bluuebunny/crossref_metadata_2025 huggingface dataset:
Heterologous expression of AHL lactonase AiiK by Lactobacillus casei MCJΔ1 with great quorum quenching ability against Aeromonas hydrophila AH-1 and AH-4
Authors: Dong Weiwei , Cai Yuyuan , Xu Zhilong , Fu Biao , Chen Qitong , Cui Yuxin , Ruan Zhiyong , Liang Yunxiang , Peng Nan , Zhao Shumiao
Published: October 2020

Background

Nowadays, microbial infections have caused increasing economic losses in aquaculture industry and deteriorated worldwide environments. Many of these infections are caused by opportunistic pathogens through cell-density mediated quorum sensing (QS). The disruption of QS, known as quorum quenching (QQ), is an effective and promising way to prevent and control pathogens, driving it be the potential bio-control agents. In our previous studies, AHL lactonase AiiK was identified with many characteristics, and constitutive expression vector pELX1 was constructed to express heterologous proteins in Lactobacillus casei MCJΔ1 (L. casei MCJΔ1). In this study, recombinant strain pELCW-aiiK/L. casei MCJΔ1 (LcAiiK) and wild-type Aeromonas hydrophila (A. hydrophila) were co-cultured to test the QQ ability of LcAiiK against A. hydrophila.

Results

A cell wall-associated expression vector pELCW for L. casei MCJΔ1 was constructed. Localization assays revealed that the expressed AiiK was anchored at the surface layer of LcAiiK via vector pELCW-aiiK. LcAiiK (OD600 = 0.5) degraded 24.13 μM of C6-HSL at 2 h, 40.99 μM of C6-HSL at 12 h, and 46.63 μM of C6-HSL at 24 h. Over 50% LcAiiK cells maintained the pELCW-aiiK plasmid after 15 generations of cultivation without erythromycin. Furthermore, LcAiiK inhibited the swimming motility, extracellular proteolytic activity, haemolytic activity and biofilm formation of A. hydrophila AH-1 and AH-4.

Conclusion

The AHL lactonase AiiK is firstly and constitutively expressed at the surface layer of L. casei MCJΔ1. LcAiiK displayed considerable AHL lactonase activity and great QQ abilities against A. hydrophila AH-1 and AH-4 by attenuating their QS processes instead of killing them. Therefore, the LcAiiK can be exploited as an anti-pathogenic drug or a bio-control agent to control the AHL-mediated QS of pathogenic bacteria.
Retraction Note to: Correlations between chromobox homolog 8 and key factors of epithelial–mesenchymal transition in hepatocellular carcinoma
Authors: Zhu Xiaonian , Luo Wei , Bei Chunhua , Kong Juan , Zhang Shidong , Fu Yuanyuan , Li Di , Tan Shengkui
Published: October 2020

This article has been retracted. Please see the retraction notice for more detail: https://doi.org/10.1186/s12935-020-01574-4.
BTG1 inhibits malignancy as a novel prognosis signature in endometrial carcinoma
Authors: Li Yibing , Huo Jianing , He Junjian , Zhang Yunzheng , Ma Xiaoxin
Published: October 2020

Background

Endometrial carcinoma (EC) is one of the three major malignant tumors of the female reproductive system. In recent years, the incidence and mortality rate of EC have increased. B-cell translocation gene 1 (BTG1) is an anti-proliferation gene that regulates the occurrence and development of a variety of tumors, but there is no research regarding this gene in EC.

Methods

Based on The Cancer Genome Atlas (TCGA) database, we used a variety of bioinformatics tools and databases to explore the expression and prognosis of BTG1. We verified expression and prognosis of BTG1 in EC using qRT-PCR and analyzed the relevant clinicopathological parameters. We functionally enriched BTG1 and related genes in EC patients through the bioinformatics website and analyzed miRNA targets of BTG1 and interacting protein networks. Cell proliferation, wound healing, transwell invasion, and cell apoptosis assays were used to detect the effects of BTG1 on the malignant biological behavior of endometrial carcinoma cells (ECCs). The effect of BTG1 on the epithelial-to-mesenchymal transition (EMT) process was detected using western blot.

Results

We analyzed the expression and prognosis of BTG1 based on TCGA and found that low expression of BTG1 was associated with poor EC prognosis. The qRT-PCR suggested that BTG1 had low expression in EC. BTG1 expression was significantly correlated with overall survival (OS) shortening. Clinicopathological analysis suggested that expression of BTG1 was related to invasion depth and the International Federation of Gynecology and Obstetrics (FIGO) stage. EC pathological tissue type, fertility history, lymphatic metastasis, menopause, estrogen receptor (ER), progesterone receptor (PR), and age of diagnosis were not related. Functional enrichment analysis showed that BTG1 plays an important role in regulating embryonic development, tumorigenesis, apoptosis, and cell cycle. Biological behavior experiments suggest that BTG1 inhibits proliferation, migration, and invasion of ECCs, and promotes apoptosis of ECCs. Western blot indicated that BTG1 inhibited the EMT process of ECCs.

