bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcriptome and proteome profiling reveal complementary scavenger and immune features of rat liver sinusoidal endothelial cells and liver macrophages
Authors: Bhandari Sabin , Li Ruomei , Simón-Santamaría Jaione , McCourt Peter , Johansen Steinar Daae , Smedsrød Bård , Martinez-Zubiaurre Inigo , Sørensen Karen Kristine
Published: November 2020

Background

Liver sinusoidal endothelial cells (LSECs) and Kupffer cells (KCs; liver resident macrophages) form the body’s most effective scavenger cell system for the removal of harmful blood-borne substances, ranging from modified self-proteins to pathogens and xenobiotics. Controversies in the literature regarding the LSEC phenotype pose a challenge when determining distinct functionalities of KCs and LSECs. This may be due to overlapping functions of the two cells, insufficient purification and/or identification of the cells, rapid dedifferentiation of LSECs in vitro, or species differences. We therefore characterized and quantitatively compared expressed gene products of freshly isolated, highly pure LSECs (fenestrated SE-1/FcγRIIb2+) and KCs (CD11b/c+) from Sprague Dawley, Crl:CD (SD), male rats using high throughput mRNA-sequencing and label-free proteomics.

Results

We observed a robust correlation between the proteomes and transcriptomes of the two cell types. Integrative analysis of the global molecular profile demonstrated the immunological aspects of LSECs. The constitutive expression of several immune genes and corresponding proteins of LSECs bore some resemblance with the expression in macrophages. LSECs and KCs both expressed high levels of scavenger receptors (SR) and C-type lectins. Equivalent expression of SR-A1 (Msr1), mannose receptor (Mrc1), SR-B1 (Scarb1), and SR-B3 (Scarb2) suggested functional similarity between the two cell types, while functional distinction between the cells was evidenced by LSEC-specific expression of the SRs stabilin-1 (Stab1) and stabilin-2 (Stab2), and the C-type lectins LSECtin (Clec4g) and DC-SIGNR (Clec4m). Many immune regulatory factors were differentially expressed in LSECs and KCs, with one cell predominantly expressing a specific cytokine/chemokine and the other cell the cognate receptor, illustrating the complex cytokine milieu of the sinusoids. Both cells expressed genes and proteins involved in antigen processing and presentation, and lymphocyte co-stimulation.

Conclusions

Our findings support complementary and partly overlapping scavenging and immune functions of LSECs and KCs. This highlights the importance of including LSECs in studies of liver immunity, and liver clearance and toxicity of large molecule drugs and nano-formulations.
Comparative transcriptome analysis of scaled and scaleless skins in Gymnocypris eckloni provides insights into the molecular mechanism of scale degeneration
Authors: Feng Xiu , Jia Yintao , Zhu Ren , Li Kemao , Guan Zhongzhi , Chen Yifeng
Published: November 2020

Background

The scale degeneration is thought to be related to the adaptation to the extreme environment with cold climate and high-altitude in schizothoracine fishes. Gymnocypris eckloni, a schizothoracine fish living in plateau waters with the elevation above 2500 m, is nearly esquamate and only covered with shoulder scales and anal scales, making it a good model species to study the molecular mechanism of scale degeneration.

Results

The transcriptomes of shoulder scaled skins (SSS), anal scaled skins (ASS) and scaleless skins (NSS) were sequenced and analyzed in G. eckloni at the age of 1 year. Histological examination showed that shoulder scale had completed its differentiation and anal scale just initiated the differentiation. A total of 578,046 unigenes were obtained from the transcriptomes, with 407,799 unigenes annotated in public databases. A total of 428 and 142 differentially expressed unigenes (DEUs) were identified between SSS and NSS, and between ASS and NSS, respectively, with 45 DEUs that were overlapped. Annotation analysis indicated that these DEUs were mainly enriched in Gene Ontology (GO) terms and KEGG pathways associated with bone and muscle formation, such as myofibril, contractile fiber, cytoskeletal protein binding, muscle structure development, cardiac muscle contraction, hypertrophic cardiomyopathy (HCM) and calcium signaling pathway.

Conclusions

Our results would provide insights into the molecular mechanisms of scale degeneration in G. eckloni and other congeneric fishes. In addition, the transcriptome data provides candidate genes and markers for future studies.
Lower methane emissions were associated with higher abundance of ruminal Prevotella in a cohort of Colombian buffalos
Authors: Aguilar-Marin Sandra Bibiana , Betancur-Murillo Claudia Lorena , Isaza Gustavo A. , Mesa Henry , Jovel Juan
Published: November 2020

Background

Ruminants burp massive amounts of methane into the atmosphere and significantly contribute to the deposition of greenhouse gases and the consequent global warming. It is therefore urgent to devise strategies to mitigate ruminant’s methane emissions to alleviate climate change. Ruminal methanogenesis is accomplished by a series of methanogen archaea in the phylum Euryarchaeota, which piggyback into carbohydrate fermentation by utilizing residual hydrogen to produce methane. Abundance of methanogens, therefore, is expected to affect methane production. Furthermore, availability of hydrogen produced by cellulolytic bacteria acting upstream of methanogens is a rate-limiting factor for methane production. The aim of our study was to identify microbes associated with the production of methane which would constitute the basis for the design of mitigation strategies.

