bluuebunny/crossref_metadata_2025_split huggingface dataset:
Types of lime binders in mortars used for the construction of the Ming Great Wall of China and their importance for the development of a conservation strategy
Authors: Dettmering Tanja , Dai Shibing 
Published: February 2022

AbstractThe most obvious characteristics of the Ming Great Wall are external masonry walls made of natural stones, bricks and lime mortars. According to the chemical and mineralogical compositions of the original bedding and pointing mortars, dolomitic lime binder was used dominantly in the construction of the Ming Great Wall in provinces such as those around Beijing and Hebei. Calcium-rich lime and air lime with low natural hydraulically reactive phases, which are hydrated and react slowly with the carbon dioxide in air to form calcium carbonate, were used in some western provinces. Chemical and microscopic investigations show that both dolomitic and calcium-rich lime mortars are almost aggregate-free. Historic dolomitic lime mortars are characterised by high strengths, low porosities and dense micro-scale textures. The most recent conservation principle is to preserve the Ming Great Wall as a ruin. Therefore, the conservation strategy should be redefined in terms of mortars. Since some of the damage to the Great Wall is related to reactions between dolomitic lime mortars and air pollutants, calcium-rich lime binders should be used for conservation and even for restoration of those parts of the Great Wall that were originally built with dolomitic lime. Binders based on natural hydraulic lime and calcium-rich lime gauged with natural pozzolana might be more compatible than other binders” for the structural consolidation of the ruins of the Great Wall.
Therapeutic use of serious games in mental health: scoping review
Authors: Dewhirst Alice , Laugharne Richard , Shankar Rohit 
Published: February 2022

BackgroundThere has been an increase in the development and application of serious games to support management of mental ill health, but their full impact is unclear.AimsEvaluation of the current evidence of acceptability and effectiveness of serious games in improving mental health disorders.MethodA PRISMA-guided scoping review was conducted, using a predefined criteria and a relevant word combination on three databases: EMBASE, Medline and PsycINFO. Each included study was examined for game format, study type, number of participants, basic demographics, disorder targeted, recruitment, setting, control conditions, duration and follow-up, study attrition, primary outcomes and their results. Each study was given a Grading of Recommendations, Assessment, Development and Evaluations rating for quality.ResultsFourteen out of 513 studies met the inclusion criteria. The serious games focused on symptoms of anxiety (n= 4), attention-deficit hyperactivity disorder (n= 3), depression (n= 2), schizophrenia (n= 2), alcohol use disorder (n= 2) and bipolar disorder (n= 1). There were multiple significant outcomes favouring serious games across conditions covered in the review. Study quality varied, with studies rated high (n= 3), moderate (n= 6), low (n= 3) and very low (n= 2).ConclusionsThe available evidence suggests that serious games could be an effective format for an intervention to reduce mental health symptoms and improve outcomes of individuals. Better designed studies would further develop confidence in this area. This is a potential vehicle of change to deliver some of the much-needed psychiatric support to both economically developed and developing regions in a resource-utilitarian manner. Partnerships between the gaming industry, researchers and health services may benefit patients.
Clinical Utility of CDK4/6 Inhibitors in Sarcoma: Successes and Future Challenges
Authors: Hsu Jocelyn Y. , Seligson Nathan D. , Hays John L. , Miles Wayne O. , Chen James L. 
Published: February 2022

PURPOSESoft tissue and bone sarcomas are rare malignancies that exhibit significant pathologic and molecular heterogeneity. Deregulation of the CDKN2A-CCND-CDK4/6-retinoblastoma 1 (Rb) pathway is frequently observed in about 25% of unselected sarcomas and is pathognomonic for specific sarcoma subtypes. This genomic specificity has fueled the clinical evaluation of selective CDK4/6 inhibitors in sarcomas. Here, we highlight successes, opportunities, and future challenges for using CDK4/6 inhibitors to treat sarcoma.MATERIALS AND METHODSThis review summarizes the current evidence for the use of CDK4/6 inhibitors in sarcoma while identifying molecular rationale and predictive biomarkers that provide the foundation for targeting the CDK4/6 pathway in sarcoma. A systematic review was performed of articles indexed in the PubMed database and the National Institutes of Health Clinical Trials Registry (ClinicalTrials.gov). For each sarcoma subtype, we discuss the preclinical rationale, case reports, and available clinical trials data.RESULTSDespite promising clinical outcomes in a subset of sarcomas, resistance to CDK4/6 inhibitors results in highly heterogeneous clinical outcomes. Current clinical data support the use of CDK4/6 inhibitors in subsets of sarcoma primarily driven by CDK4/6 deregulation. When dysregulation of the Rb pathway is a secondary driver of sarcoma, combination therapy with CDK4/6 inhibition may be an option. Developing strategies to identify responders and the mechanisms that drive resistance is important to maximize the clinical utility of these drugs in patients with sarcoma. Potential biomarkers that indicate CDK4/6 inhibitor sensitivity in sarcoma include CDK4, CCND, CCNE, RB1, E2F1, and CDKN2A.CONCLUSIONCDK4/6 inhibitors represent a major breakthrough for targeted cancer treatment. CDK4/6 inhibitor use in sarcoma has led to limited, but significant, early clinical success. Targeted future clinical research will be key to unlocking the potential of CDK4/6 inhibition in sarcoma.
Distinct Genomic Landscapes in Early-Onset and Late-Onset Endometrial Cancer
Authors: Choi Jungyoon , Holowatyj Andreana N. , Du Mengmeng , Chen Zhishan , Wen Wanqing , Schultz Nikolaus , Lipworth Loren , Guo Xingyi 
Published: February 2022