Conclusions

BTG1, as a tumor suppressor gene, plays an important role in the occurrence and development of EC. We believe that BTG1 can be used as a potential prognostic biomarker for EC.
Lure, retain, and catch malaria mosquitoes. How heat and humidity improve odour-baited trap performance
Authors: Cribellier Antoine , Spitzen Jeroen , Fairbairn Henry , van de Geer Cedric , van Leeuwen Johan L. , Muijres Florian T.
Published: October 2020

Background

When seeking a human for a blood meal, mosquitoes use several cues to detect and find their hosts. From this knowledge, counter-flow odour-baited traps have been developed that use a combination of CO2, human-mimicking odour, visual cues and circulating airflow to attract and capture mosquitoes. Initially developed for monitoring, these traps are now also being considered as promising vector control tools. The traps are attractive to host-seeking mosquitoes, but their capture efficiency is low. It has been hypothesized that the lack of short-range host cues, such as heat and increased local humidity, often prevent mosquitoes from getting close enough to get caught; this lack might even trigger avoidance manoeuvres near the capture region.

Methods

This study investigated how close-range host cues affect the flight behaviour of Anopheles female malaria mosquitoes around odour-baited traps, and how this affects trap capture performance. For this, a novel counter-flow odour-baited trap was developed, the M-Tego. In addition to the usual CO2 and odour-blend, this trap can provide the short-range host cues, heat and humidity. Systematically adding or removing these two cues tested how this affected the trap capture percentages and flight behaviour. First, capture percentages of the M-Tego with and without short-range host cues to the BG-Suna trap were compared, in both laboratory and semi-field testing. Then, machine-vision techniques were used to track the three-dimensional flight movements of mosquitoes around the M-Tego.

Results

With heat and humidity present, the M-Tego captured significantly more mosquitoes as capture percentages almost doubled. Comparing the flight behaviour around the M-Tego with variable close-range host cues showed that when these cues were present, flying mosquitoes were more attracted to the trap and spent more time there. In addition, the M-Tego was found to have a better capture mechanism than the BG-Suna, most likely because it does not elicit previously observed upward avoiding manoeuvres.

Conclusions

Results suggest that adding heat and humidity to an odour-baited trap lures more mosquitoes close to the trap and retains them there longer, resulting in higher capture performance. These findings support the development of control tools for fighting mosquito-borne diseases such as malaria.
Binding of human serum proteins to Plasmodium falciparum-infected erythrocytes and its association with malaria clinical presentation
Authors: Lopez-Perez Mary , van der Puije William , Castberg Filip C. , Ofori Michael F. , Hviid Lars
Published: October 2020

Background

The pathogenesis of Plasmodium falciparum malaria is related to the ability of parasite‑infected erythrocytes (IEs) to adhere to the vascular endothelium (cytoadhesion/sequestration) or to surrounding uninfected erythrocytes (rosetting). Both processes are mediated by the expression of members of the clonally variant PfEMP1 parasite protein family on the surface of the IEs. Recent evidence obtained with laboratory-adapted clones indicates that P. falciparum can exploit human serum factors, such as IgM and α2-macroglobulin (α2M), to increase the avidity of PfEMP1-mediated binding to erythrocyte receptors, as well as to evade host PfEMP1-specific immune responses. It has remained unclear whether PfEMP1 variants present in field isolates share these characteristics, and whether they are associated with clinical malaria severity. These issues were investigated here.

Methods

Children 1–12 years reporting with P. falciparum malaria to Hohoe Municipal Hospital, Ghana were enrolled in the study. Parasites from children with uncomplicated (UM) and severe malaria (SM) were collected. Binding of α2M and IgM from non-immune individuals to erythrocytes infected by P. falciparum isolates from 34 children (UM and SM) were analysed by flow cytometry. Rosetting in the presence of IgM or α2M was also evaluated. Experimental results were analysed according to the clinical presentation of the patients.

Results

Clinical data from 108 children classified as UM (n = 54) and SM cases (n = 54) were analysed. Prostration, severe malaria anaemia, and hyperparasitaemia were the most frequent complications. Three children were diagnosed with cerebral malaria, and one child died. Parasite isolates from UM (n = 14) and SM (n = 20) children were analysed. Most of the field isolates bound non-immune IgM (33/34), whereas the α2M-binding was less common (23/34). Binding of both non-immune IgM and α2M was higher but not significant in IEs from children with SM than from children with UM. In combination, IgM and α2M supported rosette formation at levels similar to that observed in the presence of 10% human serum.

Conclusions

The results support the hypothesis that binding of non-immune IgM and/or α2M to IEs facilitates rosette formation and perhaps contributes to P. falciparum malaria severity.
Buprenorphine therapy in the setting of induced opioid withdrawal from oral naltrexone: a case report
Authors: Szczesniak Laura M. , Calleo Vincent J. , Sullivan Ross W.
Published: October 2020

Background

Patients with opioid use disorder (OUD) frequently present to the emergency department for acute treatment of overdose and withdrawal.

Case presentation

A 29-year-old male presented to the emergency room after intravenous heroin use followed by accidental ingestion of naltrexone. He was treated with buprenorphine with significant improvement in his Clinical Opioid Withdrawal Score, from moderately severe to mild withdrawal symptoms within a few hours.

Conclusion

Buprenorphine and minimal supportive care can be used to treat acute withdrawal precipitated by oral naltrexone in patients with OUD.
Impact of non-cardiovascular comorbidities on the quality of life of patients with chronic heart failure: a scoping review
Authors: Comín-Colet Josep , Martín Lorenzo Teresa , González-Domínguez Almudena , Oliva Juan , Jiménez Merino Silvia
Published: October 2020

Purpose

To determine the impact of non-cardiovascular comorbidities on the health-related quality of life (HRQoL) of patients with chronic heart failure (CHF).

Methods

A scoping review of the scientific literature published between 2009 and 2019 was carried out. Observational studies which assessed the HRQoL of patients with CHF using validated questionnaires and its association with non-cardiovascular comorbidities were included.

