bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased expression level of ANGPTL8 in white adipose tissue under acute and chronic cold treatment
Authors: Arefanian Hossein , Al-Khairi Irina , Khalaf Nermeen Abu , Cherian Preethi , Kavalakatt Sina , Madhu Dhanya , Mathur Aditi , Qaddoumi Mohamed G. , Al-Mulla Fahd , Abubaker Jehad , Abu-Farha Mohamed
Published: September 2021

Background

Angiopoietin-like proteins (ANGPTL), primarily 3, 4, and 8, play a major role in maintaining energy homeostasis by regulating triglyceride metabolism. This study evaluated the level of ANGPTL3, 4, and 8 in the liver, brown adipose tissue (BAT), and subcutaneous white adipose tissue (SAT) of mice maintained under acute and chronic cold conditions.

Methods

C57BL/6J mice were exposed to cold temperature (4 °C) for 10 days with food provided ad libitum. Animal tissues were harvested at Day 0 (Control group, n = 5) and Days 1, 3, 5, and 10 (cold treatment groups, n = 10 per group). The expression levels of various genes were measured in the liver, SAT, and BAT. ANGPTL3, 4, and 8 expressions were measured in the liver. ANGPTL4, 8, and genes involved in browning and lipid metabolism [uncoupling protein 1 (UCP1), lipoprotein lipase (LPL), and adipose triglyceride lipase (ATGL)] were measured in SAT and BAT. Western blotting (WB) analysis and immunohistochemistry (IHC) were performed to confirm ANGPTL8 expression in these tissues.

Results

The expressions of ANGPTL3 and 8 mRNA were significantly reduced in mouse liver tissues after cold treatment (P < 0.05); however, the expression of ANGPTL4 was not significantly altered. In BAT, ANGPTL8 expression was unchanged after cold treatment, whereas ANGPTL4 expression was significantly reduced (P < 0.05). ANGPTL4 levels were also significantly reduced in SAT, whereas ANGPTL8 gene expression exhibited over a 5-fold increase. Similarly, UCP1 gene expression was also significantly increased in SAT. The mRNA levels of LPL and ATGL showed an initial increase followed by a gradual decrease with an increase in the days of cold exposure. ANGPTL8 protein overexpression was further confirmed by WB and IHC.

Conclusions

This study shows that exposure to acute and chronic cold treatment results in the differential expression of ANGPTL proteins in the liver and adipose tissues (SAT and BAT). The results show a significant reduction in ANGPTL4 in BAT, which is linked to improved thermogenesis in response to acute cold exposure. ANGPTL8 was activated under acute and chronic cold conditions in SAT, suggesting that it is involved in regulating lipolysis and enhancing SAT browning.
Highly sensitive and portable mRNA detection platform for early cancer detection
Authors: Li Hongxia , Warden Antony R. , Su Wenqiong , He Jie , Zhi Xiao , Wang Kan , Zhu Laikuan , Shen Guangxia , Ding Xianting
Published: September 2021

Pancreatic cancer, at unresectable advanced stages, presents poor prognoses, which could be prevented by early pancreatic cancer diagnosis methods. Recently, a promising early-stage pancreatic cancer biomarker, extracellular vesicles (EVs) related glypican-1 (GPC1) mRNA, is found to overexpress in pancreatic cancer cells. Current mRNA detection methods usually require expensive machinery, strict preservation environments, and time-consuming processes to guarantee detection sensitivity, specificity, and stability. Herein, we propose a novel two-step amplification method (CHAGE) via the target triggered Catalytic Hairpin Assembly strategy combined with Gold-Enhanced point-of-care-testing (POCT) technology for sensitive visual detection of pancreatic cancer biomarker. First, utilizing the catalyzed hairpin DNA circuit, low expression of the GPC1 mRNA was changed into amplification product 1 (AP1, a DNA duplex) as the next detection targets of the paper strips. Second, the AP1 was loaded onto a lateral flow assay and captured with the gold signal nanoparticles to visualize results. Finally, the detected results can be further enhanced by depositing gold to re-enlarge the sizes of gold nanoparticles in detection zones. As a result, the CHAGE methodology lowers the detection limit of mRNA to 100 fM and provides results within 2 h at 37 °C. Furthermore, we demonstrate the successful application in discriminating pancreatic cancer cells by analyzing EVs’ GPC1 mRNA expression levels. Hence, the CHAGE methodology proposed here provides a rapid and convenient POCT platform for sensitive detection of mRNAs through unique probes designs (COVID, HPV, etc.).
Endogenous microRNA triggered enzyme-free DNA logic self-assembly for amplified bioimaging and enhanced gene therapy via in situ generation of siRNAs
Authors: Jiang Qinghua , Yue Shuzhen , Yu Kaixin , Tian Tian , Zhang Jian , Chu Huijun , Cui Zhumei , Bi Sai
Published: September 2021

Background

Small interfering RNA (siRNA) has emerged as a kind of promising therapeutic agents for cancer therapy. However, the off-target effect and degradation are the main challenges for siRNAs delivery. Herein, an enzyme-free DNA amplification strategy initiated by a specific endogenous microRNA has been developed for in situ generation of siRNAs with enhanced gene therapy effect on cervical carcinoma.

