bluuebunny/crossref_metadata_2025_split huggingface dataset:
Performance Sensitivity Analysis of Natural Mineral Silicates Filled Friction Composites Using GD-ANN Approach
Authors: Saha Debarghya , Satapathy Bhabani K. 
Published: August 2022

Abstract
Structurally dissimilar clay type silicate (tubular halloysite, platy montmorillonite, and acicular wollastonite) reinforced compression molded composites were fabricated with and without MgO. The thermo-mechanical and frictional performances of natural silicate-based friction materials were systematically evaluated with respect to the silicate and silicate-MgO free composites. The morphology and hardness of the natural silicates dominated the mechanical and tribological responses of the friction materials. The worn surface morphology revealed the influence of natural silicate on braking dynamics as evident from performance sensitivity analysis, braking load, sliding speed, and temperature. The nature of sliding induced tribo-layers was ascertained from elemental mapping by EDX and Raman spectroscopy indicating the friction composition of tribo-layer to be influencing performance sensitivity. Under the variable operating conditions, halloysite-based friction materials showed excellent wear resistance, and wollastonite-based friction composites with MgO enhanced the friction coefficient (∼0.43–0.61) while exhibiting minimum load-speed sensitivity. The gradient descent learning algorithm-based artificial neural network (GD-ANN) with optimally tuned network architecture predicted (R2 ∼ 97%) both the tribological performance attributes (coefficient of friction and specific wear-rate) of the natural silicate-filled friction composites more accurately as compared to the conventional regression analysis.
Free Vibration of Timoshenko–Ehrenfest Beams and Frameworks Using Frequency-Dependent Mass and Stiffness Matrices
Authors: Banerjee J. R. 
Published: August 2022

Abstract
The frequency-dependent mass and stiffness matrices of a Timoshenko–Ehrenfest beam are developed through extensive application of symbolic computation. Explicit algebraic expressions for the frequency dependent shape functions and each of the independent elements of the frequency-dependent mass and stiffness matrices are presented concisely. The ensuing frequency-dependent mass and stiffness matrices of the Timoshenko–Ehrenfest beam are applied with particular reference to the Wittrick–Williams algorithm to investigate the free vibration characteristics of an individual Timoshenko–Ehrenfest beam and a framework. The results are discussed with significant conclusions drawn. The proposed method retains the exactness of results like the dynamic stiffness method, but importantly, it opens the possibility of including damping in the analysis.
Qualitative study exploring lessons from Liberia and the UK for building a people-centred resilient health systems response to COVID-19
Authors: McCollum Rosalind , Zaizay Zeela , Dean Laura , Watson Victoria , Frith Lucy , Alhassan Yussif , Kollie Karsor , Piotrowski Helen , Bates Imelda , Anderson de Cuevas Rachel , Harris Rebecca , Chowdhury Shahreen , Berrian Hannah , Smith John Solunta , Tate Wede Seekey , El Hajj Taghreed , Ozano Kim , Hastie Olivia , Parker Colleen , Kollie Jerry , Zawolo Georgina , Ding Yan , Dacombe Russell , Taegtmeyer Miriam , Theobald Sally 
Published: August 2022

IntroductionCOVID-19 has tested the resilience of health systems globally and exposed existing strengths and weaknesses. We sought to understand health systems COVID-19 adaptations and decision making in Liberia and Merseyside, UK.MethodsWe used a people-centred approach to carry out qualitative interviews with 24 health decision-makers at national and county level in Liberia and 42 actors at county and hospital level in the UK (Merseyside). We explored health systems’ decision-making processes and capacity to adapt and continue essential service delivery in response to COVID-19 in both contexts.ResultsStudy respondents in Liberia and Merseyside had similar experiences in responding to COVID-19, despite significant differences in health systems context, and there is an opportunity for multidirectional learning between the global south and north. The need for early preparedness; strong community engagement; clear communication within the health system and health service delivery adaptations for essential health services emerged strongly in both settings. We found the Foreign, Commonwealth and Development Office (FCDO) principles to have value as a framework for reviewing health systems changes, across settings, in response to a shock such as a pandemic. In addition to the eight original principles, we expanded to include two additional principles: (1) the need for functional structures and mechanisms for preparation and (2) adaptable governance and leadership structures to facilitate timely decision making and response coordination. We find the use of a people-centred approach also has value to prompt policy-makers to consider the acceptance of service adaptations by patients and health workers, and to continue the provision of ‘routine services’ for individuals during health systems shocks.ConclusionOur study highlights the importance of a people-centred approach, placing the person at the centre of the health system, and value in applying and adapting the FCDO principles across diverse settings.
COMPrehensive geriatric AsseSSment and multidisciplinary team intervention for hospitalised older adults (COMPASS): a protocol of pragmatic trials within a cohort
Authors: Choi Jung-Yeon , Lee Ji Yeon , Shin Jaeyong , Kim Chang Oh , Kim Kwang Joon , Hwang In Gyu , Lee Yun-Gyoo , Koh Su-Jin , Hong Soojung , Yoon Sol-Ji , Kang Min-gu , Kim Jin Won , Kim Jee Hyun , Kim Kwang-il 
Published: August 2022