Results

Moderate differences in the abundance of methanogens were observed between groups. In addition, we present three lines of evidence suggesting an apparent higher abundance of a consortium of Prevotella species in animals with lower methane emissions. First, taxonomic classification revealed increased abundance of at least 29 species of Prevotella. Second, metagenome assembly identified increased abundance of Prevotella ruminicola and another species of Prevotella. Third, metabolic profiling of predicted proteins uncovered 25 enzymes with homology to Prevotella proteins more abundant in the low methane emissions group.

Conclusions

We propose that higher abundance of ruminal Prevotella increases the production of propionic acid and, in doing so, reduces the amount of hydrogen available for methanogenesis. However, further experimentation is required to ascertain the role of Prevotella on methane production and its potential to act as a methane production mitigator.
Repeated centrifuging and washing concentrates bacterial samples in peritoneal dialysis for optimal culture: an original article
Authors: Tien Ni , You Bang-Jau , Lin Hsuan-Jen , Chang Chieh-Ying , Chou Che-Yi , Lin Hsiu-Shen , Chang Chiz-Tzung , Wang Charles C. N. , Chen Hung-Chih
Published: November 2020

Background

Bacterial cultures allow the identification of infectious disease pathogens. However, obtaining the results of conventional culture methods is time-consuming, taking at least two days. A more efficient alternative is the use of concentrated bacterial samples to accelerate culture growth. Our study focuses on the development of a high-yield sample concentrating technique.

Results

A total of 71 paired samples were obtained from patients on peritoneal dialysis (PD). The peritoneal dialysates were repeat-centrifuged and then washed with saline, namely the centrifuging and washing method (C&W method). The concentrated samples were Gram-stained and inoculated into culture plates. The equivalent unprocessed dialysates were cultured as the reference method. The times until culture results for the two methods were compared. The reference method yielded no positive Gram stain results, but the C&W method immediately gave positive Gram stain results for 28 samples (p < 0.001). The culture-negative rate was lower in the C&W method (5/71) than in the reference method (13/71) (p = 0.044). The average time for bacterial identification achieved with the C&W method (22.0 h) was shorter compared to using the reference method (72.5 h) (p < 0.001).

Conclusions

The C&W method successfully concentrated bacterial samples and superseded blood culture bottles for developing adequate bacterial cultures. The C&W method may decrease the culture report time, thus improving the treatment of infectious diseases.
Vestibular rehabilitation in multiple sclerosis: study protocol for a randomised controlled trial and cost-effectiveness analysis comparing customised with booklet based vestibular rehabilitation for vestibulopathy and a 12 month observational cohort study of the symptom reduction and recurrence rate following treatment for benign paroxysmal positional vertigo
Authors: Marsden J. , Pavlou M. , Dennett R. , Gibbon A. , Knight-Lozano R. , Jeu L. , Flavell C. , Freeman J. , Bamiou D. E. , Harris C. , Hawton A. , Goodwin E. , Jones B. , Creanor S.
Published: November 2020

Background

Symptoms arising from vestibular system dysfunction are observed in 49–59% of people with Multiple Sclerosis (MS). Symptoms may include vertigo, dizziness and/or imbalance. These impact on functional ability, contribute to falls and significant health and social care costs. In people with MS, vestibular dysfunction can be due to peripheral pathology that may include Benign Paroxysmal Positional Vertigo (BPPV), as well as central or combined pathology. Vestibular symptoms may be treated with vestibular rehabilitation (VR), and with repositioning manoeuvres in the case of BPPV. However, there is a paucity of evidence about the rate and degree of symptom recovery with VR for people with MS and vestibulopathy. In addition, given the multiplicity of symptoms and underpinning vestibular pathologies often seen in people with MS, a customised VR approach may be more clinically appropriate and cost effective than generic booklet-based approaches. Likewise, BPPV should be identified and treated appropriately.

Methods/ design

People with MS and symptoms of vertigo, dizziness and/or imbalance will be screened for central and/or peripheral vestibulopathy and/or BPPV. Following consent, people with BPPV will be treated with re-positioning manoeuvres over 1–3 sessions and followed up at 6 and 12 months to assess for any re-occurrence of BPPV. People with central and/or peripheral vestibulopathy will be entered into a randomised controlled trial (RCT). Trial participants will be randomly allocated (1:1) to either a 12-week generic booklet-based home programme with telephone support or a 12-week VR programme consisting of customised treatment including 12 face-to-face sessions and a home exercise programme. Customised or booklet-based interventions will start 2 weeks after randomisation and all trial participants will be followed up 14 and 26 weeks from randomisation. The primary clinical outcome is the Dizziness Handicap Inventory at 26 weeks and the primary economic endpoint is quality-adjusted life-years. A range of secondary outcomes associated with vestibular function will be used.

Discussion

If customised VR is demonstrated to be clinically and cost-effective compared to generic booklet-based VR this will inform practice guidelines and the development of training packages for therapists in the diagnosis and treatment of vestibulopathy in people with MS.

Trial registration

ISRCTN Number: 27374299

Date of Registration 24/09/2018

Protocol Version 15 25/09/2019
Routinely collected patient data in neurology research: a systematic mapping review
Authors: Biggin Fran , Emsley Hedley C. A. , Knight Jo
Published: November 2020

Background

This review focuses on neurology research which uses routinely collected data. The number of such studies is growing alongside the expansion of data collection. We aim to gain a broad picture of the scope of how routine healthcare data have been utilised.

Methods

This study follows a systematic mapping review approach which does not make a judgement on the quality of the papers included in the review, thereby enabling a complete overview of the field.

