bluuebunny/crossref_metadata_2025 huggingface dataset:
Epidemiology of gastroesophageal reflux disease in Iran: a systematic review and meta-analysis
Authors: Karimian Mohammad , Nourmohammadi Hassan , Salamati Majid , Hafezi Ahmadi Mohammad Reza , Kazemi Fatemeh , Azami Milad
Published: September 2020

Background

Gastroesophageal reflux disease (GERD), which leads to acid reflux into the esophagus, is a common gastrointestinal disorder. Several studies have shown the prevalence of GERD in Iranian population, but their evidence is contradictory. Therefore, the present study was conducted to investigate the epidemiology of GERD in Iran.

Methods

The entire steps of this systematic review and meta-analysis were based on the MOOSE protocol, and the results were reported accordance with the PRISMA guideline. This review is registered on PROSPERO (registration number: CRD42020142861). To find potentially relevant published articles, comprehensive search was done on international online databases Scopus, Science Direct, EMBASE, PubMed/Medline, CINAHL, EBSCO, Cochrane Library, Web of Science, Iranian online databases and the Google Scholar search engine in June 2019. Cochran test and I2index were used to assess the heterogeneity of the studies. Data were analyzed using Comprehensive Meta-Analysis software ver. 2. The significance level of the test was considered to beP <  0.05.

Results

The daily, weekly, monthly, and overall prevalence of GERD symptoms in Iranian population was 5.64% (95%CI [confidence interval]: 3.77–8.35%;N = 66,398), 12.50% (95%CI: 9.63–16.08%;N = 110,388), 18.62% (95%CI: 12.90–26.12%;N = 70,749) and 43.07% (95%CI: 35.00–51.53%;N = 73,189), respectively. The daily, weekly, monthly, and overall prevalence of heartburn in Iranian population was 2.46% (95%CI: 0.93–6.39%;N = 18,774), 9.52% (95%CI: 6.16–14.41%;N = 54,125), 8.19% (95%CI: 2.42–24.30%;N = 19,363) and 23.20% (95%CI: 13.56–36.79%;N = 26,543), respectively. The daily, weekly, monthly, and overall prevalence of regurgitation in Iranian population was 4.00% (95%CI: 1.88–8.32%;N = 18,774), 9.79% (95%CI: 5.99–15.60%;N = 41,140), 13.76% (95%CI: 6.18–44.31%;N = 19,363) and 36.53% (95%CI: 19.30–58.08%;N = 21,174), respectively. The sensitivity analysis for prevalence of all types GERD, heartburn and regurgitation symptoms by removing a study showed that the overall estimate is still robust.

Conclusion

The present meta-analysis provides comprehensive and useful information on the epidemiology of GERD in Iran for policy-makers and health care providers. This study showed a high prevalence of GERD in Iran. Therefore, effective measures on GERD-related factors such as lifestyle can be among the health policies of Iran.
Clinicopathological study of mixed cryoglobulinemic glomerulonephritis secondary to hepatitis B virus infection
Authors: Li Chao , Li Hang , Su Wei , Wen Yu-bing , Ye Wei , Ye Wen-ling , Cai Jian-fang , Qin Xu-zhen , Li Xue-mei , Li Xue-wang
Published: September 2020

Background

Cryoglobulinemic glomerulonephritis (CryoGn) caused by hepatitis B virus (HBV) infection was rarely reported. Our study aimed to investigate the clinical features, renal pathology findings, and prognosis in patients with HBV related CryoGn.

Methods

This was a retrospective study including seven Chinese patients with HBV related CryoGn in a tertiary referral hospital from April 2016 to March 2019. The clinical and pathological data were collected and analyzed.

Results

Age at renal biopsy was 47 ± 12 years, with female/male ratio 3/4. Urine protein was 5.6 (3.0, 6.6) g/d and five cases presented with nephrotic syndrome. The baseline eGFR was 23.5 (20.2, 46.3) ml/min per 1.73m2. The extrarenal manifestations included purpura (n = 6), arthralgia (n = 1), peripheral neuropathy (n = 1), and cardiomyopathy (n = 1). Six cases had type II cryoglobulinemia with IgMκ, the other one had type III. The median cryocrit was 4.0 (1.0, 15.0) %. Renal pathologic findings on light microscopy: endocapillary proliferative glomerulonephritis (Gn) (n = 3), membranoproliferative Gn (n = 3), and mesangial proliferative Gn (n = 1). On immunofluorescence microscopy, the predominant type of immunoglobulin deposits was IgM (n = 5). HBsAg and HBcAg deposits were found in one case. Ultrastructural studies showed granular subendothelial and mesangial electron-dense deposits in all patients and microtubules in one case. All patients received antiviral medications. They were given corticosteroid alone (n = 2) or combined with cyclophosphamide (n = 4) or mycophenolate mofetil (n = 1). Two patients received plasmapheresis. The median follow-up time was 18 (6, 37) months. Four patients got remission, two patients died of pneumonia, and one progressed to end-stage renal disease (ESRD). At endpoint of follow-up, 24hUP was 2.1 (0.8–5.2) g/d, and eGFR was 55.3 (20.7, 111.8) ml/min per 1.73m2. The median cryocrit decreased to 1.0 (0, 5.75) %.