IntroductionThere is an increased demand for services for hospitalised older patients with acute medical conditions due to rapidly ageing population. The COMPrehensive geriatric AsseSSment and multidisciplinary team intervention for hospitalised older adults (COMPASS) study will test the effectiveness of comprehensive geriatric assessment (CGA) and multidisciplinary intervention by comparing it with conventional care among acute hospitalised older adults in Korea.Methods and analysisA multicentre trial within a cohort comprising three substudies (randomised controlled trials) will be conducted. The intervention includes CGA and CGA-based multidisciplinary interventions by physicians (geriatricians, oncologists), nurses, nutritionists and pharmacists. The multidisciplinary intervention includes nutritional support, medication review and adjustment, rehabilitation, early discharge planning and prevention of geriatric syndromes (falls, delirium, pressure sore and urinary retention). The analysis will be based on an intention-to-treat principle. The primary outcome is living at home 3 months after discharge. In addition to assessing the economic effects of the intervention, a cost-utility analysis will be conducted.Ethics and disseminationThe study protocol was reviewed and approved by the ethics committees of Seoul National University Bundang Hospital and each study site. The study findings will be published in peer-reviewed journals. Subgroup and further in-depth analyses will subsequently be published.Trial registration numberKCT0006270.
Indirect effect of the COVID-19 pandemic on hospital mortality in patients with hip fracture: a competing risk survival analysis using linked administrative data
Authors: Grimm Fiona , Johansen Antony , Knight Hannah , Brine Richard , Deeny Sarah R 
Published: August 2022

BackgroundHip fracture is a leading cause of disability and mortality among older people. During the COVID-19 pandemic, orthopaedic care pathways in the National Health Service in England were restructured to manage pressures on hospital capacity. We examined the indirect consequences of the pandemic for hospital mortality among older patients with hip fracture, admitted from care homes or the community.MethodsRetrospective analysis of linked care home and hospital inpatient data for patients with hip fracture aged 65 years and over admitted to hospitals in England during the first year of the pandemic (1 March 2020 to 28 February 2021) or during the previous year. We performed survival analysis, adjusting for case mix and COVID-19 infection, and considered live discharge as a competing risk. We present cause-specific hazard ratios (HRCS) for the effect of admission year on hospital mortality risk.ResultsDuring the first year of the pandemic, there were 55 648 hip fracture admissions: a 5.2% decrease on the previous year. 9.5% of patients had confirmed or suspected COVID-19. Hospital stays were substantially shorter (p<0.05), and there was a higher daily chance of discharge (HRCS1.40, 95% CI 1.38 to 1.41). Overall hip fracture inpatient mortality increased (7.2% in 2020/2021 vs 6.4% in 2019/2020), but patients without concomitant COVID-19 infection had lower mortality rates compared with the year before (5.3%). Admission during the pandemic was associated with a 11% increase in the daily risk of hospital death for patients with hip fracture (HRCS1.11, 95% CI 1.05 to 1.16).ConclusionsAlthough COVID-19 infections led to increases in hospital mortality, overall hospital mortality risk for older patients with hip fracture remained largely stable during the first year of the pandemic.
Impact of pharmacist interventions provided in the emergency department on quality use of medicines: a systematic review and meta-analysis
Authors: Atey Tesfay Mehari , Peterson Gregory M , Salahudeen Mohammed Saji , Bereznicki Luke R , Wimmer Barbara C 
Published: August 2022

