bluuebunny/crossref_metadata_2025 huggingface dataset:
Keap1-targeting microRNA-941 protects endometrial cells from oxygen and glucose deprivation-re-oxygenation via activation of Nrf2 signaling
Authors: Li Shu-ping , Cheng Wei-nan , Li Ya , Xu Hong-bin , Han Hui , Li Ping , Zhang Deng-Xia
Published: February 2020

Background

Mimicking ischemia-reperfusion injury, oxygen and glucose deprivation (OGD)-re-oxygenation (OGDR) applied to endometrial cells produces significant oxidative stress and programmed necrosis, which can be inhibited by nuclear-factor-E2-related factor 2 (Nrf2) signaling. MicroRNA (miRNA)-induced repression of Keap1, a Nrf2 suppressor protein that facilitates Nrf2 degradation, is novel strategy to activate Nrf2 cascade.

Methods

MicroRNA-941 (miR-941) was exogenously expressed in HESC and primary human endometrial cells, and the Nrf2 pathway examined by Western blotting and real-time quantitative PCR analysis. The endometrial cells were treated with OGDR, cell programmed necrosis and apoptosis were tested.

Results

MiR-941 is a novel Keap1-targeting miRNA that regulates Nrf2 activity. In T-HESC cells and primary human endometrial cells, ectopic overexpression of miR-941 suppressed Keap1 3′-UTR (untranslated region) expression and downregulated its mRNA/protein expression, leading to activation of the Nrf2 cascade. Conversely, inhibition of miR-941 elevated Keap1 expression and activity in endometrial cells, resulting in suppression of Nrf2 activation. MiR-941 overexpression in endometrial cells attenuated OGDR-induced oxidative stress and programmed necrosis, whereas miR-941 inhibition enhanced oxidative stress and programmed necrosis. MiR-941 overexpression and inhibition were completely ineffective in Keap1−/Nrf2-KO T-HESC cells (using CRISPR/Cas9 strategy). Restoring Keap1 expression, using an UTR-depleted Keap1 construct, abolished miR-941-induced anti-OGDR activity in T-HESC cells. Thus Keap1-Nrf2 cascade activation is required for miR-941-induced endometrial cell protection.

Conclusions

Targeting Keap1 by miR-941 activates Nrf2 cascade to protect human endometrial cells from OGDR-induced oxidative stress and programmed necrosis.

Graphical abstract
Agglomeration of titanium dioxide nanoparticles increases toxicological responses in vitro and in vivo
Authors: Murugadoss Sivakumar , Brassinne Frederic , Sebaihi Noham , Petry Jasmine , Cokic Stevan M. , Van Landuyt Kirsten L. , Godderis Lode , Mast Jan , Lison Dominique , Hoet Peter H. , van den Brule Sybille
Published: February 2020

Background

The terms agglomerates and aggregates are frequently used in the regulatory definition(s) of nanomaterials (NMs) and hence attract attention in view of their potential influence on health effects. However, the influence of nanoparticle (NP) agglomeration and aggregation on toxicity is poorly understood although it is strongly believed that smaller the size of the NPs greater the toxicity. A toxicologically relevant definition of NMs is therefore not yet available, which affects not only the risk assessment process but also hinders the regulation of nano-products. In this study, we assessed the influence of NP agglomeration on their toxicity/biological responses in vitro and in vivo.

Results

We tested two TiO2 NPs with different primary sizes (17 and 117 nm) and prepared ad-hoc suspensions composed of small or large agglomerates with similar dispersion medium composition. For in vitro testing, human bronchial epithelial (HBE), colon epithelial (Caco2) and monocytic (THP-1) cell lines were exposed to these suspensions for 24 h and endpoints such as cytotoxicity, total glutathione, epithelial barrier integrity, inflammatory mediators and DNA damage were measured. Large agglomerates of 17 nm TiO2 induced stronger responses than small agglomerates for glutathione depletion, IL-8 and IL-1β increase, and DNA damage in THP-1, while no effect of agglomeration was observed with 117 nm TiO2.

In vivo, C57BL/6JRj mice were exposed via oropharyngeal aspiration or oral gavage to TiO2 suspensions and, after 3 days, biological parameters including cytotoxicity, inflammatory cell recruitment, DNA damage and biopersistence were measured. Mainly, we observed that large agglomerates of 117 nm TiO2 induced higher pulmonary responses in aspirated mice and blood DNA damage in gavaged mice compared to small agglomerates.

Conclusion

Agglomeration of TiO2 NPs influences their toxicity/biological responses and, large agglomerates do not appear less active than small agglomerates. This study provides a deeper insight on the toxicological relevance of NP agglomerates and contributes to the establishment of a toxicologically relevant definition for NMs.
Higher dietary fat quality is associated with lower anxiety score in women: a cross-sectional study
Authors: Fatemi Fatemeh , Siassi Fereydoun , Qorbani Mostafa , Sotoudeh Gity
Published: February 2020

Background

The relationship between anxiety and dietary fat quality (DFQ) has not been well studied. The aim of this study was to investigate the relationship between anxiety disorder and fatty acids’ intake in women.

Methods

This cross-sectional study included 300 women aged 18–49 attending healthcare centers. Dietary exposure was measured by a 168-item semi-quantitative food frequency questionnaire (FFQ). To determine the status of anxiety, the Depression, Anxiety, and Stress Scale (DASS) questionnaire was used. Based on the total score of anxiety, the participants were divided into two groups of without anxiety (< 8) and with anxiety (≥ 8). The relationship between fatty acids intake and odd ratio (OR) for anxiety was analyzed by simple logistic regression.