Conclusions

The etiology of mixed CryoGn should be screened for HBV infection. Endocapillary proliferative Gn and membranoproliferative Gn were the common pathologic patterns. Diagnosis and treatment in early stage benefit patients’ renal outcomes. Immunosuppressive therapy should be considered for severe renal disease, based on efficient antiviral therapy.
Prevalence of anemia and sociodemographic characteristics among pregnant and non-pregnant women in southwest China: a longitudinal observational study
Authors: Wu Yu , Ye Hanfeng , Liu Jihong , Ma Qiuyue , Yuan Yanling , Pang Qian , Liu Jue , Kong Cai , Liu Min
Published: September 2020

Background

Globally, the prevalence of anemia among women of reproductive age is about 29.4%, and anemia impacts about 40% of pregnant women and more than 20% of non-pregnant women. We conducted a longitudinal observational study of anemia in pregnant and non-pregnant women, and analyzed the association between the prevalence of anemia and sociodemographic characteristics of women in southwest China.

Methods

This study was a longitudinal observational study which involved 640,672 women aged 18–49 years from 129 counties in southwest China. Data were from databases of National Free Preconception Health Examination Project (NFPHEP) and electronic medical records of local hospitals. We adjusted the diagnostic thresholds of anemia for altitude. The prevalence of anemia was expressed in percentages and 95% confidence intervals (95% CI). The association between the prevalence of anemia and sociodemographic characteristics of pregnant and non-pregnant women were analyzed using univariate and multivariate logistic regression method, expressed in crude odds ratio (cOR), adjusted odds ratio (aOR) and 95%CI.

Results

Of the 640,672 participants, 121,254 women suffered from anemia, with the prevalence of 18.9% (95%CI: 18.8–19.0%). From 2014 to 2018, the prevalence of anemia declines from 23.0–16.4%.The prevalence was 21.6% in the first trimester, higher than women in non-pregnancy (17.4%) and women in the third trimester (10.5%). Results from the multivariable logistic regression showed that women aged 18–20 (aOR = 1.28) or over 35 years old (aOR = 1.07), being farmers (aOR = 1.42), being ethnic minorities (aOR: 1.19 ~ 1.73), during the first trimester (aOR = 1.32) were more likely to be anemic.

Conclusions

Although the anemia prevalence of women of reproductive age has been decreasing in recent years, the prevalence of anemia is still high in pregnant and non-pregnant women in southwest China, especially during the first trimester. Women who were older or younger, being farmers, being ethnic minorities were at high risk of anemia. Anemia in women of reproductive age cannot be neglected.
Cost-effectiveness analysis comparing companion diagnostic tests for EGFR, ALK, and ROS1 versus next-generation sequencing (NGS) in advanced adenocarcinoma lung cancer patients
Authors: Schluckebier Luciene , Caetano Rosangela , Garay Osvaldo Ulises , Montenegro Giuliana T. , Custodio Marcelo , Aran Veronica , Gil Ferreira Carlos
Published: September 2020

Background

The treatment of choice for advanced non–small cell lung cancer is selected according to the presence of specific alterations. Patients should undergo molecular testing for relevant modifications and the mutational status of EGFR and translocation of ALK and ROS1 are commonly tested to offer the best intervention. In addition, the tests costs should also be taken in consideration. Therefore, this work was performed in order to evaluate the cost-effectiveness of a unique exam using NGS (next generation sequencing) versus other routinely used tests which involve RT-PCR and FISH.

Methods

The target population was NSCLC, adenocarcinoma, and candidates to first-line therapy. Two strategies were undertaken, strategy 1 corresponded to sequential tests with EGFR RT-PCR, then FISH for ALK and ROS1. Strategy 2 differed from 1 in that ALK and ROS1 translocation testing were performed simultaneously by FISH. Strategy 3 considered single test next-generation sequencing, a platform that includes EGFR, ALK and ROS1 genes. A decision tree analysis was used to model genetic testing options. From the test results, a microsimulation model was nested to estimate survival outcomes and costs of therapeutic options.

Results

The use of NGS added 24% extra true cases as well as extra costs attributed to the molecular testing. The ICER comparing NGS with sequential tests was US$ 3479.11/correct case detected. The NGS improved a slight gain in life years and QALYs.

Conclusion

Our results indicated that, although precise, the molecular diagnosis by NGS of patients with advanced stage NSCLC adenocarcinoma histology was not cost-effective in terms of quality-adjusted life years from the perspective of the Brazilian supplementary health system.
Perceptions of key informants on the provision of cervical cancer prevention and control programme in Uganda: implication for cervical cancer policy
Authors: Obol James Henry , Harrison Reema , Lin Sophia , Obwolo Mark James , Richmond Robyn
Published: September 2020

Background

Uganda has one of the highest burdens of cervical cancer globally. In 2010 the Ugandan Ministry of Health launched the Strategic Plan for Cervical Cancer Prevention and Control with the hope of developing cervical cancer policy in Uganda. This study explored the beliefs of senior key informants in Uganda about cervical cancer prevention, the control programme, and the relevance of cervical cancer policy.

Methods

We conducted 15 key informant interviews with participants from six organisations across Northern and Central Uganda. Participants were drawn from district local government health departments, St. Mary’s Hospital Lacor, Uganda Nurses and Midwifery Council, non-governmental organisations (NGOs) and Ministry of Health in Kampala, Uganda. The interview recordings were transcribed and analysed using thematic analysis.

Results

Seven themes emerged relating to the cervical cancer prevention and control programmes in Uganda: (1) policy frameworks for cervical cancer, (2) operationalising cervical cancer prevention and control, (3) financial allocation and alignment, (4) human resources and capability, (5) essential supplies and vaccines, (6) administrative data and resource distribution, and (7) cervical cancer services.

