bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mobile health in cardiac patients: an overview on experiences and challenges of stakeholders involved in daily use and development
Authors: Kauw Dirkjan , Huisma Piter R , Medlock Stephanie K , Koole Maarten A C , Wierda Eric , Abu-Hanna Ameen , Schijven Marlies P , Mulder Barbara J M , Bouma Berto J , Winter Michiel M , Schuuring Mark J 
Published: August 2020

BackgroundMobile health (mHealth) can improve quality of care and empower cardiac patients. However, large-scale adoption is still lacking, as several challenges continue to be encountered in daily practice. We aimed to explore the mHealth experiences and challenges in cardiac patients, healthcare professionals, healthcare managers and information and communications technology (ICT) developers.MethodsA qualitative research was employed where semistructured interviews were conducted in patients, healthcare professionals, managers and ICT developers. We aimed to enrol participants of every stakeholder group, with diversity in sex, age group and occupation. Thematic analysis was used to identify themes reflecting experiences and challenges in mHealth in cardiac patients.ResultsIn total, 24 interviews were conducted in six patients, eight healthcare professionals, five managers and five ICT developers. Monitoring/care at home was reported as important advantage of mHealth (n=20, 83%). Patients valued increase of self-care (n=6, 100%) and remote reassurance (n=6, 100%), but reported medicalisation as important concern (n=4, 67%). Healthcare professionals warned for increased data burden (n=4, 50%). Managers agreed on the importance of device reliability (n=5, 100%) and ICT developers emphasised that the goal of mHealth is to replace care, rather than being supplementary (n=4, 80%). The majority of all participants (n=22, 92%) considered future use of mHealth as promising.ConclusionsAll stakeholders foresee benefit of mHealth in cardiac patients, especially for remote care and reassurance. Frequently mentioned challenges included the need to replace care with mHealth, rather than adding more workload, and employing reliable devices and applications. If collaboration can be improved and group-specific challenges overcome, success of mHealth in cardiac patients can improve significantly.
Short-course radiotherapy promotes pro-inflammatory macrophages via extracellular vesicles in human rectal cancer
Authors: Stary Victoria , Wolf Brigitte , Unterleuthner Daniela , List Julia , Talic Merjem , Längle Johannes , Beer Andrea , Strobl Johanna , Stary Georg , Dolznig Helmut , Bergmann, MD Michael 
Published: August 2020

BackgroundTumor-associated macrophages (TAM) constitute the most abundant immune cells in the tumor stroma initiating pro-inflammatory (M1) or immunosuppressive (M2) responses depending on their polarization status. Advances in tumor immunotherapy call for a detailed understanding of potential immunogenic mechanisms of irradiation routinely applied in rectal cancer patients.MethodsTo test the effects of radiotherapy on TAM, we ex vivo irradiated tissue samples of human rectal cancer and assessed the phenotype by flow cytometry. We furthermore evaluated the distribution of leucocyte subsets in tissue sections of patients after short-course radiotherapy and compared findings to non-pretreated rectal cancer using an immunostaining approach. Organotypic assays (OTA) consisting of macrophages, cancer-associated fibroblast and cancer cell lines were used to dissect the immunological consequences of irradiation in macrophages.ResultsWe demonstrate that short-course neoadjuvant radiotherapy in rectal cancer patients is associated with a shift in the polarization of TAM towards an M1-like pro-inflammatory phenotype. In addition, ex vivo irradiation caused an increase in the phagocytic activity and enhanced expression of markers associated with stimulatory signals necessary for T-cell activation. In OTA we observed that this alteration in macrophage polarization could be mediated by extracellular vesicles (EV) derived from irradiated tumor cells. We identified high mobility group box 1 in EV from irradiated tumor cells as a potential effector signal in that crosstalk.ConclusionsOur findings highlight macrophages as potential effector cells upon irradiation in rectal cancer by diminishing their immunosuppressive phenotype and activate pro-inflammation. Our data indicate that clinically applied short-term radiotherapy for rectal cancer may be exploited to stimulate immunogenic macrophages and suggest to target the polarization status of macrophages to enhance future immunotherapeutic strategies.
Characterisation of aortic stenosis severity: a retrospective analysis of echocardiography reports in a clinical laboratory
Authors: Raddatz Michael A , Gonzales Holly M , Farber-Eger Eric , Wells Quinn S , Lindman Brian R , Merryman W David 
Published: August 2020

