bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of a power strength training using elastic resistance exercises on the motor and non-motor symptoms in patients with Parkinson’s disease H&Y 1–3: study protocol for a randomised controlled trial (PARK-BAND Study)
Authors: Lima Danielle Pessoa , de Almeida Samuel Brito , Bonfadini Janine de Carvalho , Sobreira Emmanuelle Silva Tavares , Damasceno Patrícia Gomes , Viana Júnior Antonio Brazil , de Alencar Madeleine Sales , de Luna João Rafael Gomes , Rodrigues Pedro Gustavo Barros , Pereira Isabelle de Sousa , Gadelha André Luis de Castro , de Oliveira Liliane Maria , Chaves Érica Carneiro Barbosa , Carneiro Vlademir Gomes , Monteiro Rayane Rodrigues , Costa Thatyara Almeida de Macedo , Helal Lucas , Signorile Joseph , Lima Lidiane Andréa Oliveira , Sobreira-Neto Manoel Alves , Braga-Neto Pedro 
Published: October 2020

IntroductionParkinson’s disease (PD) is the second most common neurodegenerative disorder in Brazil. Physical activity is a complementary intervention in managing inherent declines associated with the disease like strength, balance, gait, and functionality and benefit health-related outcomes. Here, we report the PARK-BAND Study protocol, which aims to investigate potential benefits of power training using elastic devices in participants with PD. Our intervention will be provided in patients with PD using elastic devices like elastic bands and tubes. Therefore, we used the term Park from Parkinson’s disease and band from elastic bands.Methods and analysisThis randomised single-blind single-centre two-arm parallel, superiority trial will include 50 participants with PD attending the clinical setting. Those who meet the eligibility criteria and provide consent to participate will be randomised in a 1:1 ratio to either the exercise group, which will receive power training programme or the health education group, which will receive the education programme. Randomisation will be performed by permuted block randomisation with a block size of eight. Both groups will receive a 12-week intervention. The exercise group will have two sessions per week and the health education group will have one session per week. Changes from baseline in bradykinesia, as assessed by the Unified Parkinson's Disease Rating Scale motor examination subscore and physical functional performance, will be the primary outcomes. Secondary outcomes include other neurological, neurophysiological and physical variables, as well as the quality of life, depression, cognition, sleep quality and disturbances, assessed before and after interventions. We hypothesise that the exercise group will have greater improvement in primary and secondary outcomes than the health education group.Ethics and disseminationThe study is approved by the Research Ethics Committee of Hospital Universitário Walter Cantidio and all participants will provide their written informed consent (register number 91075318.1.0000.5045).Trial results will be disseminated via peer reviewed journal articles and conference presentations, reports for organisations involved with PD and for participants.Trial registration numberRegistro Brasileiro de Ensaios Clínicos Registry (RBR-5w2sqt); Pre-results.
Incidence and associated factors of extrauterine growth restriction (EUGR) in preterm infants, a cross-sectional study in selected NICUs in Ethiopia
Authors: Gidi Netsanet Workneh , Goldenberg Robert L , Nigussie Assaye K , McClure Elizabeth , Mekasha Amha , Worku Bogale , Siebeck Matthias , Genzel-Boroviczeny Orsolya , Muhe Lulu M 
Published: October 2020