Results

About 37.7% of individuals reported anxiety. After adjustment for covariates, an increase in the OR for anxiety was observed across the quintuples of saturated fatty acids (SFAs) (OR 3.17; 95% CI 1.43–7.00;p-trend = 0.005). In addition, higher intakes of monounsaturated fatty acids (MUFAs) (OR 0.15; 95% CI 0.05–0.44;p-trend = 0.001), oleic acid (OR 0.25; 95% CI 0.09–0.67;p-trend = 0.002), alpha-linolenic acid (ALA) (OR 0.07; 95% CI 0.02–0.23;p-trend < 0.001), andn-3:n-6 poly unsaturated fatty acids (PUFAs) (OR 0.56; 95% CI 0.24–1.03;p-trend = 0.02) were found to be related with lower OR of anxiety.

Conclusion

Intake of SFAs was positively related to anxiety disorder, whereas MUFAs, oleic acid, ALA, andn-3:n-6 PUFAs intake were inversely related to anxiety score. For investigating the association of fat intake and anxiety disorder, DFQ may be a useful measure.
Arthroscopic ankle fusion only has a limited advantage over the open operation if osseous operation type is the same: a retrospective comparative study
Authors: Wang Chenggong , Xu Can , Li Mingqing , Li Hui , Wang Long , Zhong Da , Liu Hua
Published: February 2020

Background

A great deal of research suggests that arthroscopic ankle fusion (AAF) has advantages over open ankle fusion (OAF), but these outcomes would be imprecise because of a selection bias. The purpose of this study is to verify which is better for ankle fusion, AAF or OAF. We regrouped the OAF group into two subgroups according to whether the osseous operation type is the same as AAF group. The goal is to minimize the impact of disease severity, thereby reducing selection bias to some extent.

Methods

We retrospectively analyzed the data of ankle fusion in our hospital between July 2015 and October 2018. Forty-three patients were enrolled and divided into AAF group (n = 17) and OAF group (n = 26). In order to eliminate selection bias, we divided OAF group into complex osseous operation subgroup (COO subgroup) (n = 15) and simple osseous operation subgroup (SOO subgroup) (n = 11). The osseous operation type of SOO subgroup is the same as AAF group. Then, we compared the differences between these groups. All patients were followed up at least 1 year after operation. We analyzed data, including etiology composition, surgical time, intra-op blood loss, reduction of albumin, total hospital stays, union time, fusion situation, complications, radiological examination, functional score, and questionnaire survey. Then we performed statistical analyses.

Results

We found that the etiological components of AAF group and OAF group were different; the etiological components of AAF group and SOO subgroup were similar. We found that AAF group has advantages over OAF group and COO subgroup in general. However, except in terms of surgical trauma, hospital stays, and short-term complications occurred, the AAF group has not obvious advantages over SOO subgroup, including intra-op blood loss, fusion condition, postoperative function score, and postoperative patient satisfaction; and AAF group need more surgical time than the SOO subgroup.

Conclusions

The arthroscopic ankle fusion can bring a good curative effect; however, if the osseous operation type is the same, the arthroscopic ankle fusion only has a limited advantage over the traditional open operation in perioperative soft tissue protection and enhanced recovery after surgery.
Promoting smoking abstinence in smokers willing to quit smoking through virtual reality-approach bias retraining: a study protocol for a randomized controlled trial
Authors: Machulska Alla , Eiler Tanja Joan , Grünewald Armin , Brück Rainer , Jahn Katharina , Niehaves Björn , Ullrich Heiko , Klucken Tim
Published: February 2020

Background

Automatic processes to approach smoking-related cues have been repeatedly linked to smoking status, intensity of smoking, and cigarette craving. Moreover, recent findings suggest that targeting those tendencies directly by means of approach bias modification (ABM) has merit in changing maladaptive approach tendencies for drug cues and reducing drug consumption. However, training effects tend to be small. Embedding the training into virtual reality (VR) technology could be a promising way to improve training efficacy. The present protocol describes a randomized controlled trial that aims to assess the efficacy of a newly developed VR-ABM as a means of reducing smoking-related approach biases or nicotine consumption in smokers seeking abstinence.

Methods

One hundred daily smokers who are motivated to quit smoking will be recruited into the randomized controlled trial. All participants will attend a brief smoking cessation intervention (TAU) and will be randomly assigned either to the experimental (VR-avoidance training) or the placebo-control group (VR-placebo training). During the VR-avoidance training, participants are implicitly instructed to make an avoidance movement in response to smoking-related objects (e.g., cigarettes) and an approach movement in response to alternative objects (e.g., healthy food). During the VR-placebo training, no such contingency between arm movement and item content exists. Trainings are administered in six sessions within two weeks. Training effects on automatic approach tendencies and smoking behavior are measured immediately after training and at a 7-week follow-up.

Discussion

Embedding the training into virtual reality (VR) technology could be a promising new way to improve ecological validity, realism, and immersion and thereby increase ABM training effects. The results of this study can inform future research in the optimization and advancement of treatment for addiction.