BackgroundPharmacists have an increasing role as part of the emergency department (ED) team. However, the impact of ED-based pharmacy interventions on the quality use of medicines has not been well characterised.ObjectiveThis systematic review aimed to synthesise evidence from studies examining the impact of interventions provided by pharmacists on the quality use of medicines in adults presenting to ED.MethodsA systematic literature search was conducted in MEDLINE, EMBASE and CINAHL. Two independent reviewers screened titles/abstracts and reviewed full texts. Studies that compared the impact of interventions provided by pharmacists with usual care in ED and reported medication-related primary outcomes were included. Cochrane Risk of Bias-2 and Newcastle-Ottawa tools were used to assess the risk of bias. Summary estimates were pooled using random-effects meta-analysis, along with sensitivity and sub-group analyses.ResultsThirty-one studies involving 13 242 participants were included. Pharmacists were predominantly involved in comprehensive medication review, advanced pharmacotherapy assessment, staff and patient education, identification of medication discrepancies and drug-related problems, medication prescribing and co-prescribing, and medication preparation and administration. The activities reduced the number of medication errors by a mean of 0.33 per patient (95% CI −0.42 to −0.23, I2=51%) and the proportion of patients with at least one error by 73% (risk ratio (RR)=0.27, 95% CI 0.19 to 0.40, I2=85.3%). The interventions were also associated with more complete and accurate medication histories, increased appropriateness of prescribed medications by 58% (RR=1.58, 95% CI 1.21 to 2.06, I2=95%) and quicker initiation of time-critical medications.ConclusionThe evidence indicates improved quality use of medicines when pharmacists are included in ED care teams.PROSPERO registration numberCRD42020165234.
Association between CORIN methylation and hypertension in Chinese adults
Authors: Shi Jijun , Wu Lei , Chen Yan , Zhang Mingzhi , Yu Jia , Ren Liyun , He Yan , Li Jing , Ma Shengqi , Hu Weidong , Peng Hao 
Published: August 2022

Abstract

Background
Corin, a physical activator of atrial natriuretic peptide, has been associated with hypertension with unclear mechanisms. Here, we aimed to examine whether CORIN gene methylation was involved in the underlying molecular mechanisms.

Methods
DNA methylation levels of CORIN were measured by target bisulfite sequencing using genomic DNA isolated from peripheral blood mononuclear cells in 2498 participants in the Gusu cohort (discovery sample) and 1771 independent participants (replication sample). We constructed a mediation model with DNA methylation as the predictor, serum corin as the mediator, and hypertension as the outcome, adjusting for covariates. Multiple testing was controlled by false discovery rate (FDR) approach.

Results
Of the 9 CpGs assayed, hypermethylation at all CpGs were significantly associated with a lower level of blood pressure in the discovery sample and eight associations were also significant in the replication sample (all FDR-adjusted p&lt;0.05). Serum corin mediated approximately 3.07% (p=0.004), 6.25% (p=0.002) and 10.11% (p=0.034) of the associations of hypermethylation at one CpG (Chr4:47840096) with systolic and diastolic blood pressure, and hypertension, respectively. All these mediations passed the causal inference test.

Conclusions
These results suggest that hypermethylation in the CORIN gene is associated with a lower odds of prevalent hypertension and may be involved in the role of corin in blood pressure regulation.
A Relational Program Logic with Data Abstraction and Dynamic Framing
Authors: Banerjee Anindya , Nagasamudram Ramana , Naumann David A. , Nikouei Mohammad 
Published: August 2022

Dedicated to Tony Hoare.
In a paper published in 1972, Hoare articulated the fundamental notions of hiding invariants and simulations. Hiding: invariants on encapsulated data representations need not be mentioned in specifications that comprise the API of a module. Simulation: correctness of a new data representation and implementation can be established by proving simulation between the old and new implementations using a coupling relation defined on the encapsulated state. These results were formalized semantically and for a simple model of state, though the paper claimed this could be extended to encompass dynamically allocated objects. In recent years, progress has been made toward formalizing the claim, for simulation, though mainly in semantic developments. In this article, hiding and simulation are combined with the idea in Hoare’s 1969 paper: a logic of programs. For an object-based language with dynamic allocation, we introduce a relational Hoare logic with stateful frame conditions that formalizes encapsulation, hiding of invariants, and couplings that relate two implementations. Relations and other assertions are expressed in first-order logic. Specifications can express a wide range of relational properties such as conditional equivalence and noninterference with declassification. The proof rules facilitate relational reasoning by means of convenient alignments and are shown sound with respect to a conventional operational semantics. A derived proof rule for equivalence of linked programs directly embodies representation independence. Applicability to representative examples is demonstrated using an SMT-based implementation.
Targeting RAS Mutant Colorectal Cancer with Dual Inhibition of MEK and CDK4/6
Authors: Sorokin Alexey V. , Kanikarla Marie Preeti , Bitner Lea , Syed Muddassir , Woods Melanie , Manyam Ganiraju , Kwong Lawrence N. , Johnson Benny , Morris Van K. , Jones Philip , Menter David G. , Lee Michael S. , Kopetz Scott 
Published: August 2022