PURPOSEThe spectrum of somatic mutations among women with endometrial cancer (EC) younger than 50 years (early-onset EC) remains unknown. We investigated distinct somatic mutation patterns among early-onset and late-onset (age ≥ 50 years) EC patients.METHODSThis cohort study included individuals age 18+ years diagnosed with pathologically confirmed EC in the American Association of Cancer Research (AACR) Genomics Evidence Neoplasia Information Exchange (GENIE, v9.1) consortium. We explored tumor mutational burden (TMB) and genomic patterns of EC by age at clinical sequencing using multivariable regression models adjusted for race, ethnicity, histology, sequencing assay, sample type, and TMB.RESULTSAmong 2,425 women with EC, 176 (7.3%) had early-onset EC and 1,923 (79.3%) had nonhypermutated (< 17.78 mutations/Mb) tumors. TMB significantly differed across age and histology groups. Among nonhypermutated ECs, early-onset patients had significantly lower odds of presenting with nonsilent FGFR2 and PIK3R1 somatic mutations compared with late-onset EC patients in adjusted models ( FGFR2: odds ratio [OR] = 0.18, 95% CI, 0.04 to 0.76; PIK3R1: OR = 0.54, 95% CI, 0.31 to 0.92). By contrast, early-onset EC patients had increased odds of presenting with nonsilent CTNNB1 and BRCA2 mutations compared with late-onset patients ( CTNNB1: OR = 3.32, 95% CI, 2.14 to 5.16; BRCA2: OR = 4.01, 95% CI, 1.55 to 10.38). Subsequent analyses stratified by race, ethnicity, and tumor histology identified distinct patterns of APC, KMT2D, KMT2C, and KRAS by race, ethnicity, and PTEN and APC patterns by histologic subtypes.CONCLUSIONEarly-onset EC harbors a unique genomic landscape compared with late-onset disease. A distinct molecular phenotype of early-onset EC provides novel insights into a unique etiology and may yield clinical implications for developing targeted treatment modalities for younger patients.
New Concepts in the Pathogenesis of Cystic Fibrosis–Related Diabetes
Authors: Moheet Amir , Moran Antoinette 
Published: February 2022

Abstract

Context
Cystic fibrosis–related diabetes (CFRD) is the most common extrapulmonary complication of cystic fibrosis (CF). Approximately 40% of people with CF who are older than 20 years have CFRD. Presence of CFRD is associated with poor health outcomes in people with CF.

Objective
This review summarizes current knowledge on pathophysiology of CFRD.

Methods
A PubMed review of the literature was conducted, with search terms that included CFRD, cystic fibrosis, cystic fibrosis related diabetes, and cystic fibrosis transmembrane conductance regulator (CFTR). Additional sources were identified through manual searches of reference lists.
Pathophysiology of CFRD: The pathophysiology underlying development of glucose tolerance abnormalities in CF is complex and not fully understood. β-cell loss and functional impairment of the remaining β-cell function results in progressive insulin insufficiency. Factors that may contribute to development of CFRD include local islet and systemic inflammation, alterations in the incretion hormone axis, varying degrees of insulin resistance and genetic factors related to type 2 diabetes.