Trial registration

Registered with Current Controlled Trials: study ID ISRCTN16006023. Registered on 28 March 2019.
Survey of Spanish pet owners about endoparasite infection risk and deworming frequencies
Authors: Miró Guadalupe , Gálvez Rosa , Montoya Ana , Delgado Beatriz , Drake Jason
Published: February 2020

Background

Pets may be carriers of infectious agents including parasites. As part of a larger-scale study covering the whole of Europe, this study examines deworming measures reported by Spanish pet owners and identifies risk factors.

Methods

An online questionnaire was administered to cat and dog owners in Spain. The replies provided were used to obtain information about the petsʼ living conditions and to accordingly classify each pet into one of the four ESCCAP infection risk categories (A, B, C or D) for which different deworming frequencies are recommended. Questions were also asked about pet care and ownersʼ attitude toward their pets. The Kruskal-Wallis test was used to correlate risk groups with deworming frequencies.

Results

Completed questionnaires were returned by 500 cat owners and 501 dog owners. According to responses, 96.21% of dogs were assigned to risk category D (maximum risk), and only 1.2%, 2.2% and 0.4% to A, B and C, respectively. Almost all cats were assigned to the minimum risk category A (indoor cats, 62%) or maximum risk category D (outdoor cats, 32.8%); only 3.4% and 1.8% of cats were classified as risk B and C respectively. More dogs were allocated to the higher risk group compared to cats, which were more frequently kept indoors. Cats were reportedly dewormed less frequently than dogs (2.56 and 3.13 times per year respectively), consistent with their different infestation risk. Thus, pets in the lower risk group A were either adequately dewormed or treated more often than necessary. Only a small proportion of cats were not dewormed at all (n = 14). Alarmingly, almost all pets in risk groups B, C or D (representing 95% of dogs and 39% of cats) were dewormed less often than recommended.

Conclusions

More effective health education is required for the management of zoonotic endoparasite diseases under the umbrella of One Health targeted at owners, veterinarians, general practitioners, and health authorities. To align deworming frequency with infection risk, pet owners should be provided with clear, compelling instructions.
Large-scale public data reuse to model immunotherapy response and resistance
Authors: Fu Jingxin , Li Karen , Zhang Wubing , Wan Changxin , Zhang Jing , Jiang Peng , Liu X. Shirley
Published: February 2020

Despite growing numbers of immune checkpoint blockade (ICB) trials with available omics data, it remains challenging to evaluate the robustness of ICB response and immune evasion mechanisms comprehensively. To address these challenges, we integrated large-scale omics data and biomarkers on published ICB trials, non-immunotherapy tumor profiles, and CRISPR screens on a web platform TIDE (http://tide.dfci.harvard.edu). We processed the omics data for over 33K samples in 188 tumor cohorts from public databases, 998 tumors from 12 ICB clinical studies, and eight CRISPR screens that identified gene modulators of the anticancer immune response. Integrating these data on the TIDE web platform with three interactive analysis modules, we demonstrate the utility of public data reuse in hypothesis generation, biomarker optimization, and patient stratification.
Production of high-value bioproducts enriched with γ-linolenic acid and β-carotene by filamentous fungi Umbelopsis isabellina using solid-state fermentations
Authors: Slaný Ondrej , Klempová Tatiana , Marcinčák Slavomír , Čertík Milan
Published: February 2020

Solid-state fermentation is a useful tool for utilizing different plant-based materials as cultivation substrates in order to produce potentially high-value fermented bioproducts. The aim of the present study was to successfully prepare various types of such bioproducts, using a zygomycetous strain Umbelopsis isabellina CCF2412. Various legume and cereal substrates were utilized effectively, while a few of them were obtained from agricultural waste, which is particularly advantageous from ecological and economic point of view. A common feature of the produced fermented materials was the increased content of different polyunsaturated fatty acids and carotenoid pigments in these bioproducts. Subsequent to the optimization of the solid-state fermentation process using cornmeal as the cultivation substrate, bioproducts enriched with γ-linolenic acid (11.45 mg γ-linolenic acid per gram of bioproduct), β-carotene (50.90 μg β-carotene per gram of bioproduct), and various microbial sterols were obtained. Appropriate n–6/n–3 acid ratio and enrichment of other microbial substances, such as the pigments and sterols mentioned above, in the fermented bioproducts widens the applicability of these bioproducts in different industries. The fermented cereal bioproducts produced in the present study from fermented wheat bran substrate were used for evaluating their application as feed for broiler chicken, and satisfactory results were obtained. Therefore, the present study creates novel opportunities for improving the quality of fermented bioproducts obtained during solid-state fermentation processes, especially for application in the feed industry.
The necessity for standardization of glioma stem cell culture: a systematic review
Authors: Zhang Lei , Yu Hongwei , Yuan Yuhui , Yu John S. , Lou Zhenkun , Xue Yixue , Liu Yunhui
Published: February 2020

Background

The cancer stem cell hypothesis is an old idea which has been revived in recent years for many cancers, including gliomas. However, this concept has become controversial due to a series of studies with conflicting results.

Methods

A systematic literature search was conducted in PubMed and the Web of Science database to analyze studies using serum-free medium and its components in glioma stem cells, glioma stem-like cells, glioma-initiating cells, or glioma neurosphere cultures. All the studies reviewed were published between 1970 and 2019. We found that no standardized culture method was used, and the data were incomparable due to differing culture conditions and the use of media with different components.

