bluuebunny/crossref_metadata_2025_split huggingface dataset:
Progressive resistance training compared to neuromuscular exercise in patients with hip osteoarthritis and the additive effect of exercise booster sessions: protocol for a multicentre cluster randomised controlled trial (The Hip Booster Trial)
Authors: Kjeldsen Troels , Dalgas Ulrik , Skou Søren T , van Tulder Maurits , Bibby Bo M , Mechlenburg Inger 
Published: September 2022

IntroductionThe primary aim of this randomised controlled trial is to investigate the effectiveness of 3 months of progressive resistance training (PRT) compared to neuromuscular exercise (NEMEX) on functional performance in patients with hip osteoarthritis (OA). Secondary aims are to investigate the effectiveness of exercise booster sessions (EBS) in prolonging the effects of the initial exercise interventions as well as to investigate the cost-effectiveness of PRT, NEMEX and EBS at 12-month follow-up.Methods and analysisThis multicentre cluster randomised controlled trial will be conducted at hospitals and physiotherapy clinics across Denmark. A total of 160 participants with clinically diagnosed hip OA will be recruited. Participants will be cluster randomised to a 3-month intervention of either PRT or NEMEX and to receive EBS or not, resulting in four treatment arms.The primary outcome is change in functional performance, measured by the 30 s chair stand test at 3 months for the primary comparison and at 12 months for the EBS comparisons. Secondary outcomes include changes in 40 m fast-paced walk test, 9-step timed stair climb test, leg extensor muscle power and maximal strength, Hip disability and Osteoarthritis Outcome Score subscales, EuroQol Group 5-dimension, global perceived effect, physical activity and pain. Outcomes are measured at baseline, after the initial 3 months of intervention, and at 6-month, 9-month and 12-month follow-up. An intention-to-treat approach will be used for analysing changes in the primary and secondary outcome measures.Ethics and disseminationThe trial has been approved by the Central Denmark Region Committee on Biomedical Research Ethics (Journal No 1-10-72-267-20) and registered at the Danish Data Protection Agency (Journal No 1-16-02-11-21). Results will be published in international peer-reviewed scientific journals.Trial registration numberNCT04714047.
Conditions associated with the initiation of domiciliary care following a hospital admission: a cohort study in East London, England
Authors: Grimm Fiona , Lewer Dan , Craig John , Rogans-Watson Rafi , Shand Jenny 
Published: September 2022

ObjectiveOlder people and people with complex needs often require both health and social care services, but there is limited insight into individual journeys across these services. To help inform joint health and social care planning, we aimed to assess the relationship between hospital admissions and domiciliary care receipt.DesignRetrospective cohort study, using linked data on primary care activity, hospital admissions and social care records.SettingLondon Borough of Barking and Dagenham, England.ParticipantsAdults aged 19 and over who lived in the area on 1 April 2018 and who were registered at a general practice in East London between 1 April 2018 and 31 March 2020 (n=140 987).Outcome measuresThe outcome was initiation of domiciliary care. We estimated the rate of hospital-associated care package initiation, and of care packages unrelated to hospital admission. We also described the characteristics of hospital admissions that preceded domiciliary care, including primary diagnosis codes.Results2041/140 987 (1.4%) participants had a domiciliary care package during a median follow-up of 1.87 years. 32.6% of packages were initiated during a hospital stay or within 7 days of discharge. The rate of new domiciliary care packages was 120 times greater (95% CI 110 to 130) during or after a hospital stay than at other times, and this association was present for all age groups. Primary admission reasons accounting for the largest number of domiciliary care packages were hip fracture, pneumonia, stroke, urinary tract infection, septicaemia and exacerbations of long-term conditions (chronic obstructive pulmonary disease and heart failure). Admission reasons with the greatest likelihood of a subsequent domiciliary care package were fractures and strokes.ConclusionHospitals are a major referral route into domiciliary care. While patients admitted due to new and acute illnesses account for many domiciliary care packages, exacerbations of long-term conditions and age-related and frailty-related conditions are also important drivers.
Impact of spiritual healing on moderate depression in adults: a study protocol of a pilot randomised controlled trial (RCT)
Authors: Stub Trine , Irgens Audun Campell , Hansen Anne Helen , Knudsen-Baas Olav , Gåskjenn Cornelia , Kristoffersen Agnete E 
Published: September 2022