Results

The search identified 1904 studies, of which 21 fulfilled the inclusion criteria to be included for analysis. HRQoL was measured through specific, generic, or both types of questionnaires in 72.2%, 16.7%, and 11.1% of the studies, respectively. The most common comorbidities studied were diabetes mellitus (12 studies), mental and behavioral disorders (8 studies), anemia and/or iron deficiency (7 studies), and respiratory diseases (6 studies). Across studies, 93 possible associations between non-cardiovascular comorbidities and HRQoL were tested, of which 21.5% regarded anemia or iron deficiency, 20.4% mental and behavioral disorders, 20.4% diabetes mellitus, and 14.0% respiratory diseases. Despite the large heterogeneity across studies, all 21 showed that the presence of a non-cardiovascular comorbidity had a negative impact on the HRQoL of patients with CHF. A statistically significant impact on worse HRQoL was found in 84.2% of associations between mental and behavioral disorders and HRQoL (patients with depression had up to 200% worse HRQoL than patients without depression); 73.7% of associations between diabetes mellitus and HRQoL (patients with diabetes mellitus had up to 21.8% worse HRQoL than patients without diabetes mellitus); 75% of associations between anemia and/or iron deficiency and HRQoL (patients with anemia and/or iron deficiency had up to 25.6% worse HRQoL than between patients without anemia and/or iron deficiency); and 61.5% of associations between respiratory diseases and HRQoL (patients with a respiratory disease had up to 21.3% worse HRQoL than patients without a respiratory disease).

Conclusion

The comprehensive management of patients with CHF should include the management of comorbidities which have been associated with a worse HRQoL, with special emphasis on anemia and iron deficiency, mental and behavioral disorders, diabetes mellitus, and respiratory diseases. An adequate control of these comorbidities may have a positive impact on the HRQoL of patients.
Determinants of health-related quality of life decline in interstitial lung disease
Authors: Maqhuzu Phillen Nozibuyiso , Szentes Boglarka L. , Kreuter Michael , Bahmer Thomas , Kahn Nicolas , Claussen Martin , Holle Rolf , Schwarzkopf Larissa
Published: October 2020

Background

Health-related quality of life (HRQL) in interstitial lung disease (ILD) patients is impaired. We aimed to identify baseline predictors for HRQL decline within a 12-month observation period.

Methods

We analyzed 194 ILD patients from two German ILD-centers in the observational HILDA study. We employed the disease-specific King’s Brief Interstitial Lung Disease questionnaire (K-BILD) with the subdomains ‘psychological impact’, ‘chest symptoms’ and ‘breathlessness and activities’, and the generic EQ-5D Visual Analog Scale (VAS). We evaluated how many patients experienced a clinically meaningful decline in HRQL. Subsequently, we investigated medical and sociodemographic factors as potential predictors of HRQL deterioration.

Results

Within the study population (34.0% male, Ø age 61.7) mean HRQL scores hardly changed between baseline and follow up (K-BILD: 52.8 vs. 52.5 | VAS: 60.0 vs. 57.3). On the intra-individual level, 30.4% (n = 59) experienced a clinically relevant deterioration in K-BILD total score and 35.4% (n = 68) in VAS. Lower baseline forced vital capacity (FVC) % predicted determined HRQL decline in K-BILD total score (ß-coefficient: − 0.02, p = 0.007), VAS (ß-coefficient: − 0.03, p < 0.0001), and in the subdomain ‘psychological impact’ (ß-coefficient: − 0.02, p = 0.014). Lower baseline diffusing capacity of carbon monoxide (DLCO) % predicted determined deterioration in ‘breathlessness and activities’ (ß-coefficient: − 0.04, p = 0.003) and ‘chest symptoms’ (ß-coefficient: − 0.04, p = 0.002). Additionally, increasing age predicted decline in ‘psychological impact’ (ß-coefficient: 0.06, p < 0.007).

Conclusion

Around a third of ILD patients experienced a clinically relevant HRQL deterioration in a 12-month period, which was associated with baseline lung function values in all K-BILD domains. As lung function values are time-dependent variables with possible improvements, in contrast to age and ILD subtype, it, thus, seems important to improve lung function and prevent its decline in order to maintain HRQL on the possibly highest level.
Chemotherapy use and quality of life in cancer patients at the end of life: an integrative review
Authors: Akhlaghi Elham , Lehto Rebecca H. , Torabikhah Mohsen , Sharif Nia Hamid , Taheri Ahmad , Zaboli Ehsan , Yaghoobzadeh Ameneh
Published: October 2020

Background

When curative treatments are no longer available for cancer patients, the aim of treatment is palliative. The emphasis of palliative care is on optimizing quality of life and provided support for patients nearing end of life. However, chemotherapy is often offered as a palliative therapy for patients with advanced cancer nearing death. The purpose of this review was to evaluate the state of the science relative to use of palliative chemotherapy and maintenance of quality of life in patients with advanced cancer who were at end of life.

Materials and methods

Published research from January 2010 to December 2019 was reviewed using PRISMA guidelines using PubMed, Proquest, ISI web of science, Science Direct, and Scopus databases. MeSH keywords including quality of life, health related quality of life, cancer chemotherapy, drug therapy, end of life care, palliative care, palliative therapy, and palliative treatment.

Findings

13 studies were evaluated based on inclusion criteria. Most of these studies identified that reduced quality of life was associated with receipt of palliative chemotherapy in patients with advanced cancer at the end of life.

