‘upregulated’ ceRNA network consists of 6 upregulated lncRNAs, 3 downregulated miRNAs and 5 upregulated mRNAs, and the ‘downregulated’ network includes 4 downregulated lncRNAs, 12 upregulated miRNAs and 67 downregulated mRNAs. Survival analysis of the genes in the ceRNA networks demonstrated that 20 mRNAs were significantly associated with recurrence-free survival (RFS). Based on the prognostic mRNAs, a four-gene signature (ADH4, DNASE1L3, HGFAC and MELK) was established with the least absolute shrinkage and selection operator (LASSO) algorithm to predict the RFS of HCC patients, the performance of which was evaluated by receiver operating characteristic curves. The signature was also validated in two external cohort and displayed effective discrimination and prediction for the RFS of HCC patients.

Conclusions

In conclusion, the present study elucidated the underlying mechanisms of tumorigenesis and progression, provided two visualized ceRNA networks and successfully identified several potential biomarkers for HCC recurrence prediction and targeted therapies.
Oral candidal carriage and its association with dental carious lesions in asymptomatic adults: a cross-sectional study from the UAE
Authors: Al-Amad Suhail H. , Rahman Betul , Khalifa Nadia , Awad Manal A.
Published: April 2021

Background

Candida’spotential association with dental caries has previously been reported in children. This research aimed at investigating the associations betweenCandidaspecies in whole saliva and dental and periodontal health indices in a sample of adult patients.

Methods

A cross-sectional study involving 160 patients investigated the associations betweenCandidaspecies collected by oral rinse technique, and Decayed, Missing, and Filled Surfaces (DMFS), and periodontal health indices. Chi-square and Independent Samplest-test were used to assess the associations betweenCandidacarriage and confounding variables. Binary logistic regression was used to assess association strengths betweenCandidacarriage and DMFS, adjusted for socio-demographic variables, diabetes mellitus and plaque index.

Results

Candidacolonies were identified in 49 (30.6%) patients with CFUs ranging from 103to 105colonies per mL. The quantity ofCandidaCFUs increased with age (r = 0.200;p < 0.05). Among all dental and periodontal health indices, only DMFS was significantly associated with higher values ofCandidacarriage (p = 0.034), and this association was independent from sex, age, smoking, diabetes mellitus and plaque index (OR: 1.014; 95% CI 1.0–1.03;p = 0.048).

Conclusion

The association betweenCandidaspecies in whole saliva and DMFS reported here supports an etiological role ofCandidain dental cariogenesis among adults.
Baseline audiological profiling of South African females with cervical cancer: an important attribute for assessing cisplatin-associated ototoxicity
Authors: Paken Jessica , Govender Cyril D. , Pillay Mershen , Ayele Birhanu T. , Sewram Vikash
Published: April 2021

Background

Cisplatin is a popular antineoplastic agent used to treat cervical cancer in women from low and middle-income countries. Cisplatin treatment is associated with ototoxicity, often resulting in hearing loss. In light of this, it is crucial to conduct baseline audiological assessments prior to treatment initiation in order to evaluate the extent of cisplatin-associated-ototoxicity. Additionally, the identification of inherent risk factors and hearing patterns in specific patient cohorts is needed, especially in South Africa, a middle-income country characterized by the quadruple burden of disease (Human Immunodeficiency Virus (HIV), Tuberculosis (TB), Diabetes and Hypertension).

Methods

This study aimed to describe a profile of risk factors and hearing in a cohort of females with cervical cancer before cisplatin treatment commenced. A descriptive study design that included 82 cervical cancer patients, who underwent audiological evaluation prescribed for ototoxicity monitoring was conducted.

Results

All participants (n = 82) presented with risk factors (diabetes, hypertension, HIV, and antiretroviral therapy) for cisplatin ototoxicity and/or pre-existing sensorineural hearing loss. High-frequency tinnitus was the most common otological symptom experienced by 25 (31%) participants. Fifty-nine (72%) participants presented with normal hearing, twenty-two (27%) with a sensorineural hearing loss, and 36% were diagnosed with mild hearing loss. Abnormal Distortion Product Otoacoustic Emissions (DPOAE) findings were obtained bilaterally in two participants (2.4%), in the right ear only of another two (2.4%) participants and the left ear of three participants (3.7%). Most participants (94%) had excellent word recognition scores, demonstrating an excellent ability to recognize words within normal conversational levels under optimal listening conditions. Age was significantly associated with hearing loss at all thresholds. Among the co-morbidities, an HIV positive status significantly triggered hearing loss, especially at higher frequencies.