IntroductionDepression is a common mental disorder and the (global) leading cause of all non-fatal burden of disease worldwide. Currently, supported treatment for depression is antidepressant medication and different psychotherapeutic interventions. Many patients experience, however, adverse effects of antidepressant medication, while at the same time the access to psychotherapeutic interventions are limited. Many patients who suffer from depression turn to complementary medicine and among those modalities often spiritual healing. There is some evidence that consulting a spiritual healer can be beneficial for patients who suffer from depression, and that spiritual healing is associated with low risk. The aim of this protocol is to conduct a pilot randomised controlled trial (RCT) (spiritual healing as addition to usual care vs usual care alone) in preparation of a larger trial in adults with moderate depression, to examine feasibility and individuals’ experience of spiritual healing.Methods and analysisThis study is a pilot RCT with two parallel groups. A total of 28 adult patients with moderate depression, diagnosed by the physician and according to the Montgomery and Åsberg Depression Rating Scale criteria will be randomised to spiritual healing in addition to usual care (n=14) or usual care alone (n=14). To determine if there is a statistical indication of an effect of healing warranting a full-scale study; the separation test will be used. To investigate participants’ experience with spiritual healing, a qualitative study will be included using semistructured interviews. The data will be analysed based on a direct content analysis.Ethics and disseminationThis protocol was approved by regional committees for medical and health research ethics by the identifier (63692). The results will be disseminated through open-access, peer-reviewed publications, in addition to stakeholders’ reporting and presenting at conferences.Trial registrationNorwegian Centre for Research Data (845302) and clinicaltrials.gov (ID: NCT04766242)
GATA4 and GATA6 loss-of-expression is associated with extinction of the classical programme and poor outcome in pancreatic ductal adenocarcinoma
Authors: de Andrés Mónica P , Jackson Richard J , Felipe Irene , Zagorac Sladjana , Pilarsky Christian , Schlitter Anna Melissa , Martinez de Villareal Jaime , Jang Gun Ho , Costello Eithne , Gallinger Steve , Ghaneh Paula , Greenhalf William , Knösel Thomas , Palmer Daniel H , Ruemmele Petra , Weichert Wilko , Buechler Markus , Hackert Thilo , Neoptolemos John P , Notta Faiyaz , Malats Núria , Martinelli Paola , Real Francisco X 
Published: September 2022

ObjectiveGATA6 is a key regulator of the classical phenotype in pancreatic ductal adenocarcinoma (PDAC). Low GATA6 expression associates with poor patient outcome.GATA4is the second most expressed GATA factor in the pancreas. We assessed whether, and how, GATA4 contributes to PDAC phenotype and analysed the association of expression with outcome and response to chemotherapy.DesignWe analysed PDAC transcriptomic data, stratifying cases according toGATA4andGATA6expression and identified differentially expressed genes and pathways. The genome-wide distribution of GATA4 was assessed, as well as the effects ofGATA4knockdown. A multicentre tissue microarray study to assess GATA4 and GATA6 expression in samples (n=745) from patients with resectable was performed. GATA4 and GATA6 levels were dichotomised into high/low categorical variables; association with outcome was assessed using univariable and multivariable Cox regression models.ResultsGATA4messenger RNA is enriched in classical, compared with basal-like tumours. We classified samples in 4 groups as high/low forGATA4andGATA6. Reduced expression ofGATA4had a minor transcriptional impact but low expression ofGATA4enhanced the effects ofGATA6low expression. GATA4 and GATA6 display a partially overlapping genome-wide distribution, mainly at promoters. Reduced expression of both proteins in tumours was associated with the worst patient survival.GATA4andGATA6expression significantly decreased in metastases and negatively correlated with basal markers.ConclusionsGATA4andGATA6cooperate to maintain the classical phenotype. Our findings provide compelling rationale to assess their expression as biomarkers of poor prognosis and therapeutic response.
Unitarity problems for an effective field theory description of early universe cosmology
Authors: Brandenberger Robert , Kamali Vahid 
Published: September 2022

AbstractIn the context of Effective Field Theory, the Hilbert space of states increases in an expanding universe. Hence, the time evolution cannot be unitary. The formation of structure is usually studied using effective field theory techniques. We study the constraints on effective field theory analyses of early universe models which come from demanding that the factor of the space of states corresponding to length scales where the primordial fluctuations are manifest does not suffer from the unitarity problem. For bouncing and emergent cosmologies, no constraints arise provided that the energy scale of the bounce or emergent phases is smaller than the ultraviolet (UV) cutoff scale. On the other hand, in the case of the inflationary scenario, non-trivial upper bounds on the energy scale of inflation arise.
Bioinformatic Data Mining for Candidate Drugs Affecting Risk of Bisphosphonate-Related Osteonecrosis of the Jaw (BRONJ) in Cancer Patients
Authors: Zhuang Jinpeng , Zu Jianing , Zhou Changlong , Sun Yi , Kong Pengyu , Jing Yongbin 
Published: September 2022