Conclusions

The key informants perceive that the lack of a cervical cancer policy in Uganda is hindering cervical cancer prevention and control programmes. Therefore, the Ministry of Health and stakeholders need to work together in coming up with an effective policy framework that will accelerate efforts towards cervical cancer prevention and control in Uganda.
Coexistence between human and wildlife: the nature, causes and mitigations of human wildlife conflict around Bale Mountains National Park, Southeast Ethiopia
Authors: Mekonen Sefi
Published: September 2020

Human–wildlife conflict occurs when the needs and behavior of wildlife impact negatively on humans or when humans negatively affect the needs of wildlife. To explore the nature, causes and mitigations of human wildlife conflict, the coexistence between human and wildlife assessment was conducted around Bale Mountains National Park. Data were collected by means of household questionnaires, focus group discussion, interview, field observation and secondary sources. The nature and extent of human wildlife conflict in the study area were profoundly impacted humans, wild animal and the environment through crop damage, habitat disturbance and destruction, livestock predation, and killing of wildlife and human. The major causes of conflict manifested that agricultural expansion (30%), human settlement (24%), overgrazing by livestock (14%), deforestation (18%), illegal grass collection (10%) and poaching (4%). To defend crop raider, farmers have been practiced crop guarding (34%), live fencing (26%), scarecrow (22%), chasing (14%), and smoking (5%). However, fencing (38%), chasing (30%), scarecrow (24%) and guarding (8%) were controlling techniques to defend livestock predator animals. As emphasized in this study, human–wildlife conflicts are negative impacts on both human and wildlife. Accordingly, possible mitigate possibilities for peaceful co-existence between human and wildlife should be create awareness and training to the local communities, identifying clear border between the closure area and the land owned by the residents, formulate rules and regulation for performed local communities, equal benefit sharing of the local communities and reduction of human settlement encroachment into the national park range. Generally, researcher recommended that stakeholders and concerned bodies should be creating awareness to local community for the use of wildlife and human–wildlife conflict mitigation strategies.
Determinants of early sexual initiation among female youth in Ethiopia: a multilevel analysis of 2016 Ethiopian Demographic and Health Survey
Authors: Arefaynie Mastewal , Yalew Melaku , Damtie Yitayish , Kefale Bereket
Published: September 2020

Background

Evidences on determinants of early sexual initiation among female youth is still limited especially; community-level factors are not investigated in Ethiopia. Therefore, the aim of this study was to assess individual and community-level factors associated with early sexual initiation among female youth in Ethiopia.

Methods

The 2016 Ethiopian Demographic and Health Survey (EDHS) dataset were used and a total of 6143 participants (female youth) were included. Multi-level mixed-effect logistic regression was done to identify individual and community-level factors. Adjusted odds ratio along with 95% confidence interval was used to show the strength and direction of the association. Finally, the level of statistical significance was declared atPvalue less than 0.05.

Results

Individual-level factors significantly associated with early sexual initiation among female youth were; age group from 19 to 24 years [AOR = 5.8, 95% CI = (4.6, 7.3)], not attending school [AOR = 14.1, 95% CI = (8.1, 24.7)], ever chewing Chat [AOR = 2.0, 95% CI = (1.3, 3.0)]. From community-level factors: living in Addis Ababa [AOR = 0.3, 95% CI = (0.2, 0.5)], living in Gambella [AOR = 2.7, 95% CI = (1.7, 4.3)] and live in a low proportion of poor communities [AOR = 0.7, 95% CI = (0.5, 0.9)] were significantly associated with early sexual initiation among female youth in Ethiopia.

Conclusions

Age, low educational status, ever chewing Chat, region and live in a high proportion of poor community had a statistical association with early sexual initiation among female youth in Ethiopia. Improving educational coverage and community-level of wealth status are important intervention areas to delay the age of early sexual initiation.
Study on metastasis inhibition of Kejinyan decoction on lung cancer by affecting tumor microenvironment
Authors: Chen Meijuan , Hu Cheng , Gao Qian , Li Liqiu , Cheng Ziyu , Li Qirui , Li Zhihui , Wang Zhaohui , Mao Zejia , Tian Weiqian , Zhang Xu
Published: September 2020

Background

Kejinyan decoction, as an experienced formula of Zhou Zhongying (the Master of Traditional Chinese Medicine) has been widely used in clinic for lung cancer treatment in China, while the anti-lung cancer mechanism of it is still remained to be elucidated. Herein, our basic study found that the survival of lung cancer xenograft mice was significantly prolonged after intragastrically administered high dose of Kejinyan decoction (3.8 g per kg BW) for 15 days. More importantly, we found that Kejinyan decoction inhibited the metastasis of lung cancer cells in vivo. Thus in this study, we aim to elucidate the anti-metastasis effects of Kejinyan decoction.

Methods

RNA-Seq was used to find out the gene regulation of Kejinyan decoction on the mice, flow cytometry assay was used to detect the immunocytes in the spleen, ELISA assay was used to detect the inflammatory factors in the serum and spleen, and immunofluorescence assay was used to detect the level of immune cells and the expression of glycol-metabolism related enzymes in situ. Also, we established a lung cancer orthotopic xenograft tumor model to assess the influence of Kejinyan decoction on the metastatic ability of lung cancer cells in vivo.

Results

GO analysis of gene sequencing of tumor tissue samples showed that Kejinyan decoction regulated immune response. Further flow cytometry analysis of splenic lymphocyte showed that Kejinyan decoction upregulated M1 macrophages and downregulated M2 macrophages, while the total level of macrophages changed little, which was verified by detection of CD68, F4/80, CD206, and CD86 in tumor tissue section. Moreover, detection of inflammatory cytokines showed that Kejinyan decoction downregulated TNF-α, IFN-γ, IL-6, as well as IL-4, IL-13 in tumor microenvironment. Further studies also showed that Kejinyan decoction had little effect on tumor hypoxia, but downregulated glycolysis in tumor tissues. More importantly, we found that Kejinyan decoction inhibited the metastasis of lung cancer cells in vivo.