Conclusion

This study demonstrated that South African females with cervical cancer present with various co-morbidities, which may predispose them to develop cisplatin-associated -ototoxic hearing loss. Identification of these co-morbidities and hearing loss is essential for the accurate monitoring of cisplatin toxicities. Appropriate management of these patients is pivotal to reduce the adverse effects that hearing impairment can have on an individual’s quality of life and to facilitate informed decision-making regarding the commencement of cisplatin chemotherapy.
Unapproved clinical trials in Russia: exception or norm?
Authors: Talantov Petr , Niyazov Ravil , Viryasova Galina , Dranitsyna Margarita , Yasny Ilya
Published: April 2021

Background

In modern Russia, any clinical investigation of a pharmaceutical for use in humans is subject to prior evaluation and approval by the Ministry of Health and its Central Ethics Committee. Despite this, some researchers and trial sponsors fail to comply, this is particularly true in case of the studies initiated by domestic sponsors or sponsor-investigators and published in Russian language medical journals. This exploratory research aims to discover whether it is a sporadic non-compliance with regulations or a common practice.

Methods

We searched the Russian language database eLIBRARY for the phrase ‘results of a randomised trial’. We selected publications reporting clinical trials and conducted in Russia. For each of the selected studies, we searched the state register of the approved clinical trials. We assessed whether (1) the investigational medicinal product was approved for marketing in Russia; (2) the therapeutic indications, posology, and administration method in the clinical trial were consistent with the approved labelling; (3) the issue of the journal included an advertisement of the medicinal product in question; and (4) the full description of the methodology corroborated that the clinical trial was randomised, as was stated in the title or abstract.

Results

Of the 26 selected articles, 22 reported the results of unauthorised clinical trials. Three of those trials were conducted in children. Twenty-one studies reported on data from unauthorised trials for investigational products approved for marketing in Russia. However, in nine cases, the therapeutic indications, posology, or administration method did not match the conditions indicated in the labelling. Moreover, in one case, the unauthorised trial included a drug therapy intervention where the active substance was not approved for use in any medicinal product marketed in Russia. In 14 of the 26 articles, the issue of the journal or the article itself contained an advertisement for the same medicinal product or, in one case, its manufacturer. All publications accompanied by advertisements claimed that the medicinal product in question was efficacious.

Conclusions

A substantial fraction of the clinical trials initiated by domestic sponsors and reported in Russian medical journals failed to obtain the mandatory prior evaluation and approval from the regulator. This can affect the rights and well-being of the study participants and the scientific validity of the studies.
The positive externalities of migrant-based TB control strategy in a Chinese urban population with internal migration: a transmission-dynamic modeling study
Authors: Yang Chongguang , Kang Jian , Lu Liping , Guo Xiaoqin , Shen Xin , Cohen Ted , Menzies Nicolas A.
Published: April 2021

Background

Large-scale rural-to-urban migration has changed the epidemiology of tuberculosis (TB) in large Chinese cities. We estimated the contribution of TB importation, reactivation of latent infection, and local transmission to new TB cases in Shanghai, and compared the potential impact of intervention options.

Methods

We developed a transmission dynamic model of TB for Songjiang District, Shanghai, which has experienced high migration over the past 25 years. We calibrated the model to local demographic data, TB notifications, and molecular epidemiologic studies. We estimated epidemiological drivers as well as future outcomes of current TB policies and compared this base-case scenario with scenarios describing additional targeted interventions focusing on migrants or vulnerable residents.

Results

The model captured key demographic and epidemiological features of TB among migrant and resident populations in Songjiang District, Shanghai. Between 2020 and 2035, we estimate that over 60% of TB cases will occur among migrants and that approximately 43% of these cases will result from recent infection. While TB incidence will decline under current policies, we estimate that additional interventions—including active screening and preventive treatment for migrants—could reduce TB incidence by an additional 20% by 2035.

