bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-term survival in patients with isolated pulmonary valve stenosis: a not so benign disease?
Authors: Skoglund Kristofer , Rosengren Annika , Lappas Georgios , Fedchenko Maria , Mandalenakis Zacharias 
Published: September 2021

Background and objectivesDuring the last decades, the survival rates in patients with congenital heart disease have increased dramatically, particularly in patients with complex heart malformations. However, the survival in patients with simple defects is still unknown. We aimed to determine the characteristics and the risk of mortality in patients with isolated pulmonary valve stenosis (PS).MethodsSwedish inpatient, outpatient and cause of death registries were used to identify patients born between 1970 and 2017 with a diagnosis of PS, without any other concomitant congenital heart lesion. For each patient with PS, 10 control individuals without congenital heart disease were matched by birth year and sex from the total population registry. We used median-unbiased method and Kaplan-Meier survival analysis to examine the risk of mortality.ResultsWe included 3910 patients with PS and 38 770 matched controls. The median age of diagnosis of PS was 0.7 years (IQR 0.3–7.0). During a median follow-up of 13.5 years (IQR 6.5–23.5), 88 patients with PS and 192 controls died; 500 patients with PS (12%) underwent at least one transcatheter or surgical valve intervention. The overall mortality rate was significantly higher in patients with PS compared with matched controls (HR 4.67, 95% CI 3.61 to 5.99, p=0.001). Patients with an early diagnosis of PS (0–1 year) had the highest risk of mortality (HR 10.99, 95% CI 7.84 to 15.45).ConclusionsIn this nationwide, register-based cohort study, we found that the risk of mortality in patients with PS is almost five times higher compared with matched controls. Patients with an early diagnosis of PS appears to be the most vulnerable group and the regular follow-up in tertiary congenital heart units may be the key to prevention.
$$X_1(2900)$$ as a $$\bar{D}_1 K$$ molecule
Authors: Chen Hao , Qi Hong-Rong , Zheng Han-Qing 
Published: September 2021

AbstractThe analyses of the LHCb data on X(2900) in the $$D^- K^+$$

D
-

K
+

spectrum are performed. Both dynamically generated and explicitly introduced $$X_1(2900)$$

X
1

(
2900
)

are considered. The results show that both these two approaches support the interpretation of $$X_1(2900)$$

X
1

(
2900
)

as a $$\bar{D}_1 K$$

D

¯

1

K

molecular state, with $$J^{P}=1^-$$

J
P

=

1
-

and an iso-singlet interpretation is much more favorable. The effect of triangle singularity on the production of $$X_1(2900)$$

X
1

(
2900
)

is also discussed, and it is found that it cannot be interpreted as a pure triangle cusp.
DOES CULTURAL DIVERSITY MATTER FOR TEAM PERFORMANCE IN MULTINATIONAL COMPANIES? AN ANALYSIS OF CONFLICT, COMMUNICATION, SOCIAL INTEGRATION, CREATIVITY AND SATISFACTION
Authors: OBSUWAN SORNSAWAN , CHANDRASHEKAR DEEPAK , KRAUS SASCHA , BREM ALEXANDER , BOUNCKEN RICARDA 
Published: September 2021

Team performance is key in each organisation. Hence, cultural effects in teams are a relevant matter of subject clarifying the ambiguous findings from previous research. With this background, we investigate how the macro-constructs of conflict, communication effectiveness, social integration, creativity and satisfaction interact with cultural diversity on team performance in an environment characterised by a largely homogeneous and ethnic workforce. We test our hypotheses on a sample of firms in Thailand. Our results indicate that creativity and satisfaction have a significant positive impact on team performance whereas cultural diversity has a significant positive impact on influencing conflict in a team-based environment. However, cultural diversity has no significant impact on communication effectiveness and social integration, and it has no significant impact on team performance.The key theoretical contributions from our study are that cultural diversity can contribute to conflict even in a team composition that is seemingly cohesive and homogeneous in nature. Further, our study establishes that creativity and satisfaction have a positive effect on team performance even in the context of a homogeneous and ethnically majority-based team. For the practitioners, the results of the study indicate that initial actions need to be taken by the leaders of multicultural teams as they create teams to avoid the initial pitfalls due to conflict.
QoS–aware Mesh-based Multicast Routing Protocols in Edge Ad Hoc Networks: Concepts and Challenges
Authors: Singal Gaurav , Laxmi Vijay , Gaur Manoj Singh , Rao D. Vijay , Kushwaha Riti , Garg Deepak , Kumar Neeraj 
Published: September 2021