Conclusions

Here, we review the most commonly used serum-free media and added components for glioma stem cell culture while highlighting the function of each component used in the media. We emphasize the necessity for standardization of glioma stem cell culture and propose a standard culture medium to prevent bias in glioma stem cell research.
Is maxillary diastema an appropriate site for implantation in rats?
Authors: Yue Gang , Edani Husham , Sullivan Andrew , Jiang Shuying , Kazerani Hamed , Saghiri Mohammad Ali
Published: February 2020

Background

Implantology or implant dentistry is growing fast during last four decades. Facing the growing demand of implant treatment, there are extreme challenges to clinicians and researchers. First is peri-implantitis with remarkable prevalence. Though investigators have revealed that the etiology of the peri-implant infection is similar to periodontitis, clinically there is no effective treatment. Second, implantation in patients with severe systemic conditions, i.e., severe diabetes, lupus, osteoporosis, organ transplant, and cancer with intensive radiotherapy and/or chemotherapy, is another challenge to implant treatment for lack of scientific research data. Animal models are crucial to help investigators reveal the mechanisms underlying these disorders. Murine models are used most commonly. Rats are the better subject in dental implant research, due to mice could not provide clinical compatible and macro-level measurable data for implant osseointegration and peri-implantitis in oral cavity for lacking enough cancellous bone to support an implant more than 1 mm in length.

Objective

Our aim of this research is to find a clinical comparable rat dental implant model.

Methods

Six male Sprague-Dawley rats with body weight more than 500 g were used in the experiment. Each rat received two implants. One implant was placed at maxillary diastema in each side. Seven weeks after the implantation, only one implant successfully osseointegrated without movement and inflammation. Implant success and failure rate is analyzed by using Clopper-Pearson’s exact method at 95% confidence interval.

Results

The present data indicate that the true success rate of implantation in maxillary natural diastema in rat is less than 38.4% at a confident level of 95%. Meanwhile, Micro-CT indicates maxillary first molar position will be a promising site for implantation.

Conclusion

Maxillary nature diastema may not be an appropriate site for implantation research for its low successful rate, but maxillary first molar position could be a candidate for implantation research. Further researches are required to illustrate the details.
Redeveloping a global MOOC to be more locally relevant: design-based research
Authors: Chen Ken-Zen , Oakley Barbara
Published: February 2020

This study demonstrated a globally and locally relevant MOOC design model. By redeveloping a culturally responsive MOOC based on the course “Learning How to Learn (LHTL)” on the Coursera, the researchers created a sister MOOC to meet the local needs of Chinese learners. In this three-year design-based research study, four major iterations were conducted: (1) to analyze and prototype culturally responsive course contents for Chinese MOOCs learners; (2 and 3) to redevelop, pilot, field-test, and improve the new MOOC; and (4) to develop research-supported instructional practice for continued growth. This research contributed to the study of MOOCs by providing a thorough understanding of the design principles of, and theoretical claims about, the development of a culturally responsive MOOC. We hope this effort will help underpin further studies involving culturally responsive and comparable sister courses to advance MOOC research.
Relevance of reactive oxygen species in liver disease observed in transgenic mice expressing the hepatitis B virus X protein
Authors: Yu Dae-Yeul
Published: February 2020

The hepatitis B virus (HBV) infects approximately 240 million people worldwide, causing chronic liver disease (CLD) and liver cancer. Although numerous studies have been performed to date, unfortunately there is no conclusive drug or treatment for HBV induced liver disease. The hepatitis B virus X (HBx) is considered a key player in inducing CLD and hepatocellular carcinoma (HCC). We generated transgenic (Tg) mice expressing HBx protein, inducing HCC at the age of 11–18 months. The incidence of histological phenotype, including liver tumor, differed depending on the genetic background of HBx Tg mice. Fatty change and tumor generation were observed much earlier in livers of HBx Tg hybrid (C57BL/6 and CBA) (HBx-Tg hybrid) mice than in HBx Tg C57BL/6 (HBx-Tg B6) mice. Inflammation was also enhanced in the HBx-Tg B6 mice as compared to HBx-Tg hybrid mice. HBx may be involved in inducing and promoting hepatic steatosis, glycemia, hepatic fibrosis, and liver cancer. Reactive oxygen species (ROS) generation was remarkably increased in livers of HBx Tg young mice compared to young wild type control mice. Previous studies on HBx Tg mice indicate that the HBx-induced ROS plays a role in inducing and promoting CLD and HCC.
Identification of newborns at risk for autism using electronic medical records and machine learning
Authors: Rahman Rayees , Kodesh Arad , Levine Stephen Z. , Sandin Sven , Reichenberg Abraham , Schlessinger Avner
Published: February 2020

Background.

Current approaches for early identification of individuals at high risk for autism spectrum disorder (ASD) in the general population are limited, and most ASD patients are not identified until after the age of 4. This is despite substantial evidence suggesting that early diagnosis and intervention improves developmental course and outcome. The aim of the current study was to test the ability of machine learning (ML) models applied to electronic medical records (EMRs) to predict ASD early in life, in a general population sample.

Methods.

We used EMR data from a single Israeli Health Maintenance Organization, including EMR information for parents of 1,397 ASD children (ICD-9/10) and 94,741 non-ASD children born between January 1st, 1997 and December 31st, 2008. Routinely available parental sociodemographic information, parental medical histories, and prescribed medications data were used to generate features to train various ML algorithms, including multivariate logistic regression, artificial neural networks, and random forest. Prediction performance was evaluated with 10-fold cross-validation by computing the area under the receiver operating characteristic curve (AUC; C-statistic), sensitivity, specificity, accuracy, false positive rate, and precision (positive predictive value [PPV]).