Conclusions

Migrant-focused TB interventions could produce meaningful health benefits for migrants, as well as for young residents who receive indirect protection as a result of reduced TB transmission in Shanghai. Further studies to measure cost-effectiveness are needed to evaluate the feasibility of these interventions in Shanghai and similar urban centers experiencing high migration volumes.
Susceptibility loci for pancreatic cancer in the Brazilian population
Authors: Aoki Mateus Nóbrega , Stein Angelika , de Oliveira Jaqueline Carvalho , Chammas Roger , Uno Miyuki , Munhoz Francielle Boçon de Araújo , Marin Anelis Maria , Canzian Federico
Published: April 2021

Background

Pancreatic adenocarcinoma (PA) is a very aggressive cancer and has one of the poorest prognoses. Usually, the diagnosis is late and resistant to conventional treatment. Environmental and genetic factors contribute to the etiology, such as tobacco and alcohol consumption, chronic pancreatitis, diabetes and obesity. Somatic mutation in pancreatic cancer cells are known and SNP profile by GWAS could access novel genetic risk factors for this disease in different population context. Here we describe a SNP panel for Brazilian pancreatic cancer, together with clinical and epidemiological data.

Methods

78 pancreatic adenocarcinoma and 256 non-pancreatic cancer subjects had 25 SNPs genotyped by real-time PCR. Unconditional logistic regression methods were used to assess the main effects on PA risk, using allelic, co-dominant and dominant inheritance models.

Results

9 SNPs were nominally associated with pancreatic adenocarcinoma risk, with 5 of the minor alleles conferring protective effect while 4 related as risk factor. In epidemiological and clinical data, tobacco smoking, diabetes and pancreatitis history were significantly related to pancreatic adenocarcinoma risk. Polygenic risk scores computed using the SNPs in the study showed strong associations with PA risk.

Conclusion

We could assess for the first time some SNPs related with PA in Brazilian populations, a result that could be used for genetic screening in risk population such as familial pancreatic cancer, smokers, alcohol users and diabetes patients.
Impact of bronchoalveolar lavage lymphocytosis on the effects of anti-inflammatory therapy in idiopathic non-specific interstitial pneumonia, idiopathic pleuroparenchymal fibroelastosis, and unclassifiable idiopathic interstitial pneumonia
Authors: Yamagata Akira , Arita Machiko , Tachibana Hiromasa , Tokioka Fumiaki , Sugimoto Chikatoshi , Sumikawa Hiromitsu , Tanaka Tomonori , Yasui Hideki , Fujisawa Tomoyuki , Nakamura Yutaro , Suda Takafumi , Ishida Tadashi
Published: April 2021

Background

Idiopathic non-specific interstitial pneumonia (iNSIP), idiopathic pleuroparenchymal fibroelastosis (iPPFE), and unclassifiable idiopathic interstitial pneumonia (IIP) are IIPs with chronic fibrotic phenotypes, and unlike idiopathic pulmonary fibrosis, they have often been treated with anti-inflammatory drugs, including corticosteroids and immunosuppressants. However, the impact of bronchoalveolar lavage (BAL) lymphocytosis on the effects of anti-inflammatory therapy has never been evaluated. This study aimed to elucidate whether BAL lymphocytosis can be used to predict the efficacy of anti-inflammatory drugs for iNSIP, iPPFE, and unclassifiable IIP.

Methods

Japanese patients diagnosed with iNSIP, iPPFE, and unclassifiable IIP by multidisciplinary discussion were identified using the nationwide registry. Eligible patients were stratified into four groups with and without BAL lymphocytosis and anti-inflammatory therapy to compare overall survival (OS) and changes in lung function. BAL lymphocytosis was defined as a lymphocyte differential count > 15%, and the cut-off was corroborated by survival classification and regression tree analysis.