Results

Of 4481 publications retrieved, 386 met the eligibility criteria for this study. These publications covered a wide range of conditions, but the majority were based on one or only a small number of neurological conditions. In particular, publications concerned with three discrete areas of neurological practice - multiple sclerosis (MS), epilepsy/seizure and Parkinson’s disease - accounted for 60% of the total. MS was the focus of the highest proportion of eligible studies (35%), yet in the recent Global Burden of Neurological Disease study it ranks only 14th out of 15 neurological disorders for DALY rates. In contrast, migraine is the neurological disorder with the highest ranking of DALYs globally (after stroke) and yet it was represented by only 4% of eligible studies.

Conclusion

This review shows that there is a disproportionately large body of literature pertaining to relatively rare disorders, and a correspondingly small body of literature describing more common conditions. Therefore, there is potential for future research to redress this balance.
Both EZH2 and JMJD6 regulate cell cycle genes in breast cancer
Authors: Biswas Antara , Mukherjee Geetashree , Kondaiah Paturu , Desai Kartiki V.
Published: November 2020

Background

Strong evidences support the critical role of Jumonji domain containing 6 (JMJD6) in progression of breast cancer. Here we explore potential partners that coregulate gene expression, to understand additional pathways that are activated by higher amounts of JMJD6.

Methods

We used Gene Set Enrichment Analysis (GSEA) data to identify factors that display gene expression similar to cells treated with JMJD6 siRNA. Using chromatin immunoprecipitations (ChIP) against genomic regions that bind JMJD6 identified by in house and public database Encyclopaedia of DNA Elements (ENCODE), we confirmed JMJD6 occupancy by ChIP PCR. We tested the association of co-regulated genes with patient prognosis using The Cancer Genome Atlas (TCGA) datasets.

Results

JMJD6 profiles overlapped with those of Enhancer of Zeste homolog 2 (EZH2) and together they appear to co-regulate a unique cassette of genes in both ER+ and ER- cells. 496 genes including aurora kinases, which are currently being tested as novel therapeutic targets in breast cancer were co-regulated in MDA MB 231 cells. JMJD6 and EZH2 neither inter-regulated nor physically interacted with one another. Since both proteins are chromatin modulators, we performed ChIP linked PCR analysis and show that JMJD6 bound in the neighbourhood of co-regulated genes, though EZH2 data did not show any peaks within 100 kb of these sites. Alignment of binding site sequences suggested that atleast two types of binding partners could offer their DNA binding properties to enrich JMJD6 at regulatory sites. In clinical samples, JMJD6 and EZH2 expression significantly correlated in both normal and tumor samples, however the strongest correlation was observed in triple-negative breast cancer (TNBC) subtype. Co-expression of JMJD6 and EZH2 imposed poorer prognosis in breast cancer.

Conclusions

JMJD6 and EZH2 regulate the same crucial cell cycle regulatory and therapeutic targets but their mechanisms appear to be independent of each other. Blocking of a single molecule may not axe cell proliferation completely and blocking both JMJD6 and EZH2 simultaneously may be more effective in breast cancer patients.
An aggressive systemic mastocytosis preceded by ovarian dysgerminoma
Authors: Tsutsumi Makiko , Miura Hiroki , Inagaki Hidehito , Shinkai Yasuko , Kato Asuka , Kato Takema , Hamada-Tsutsumi Susumu , Tanaka Makito , Kudo Kazuko , Yoshikawa Tetsushi , Kurahashi Hiroki
Published: November 2020

Background

Aggressive systemic mastocytosis (ASM) is a rare malignant disease characterized by disordered mast cell accumulation in various organs. We here describe a female ASM patient with a previous history of ovarian dysgerminoma.

Methods

Molecular cytogenomic analyses were performed to elucidate an etiological link between the ASM and dysgerminoma of the patient.

Results

This patient was affected by ovarian dysgerminoma which was treated by chemotherapy and surgical resection. Having subsequently been in complete remission for 2 years, she developed symptoms of ASM. A somatic D816A mutation in the KIT gene was detected in her bone marrow, which facilitated the diagnosis of ASM. Unexpectedly, this KIT D816A variant was also detected in the prior ovarian dysgerminoma sample. Whole-exome sequencing allowed us to identify a somatic nonsense mutation of the TP53 gene in the bone marrow, but not in the dysgerminoma. Microarray analysis of the patient’s bone marrow revealed a copy-number-neutral loss of heterozygosity at the TP53 locus, suggestive of the homozygous nonsense mutation in the TP53 gene. In addition, the loss of heterozygosity at the TP53 locus was also detected in the dysgerminoma.

Conclusions

These results indicated that either the mast cells causing the ASM in this case had originated from the preceding ovarian dysgerminoma as a clonal evolution of a residual tumor cell, which acquired the TP53 mutation, or that both tumors developed from a common cancer stem cell carrying the KIT D816A variation.
Phase II randomized trial of capecitabine with bevacizumab and external beam radiation therapy as preoperative treatment for patients with resectable locally advanced rectal adenocarcinoma: long term results
Authors:   on behalf of the Spanish Cooperative Group for the Treatment of Digestive Tumors (TTD), Salazar Ramón , Capdevila Jaume , Manzano Jose Luis , Pericay Carles , Martínez-Villacampa Mercedes , López Carlos , Losa Ferrán , Safont María José , Gómez-España Auxiliadora , Alonso-Orduña Vicente , Escudero Pilar , Gallego Javier , García-Paredes Beatriz , Palacios Amalia , Biondo Sebastiano , Grávalos Cristina , Aranda Enrique
Published: November 2020

Background

Preoperative chemoradiotherapy with capecitabine is considered as a standard of care for locally advanced rectal cancer. The “Tratamiento de Tumores Digestivos” group (TTD) previously reported in a randomized Ph II study that the addition of Bevacizumab to capecitabine-RT conferred no differences in the pre-defined efficacy endpoint (pathological complete response).