Conclusion

Studies have primarily been conducted in European and American countries. Cultural background of patients may impact quality of life at end of life. More research is needed in developing countries including Mideastern and Asian countries.
Cross-cultural adaptation, validity, and reliability of the Nepali version of the Exercise Adherence Rating Scale: a methodological study
Authors: Adhikari Shambhu P. , Dev Rubee , Shrestha Jayana N.
Published: October 2020

Background

The Exercise Adherence Rating Scale (EARS) is a commonly used outcome tool, which helps to identify the adherence rate of exercises and reasons for adherence and non-adherence. There is no evidence of the availability of any measurement tools to assess exercise adherence in the Nepalese context and cultural background. Therefore, we conducted a cross-cultural adaptation of the EARS into the Nepali language and investigated its reliability and validity.

Methods

Cross-cultural adaptation of the EARS was done based on Beaton guidelines. Psychometric properties were evaluated among 18 participants aged 18 years or older with pre-diabetes or confirmed diagnosis of any disease who were prescribed with home exercises by physiotherapists. Any disease that limited participants from doing exercise and individuals unwilling to participate were excluded. Reliability was evaluated through internal consistency, using Cronbach’s alpha. Exploratory Factor Analysis (EFA) was performed to explore construct validity and confirm its unidimensionality. Receiver Operating Characteristic (ROC) curve was analyzed to identify cut-off score, sensitivity and specificity of the tool.

Results

The Cronbach’s alpha was 0.94 for EARS-adherence behavior. The EFA of 6-items adherence behavior revealed the presence of one factor with an eigenvalue exceeding one. The scree-plot suggested for extraction of only one factor with strong loading (75.84%). The Area Under the Curve was 0.91 with 95% confidence interval 0.77–1.00 at p = 0.004. The cutoff score was found 17.5 with 89% sensitivity and 78% specificity.

Conclusions

The EARS was cross-culturally adapted to the Nepali language. The reliability and construct validity of the Nepali version of the EARS were acceptable to assess exercise adherence in Nepali-speaking individuals. This validated tool might facilitate the evaluation of exercise-related interventions. Future studies could investigate other psychometric properties of the Nepali EARS.
Translation, cross-cultural adaptation and validation of the Slovenian version of Harris Hip Score
Authors: Josipović Petra , Moharič Metka , Salamon Dea
Published: October 2020

Introduction

The Harris Hip Score is the most widely used outcome measure for the assessment of hip pathologies. An official Slovenian version has not been culturally adapted and validated. The aim of this study was to create a Slovenian valid and reliable version of the HHS.

Materials and method

The HHS was translated and modified in Slovenian. The measurement properties of the Slovenian HHS were tested in 42 patients suffering from different hip pathologies. Reliability, responsiveness, construct validity, convergent/divergent validity and content validity of the Slovenian version of the HHS were tested.

Results

Only minor adaptation was required in the translation process. The internal consistency of the HHS expressed by Cronbach’s alpha was 0.94. The test–retest reliability expressed by the intraclass correlation coefficient was 0.983. The correlations of the HHS scale with the WOMAC scale (r = − 0.877) and the VAS scale (r = − 0.717) were statistically significant. The highest correlation between the HHS and SF-36 was with the General Health dimension (r = 0.61). while the lowest correlation was with the SF-36 Mental Health dimension (r = 0.43). MDC95% was 10.1. No floor or ceiling effects were found.

Conclusion

Slovenian version of HHS seems to has an acceptable level of reliability and validity. Slovenian HHS is short, comprehensible and easy to administer and interpret.

Trial registration

Approved by the Slovenian National Medical Ethics Committee (0120-46/2019/19).
Clinical benefits of adjuvant chemotherapy with carboplatin and gemcitabine in patients with non-small cell lung cancer: a single-center retrospective study
Authors: Takashima Shinogu , Imai Kazuhiro , Atari Maiko , Matsuo Tsubasa , Nakayama Katsutoshi , Sato Yusuke , Motoyama Satoru , Shibata Hiroyuki , Nomura Kyoko , Minamiya Yoshihiro
Published: October 2020

Purpose

In cases of non-small cell lung cancer (NSCLC), surgery remains the best option for cure, but surgery is of benefit only when the disease is localized. Although adjuvant chemotherapy reportedly has a significant beneficial effect on survival, the benefit of a carboplatin (CBDCA) regimen is unclear. We therefore investigated the efficacy and tolerability of CBDCA (area under the curve 5) plus gemcitabine (GEM, 1000 mg/m2) as adjuvant chemotherapy.

Methods

A total of 82 pStage IB-IIIA NSCLC patients who had undergone complete resection and received adjuvant chemotherapy were analyzed retrospectively. Among them, 65 patients received CBDCA + GEM and 17 received CDDP + VNR. Propensity score analysis generated 17 matched pairs of both groups.

Results

Sixty-five patients received CBDCA + GEM. Their 5-year relapse-free survival (RFS) and overall survival were 47.8% (median, 52.5 months) and 76.9% (median, 90.1 months), respectively. Toxicities, which included neutropenia, nausea/anorexia, fatigue, and vasculitis, were significantly milder than with CDDP + VNR. There were no significant differences in RFS between CBDCA + GEM and CDDP + VNR (p = 0.079) after matching for age, performance status, and pStage.