Results.

All ML models tested had similar performance. The average performance across all models had C-statistic of 0.709, sensitivity of 29.93%, specificity of 98.18%, accuracy of 95.62%, false positive rate of 1.81%, and PPV of 43.35% for predicting ASD in this dataset.

Conclusions.

We conclude that ML algorithms combined with EMR capture early life ASD risk as well as reveal previously unknown features to be associated with ASD-risk. Such approaches may be able to enhance the ability for accurate and efficient early detection of ASD in large populations of children.
Development of an Art of Oncology Curriculum to Mitigate Burnout and Foster Solidarity Among Hematology/Oncology Fellows
Authors: Richardson Daniel R. , Tan Xianming , Winzelberg Gary , Rosenstein Donald L. , Collichio Frances A.
Published: February 2020

PURPOSE:

Oncologists and fellows in hematology/oncology (HO) training programs report high levels of burnout. The Accreditation Council for Graduate Medical Education requires accredited programs to have a mechanism to foster well-being among fellows.

METHODS:

Through an iterative process involving a multidisciplinary committee, we created a 3-year longitudinal Art of Oncology (AOO) curriculum intended to address burnout and foster solidary among HO fellows. Sessions used narratives to promote the formation of a shared mental model through discussion of the mutual experience of caring for patients with cancer. We tested the feasibility, acceptability, and initial effectiveness of implementing the curriculum into traditional didactic lectures as a pilot intervention from 2018 to 2019. Eight sessions were completed.

RESULTS:

Sixteen fellows participated. Most were married (63%) and planned on pursuing careers in academic medicine (75%). The sample was racially and ethnically diverse (31% minority representation). Thirty-eight percent of fellows reported burnout symptoms. AOO sessions had higher attendance than didactic lectures ( P = .04). Of 14 fellows who completed all follow-up assessments (87.5% response rate), 93% (13 of 14 fellows) felt the sessions were very or somewhat helpful and that sessions improved solidarity. Preparedness in managing work-life balance significantly improved (paired t test, mean difference, 0.53; P = .04). Measured levels of burnout did not significantly improve from baseline (mean difference, −0.133; P = .67). Work-life balance was associated with burnout on multivariable analysis (coefficient, 0.40; P = .03).

CONCLUSION:

The implementation of a dedicated AOO curriculum is feasible and viewed as helpful by HO fellows. Larger studies are needed to assess the efficacy of this curricular intervention.
Cardiorespiratory Fitness and Muscular Strength on Arterial Stiffness in Older Adults
Authors: ALBIN EMMA E. , BRELLENTHIN ANGELIQUE G. , LANG JAMES A. , MEYER JACOB D. , LEE DUCK-CHUL
Published: February 2020

Purpose

To evaluate the independent and combined associations of cardiorespiratory fitness (CRF) and muscular strength (MS) with arterial stiffness (AS), a strong predictor of cardiovascular disease, in older adults.

Methods

This cross-sectional study included 405 older adults (mean age, 72 yr). Cardiorespiratory fitness was assessed by time (s) to complete a 400-m walking test and MS by maximal handgrip strength (kg). Carotid-femoral pulse wave velocity was used to assess AS. High AS was defined as a pulse wave velocity of ≥10 m·s−1, a previously established threshold for increased cardiovascular risk. Poisson regression was used to calculate prevalence ratios (PR) and 95% confidence intervals (CI) of having high AS across sex-specific tertiles of CRF and MS. Muscular strength and CRF were further dichotomized into either “weak” or “unfit” (lower one third for each), or “strong” or “fit” (upper two thirds for each) to investigate the combined associations of CRF and MS with high AS. All analyses were adjusted for potential confounders, including MS for CRF and CRF for MS.

Results

Sixty-nine (17%) participants had high AS. Compared with lower CRF, PR (95% CI) of having high AS were 0.53 (0.30–0.95) and 0.69 (0.38–1.23) for middle and upper CRF, respectively. Compared with lower MS, PR (95% CI) of having high AS were 0.81 (0.49–1.34) and 0.52 (0.29–0.92) for middle and upper MS, respectively. In the joint analysis, compared with the “unfit and weak” group, PR (95% CI) of having high AS were 0.72 (0.38–1.35), 0.58 (0.29–1.16), and 0.46 (0.25–0.85) for “unfit and strong,” “fit and weak,” and “fit and strong” groups, respectively.

Conclusions

Higher levels of CRF and MS were independently associated with lower (healthier) levels of AS in older adults.
Heat Acclimation with Controlled Heart Rate: Influence of Hydration Status
Authors: TRAVERS GAVIN , NICHOLS DAVID , RIDING NATHAN , GONZÁLEZ-ALONSO JOSÉ , PÉRIARD JULIEN D.
Published: February 2020

Purpose

This study aimed to characterize the adaptive responses to heat acclimation (HA) with controlled heart rate (HR) and determine whether hydration strategy alters adaptations. The influence of HA on maximal oxygen uptake (V˙O2max) in cool conditions and self-paced exercise in the heat was also determined.

Methods

Eight men (V˙O2max, 55 ± 7 mL·kg−1·min−1) completed two 10-d interventions in a counterbalanced crossover design. Fluid intakes differed between interventions to either maintain euhydration (HA-EUH) or elicit similar daily body mass deficits (2.85% ± 0.26%; HA-DEH). HA consisted of 90 min of cycling in 40°C and 40% relative humidity. Initial workload (172 ± 22 W) was adjusted over the last 75 min to maintain exercising HR equivalent to 65% V˙O2max. A V˙O2maxtest in cool conditions and 30-min time trial in hot-humid conditions were completed before and after HA.