BackgroundPreterm infants have high risk of developing growth restriction and long-term complications. Enteral feeding is often delayed in neonatal intensive care units (NICUs) for the fear of feeding intolerance and the associated necrotising enterocolitis, and recent advances in nutritional support are unavailable in low-income countries.ObjectiveThe aim of this study was to assess the incidence and associated factors of extrauterine growth restriction (EUGR) among preterm infants in selected NICUs in Ethiopia.MethodThis was a cross-sectional study involving a subgroup analysis of preterm infants admitted to hospitals, from a multicentre descriptive study of cause of illness and death in preterm infants in Ethiopia, conducted from 2016 to 2018. EUGR was defined as weight at discharge Z-scores <−1.29 for corrected age. Clinical profiles of the infants were analysed for associated factors. SPSS V.23 software was used for analysis with a significance level of 5% and 95% CI.ResultFrom 436 preterm infants included in the analysis, 223 (51%) were male, 224 (51.4%) very low birth weight (VLBW) and 185 (42.4%) small for gestational age (SGA). The mean (SD) of weight for corrected age Z-score at the time of discharge was −2.5 (1.1). The incidence of EUGR was 86.2%. Infants who were SGA, VLBW and longer hospital stay over 21 days had increased risk of growth restriction (p-value<0.01). SGA infants had a 15-fold higher risk of developing EUGR at the time of discharge from hospital than those who were appropriate or large for gestational age (OR (95% CI)=15.2 (4.6 to 50.1).ConclusionThe majority of the infants had EUGR at the time of discharge from the hospital, which indicates suboptimal nutrition. Revision of national guidelines for preterm infants feeding and improvement in clinical practice is highly required.
What is the impact of clinically assisted hydration in the last days of life? A systematic literature review and narrative synthesis
Authors: Kingdon Arjun , Spathis Anna , Brodrick Robert , Clarke Gemma , Kuhn Isla , Barclay Stephen 
Published: October 2020

BackgroundClinically assisted hydration (CAH) can be provided in the last days of life as drinking declines. The impact of this practice on quality of life or survival in the last days of life is unclear. Practice varies worldwide concerning this emotive issue.MethodSystematic literature review and narrative synthesis of studies evaluating the impact of, or attitudes toward, CAH in the last days of life. Databases were searched up to December 2019. Studies were included if the majority of participants were in the last 7 days of life, and were evaluated using Gough’s 'Weight of Evidence' framework. Review protocol registered with PROSPERO, registration number CRD42019125837.ResultsFifteen studies were included in the synthesis. None were judged to be both of high quality and relevance. No evidence was found that the provision of CAH has an impact on symptoms or survival. Patient and family carer attitudes toward assisted hydration were diverse.ConclusionThere is currently insufficient evidence to draw firm conclusions on the impact of CAH in the last days of life. Future research needs to focus on patients specifically in the last days of life, include those with non-malignant diagnoses, and evaluate best ways to communicate effectively about this complex topic with patients and their families.
Changes in quality of life, cognition and functional status following catheter ablation of atrial fibrillation
Authors: Piccini Jonathan P , Todd Derick M , Massaro Tyler , Lougee Aimee , Haeusler Karl Georg , Blank Benjamin , de Bono Joseph Paul , Callans David J , Elvan Arif , Fetsch Thomas , Van Gelder Isabelle , Gentlesk Philip , Grimaldi Massimo , Hansen Jim , Hindricks Gerhard , Al-Khalidi Hussein , Mont Lluis , Nielsen Jens Cosedis , Noelker Georg , De Potter Tom , Scherr Daniel , Schotten Ulrich , Themistoclakis Sakis , Vijgen Johan , Di Biase Luigi , Kirchhof Paulus 
Published: October 2020