We present the follow-up results of progression-free survival, distant relapse-free survival, and overall survival data at 3 and 5 years.

Methods

Patients (pts) were randomized to receive 5 weeks of radiotherapy (45 Gy/25 fractions) with concurrent Capecitabine 825 mg/m2 twice daily, 5 days per week with (arm A) or without (arm b) bevacizumab (5 mg/kg once every 2 weeks).

Results

In our study, the addition of bevacizumab to capecitabine and radiotherapy in the neoadjuvant setting shows no differences in pathological complete response (15.9% vs 10.9%), distant relapse-free survival (81.0 vs 80.4 and 76.2% vs 78.2% at 3 and 5 years respectively), disease-free survival (75% vs 71.7 and 68.1% vs 69.57% at 3 and 5 years respectively) nor overall survival at 5-years of follow-up (81.8% vs 86.9%).

Conclusions

the addition of bevacizumab to capecitabine plus radiotherapy does not confer statistically significant advantages neither in distant relapse-free survival nor in disease-free survival nor in Overall Survival in the short or long term.

Trial registration

EudraCT number: 2009–010192-24.

Clinicaltrials.gov number: NCT01043484.
A novel TGF-β receptor II mutation (I227T/N236D) promotes aggressive phenotype of oral squamous cell carcinoma via enhanced EGFR signaling
Authors: Son Hwa-Kyung , Kim Dokyeong , Lim Yongwoon , Kim Jin , Park Iha
Published: November 2020

Background

Transforming growth factor-β (TGF-β) signaling is a double-edged sword in cancer development and progression. TGF-β signaling plays a tumor suppressive role during the early stages of tumor development but promotes tumor progression in later stages. We have previously identified various mutations of TGF-β receptor II (TβRII) in human oral squamous cell carcinoma (OSCC) samples. In the present study we analyzed I227T/N236D mutation of TβRII, which was detected in the metastatic lymph node of an OSCC patient.

Methods

The effect of I227T/N236D TβRII mutation on transcriptional activities was measured using DR26 cells, which lack functional TβRII. HSC2 human OSCC cells stably expressing wild-type and I227T/N236D mutant TβRII were generated and used to examine the effect of I227T/N236D TβRII mutation on xenograft tumor growth, in vitro cell proliferation, apoptosis, migration, and invasion.

Results

The I227T/N236D mutation of TβRII upregulated TGF-β signaling and promoted xenograft tumor growth when compared with the wild-type, without affecting the in vitro proliferative capacities. To delineate the differences in proliferative capacities in vivo and in vitro, the apoptotic and survival signals were analyzed following curcumin treatment. Concomitant with apoptotic induction, epidermal growth factor receptor (EGFR) activation was observed upon curcumin treatment, which was further activated in I227T/N236D mutant transfectant cells when compared with wild-type cells. Enhanced EGFR activation correlated with cell survival and apoptotic resistance. Enhanced migratory and invasive capabilities of I227T/N236D mutant cells also depended on EGFR signaling.

Conclusions

These results suggest that enhanced EGFR signaling via upregulated TGF-β signaling shifted the balance toward survival and promoted cell migration and invasion in I227T/N236D mutant cells, elucidating the role of I227T/N236D mutation of TβRII in OSCC progression.
Health behaviors in major chronic diseases patients: trends and regional variations analysis, 2008–2017, Korea
Authors: Jeon Young-Jee , Pyo Jeehee , Park Young-Kwon , Ock Minsu
Published: November 2020

Background

Improving the health behaviors of those with chronic diseases such as hypertension and diabetes is important for disease management. Few in-depth studies have been conducted in Korea on the health behaviors of chronic disease patients. This study examined the health behaviors of chronic disease patients over time and compared them with those of the general population.

Methods

Cross-sectional time-series data obtained from the Korea Community Health Survey from 2008 to 2017 were analyzed. Thirteen diseases were included in this analysis, namely, hypertension, diabetes, dyslipidemia, stroke, myocardial infarction, angina, osteoarthritis, osteoporosis, asthma, allergic rhinitis, atopic dermatitis, cataract, and depression. The current smoking rate, drinking rate, and the walking rate, which are leading health behaviors necessary for preventing chronic diseases, were analyzed by disease type. We compared patients’ health behaviors with those of the general population and identified regional variations.

Results

Although the current overall smoking rate was seemingly declining, the overall monthly drinking and high-risk drinking rates were increasing. In 2017, patients experiencing depression symptoms had a higher smoking rate than did the general population; hypertension and diabetes patients had a higher risk-drinking rate than did the latter. The general population’s walking rate was highest. There were considerable variations by region among chronic disease patients.

Conclusions

Chronic disease patients displayed worse health behaviors than those of the general population, in some instances. Rather than focusing only on chronic disease patients’ medication adherence, strategies must be devised to increase their smoking cessation rate, decrease their drinking rate, and increase their walking rate.
Clinical features of patients with hepatic portal venous gas
Authors: Fujii Manato , Yamashita Suguru , Tanaka Mayuko , Tashiro Jo , Takenaka Yoshiharu , Yamasaki Kazuki , Masaki Yukiyoshi
Published: November 2020

Background

Hepatic portal venous gas (HPVG) is a rare clinical condition that is caused by a variety of underlying diseases. However, the factors that would permit accurate identification of bowel ischemia, requiring surgery, in patients with HPVG have not been fully investigated.