Conclusion

CBDCA + GEM was effective and well tolerated as adjuvant chemotherapy, with a manageable toxicity profile.
Sensing form - finger gaiting as key to
tactile object exploration - a data glove analysis of a prototypical daily
task
Authors: Krammer Werner , Missimer John H. , Habegger Simon , Pastore-Wapp Manuela , Wiest Roland , Weder Bruno J.
Published: October 2020

Background

Motor hand skill and associated dexterity is important for meeting
the challenges of daily activity and an important resource post-stroke. In this
context, the present study investigated the finger movements of right-handed
subjects during tactile manipulation of a cuboid, a prototypical task underlying
tactile exploration. During one motor act, the thumb and fingers of one hand
surround the cuboid in a continuous and regular manner. While the object is
moved by the guiding thumb, the opposed supporting fingers are replaced once
they reach their joint limits by free fingers, a mechanism termed finger
gaiting.

Methods

For both hands of 22 subjects, we acquired the time series of
consecutive manipulations of a cuboid at a frequency of 1 Hz, using a digital
data glove consisting of 29 sensors. Using principle component analysis, we
decomposed the short action into motor patterns related to successive
manipulations of the cuboid. The components purport to represent changing grasp
configurations involving the stabilizing fingers and guiding thumb. The temporal
features of the components permits testing whether the distinct configurations
occur at the frequency of 1 Hz, i.e. within the time window of 1 s, and, thus,
taxonomic classification of the manipulation as finger gaiting.

Results

The fraction of variance described by the principal components
indicated that three components described the salient features of the single
motor acts for each hand. Striking in the finger patterns was the prominent and
varying roles of the MCP and PIP joints of the fingers, and the CMC joint of the
thumb. An important aspect of the three components was their representation of
distinct finger configurations within the same motor act. Principal component
and graph theory analysis confirmed modular, functionally synchronous action of
the involved joints. The computation of finger trajectories in one subject
illustrated the workspace of the task, which differed for the right and left
hands.

Conclusion

In this task one complex motor act of 1 s duration could be
described by three elementary and hierarchically ordered grasp configurations
occurring at the prescribed frequency of 1 Hz. Therefore, these configurations
represent finger gaiting, described until now only in artificial systems, as the
principal mechanism underlying this prototypical task.

Trial registration

clinicaltrials.gov, NCT02865642, registered 12 August 2016.
Rhythmic neural activity is comodulated with short-term gait modifications during first-time use of a dummy prosthesis: a pilot study
Authors: Kooiman Vera G. M. , van Keeken Helco G. , Maurits Natasha M. , Weerdesteyn Vivian , Solis-Escalante Teodoro
Published: October 2020

Background

After transfemoral amputation, many hours of practice are needed to re-learn walking with a prosthesis. The long adaptation process that consolidates a novel gait pattern seems to depend on cerebellar function for reinforcement of specific gait modifications, but the precise, step-by-step gait modifications (e.g., foot placement) most likely rely on top-down commands from the brainstem and cerebral cortex. The aim of this study was to identify, in able-bodied individuals, the specific modulations of cortical rhythms that accompany short-term gait modifications during first-time use of a dummy prosthesis.

Methods

Fourteen naïve participants walked on a treadmill without (one block, 4 min) and with a dummy prosthesis (three blocks, 3 × 4 min), while ground reaction forces and 32-channel EEG were recorded. Gait cycle duration, stance phase duration, step width, maximal ground reaction force and, ground reaction force trace over time were measured to identify gait modifications. Independent component analysis of EEG data isolated brain-related activity from distinct anatomical sources. The source-level data were segmented into gait cycles and analyzed in the time–frequency domain to reveal relative enhancement or suppression of intrinsic cortical oscillations. Differences between walking conditions were evaluated with one-way ANOVA and post-hoc testing (α = 0.05).

Results

Immediate modifications occurred in the gait parameters when participants were introduced to the dummy prosthesis. Except for gait cycle duration, these modifications remained throughout the duration of the experimental session. Power modulations of the theta, mu, beta, and gamma rhythms, of sources presumably from the fronto-central and the parietal cortices, were found across the experimental session. Significant power modulations of the theta, beta, and gamma rhythms within the gait cycle were predominately found around the heel strike of both feet and the swing phase of the right (prosthetic) leg.

Conclusions

The modulations of cortical activity could be related to whole-body coordination, including the swing phase and placing of the prosthesis, and the bodyweight transfer between legs and arms. Reduced power modulation of the gamma rhythm within the experimental session may indicate initial motor memories being formed. Better understanding of the sensorimotor processes behind gait modifications may inform the development of neurofeedback strategies to assist gait rehabilitation.
Oatmeal induced gut microbiota alteration and its relationship with improved lipid profiles: a secondary analysis of a randomized clinical trial
Authors: Ye Mengyao , Sun Jianqin , Chen Yanqiu , Ren Qian , Li Zhen , Zhao Yanfang , Pan Yiru , Xue Huijun
Published: October 2020

Background

In vitro and animal experiments reported a microbiota-regulating ability of oatmeal, however, related in vivo evidences remained limited. Thus, we conducted this study aiming to investigate the oatmeal-induced alteration of gut microbiota and its potential relationship with the improvements of lipid profiles.

Methods and study design

Data of anthropometric measurements and biochemical parameters were extracted from a randomized, controlled clinical trial, in which 62 hypercholesterolemic men and women (18–65 years old) were provided with either treatment of 80 g/day oatmeal or 80 g/day refined white rice for 45 days. Fasting blood samples and fecal samples were collected both at baseline and endpoint of the study for lipid profiling and microbiota 16S rRNA amplicon sequencing, respectively.