ObjectiveTo investigate changes in quality of life (QoL), cognition and functional status according to arrhythmia recurrence after atrial fibrillation (AF) ablation.MethodsWe compared QoL, cognition and functional status in patients with recurrent atrial tachycardia (AT)/AF versus those without recurrent AT/AF in the AXAFA–AFNET 5 clinical trial. We also sought to identify factors associated with improvement in QoL and functional status following AF ablation by overall change scores with and without analysis of covariance (ANCOVA).ResultsAmong 518 patients who underwent AF ablation, 154 (29.7%) experienced recurrent AT/AF at 3 months. Patients with recurrent AT/AF had higher mean CHA2DS2-VASc scores (2.8 vs 2.3, p<0.001) and more persistent forms of AF (51 vs 39%, p=0.012). Median changes in the SF-12 physical (3 (25th, 75th: −1, 8) vs 1 (−5, 8), p=0.026) and mental scores (2 (−3, 9) vs 0 (−4, 5), p=0.004), EQ-5D (0 (0,2) vs 0 (−0.1, 0.1), p=0.027) and Karnofsky functional status scores (10 (0, 10) vs 0 (0, 10), p=0.001) were more favourable in patients without recurrent AT/AF. In the overall cohort, the proportion with at least mild cognitive impairment (Montreal Cognitive Assessment <26) declined from 30.3% (n=157) at baseline to 21.8% (n=113) at follow-up. ANCOVA identified greater improvement in Karnofsky functional status (p<0.001) but not SF-12 physical (p=0.238) or mental scores (p=0.065) in those without recurrent AT/AF compared with patients with recurrent AT/AF.ConclusionsPatients without recurrent AT/AF appear to experience greater improvement in functional status but similar QoL as those with recurrent AT/AF after AF ablation.
Research priorities in cardiovascular imaging
Authors: Yong Guo Liang , Weir-McCall Jonathan , Wilson Michael , Roditi Giles H , Bull Russell , Williams Michelle Claire , Schmitt Matthias 
Published: October 2020

AimA modified Delphi approach was used to develop consensus opinion among British Society for Cardiac Imaging/British Society of Cardiac CT (BSCI/BSCCT) members in order to prioritise research questions in cardiovascular imaging.MethodsAll members of the BSCI/BSCCT were invited to submit research questions that they considered to be of the highest clinical and/or academic priority in the field of cardiovascular imaging (phase 1). Subsequently a steering committee removed duplicate questions and combined questions of a similar theme by consensus agreement where appropriate. BSCI/BSCCT members were invited to rank the resulting research questions in two further iterative rounds (phases 2 and 3) to determine a final list of high-priority research questions.ResultsA total of 111 research questions were submitted in phase 1 by 30 BSCI/BSCCT members. While there was a broad range of topics, from determining the optimal features/markers of the vulnerable plaque to investigating how cardiac imaging can best be used to maximise clinical outcomes and economic costs, multimodality imaging-related (n=44, 40%) questions dominated the categories and coronary artery imaging (n=40, 36%) was the most common topic. Over two iterative rounds of prioritisation of these research questions, the original 111 were reduced to 75 questions in round 2, and 25 in round 3. From these 25 a finalTop 10 listwas distilled by consensus grouping.ConclusionThis study has identified and ranked the top research priorities in cardiovascular imaging, as identified by the BSCI/BSCCT membership. This is a first step towards identifying the cardiovascular imaging research priorities within the UK and may assist researchers and funding bodies alike in setting priorities.
Ultrathin-strut biodegradable polymer versus durable polymer drug-eluting stents: a meta-analysis
Authors: Monjur Mohammad Riashad , Said Christian F , Bamford Paul , Parkinson Michael , Szirt Richard , Ford Thomas 
Published: October 2020

ObjectivesDetermine whether an ultrathin biodegradable polymer sirolimus-eluting stent (‘Orsiro’—BP-SES) has clinical benefits over second-generation durable polymer drug-eluting stents (DP-DES).MethodsWe conducted a prospective systematic review and meta-analysis of randomised clinical trials comparing Orsiro BP-SES against DP-DES (PROSPERO Registration: CRD42019147136). The primary outcome was target lesion failure (TLF): composite of cardiac death, target vessel myocardial infarction (TVMI) and clinically indicated target lesion revascularisation (TLR)) evaluated at the longest available follow-up.ResultsNine trials randomised 11 302 patients to either Orsiro BP-SES or DP-DES. At mean weighted follow-up of 2.8 years, the primary outcome (TLF) occurred in 501 of 6089 (8.2%) participants with BP-SES compared with 495 of 5213 (9.5%) participants with DP-DES. This equates to an absolute risk reduction of 1.3% in TLF in favour of Orsiro BP-SES (OR 0.82; 95% CI 0.69 to 0.98; p=0.03). This was driven by a reduction in TVMI (OR 0.80; 95% CI 0.65 to 0.98; p=0.03). There were no significant differences in other clinical endpoints: cardiac death, TLR and stent thrombosis.ConclusionThe Orsiro BP-SES shows promising clinical outcomes in patients undergoing percutaneous coronary intervention compared with contemporary second-generation DES at a short to medium term follow-up. More research is warranted to evaluate performance over a longer follow-up period and in different clinical and lesion subsets.
Influencer prevalence and role on cigar brand Instagram pages
Authors: Navarro Mario Antonio , O'Brien Erin Keely , Ganz Ollie , Hoffman Leah 
Published: October 2020