Methods

Thirty patients that had been diagnosed with HPVG using computed tomography between 2010 and 2019 were allocated to two groups on the basis of clinical and intraoperative findings: those with (Group 1; n = 12 [40%]) and without (Group 2; n = 18 [60%]) bowel ischemia. Eleven patients underwent emergency surgery, and bowel ischemia was identified in eight of these (73%). Four patients in Group 1 were diagnosed with bowel ischemia, but treated palliatively because of their general condition. We compared the characteristics and outcomes of Groups 1 and 2 and identified possible prognostic factors for bowel ischemia.

Results

At admission, patients in Group 1 more commonly showed the peritoneal irritation sign, had lower base excess, higher lactate, and higher C-reactive protein, and more frequently had comorbid intestinal pneumatosis. Of the eight bowel ischemia surgery patients, four (50%) died, mainly because of anastomotic leak following bowel resection and primary anastomosis (3/4, 75%). All except one patient in Group 2, who presented with aspiration pneumonia, responded better to treatment.

Conclusions

Earlier identification and grading of bowel ischemia according to the findings at admission should benefit patients with HPVG by reducing the incidence of unnecessary surgery and increasing the use of safer procedures, such as prophylactic stoma placement.
Identifying the vegetation type in Google Earth images using a convolutional neural network: a case study for Japanese bamboo forests
Authors: Watanabe Shuntaro , Sumi Kazuaki , Ise Takeshi
Published: November 2020

Background

Classifying and mapping vegetation are crucial tasks in environmental science and natural resource management. However, these tasks are difficult because conventional methods such as field surveys are highly labor-intensive. Identification of target objects from visual data using computer techniques is one of the most promising techniques to reduce the costs and labor for vegetation mapping. Although deep learning and convolutional neural networks (CNNs) have become a new solution for image recognition and classification recently, in general, detection of ambiguous objects such as vegetation is still difficult. In this study, we investigated the effectiveness of adopting the chopped picture method, a recently described protocol for CNNs, and evaluated the efficiency of CNN for plant community detection from Google Earth images.

Results

We selected bamboo forests as the target and obtained Google Earth images from three regions in Japan. By applying CNN, the best trained model correctly detected over 90% of the targets. Our results showed that the identification accuracy of CNN is higher than that of conventional machine learning methods.

Conclusions

Our results demonstrated that CNN and the chopped picture method are potentially powerful tools for high-accuracy automated detection and mapping of vegetation.
A case report of thyroid-associated Orbitopathy with elevated TPO antibodies
Authors: El Othman Radwan , Ephrem Christelle , Touma Elsie , Hallit Souheil , El Othman Rola
Published: November 2020

Background

Thyroid associated orbitopathy (TAO) is defined as an immune mediated inflammatory process affecting the extraocular muscles, connective and adipose tissue of uncertain etiopathogenesis. TAO are classically described in Grave’s disease (GD) however it may occur in euthyroid and hypothyroid patients. Those patients usually test positive for Thyroid Stimulating Hormone receptor antibodies (TRAb). For instance, only few cases of severe Hashimoto’s thyroiditis (HT) associated orbitopathy with negative TRAb are reported to date.

Case presentation

Herewith we report a rare case of a middle-aged female who presented with bilateral progressive upper and lower palpebral edema and a unilateral marked proptosis associated with asthenia, headache and decrease in visual acuity. Biological investigation was notable for high levels of anti-thyroid peroxidase antibodies (Anti-TPO) in an otherwise euthyroid patient with negative TRAb. Orbital Magnetic resonance imaging revealed edema of the extraocular muscles and inflammation of periorbital soft tissue. The patient received a treatment with intravenous methylprednisolone followed by oral treatment with prednisone. This regimen was both effective and safe with minimal metabolic side effects in our patient.

Conclusion

Minor ocular manifestations of HT are common; however, severe sight threatening ophtalmopathy in the absence of TRAb is rare. Multiple differential diagnosis should be considered and investigated before diagnosing this rare entity. Management of similar cases is currently based on reports and no clear guidelines have been elaborated, corticosteroids is the mainstream of treatment with a potential benefit of selenium supplementation in mild to moderate cases.
Identification of the anti-breast cancer targets of triterpenoids in Liquidambaris Fructus and the hints for its traditional applications
Authors: Qian Ping , Mu Xiao-Ting , Su Bing , Gao Lu , Zhang Dong-Fang
Published: November 2020

Background

Liquidambaris Fructus is the infructescences of Liquidambar formosana Hance and it has been used to treat some breast disease in Traditional Chinese Medicine. In the previous study we found the anti-breast cancer effect of triterpenoid in Liquidambaris Fructus. This study is a further investigation of the triterpenoids in Liquidambaris Fructus and aims to identify their anti-breast cancer targets, meanwhile, to estimate the rationality of the traditional applications of Liquidambaris Fructus.