Conclusion

Our findings conclude that Kejinyan decoction inhibited lung cancer cell metastasis through affecting macrophage polarization and energy reprogramming.
Long non-coding RNA BCYRN1 exerts an oncogenic role in colorectal cancer by regulating the miR-204-3p/KRAS axis
Authors: Yang Liu , Zhang Yinan , Bao Jun , Feng Ji-Feng
Published: September 2020

Background

It has been well documented that long non-coding RNAs (lncRNAs) regulate numerous characteristics of cancer, including proliferation, migration, metastasis, apoptosis, and even metabolism. LncRNA BCYRN1 (BCYRN1) is a newly identified brain cytoplasmic lncRNA with 200 nucleotides that was discovered to be highly expressed in tumour tissues, including those of hepatocellular carcinoma, gastric cancer and lung cancer. However, the roles of BCYRN1 in colorectal cancer (CRC) remain obscure. This study was designed to reveal the role of BCYRN1 in the occurrence and progression of CRC.

Methods

RT-PCR was used to detect the expression level of BCYRN1 in tumour tissues and CRC cell lines. BCYRN1 was knocked down in CRC cells, and cell proliferation changes were evaluated by cell counting kit-8 (CCK-8), 5-ethynyl-2′-deoxyuridine (EdU), and Ki-67 and proliferating cell nuclear antigen (PCNA) expression assays. Cell migration and invasion changes were evaluated by wound healing, Transwell and invasion-related protein expression assays. Flow cytometry analysis was used to assess whether BCYRN1 regulates the apoptosis of CRC cells. The dual luciferase reporter gene detects the competitive binding of BCYRN1 to miR-204-3p. In vivo experiments were performed to evaluate the effect of BCYRN1 on tumour development. TargetScan analysis and dual luciferase reporter gene assays were applied to detect the target gene of miR-204-3p. Rescue experiments verified that BCYRN1 affects CRC by regulating the effect of miR-204-3p on KRAS.

Results

We found that compared with normal tissues and human intestinal epithelial cells (HIECs), CRC tumour tissues and cell lines had significantly increased BCYRN1 levels. We further determined that knockdown of BCYRN1 inhibited the proliferation, migration, and invasion and promoted the apoptosis of CRC cells. In addition, bioinformatics analysis and dual luciferase reporter assay showed that BCYRN1 served as a competitive endogenous RNA (ceRNA) to regulate the development of CRC through competitively binding to miR-204-3p. Further studies proved that overexpression of miR-204-3p reversed the effects of BCYRN1 on CRC. Next, TargetScan analysis and dual luciferase reporter assay indicated that KRAS is a target gene of miR-204-3p and is negatively regulated by miR-204-3p. A series of rescue experiments showed that BCYRN1 affected the occurrence and development of CRC by regulating the effects of miR-204-3p on KRAS. In addition, tumorigenesis experiments in a CRC mouse model confirmed that BCYRN1 downregulation effectively inhibited tumour growth.

Conclusions

Our findings suggest that BCYRN1 plays a carcinogenic role in CRC by regulating the miR-204-3p/KRAS axis.
Correction to: Prevalence and clinical impact of malaria infections detected with a highly sensitive HRP2 rapid diagnostic test in Beninese pregnant women
Authors: Briand Valérie , Cottrell Gilles , Tuikue Ndam Nicaise , Martiáñez–Vendrell Xavier , Vianou Bertin , Mama Atika , Kouwaye Bienvenue , Houzé Sandrine , Bailly Justine , Gbaguidi Erasme , Sossou Darius , Massougbodji Achille , Accrombessi Manfred , Mayor Alfredo , Ding Xavier C. , Fievet Nadine
Published: September 2020

An amendment to this paper has been published and can be accessed via the original article.
Identification of the largest non-essential regions of the C-terminal portion in 3A protein of foot-and-mouth disease virus for replication in cell culture
Authors: Li Pinghua , Ma Xueqing , Bai Xingwen , Sun Pu , Yuan Hong , Cao Yimei , Li Kun , Bao Huifang , Fu Yuanfang , Zhang Jing , Chen Yingli , Li Dong , Li Zhiyong , Lu Zengjun , Liu Zaixin
Published: September 2020

Background

Recent study has shown that the C-terminal portion of 3A (amino acids (aa) 81–153) is not essential for foot-and-mouth disease virus replication in cell culture, however, the complete C-terminal portion (aa 77–153) of 3A is highly variable and prone to occur deletions and mutations, therefore, we presume that this region plays a very limited role and probablely is completely nonessential for virus viability.

Methods

In this study, to identify the largest non-essential region of the C-terminal portion in 3A for FMDV viability, several deletions containing aa 80–153, 77–153 and 76–153 of 3A protein were introduced into an FMDV full-length infectious cDNA clone pOFS by the overlapping extension PCR. Additionally, to explore the importance of the highly conserved residue 76 L of 3A for the FMDV of Cathay topotype, two mutants containing 3A L76I and 3A L76V were generated based on the 3A deletion mutant by point mutation. We also introduced the enhanced green fluorescent protein (eGFP) into one of the 3A deletion mutants by the extension PCR to investigate the genetic flexibility of 3A to express foreign genes. All linearized full plasmids were transfected into BSR/T7 cells to rescue infectious foot-and-mouth disease viruses. The rescused viruses were analyzed by RT-PCR, nucleotide sequencing, immunofluorescence assay and western blot and were characterized by plaque assays and one-step growth kinetics.