Results

Totally 28 participants (56 fecal samples) qualified with the new criteria and were thus included in this secondary analysis. The results of microbiota analysis showed that no significant difference was observed in the alteration of its overall α or β diversity between two groups throughout the study. Nor did any notable between-group difference was found in the relative abundance changes of microorganism at different taxonomies. However, results from linear discriminant analysis effect size in the oatmeal group indicated a significant positive response of Firmicutes phylum following oatmeal consumption. Further Procrustes analysis suggested a concordance trend between microorganism alteration and alleviation of hypercholesterolemia phenotypes throughout the study (P = 0.05). The results of within-group comparison from Spearman’s correlation in the oatmeal group demonstrated a significant association between the enrichment of Blautia genus and the reduction of serum total cholesterol (P < 0.05), low-density lipoprotein cholesterol (P < 0.01), and apolipoprotein B (P < 0.05).

Conclusions

Positive response of Firmicutes phylum might be a critical characteristic of oatmeal-induced alteration of microbiota, whereas, one of the underlying cholesterol-lowering mechanism of oatmeal consumption might be its microbiota-manipulating ability, in which the enrichment of Blautia genus played a potentially significant role. Current results should be taken cautiously and more studies were needed for further verification.

Trial registration: ChiCTR, ChiCTR180001864. Registered 30 September 2018, http://www.chictr.org.cn/showproj.aspx?proj=31469.
Health technology assessment and reimbursement policy for oncology orphan drugs in Central and Eastern Europe
Authors: Malinowski Krzysztof Piotr , Kawalec Paweł , Trąbka Wojciech , Sowada Christoph , Petrova Guenka , Manova Manoela , Savova Alexandra , Draganić Pero , Slabý Juraj , Männik Agnes , Márky Kristóf , Rugaja Zinta , Gulbinovic Jolanta , Tesar Tomas , Paveliu Marian Sorin
Published: October 2020

Background

The reimbursement of orphan drugs (OD) is an increasingly important for country policymakers, and still insufficiently understood, especially in Central and Eastern Europe. The aim of this research was to provide a comprehensive description of country-specific health technology assessment (HTA) policies as well as evaluate the percentage of HTA recommendations and reimbursement decisions for oncology OD. In addition, the study was designed to elucidate the impact of reimbursement of these drugs on the public budget and the agreement between HTA recommendations and reimbursement decisions in the analysed countries. A questionnaire survey was used to collect data on the reimbursement status, HTA recommendation, marketing authorisation, and public expenses on reimbursement in 2014, 2015, and 2016 for all oncology drugs with an orphan designation by the European Medicine Agency in 2017 in Bulgaria, Croatia, Czechia, Estonia, Hungary, Latvia, Lithuania, Poland, Romania, and Slovakia. The agreement between the HTA recommendation and reimbursement status was assessed using the kappa coefficient. The Pearson’s correlation was used to analyse the relationship between gross domestic product (GDP) and GDP per capita and reimbursement expenses.

Results

A total of 36 drugs were analysed (25% conditionally approved; 5.56% approved under exceptional circumstances). The share of reimbursed drugs ranged from 11.11% in Latvia to 41.67% in Poland. The highest share of positive recommendations was observed for Bulgaria and Estonia (36.11%), and the lowest, for Latvia (11.11%). The agreement varied from 0.4 for Poland to 1 for Latvia, Hungary, and Slovakia. Expenses were correlated with GDP (0.95 [0.81–0.99]), and not with GDP per capita (0.54 [− 0.136 to 0.873]). Expenses per capita were not correlated with GDP per capita (0.52 [− 0.15 to 0.87]).

Conclusions

In Hungary, Latvia, and Slovakia, a positive recommendation was associated with a reimbursement, and a negative one, with the lack of reimbursement. The reimbursement of oncology OD is associated with a growing burden for public budget, and the expenses are correlated with the total GDP. The highest share of drugs with any recommendation was observed in Poland, and the lowest, in Latvia and Romania. The share of reimbursed drugs was the lowest in Latvia and the highest in Poland.
Decreased intrinsic excitability of cerebellar Purkinje cells following optokinetic learning in mice
Authors: Kim Yong Gyu , Kim Sang Jeong
Published: October 2020

The optokinetic response (OKR), a reflexive eye movement evoked by a motion of the visual field, is known to adapt its strength to cope with an environmental change throughout life, which is a type of cerebellum-dependent learning. Previous studies suggested that OKR learning induces changes in in-vivo spiking activity and synaptic transmission of the cerebellar Purkinje cell (PC). Despite the recent emphasis on the importance of the intrinsic excitability related to learning and memory, the direct correlation between the intrinsic excitability of PCs and OKR learning has not been tested. In the present study, by utilizing the whole-cell patch-clamp recording, we compared the responses of cerebellar PCs to somatic current injection between the control and learned groups. We found that the neurons from the learned group showed a significant reduction in mean firing rate compared with neurons in the control group. In the analysis of single action potential (AP), we revealed that the rheobase current for the generation of single AP was increased by OKR learning, while AP threshold, AP amplitude, and afterhyperpolarization amplitude were not altered. Taken together, our result suggests that the decrease in the intrinsic excitability was induced in the cerebellar PC of learned group by an increase in the current threshold for generating AP.
Calreticulin promotes EMT in pancreatic cancer via mediating Ca2+ dependent acute and chronic endoplasmic reticulum stress
Authors: Sheng Weiwei , Wang Guosen , Tang Jingtong , Shi Xiaoyang , Cao Rongxian , Sun Jian , Lin Yi Heng , Jia Chao , Chen Chuanping , Zhou Jianping , Dong Ming
Published: October 2020

Background

Our previous study showed that calreticulin (CRT) promoted EGF-induced epithelial-mesenchymal transition (EMT) in pancreatic cancer (PC) via Integrin/EGFR-ERK/MAPK signaling. We next investigated the novel signal pathway and molecular mechanism involving the oncogenic role of CRT in PC.