Methods

This strategy contains three DNA hairpins (H1, H2/PS and H3) which can be triggered by microRNA-21 (miR-21) for self-assembly of DNA nanowheels (DNWs). Notably, this system is consistent with the operation of a DNA logic circuitry containing cascaded “AND” gates with feedback mechanism. Accordingly, a versatile biosensing and bioimaging platform is fabricated for sensitive and specific analysis of miR-21 in HeLa cells via fluorescence resonance energy transfer (FRET). Meanwhile, since the vascular endothelial growth factor (VEGF) antisense and sense sequences are encoded in hairpin reactants, the performance of this DNA circuit leads to in situ assembly of VEGF siRNAs in DNWs, which can be specifically recognized and cleaved by Dicer for gene therapy of cervical carcinoma.

Results

The proposed isothermal amplification approach exhibits high sensitivity for miR-21 with a detection limit of 0.25 pM and indicates excellent specificity to discriminate target miR-21 from the single-base mismatched sequence. Furthermore, this strategy achieves accurate and sensitive imaging analysis of the expression and distribution of miR-21 in different living cells. To note, compared to naked siRNAs alone, in situ siRNA generation shows a significantly enhanced gene silencing and anti-tumor effect due to the high reaction efficiency of DNA circuit and improved delivery stability of siRNAs.

Conclusions

The endogenous miRNA-activated DNA circuit provides an exciting opportunity to construct a general nanoplatform for precise cancer diagnosis and efficient gene therapy, which has an important significance in clinical translation.

Graphic abstract
Development of a competitive chemiluminescence immunoassay using a monoclonal antibody recognizing 3B of foot-and-mouth disease virus for the rapid detection of antibodies induced by FMDV infection
Authors: Liu Wei , Zhang Guanglei , Yang Sicheng , Li Junhui , Gao Zhan , Ge Sudan , Yang Huihui , Shao Junjun , Chang Huiyun
Published: September 2021

Background

Foot-and-mouth disease (FMD) is a devastating animal disease. Anti-non-structural protein (NSP) antibody detection is very important for confirming suspected cases, evaluating the prevalence of infection, certifying animals for trade and controlling the disease.

Methods

In this study, a competitive chemiluminescence immunoassay (3B-cCLIA) was developed for the rapid detection of antibodies against NSPs in different species of livestock animals using the monoclonal antibody (mAb) 9E2 as a competitive antibody that recognizes NSP 3B.

Results

The cut-off value (50%), diagnostic sensitivity (Dsn) (97.20%, 95.71%, and 96.15%) and diagnostic specificity (Dsp) (99.51%, 99.43%, and 98.36) of the assay were estimated by testing a panel of known-background sera from swine, cattle and sheep, respectively. The accuracy rate of the 3B-cCLIA was further validated and subsequently compared with that of two commercial diagnostic kits. The early diagnostic results showed that antibodies recognizing NSPs developed later (approximately 1–2 days) than antibodies recognizing structural proteins. Furthermore, anti-NSP antibody presence in animals vaccinated multiple times (false positives), especially cattle and sheep, was confirmed, and the false-positive rate increased with the number of vaccinations.

Conclusions

These results indicate that the 3B-cCLIA is suitable for the rapid detection of antibodies against FMDV NSP 3B in a wide range of species.
Regulation of plant antiviral defense genes via host RNA-silencing mechanisms
Authors: Leonetti Paola , Stuttmann Johannes , Pantaleo Vitantonio
Published: September 2021

Background

Plants in nature or crops in the field interact with a multitude of beneficial or parasitic organisms, including bacteria, fungi and viruses. Viruses are highly specialized to infect a limited range of host plants, leading in extreme cases to the full invasion of the host and a diseased phenotype. Resistance to viruses can be mediated by various passive or active mechanisms, including the RNA-silencing machinery and the innate immune system.

Main text

RNA-silencing mechanisms may inhibit viral replication, while viral components can elicit the innate immune system. Viruses that successfully enter the plant cell can elicit pattern-triggered immunity (PTI), albeit by yet unknown mechanisms. As a counter defense, viruses suppress PTI. Furthermore, viral Avirulence proteins (Avr) may be detected by intracellular immune receptors (Resistance proteins) to elicit effector-triggered immunity (ETI). ETI often culminates in a localized programmed cell death reaction, the hypersensitive response (HR), and is accompanied by a potent systemic defense response. In a dichotomous view, RNA silencing and innate immunity are seen as two separate mechanisms of resistance. Here, we review the intricate connections and similarities between these two regulatory systems, which are collectively required to ensure plant fitness and resilience.

Conclusions

The detailed understanding of immune regulation at the transcriptional level provides novel opportunities for enhancing plant resistance to viruses by RNA-based technologies. However, extensive use of RNA technologies requires a thorough understanding of the molecular mechanisms of RNA gene regulation. We describe the main examples of host RNA-mediated regulation of virus resistance.
Surface charge-dependent mitochondrial response to similar intracellular nanoparticle contents at sublethal dosages
Authors: Jin Xiaoting , Yu Haiyi , Zhang Ze , Cui Tenglong , Wu Qi , Liu Xiaolei , Gao Jie , Zhao Xingchen , Shi Jianbo , Qu Guangbo , Jiang Guibin
Published: September 2021

Background

Considering the inevitability for humans to be frequently exposed to nanoparticles (NPs), understanding the biosafety of NPs is important for rational usage. As an important part of the innate immune system, macrophages are widely distributed in vital tissues and are also a dominant cell type that engulfs particles. Mitochondria are one of the most sensitive organelles when macrophages are exposed to NPs. However, previous studies have mainly reported the mitochondrial response upon high-dose NP treatment. Herein, with gold nanoparticles (AuNPs) as a model, we investigated the mitochondrial alterations induced by NPs at a sublethal concentration.