PurposeInfluencers market products for tobacco companies on social media. This is the first study to systematically examine leading cigar brands’ use of influencers on their brand Instagram pages.MethodsWe identified 24 leading cigar brands, using July 2017–June 2018 US retail data. We identified cigar brands that had official appearing Instagram pages, with at least one influencer in the past 20 posts. We coded characteristics of the past three posts from each of five brand pages that contained influencers, such as setting and what the influencer was doing. Finally, we described influencer characteristics.ResultsApproximately one-third of the 24 brands had official Instagram accounts with at least one influencer in the past 20 posts. We identified 28 influencers, typically people of colour from the hip-hop music industry, some with millions of followers. Influencers included Bella Thorne (@bellathorne), Shaquille O’Neal (@shaq) and T.I. (@troubleman31). Brands’ posts that contained influencers showed the influencer using/holding a product, wearing branded merchandise or appearing in photos with a brand watermark. Three brands’ pages posted sponsored event photos (ie, concerts and events using branded backgrounds).DiscussionCigar brands commonly use influencers to market their products on brand Instagram pages. Results are consistent with previous findings that cigar companies’ marketing may target younger African Americans and highlight the potential utility of education campaigns that similarly engage influencers.
Enhanced CP asymmetries in $$B \rightarrow K \mu ^+ \mu ^-$$
Authors: Bečirević Damir , Fajfer Svjetlana , Košnik Nejc , Smolkovič Aleks 
Published: October 2020

AbstractWe show that the current values of $$R_K^\mathrm {exp}$$

R
K
exp

and $$R_{K^*}^\mathrm {exp}$$

R

K
∗

exp

can be accommodated by allowing a nonzero New Physics coupling $$\delta C_9^{\mu \mu }$$

δ

C
9

μ
μ

to be complex, both in the scenario in which only $$\delta C_9^{\mu \mu }$$

δ

C
9

μ
μ

is affected, and in the scenario with complex $$\delta C_{9,10}^{\mu \mu }$$

δ

C

9
,
10

μ
μ

satisfying $$\delta C_{9}^{\mu \mu }=-\delta C_{10}^{\mu \mu }$$

δ

C

9

μ
μ

=
-
δ

C

10

μ
μ

. A presence of the weak CP-violating phase can then be tested by measuring the CP-asymmetry, $$\mathcal {A}_\mathrm {CP}$$

A
CP

. We show that this asymmetry is enhanced around the peak of each $$c\bar{c}$$

c

c

¯

-resonance, and in fact more pronounced in the close vicinity of $$J/\psi $$

J
/
ψ

and $$\psi (2S)$$

ψ
(
2
S
)

. Therefore, measuring $$\mathcal {A}_\mathrm {CP}$$

A
CP

before and after the resonances’ peak could be revelatory of the CP-violation that originates from beyond the Standard Model, or to be a significant constrain when building a realistic scenario of New Physics.
SIRT1-Mediated Expression of CD24 and Epigenetic Suppression of Novel Tumor Suppressor miR-1185-1 Increases Colorectal Cancer Stemness
Authors: Wang Teh-Wei , Chern Edward , Hsu Chao-Wei , Tseng Kuo-Chang , Chao Hsiao-Mei 
Published: October 2020