Methods

Triterpenoids in Liquidambaris Fructus were isolated and their structures were identified by NMR spectrums. Potential targets of these triterpenoids were predicted using a reverse pharmacophore mapping strategy. Associations between these targets and the therapeutic targets of breast cancer were analyzed by constructing protein-protein interaction network, and targets played important roles in the network were identified using Molecular Complex Detection method. Binding affinity between the targets and triterpenoids was studied using molecular docking method. Gene ontology enrichment analysis was conducted to reveal the biological process and signaling pathways that the identified targets were involved in.

Results

Thirteen triterpenoids were identified and 6 of them were the first time isolated from Liquidambaris Fructus. Predicted ADME properties revealed a good druggability of these triterpenoids. We identified 18 protein targets which were closely related to breast cancer progression, especially triple-negative, basal-like or advanced stage breast cancers. The triterpenoids could bind with these targets as their inhibitors: hydrophobic skeleton is a favorable factor for them to stabilize at binding site and polar C17- or C3- substituent was necessary for binding. GO enrichment analysis indicated that inhibition of protein tyrosine kinases autophosphorylation might be the primary mechanism for the anti-breast cancer effect of the triterpenoids, and ErbB4 and EGFR were the most relevant targets.

Conclusions

The study revealed that triterpenoids from Liquidambaris Fructus might exert anti-breast cancer effect by directly inhibit multiple protein targets and signaling pathways, especially ErbB4 and EGFR and related pathways. This study also brings up another hint that the traditional applications of Liquidambaris Fructus on hypogalactia should be reassessed systematically because it might suppress rather than promote lactation by inhibiting the activity of ErbB4.
Pursue today and assess tomorrow - how students’ subjective perceptions influence their preference for self- and peer assessments
Authors: Capan Melser Meskuere , Lettner Stefan , Bäwert Andjela , Puttinger Claudia , Holzinger Anita
Published: November 2020

Background

Alternative assessments engage students in the assessment process to improve both short- and long-term outcomes by developing their judgments and responsibility about their own learning, and that of their peers. In this study, we investigated students’ perception towards self- and peer-assessment, their objectivity and impact on students’ learning.

Methods

The study was conducted at the Medical University of Vienna. Attitudes of second year undergraduate medical students towards self- and peer-assessment, and their objectivity, appropriateness, and the impact of these assessments on students’ learning activities, was inquired using a self-developed questionnaire.

Results

Four hundred twenty-three students participated in this study. Self-assessment was found more appropriate method to assess students’ knowledge. Most of students agreed that peer-assessment is not objective (M = − 0.07). Majority of students evaluated that peer assessment has no or little impact on their active and passive learning (M = − 0.23, − 0.35), on the other hand self-assessment was reported as a helpful tool for gaining long-term knowledge (M = 0.13) and following the content of courses (M = 0.16).

Conclusion

Based on our results, students’ perspective on peer assessment were negative, on the whole, students had positive attitudes towards self-assessment and negative attitudes towards peer-assessment. This study also determined that self-assessment leads to the promotion of students’ learning.
Impact of co-payment level increase of antidiabetic medications on glycaemic control: an interrupted time-series study among Finnish patients with type 2 diabetes
Authors: Lavikainen Piia , Aarnio Emma , Jalkanen Kari , Tirkkonen Hilkka , Rautiainen Päivi , Laatikainen Tiina , Martikainen Janne
Published: November 2020

Background

A new special reimbursement scheme (SRS) for non-insulin medications used for treatment of hyperglycaemia in type 2 diabetes (T2D) was implemented in Finland on January 1, 2017. The new SRS affected all community-dwelling Finnish T2D patients as all community-dwelling residents are eligible for reimbursement for prescription medications. The aim of the study was to evaluate the impact of this co-payment increase on glycaemic control among Finnish T2D patients.

Methods

Data on glycaemic control were collected with HbA1c measures from electronic health records from primary health care and specialized care in the North Karelia region, Finland, from patients with a confirmed T2D diagnosis in 2012 who were alive on January 1, 2017 (n = 8436). Average HbA1c levels were measured monthly 36 months before and 33 months after the policy change. Consumption of diabetes medications was measured with defined daily doses (DDDs) based on reimbursed medication purchases. Interrupted time series design analysed with segmented regression model was applied to examine the effect of the policy change on average HbA1c levels.

Results

Eight thousand one hundred forty-three T2D patients had at least one HbA1c measurement within 01/2014–9/2019. Mean age of the patients was 68.1 (SD 11.3) years and 53.0% were women. Average time since T2D diagnosis was 11.5 (SD 6.1) years. An estimated increase of 0.81 (95% confidence interval, CI, 0.04–1.58) mmol/mol in average HbA1c levels was detected at the time of the policy change. In subgroup analyses, strongest effects were detected among patients who used only other diabetes medications than insulin or metformin in 2016 (3.56 mmol/mol, 95% CI 2.50–4.62). Meanwhile, yearly consumption of diabetes medications decreased slightly from 618.9 (SD 487.8) DDDs/patient in 2016 to 602.9 (SD 475.6) DDDs/patient in 2017 (p = 0.048).

