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Aim: Pexidartinib was approved for the treatment of tenosynovial giant cell tumors with a required Risk Evaluation and Mitigation Strategy (REMS) to ensure its safe use. As required by the REMS, a survey was conducted to document the knowledge, attitudes and behavior (KAB) of patients/caregivers and healthcare providers (HCPs) regarding the risk of serious and potentially fatal liver injury due to pexidartinib, the need for liver testing prior to and during treatment and the need for patient counseling about this risk. Patients & methods: The KAB survey was conducted among 40 patients and 18 HCPs enrolled in the pexidartinib REMS. Results: Among patients, 87.5% demonstrated understanding of key risk message (KRM) 1 (risk of serious liver injury), 87.5% demonstrated understanding of KRM2 (liver testing requirement) and 77.5% demonstrated understanding of both KRMs. Among HCPs, 83.3% demonstrated understanding of KRM1, 88.9% demonstrated understanding of KRM2, 100% demonstrated understanding of KRM3 (patient counseling) and 83.3% demonstrated understanding of all three KRMs. Conclusion: The KAB surveys demonstrated that the educational goals of the pexidartinib REMS were being achieved.

Pakistan has been a victim of terrorist activities for the past two decades. No place has been left out as not only military installations, training centers of law enforcing agencies were targeted but soft belly targets like schools, hospitals, mosques, public parks, courts, hotels and restaurants were also chosen by the terrorists. Pakistan Army is a team of professionals having a mastery at their work have been fighting the menace of terrorism effectively but Army alone cannot control it to the fullest without the will and support of the general public and without a ‘hand & glove’ relation with other facets of the society. The objective of this article is to analyze those factors which gave birth to terrorism in Pakistan. Keeping in mind theoretical nature of the study, secondary data analysis method has been used to argue the issue. This study determines that the military operations are not the only solution to counter terrorism in the Pakistan but public opinion, political will and a close and friendly cooperation and coordination is a must to address the issue. Need of the hour is to take all the political, social and economic stakeholders onboard to tackle the issue, of terrorism bluntly.

Inclusion of tangible user interfaces can facilitate learning through contextual experience, interaction with the provided information, and epistemic actions, resulting in effecting learning in design education. The goal of this study is to investigate how tangible user interface (TUI) affects design learning through the cognitive load. Extended reality-based TUI and traditional desktop-based GUI were utilized to deliver the same information to two groups of students. The NASA TLX tool was used to measure students' perceived cognitive load after receiving information through the two modalities. Contemporary design pedagogy, the potential use of XR, design cognition, today's design learners experience-oriented lifestyle were combined to provide a theoretical framework to understand how information delivery modalities affect design learning. The results reveal that the use of XR-based TUIs decreases cognitive load resulting in enhanced experience and effective learning in design studios.

This is a preface for the special section.

A short post publication review of a recent AJIS paper.

Background Dilated cardiomyopathy (DCM) is a leading cause of heart failure and death. The etiology of DCM is genetically heterogeneous. Objectives We sought to define the prevalence of mutations in the RNA splicing protein RBM20 in a large cohort with DCM and to determine whether genetic variation in RBM20 is associated with clinical outcomes. Methods Subjects included in the Genetic Risk Assessment of Defibrillator Events (GRADE) study were aged at least 18 years, had an ejection fraction of ≤30%, and an implantable cardioverter-defibrillator (ICD). The coding region and splice junctions of RBM20 were screened in subjects with DCM; 2 common polymorphisms in RBM20 , rs942077 and rs35141404, were genotyped in all GRADE subjects. Results A total of 1465 subjects were enrolled in the GRADE study, and 283 with DCM were screened for RBM20 mutations. The mean age of subjects with DCM was 58 ± 13 years, 64% were males, and the mean follow-up time was 24.2 ± 17.1 months after ICD placement. RBM20 mutations were identified in 8 subjects with DCM (2.8%). Mutation carriers had a similar survival, transplantation rate, and frequency of ICD therapy compared with nonmutation carriers. Three of 8 subjects with RBM20 mutations (37.5%) had atrial fibrillation (AF), whereas 19 subjects without mutations (7.4%) had AF ( P = .02). Among all GRADE subjects, rs35141404 was associated with AF (minor allele odds ratio=0.62; 95% confidence interval=0.44–0.86; P = .006). In the subset of GRADE subjects with DCM, rs35141404 was associated with AF (minor allele odds ratio=0.58; P = .047). Conclusions Mutations in RBM20 were observed in approximately 3% of subjects with DCM. There were no differences in survival, transplantation rate, and frequency of ICD therapy in mutation carriers.