Conclusion
The prevalence of CFRD is expected to further increase with improving life expectancy of people with CF. Further research is needed to better understand the mechanisms underlying the development of CFRD and the impact of diabetes on clinical outcomes in CF.
Insights into cisplatin-induced neurotoxicity and mitochondrial dysfunction in Caenorhabditis elegans
Authors: Martínez-Fernández Carmen , Bergamino Milana , Schiavi Alfonso , Brena David , Ventura Natascia , Honnen Sebastian , Villanueva Alberto , Nadal Ernest , Cerón Julián 
Published: February 2022

Cisplatin is the most common drug in first-line chemotherapy against solid tumors. We and others have previously used the nematode Caenorhabditis elegans to identify genetic factors influencing the sensitivity and resistance to cisplatin. In this study, we use C. elegans to explore cisplatin effects on mitochondrial functions and investigate cisplatin-induced neurotoxicity through a high-resolution system for evaluating locomotion.
Firstly, we report that a high-glucose diet sensitizes C. elegans to cisplatin at the physiological level and that mitochondrial CED-13 protects the cell from cisplatin-induced oxidative stress. Additionally, by assessing mitochondrial function with a Seahorse Analyzer, we observed a detrimental effect of cisplatin and glucose in mitochondrial respiration. Secondly, since catechol-O-methyltransferases (involved in dopamine degradation) are upregulated upon cisplatin exposure, we studied the protective role of dopamine against cisplatin-induced neurotoxicity. To implement the use of the Tierpsy Tracker system for measuring neurotoxicity, we showed that abnormal displacements and body postures in cat-2 mutants, which have the dopamine synthesis disrupted, can be rescued by adding dopamine. Then, we demonstrated that dopamine treatment protects from the dose-dependent neurotoxicity caused by cisplatin.
Effect of training of frontline health workers on tuberculosis: a cluster randomized control trial in South Nigeria
Authors: Akwaowo Christie , Umoh Idongesit , Motilewa Oluseyi , Umoh Victor , Usoroh Eno , Adeboye Stella , Idiong Uduak , Antia Etop 
Published: February 2022

Background:Intensified efforts to improve tuberculosis (TB) diagnosis, treatment, and prevention are needed to meet global EndTB targets. Community health workers’ (CHWs) knowledge with respect to case finding is vital in tuberculosis elimination. This study aimed to determine the effect of tuberculosis training on the knowledge of community health workers in Nigeria.Methods:As part of a larger multicomponent intervention study, a randomised control trial was conducted with CHWs in 18 primary health care (PHC) clusters in Nigeria. The clusters were allocated to three arms: training and cash incentive (A), training only (B), and control (C) arms. Arms (A) and (B) received training on tuberculosis symptoms, prevention, diagnosis and treatment while the control arm (C) did not receive training. Participants’ knowledge on tuberculosis was assessed using questionnaires administered pre- and post-intervention. Data was analyzed using GraphPad Prism. Descriptive data was presented in tables and bivariate data was analyzed using chi square. Statistical significance was set as P<0.05.Results:There was a significant increase in the total knowledge score (25.4%), knowledge of general symptoms (24.4%), prevention (22.6%) and diagnosis and treatment (30.0%) across all study arms post-intervention (p<0.0001). Compared with the control arm, the training arm (A) had a higher proportion of good total knowledge score (94.4%) and arm (B) had a lower proportion of good total knowledge score (83.1%) when compared to the control group (93.1%). These were, however, not statistically significant.Conclusions:An improvement in the CHWs’ knowledge of symptoms, prevention, diagnosis and treatment of tuberculosis was observed after a training intervention was done. Integration of routine tuberculosis training is recommended to improve tuberculosis case finding in high burden communities.Pan African Clinical Trial Registry registration:PACTR202010691865364 (14/01/2020)
Continuation and user satisfaction of the levonorgestrel intrauterine system (LNG IUS) contraceptive in Nigeria
Authors: Nwala Anthony , Udoh Ekerette , Anyanti Jennifer , Fajemisin Adewole 
Published: February 2022

Background: The hormonal intrauterine device or intrauterine system (IUS) also known as the levonorgestrel intrauterine system (LNG-IUS) is a highly effective hormonal intra-uterine contraceptive. However, services offering the method are not widely available in Nigeria and little evidence exists on the dynamics of its use. We examined the continuation rate and satisfaction with the IUS among the user population. Methods: This prospective longitudinal phone survey involved a baseline survey of users at two-weeks post-insertion of the LNG IUS, recruited from 40 clinics across 17 states in Nigeria, with a follow-up survey at the 3rd and 12th months. A total of 208 users were interviewed at baseline, 98 at three months, and 73 at 12 months. User family planning and the IUS use experiences were elicited, as well as the continuation rate and satisfaction with the method at three and 12 months. Results: At three- and 12 months post-insertion, 96.9% (95% CI: 91.3, 99.3) and 91.8% (95% CI: 82.9, 96.9), respectively, reported still using the LNG IUS, with none out of the few users who discontinued the method reporting a method failure. Discontinuation was mainly a result of the experience of menstrual bleeding or amenorrhea (25.0%), experiences of pain with the method (18.8%), and partner complaining about strings (16.7%). High satisfaction with the LNG IUS (76.5% at three months and 86.3% at 12 months post-insertion) was reported. Satisfaction with LNG IUS was significantly associated with not having breast tenderness/pain (88.2%) and no vaginal bacterial infection (87.5%) at 12 months compared to experiencing breast tender/pain (50.0%) and vaginal infection (0.0%) (p<0.05). Conclusion: High user continuation and satisfaction with IUS indicates the positive potential of the method as a contraceptive in Nigeria.
Monte Carlo and Quasi–Monte Carlo Density Estimation via Conditioning
Authors: L’Ecuyer Pierre , Puchhammer Florian , Ben Abdellah Amal 
Published: February 2022