Multicast communication plays a pivotal role in Edge based Mobile Ad hoc Networks (MANETs). MANETs can provide low-cost self-configuring devices for multimedia data communication that can be used in military battlefield, disaster management, connected living, and public safety networks. A Multicast communication should increase the network performance by decreasing the bandwidth consumption, battery power, and routing overhead. In recent years, a number of multicast routing protocols (MRPs) have been proposed to resolve above listed challenges. Some of them are used for dynamic establishment of reliable route for multimedia data communication. This article provides a detailed survey of the merits and demerits of the recently developed techniques. An ample study of various Quality of Service (QoS) techniques and enhancement is also presented. Later, mesh topology-based MRPs are classified according to enhancement in routing mechanism and QoS modification. This article covers the most recent, robust, and reliable QoS-aware mesh based MRPs, classified on the basis of their operational features, and pros and cons. Finally, a comparative study has been presented on the basis of their performance parameters on the proposed protocols.
Multi-Head Spatio-Temporal Attention Mechanism for Urban Anomaly Event Prediction
Authors: Huang Huiqun , Yang Xi , He Suining 
Published: September 2021

Timely forecasting the urban anomaly events in advance is of great importance to the city management and planning. However, anomaly event prediction is highly challenging due to the sparseness of data, geographic heterogeneity (e.g., complex spatial correlation, skewed spatial distribution of anomaly events and crowd flows), and the dynamic temporal dependencies.
In this study, we propose M-STAP, a novel Multi-head Spatio-Temporal Attention Prediction approach to address the problem of multi-region urban anomaly event prediction. Specifically, M-STAP considers the problem from three main aspects: (1) extracting the spatial characteristics of the anomaly events in different regions, and the spatial correlations between anomaly events and crowd flows; (2) modeling the impacts of crowd flow dynamic of the most relevant regions in each time step on the anomaly events; and (3) employing attention mechanism to analyze the varying impacts of the historical anomaly events on the predicted data. We have conducted extensive experimental studies on the crowd flows and anomaly events data of New York City, Melbourne and Chicago. Our proposed model shows higher accuracy (41.91% improvement on average) in predicting multi-region anomaly events compared with the state-of-the-arts.
Targeting Tumor–Stromal IL6/STAT3 Signaling through IL1 Receptor Inhibition in Pancreatic Cancer
Authors: Dosch Austin R. , Singh Samara , Dai Xizi , Mehra Siddharth , Silva Iago De Castro , Bianchi Anna , Srinivasan Supriya , Gao Zhen , Ban Yuguang , Chen Xi , Banerjee Sulagna , Nagathihalli Nagaraj S. , Datta Jashodeep , Merchant Nipun B. 
Published: September 2021