Glioblastoma is a deadly brain tumor with a median survival of 1.3 years after surgery, radiotherapy and chemotherapy. The dismal prognosis is due to the propensity of the tumor to invade adjacent normal brain. Although next generation sequencing (NGS) led to genomic landscaping of glioblastoma, there is little insight into the mechanism of neoplastic cell invasion, the detection of the invasive cells or their therapeutic targeting. To address these critical issues, we developed a murine model of invasive glioblastoma that mimics the human disease. Using a cancer stem-cell like human glioblastoma cell line in an orthotopic model, we isolated pairs of neoplastic cells growing either in the core of the tumor, or away for the core, in invasive secondary foci. A phenotypic assessment showed significantly decreased animal survival, increased cancer stemness and invasion in the invasive cells in comparison to core cells. Expression profiling of Core and Inv cells resulted in the identification of differentially expressed gene targets controlling metabolic pathways, cell-cell and cell-matrix adhesion and cell differentiation. A 300 gene library, including these targets, was designed for NGS of high grade diffuse glioma cases. In a series of 4 pediatric and adult WHO grade IV diffuse glioma autopsy cases with a total of 28 sequenced distinct primary and secondary tumor foci, as well as normal brain, we found mutations in several of the genes identified in the mouse model. Two categories of novel targets potentially relevant for therapy were confirmed and further addressed: extracellular matrix proteases and metabolic enzymes. These translational findings and the implications for the molecular diagnosis and therapy of glioblastoma will be discussed.

High quality bilingual dictionaries are rarely available for lower-density language pairs, especially for those that are closely related. Using a third language as a pivot to link two other languages is a well-known solution, and usually requires only two input bilingual dictionaries to automatically induce the new one. This approach, however, produces many incorrect translation pairs because the dictionary entries are normally are not transitive due to polysemy and the ambiguous words in the pivot language. Utilizing the complete structures of the input bilingual dictionaries positively influences the result since dropped meanings can be countered. Moreover, an additional input dictionary may provide more complete information for calculating the semantic distance between word senses which is key to suppressing wrong sense matches. This paper proposes an extended constraint optimization model to inducing new dictionaries of closely related languages from multiple input dictionaries, and its formalization based on Integer Linear Programming. Evaluations indicated that the proposal not only outperforms the baseline method, but also shows improvements in performance and scalability as more dictionaries are utilized.

Samir Saba,* Haider Mehdi,* William Barrington, Fardeen Mehdi, Zahid Islam, Barry LondonCardiovascular Institute of the University of Pittsburgh Medical Center, Pittsburgh, PA, USA*These authors contributed equally to this workBackground: Improved clinical and echocardiographic parameters have been documented with biventricular (BIV) pacing in patients after myocardial infarction (MI). We investigated the changes in gene expression in cardiac tissue with BIV pacing, using a rabbit model of MI.Method: New Zealand White rabbits were divided into four groups: sham-operated controls, MI with no pacing, MI with right ventricle (RV) pacing (MI + RV), and MI with BIV pacing (MI + BIV). Pacing was initiated 1–2 weeks after the coronary ligation. At 5 weeks, the hearts were excised. The tissue extracted from the left ventricle (LV) and RV underwent analysis for protein and messenger ribonucleic acid (mRNA) levels.Results: The ether-a-go-go-related gene (ERG) protein levels recovered from the base of the LV away from the MI area were two- to threefold lower in the MI and the MI + RV compared with the MI + BIV groups (P = 0.07). The ERG protein levels were similar between the MI + BIV and the control groups. However, the RNA levels were comparable between the four study groups, suggesting that a posttranscriptional mechanism accounted for the difference in protein levels.Conclusion: In this rabbit model of MI, we demonstrated a recovery in ERG protein levels with BIV pacing, after MI. This recovery may underlie some of the benefits seen with BIV pacing in ischemic cardiomyopathy.Keywords: heart failure, biventricular pacing, cardiac reverse remodeling, ether-a-go-go-related gene