Results

The results demonstrated that the deletion of aa 80–153 and aa 77–153 and the substitutions of 3A L76I and 3A L76V did not affect the production of infectious virus, while the fusion of the eGFP gene to the C-terminus of 3A resulted in nonviable FMDV.

Conclusions

Our results firstly reported that the aa 77–153 rather than aa 81–153 of 3A protein was dispensable for FMDV replication in cell culture. This study is of great significance for development of FMD marker vaccine and foreign gene expression in the future.
Atypical periprosthetic femoral fracture associated with long-term bisphosphonate therapy
Authors: Dózsai Dávid , Ecseri Tamás , Csonka István , Gárgyán István , Doró Péter , Csonka Ákos
Published: September 2020

Background

Atypical femoral fracture is one of the many complications after the long-term use of bisphosphonates. The American Society for Bone and Mineral Research has officially excluded periprosthetic femoral fractures (PFFs) from the definition of atypical femoral fractures (AFFs). Several case reports found that PFFs can occur with characteristics similar to those of AFFs. The purpose of our study was to evaluate the proportion of atypical fractures among Vancouver type B1 fractures, and to determine the association between the long-term use of bisphosphonates and the occurrence of atypical periprosthetic femoral fractures (APFFs).

Methods

In this retrospective study, we reviewed 41 patients with Vancouver type B1 periprosthetic fractures between January 1, 2011 and December 31, 2018. We classified them into two groups, namely atypical and typical PFFs, based on the fracture morphology. We noted the proportion of atypical periprosthetic fractures among B1 fractures and identified risk factors.

Results

Among the 41 PFFs, 5 (13%) fractures were classified as atypical PFF based on the radiological characteristics. The longer duration of bisphosphonate use was probably the only independent risk factor that significantly increases the occurrence of APFF (p = 0.03, 0.08 (CI 0.008 – 0.16)). There were no significant differences in age, gender, body mass index, comorbidities, corticosteroid use, positioning of the femoral stem, the method of fixation (cemented or cementless) and time lapse from before the primary prosthesis implantation to the PFF in the development of atypical fracture type.

Conclusions

There seems to be a correlation between the long-term intake of bisphosphonates and the atypical periprosthetic fracture. Atypical femoral fracture can also occur in the periprosthetic form.

Trial registration

Study number: 22/2019-SZTE, http://www.klinikaikutatas.hu/hu/kutatasetika/jovahagyott-vizsgalatok-koezerdeku-adatai/category/25-jovahagyott-vizsgalatok-kozerdeku-adatai-rkeb-2019.html?download=985:22-2019.
Tie2-mediated vascular remodeling by ferritin-based protein C nanoparticles confers antitumor and anti-metastatic activities
Authors: Choi Young Sun , Jang Hyeonha , Gupta Biki , Jeong Ji-Hak , Ge Yun , Yong Chul Soon , Kim Jong Oh , Bae Jong-Sup , Song Im-Sook , Kim In-San , Lee You Mie
Published: September 2020

Background

Conventional therapeutic approaches for tumor angiogenesis, which are primarily focused on the inhibition of active angiogenesis to starve cancerous cells, target the vascular endothelial growth factor signaling pathway. This aggravates hypoxia within the tumor core and ultimately leads to increased tumor proliferation and metastasis. To overcome this limitation, we developed nanoparticles with antiseptic activity that target tumor vascular abnormalities.

Methods

Ferritin-based protein C nanoparticles (PCNs), known as TFG and TFMG, were generated and tested in Lewis lung carcinoma (LLC) allograft and MMTV-PyMT spontaneous breast cancer models. Immunohistochemical analysis was performed on tumor samples to evaluate the tumor vasculature. Western blot and permeability assays were used to explore the role and mechanism of the antitumor effects of PCNs in vivo. For knocking down proteins of interest, endothelial cells were transfected with siRNAs. Statistical analysis was performed using one-way ANOVA followed by post hoc Dunnett’s multiple comparison test.

Results

PCNs significantly inhibited hypoxia and increased pericyte coverage, leading to the inhibition of tumor growth and metastasis, while increasing survival in LLC allograft and MMTV-PyMT spontaneous breast cancer models. The coadministration of cisplatin with PCNs induced a synergistic suppression of tumor growth by improving drug delivery as evidenced by increased blood prefusion and decreased vascular permeability. Moreover, PCNs altered the immune cell profiles within the tumor by increasing cytotoxic T cells and M1-like macrophages with antitumor activity. PCNs induced PAR-1/PAR-3 heterodimerization through EPCR occupation and PAR-1 activation, which resulted in Gα13-RhoA-mediated-Tie2 activation and stabilized vascular tight junctions via the Akt-FoxO3a signaling pathway.

Conclusions

Cancer treatment targeting the tumor vasculature by inducing antitumor immune responses and enhancing the delivery of a chemotherapeutic agent with PCNs resulted in tumor regression and may provide an effective therapeutic strategy.
Current understanding of extrachromosomal circular DNA in cancer pathogenesis and therapeutic resistance
Authors: Yan Yuanliang , Guo Guijie , Huang Jinzhou , Gao Ming , Zhu Qian , Zeng Shuangshuang , Gong Zhicheng , Xu Zhijie
Published: September 2020