Estimating the unknown density from which a given independent sample originates is more difficult than estimating the mean in the sense that, for the best popular nonparametric density estimators, the mean integrated square error converges more slowly than at the canonical rate of [Formula: see text]. When the sample is generated from a simulation model and we have control over how this is done, we can do better. We examine an approach in which conditional Monte Carlo yields, under certain conditions, a random conditional density that is an unbiased estimator of the true density at any point. By averaging independent replications, we obtain a density estimator that converges at a faster rate than the usual ones. Moreover, combining this new type of estimator with randomized quasi–Monte Carlo to generate the samples typically brings a larger improvement on the error and convergence rate than for the usual estimators because the new estimator is smoother as a function of the underlying uniform random numbers. Summary of Contribution: Stochastic simulation is commonly used to estimate the mathematical expectation of some output random variable X together with a confidence interval for this expectation. But the simulations usually provide information to do much more, such as estimating the entire distribution (or density) of X. Histograms are routinely provided by standard simulation software, but they are very primitive density estimators. Kernel density estimators perform better, but they are trickier to use, have bias, and their mean square error converges more slowly than the canonical rate of O(1/n) with n independent samples. In this paper, we explain how to construct unbiased density estimators that converge at the canonical rate and even much faster when combined with randomized quasi–Monte Carlo. The key idea is to use conditional Monte Carlo to hide appropriate information and obtain a computable (random) conditional density, which acts (under certain conditions) as an unbiased density estimator. Moreover, this sample density is typically smoother than the classic density estimators as a function of the underlying uniform random numbers, so it can get along much better with randomized quasi–Monte Carlo methods. This offers an opportunity to further improve the O(1/n) rate. We observe rates near O(1/n2) on some examples, and we give conditions under which this type of rate provably holds. The proposed approach is simple, easy to implement, and extremely effective, so it provides a significant addition to the stochastic simulation toolbox.
Extended Graph Formulation for the Inequity Aversion Pricing Problem on Social Networks
Authors: Chopra Sunil , Park Hyunwoo , Shim Sangho 
Published: February 2022

The inequity aversion pricing problem aims to maximize revenue while providing prices to people connected in a social network such that connected people receive prices that are not too different. This problem is known to be NP-hard even when the number of prices offered is three. This paper provides an extended graph formulation for the problem whose LP-relaxation is shown to be very strong. We show that the extended graph relaxation is integral on a network without any cycle. We develop extended cycle inequalities and show that the extended cycle inequalities cut off all the fractional extreme points of the extended graph relaxation on a cycle. We generalize cycle inequalities to zero half cuts performing a Chvátal–Gomory procedure on a cycle. Computational experiments show that the extended graph relaxation results in an integer solution for most problem instances with very small gaps (less than 3%) from optimality for the remaining instances. The addition of zero half cuts reduces the integrality gap significantly on the few difficult instances. Summary of Contribution: The inequity aversion pricing problem aims to maximize revenue while providing prices to people connected in a social network such that connected people receive prices that are not too different. This paper provides an extended graph formulation of this practical revenue management problem whose LP-relaxation is shown to be very strong. The authors show that the extended graph relaxation is integral on a network without any cycle. They develop extended cycle inequalities and generalize them to zero-half cuts. Computational experiments show that the extended graph formulation results in an integer solution or a very small integrality gap. For difficult instances, the addition of zero half cuts significantly reduces the integrality gap.
Capacity Games with Supply Function Competition
Authors: Anderson Edward , Chen Bo , Shao Lusheng 
Published: February 2022

Procurement Auctions with Capacity Reservation It frequently happens that a supplier needs to invest in building capacity prior to supplying a product. Then the buyer will need to reserve capacity from suppliers and pay for this in advance of knowing the final demand. “Capacity Games with Supply Function Competition” by Edward Anderson, Bo Chen, and Lusheng Shao studies a very general version of this problem, in which both capacity and production costs are volume dependent. They explore how an auction will operate in this setting and allow supply function bids from suppliers. They apply this framework to a newsvendor problem with unreliable suppliers, a portfolio procurement setting with supply options and a spot market, and a bundling problem with nonsubstitutable products. This helps to understand when we may expect the buyer to make a reservation choice that maximizes the overall supply chain profit. The key to these results is to show that the supply chain optimal profit is submodular in the set of suppliers.