Results

HR at the end of the initial 15 min workload was 10 ± 5 bpm lower on day 10 in both interventions (P< 0.001). The workload necessary to maintain exercising HR (145 ± 7 bpm) increased throughout HA-EUH (25 ± 10 W,P= 0.001) and HA-DEH (16 ± 18 W,P= 0.02). There was a main effect of HA on sweat rate (P= 0.014), which tended to increase with HA-EUH (0.19 ± 0.18 L·h−1,P= 0.06), but not HA-DEH (P= 0.12). Skin temperature decreased during HA-EUH (0.6°C ± 0.5°C,P= 0.03), but not HA-DEH (P= 0.30). There was a main effect of HA on V˙O2max(~3 mL·kg−1·min−1,P= 0.02); however, neither intervention independently increased V˙O2max(both,P= 0.08). Time-trial performance increased after HA-EUH (19 ± 16 W,P= 0.02), but not HA-DEH (P= 0.21).

Conclusions

Controlled HR exercise in the heat induces several HA adaptations, which may be optimized by maintaining euhydration. HA-EUH also improves self-paced exercise performance in the heat. However, HA does not seem to significantly increase V˙O2maxin cool conditions.
Does Mental Fatigue Negatively Affect Outcomes of Functional Performance Tests?
Authors: VERSCHUEREN JO , TASSIGNON BRUNO , PROOST MATTHIAS , TEUGELS AMBER , VAN CUTSEM JEROEN , ROELANDS BART , VERHAGEN EVERT , MEEUSEN ROMAIN
Published: February 2020

Purpose

Mental fatigue impairs psychomotor skill performance by affecting visuomotor reaction time, accuracy, and decision-making. Recently, neurocognitive functional performance tests (FPT) that integrate these outcomes have been developed. The aim of this study was to assess the effect of mental fatigue on traditional and neurocognitive FPT in healthy adults.

Methods

Fourteen volunteers (four women; mean ± SD age, 22 ± 1 yr; height, 176.9 ± 8.4 cm; weight, 69.7 ± 10.4 kg) participated in a randomized counterbalanced crossover design. A 100% incongruent Stroop color word test of 90 min was used to induce mental fatigue and the control task encompassed watching a 90-min documentary. Traditional FPT comprised a single-leg hop for distance, countermovement jump, and Y-balance test, whereas the neurocognitive FPT encompassed the reactive balance test (RBT). All FPTs were evaluated pre–post the 90-min task. Mental fatigue was assessed using the Stroop task, visual analog scale for mental fatigue, and the Eriksen–Flanker task.

Results

Mental fatigue was successfully induced, as shown by a significant increase in visual analog scale for mental fatigue (P < 0.001), with no decrease in performance on the Stroop and Eriksen–Flanker task. No interaction effect of mental fatigue was found for the Y-balance test, single-leg hop, and countermovement jump. For the RBT accuracy, a significant interaction effect of mental fatigue and time was observed (P = 0.024), with participants performing significantly worse when mentally fatigued. No interaction effect or main effect of condition and time was observed when considering the effect of mental fatigue on visuomotor reaction time in the RBT.

Conclusions

Mental fatigue negatively affects a neurocognitive FPT, indicated by a decreased accuracy in response to visual stimuli in the RBT. Traditional FPT remained unaffected by mental fatigue.
Utility of microcatheter in adrenal venous sampling for primary aldosteronism
Authors: Noda Yoshifumi , Goshima Satoshi , Nagata Shoma , Kawada Hiroshi , Tanahashi Yukichi , Kato Takehiro , Suwa Tetsuya , Kawai Nobuyuki , Yabe Daisuke , Matsuo Masayuki
Published: February 2020

Objective:

To evaluate the utility of microcatheter in adrenal venous sampling (AVS) for assessing aldosterone hypersecretion and the laterality in patients with primary aldosteronism.

Methods:

This retrospective study was approved by the institutional review board of Gifu University Hospital, and written informed consent was waived. A total of 37 consecutive patients with primary aldosteronism underwent AVS by inserting a microcatheter into the right adrenal central vein (RCV), left adrenal central vein (LCV), and left adrenal common trunk (CT) followed by AVS with 5-French (5-Fr) catheter. The diagnosis of aldosterone hypersecretion was confirmed if the plasma aldosterone level after the administration of cosyntropin injection was ≥14,000 pg/ml. The laterality of aldosterone hypersecretion was determined based on the lateralized and contralateral ratios. Aldosterone hypersecretion and the laterality were diagnosed and compared based on the results obtained using 5-Fr catheter and microcatheter.

Results:

Plasma aldosterone levels were significantly higher in the RCV, LCV, and CT selected using microcatheter than in the right and left adrenal veins (LAVs) selected using 5-Fr catheter (p < 0.0001–0.029). More aldosterone hypersecretion from the left adrenal gland was observed in the LCV (n = 28) and CT (n = 25) selected using microcatheter compared to the LAV selected using 5-Fr catheter (n = 6) (p < 0.0001). Diagnostic changes in the laterality from unilateral to bilateral were noted in 3 (8%) patients using microcatheter.

Conclusion:

Microcatheter can effectively assess aldosterone hypersecretion and the laterality, especially in the LAV.