Results

At a similar internal exposure dose, different AuNPs showed distinct degrees of effects on mitochondrial alterations, including reduced tubular mitochondria, damaged mitochondria, increased reactive oxygen species, and decreased adenosine triphosphate. Cluster analysis, two-way ANOVA, and multiple linear regression suggested that the surface properties of AuNPs were the dominant determinants of the mitochondrial response. Based on the correlation analysis, the mitochondrial response was increased with the change in zeta potential from negative to positive. The alterations in mitochondrial respiratory chain proteins indicated that complex V was an indicator of the mitochondrial response to low-dose NPs.

Conclusion

Our current study suggests potential hazards of modified AuNPs on mitochondria even under sublethal dose, indicates the possibility of surface modification in biocompatibility improvement, and provides a new way to better evaluation of nanomaterials biosafety.
Familiar but neglected: identification of gaps and recommendations to close them on exclusive breastfeeding support in health facilities in Malawi
Authors: Nyondo-Mipando Alinane Linda , Kinshella Mai-Lei Woo , Salimu Sangwani , Chiwaya Brandina , Chikoti Felix , Chirambo Lusungu , Mwaungulu Ephrida , Banda Mwai , Newberry Laura , Hiwa Tamanda , Vidler Marianne , Dube Queen , Molyneux Elizabeth , Mfutso-Bengo Joseph , Goldfarb David M. , Kawaza Kondwani
Published: September 2021

Background

Exclusive breastfeeding is widely accepted as a key intervention with proven efficacy for improving newborn survival. Despite international commitments and targets to support and promote breastfeeding, there are still gaps in meeting and maintain coverage in many sub-Saharan African countries. This paper aimed to triangulate the perspectives of health workers, mothers, and their family members with facility assessments to identify gaps to improve breastfeeding support in in Malawi.

Methods

The study on breastfeeding barriers and facilitators was conducted in 2019 at one tertiary hospital and three secondary-level hospitals in Malawi. We conducted 61 semi-structured interviews with health workers, postnatal mothers, grandmothers, aunts, and fathers. In 2017, we carried out a neonatal care facility assessment using the World Health Organization (WHO) Integrated Maternal, Neonatal, and Child Quality of Care Assessment and Improvement Tool. Qualitative data were analysed using a thematic analysis approach within the Systems Framework for Health Policy.

Results

The district-level hospitals rated high with an average score of 4.8 out of 5 across the three facilities indicating that only minor improvements are needed to meet standards of care for early and exclusive breastfeeding. However, the score fell to an average of 3.5 out of 5 for feeding needs with sick neonates indicating that several improvements are needed in this area. The qualitative data demonstrated that breastfeeding was normalized as part of routine newborn care. However, the focus on routine practice and reliance on breastfeeding knowledge from prenatal counselling highlights inequities and neglect in specialized care and counselling among vulnerable mothers and newborns. Revitalisation of breastfeeding in Malawian facilities will require a systems approach that reinforces policies and guidelines; contextualises knowledge; engagement and empowerment of other relatives to the baby and task-sharing among health workers.

Conclusions

Breastfeeding is accepted as a social norm among health workers, mothers, grandmothers, aunts, and fathers in Malawi, yet vulnerable groups are underserved. Neglect in breastfeeding support among vulnerable populations exacerbates health inequities. Health systems strengthening related to breastfeeding requires a concerted effort among health workers, mothers, grandmothers, aunts, and fathers while remaining grounded in contexts to support family-centered hospital care.
Socioeconomic correlates of incident and fatal opioid overdose among Swedish people with opioid use disorder
Authors: Dahlman Disa , Ohlsson Henrik , Edwards Alexis C. , Sundquist Jan , Håkansson Anders , Sundquist Kristina
Published: September 2021

Background

Opioid overdose (OD) and opioid OD death are major health threats to people with opioid use disorder (OUD). Socioeconomic factors are underexplored potential determinants of opioid OD. In this study, we assessed socioeconomic and other factors and their associations with incident and fatal opioid OD, in a cohort consisting of 22,079 individuals with OUD.

Methods

We performed a retrospective, longitudinal study based on Swedish national register data for the period January 2005–December 2017. We used Cox proportional hazard models to investigate the risk of incident and fatal opioid OD as a function of several individual, parental and neighborhood covariates.

Results

Univariate analysis showed that several covariates were associated with incident and fatal opioid OD. In the multivariate analysis, incident opioid OD was associated with educational attainment (Hazard ratio [HR] 0.96; 95% confidence interval [CI] 0.94–0.97), having received social welfare (HR 1.31; 95% CI 1.22–1.39), and criminal conviction (HR 1.53; 95% CI 1.42–1.65). Fatal opioid OD was also associated with criminal conviction (HR 1.93; 95% CI 1.61–2.32).

Conclusion

Individuals with low education and receipt of social welfare had higher risks of incident opioid OD and individuals with criminal conviction were identified as a risk group for both incident and fatal opioid OD. Our findings should raise attention among health prevention policy makers in general, and among decision-makers within the criminal justice system and social services in particular.
Evaluating differences in respiratory motion estimates during radiotherapy: a single planning 4DMRI versus daily 4DMRI
Authors: den Boer Duncan , Veldman Johannes K. , van Tienhoven Geertjan , Bel Arjan , van Kesteren Zdenko
Published: September 2021

Background

In radiotherapy, respiratory-induced tumor motion is typically measured using a single four-dimensional computed tomography acquisition (4DCT). Irregular breathing leads to inaccurate motion estimates, potentially resulting in undertreatment of the tumor and unnecessary dose to healthy tissue. The aim of the research was to determine if a daily pre-treatment 4DMRI-strategy led to a significantly improved motion estimate compared to single planning 4DMRI (with or without outlier rejection).