There is a scarcity of cardiac tissue available for research.(1) To investigate the feasibility of obtaining myocardial tissue from extracted pacemaker and defibrillator leads for gene expression analysis and (2) to examine the nitric oxide 1 adaptor protein (NOS1AP) RNA expression as a function of patient genotype.Seventeen patients (age = 56 ± 20 years; 12 men; 5 pacemakers; 12 defibrillators) undergoing lead extractions for standard indications (5 device erosion; 1 vascular occlusion; 11 lead malfunction or recall) were genotyped for 2 NOS1AP single nucleotide polymorphisms-rs10494366 (T to G) and rs10918594 (C to G)-and had RNA levels measured by real-time polymerase chain reaction for collagen I, troponin I, Ca(v)1.2, Kv4.3, HERG, KvLQT1, connexin 43, NOS1AP, and sodium-calcium exchanger. Ventricular tissue obtained from 3 failing hearts at transplantation served as reference.A high ratio of cardiac troponin I/collagen I RNA identified 9 of the 17 patient samples (muscle rich), in which the gene expression profile was similar to that of the reference ventricular samples and significantly different (P.003) from the expression profile of samples with a low troponin I/collagen ratio (muscle poor). TT and CC polymorphisms were associated with significantly lower NOS1AP RNA levels (P.01 compared with the GG genotype).Performing gene expression analyses on right ventricular tissue samples extracted with pacemaker and defibrillator leads is feasible. A significant number of samples contain cardiomyocytes that express troponin I and ion channels at levels comparable to those seen in explanted hearts. Decreased NOS1AP expression in rs10494366 TT and rs10918594 CC homozygotes may underlie shorter repolarization times.

The relationship among Board, CEO and Chair has attracted much attention in recent years due to the growing need for effective corporate governance. The objective of this paper is to analyze the Board-CEO-Chair relationship. After reviewing previous literature, we tried to integrate them to address the knowledge gap. There are a handful studies done on Board-CEO relationship, these are primarily focused on specific geographic areas. A fewer research work has been done on CEO-Chair relationship. Most importantly, the research work on the combined relationship of Board-CEO-Chair is even less. Hence, there is a greater need for research work in this area.Our finding suggests that there should be mutual respect between CEO and Chair and both have to be honest and transparent to each other. Both Chair and CEO should be able to communicate at ease with each other regarding any trivial matters concerning the company. The relationship between Board and CEO should be complementary rather than competing. The role of the Board and the CEO should be based on mutual trust, they should work as a team. Understanding how Board, CEO and Chair add value to the corporations is an important topic for regulators, academics and practitioners. This paper represents a first step in understanding how Board-CEO-Chair work as a team. We can greatly benefit from this research by understanding the type of relationship and how they vary in different cultural context and geographic locations. Our study also opens up new avenues for research on Board-CEO-Chair combined relationship.

This paper examined the cost structures of 216 MFIs in Bangladesh with a view to determine whether the country’s MFI’s will be able to achieve financial sustainability given the newly introduced interest rate cap. We measured financial sustainability through Return on Assets (ROA) and Operational Self Sufficiency (OSS). The results suggest that there are two key factors that are significantly related to financial sustainability: interest rate spread and general administrative costs. We conclude that MFIs that have lower proportions of administrative costs and a large interest rate spread are more likely to achieve financial sustainability even with the newly introduced interest cap.

This paper examines the cost structures of 215 MFIs reported by the Microcredit Regulatory Authority of Bangladesh with a view to identify the main determinants of sustainability. MFIs in Bangladesh are an important case to study, as it is the first country to introduce an interest rate cap. Using management accounting ideas and frameworks, principally contingency theory to identify components of MFI’s cost structure, this study measures Operational Self Sufficiency (OSS) as the result of administrative costs, financial costs, interest rate spread and size/complexity. The results suggest that there are two key factors that are significantly related to MFI sustainability: interest rate spread and general administrative costs. We conclude that MFIs that have lower administrative costs and a large interest rate spread are more likely to achieve sustainability prior to the introduction of the interest cap.

Ontology-based clustering has gained attention in recent years due to the potential benefits of ontology. Current ontology-based clustering approaches have mainly been applied to reduce the dimensionality of attributes in text document clustering. Reduction in dimensionality of attributes using ontology helps to produce high quality clusters for a dataset. However, ontology-based approaches in clustering numerical datasets have not been gained enough attention. Moreover, some literature mentions that ontology-based clustering can produce either high quality or low-quality clusters from a dataset. Therefore, in this paper we present a clustering approach that is based on domain ontology to reduce the dimensionality of attributes in a numerical dataset using domain ontology and to produce high quality clusters. For every dataset, we produce three datasets using domain ontology. We then cluster these datasets using a genetic algorithm-based clustering technique called GenClust++. The clusters of each dataset are evaluated in terms of Sum of Squared-Error (SSE). We use six numerical datasets to evaluate the performance of our ontology-based approach. The experimental results of our approach indicate that cluster quality gradually improves from lower to the higher levels of a domain ontology., Comment: 6 Pages, IEEE CSDE2022 Conference Paper