Methods

We investigated the potential role and mechanism of CRT in regulating intracellular free Ca2+ dependent acute and chronic endoplasmic reticulum stress (ERS)-induced EMT in PC in vitro and vivo.

Results

Thapsigargin (TG) induced acute ERS via increasing intracellular free Ca2+ in PC cells, which was reversed by CRT silencing. Additionally, CRT silencing inhibited TG-induced EMT in vitro by reversing TG-induced changes of the key proteins in EMT signaling (ZO-1, E-cadherin and Slug) and ERK/MAPK signaling (pERK). TG-promoted cell invasion and migration was also rescued by CRT silencing but enhanced by IRE1α silencing (one of the key stressors in unfolded protein response). Meanwhile, CRT was co-immunoprecipitated and co-localized with IRE1α in vitro and its silencing led to the chronic ERS via upregulating IRE1α independent of IRE1-XBP1 axis. Moreover, CRT silencing inhibited IRE1α silencing-promoted EMT, including inhibiting the activation of EMT and ERK/MAPK signaling and the promotion of cell mobility. In vivo, CRT silencing decreased subcutaneous tumor size and distant liver metastasis following with the increase of IRE1α expression. A negative relationship between CRT and IRE1α was also observed in clinical PC samples, which coordinately promoted the advanced clinical stages and poor prognosis of PC patients.

Conclusions

CRT promotes EMT in PC via mediating intracellular free Ca2+ dependent TG-induced acute ERS and IRE1α-mediated chronic ERS via Slug and ERK/MAPK signaling.
Nicotinamide inhibits melanoma in vitro and in vivo
Authors: Scatozza Francesca , Moschella Federica , D’Arcangelo Daniela , Rossi Stefania , Tabolacci Claudio , Giampietri Claudia , Proietti Enrico , Facchiano Francesco , Facchiano Antonio
Published: October 2020

Background

Even though new therapies are available against melanoma, novel approaches are needed to overcome resistance and high-toxicity issues. In the present study the anti-melanoma activity of Nicotinamide (NAM), the amide form of Niacin, was assessed in vitro and in vivo.

Methods

Human (A375, SK-MEL-28) and mouse (B16-F10) melanoma cell lines were used for in vitro investigations. Viability, cell-death, cell-cycle distribution, apoptosis, Nicotinamide Adenine Dinucleotide+ (NAD+), Adenosine Triphosphate (ATP), and Reactive Oxygen Species (ROS) levels were measured after NAM treatment. NAM anti-SIRT2 activity was tested in vitro; SIRT2 expression level was investigated by in silico transcriptomic analyses. Melanoma growth in vivo was measured in thirty-five C57BL/6 mice injected subcutaneously with B16-F10 melanoma cells and treated intraperitoneally with NAM. Interferon (IFN)-γ-secreting murine cells were counted with ELISPOT assay. Cytokine/chemokine plasmatic levels were measured by xMAP technology. Niacin receptors expression in human melanoma samples was also investigated by in silico transcriptomic analyses.

Results

NAM reduced up to 90% melanoma cell number and induced: i) accumulation in G1-phase (40% increase), ii) reduction in S- and G2-phase (about 50% decrease), iii) a 10-fold increase of cell-death and 2.5-fold increase of apoptosis in sub-G1 phase, iv) a significant increase of NAD+, ATP, and ROS levels, v) a strong inhibition of SIRT2 activity in vitro. NAM significantly delayed tumor growth in vivo (p ≤ 0.0005) and improved survival of melanoma-bearing mice (p ≤ 0.0001). About 3-fold increase (p ≤ 0.05) of Interferon-gamma (IFN-γ) producing cells was observed in NAM treated mice. The plasmatic expression levels of 6 cytokines (namely: Interleukin 5 (IL-5), Eotaxin, Interleukin 12 (p40) (IL12(p40)), Interleukin 3 (IL-3), Interleukin 10 (IL-10) and Regulated on Activation Normal T Expressed and Secreted (RANTES) were significantly changed in the blood of NAM treated mice, suggesting a key role of the immune response. The observed inhibitory effect of NAM on SIRT2 enzymatic activity confirmed previous evidence; we show here that SIRT2 expression is significantly increased in melanoma and inversely related to melanoma-patients survival. Finally, we show for the first time that the expression levels of Niacin receptors HCAR2 and HCAR3 is almost abolished in human melanoma samples.

Conclusion

NAM shows a relevant anti-melanoma activity in vitro and in vivo and is a suitable candidate for further clinical investigations.
The Mayaro virus and its potential epidemiological consequences in Colombia: an exploratory biomathematics analysis
Authors: Valencia-Marín Bryan Steven , Gandica Irene Duarte , Aguirre-Obando Oscar Alexander
Published: October 2020

Background

Mayaro virus (Togaviridae) is an endemic arbovirus of the Americas with epidemiological similarities with the agents of other more prominent diseases such as dengue (Flaviviridae), Zika (Flaviviridae), and chikungunya (Togaviridae). It is naturally transmitted in a sylvatic/rural cycle byHaemagogusspp., but, potentially, it could be incorporated and transmitted in an urban cycle byAedes aegypti, a vector widely disseminated in the Americas.