Results

Overall, 186 patients (37 iNSIP, 16 iPPFE, and 133 unclassifiable IIP) were analyzed. Limited to patients treated with anti-inflammatory drugs (n = 123), patients with BAL lymphocytosis had a better prognosis [hazard ratio (HR), 0.26; 95% confidence interval (CI), 0.11–0.63; P = 0.003], higher slope of forced vital capacity (FVC) % predicted for 2 years, and longer OS (log-rank test, P = 0.012) than those without BAL lymphocytosis. On multivariate analysis, BAL lymphocytosis (HR 0.31; 95% CI 0.13–0.75; P = 0.009) was a prognostic factor for OS, along with age and FVC % predicted. Conversely, for patients managed without anti-inflammatory therapy (n = 63), the presence or absence of BAL lymphocytosis had no prognostic value.

Conclusions

BAL lymphocytosis is associated with good outcomes in patients treated with anti-inflammatory drugs, but has no prognostic value when anti-inflammatory drugs are not used. BAL lymphocytosis may provide a predictive biomarker for identifying patients with iNSIP, iPPFE and unclassifiable IIP who are likely to benefit from anti-inflammatory drugs.
The effect of miR-539 regulating TRIAP1 on the apoptosis, proliferation, migration and invasion of osteosarcoma cells
Authors: Liu Huowen , Yang Min , Zhang Yufeng , Yang Zhiqiang , Chen Zhe , Xie Yuanlong , Peng Binglong , Cai Lin
Published: April 2021

Objective

The purpose of this study is to explore the effect of miRNA-539 on osteosarcoma (OS) and the underlying mechanism, so as to find a new method for early diagnosis and treatment of osteosarcoma.

Method

miRNA-539 mimics was transfected into osteosarcoma cells 143b and MG-63 and upregulated the expression of miR-539. QT-PCR was used to detect transfection efficacy. CCK-8 method was used to detect proliferation of 143b and MG-63 osteosarcoma cells and flow cytometry was used to detect the apoptosis of osteosarcoma cells 143b and MG-63. Wound-healing test and Transwell test were used to detect the migration and invasion ability of osteosarcoma cells. TRIAP1 was found to be the potential target gene of miRNA-539 by online bioinformatics software and the expression level of TRIAP1 in osteosarcoma cells overexpressing miRNA-539 was detected by qT-PCR. Western blot was used to detect the level of expression of TRIAP1 and its downstream genes (p53, p21, apaf1 and caspase9) in osteosarcoma cells 143b and MG63 transfected with miR-539 mimics or miR-539 mimics-NC. A model of osteosarcoma subcutaneously transplanted in nude mice was constructed to observe the effect of miRNA-539 on the growth rate of osteosarcoma in vivo.

Results

After transfection of miRNA-539 mimics in osteosarcoma cells 143b and MG63, the proliferation level, migration ability, and invasion ability of the osteosarcoma cells were significantly lower than that in the control group, and the apoptosis level was significantly higher than that in the control group (P < 0.01). The dual luciferase reporter confirmed that TRIAP1 was the target of miR-539, and the expression level of TRIAP1 in 143b and MG63 transfected with miRNA-539 mimics was proved to be significantly lower than that in the control group (P < 0.01).The western blot showed the expression of genes targeted by TRIAP1 was upregulated when the expression of TRIAP1 was downregulated. In vivo, the osteosarcoma growth rate in the miRNA-539 mimics group was significantly slower than that in the control group (P < 0.01).

Conclusions

MiRNA-539 may inhibit the cell proliferation, migration and invasion of osteosarcoma cells and promote the apoptosis of osteosarcoma cells by targeting on TRIAP1.
Cyproheptadine, an epigenetic modifier, exhibits anti-tumor activity by reversing the epigenetic silencing of IRF6 in urothelial carcinoma
Authors: Jou Yeong-Chin , Lin Guan-Ling , Lin Hon-Yi , Huang Wan-Hong , Chuang Yu-Ming , Lin Ru-Inn , Chen Pie-Che , Wu Shu-Fen , Shen Cheng-Huang , Chan Michael W. Y.
Published: April 2021

Background

Urothelial carcinoma (UC) is the second most common malignancy of the urinary system with high rate of recurrence, UC patients therefore needed to be treated with surgery followed by chemotherapy. Development of novel therapeutics with minimal side-effect is an urgent issue. Our previous study showed that cyproheptadine (CPH), an anti-histamine, exhibited antitumor activity in UC in vitro and in an xenograft model. However, the molecular mechanism of how CPH inhibits tumor progression is not fully understood.