Background. Bisphosphonate-related osteonecrosis of the jaw (BRONJ) leads to significant morbidity. Other coadministered drugs may modulate the risk for BRONJ. The present study aimed to leverage bioinformatic data mining to identify drugs that potentially modulate the risk of BRONJ in cancer. Methods. A GEO gene expression dataset of peripheral blood mononuclear cells related to BRONJ in multiple myeloma patients was downloaded, and differentially expressed genes (DEGs) in patients with BRONJ versus those without BRONJ were identified. A protein-protein interaction network of the DEGs was constructed using experimentally validated interactions in the STRING database. Overrepresented Gene Ontology (GO) molecular function terms and KEGG pathways in the network were analysed. Network topology was determined, and ‘hub genes’ with degree ≥2 in the network were identified. Known drug targets of the hub genes were mined from the ‘drug gene interaction database’ (DGIdb) and labelled as candidate drugs affecting the risk of BRONJ. Results. 751 annotated DEGs (

log

FC
≥
1.5

,

p
<
0.05

) were obtained from the microarray gene expression dataset GSE7116. A PPI network with 633 nodes and 168 edges was constructed. Data mining for drugs interacting with 49 gene nodes was performed. 37 drug interactions were found for 9 of the hub genes including TBP, TAF1, PPP2CA, PRPF31, CASP8, UQCRB, ACTR2, CFLAR, and FAS. Interactions were found for several established and novel anticancer chemotherapeutic, kinase inhibitor, caspase inhibitor, antiangiogenic, and immunomodulatory agents. Aspirin, metformin, atrovastatin, thrombin, androgen and antiandrogen drugs, progesterone, Vitamin D, and Ginsengoside 20(S)-Protopanaxadiol were also documented. Conclusions. A bioinformatic data mining strategy identified several anticancer, immunomodulator, and other candidate drugs that may affect the risk of BRONJ in cancer patients.
Sugar- and Artificially-Sweetened Beverages and Cancer Mortality in a Large U.S. Prospective Cohort
Authors: McCullough Marjorie L. , Hodge Rebecca A. , Campbell Peter T. , Guinter Mark A. , Patel Alpa V. 
Published: September 2022

Abstract

Background:
Sugar-sweetened beverage (SSB) consumption may be associated with cancer mortality independent of, or indirectly through, established influences on increased body adiposity.

Methods:
We examined the associations of SSBs and artificially-sweetened beverages (ASB) with mortality from all-cancers combined, obesity-related cancers combined, and 20 cancer types, among men and women in the Cancer Prevention Study-II (CPS-II) prospective cohort. In 1982, 934,777 cancer-free participants provided information on usual SSB and ASB consumption. Deaths were identified through 2016. Multivariable Cox proportional hazards regression models examined associations of beverage types with cancer mortality, without and with BMI adjustment.

Results:
During follow-up, 135,093 CPS-II participants died from cancer. Consumption of ≥2 SSB drinks/day vs. never was not associated with all-cancer mortality, but was associated with increased risk of obesity-related cancers [HR, 1.05; 95% confidence intervals (CI), 1.01–1.08; Ptrend = 0.057], which became null after adjustment for BMI. SSBs were associated with increased mortality from colorectal (HR, 1.09; 95% CI, 1.02–1.17; Ptrend = 0.011), and kidney (HR, 1.17; 95% CI, 1.03–1.34; Ptrend = 0.056) cancers, which remained after BMI adjustment. A positive association of ASB consumption with obesity-related cancers (HR, 1.05; 95% CI, 1.01–1.08; Ptrend = 0.001) was null after controlling for BMI; however, an increased risk of pancreatic cancer was robust to BMI adjustment (HR, 1.11; 95% CI, 1.02–1.20; Ptrend &lt; 0.008).

Conclusions:
SSB consumption was associated with higher mortality from certain cancers, partially mediated through obesity. Associations of ASB consumption and increased pancreatic cancer risk merit further study.