Abstract

NAD-dependent deacetylase sirtuin-1 (SIRT1) is a class III histone deacetylase that positively regulates cancer-related pathways such as proliferation and stress resistance. SIRT1 has been shown to promote progression of colorectal cancer and is associated with cancer stemness, yet the precise mechanism between colorectal cancer stemness and SIRT1 remains to be further clarified. Here we report that SIRT1 signaling regulates colorectal cancer stemness by enhancing expression of CD24, a colorectal cancer stemness promoter. A novel miRNA, miR-1185-1, suppressed the expression of CD24 by targeting its 3′UTR (untranslated region) and could be inhibited by SIRT1 via histone deacetylation. Targeting SIRT1 by RNAi led to elevated H3 lysine 9 acetylation on the promoter region of miR-1185-1, which increased expression of miR-1185-1 and further repressed CD24 translation and colorectal cancer stemness. In a mouse xenograft model, overexpression of miR-1185-1 in colorectal cancer cells substantially reduced tumor growth. In addition, expression of miR-1185-1 was downregulated in human colorectal cancer tissues, whereas expression of CD24 was increased. In conclusion, this study not only demonstrates the essential roles of a SIRT1–miR-1185-1–CD24 axis in both colorectal cancer stemness properties and tumorigenesis but provides a potential therapeutic target for colorectal cancer treatment.

Significance:
A novel tumor suppressor miR-1185-1 is involved in molecular regulation of CD24- and SIRT1-related cancer stemness networks, marking it a potential therapeutic target in colorectal cancer.
PI3K Driver Mutations: A Biophysical Membrane-Centric Perspective
Authors: Zhang Mingzhen , Jang Hyunbum , Nussinov Ruth 
Published: October 2020

AbstractRas activates its effectors at the membrane. Active PI3Kα and its associated kinases/phosphatases assemble at membrane regions enriched in signaling lipids. In contrast, the Raf kinase domain extends into the cytoplasm and its assembly is away from the crowded membrane surface. Our structural membrane-centric outlook underscores the spatiotemporal principles of membrane and signaling lipids, which helps clarify PI3Kα activation. Here we focus on mechanisms of activation driven by PI3Kα driver mutations, spotlighting the PI3Kα double (multiple) activating mutations. Single mutations can be potent, but double mutations are stronger: their combination is specific, a single strong driver cannot fully activate PI3K, and two weak drivers may or may not do so. In contrast, two strong drivers may successfully activate PI3K, where one, for example, H1047R, modulates membrane interactions facilitating substrate binding at the active site (km) and the other, for example, E542K and E545K, reduces the transition state barrier (ka), releasing autoinhibition by nSH2. Although mostly unidentified, weak drivers are expected to be common, so we ask here how common double mutations are likely to be and why PI3Kα with double mutations responds effectively to inhibitors. We provide a structural view of hotspot and weak driver mutations in PI3Kα activation, explain their mechanisms, compare these with mechanisms of Raf activation, and point to targeting cell-specific, chromatin-accessible, and parallel (or redundant) pathways to thwart the expected emergence of drug resistance. Collectively, our biophysical outlook delineates activation and highlights the challenges of drug resistance.
Role of Tumor Mutation Burden Analysis in Detecting Lynch Syndrome in Precision Medicine: Analysis of 2,501 Japanese Cancer Patients
Authors: Kiyozumi Yoshimi , Matsubayashi Hiroyuki , Higashigawa Satomi , Horiuchi Yasue , Kado Nobuhiro , Hirashima Yasuyuki , Shiomi Akio , Oishi Takuma , Ohnami Sumiko , Ohshima Keiichi , Urakami Kenichi , Nagashima Takeshi , Yamaguchi Ken 
Published: October 2020

Abstract

Background:
Tumor mutation burden (TMB) is the total exonic mutation count per megabase of tumor DNA. Recent advances in precision medicine occasionally detect Lynch syndrome (LS) by germline sequencing for mismatch-repair (g.MMR) genes but not using TMB. The current study analyzes the utility of TMB in detecting LS.