Methods

Genes that were upregulated after treatment with CPH in UC cells, were examined by RNA-Seq. Real-time quantitative PCR (RT-qPCR) was employed to detect IRF6 expression while COBRA assay and bisulphite pyrosequencing were used to examine promoter methylation of IRF6. Enrichment of total H3K27 acetylation and H3K4 mono-methylation were detected by western blotting. Colony formation and flow cytometry were used to examine proliferation and apoptosis in UC cells overexpressed or depleted with IRF6. Nude mice xenograft model was used to examine the effect of IRF6 in UC.

Results

Our result showed that several genes, including IRF6 were upregulated after treatment with CPH in BFTC905 UC cells. Further experiments found that treatment of CPH could restore the expression of IRF6 in several other UC cell lines, probably due to promoter hypomethylation and enrichment of H3K27 acetylation and H3K4 mono-methylation. These results may be due to the fact that CPH could alter the activity, but not the expression of epigenetic modifiers. Finally, re-expression of IRF6 in UC inhibited tumor growth in vitro and in an xenograft mouse model, by inducing apoptosis.

Conclusion

In conclusion, our results suggested that CPH may be an epigenetic modifier, modulating the expression of the potential tumor suppressor IRF6, in inhibiting tumor growth in UC.
Needs and resources of people with type 2 diabetes in peri-urban Cochabamba, Bolivia: a people-centred perspective
Authors: Leyns Christine Cécile , Couvreur Niek , Willems Sara , Van Hecke Ann
Published: April 2021

Background

The rising prevalence of type 2 diabetes results in a worldwide public healthcare crisis, especially in low- and middle-income countries (LMICs) with unprepared and overburdened health systems mainly focused on infectious diseases and maternal and child health. Studies regarding type 2 diabetes in LMICs describe specific interventions ignoring a comprehensive analysis of the local factors people see influential to their health. This study aims to meet this research gap by exploring what people with type 2 diabetes in Bolivia need to maintain or improve their health, how important they perceive those identified needs and to what extent these needs are met.

Methods

From March until May 2019, 33 persons with type 2 diabetes from three periurban municipalities of the department of Cochabamba participated in this study. The concept mapping methodology by Trochim, a highly structured qualitative brainstorming method, was used to generate and structure a broad range of perspectives on what the participants considered instrumental for their health.

Results

The brainstorming resulted in 156 original statements condensed into 72 conceptually different needs and resources, structured under nine conceptual clusters and four action domains. These domains illustrated with vital needs were: (1) self-management with use of plants and the possibility to measure sugar levels periodically; (2) healthcare providers with the need to trust and receive a uniform diagnosis and treatment plan; (3) health system with opportune access to care and (4) community with community participation in health and safety, including removal of stray dogs.

Conclusions

This study identifies mostly contextual factors like low literacy levels, linguistic problems in care, the need to articulate people’s worldview including traditional use of natural remedies with the Bolivian health system and the lack of expertise on type 2 diabetes by primary health care providers. Understanding the needs and structuring them in different areas wherein action is required serves as a foundation for the planning and evaluation of an integrated people centred care program for people with type 2 diabetes. This participative method serves as a tool to implement the often theoretical concept of integrated people centred health care in health policy and program development.
Management strategy and novel ophthalmological findings in neonatal severe hypertriglyceridemia: a case report and literature review
Authors: El-koofy Nehal M. , Abdo Yasmeen A. , El-Fayoumi Dina , Esmael Amanne F. , Elmonem Mohamed. A. , Ezzeldin Zahraa
Published: April 2021

Background

Neonatal severe hypertriglyceridemia is rarely reported in the literature and there is no consensus for hypertriglyceridemia management at this age group.