Methods

4DMRI data sets from 10 healthy volunteers were acquired. The first acquisition simulated a planning MRI, the respiratory motion estimate (constructed from the respiratory signal, i.e. the 1D navigator) was compared to the respiratory signal in the subsequent scans (simulating 5–29 treatment fractions). The same procedure was performed using the first acquisition of each day as an estimate for the subsequent acquisitions that day (2 per day, 4–20 per volunteer), simulating a daily MRI strategy. This was done for three outlier strategies: no outlier rejection (NoOR); excluding 5% of the respiratory signal whilst minimizing the range (Min95) and excluding the datapoints outside the mean end-inhalation and end-exhalation positions (MeanIE).

Results

The planning MRI median motion estimates were 27 mm for NoOR, 18 mm for Min95, and 13 mm for MeanIE. The daily MRI median motion estimates were 29 mm for NoOR, 19 mm for Min95 and 15 mm for MeanIE. The percentage of time outside the motion estimate were for the planning MRI: 2%, 10% and 32% for NoOR, Min95 and MeanIE respectively. These values were reduced with the daily MRI strategy: 0%, 6% and 17%. Applying Min95 accounted for a 30% decrease in motion estimate compared to NoOR.

Conclusion

A daily MRI improved the estimation of respiratory motion as compared to a single 4D (planning) MRI significantly. Combining the Min95 technique with a daily 4DMRI resulted in a decrease of inclusion time of 6% with a 30% decrease of motion. Outlier rejection alone on a planning MRI often led to underestimation of the movement and could potentially lead to an underdosage.

Trial registration: protocol W15_373#16.007
Fibular osteotomy is helpful for talar reduction in the treatment of varus ankle osteoarthritis with supramalleolar osteotomy
Authors: Liang Jing-Qi , Wang Jun-Hu , Zhang Yan , Wen Xiao-Dong , Liu Pei-Long , Liang Xiao-Jun , Lu Jun , Li Yi , Zhao Hong-Mou
Published: September 2021

Background

There have been debates on the necessity of fibular osteotomy (FO) in supramalleolar osteotomy (SMOT) for the treatment of varus ankle osteoarthritis. The purpose of the current study was to compare the clinical and radiological outcomes between SMOT with and without FO in the treatment of varus ankle osteoarthritis.

Methods

The SMOT group included 39 patients, and the SMOT with FO group included 24 patients. The basic information reached no significant difference between groups. The American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot score, Ankle Osteoarthritis Scale (AOS), modified Takakura stage and range of motion (ROM) were used for the functional evaluation. The radiologic parameters were assessed at the last follow-up to compare the degree of talar reduction between the two groups.

Results

Both groups achieved significant improvements in AOFAS scores, modified Takakura stage, as well as AOS pain and functional scores (P < 0.001). The ROM of the ankle joint in the SMOT group was significantly decreased (P = 0.022). In both groups, all of the radiological parameters were significantly improved (P < 0.01). The tibiofibular clear space (TFCS) was significantly widened in the SMOT group (P < 0.001). No significant difference was found between the two groups according to the functional outcomes. However, the talar tilt angle (TT) and hindfoot alignment angle (HFA) in the SMOT with FO group were significantly smaller than those in the SMOT group (P < 0.05). The TFCS was significantly widened in the SMOT group (P = 0.001). The medial displacement of the talus (MDT) was better reduced in the SMOT with FO group (P = 0.006).

Conclusion

SMOT is a promising procedure for functional improvement and malalignment correction in varus ankle osteoarthritis but reduces ankle range of motion. If SMOT is combined with FO, talar tilt and medial displacement will be better reduced.
Clinical features of lupus enteritis: a single-center retrospective study
Authors: Chen Long , He Qin , Luo Man , Gou Yuxiao , Jiang Dan , Zheng Xiaoqin , Yan Gaowu , He Fang
Published: September 2021

Background

Lupus enteritis (LEn) is a rare complication of systemic lupus erythematosus (SLE). Timely diagnosis and treatment of LEn are necessary to prevent the most serious consequences — intestinal perforation, gastrointestinal bleeding, and death. We compared the clinical features of SLE patients with and without LEn.

Methods

The clinical data of LEn inpatients at Suining Central Hospital from July 2012 to June 2020 were examined. These LEn patients were matched (1:2 ratio) with concurrently hospitalized SLE patients who did not have LEn. The two groups were compared using multivariate logistic regression.

Results

We compared SLE inpatients with LEn (n = 43) and SLE inpatients without LEn (n = 86) at our institution. Multivariate logistic regression showed that ascites (odds ratio [OR]: 9.961, 95%CI: 2.215–44.802, P = 0.003), hydronephrosis (OR: 28.060, 95%CI: 2.303–341.962, P = 0.009), leukopenia (OR: 5.890, 95%CI: 1.813–19.135, P = 0.003), reduced complement C3 level (OR: 4.791, 95%CI: 1.605–14.300, P = 0.005), and elevated immunoglobin (Ig)A level (OR: 4.040, 95%CI: 1.307–12.487, P = 0.015) were independently associated with LEn. Within the LEn group, abdominal pain was the most common abdominal symptom (88.4%), and increased mesenteric fat attenuation (74.4%) and bowel wall thickening (58.1%) were the most common computed tomography (CT) findings. Most LEn patients (88.4%) required high-dose glucocorticoid therapy (≥ 80 mg methylprednisolone/day), and cyclophosphamide was the most commonly used immunosuppressant (62.8%).