Impact:
Future research should consider the role of BMI in studies of sweetened beverages and cancer risk. These results should inform policy regarding sweetened beverage consumption.
Abstract B004: ATR-CHK1-WEE1 pathway is a critical dependency in the context of DNA damage and replicative stress in osteosarcoma
Authors: Sayles Leanne C. , Martell Henry , Koehne Amanda , Ang Kean-Hooi , Wilson Chris , Arkin Michelle , Sweet-Cordero E. Alejandro 
Published: September 2022

Abstract
Osteosarcoma (OS) is characterized by widespread somatic copy number alterations (SCNAs) and structural variations (SVs) with few recurrent point mutations. We previously demonstrated proof-of-principle for a genome-informed strategy for treatment of OS based on rank-ordering SCNAs within specific oncogenes identified by WGS and RNAseq. Although we identified several potentially effective therapeutic strategies using this approach, it is likely that effective therapy for OS will require use of combination therapies. To identify new combination therapy approaches for OS, we used a panel of PDX-derived cell lines (PDXC) and performed a combination drug screen. We assessed 5 drug backbones against 15 targeted agents in 8 PDXC and 2 established OS cell lines. When we combined Gemcitabine with agents that target the ATR-CHK1-WEE1 pathway, we observed strong synergy across all PDXC tested. These results were validated in a secondary screen using a combination matrix across 10 PDXC. Use of targeted agents inhibiting ATR, CHK1 or WEE1 in combination with Gemcitabine led to decreased proliferation and a marked increase in apoptosis in vitro. In subcutaneous tumor models, we observed that decreased tumor growth with either ATRi or Gemcitabine alone, whereas tumors shrank when treated with the combination. However, when we treated OS774 in vivo, there was no effect on tumor growth for either single agent alone or when in combination. This effect was dependent on the presence of ATR as a PDXC with no ATR detectable by western blotting showed not effect in vivo. In an orthotopic model in which PDXC are implanted along the tibia, this combination therapy effectively decreased tumor growth. In a lung metastasis model, ATRi and Gemcitabine resulted a durable reduction in metastatic lesions over time. In summary, we have identified a susceptibility to the ATR-CHK1-WEE1 pathway when combined with gemcitabine. These studies suggest that further investigation ATR-CHK1-WEE1 and gemcitabine are warranted to address the unmet need for new therapeutic approaches for relapsed and recurrent OS patients.
Citation Format: Leanne C. Sayles, Henry Martell, Amanda Koehne, Kean-Hooi Ang, Chris Wilson, Michelle Arkin, E. Alejandro Sweet-Cordero. ATR-CHK1-WEE1 pathway is a critical dependency in the context of DNA damage and replicative stress in osteosarcoma [abstract]. In: Proceedings of the AACR Special Conference: Sarcomas; 2022 May 9-12; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2022;28(18_Suppl):Abstract nr B004.
Strain self-sensing capability of a tidal turbine blade fabricated of PU-foam/glass fiber/epoxy composites using MWCNTs
Authors: Rubio-González Carlos , José-Trujillo Eduardo , Alejandro Rodríguez-González Julio , Espinoza-Hernández Jaime , Manzo-Preciado José Alfredo 
Published: September 2022

A novel marine composite structure (experimental tidal turbine blade) made up of a polyurethane (PU) foam/glass fiber/epoxy resin composite with multiwall carbon nanotubes (MWCNTs) is proposed herein to self-sense its strain under a structural test scenario. To achieve this, MWCNTs were deposited onto glass fiber fabric by spray-coating technique in order to form an effective electrical percolation network onto the external skin surface of the tidal turbine blade which enables piezoresistive capability. After MWCNT deposition, the blade was manufactured by means of one-shot resin transfer molding (RTM) in a closed and heated metallic mold specially designed with a blade geometry of 67 cm length. The results confirm that the spray coating technique is a viable method to deposit MWCNTs onto glass fiber surface and form electrical networks into the blade at a relatively low MWCNT concentration. Finite element analysis (FEA) predicted a suitable structural blade design with a maximum failure index value of 0.9 attained in the blade shear web. The measured longitudinal strains of the tidal turbine blade were in good agreement with the numerical strain values predicted with FEA. Electromechanical tests carried out on a structural test rig designed and instrumented for tidal turbine blades showed that the electrical resistance change response of carbon nanotube (CNT) network integrated into the blade was capable of following the mechanical curve response up to the blade limit load, confirming its ability to self-sense its strain in real time.
Down Syndrome Detection Through Graphical Analysis of Facial Dysmorphic Features in Newborn Children With Ethnicity/Racial Slicing: An AI/ML-Based Approach
Authors: Mehra Saanvi , Shah Binoy , Sethi Ankur , Puri Ratna , Nimbalkar Somashekhar 
Published: September 2022