ObjectiveTo evaluate how common echocardiographic metrics of aortic stenosis (AS) influence the proportion of patients who may be categorised as having severe stenosis and therefore considered for valve replacement.MethodsRetrospective analysis was performed of all echocardiograms with aortic valve area (AVA) ≤1.2 cm2and peak jet velocity (Vmax) ≥3 m/s from 1 December 2014 through 30 October 2017 at a single academic medical centre. Echocardiographic indices collected include AVA, Vmax, left ventricular ejection fraction, stroke volume and annotated aortic stenosis severity.ResultsAmong 807 patients with AVA ≤1.2 cm2and Vmax≥3 m/s (44.0% female, median age 74 years (IQR: 66–81)), 45.6% had Vmax≥4 m/s, while 75.8% had AVA ≤1 cm2. 40.0% of patients had concordant indices (Vmax≥4 m/s and AVA ≤1 cm2), and 35.8% had discordant indices (Vmax<4 m/s and AVA ≤1 cm2) of severe AS. Compared with those with concordant indices, patients with discordant indices were more commonly female (54.0% vs 44.3%, p<0.05) and less commonly characterised as severe (42.6% vs 93.8%, p<0.001). Patients with paradoxical low-flow, low-gradient severe AS by echocardiography were disproportionately female (61.5% vs 41.8%, p<0.001), and their disease was characterised as severe only 49.5% of the time.ConclusionsPatients with discordant indices, who are disproportionately female, are commonly described in clinical echocardiography reports as having less than severe AS. Given the potential benefit of AVR in patients with AVA ≤1 cm2regardless of Vmax, this could have important clinical implications.
Reactions to, and trial intentions for, three dissuasive cigarette designs: a cross-sectional survey of adolescents in Scotland
Authors: Mitchell Danielle , Critchlow Nathan , Moodie Crawford , Bauld Linda 
Published: August 2020

ObjectivesThere has been growing academic and policy interest in opportunities to decrease the appeal of cigarette sticks, such as making them an unattractive colour or requiring them to display a health warning. We therefore explored reactions to, and trial intentions for, three ‘dissuasive’ cigarette designs among adolescents in Scotland.MethodsA cross-sectional survey with 12–17 year olds in Scotland (n=594) was conducted between November 2017 and November 2018. Participants were shown one ‘standard’ cigarette (imitation cork filter with white paper casing) and three dissuasive cigarettes: (1) a cigarette with the warning ‘smoking kills’; (2) a cigarette with the warning ‘toxic’ and a skull and cross-bones image and (3) a dark green cigarette. Participants rated each cigarette on nine five-point reaction measures (eg, appealing/unappealing or attractive/unattractive). A composite reaction score was computed for each cigarette, which was binary coded (overall negative reactions vs neutral/positive reactions). Participants also indicated whether they would try each cigarette (coded: Yes/No). Demographics, smoking status and smoking susceptibility were also measured.ResultsMore participants had negative reactions to the dark green (93% of adolescents), ‘smoking kills’ (94%) and ‘toxic’ (96%) cigarettes, compared with the standard cigarette (85%). For all three dissuasive designs, Chi-square tests found that negative reactions were more likely among younger adolescents (vs older adolescents), never-smokers (vs ever smokers) and non-susceptible never-smokers (vs susceptible never-smokers). Most participants indicated that they would not try any of the cigarettes (range: 84%–91%).ConclusionDissuasive cigarettes present an opportunity to further reduce the appeal of smoking among adolescents.
Aerobic exercise training attenuates detrimental effects of cigarette smoke exposure on peripheral muscle through stimulation of the Nrf2 pathway and cytokines: a time-course study in mice
Authors: Toledo-Arruda Alessandra C. , Sousa Neto Ivo Vieira de , Vieira Rodolfo P. , Guarnier Flávia A. , Caleman-Neto Agostinho , Suehiro Camila L. , Olivo Clarice R. , Cecchini Rubens , Prado Carla M. , Lin Chin J. , Durigan João Luiz Quaglioti , Martins Milton A. 
Published: August 2020