Advances in knowledge:

Especially for the left adrenal venous sampling, the tip of microcatheter could certainly reach the left adrenal vein orifice compared with 5-Fr catheter, therefore correct diagnosis is made and this leads to appropriate treatment.
Intraoperative breast specimen assessment in breast conserving surgery: comparison between standard mammography imaging and a remote radiological system
Authors: Mariscotti Giovanna , Durando Manuela , Pavan Luca Jacopo , Tagliafico Alberto , Campanino Pier Paolo , Castellano Isabella , Bussone Riccardo , Ala Ada , De Sanctis Corrado , Bergamasco Laura , Fonio Paolo , Houssami Nehmat
Published: February 2020

Objective:

To compare standard specimen mammography (SSM) with remote intraoperative specimen mammography (ISM) assessment in breast conserving-surgery (BCS) based on operative times, intraoperative additional excision (IAE) and re-intervention rates.

Methods and materials:

We retrospectively compared 129 consecutive patients (136 lesions) who had BCS with SSM at our centre between 11/2011 and 02/2013 with 138 consecutive patients (144 lesions) who underwent BCS with ISM between 08/2014 and 02/2015.

SSM or ISM were performed to confirm the target lesions within the excised specimen and margin adequacy. The utility of SMM and ISM was evaluated considering pathology as gold-standard, using χ2 or Fisher’s exact tests for comparison of categorical variables, and non-parametric Mann–Whitney test for continuous variables.

Results:

The two groups did not statistically differ for age (p = 0.20), lesion size (p = 0.29) and morphology (p = 0.82) or tumor histology type (p = 0.65). Intraoperative time was significantly longer (p < 0.00001) for SSM (132 ± 43 min) than for ISM (90 ± 42 min). The proportions requiring IAE did not significantly differ between SSM group (39/136 lesions (40%)) and ISM group (52/144 lesions (57%)) (p = 0.19), overall and in stratified analysis by mammographic features. Re-intervention rates were not statistically different between the two groups [SSM:19/136 (14%), ISM:13/144 (9%); p = 0.27].

Conclusion:

The introduction of ISM in BCS significantly reduced surgical time but did not change IAE and re-intervention rates, highlighting facilitated communication between surgeons and radiologists.

Advances in knowledge:

Compared to standard mammography imaging, the use of ISM significantly reduced surgical time.
Diagnostic performance of deep learning-based vascular extraction and stenosis detection technique for coronary artery disease
Authors: Chen Meng , Wang Ximing , Hao Guangyu , Cheng Xujie , Ma Chune , Guo Ning , Hu Su , Tao Qing , Yao Feirong , Hu Chunhong
Published: February 2020

Objective:

To investigate the diagnostic performance of deep learning (DL)-based vascular extraction and stenosis detection technology in assessing coronary artery disease (CAD).

Methods:

The diagnostic performance of DL technology was evaluated by retrospective analysis of coronary computed tomography angiography in 124 suspected CAD patients, using invasive coronary angiography as reference standard. Lumen diameter stenosis ≥50% was considered obstructive, and the diagnostic performances were evaluated at per-patient, per-vessel and per-segment levels. The diagnostic performances between DL model and reader model were compared by the areas under the receiver operating characteristics curves (AUCs).

Results:

In patient-based analysis, AUC of 0.78 was obtained by DL model to detect obstructive CAD [sensitivity of 94%, specificity of 63%, positive predictive value of 94%, and negative predictive value of 59%], While AUC by reader model was 0.74 (sensitivity of 97%, specificity of 50%, positive predictive value of 93%, negative predictive value of 73%). In vessel-based analysis, the AUCs of DL model and reader model were 0.87 and 0.89 respectively. In segment-based analysis, the AUCs of 0.84 and 0.89 were obtained by DL model and reader model respectively. It took 0.47 min to analyze all segments per patient by DL model, which is significantly less than reader model (29.65 min) (p < 0.001).

Conclusion:

The DL technology can accurately and effectively identify obstructive CAD, with less time-consuming, and it could be a reliable diagnostic tool to detect CAD.

Advances in knowledge:

The DL technology has valuable prospect with the diagnostic ability to detect CAD.
The abscopal effect 67 years later: from a side story to center stage
Authors: Demaria Sandra , Formenti Silvia C
Published: February 2020

For over a century, ionising radiation has been used to treat cancer based on its cytotoxic effects on tumour cells. Technical progress has enabled more precise targeting of the tumour to reduce normal tissue toxicity while delivering higher radiation doses per fraction of treatment.

In 1953, unexpected regression in lesions outside of the irradiated field were noted by an observant physician, RH Mole, who named such phenomenon “abscopal effect” from the Latin ab (position away from) and scopus (mark or target), in an article published in this journal. Clinical abscopal responses have been reported over the years but because of their very rare occurrence they could not be methodically studied, remaining akin to a curiosity. Nevertheless, their occurrence has ignited interest in studying the systemic effects of radiotherapy. Progress in dissecting the mechanisms that govern the function of the immune system in cancer has enabled to study the implication of immunity in the abscopal effect of radiation. It has become clear that ionising radiation activates canonical pathways of response to viral infections, and can stimulate antitumour immunity. These immune stimulatory effects of radiation have become clinically relevant in the current era of cancer immunotherapy, rendering abscopal responses in patients an attainable aim. Here, we will briefly review the parallel evolutions of two separate fields of medicine, radiation therapy and cancer immunology, and discuss their therapeutic partnership.
Custom-designed Small Animal focal iRradiation Jig (SARJ): design, manufacture and dosimetric evaluation
Authors: Selvaraj Jothy , Rhall Graham , Ibrahim Mounir , Mahmood Talat , Freeman Nigel , Gromek Zennon , Buchanan Grant , Syed Farhan , Elsaleh Hany , Quah Ben J. C.
Published: February 2020