Methods

The Mayaro arbovirus dynamics was simulated mathematically in the colombian population in the eight biogeographical provinces, bearing in mind the vector’s population movement between provinces through passive transportviatruck cargo. The parameters involved in the virus epidemiological dynamics, as well as the vital rates ofAe. aegyptiin each of the biogeographical provinces were obtained from the literature. These data were included in a meta-population model in differential equations, represented by a model structured by age for the dynamic population ofAe. aegypticombined with an epidemiological SEI/SEIR-type model. In addition, the model was incorporated with a term of migration to represent the connectivity between the biogeographical provinces.

Results

The vital rates and the development cycle ofAe. aegyptivaried between provinces, having greater biological potential between 23 °C and 28 °C in provinces of Imerí, biogeographical Chocó, and Magdalena, with respect to the North-Andean Moorland (9.33–21.38 °C). Magdalena and Maracaibo had the highest flow of land cargo. The results of the simulations indicate that Magdalena, Imerí, and biogeographical Chocó would be the most affected regarding the number of cases of people infected by Mayaro virus over time.

Conclusions

The temperature in each of the provinces influences the local population dynamics ofAe. aegyptiand passive migrationviatransport of land cargo plays an important role on how the Mayaro virus would be disseminated in the human population. Once this arbovirus begins an urban cycle, the most-affected departments would be Antioquia, Santander, Norte de Santander, Cesar (Provinces of Magdalena), and Valle del Cauca, and Chocó (biogeographical province of Chocó), which is why vector control programmes must aim their efforts at these departments and include some type of vector control to the transport of land cargo to avoid a future Mayaro epidemic.
Interplay of pericentromeric genome organization and chromatin landscape regulates the expression of Drosophila melanogaster heterochromatic genes
Authors: Saha Parna , Sowpati Divya Tej , Soujanya Mamilla , Srivastava Ishanee , Mishra Rakesh Kumar
Published: October 2020

Background

Transcription of genes residing within constitutive heterochromatin is paradoxical to the tenets of epigenetic code. The regulatory mechanisms of Drosophila melanogaster heterochromatic gene transcription remain largely unknown. Emerging evidence suggests that genome organization and transcriptional regulation are inter-linked. However, the pericentromeric genome organization is relatively less studied. Therefore, we sought to characterize the pericentromeric genome organization and understand how this organization along with the pericentromeric factors influences heterochromatic gene expression.

Results

Here, we characterized the pericentromeric genome organization in Drosophila melanogaster using 5C sequencing. Heterochromatic topologically associating domains (Het TADs) correlate with distinct epigenomic domains of active and repressed heterochromatic genes at the pericentromeres. These genes are known to depend on the heterochromatic landscape for their expression. However, HP1a or Su(var)3-9 RNAi has minimal effects on heterochromatic gene expression, despite causing significant changes in the global Het TAD organization. Probing further into this observation, we report the role of two other chromatin proteins enriched at the pericentromeres-dMES-4 and dADD1 in regulating the expression of a subset of heterochromatic genes.

Conclusions

Distinct pericentromeric genome organization and chromatin landscapes maintained by the interplay of heterochromatic factors (HP1a, H3K9me3, dMES-4 and dADD1) are sufficient to support heterochromatic gene expression despite the loss of global Het TAD structure. These findings open new avenues for future investigations into the mechanisms of heterochromatic gene expression.
Efficient and accurate determination of genome-wide DNA methylation patterns in Arabidopsis thaliana with enzymatic methyl sequencing
Authors: Feng Suhua , Zhong Zhenhui , Wang Ming , Jacobsen Steven E.
Published: October 2020

Background

5′ methylation of cytosines in DNA molecules is an important epigenetic mark in eukaryotes. Bisulfite sequencing is the gold standard of DNA methylation detection, and whole-genome bisulfite sequencing (WGBS) has been widely used to detect methylation at single-nucleotide resolution on a genome-wide scale. However, sodium bisulfite is known to severely degrade DNA, which, in combination with biases introduced during PCR amplification, leads to unbalanced base representation in the final sequencing libraries. Enzymatic conversion of unmethylated cytosines to uracils can achieve the same end product for sequencing as does bisulfite treatment and does not affect the integrity of the DNA; enzymatic methylation sequencing may, thus, provide advantages over bisulfite sequencing.

Results

Using an enzymatic methyl-seq (EM-seq) technique to selectively deaminate unmethylated cytosines to uracils, we generated and sequenced libraries based on different amounts of Arabidopsis input DNA and different numbers of PCR cycles, and compared these data to results from traditional whole-genome bisulfite sequencing. We found that EM-seq libraries were more consistent between replicates and had higher mapping and lower duplication rates, lower background noise, higher average coverage, and higher coverage of total cytosines. Differential methylation region (DMR) analysis showed that WGBS tended to over-estimate methylation levels especially in CHG and CHH contexts, whereas EM-seq detected higher CG methylation levels in certain highly methylated areas. These phenomena can be mostly explained by a correlation of WGBS methylation estimation with GC content and methylated cytosine density. We used EM-seq to compare methylation between leaves and flowers, and found that CHG methylation level is greatly elevated in flowers, especially in pericentromeric regions.

Conclusion

We suggest that EM-seq is a more accurate and reliable approach than WGBS to detect methylation. Compared to WGBS, the results of EM-seq are less affected by differences in library preparation conditions or by the skewed base composition in the converted DNA. It may therefore be more desirable to use EM-seq in methylation studies.