AbstractA hallmark of pancreatic ductal adenocarcinoma (PDAC) is the presence of a dense, desmoplastic stroma and the consequent altered interactions between cancer cells and their surrounding tumor microenvironment (TME) that promote disease progression, metastasis, and chemoresistance. We have previously shown that IL6 secreted from pancreatic stellate cells (PSC) stimulates the activation of STAT3 signaling in tumor cells, an established mechanism of therapeutic resistance in PDAC. We have now identified the tumor cell–derived cytokine IL1α as an upstream mediator of IL6 release from PSCs that is involved in STAT3 activation within the TME. Herein, we show that IL1α is overexpressed in both murine and human PDAC tumors and engages with its cognate receptor IL1R1, which is strongly expressed on stromal cells. Further, we show that IL1R1 inhibition using anakinra (recombinant IL1 receptor antagonist) significantly reduces stromal-derived IL6, thereby suppressing IL6-dependent STAT3 activation in human PDAC cell lines. Anakinra treatment results in significant reduction in IL6 and activated STAT3 levels in pancreatic tumors from Ptf1aCre/+;LSL-KrasG12D/+; Tgfbr2flox/flox (PKT) mice. Additionally, the combination of anakinra with cytotoxic chemotherapy significantly extends overall survival compared with vehicle treatment or anakinra monotherapy in this aggressive genetic mouse model of PDAC. These data highlight the importance of IL1 in mediating tumor–stromal IL6/STAT3 cross-talk in the TME and provide a preclinical rationale for targeting IL1 signaling as a therapeutic strategy in PDAC.
Characterization of KRAS Mutation Subtypes in Non–small Cell Lung Cancer
Authors: Judd Julia , Abdel Karim Nagla , Khan Hina , Naqash Abdul Rafeh , Baca Yasmine , Xiu Joanne , VanderWalde Ari M. , Mamdani Hirva , Raez Luis E. , Nagasaka Misako , Pai Sachin Gopalkrishna , Socinski Mark A. , Nieva Jorge J. , Kim Chul , Wozniak Antoinette J. , Ikpeazu Chukwuemeka , de Lima Lopes Gilberto , Spira Alexander I. , Korn W. Michael , Kim Edward S. , Liu Stephen V. , Borghaei Hossein 
Published: September 2021

Abstract
KRAS is the most commonly mutated oncogene in NSCLC and development of direct KRAS inhibitors has renewed interest in this molecular variant. Different KRAS mutations may represent a unique biologic context with different prognostic and therapeutic impact. We sought to characterize genomic landscapes of advanced, KRAS-mutated non–small cell lung cancer (NSCLC) in a large national cohort to help guide future therapeutic development.
Molecular profiles of 17,095 NSCLC specimens were obtained using DNA next-generation sequencing of 592 genes (Caris Life Sciences) and classified on the basis of presence and subtype of KRAS mutations. Co-occurring genomic alterations, tumor mutational burden (TMB), and PD-L1 expression [22C3, tumor proportion score (TPS) score] were analyzed by KRAS mutation type.
Across the cohort, 4,706 (27.5%) samples harbored a KRAS mutation. The most common subtype was G12C (40%), followed by G12V (19%) and G12D (15%). The prevalence of KRAS mutations was 37.2% among adenocarcinomas and 4.4% in squamous cell carcinomas. Rates of high TMB (≥10 mutations/Mb) and PD-L1 expression varied across KRAS mutation subtypes. KRAS G12C was the most likely to be PD-L1 positive (65.5% TPS ≥ 1%) and PD-L1 high (41.3% TPS ≥ 50%). STK11 was mutated in 8.6% of KRAS wild-type NSCLC but more frequent in KRAS-mutant NSCLC, with the highest rate in G13 (36.2%). TP53 mutations were more frequent in KRAS wild-type NSCLC (73.6%).
KRAS mutation subtypes have different co-occurring mutations and a distinct genomic landscape. The clinical relevance of these differences in the context of specific therapeutic interventions warrants investigation.
Epigenetic Regulation of Fanconi Anemia Genes Implicates PRMT5 Blockage as a Strategy for Tumor Chemosensitization
Authors: Du Changzheng , Li Steven W. , Singh Simranjit X. , Roso Kristen , Sun Michael A. , Pirozzi Christopher J. , Yang Rui , Li Jian-Liang , He Yiping 
Published: September 2021

Abstract

Strengthened DNA repair pathways in tumor cells contribute to the development of resistance to DNA-damaging agents. Consequently, targeting proteins in these pathways is a promising strategy for tumor chemosensitization. Here, we show that the expression of a subset of Fanconi anemia (FA) genes is attenuated in glioblastoma tumor cells deficient in methylthioadenosine phosphorylase (MTAP), a common genetic alteration in a variety of cancers. Subsequent experiments in cell line models of different cancer types illustrate that this reduced transcription of FA genes can be recapitulated by blockage of Protein Arginine Methyltransferase 5 (PRMT5), a promising therapeutically targetable epigenetic regulator whose enzymatic activity is compromised in MTAP-deficient cells. Further analyses provide evidence to support that PRMT5 can function as an epigenetic regulator that contributes to the increased expression of FA genes in cancer cells. Most notably and consistent with the essential roles of FA proteins in resolving DNA damage elicited by interstrand crosslinking (ICL) agents, PRMT5 blockage, as well as MTAP loss, sensitizes tumor cells to ICL agents both in vitro and in xenografts. Collectively, these findings reveal a novel epigenetic mechanism underlying the upregulated expression of FA genes in cancer cells and suggest that therapeutically targeting PRMT5 can have an additional benefit of chemosensitizing tumor cells to ICL agents.