Objective:

Preclinical animal models allow testing and refinement of novel therapeutic strategies. The most common preclinical animal irradiators are fixed source cabinet irradiators, which are vastly inferior to clinical linear accelerators capable of delivering highly conformal and precise treatments. The purpose of this study was to design, manufacture and test an irradiation jig (small animal focal irradiation jig, SARJ) that would enable focal irradiation of subcutaneous tumours in a standard fixed source cabinet irradiator.

Methods and materials:

A lead shielded SARJ was designed to rotate animal holders about the longitudinal axis and slide vertically from the base plate. Radiation dosimetry was undertaken using the built-in ion chamber and GAFChromic RTQA2 and EBT-XD films. Treatment effectiveness was determined by irradiating mice with subcutaneous melanoma lesions using a dose of 36 Gy in three fractions (12 Gy x 3) over three consecutive days.

Results:

The SARJ was tested for X-ray shielding effectiveness, verification of dose rate, total dose delivered to tumour and dose uniformity. Accurate and uniform delivery of X-ray dose was achieved. X-ray doses were limited to the tumour site when animal holders were rotated around their longitudinal axis to 15o and 195o, allowing sequential dose delivery using parallel-opposed tangential beams. Irradiation of subcutaneous melanoma tumour established on the flanks of mice showed regression.

Conclusion:

SARJ enabled delivery of tangential parallel-opposed radiation beams to subcutaneous tumours in up to five mice simultaneously. SARJ allowed high throughput testing of clinically relevant dose delivery using a standard cabinet-style fixed source irradiator.

Advances in knowledge:

A custom designed jig has been manufactured to fit into conventional cabinet irradiators and is dosimetrically validated to deliver clinically relevant dose distributions to subcutaneous tumours in mice for preclinical studies.
Improvement of bone-erosive temporomandibular joint (TMJ) abnormalities in adolescents undergoing non-surgical treatment: a longitudinal study
Authors: Abrahamsson Anna-Karin , Arvidsson Linda Z , Småstuen Milada Cvancarova , Larheim Tore A
Published: February 2020

Objectives:

To investigate the longitudinal changes of the imaging temporomandibular joint (TMJ) characteristics in young patients with TMJ-related symptoms and treated with non-surgical methods. The severity of self-reported symptoms at follow-up was also investigated.

Methods:

A cone beam CT (CBCT)/CT follow-up examination [median follow-up 4.1 (1.3–6.4) years] was performed in 22 patients with erosive TMJ abnormalities [baseline median age 16 (12–18) years]. Imaging characteristics were analyzed and the changes between the examinations were categorized as (A) improvement, (B) no change, or (C) worsening. Severity of follow-up symptoms was evaluated using Jaw Functional Limitation Scale (JFLS-8) and Graded Chronic Pain Scale (Grade 0–IV). Analyses were performed separately for left and right TMJ. Findings at baseline and follow-up were compared using McNemar test to account for dependencies. Changes in proportions of hard tissue findings between examinations were assessed using Wilcoxon signed ranks test.

Results:

A significant reduction in the proportion of patients with erosive abnormalities was found [59.1%, 95% CI (36.4–79.3) %]. Baseline erosions improved in 9/12 (75%) right and 14/15 (93%) left TMJs. About half repaired; developed an intact cortical outline. Number of joints with osteophytes increased (right: p < 0.04, left: p < 0.003). New osteophytes were mostly found in joints with erosive findings. Low or no limitation of jaw function (Jaw Functional Limitation Scale) was found in 12/22 (55%) and no or low intensity of pain (Graded Chronic Pain Scale Grade 0 or I) in 19/22 (86%) at follow-up.

Conclusion:

We found a high potential for repair of erosive TMJ abnormalities. However, the patient series was small. The majority of patients assessed their symptom severity at follow-up as low.
Complement proteins in unexpected places: why we should be excited, not concerned!
Authors: Ghebrehiwet Berhane
Published: February 2020

The complement system consists of more than 30 plasma as well as cell surface proteins that together constitute a major arm of the immune system. The long-held belief is that most of the complement components are synthesized by hepatocytes in the liver and then secreted into the blood. However, there is also substantial evidence that several if not all of the complement proteins are synthesized extrahepatically by a wide range of cell types, including polymorphonuclear leukocytes, monocytes, macrophages, dendritic cells, lymphocytes, epithelial cells, fibroblasts, and neuronal cells. However, despite the proven evidence that complement proteins indeed could be synthesized non-hepatic cells and even found in unexpected places, the recent finding that certain complement proteins could be activated in intracellular spaces nonetheless has opened up a new debate. In fact, some in the field unfortunately seem to be in favor of rejecting this notion rather vehemently on the untenable and myopic grounds that complement proteinscould notbe found in intracellular compartments despite evidence to the contrary. Therefore, this opinion article is meant to remind colleagues in the field that new discoveries with the potential to shift established functional paradigms should be encouraged and celebrated even if, at first glance, they seem to defy the odds.