Cigarette smoke (CS) exposure reduces skeletal muscle function; however, the mechanisms involved have been poorly investigated. The current study evaluated the temporal effects of aerobic exercise training on oxidant and antioxidant systems as well as inflammatory markers in skeletal muscle of mice exposed to CS. Mice were randomly allocated to control, exercise, smoke, and smoke+exercise groups and 3 time points (4, 8, and 12 weeks; n = 12 per group). Exercise training and CS exposure were performed for 30 min/day, twice a day, 5 days/week for 4, 8, and 12 weeks. Aerobic exercise improved functional capacity and attenuated the increase in the cachexia index induced by CS exposure after 12 weeks. Concomitantly, exercise training downregulated tumor necrosis factor α concentration, glutathione oxidation, and messenger RNA (mRNA) expression of Keap1 (P < 0.01) and upregulated interleukin 10 concentration, total antioxidant capacity, and mRNA expression of Nrf2, Gsr, and Txn1 (P < 0.01) in muscle. Exercise increased mRNA expression of Hmox1 compared with the control after 12 weeks (P < 0.05). There were no significant differences between smoke groups for superoxide dismutase activity and Hmox1 mRNA expression. Exercise training improved the ability of skeletal muscle to adequately upregulate key antioxidant and anti-inflammatory defenses to detoxify electrophilic compounds induced by CS exposure, and these effects were more pronounced after 12 weeks. Novelty Exercise attenuates oxidative stress in skeletal muscle from animals exposed to CS via Nrf2 and glutathione pathways. Exercise is a helpful tool to control the inflammatory balance in skeletal muscle from animals exposed to CS. These beneficial effects were evident after 12 weeks.
Direct comparison of sterile neutrino constraints from cosmological data, $$\nu _{e}$$ disappearance data and $$\nu _{\mu } \rightarrow \nu _{e} $$ appearance data in a $$3+1$$ model
Authors: Adams Matthew , Bezrukov Fedor , Elvin-Poole Jack , Evans Justin J. , Guzowski Pawel , Fearraigh Brían Ó , Söldner-Rembold Stefan 
Published: August 2020