Conclusions

Simultaneously with the increase of the co-payment level, the average HbA1c level increased among T2D patients from the North Karelia region, Finland. This may be explained by the decreased consumption of diabetes medications between 2016 and 2017. Special attention should be allocated to glycaemic control of patients utilizing only other antidiabetic medications than metformin or insulin.
miR-31-5p regulates cold acclimation of the wood-boring beetle Monochamus alternatus via ascaroside signaling
Authors: Zhang Bin , Zhao Lilin , Ning Jing , Wickham Jacob D. , Tian Haokai , Zhang Xiaoming , Yang Meiling , Wang Xiangming , Sun Jianghua
Published: November 2020

Background

Survival to cold stress in insects living in temperate environments requires the deployment of strategies that lead to physiological changes involved in freeze tolerance or freeze avoidance. These strategies may consist of, for instance, the induction of metabolic depression, accumulation of cryoprotectants, or the production of antifreeze proteins, however, little is known about the way such mechanisms are regulated and the signals involved in their activation. Ascarosides are signaling molecules usually known to regulate nematode behavior and development, whose expression was recently found to relate to thermal plasticity in the Japanese pine sawyer beetle Monochamus alternatus. Accumulating evidence also points to miRNAs as another class of regulators differentially expressed in response to cold stress, which are predicted to target genes involved in cold adaptation of insects. Here, we demonstrate a novel pathway involved in insect cold acclimation, through miRNA-mediated regulation of ascaroside function.

Results

We initially discovered that experimental cold acclimation can enhance the beetle’s cold hardiness. Through screening and functional verification, we found miR-31-5p, upregulated under cold stress, significantly contributes to this enhancement. Mechanistically, miR-31-5p promotes production of an ascaroside (asc-C9) in the beetle by negatively targeting the rate-limiting enzyme, acyl-CoA oxidase in peroxisomal β-oxidation cycles. Feeding experiments with synthetic asc-C9 suggests it may serve as a signal to promote cold acclimation through metabolic depression and accumulation of cryoprotectants with specific gene expression patterns.

Conclusions

Our results point to important roles of miRNA-mediated regulation of ascaroside function in insect cold adaptation. This enhanced cold tolerance may allow higher survival of M. alternatus in winter and be pivotal in shaping its wide distribution range, greatly expanding the threat of pine wilt disease, and thus can also inspire the development of ascaroside-based pest management strategies.
The role of cortisol in ischemic heart disease, ischemic stroke, type 2 diabetes, and cardiovascular disease risk factors: a bi-directional Mendelian randomization study
Authors: Kwok Man Ki , Kawachi Ichiro , Rehkopf David , Schooling Catherine Mary
Published: November 2020

Background

Cortisol, a steroid hormone frequently used as a biomarker of stress, is associated with cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM). To clarify whether cortisol causes these outcomes, we assessed the role of cortisol in ischemic heart disease (IHD), ischemic stroke, T2DM, and CVD risk factors using a bi-directional Mendelian randomization (MR) study.

Methods

Single nucleotide polymorphisms (SNPs) strongly (P < 5 × 10−6) and independently (r2 < 0.001) predicting cortisol were obtained from the CORtisol NETwork (CORNET) consortium (n = 12,597) and two metabolomics genome-wide association studies (GWAS) (n = 7824 and n = 2049). They were applied to GWAS of the primary outcomes (IHD, ischemic stroke and T2DM) and secondary outcomes (adiposity, glycemic traits, blood pressure and lipids) to obtain estimates using inverse variance weighting, with weighted median, MR-Egger, and MR-PRESSO as sensitivity analyses. Conversely, SNPs predicting IHD, ischemic stroke, and T2DM were applied to the cortisol GWAS.

Results

Genetically predicted cortisol (based on 6 SNPs from CORNET; F-statistic = 28.3) was not associated with IHD (odds ratio (OR) 0.98 per 1 unit increase in log-transformed cortisol, 95% confidence interval (CI) 0.93–1.03), ischemic stroke (0.99, 95% CI 0.91–1.08), T2DM (1.00, 95% CI 0.96–1.04), or CVD risk factors. Genetically predicted IHD, ischemic stroke, and T2DM were not associated with cortisol.

Conclusions

Contrary to observational studies, genetically predicted cortisol was unrelated to IHD, ischemic stroke, T2DM, or CVD risk factors, or vice versa. Our MR results find no evidence that cortisol plays a role in cardiovascular risk, casting doubts on the cortisol-related pathway, although replication is warranted.
A serological framework to investigate acute primary and post-primary dengue cases reporting across the Philippines
Authors: Biggs Joseph R. , Sy Ava Kristy , Brady Oliver J. , Kucharski Adam J. , Funk Sebastian , Reyes Mary Anne Joy , Quinones Mary Ann , Jones-Warner William , Tu Yun-Hung , Avelino Ferchito L. , Sucaldito Nemia L. , Mai Huynh Kim , Lien Le Thuy , Do Thai Hung , Nguyen Hien Anh Thi , Anh Dang Duc , Iwasaki Chihiro , Kitamura Noriko , Yoshida Lay-Myint , Tandoc Amado O. , la Paz Eva Cutiongco-de , Capeding Maria Rosario Z. , Padilla Carmencita D. , Hafalla Julius Clemence R. , Hibberd Martin L.
Published: November 2020

Background

In dengue-endemic countries, targeting limited control interventions to populations at risk of severe disease could enable increased efficiency. Individuals who have had their first (primary) dengue infection are at risk of developing more severe secondary disease, thus could be targeted for disease prevention. Currently, there is no reliable algorithm for determining primary and post-primary (infection with more than one flavivirus) status from a single serum sample. In this study, we developed and validated an immune status algorithm using single acute serum samples from reporting patients and investigated dengue immuno-epidemiological patterns across the Philippines.