Methods:
Whole-exome sequencing (ion-semiconductor sequencing) was performed for somatic and germline DNA from 2,501 various cancer patients to detect TMB and g.MMR sequencing. MMR IHC was conducted when high TMB (≥10) was detected in LS-related cancers with an additional condition of wild-type BRAF in colorectal cancers. Target sequencing and multiplex ligation-dependent probe amplification (MLPA) were further performed for g.MMR genes in MMR-deficient cancers (TMB-based g.MMR target sequencing). We compared universal sequencing and TMB-based target sequencing in their sensitivity for detecting LS.

Results:
LS was detected in 16 (0.6%) of the 2,501 patients: 1.1% (9/826) of colorectal cancer patients, 16.2% (6/37) of endometrial cancer patients, and 14.3% (1/7) of small intestine cancer patients. TMB-based g.MMR target sequencing (81.3%) showed superior sensitivity for detecting LS than universal g.MMR sequencing (56.3%; P = 0.127) but missed 3 LS patients (1 with a low-TMB cancer, 1 with a BRAF-mutant colorectal cancer, and 1 with an MMR-proficient cancer). Ion-semiconductor sequencing could detect single-nucleotide substitutions but not large deletions. POL-mutated cancers showed extremely high TMBs (48.4–749.2).

Conclusions:
g.MMR target sequencing, combined with TMB, somatic BRAF mutation, and MMR IHC is an effective strategy for detecting LS.

Impact:
TMB can be a biomarker for detecting LS in precision medicine.
Combinations with Allosteric SHP2 Inhibitor TNO155 to Block Receptor Tyrosine Kinase Signaling
Authors: Liu Chen , Lu Hengyu , Wang Hongyun , Loo Alice , Zhang Xiamei , Yang Guizhi , Kowal Colleen , Delach Scott , Wang Ye , Goldoni Silvia , Hastings William D. , Wong Karrie , Gao Hui , Meyer Matthew J. , Moody Susan E. , LaMarche Matthew J. , Engelman Jeffrey A. , Williams Juliet A. , Hammerman Peter S. , Abrams Tinya J. , Mohseni Morvarid , Caponigro Giordano , Hao Huai-Xiang 
Published: October 2020

Abstract

Purpose:
SHP2 inhibitors offer an appealing and novel approach to inhibit receptor tyrosine kinase (RTK) signaling, which is the oncogenic driver in many tumors or is frequently feedback activated in response to targeted therapies including RTK inhibitors and MAPK inhibitors. We seek to evaluate the efficacy and synergistic mechanisms of combinations with a novel SHP2 inhibitor, TNO155, to inform their clinical development.

Experimental Design:
The combinations of TNO155 with EGFR inhibitors (EGFRi), BRAFi, KRASG12Ci, CDK4/6i, and anti–programmed cell death-1 (PD-1) antibody were tested in appropriate cancer models in vitro and in vivo, and their effects on downstream signaling were examined.

Results:
In EGFR-mutant lung cancer models, combination benefit of TNO155 and the EGFRi nazartinib was observed, coincident with sustained ERK inhibition. In BRAFV600E colorectal cancer models, TNO155 synergized with BRAF plus MEK inhibitors by blocking ERK feedback activation by different RTKs. In KRASG12C cancer cells, TNO155 effectively blocked the feedback activation of wild-type KRAS or other RAS isoforms induced by KRASG12Ci and greatly enhanced efficacy. In addition, TNO155 and the CDK4/6 inhibitor ribociclib showed combination benefit in a large panel of lung and colorectal cancer patient–derived xenografts, including those with KRAS mutations. Finally, TNO155 effectively inhibited RAS activation by colony-stimulating factor 1 receptor, which is critical for the maturation of immunosuppressive tumor-associated macrophages, and showed combination activity with anti–PD-1 antibody.

Conclusions:
Our findings suggest TNO155 is an effective agent for blocking both tumor-promoting and immune-suppressive RTK signaling in RTK- and MAPK-driven cancers and their tumor microenvironment. Our data provide the rationale for evaluating these combinations clinically.