Conclusions

Abdominal pain was the most common clinical symptom of LEn. Abdominal CT provides important information for detection and diagnosis of LEn. Ascites, hydronephrosis, leukopenia, hypocomplementemia (C3), and increased IgA were independently associated with LEn.
Measuring mental health in humanitarian crises: a practitioner’s guide to validity
Authors: Kohrt Brandon A. , Kaiser Bonnie N.
Published: September 2021

Background

There are ongoing methodological advances in measuring mental health in humanitarian crises. This Special Section describes numerous innovations. Here we take a practitioner's view in understanding the key issues related to assessment of mental health in humanitarian contexts and how the innovations contribute to the field.

Main body

In this guide for practitioners, we address the following issues: (1) clarifying the intended purpose of conducting mental health assessment in humanitarian crises: why is this information collected and for what intended purposes?; (2) determining what type of tool should be selected and the types of psychometric properties that are important for tools serving this particular purpose; (3) when a validated tool is not available, considering how qualitative and quantitative methods should be used to generate information on validity; and finally, (4) how to report on validity and its implications for interpreting information for humanitarian practitioners, governments, care providers, and other stakeholders supporting people affected by humanitarian emergencies.

Conclusion

Ultimately, mental health assessment tools are not independent of the group with which they were designed, nor are the psychometric properties of the tools or their utility universal across purposes. Therefore, organizations and stakeholders will optimize their positive impact when choosing tools wisely, appropriately adapting and validating tools, and providing guidance on how to interpret those findings to best serve populations in need.
Risk reduction strategies for BRCA1/2 hereditary ovarian cancer syndromes: a clinical practice guideline
Authors: Jacobson Michelle , Coakley Nadia , Bernardini Marcus , Branco Kelly-Ann , Elit Laurie , Ferguson Sarah , Kim Raymond
Published: September 2021

Objective

The purpose of this guideline is to make recommendations regarding the care of women who harbour a pathogenic or likely pathogenic variant in BRCA1 and BRCA2.

Methods

Draft recommendations were formulated based on evidence obtained through a systematic review of RCTs, comparative retrospective studies and guideline endorsement. The draft recommendations underwent an internal review by clinical and methodology experts, and an external review by clinical practitioners.

Results

The literature search yielded 1 guideline, 5 systematic reviews, and 15 studies that met the eligibility criteria.

Conclusions

In women who harbour a pathogenic or likely pathogenic variant in BRCA1 and BRCA2 screening for ovarian cancer is not recommended. Risk-reducing surgery is recommended to reduce the risk of ovarian cancer. In the absence of contraindications, premenopausal women undergoing RRSO should be offered hormone therapy until menopause. Systemic hormone replacement therapy, is not recommended for women who have had a personal history of breast cancer. RRSO should be considered for breast cancer risk reduction in women younger than 50 years. After a breast cancer diagnosis, RRSO for breast cancer mortality reduction can be considered within two years to women who harbour a pathogenic or likely pathogenic variant in BRCA1 if younger than the recommended age range for ovarian cancer risk reduction. RRSO before the age of 40 and specifically for breast cancer treatment in BRCA2 should be considered only if recommended by their breast cancer oncologist. Following RRSO, it is not recommended to do surveillance for peritoneal cancer.
A matrisome RNA signature from early-pregnancy mouse mammary fibroblasts predicts distant metastasis-free breast cancer survival in humans
Authors: Ibrahim Ayman M. , Bilsland Alan , Rickelt Steffen , Morris Joanna S. , Stein Torsten
Published: September 2021

Background

During pregnancy, the mouse mammary ductal epithelium branches and grows into the surrounding stroma, requiring extensive extracellular matrix (ECM) and tissue remodelling. It therefore shows parallels to cancer invasion. We hypothesised that similar molecular mechanisms may be utilised in both processes, and that assessment of the stromal changes during pregnancy-associated branching may depict the stromal involvement during human breast cancer progression.

Methods

Immunohistochemistry (IHC) was employed to assess the alterations within the mouse mammary gland extracellular matrix during early pregnancy when lateral branching of the primary ductal epithelium is initiated. Primary mouse mammary fibroblasts from three-day pregnant and age-matched non-pregnant control mice, respectively, were 3D co-cultured with mammary epithelial cells to assess differences in their abilities to induce branching morphogenesis in vitro. Transcriptome analysis was performed to identify the underlying molecular changes. A signature of the human orthologues of the differentially expressed matrisome RNAs was analysed by Kaplan–Meier and multi-variate analysis in two large breast cancer RNA datasets (Gene expression-based Outcome for Breast cancer Online (GOBO) und Kaplan–Meier Plotter), respectively, to test for similarities in expression between early-pregnancy mouse mammary gland development and breast cancer progression.