Methods

During 2015/2016, a cross-sectional sample of 10,137 dengue case reports provided serum for molecular (anti-DENV PCR) and serological (anti-DENV IgM/G capture ELISA) assay. Using mixture modelling, we re-assessed IgM/G seroprevalence and estimated functional, disease day-specific, IgG:IgM ratios that categorised the reporting population as negative, historical, primary and post-primary for dengue. We validated our algorithm against WHO gold standard criteria and investigated cross-reactivity with Zika by assaying a random subset for anti-ZIKV IgM and IgG. Lastly, using our algorithm, we explored immuno-epidemiological patterns of dengue across the Philippines.

Results

Our modelled IgM and IgG seroprevalence thresholds were lower than kit-provided thresholds. Individuals anti-DENV PCR+ or IgM+ were classified as active dengue infections (83.1%, 6998/8425). IgG− and IgG+ active dengue infections on disease days 1 and 2 were categorised as primary and post-primary, respectively, while those on disease days 3 to 5 with IgG:IgM ratios below and above 0.45 were classified as primary and post-primary, respectively. A significant proportion of post-primary dengue infections had elevated anti-ZIKV IgG inferring previous Zika exposure. Our algorithm achieved 90.5% serological agreement with WHO standard practice. Post-primary dengue infections were more likely to be older and present with severe symptoms. Finally, we identified a spatio-temporal cluster of primary dengue case reporting in northern Luzon during 2016.

Conclusions

Our dengue immune status algorithm can equip surveillance operations with the means to target dengue control efforts. The algorithm accurately identified primary dengue infections who are at risk of future severe disease.
Brazilian owners perception of the body condition score of dogs and cats
Authors: Teixeira Fabio Alves , Queiroz Mariana Ramos , Oba Patrícia Massae , Olivindo Rodrigo Fernando Gomes , Ernandes Mariane Ceschin , Duarte Caio Nogueira , Rentas Mariana Fragoso , Brunetto Marcio Antonio
Published: November 2020

Background

The knowledge of how owners view the body condition of their animals is an important factor for the success of the prevention/treatment of obesity and the engagement/adherence to nutritional interventions, which are fundamental to improve the animal prognosis. For this reason, the objective of this study was to evaluate the perception of the owners regarding the body condition score of their animals, compare the perception between cat vs. dog owners, and owners from the countryside vs. metropolitan region of São Paulo State in Brazil.

Results

601 dogs and 110 cats were included in this study. There was no significant difference in body condition score assigned by owners by species. Owners of dogs and cats classified by the veterinarian as ideal, overweight, and obese who disagree with body condition score assigned by veterinarian mainly underestimate the body condition score of their animals, while lean dogs’ owners overestimate it. Countryside dog owners had a higher rate of disagreement with the veterinarian and more often underestimate the body condition score than owners from the metropolitan region. The owners of lean cats have the same judgments with veterinarians.

Conclusions

Owners of dogs and cats have difficulty assessing the body condition score, especially owners from countryside.
Long non-coding RNA NORAD contributes to the proliferation, invasion and EMT progression of prostate cancer via the miR-30a-5p/RAB11A/WNT/β-catenin pathway
Authors: Zhang Yunxia , Li Yang
Published: November 2020

Background

Prostate cancer (PC) is common male cancer with high mortality worldwide. Emerging evidence demonstrated that long noncoding RNAs (lncRNAs) play critical roles in various type of cancers including PC by serving as competing endogenous RNAs (ceRNAs) to modulate microRNAs (miRNAs). LncRNA activated by DNA damage (NORAD) was found to be upregulated in PC cells, while the detailed function and regulatory mechanism of NORAD in PC progression remains largely unclear.

Methods

Expression of NORAD in PC tissues and cell lines were detected by real-time quantitative PCR (qRT-PCR). NORAD was respectively overexpressed and knocked down by transfection with pcDNA-NORAD and NORAD siRNA into PC-3 and LNCap cells. Cell proliferation, invasion and apoptosis were determined by using CCK-8, Transwell and Flow cytometry assays, respectively. The target correlations between miR-30-5p and NORAD or RAB11A were confirmed by using dual luciferase reporter assay. Moreover, expression levels of RAB11A, the epithelial-mesenchymal transition (EMT) marker proteins and the Wnt pathway related proteins were measured by Western blotting. Tumor xenograft assay was used to study the effect of NORAD on tumor growth in vivo.

Results

NORAD was upregulated in PC tissues and cells. Overexpression of NORAD promoted cell proliferation, invasion, EMT, and inhibited cell apoptosis; while knockdown of NORAD had the opposite effect. NORAD was found to be functioned as a ceRNA to bind and downregulated miR-30a-5p that was downregulated in PC tumor tissues. Rescue experiments revealed that miR-30a-5p could weaken the NORAD-mediated promoting effects on cell proliferation, invasion and EMT. Furthermore, RAB11A that belongs to a member of RAS oncogene family was verified as a target of miR-30a-5p, and reintroduction of RAB11A attenuated the effects of miR-30a-5p overexpression on cell proliferation, invasion, EMT and apoptosis of PC cells. More importantly, silencing RAB11A partially reversed the promoting effects of NORAD overexpression on cell proliferation, invasion and EMT of PC cells via the WNT/β-catenin pathway. Lastly, tumorigenicity assay in vivo demonstrated that NORAD increased tumor volume and weight via miR-30a-5p /RAB11A pathway.

Conclusion

Our results indicated a significant role of NORAD in mechanisms associated with PC progression. NORAD promoted cell proliferation, invasion and EMT via the miR-30a-5p/RAB11A/WNT/β-catenin pathway, thus inducing PC tumor growth.