Methods

The index case is a 4-week-old male infant with severe hypertriglyceridemia accidentally discovered during a circumcision surgery. His clinical and genetic characteristics and his successful management strategy are described. Furthermore, a detailed ophthalmological examination of the proband was conducted at 3 and 6 months of age using Fourier-domain-optical coherence tomography.

Results

Triglycerides level at presentation was extremely high 33,727 mg/dL (380.8 mmol/L). Two sessions of exchange blood transfusion on two consecutive days successfully reduced triglycerides to 382 mg/dL (4.3 mmol/L) with no adverse effects. The infant was discharged 3 days later. At discharge, the mother was advised to continue breastfeeding together with a medium-chain triglycerides formula. Satisfactory growth parameters and lipid profile values were obtained for a follow-up duration of 5 months with no reported attacks of acute pancreatitis. Lipoprotein lipase deficiency was confirmed by the detection of the LPL homozygous pathogenic variant c.805G > A; p.(Glu269Lys). Early corneal and macular lesions were detected and persisted on follow-up despite relatively good lipemic control.

Conclusion

This case highlights the importance of the early discovery of severe hypertriglyceridemia during the neonatal period, which is needed for prompt management and prevention of severe complications. Rationalized breastfeeding can be tolerated within the diet plan of the disease with satisfactory outcomes. To our knowledge, it is the first study reporting early corneal and macular affection by severe hypertriglyceridemia in a neonate. Prolonged follow-up is needed to determine the extent of ophthalmological lesions.
Gender- and age-related differences of statin use on incident dementia in patients with rheumatoid arthritis: a Nationwide population-based cohort study
Authors: Lin Tsung-Kun , Huang Jing-Yang , Pan Lung-Fa , Jong Gwo-Ping
Published: April 2021

Background

Some observational studies have found a significant association between the use of statin and a reduced risk of dementia. However, the results of these studies are unclear in patients with rheumatoid arthritis (RA). This study is to determine the association between the use of statins and the incidence of dementia according to sex and age-related differences in patients with RA.

Methods

We conducted a nationwide retrospective cohort study using the Taiwan Health Insurance Review and Assessment Service database (2003–2016). The primary outcome assessed was the risk of dementia by estimating hazard ratios (HRs) and 95% confidence intervals (CIs). Multiple Cox regression was used to estimate the adjusted hazard ratio of new-onset dementia. Subgroup analysis was also conducted.

Results

Among the 264,036 eligible patients with RA aged > 40 years, statin users were compared with non-statin users by propensity score matching at a ratio of 1:1 (25,764 in each group). However, no association was found between the use of statins and the risk of new-onset dementia (NOD) in patients with RA (HR: 1.01; 95% CI: 0.97–1.06). The subgroup analysis identified the use of statin as having a protective effect against developing NOD in male and older patients.

Conclusion

No association was observed between the use of a statin and the risk of NOD in patients with RA, including patients of both genders and aged 40–60 years, but these parameters were affected by gender and age. The decreased risk of NOD in patients with RA was greater among older male patients. Use of a statin in older male (> 60 years) patients with RA may be needed in clinical practice to prevent dementia.
Autophagy blockade synergistically enhances nanosonosensitizer-enabled sonodynamic cancer nanotherapeutics
Authors: Zhou Liqiang , Huo Minfeng , Qian Xiaoqin , Ding Li , Yu Luodan , Feng Wei , Cui Xinwu , Chen Yu
Published: April 2021