Abstract

KRAS and NRAS mutations occur in 45% of colorectal cancers, with combined MAPK pathway and CDK4/6 inhibition identified as a potential therapeutic strategy. In the current study, this combinatorial treatment approach was evaluated in a co-clinical trial in patient-derived xenografts (PDX), and safety was established in a clinical trial of binimetinib and palbociclib in patients with metastatic colorectal cancer with RAS mutations. Across 18 PDX models undergoing dual inhibition of MEK and CDK4/6, 60% of tumors regressed, meeting the co-clinical trial primary endpoint. Prolonged duration of response occurred predominantly in TP53 wild-type models. Clinical evaluation of binimetinib and palbociclib in a safety lead-in confirmed safety and provided preliminary evidence of activity. Prolonged treatment in PDX models resulted in feedback activation of receptor tyrosine kinases and acquired resistance, which was reversed with a SHP2 inhibitor. These results highlight the clinical potential of this combination in colorectal cancer, along with the utility of PDX-based co-clinical trial platforms for drug development.

Significance:
This co-clinical trial of combined MEK-CDK4/6 inhibition in RAS mutant colorectal cancer demonstrates therapeutic efficacy in patient-derived xenografts and safety in patients, identifies biomarkers of response, and uncovers targetable mechanisms of resistance.
MRI-Based Digital Models Forecast Patient-Specific Treatment Responses to Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer
Authors: Wu Chengyue , Jarrett Angela M. , Zhou Zijian , Elshafeey Nabil , Adrada Beatriz E. , Candelaria Rosalind P. , Mohamed Rania M.M. , Boge Medine , Huo Lei , White Jason B. , Tripathy Debu , Valero Vicente , Litton Jennifer K. , Yam Clinton , Son Jong Bum , Ma Jingfei , Rauch Gaiane M. , Yankeelov Thomas E. 
Published: August 2022

Abstract

Triple-negative breast cancer (TNBC) is persistently refractory to therapy, and methods to improve targeting and evaluation of responses to therapy in this disease are needed. Here, we integrate quantitative MRI data with biologically based mathematical modeling to accurately predict the response of TNBC to neoadjuvant systemic therapy (NAST) on an individual basis. Specifically, 56 patients with TNBC enrolled in the ARTEMIS trial (NCT02276443) underwent standard-of-care doxorubicin/cyclophosphamide (A/C) and then paclitaxel for NAST, where dynamic contrast-enhanced MRI and diffusion-weighted MRI were acquired before treatment and after two and four cycles of A/C. A biologically based model was established to characterize tumor cell movement, proliferation, and treatment-induced cell death. Two evaluation frameworks were investigated using: (i) images acquired before and after two cycles of A/C for calibration and predicting tumor status after A/C, and (ii) images acquired before, after two cycles, and after four cycles of A/C for calibration and predicting response following NAST. For Framework 1, the concordance correlation coefficients between the predicted and measured patient-specific, post-A/C changes in tumor cellularity and volume were 0.95 and 0.94, respectively. For Framework 2, the biologically based model achieved an area under the receiver operator characteristic curve of 0.89 (sensitivity/specificity = 0.72/0.95) for differentiating pathological complete response (pCR) from non-pCR, which is statistically superior (P &lt; 0.05) to the value of 0.78 (sensitivity/specificity = 0.72/0.79) achieved by tumor volume measured after four cycles of A/C. Overall, this model successfully captured patient-specific, spatiotemporal dynamics of TNBC response to NAST, providing highly accurate predictions of NAST response.