AbstractWe present a quantitative, direct comparison of constraints on sterile neutrinos derived from neutrino oscillation experiments and from Planck data, interpreted assuming standard cosmological evolution. We extend a$$1+1$$1+1model, which is used to compare exclusion contours at the 95% Cl derived from Planck data to those from$$\nu _{e}$$νe-disappearance measurements, to a$$3+1$$3+1model. This allows us to compare the Planck constraints with those obtained through$$\nu _{\mu }\rightarrow \nu _{e}$$νμ→νeappearance searches, which are sensitive to more than one active-sterile mixing angle. We find that the cosmological data fully exclude the allowed regions published by the LSND, MiniBooNE and Neutrino-4 collaborations, and those from the gallium and rector anomalies, at the 95% Cl. Compared to the exclusion region from the Daya Bay$$\nu _{e}$$νe-disappearance search, the Planck data are more strongly excluding above$$|\Delta m^{2}_{41}|\approx 0.1\,\mathrm {eV}^{2}$$|Δm412|≈0.1eV2and$$m_\mathrm {eff}^\mathrm {sterile}\approx 0.2\,\mathrm {eV}$$meffsterile≈0.2eV, with the Daya Bay exclusion being stronger below these values. Compared to the combined Daya Bay/Bugey/MINOS exclusion region on$$\nu _{\mu }\rightarrow \nu _{e}$$νμ→νeappearance, the Planck data is more strongly excluding above$$\Delta m^{2}_{41}\approx 5\times 10^{-2}\,\mathrm {eV}^{2}$$Δm412≈5×10-2eV2, with the exclusion strengths of the Planck data and the Daya Bay/Bugey/MINOS combination becoming comparable below this value.
Slow-Cycling Cancer Stem Cells Regulate Progression and Chemoresistance in Colon Cancer
Authors: Shiokawa Daisuke , Sakai Hiroaki , Ohata Hirokazu , Miyazaki Toshiaki , Kanda Yusuke , Sekine Shigeki , Narushima Daichi , Hosokawa Masahito , Kato Mamoru , Suzuki Yutaka , Takeyama Haruko , Kambara Hideki , Nakagama Hitoshi , Okamoto Koji 
Published: August 2020

Abstract

Cancer chemoresistance is often attributed to the presence of cancer stem cell (CSC)-like cells, but whether they are homogeneously chemoresistant remains unclear. We previously showed that in colon tumors, a subpopulation of LGR5+ CSC-like cells driven by TCF1 (TCF7), a Wnt-responsive transcription factor, were responsible for tumorigenicity. Here we demonstrate that the tumorigenic subpopulation of mouse LGR5+ cells exists in a slow-cycling state and identify a unique 22-gene signature that characterizes these slow-cycling CSC. Seven of the signature genes are specifically expressed in slow-cycling LGR5+ cells from xenografted human colon tumors and are upregulated in colon cancer clinical specimens. Among these seven, four genes (APCDD1, NOTUM, PROX1, and SP5) are known to be direct Wnt target genes, and PROX1 was expressed in the invasive fronts of colon tumors. PROX1 was activated by TCF1 to induce CDKN1C and maintain a slow-cycling state in colon cancer organoids. Strikingly, PROX1 was required for recurrent growth after chemotherapeutic treatment, suggesting that inhibition of slow-cycling CSC by targeting the TCF1–PROX1–CDKN1C pathway is an effective strategy to combat refractory colon cancer in combination with conventional chemotherapy.

Significance:
These findings illustrate the importance of a slow-cycling CSC subpopulation in colon cancer development and chemoresistance, with potential implications for the identified slow-cycling CSC signatures and the TCF1–PROX1–CDKN1C pathway as therapeutic targets.
EZH2-Mediated Downregulation of the Tumor Suppressor DAB2IP Maintains Ovarian Cancer Stem Cells
Authors: Zong Xingyue , Wang Weini , Ozes Ali , Fang Fang , Sandusky George E. , Nephew Kenneth P. 
Published: August 2020

Abstract

The majority of women diagnosed with epithelial ovarian cancer eventually develop recurrence, which rapidly evolves into chemoresistant disease. Persistence of ovarian cancer stem cells (OCSC) at the end of therapy may be responsible for emergence of resistant tumors. In this study, we demonstrate that in OCSC, the tumor suppressor disabled homolog 2–interacting protein (DAB2IP) is silenced by EZH2-mediated H3K27 trimethylation of the DAB2IP promoter. CRISPR/Cas9-mediated deletion of DAB2IP in epithelial ovarian cancer cell lines upregulated expression of stemness-related genes and induced conversion of non-CSC to CSC, while enforced expression of DAB2IP suppressed CSC properties. Transcriptomic analysis showed that overexpression of DAB2IP in ovarian cancer significantly altered stemness-associated genes and bioinformatic analysis revealed WNT signaling as a dominant pathway mediating the CSC inhibitory effect of DAB2IP. Specifically, DAB2IP inhibited WNT signaling via downregulation of WNT5B, an important stemness inducer. Reverse phase protein array further demonstrated activation of noncanonical WNT signaling via C-JUN as a downstream target of WNT5B, which was blocked by inhibiting RAC1, a prominent regulator of C-JUN activation. Coadministration of EZH2 inhibitor GSK126 and RAC1 inhibitor NSC23766 suppressed OCSC survival in vitro and inhibited tumor growth and increased platinum sensitivity in vivo. Overall, these data establish that DAB2IP suppresses the cancer stem cell phenotype via inhibition of WNT5B-induced activation of C-JUN and can be epigenetically silenced by EZH2 in OCSC. Targeting the EZH2/DAB2IP/C-JUN axis therefore presents a promising strategy to prevent ovarian cancer recurrence and has potential for clinical translation.