Extrachromosomal circular DNA was recently found to be particularly abundant in multiple human cancer cells, although its frequency varies among different tumor types. Elevated levels of extrachromosomal circular DNA have been considered an effective biomarker of cancer pathogenesis. Multiple reports have demonstrated that the amplification of oncogenes and therapeutic resistance genes located on extrachromosomal DNA is a frequent event that drives intratumoral genetic heterogeneity and provides a potential evolutionary advantage. This review highlights the current understanding of the extrachromosomal circular DNA present in the tissues and circulation of patients with advanced cancers and provides a detailed discussion of their substantial roles in tumor regulation. Confirming the presence of cancer-related extrachromosomal circular DNA would provide a putative testing strategy for the precision diagnosis and treatment of human malignancies in clinical practice.
Studies on sugar transporter CRT1 reveal new characteristics that are critical for cellulase induction in Trichoderma reesei
Authors: Havukainen Sami , Valkonen Mari , Koivuranta Kari , Landowski Christopher P.
Published: September 2020

Background

Trichoderma reesei is an ascomycete fungus that has a tremendous capability of secreting extracellular proteins, mostly lignocellulose-degrading enzymes. Although many aspects of the biology of this organism have been unfolded, the roles of the many sugar transporters coded in its genome are still a mystery with a few exceptions. One of the most interesting sugar transporters that has thus far been discovered is the cellulose response transporter 1 (CRT1), which has been suggested to be either a sugar transporter or a sensor due to its seemingly important role in cellulase induction.

Results

Here we show that CRT1 is a high-affinity cellobiose transporter, whose function can be complemented by the expression of other known cellobiose transporters. Expression of two sequence variants of the crt1 gene in Saccharomyces cerevisiae revealed that only the variant listed in the RUT-C30 genome annotation has the capability to transport cellobiose and lactose. When expressed in the $$\Delta$$
Δ
crt1 strain, the variant listed in the QM6a genome annotation offers partial complementation of the cellulase induction, while the expression of the RUT-C30 variant or cellobiose transporters from two other fungal species fully restore the cellulase induction.

Conclusions

These results add to our knowledge about the fungal metabolism of cellulose-derived oligosaccharides, which have the capability of inducing the cellulase production in many species. They also help us to deepen our understanding of the T. reesei lactose metabolism, which can have important consequences as this sugar is used as the inducer of protein secretion in many industrial processes which employ this species.
Assessing the vertical transmission potential of dengue virus in field-reared Aedes aegypti using patient-derived blood meals in Ho Chi Minh City, Vietnam
Authors: Goncalves Daniela da Silva , Hue Kien Duong Thi , Thuy Vi Tran , Tuyet Nhu Vu , Thi Giang Nguyen , Thi Thuy Van Huynh , Xuan Trang Huynh Thi , Thi Dui Le , Vo Long Thi , Le Anh Huy Huynh , Van Thuy Nguyen Thi , Wills Bridget A. , Thanh Phong Nguyen , Simmons Cameron P. , Carrington Lauren B.
Published: September 2020

Background

Dengue viruses (DENV) can be transmitted from an adult female Aedes aegypti mosquito through the germ line to the progeny; however, there is uncertainty if this occurs at a frequency that is epidemiologically significant. We measured vertical transmission of DENV from field-reared Ae. aegypti to their F1 progeny after feeding upon blood from dengue patients. We also examined the transmission potential of F1 females.

Methods

We examined the frequency of vertical transmission in field-reared mosquitoes, who fed upon blood from acutely viremic dengue patients, and the capacity for vertically infected females to subsequently transmit virus horizontally, in two sets of experiments: (i) compared vertical transmission frequency of field-reared Ae. aegypti and Ae. albopictus, in individual progeny; and (ii) in pooled progeny derived from field- and laboratory-reared Ae. aegypti.

Results

Of 41 DENV-infected and isofemaled females who laid eggs, only a single female (2.43%) transmitted virus to one of the F1 progeny, but this F1 female did not have detectable virus in the saliva when 14 days-old. We complemented this initial study by testing for vertical transmission in another 460 field-reared females and > 900 laboratory-reared counterparts but failed to provide any further evidence of vertical virus transmission.

Conclusions

In summary, these results using field-reared mosquitoes and viremic blood from dengue cases suggest that vertical transmission is uncommon. Field-based studies that build on these observations are needed to better define the contribution of vertical DENV transmission to dengue epidemiology.
Association between lone star tick bites and increased alpha-gal sensitization: evidence from a prospective cohort of outdoor workers
Authors: Mitchell Cedar L. , Lin Feng-Chang , Vaughn Meagan , Apperson Charles S. , Meshnick Steven R. , Commins Scott P.
Published: September 2020

Background

Alpha-gal is an oligosaccharide implicated in delayed anaphylaxis following red meat consumption. Exposure to tick bites has been correlated with development of an allergic response to alpha-gal. However, evidence prospectively linking exposure to a single tick species and an immune response to alpha-gal is lacking.

Methods

We used serum samples from a prior study cohort of outdoor workers in North Carolina, USA, with high exposure to the lone star tick, Amblyomma americanum, to prospectively evaluate the relationship between tick bites and anti-alpha-gal IgE antibodies.

Results

Individuals who reported exposure to one or more tick bites were significantly more likely to have a positive change in anti-alpha-gal IgE compared to individuals with no reported tick bites. This relationship was not dependent on time. A trend toward increasing number of tick bites and increased anti-alpha-gal IgE levels was observed but not statistically significant.

Conclusion

To our knowledge, this is the first study to prospectively link documented exposure to A. americanum bites and increased sensitization to alpha-gal in a cohort of outdoor workers. Our results support the role of A. americanum as likely agents for eliciting an allergic response to red meat, and highlight the importance of preventing tick bites.
The impact of systemic lupus erythematosus on the risk of infection after total hip arthroplasty: a nationwide population-based matched cohort study
Authors: Chen Chien-Hao , Chen Tien-Hsing , Lin Yu-Sheng , Chen Dave W. , Sun Chi-Chin , Kuo Liang-Tseng , Shao Shih-Chieh
Published: September 2020

Background

We aimed to assess the impact of systemic lupus erythematosus (SLE) on the risk of infection after total hip arthroplasty (THA).