Results

The ECM surrounding the primary ductal network showed significant differences in collagen and basement membrane protein distribution early during pregnancy. Pregnancy-associated fibroblasts (PAFs) significantly enhanced branching initiation compared to age-matched control fibroblast. A combined signature of 64 differentially expressed RNAs, encoding matrisome proteins, was a strong prognostic indicator of distant metastasis-free survival (DMFS) independent of other clinical parameters. The prognostic power could be significantly strengthened by using only a subset of 18 RNAs (LogRankP ≤ 1.00e−13; Hazard ratio (HR) = 2.42 (1.8–3.26);p = 5.61e−09). The prognostic power was confirmed in a second breast cancer dataset, as well as in datasets from ovarian and lung cancer patients.

Conclusions

Our results describe for the first time the early stromal changes that accompany pregnancy-associated branching morphogenesis in mice, specify the early pregnancy-associated molecular alterations in mouse mammary fibroblasts, and identify a matrisome signature as a strong prognostic indicator of human breast cancer progression, with particular strength in oestrogen receptor (ER)-negative breast cancers.
Comparison of effect of auriculotherapy and mefenamic acid on the severity and systemic symptoms of primary dysmenorrhea: a randomized clinical trial
Authors: Vahedi Masoomeh , Hasanpoor-Azghady Seyedeh Batool , Amiri-Farahani Leila , Khaki Imaneh
Published: September 2021

Background

Primary dysmenorrhea (PD) is the most common complaint in young women and adolescents. Side effects of non-steroidal anti-inflammatory drugs can limit their use. Therefore, non-pharmacological pain relief methods such as auriculotherapy may play an important role in PD management. This study was conducted to compare the effect of auriculotherapy and mefenamic acid on the severity and systemic symptoms of PD.

Methods

In a randomized clinical trial, 83 students were randomized into two groups. In the auriculotherapy group, electrical stimulation of the ear was conducted once a week for two menstrual cycles. In each cycle close to menstruation, ear seeds were inserted on pressure points to be pressed in times of pain. In the mefenamic acid group, subjects took mefenamic acid capsules upon seeing the initial symptoms of menstruation until the pain reduces. The primary outcomes were mean pain intensity and systemic symptoms associated with it. Pain intensity was measured through the visual analog scale (VAS) and the verbal multidimensional scoring system (VMS). Systemic symptoms were assessed using VMS, as well as the yes/no question form.

Results

Mean pain intensity with the VAS was significantly lower in the auriculotherapy group than the mefenamic acid group in the first and second cycles of intervention. There was a significant difference in VMS grade between both groups during the second cycle of intervention. In terms of the systemic symptoms in the second cycle of intervention, no subjects had dysmenorrhea grade 3 (common systemic symptoms) in the auriculotherapy group. Whereas in the mefenamic acid group, 16.7% of the subjects still had dysmenorrhea grade 3. There was no significant difference between the two groups in the frequency of systemic symptoms of PD. There was a significant decrease in the frequency of fatigue and diarrhea in both groups. However, there was a significant reduction in the frequency of nausea, headache, and anger in the auriculotherapy group.

Conclusion

Mean pain intensity with the VAS was lower with the auriculotherapy. Also, 65.9% of auriculotherapy group subjects were in the dysmenorrhea grades 0 and 1. Therefore, auriculotherapy is recommended because of its fewer complications and more effect on PD.

Trial registration

ClinicalTrials.gov IRCT20181207041873N1. Registered on February 24, 2019. https://en.irct.ir/user/trial/35967/view
Anti-osteosarcoma effect of antiserum against cross antigen TPD52 between osteosarcoma and Trichinella spiralis
Authors: Yue Tao-Tao , Zhang Nan , Li Jian-Hua , Lu Xiang-Yun , Wang Xiao-Cen , Li Xin , Zhang Hong-Bo , Cheng Shu-Qin , Wang Bo-Bo , Gong Peng-Tao , Zhang Xi-Chen
Published: September 2021

Background

Trichinella spiralis (T. spiralis) is a parasite occurring worldwide that has been proven to have antitumour ability. However, studies on the antitumour effects of cross antigens between the tumour and T. spiralis or antibodies against cross antigens between tumours and T. spiralis are rare.

Methods

To study the role of cross antigens between osteosarcoma and T. spiralis, we first screened the cDNA expression library of T. spiralis muscle larvae to obtain the cross antigen gene tumour protein D52 (TPD52), and prepared fusion protein TPD52 and its antiserum. The anti-osteosarcoma effect of the anti-TPD52 antiserum was studied using cell proliferation and cytotoxicity assays as well as in vivo animal models; preliminary data on the mechanism were obtained using western blot and immunohistochemistry analyses.

Results

Our results indicated that TPD52 was mainly localized in the cytoplasm of MG-63 cells. Anti-TPD52 antiserum inhibited the proliferation of MG-63 cells and the growth of osteosarcoma in a dose-dependent manner. The tumour inhibition rate in the 100 μg treatment group was 61.95%. Enzyme-linked immunosorbent assay showed that injection of anti-TPD52 antiserum increased the serum levels of IFN-γ, TNF-α, and IL-12 in nude mice. Haematoxylin and eosin staining showed that anti-TPD52 antiserum did not cause significant pathological damage. Apoptosis of osteosarcoma cells was induced by anti-TPD52 antiserum in vivo and in vitro.

Conclusions

Anti-TPD52 antiserum exerts an anti-osteosarcoma effect by inducing apoptosis without causing histopathological damage.