Significance:
These findings show that combining an epigenetic therapy with a noncanonical WNT signaling pathway inhibitor has the potential to eradicate ovarian cancer stem cells and to prevent ovarian cancer recurrence.
ARC Is a Critical Protector against Inflammatory Bowel Disease (IBD) and IBD-Associated Colorectal Tumorigenesis
Authors: Wang Qiushi , Zhang Tianshun , Chang Xiaoyu , Lim Do Young , Wang Keke , Bai Ruihua , Wang Ting , Ryu Joohyun , Chen Hanyong , Yao Ke , Ma Wei-Ya , Boardman Lisa A. , Bode Ann M. , Dong Zigang 
Published: August 2020

Abstract

The key functional molecules involved in inflammatory bowel disease (IBD) and IBD-induced colorectal tumorigenesis remain unclear. In this study, we found that the apoptosis repressor with caspase recruitment domain (ARC) protein plays critical roles in IBD. ARC-deficient mice exhibited substantially higher susceptibility to dextran sulfate sodium (DSS)-induced IBD compared with wild-type mice. The inflammatory burden induced in ARC-deficient conditions was inversely correlated with CCL5 and CXCL5 levels in immune cells, especially CD4-positive T cells. Pathologically, ARC expression in immune cells was significantly decreased in clinical biopsy specimens from patients with IBD compared with normal subjects. In addition, ARC levels inversely correlated with CCL5 and CXCL5 levels in human biopsy specimens. ARC interacted with TNF receptor associated factor (TRAF) 6, regulating ubiquitination of TRAF6, which was associated with NF-κB signaling. Importantly, we identified a novel ubiquitination site at lysine 461, which was critical in the function of ARC in IBD. ARC played a critical role in IBD and IBD-associated colon cancer in a bone marrow transplantation model and azoxymethane/DSS-induced colitis cancer mouse models. Overall, these findings reveal that ARC is critically involved in the maintenance of intestinal homeostasis and protection against IBD through its ubiquitination of TRAF6 and subsequent modulation of NF-κB activation in T cells.

Significance:
This study uncovers a crucial role of ARC in the immune system and IBD, giving rise to a novel strategy for IBD and IBD-associated colon cancer therapy.
Cardiac Conduction Disorders as Markers of Cardiac Events in Myotonic Dystrophy Type 1
Authors: Itoh Hideki , Hisamatsu Takashi , Tamura Takuhisa , Segawa Kazuhiko , Takahashi Toshiaki , Takada Hiroto , Kuru Satoshi , Wada Chizu , Suzuki Mikiya , Suwazono Shugo , Sasaki Shingo , Okumura Ken , Horie Minoru , Takahashi Masanori P. , Matumura Tsuyoshi 
Published: August 2020

Background
Myotonic dystrophy type 1 involves cardiac conduction disorders. Cardiac conduction disease can cause fatal arrhythmias or sudden death in patients with myotonic dystrophy type 1.