Methods

We identified patients undergoing primary THA (1996–2013) in Taiwan National Health Insurance Research Database (NHIRD). Patients were then divided into the SLE and control groups according to the diagnosis of SLE. We used 1:1 propensity score to match the control to the SLE group by age, sex, and comorbidities. The primary outcome was infection, including early and late superficial wound infection and periprosthetic joint infection (PJI). The secondary outcome was in-hospital complications.

Results

We enrolled 325 patients in each group. In the primary outcome, the incidence of early superficial wound infection and PJI was comparable between the SLE and matched-control group. However, the incidence of late superficial wound infection and PJI in the SLE group was higher than that in matched-control group (11.4% vs. 5.5%, P = 0.01; 5.2% vs 2.2%, P = 0.04, respectively). Furthermore, the SLE group had a higher risk for late superficial wound infection and PJI (hazard ratio = 2.37, 95% confidence interval (CI) 1.35–4.16; HR = 2.74, 95% CI 1.14–6.64, respectively) than the matched-control. Complications other than infection and in-hospital mortality cannot be compared because of very low incidence.

Conclusions

SLE is a risk factor for developing late superficial wound infection and PJI, but not for early postoperative complications following THA. Clinical presentations should be monitored to avoid misdiagnosis of PJI in SLE patients after THA.
Detection of colonisation by extended-spectrum beta-lactamase or carbapenemase producing Enterobacterales from frozen stool specimens
Authors: Tan Pisey , Singh Shweta R. , Mao Bunsoth , Evdokimov Konstantin , Saphonn Vonthanak , Hsu Li Yang , Turner Paul
Published: September 2020

Objective

To determine the impact of pre-culture ultra-low temperature (ULT, − 80 °C) storage of human stool specimens on recovery of Extended-Spectrum Beta-Lactamase (ESBL) or Carbapenemase (CPM) producing Enterobacterales.

Results

Twenty stool specimens from a community-based household colonisation study in Cambodia were cultured fresh and after 4–5 days and ~ 6 months of ULT storage (as a slurry in tryptone soya broth–10% glycerol). Presumptive ESBL- and CPM-Escherichia coli isolates were detected in 19/20 (95%) and 1/20 (5%) freshly cultured specimens, respectively. The specimens yielded identical results when re-cultured after ULT storage at both time points. Detection of presumptive ESBL- and CPM-Klebsiella / Enterobacter / Citrobacter group was less frequent and slightly less stable over time. Comparison of antimicrobial susceptibility test profiles between pairs of E. coli and K. pneumoniae isolates from the two frozen culture time points revealed concordance in only 13/28 (46%) pairs, indicating likely colonisation by multiple strains. In conclusion, ULT storage of human stool specimens prior to culture appears to be an acceptable method for managing laboratory workflow in culture-based ESBL / CPM Enterobacterales colonisation studies in high prevalence settings.
Newborn’s first bath: any preferred timing? A pilot study from Lebanon
Authors: Mardini Joelle , Rahme Clara , Matar Odette , Abou Khalil Sophia , Hallit Souheil , Fadous Khalife Marie-Claude
Published: September 2020

Objective

To try to find the most appropriate time for the newborn’s first bath. This prospective randomized study was conducted in one hospital (July–September 2017).

Results

A higher percentage of newborns who had a skin-to-skin contact with their mothers had their bath at 24 h vs 2 h after birth (65.2% vs 33.3%; p = 0.01). A higher percentage of mothers who helped in their baby’s bath had their baby’s bath at 24 h vs 2 h (65.2% vs 5.9%; p < 0.001) and vs 6 h (65.2% vs 15.7%; p < 0.001) respectively. A higher mean incubation time was seen between newborns who had their bath at 2 h (2.10 vs 1.78; p = 0.002) and 6 h (2.18 vs 1.78; p = 0.003) compared to those who had their bath at 24 h respectively. A higher percentage of newborns who took their first bath 24 h after birth were calm compared to crying vigorously (38.6% vs 9.1%; p = 0.04). Delaying newborn first bath until 24 h of life was associated with benefits (reducing hypothermia and vigorous crying, benefit from the vernix caseosa on the skin and adequate time of skin-to-skin contact and mother participation in her child’s bathing.
Unraveling the therapeutic effects of mesenchymal stem cells in asthma
Authors: Mirershadi Fatemeh , Ahmadi Mahdi , Rezabakhsh Aysa , Rajabi Hadi , Rahbarghazi Reza , Keyhanmanesh Rana
Published: September 2020

Asthma is a chronic inflammatory disease associated with airway hyper-responsiveness, chronic inflammatory response, and excessive structural remodeling. The current therapeutic strategies in asthmatic patients are based on controlling the activity of type 2 T helper lymphocytes in the pulmonary tissue. However, most of the available therapies are symptomatic and expensive and with diverse side outcomes in which the interruption of these modalities contributes to the relapse of asthmatic symptoms. Up to date, different reports highlighted the advantages and beneficial outcomes regarding the transplantation of different stem cell sources, and relevant products from for the diseases’ alleviation and restoration of injured sites. However, efforts to better understand by which these cells elicit therapeutic effects are already underway. The precise understanding of these mechanisms will help us to translate stem cells into the clinical setting. In this review article, we described current knowledge and future perspectives related to the therapeutic application of stem cell-based therapy in animal models of asthma, with emphasis on the underlying therapeutic mechanisms.
Acute and long-term effects of antibiotics commonly used in laboratory animal medicine on the fecal microbiota
Authors: Korte Scott W. , Dorfmeyer Rebecca A. , Franklin Craig L. , Ericsson Aaron C.
Published: September 2020