Graphical abstract
Evaluating and strengthening the health system of Curaҫao to improve its performance for future outbreaks of vector-borne diseases
Authors: Mulderij-Jansen Vaitiare , Gerstenbluth Izzy , Duits Ashley , Tami Adriana , Bailey Ajay
Published: September 2021

Background

Vector-borne diseases (VBDs) such as dengue, chikungunya, and Zika pose a significant challenge to health systems in countries they affect, especially countries with less developed healthcare systems. Therefore, countries are encouraged to work towards more resilient health systems. This qualitative study aims to examine the performance of the health system of the Dutch Caribbean island of Curaҫao regarding the prevention and control of VBDs in the last decade by using the WHO health system building blocks.

Methods

From November 2018 to December 2020, a multi-method qualitative study was performed in Curaçao, applying content analysis of documents (n = 50), five focus group discussions (n = 30), interviews with experts (n = 11) and 15 observation sessions. The study was designed based on the WHO framework: health system building blocks. Two cycles of inductive and deductive coding were employed, and Nvivo software was used to analyse the data.

Results

This study’s data highlighted the challenges (e.g. insufficient oversight, coordination, leadership skills, structure and communication) that the departments of the health system of Curaҫao faced during the last three epidemics of VBDs (2010–2020). Furthermore, low levels of collaboration between governmental and non-governmental organisations (e.g. semi-governmental and private laboratories) and insufficient capacity building to improve skills (e.g. entomological, surveillance skills) were also observed. Lastly, we observed how bottlenecks in one building block negatively influenced other building blocks (e.g. inadequate leadership/governance obstructed the workforce's performance).

Conclusions

This study uncovers potential organisational bottlenecks that have affected the performance of the health system of Curaҫao negatively. We recommend starting with the reinforcement of oversight of the integrated vector management programme to ensure the development, implementation and evaluation of related legislation, policies and interventions. Also, we recommend evaluating and reforming the existing administrative and organisational structure of the health system by considering the cultural style, challenges and barriers of the current health system. More efforts are needed to improve the documentation of agreements, recruitment and evaluation of the workforce's performance. Based on our findings, we conceptualised actions to strengthen the health system's building blocks to improve its performance for future outbreaks of infectious diseases.

Graphical abstract
Analysis of the spatial distribution of Aedes albopictus in an urban area of Shanghai, China
Authors: Zhou Yibin , Liu Hongxia , Leng Peien , Zhu Jiang , Yao Shenjun , Zhu Yiyi , Wu Huanyu
Published: September 2021

Background

Aedes albopictus is a vector of major arboviral diseases and a primary pest in tropical and temperate regions of China. In most cities of China, the current monitoring system for the spread of Ae. albopictus is based on the subdistrict scale and does not consider spatial distribution for analysis of species density. Thus, the system is not sufficiently accurate for epidemic investigations, especially in large cities.

Methods

This study used an improved surveillance program, with the mosquito oviposition trap (MOT) method, integrating the actual monitoring locations to investigate the temporal and spatial distribution of Ae. albopictus abundance in an urban area of Shanghai, China from 2018 to 2019. A total of 133 monitoring units were selected for surveillance of Ae. albopictus density in the study area, which was composed of 14 subdistricts. The vector abundance and spatial structure of Ae. albopictus were predicted using a binomial areal kriging model based on eight MOTs in each unit. Results were compared to the light trap (LT) method of the traditional monitoring scheme.

Results

A total of 8,192 MOTs were placed in the study area in 2018, and 7917 (96.6%) were retrieved, with a positive rate of 6.45%. In 2019, 22,715 (97.0%) of 23,408 MOTs were recovered, with a positive rate of 5.44%. Using the LT method, 273 (93.5%) and 312 (94.5%) adult female Ae. albopictus were gathered in 2018 and 2019, respectively. The Ae. albopictus populations increased slowly from May, reached a peak in July, and declined gradually from September. The MOT positivity index (MPI) showed significant positive spatial autocorrelation across the study area, whereas LT collections indicated a nonsignificant spatial autocorrelation. The MPI was suitable for spatial interpolation using the binomial areal kriging model and showed different hot spots in different years.

Conclusions

The improved surveillance system integrated with a geographical information system (GIS) can improve our understanding of the spatial and temporal distribution of Ae. albopictus in urban areas and provide a practical method for decision-makers to implement vector control and mosquito management.

Graphical abstract
iPSYcare: the development of a linked electronic medical records database to study and optimize psychiatric care in Antwerp
Authors: Rens Eva , Michielsen Joris , Dom Geert , Remmen Roy , Van den Broeck Kris
Published: September 2021

Objective

The study of care trajectories of psychiatric patients across hospitals was previously not possible in Belgium as each hospital stores its data autonomously, and government-related registrations do not contain a unique identifier or are incomplete. A new longitudinal database called iPSYcare (Improved Psychiatric Care and Research) was therefore constructed in 2021, and links the electronic medical records of patients in psychiatric units of eight hospitals in the Antwerp Province, Belgium. The database provides a wide range of information on patients, care trajectories and delivered care in the region. In a first phase, the database will only contain information about adult patients who were admitted to a hospital or treated by an outreach team and who gave explicit consent. In the future, the database may be expanded to other regions and additional data on outpatient care may be added.