Implications:
PRMT5 positively regulates the expression of FA genes. Inhibition of PRMT5 attenuates FA-dependent DNA repair pathway and sensitizes tumor cells to ICL agents.
Improving Outcome Predictions for Patients Receiving Mechanical Circulatory Support by Optimizing Imputation of Missing Values
Authors: Jaeger Byron C. , Cantor Ryan , Sthanam Venkata , Xie Rongbing , Kirklin James K. , Rudraraju Ramaraju 
Published: September 2021

Background:Risk prediction models play an important role in clinical decision making. When developing risk prediction models, practitioners often impute missing values to the mean. We evaluated the impact of applying other strategies to impute missing values on the prognostic accuracy of downstream risk prediction models, that is, models fitted to the imputed data. A secondary objective was to compare the accuracy of imputation methods based on artificially induced missing values. To complete these objectives, we used data from the Interagency Registry for Mechanically Assisted Circulatory Support.Methods:We applied 12 imputation strategies in combination with 2 different modeling strategies for mortality and transplant risk prediction following surgery to receive mechanical circulatory support. Model performance was evaluated using Monte-Carlo cross-validation and measured based on outcomes 6 months following surgery using the scaled Brier score, concordance index, and calibration error. We used Bayesian hierarchical models to compare model performance.Results:Multiple imputation with random forests emerged as a robust strategy to impute missing values, increasing model concordance by 0.0030 (25th–75th percentile: 0.0008–0.0052) compared with imputation to the mean for mortality risk prediction using a downstream proportional hazards model. The posterior probability that single and multiple imputation using random forests would improve concordance versus mean imputation was 0.464 and >0.999, respectively.Conclusions:Selecting an optimal strategy to impute missing values such as random forests and applying multiple imputation can improve the prognostic accuracy of downstream risk prediction models.
Characteristics and Quality of National Cardiac Registries: A Systematic Review
Authors: Dawson Luke P. , Biswas Sinjini , Lefkovits Jeffrey , Stub Dion , Burchill Luke , Evans Sue M. , Reid Christopher , Eccleston David 
Published: September 2021

Background:
National cardiac registries are increasingly used for informing health policy, improving the quality and cost-effectiveness of patient care, clinical research, and monitoring the safety of novel treatments. However, the quality of registries is variable. We aimed to assess the characteristics and quality of national cardiac registries across all subspecialties of cardiac care.

Methods:
Publications relating to national cardiac registries across six cardiac subspecialty domains were identified by searching MEDLINE and the Google advanced search function with 26 438 citations and 4812 full-text articles reviewed.

Results:
A total of 155 registries, representing 49 countries, were included in the study. Of these, 45 related to coronary disease or percutaneous coronary intervention, 28 related to devices, arrhythmia, and electrophysiology, 24 related to heart failure, transplant, and mechanical support, 21 related to structural heart disease, 21 related to congenital heart disease, and 16 related to cardiac surgery. Enrollment was procedure-based in 60% and disease-based in 40%. A total of 73.10 million patients were estimated to have been enrolled in cardiac registries. Quality scoring was performed using a validated registry grading system, with registries performing best in the use of explicit variable definitions and worst in assessment of data reliability. Higher quality scores were associated with government funding, mandated enrollment, linkage to other registries, and outcome risk adjustment. Quality scores and number of registries within a country were positively correlated with each other and with measures of national economic output, health expenditure, and urbanization.

Conclusions:
There has been remarkable growth in the uptake of national cardiac registries across the last few decades. However, the quality of processes used to ensure data completeness and accuracy remain variable and few countries have integrated registries covering multiple subspecialty domains. Clinicians, funders, and health policymakers should be encouraged to focus on the range, quality, and integration of these registries.