Biomedical research relies on the use of animal models, and the animals used in those models receive medical care, including antibiotics for brief periods of time to treat conditions such as dermatitis, fight wounds, and suspected bacterial pathogens of unknown etiology. As many mouse model phenotypes are sensitive to changes in the gut microbiota, our goal was to examine the effect of antibiotics commonly administered to mice. Therefore, four treatment groups (subcutaneous enrofloxacin for 7 days, oral enrofloxacin for 14 days, oral trimethoprim-sulfamethoxazole for 14 days, and topical triple antibiotic ointment for 14 days) alongside a fifth control group receiving no treatment (n = 12/group) were included in our study. Fecal samples were collected prior to treatment, immediately after two weeks of exposure, and four weeks after cessation of treatment, and subjected to 16S rRNA library sequencing. The entire experimental design was replicated in mice from two different suppliers. As expected, several treatments including enrofloxacin and triple antibiotic ointment substantially decreased the amount of DNA recovered from fecal material, as well as the microbial richness. Notably, many of these effects were long-lasting with diminished gut microbiota (GM) richness four weeks following exposure, in both substrains of mice. Trimethoprim-sulfamethoxazole induced minimal to no discernible changes in the taxonomic composition beyond that seen in control mice. Collectively, these data highlight the need to consider the impact on GM of brief and seemingly routine use of antibiotics in the clinical care of research animals.
A novel genotyping technique for discriminating LVAS-associated high-frequency variants in SLC26A4 gene
Authors: Zhou Chen , Zou Xiangman , Peng Cuiying , Gao Guoqiang , Guo Zifen
Published: September 2020

An increasing number of biological and epidemiological evidence suggests that c.919-2A > G and c.2168A > G variants of solute carrier family 26, member 4 (SLC26A4) gene play a critical role in the development of large vestibular aqueduct syndrome (LVAS). In this study, we developed a rapid genotyping method for discriminating LVAS-associated high-frequency variants in SLC26A4 gene. The genotyping technique consists of 3′ terminal exonuclease-resistant phosphorothioate-modified allele specific primer extension mediated by exo+ polymerase. In PCR amplification by Pfu polymerase, allelic specific primers perfectly matching wild type allele were extended while no specific products were yielded from primers targeting variant allele. Similarly, allelic specific primers perfectly matching variant allele were extended and no specific products were observed from primers targeting wild type allele. The clinical application of 3′ terminal phosphorothioate-modified allele specific primer extension mediated by Pfu polymerase identified both homozygous for SLC26A4 gene c.919-2A > G variant in two patients clinically diagnosed as LVAS by temporal bone CT scan. The genetic results from this method are consistent with that of DNA sequencing. The data suggest that exo+ polymerase-mediated 3′ terminal phosphorothioate-modified primer extension is reliable in the identification of SLC26A4 gene high-frequency variant prior to high-resolution CT scan. The method is extremely suitable for quickly molecular etiologic screening and early diagnosis and aggressive prevention therapy of LVAS.
Correction to: Highlights and recent developments in skin allergy and related diseases in EAACI journals (2018)
Authors: Akdis C. A. , Bousquet J. , Grattan C. E. , Eigenmann P. A. , Hofmann-Sommergruber K. , Agache I. , Jutel M.
Published: September 2020

An amendment to this paper has been published and can be accessed via the original article.
Potential risks in using midodrine for persistent hypotension after cardiac surgery: a comparative cohort study
Authors: Tremblay Jan-Alexis , Laramée Philippe , Lamarche Yoan , Denault André , Beaubien-Souligny William , Frenette Anne-Julie , Kontar Loay , Serri Karim , Charbonney Emmanuel
Published: September 2020

Background

Persistent hypotension is a frequent complication after cardiac surgery with cardiopulmonary bypass (CPB). Midodrine, an orally administered alpha agonist, could potentially reduce intravenous vasopressor use and accelerate ICU discharge of otherwise stable patients. The main objective of this study was to explore the clinical impacts of administering midodrine in patients with persistent hypotension after CPB. Our hypothesis was that midodrine would safely accelerate ICU discharge and be associated with more days free from ICU at 30 days.

Results

We performed a retrospective cohort study that included all consecutive patients having received midodrine while being on vasopressor support in the ICU within the first week after cardiac surgery with CPB, between January 2014 and January 2018 at the Montreal Heart Institute. A contemporary propensity score matched control group that included patients who presented similarly prolonged hypotension after cardiac surgery was formed.

After matching, 74 pairs of patients (1:1) fulfilled inclusion criteria for the study and control groups. Midodrine use was associated with fewer days free from ICU (25.8 [23.7–27.1] vs 27.2 [25.9–28] days, p = 0.002), higher mortality (10 (13.5%) vs 1 (1.4%), p = 0.036) and longer ICU length of stay (99 [68–146] vs 68 [48–99] hours, p = 0.001). There was no difference in length of intravenous vasopressors (63 [40–87] vs 44 [26–66] hours, p = 0.052), rate of ICU readmission (6 (8.1%) vs 2 (2.7%), p = 0.092) and occurrence of severe kidney injury (11 (14.9%) vs 10 (13.5%) patients, p = 0.462) between groups.

Conclusion

The administration of midodrine for sustained hypotension after cardiac surgery with CPB was associated with fewer days free from ICU and higher mortality. Routine prescription of midodrine to hasten ICU discharge after cardiac surgery should be used with caution until further prospective studies are conducted.