Ultrasound-triggered sonodynamic therapy (SDT) represents an emerging therapeutic modality for cancer treatment based on its specific feature of noninvasiveness, high tissue-penetrating depth and desirable therapeutic efficacy, but the SDT-induced pro-survival cancer-cell autophagy would significantly lower the SDT efficacy for cancer treatment. Here we propose an “all-in-one” combined tumor-therapeutic strategy by integrating nanosonosensitizers-augmented noninvasive SDT with autophagy inhibition based on the rationally constructed nanoliposomes that co-encapsulates clinically approved sonosensitizers protoporphyrin IX (PpIX) and early-phase autophagy-blocking agent 3-methyladenine (3-MA). It has been systematically demonstrated that nanosonosensitizers-augmented SDT induced cytoprotective pro-survival autophagy through activation of MAPK signaling pathway and inhibition of AMPK signaling pathway, and this could be efficaciously inhibited by 3-MA in early-phase autophagy, which significantly decreased the cell resistance to intracellular oxidative stress and complied a remarkable synergistic effect on SDT medicated cancer-cell apoptosis both in vitro at cellular level and in vivo on tumor-bearing animal model. Therefore, our results provide a proof-of-concept combinatorial tumor therapeutics based on nanosonosensitizers for the treatment of ROS-resistant cancer by autophagy inhibition-augmented SDT.
Successful birth after preimplantation genetic testing for a couple with two different reciprocal translocations and review of the literature
Authors: Liu Dun , Chen Chuangqi , Zhang Xiqian , Dong Mei , He Tianwen , Dong Yunqiao , Lu Jian , Yu Lihua , Yang Chuanchun , Liu Fenghua
Published: April 2021

Background

Preimplantation genetic testing for chromosomal structural rearrangements (PGT-SR) is widely applied in couples with single reciprocal translocation to increase the chance for a healthy live birth. However, limited knowledge is known on the data of PGT-SR when both parents have a reciprocal translocation. Here, we for the first time present a rare instance of PGT-SR for a non-consanguineous couple in which both parents carried an independent balanced reciprocal translocation and show how relevant genetic counseling data can be generated.

Methods

The precise translocation breakpoints were identified by whole genome low-coverage sequencing (WGLCS) and Sanger sequencing. Next-generation sequencing (NGS) combining with breakpoint-specific polymerase chain reaction (PCR) was used to define 24-chromosome and the carrier status of the euploid embryos.

Results

Surprisingly, 2 out of 3 day-5 blastocysts were found to be balanced for maternal reciprocal translocation while being normal for paternal translocation and thus transferable. The transferable embryo rate was significantly higher than that which would be expected theoretically. Transfer of one balanced embryo resulted in the birth of a healthy boy.

Conclusion(s)

Our data of PGT-SR together with a systematic review of the literature should help in providing couples carrying two different reciprocal translocations undergoing PGT-SR with more appropriate genetic counseling.
An evaluation of venous thromboembolism by whole-body enhanced CT scan for critical COVID-19 pneumonia with markedly rises of coagulopathy related factors: a case series study
Authors: Ogawa Fumihiro , Oi Yasufumi , Nakajima Kento , Matsumura Reo , Nakagawa Tomoki , Miyagawa Takao , Abe Takeru , Takeuchi Ichiro
Published: April 2021

Background

Coronavirus disease (COVID-19) pneumonitis associated with severe respiratory failure has a high mortality rate. Based on recent reports, the most severely ill patients present with coagulopathy, and disseminated intravascular coagulation (DIC)-like massive intravascular clot formation is frequently observed. Coagulopathy has emerged as a significant contributor to thrombotic complications. Although recommendations have been made for anticoagulant use for COVID-19, no guidelines have been specified.

Case summary

We describe four cases of critical COVID-19 with thrombosis detected by enhanced CT scan. The CT findings of all cases demonstrated typical findings of COVID-19 and pulmonary embolism or deep venous thrombus without critical exacerbation. Two patients died of respiratory failure due to COVID-19.

Discussion

Previous reports have suggested coagulopathy with thrombotic signs as the main pathological feature of COVID-19, but no previous reports have focused on coagulopathy evaluated by whole-body enhanced CT scan. Changes in hemostatic biomarkers, represented by an increase in D-dimer and fibrin/fibrinogen degradation products, indicated that the essence of coagulopathy was massive fibrin formation. Although there were no clinical symptoms related to their prognosis, critical COVID-19-induced systemic thrombus formation was observed.