Registration:

URL:
https://www.crd.york.ac.uk/prospero
; Unique identifier: CRD42020204224.
NLRP3 Inflammasome Mediates Immune-Stromal Interactions in Vasculitis
Authors: Porritt Rebecca A. , Zemmour David , Abe Masanori , Lee Youngho , Narayanan Meena , Carvalho Thacyana T. , Gomez Angela C. , Martinon Daisy , Santiskulvong Chintda , Fishbein Michael C. , Chen Shuang , Crother Timothy R. , Shimada Kenichi , Arditi Moshe , Noval Rivas Magali 
Published: September 2021

Rationale:
NLRP3 (NLR family pyrin domain containing 3) activation and IL-1β (interleukin-1β) production are implicated in Kawasaki disease (KD) pathogenesis; however, a detailed and complete characterization of the molecular networks and cellular subsets involved in the development of cardiovascular lesions is still lacking.

Objective:
Here, in a murine model of KD vasculitis, we used single-cell RNA sequencing and spatial transcriptomics to determine the cellular landscape of inflamed vascular tissues.

Methods and Results:

We observe infiltrations of innate and adaptive immune cells in murine KD cardiovascular lesions, associated with increased expression of
Nlrp3
and
Il1b
. Monocytes, macrophages, and dendritic cells were the main sources of IL-1β, whereas fibroblasts and vascular smooth muscle cells (VSMCs) expressed high levels of IL-1 receptor. VSMCs type 1 surrounding the inflamed coronary artery undergo a phenotype switch to become VSMCs type 2, which are characterized by gene expression changes associated with decreased contraction and enhanced migration and proliferation. Genetic inhibition of IL-1β signaling on VSMCs efficiently attenuated the VSMCs type 2 phenotypic switch and the development of cardiovascular lesions during murine KD vasculitis. In addition, pharmacological inhibition of NLRP3 prevented the development of cardiovascular inflammation.

Conclusions:
Our studies unravel the cellular diversity involved in IL-1β production and signaling in murine KD cardiovascular lesions and provide the rationale for therapeutic strategies targeting NLRP3 to inhibit cardiovascular lesions associated with KD.
Multiple Chronic Conditions Explain Ethnic Differences in Functional Outcome Among Patients With Ischemic Stroke
Authors: Jiang Xiaqing , Morgenstern Lewis B. , Cigolle Christine T. , Wang Lu , Claflin Edward S. , Lisabeth Lynda D. 
Published: September 2021

Background and Purpose:
Mexican Americans (MAs) have worse stroke outcomes and a different profile of multiple chronic conditions (MCC) compared with non-Hispanic White people. MCC has implications for stroke treatment, complications, and poststroke care, which impact poststroke functional outcome (FO). We sought to assess the contribution of MCC to the ethnic difference in FO at 90 days between MAs and non-Hispanic White people.

Methods:
In a prospective cohort of ischemic stroke patients (2008–2016) from Nueces County, Texas, data were collected from patient interviews, medical records, and hospital discharge data. MCC was assessed using a stroke-specific and function-relevant index (range, 0–35; higher scores greater MCC burden). Poststroke FO was measured by an average score of 22 activities of daily living (ADLs) and instrumental ADLs at 90 days (range, 1–4; higher scores worse FO). The contribution of MCC to the ethnic difference in FO was assessed using Tobit regression. Effect modification by ethnicity was examined.

Results:
Among the 896 patients, 70% were MA and 51% were women. Mean age was 68±12.2 years; 33% of patients were dependent in ADL/instrumental ADLs (FO score >3, representing a lot of difficulty with ADL/instrumental ADLs) at 90 days. MAs had significantly higher age-adjusted MCC burden compared with non-Hispanic White people. Patients with high MCC score (at the 75th percentile) on average scored 0.70 points higher in the FO score (indicating worse FO) compared with those with low MCC score (at the 25th percentile) after adjusting for age, initial National Institutes of Health Stroke Scale, and sociodemographic factors. MCC explained 19% of the ethnic difference in FO, while effect modification by ethnicity was not statistically significant.

Conclusions:
MAs had a higher age-adjusted MCC burden, which partially explained the ethnic difference in FO. The prevention and treatment of MCC could potentially mitigate poststroke functional impairment and lessen ethnic disparities in stroke outcomes.