Significance:
Integrating MRI data with biologically based mathematical modeling successfully predicts breast cancer response to chemotherapy, suggesting digital twins could facilitate a paradigm shift from simply assessing response to predicting and optimizing therapeutic efficacy.
Impact of a Multi-Level, Multi-Component, System Intervention on HPV Vaccination in a Federally Qualified Health Center
Authors: Glenn Beth A. , Nonzee Narissa J. , Herrmann Alison K. , Crespi Catherine M. , Haroutunian G. Greg , Sundin Phillip , Chang L. Cindy , Singhal Rita , Taylor Victoria M. , Bastani Roshan 
Published: August 2022

Abstract

Background:
Human papillomavirus (HPV) vaccines can significantly reduce the burden of HPV-associated cancers, but remain underutilized. We evaluated a multi-component, system-level intervention to improve HPV vaccination in a large Federally Qualified Health Center (FQHC) that serves a primarily low income Latino population.

Methods:
From January 2015 through March 2017, we evaluated the effectiveness of a multi-component, system-level intervention to improve HPV vaccination rates in eight clinics randomly assigned to study condition (four intervention, four usual care). The intervention included parent reminders for HPV vaccine series completion, provider training, clinic-level audit and feedback, and workflow modifications to reduce missed opportunities for vaccination. Using a difference-in-differences approach, we compared HPV vaccination rates among patients, ages 11 to 17 during a 12-month preintervention period and a 15-month intervention period. Linear mixed models were used to estimate intervention effects on vaccine initiation and completion.

Results:
The sample included approximately 15,000 adolescents each quarter (range 14,773–15,571; mean age 14 years; 51% female, 88% Latino). A significantly greater quarterly increase in HPV vaccine initiation was observed for intervention compared with usual care clinics (0.75 percentage point greater increase, P &lt; 0.001), corresponding to 114 additional adolescents vaccinated per quarter. The intervention led to a greater increase in HPV vaccine completion rates among boys (0.65 percentage point greater increase, P &lt; 0.001), but not girls.

Conclusions:
Our system-level intervention was associated with modest improvements in HPV vaccine initiation overall and completion among boys.

Impact:
Study findings have implications for reducing HPV-related cancers in safety net populations.
Loss of PTEN Expression, PIK3CA Mutations, and Breast Cancer Survival in the Nurses’ Health Studies
Authors: Wang Tengteng , Heng Yujing J. , Baker Gabrielle M. , Bret-Mounet Vanessa C. , Quintana Liza M. , Frueh Lisa , Hankinson Susan E. , Holmes Michelle D. , Chen Wendy Y. , Willett Walter C. , Rosner Bernard , Tamimi Rulla M. , Eliassen A. Heather 
Published: August 2022

Abstract

Background:
The relationships between PTEN loss and/or PIK3CA mutation and breast cancer prognosis remain controversial. We aim to examine the associations in large epidemiologic cohorts.

Methods:
We followed women with invasive breast cancer from the Nurses’ Health Studies with available data on tumor PTEN expression (n = 4,111) and PIK3CA mutation (n = 2,930). PTEN expression was evaluated by IHC and digitally scored (0%–100%). Pyrosequencing of six hotspot mutations of PIK3CA was performed.

Results:
We found loss of PTEN expression (≤10%) occurred in 17% of cases, and PIK3CA mutations were detected in 11% of cases. After adjusting for clinical and lifestyle factors, PTEN loss was not associated with worse breast cancer-specific mortality among all samples [HR, 0.85; 95% confidence intervals (CI), 0.71–1.03] or among estrogen receptor (ER)-positive tumors (HR, 0.99; 95% CI, 0.79–1.24). However, among ER-negative tumors, PTEN loss was associated with lower breast cancer-specific mortality (HR, 0.68; 95% CI, 0.48–0.95). PIK3CA mutation was not strongly associated with breast cancer-specific mortality (HR, 0.89; 95% CI, 0.67–1.17). Compared with tumors without PTEN loss and without PIK3CA mutation, those with alterations (n = 540) were not at higher risk (HR, 1.07; 95% CI, 0.86–1.34). However, women with both PTEN loss and PIK3CA mutation (n = 38) were at an increased risk of breast cancer-specific mortality (HR, 1.65; 95% CI, 0.83–3.26).

Conclusions:
In this large epidemiologic study, the PTEN-mortality association was more pronounced for ER-negative tumors, and the joint PTEN loss and PIK3CA mutation may be associated with worse prognosis.

Impact:
Further studies with a larger sample of ER-negative tumors are needed to replicate our findings and elucidate underlying mechanisms.