Conclusions

Therapeutic dose anticoagulants should be considered for critical COVID-19 because of induced coagulopathy, and aggressive follow-up by whole body enhanced CT scan for systemic venous thromboembolism (VTE) is necessary.
Increasing nursing student interest in rural healthcare: lessons from a rural rotation program in Democratic Republic of the Congo
Authors: Michaels-Strasser Susan , Thurman Paul W. , Kasongo Narcisse Mwinkeu , Kapenda Daniel , Ngulefac John , Lukeni Beatrice , Matumaini Serge , Parmley Lauren , Hughes Rebekah , Malele Faustin
Published: April 2021

Background

Many challenges exist in providing equitable access to rural healthcare in the Democratic Republic of the Congo (DRC). WHO recommends student exposure to rural clinical rotations to promote interest in rural healthcare. Challenges to rural engagement include lack of adequate infrastructure and staff to lead rural education. This case report highlights key steps in developing a rural rotation program for DRC nursing students.

Case presentation

To implement a rural rotation (RR) program, ICAP at Columbia University (ICAP) consulted with students, the Ministries of Health (MoH) and Education (MoE), and nursing schools to pilot and expand a rural rotation program. Nursing schools agreed to place students in rural clinics and communities. Key stakeholders collaborated to assess and select rural sites based on availability of nursing mentors, educational resources, security, accessibility, and patient volume. To support this, 85 preceptors from 55 target schools and 30 rural health facilities were trained of which 30 were selected to be “master trainers”. These master trainers led the remaining 55 preceptors implementing the rural rotation program. We worked with rural facilities to engage community leaders and secure accommodation for students.

A total of 583 students from five Lubumbashi schools and two rural schools outside Kinshasa participated across 16 rural sites (298 students in 2018–2019 school year and 285 in 2019–2020). Feedback from 274 students and 25 preceptors and nursing school leaders was positive with many students actively seeking rural assignments upon graduation. For example, 97% agreed or strongly agreed that their RR programs had strengthened their educational experience. Key challenges, however, were long-term financial support (35%) for rural rotations, adequate student housing (30%) and advocacy for expanding the rural workforce.

Conclusions

With nearly 600 participants, this project showed that a RR program is feasible and acceptable in resource-limited settings yet availability of ample student accommodation and increasing availability of rural jobs remain health system challenges. Using a multipronged approach to rural health investment as outlined by WHO over two decades ago remains essential. Attracting future nurses to rural health is necessary but not sufficient to achieve equitable health workforce distribution.
Household preferences and willingness to pay for health insurance in Kampala City: a discrete choice experiment
Authors: Kalyango Edward , Kananura Rornald Muhumuza , Kiracho Elizabeth Ekirapa
Published: April 2021

Introduction

Uganda is in discussions to introduce a national health insurance scheme. However, there is a paucity of information on household preferences and willingness to pay for health insurance attributes that may guide the design of an acceptable health insurance scheme. Our study sought to assess household preferences and willingness to pay for health insurance in Kampala city using a discrete choice experiment.

Methods

This study was conducted from 16th February 2020 to 10th April 2020 on 240 households in the Kawempe division of Kampala city stratified into slum and non-slum communities in order to get a representative sample of the area. We purposively selected the communities that represented slum and non-slum communities and thereafter applied systematic sampling in the selection of the households that participated in the study from each of the communities. Four household and policy-relevant attributes were used in the experimental design of the study. Each respondent attended to 9 binary choice sets of health insurance plans that included one fixed choice set. Data were analyzed using mixed logit models.

Results

Households in both the non-slum and slum communities had a high preference for health insurance plans that included both private and public health care providers as compared to plans that included public health care providers only (non-slum coefficient β = 0.81, P < 0.05; slum β = 0.87, p < 0.05) and; health insurance plans that covered extended family members as compared to plans that had limitations on the number of family members allowed (non-slum β = 0.44, P < 0.05; slum β = 0.36, p < 0.05). Households in non-slum communities, in particular, had a high preference for health insurance plans that covered chronic illnesses and major surgeries to other plans (0.97 β, P < 0.05). Our findings suggest that location of the household influences willingness to pay with households from non-slum communities willing to pay more for the preferred attributes.

Conclusion

Potential health insurance schemes should consider including both private and public health care providers and allow more household members to be enrolled in both slum and non-slum communities. However, the inclusion of more HH members should be weighed against the possible depletion of resources and other attributes. Potential health insurance schemes should also prioritize coverage for chronic illnesses and major surgeries in non-slum communities, in particular, to make the scheme attractive and acceptable for these communities.