Methods and Results

This study enrolled 506 patients with myotonic dystrophy type 1 (aged ≥15 years; >50 cytosine‐thymine‐guanine repeats) and was treated in 9 Japanese hospitals for neuromuscular diseases from January 2006 to August 2016. We investigated genetic and clinical backgrounds including health care, activities of daily living, dietary intake, cardiac involvement, and respiratory involvement during follow‐up. The cause of death or the occurrence of composite cardiac events (ie, ventricular arrhythmias, advanced atrioventricular blocks, and device implantations) were evaluated as significant outcomes. During a median follow‐up period of 87 months (Q1–Q3, 37–138 months), 71 patients expired. In the univariate analysis, pacemaker implantations (hazard ratio [HR], 4.35; 95% CI, 1.22–15.50) were associated with sudden death. In contrast, PQ interval ≥240 ms, QRS duration ≥120 ms, nutrition, or respiratory failure were not associated with the incidence of sudden death. The multivariable analysis revealed that a PQ interval ≥240 ms (HR, 2.79; 95% CI, 1.9–7.19,
P
<0.05) or QRS duration ≥120 ms (HR, 9.41; 95% CI, 2.62–33.77,
P
< 0.01) were independent factors associated with a higher occurrence of cardiac events than those observed with a PQ interval <240 ms or QRS duration <120 ms; these cardiac conduction parameters were not related to sudden death.

Conclusions
Cardiac conduction disorders are independent markers associated with cardiac events. Further investigation on the prediction of occurrence of sudden death is warranted.
The Incidence and Associated Factors of Early Neurological Deterioration After Thrombolysis
Authors: Yu Wai M. , Abdul-Rahim Azmil H. , Cameron Alan C. , Kõrv Janika , Sevcik Petr , Toni Danilo , Lees Kennedy R. , Wahlgren N. , Ahmed N. , Caso V. , Roffe C. , Kobayashi A. , Tsivgoulis G. , Toni D. , Ford G.A. , Lees K.R. , Ringleb P. 
Published: August 2020

Background and purpose:
Early neurological deterioration (END) after stroke onset may predict severe outcomes. Estimated rates of END after intravenous thrombolysis among small patient samples have been reported up to 29.8%. We studied the incidence and factors associated with END among patients following intravenous thrombolysis.

Methods:

We analyzed SITS-International Stroke Thrombolysis registry patients with known outcomes enrolled in 2010 to 2017. END was defined as an increase in National Institutes of Health Stroke Scale score ≥4 or death within 24 hours from baseline National Institutes of Health Stroke Scale. We determined the incidence of END and used logistic regression models to inspect its associated factors. We adjusted for variables found significant in univariate analyses (
P
<0.05). Main outcomes were incidence of END, associated predictors of END, ordinal day-90 mRS, and day-90 mortality.

Results:

We excluded 53 539 patients and included 50 726 patients. The incidence of END was 3415/50 726 (6.7% [95% CI, 6.5%–7.0%]). Factors independently associated with END on multivariate analysis were intracerebral hemorrhage (OR, 3.23 [95% CI, 2.96–3.54],
P
<0.001), large vessel disease (LVD) with carotid stenosis (OR, 2.97 [95% CI, 2.45–3.61],
P
<0.001), other LVD (OR, 2.41 [95% CI, 2.03–2.88],
P
<0.001), and ischemic stroke versus transient ischemic attack (TIA)/stroke mimics (OR, 16.14 [95% CI, 3.99–65.3],
P
<0.001). END was associated with worse outcome on ordinal mRS: adjusted OR 2.48 (95% CI, 2.39–2.57,
P
<0.001) by day-90 compared with no END. The adjusted OR for day-90 mortality was 9.70 (95% CI, 8.36–11.26,
P
<0.001).

Conclusions:
The routinely observed rate of END reflected by real-world data is low, but END greatly increases risk of disability and mortality. Readily identifiable factors predict END and may help with understanding causal mechanisms to assist prevention of END.