Background Down syndrome (DS) is associated with high mortality in India, due to nondiagnosis/late-diagnosis caused by unavailability of qualified doctors and/or lack of access to expensive medical/diagnostic facilities, especially in rural India. Using artificial intelligence/machine learning graphical pattern recognition tools, relevant facial points can be extracted from children’s photographs, facial anomalies can be identified, and probability of DS affliction can be predicted. Methods: Trained Google’s Cloud Vision AutoML Image Classification model was employed with ~2,000 photographs of DS positive children and ~3,000 photographs of DS negative children. A subset of 300 images, 100 each of Asian, Caucasian, and Other-Race children, was used to train and test 3 race-specific models. These results were compared against a unified model trained and tested with same 300 images. Results: The CloudML model trained with ~5,000 images initially achieved: Sensitivity—94.6%, specificity—96.9%, and accuracy—96.0%. Upon optimizing confidence threshold to 0.1, model maximized sensitivity at 99.6%, specificity dropped to 93.8%, and accuracy maintained at 96.0%. Each of the race-specific models trained with 100 images each, after optimization, yielded perfect scores on sensitivity, specificity, and accuracy of 100% each. Against this, the unified model with 300 images yielded overall accuracy of 98% (100% sensitivity, 83% specificity for Caucasian children, and 100% sensitivity, 100% specificity for Asian/Other children). Conclusions: Post optimization, this model can be used as an effective postnatal screening tool for DS detection. Preliminary results indicate that race-specific models can achieve even higher accuracy, sensitivity, and specificity.
An Improved Nomogram to Reduce False-Positive Biopsy Rates of Breast Imaging Reporting and Data System Ultrasonography Category 4A Lesions
Authors: Hai Linyue , Feng Youqin , Zhao Jingjing , Tang Qiang , Wang Xuefei , Cao Xuchen , Xiao Chunhua 
Published: September 2022

Background: The NCCN clinical guidelines recommended core needle biopsy for breast lesions classified as Breast Imaging Reporting and Data System (BI-RADS) 4, while category 4A lesions are only 2-10% likely to be malignant. Thus, a large number of biopsies of BI-RADS 4A lesions were ultimately determined to be benign, and those unnecessary biopsies may incur additional costs and pains. However, it is important to emphasize that the current risk prediction model focuses primarily on the details and complex risk features of US or MG findings, which may be difficult to apply in order to benefit from the model. To stratify and manage BI-RADS 4A lesions effectively and efficiently, a more effective and practical predictive model must be developed. Methods: We retrospectively analyzed 465 patients with BI-RADS ultrasonography (US) category 4A lesions, diagnosed between January 2019 and July 2019 in Tianjin Medical University Cancer Institute and Hospital and National Clinical Research Center for Cancer. Univariate and multivariate logistic regression analyses were conducted to identify risk factors. To stratify and predict the malignancy of BI-RADS 4A lesions, a nomogram combining the risk factors was constructed based on the multivariate logistic regression results. In order to determine the predictive performance of our predictive model, we used the concordance index (C-index), calibration curve, and receiver operating characteristic (ROC), and the decision curve analysis (DCA) to assess the clinical benefits. Results: Based on our analysis, 16.3% (76 out of 465) of patients were pathologically diagnosed with malignant lesions, while 83.6% (389 out of 465) were diagnosed with benign lesions. According to univariate and multivariate logistic regression analysis, age (OR = 3.414, 95%CI:1.849-6.303), nipple discharge (OR = .326, 95%CI:0.157-.835), palpable lesions (OR = 1.907, 95%CI:1.004-3.621), uncircumscribed margin (US) (OR = 1.732, 95%CI:1.033-2.905), calcification (mammography, MG) (OR = 2.384, 95%CI:1.366-4.161), BI-RADS(MG) (OR = 5.345, 95%CI:2.934-9.736) were incorporated into the predictive nomogram (C-index = .773). There was good agreement between the predicted risk and the observed probability of recurrence. Furthermore, we determined that 153 was the best cutoff score for distinguishing between patients in the low- and high-risk groups. Malignant lesions were significantly more prevalent in high-risk patients than in low-risk patients. Conclusion: Based on clinical, US, and MG features, we present a predictive nomogram to reliably predict the malignancy risk of BI-RADS(US) 4A lesions, which may assist clinicians in the selection of patients at low risk of malignancy and reduce the number of false-positive biopsies.