Results

IPSYcare is a close collaboration between the University of Antwerp and hospitals in the province of Antwerp. This paper describes the development of the database, how privacy and ethical issues will be handled, and how the governance of the database will be organized.
Improved library preparation protocols for amplicon sequencing-based noninvasive fetal genotyping for RHD-positive D antigen-negative alleles
Authors: Hori Asuka , Ogata-Kawata Hiroko , Sasaki Aiko , Takahashi Ken , Taniguchi Kosuke , Migita Ohsuke , Kawashima Akihiro , Okamoto Aikou , Sekizawa Akihiko , Sago Haruhiko , Takada Fumio , Nakabayashi Kazuhiko , Hata Kenichiro
Published: September 2021

Objective

We aimed to simplify our fetal RHD genotyping protocol by changing the method to attach Illumina’s sequencing adaptors to PCR products from the ligation-based method to a PCR-based method, and to improve its reliability and robustness by introducing unique molecular indexes, which allow us to count the numbers of DNA fragments used as PCR templates and to minimize the effects of PCR and sequencing errors.

Results

Both of the newly established protocols reduced time and cost compared with our conventional protocol. Removal of PCR duplicates using UMIs reduced the frequencies of erroneously mapped sequences reads likely generated by PCR and sequencing errors. The modified protocols will help us facilitate implementing fetal RHD genotyping for East Asian populations into clinical practice.
Mathematical and numerical analyses of a stochastic impulse control model with imperfect interventions
Authors: Yoshioka Hidekazu , Yaegashi Yuta
Published: September 2021

A stochastic impulse control problem with imperfect controllability of interventions is formulated with an emphasis on applications to ecological and environmental management problems. The imperfectness comes from uncertainties with respect to the magnitude of interventions. Our model is based on a dynamic programming formalism to impulsively control a 1-D diffusion process of a geometric Brownian type. The imperfectness leads to a non-local operator different from the many conventional ones, and evokes a slightly different optimal intervention policy. We give viscosity characterizations of the Hamilton–Jacobi–Bellman Quasi-Variational Inequality (HJBQVI) governing the value function focusing on its numerical computation. Uniqueness and verification results of the HJBQVI are presented and a candidate exact solution is constructed. The HJBQVI is solved with the two different numerical methods, an ordinary differential equation (ODE) based method and a finite difference scheme, demonstrating their consistency. Furthermore, the resulting controlled dynamics are extensively analyzed focusing on a bird population management case from a statistical standpoint.
Assessment of knowledge, attitude and practice of mothers/caregivers on infant and young child feeding in Assosa Woreda, Assosa Zone, Benshangul Gumuz Region, Western Ethiopia: a cross-sectional study
Authors: Assefa Dawit Getachew , Woldesenbet Tigist Tekle , Molla Wondowsen , Zeleke Eden Dagnachew , Simie Timsel Girma
Published: September 2021

Background

Through the health extension package, Ethiopia had practiced infant and young child feeding. However, infant and young child feeding (IYCF) practice has been poor. Hence, in this study, the knowledge, attitude, and practice of the mothers/caregivers on infant and young child feeding were assessed.

Methods

A cross-sectional study was carried out among 486 mothers/caregivers from Assosa Districts in the Assosa Zone of Benshangul Gumuz Region, Western Ethiopia. A semi-structured interviewer-administered questionnaire was used. To isolate independent predictors for good knowledge, good practice, and favorable attitude of the mothers/caregivers related to child feeding, multivariable logistic regression analyses were performed.

Results

Out of 486 study participants, 456 (93.8 %) of mothers had good knowledge, 432 (88.9 %) had a positive attitude, and 380 (78.2 %) mothers had good practice of IYCF practice recommendations. Furthermore, age of mothers, educational status of the mother, place of delivery, father’s educational status, father’s involvement & support, previous knowledge about IYCF, discussion with their husband about IYCF, and ANC follows up were significantly associated with mother’s knowledge on IYCF recommendation.

Conclusions

Overall mothers had good knowledge and a positive attitude about IYCF practices. To support IYCF practices, behavior change communications intervention strategies should be introduced in mothers to bridge the gap between knowledge and practices.
Synchronous supratentorial and infratentorial oligodendrogliomas with incongruous IDH1 mutations, a case report
Authors: Agopyan-Miu Alexander H. C. W. , Banu Matei A. , Miller Michael L. , Troy Christopher , Hargus Gunnar , Canoll Peter , Wang Tony J. C. , Feldstein Neil , Haggiagi Aya , McKhann Guy M.
Published: September 2021

Infratentorial oligodendrogliomas, a rare pathological entity, are generally considered metastatic lesions from supratentorial primary tumors. Here, we report the case of a 23-year-old man presenting with a histopathologically confirmed right precentral gyrus grade 2 oligodendroglioma and a concurrent pontine grade 3 oligodendroglioma. The pontine lesion was biopsied approximately a year after the biopsy of the precentral lesion due to disease progression despite 4 cycles of procarbazine-CCNU-vincristine (PCV) chemotherapy and stable supratentorial disease. Histology and genetic analysis of the pontine biopsy were consistent with grade 3 oligodendroglioma, and comparison of the two lesions demonstrated common 1p/19q co-deletions and TERT promoter mutations but distinct IDH1 mutations, with a non-canonical IDH1 R132G mutation identified in the infratentorial lesion and a R132H mutation identified in the cortical lesion. Initiation of Temozolomide led to complete response of the supratentorial lesion and durable disease control, while Temozolomide with subsequent radiation therapy of 54 Gy in 30 fractions resulted in partial response of the pontine lesion. This case report supports possible distinct molecular pathogenesis in supratentorial and infratentorial oligodendrogliomas and raises questions about the role of different IDH1 mutant isoforms in explaining treatment resistance to different chemotherapy regimens. Importantly, this case suggests that biopsies of all radiographic lesions, when feasible and safe, should be considered in order to adequately guide management in multicentric oligodendrogliomas.