bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deep indel mutagenesis reveals the regulatory and modulatory architecture of alternative exon splicing
Authors: Baeza-Centurion Pablo , Miñana Belén , Faure Andre J. , Thompson Mike , Bonnal Sophie , Quarantani Gioia , Lehner Ben , Valcárcel Juan 
Published: April 2024

AbstractAltered splicing is a frequent mechanism by which genetic variants cause disease and antisense oligonucleotides (AONs) that target pre-mRNA splicing have been approved as therapeutics for multiple pathologies including patient-customized treatments for rare diseases. However, the regulatory architecture of human exons remains poorly understood and AON discovery is currently slow and expensive, limiting the wider adoption of the approach. Here we show that that systematic deletion scans –which can be made experimentally at very low cost – provide an efficient strategy to chart the regulatory landscape of human exons and to rapidly identify effective splicing-modulating oligonucleotides in a fully quantitative manner. Our results suggest a mechanism for the evolutionary origins of unusually short microexons and the repression of transmembrane domain-encoding exons, and reveal a checkerboard architecture of sequential enhancers and silencers in a model alternative exon. Accurate prediction of the effects of deletions using deep learning provides a resource, DANGO, that maps the splicing regulatory landscape of all human exons and predicts effective splicing-altering antisense oligonucleotides genome-wide.
Targeted proteomics upon Tofersen identifies candidate response markers for SOD1-linked amyotrophic lateral sclerosis
Authors: Steffke Christina , Baskar Karthik , Wiesenfarth Maximilian , Dorst Johannes , Schuster Joachim , Schöberl Florian , Reilich Peter , Regensburger Martin , German Alexander , Günther René , Vidovic Maximilian , Petri Susanne , Weishaupt Jochen H. , Meyer Thomas , Hagenacker Tim , Grosskreutz Julian , Weyen Ute , Weydt Patrick , Haarmeier Thomas , Lingor Paul , Wolf Joachim , Hermann Andreas , Prudlo Johannes , Günther Kornelia , Knehr Antje , Elmas Zeynep , Parlak Özlem , Uzelac Zeljko , Witzel Simon , Ruf Wolfgang Philipp , Tumani Hayrettin , Ludolph Albert C. , Freischmidt Axel , Oeckl Patrick , Ho Ritchie , Brenner David , Catanese Alberto 
Published: April 2024

AbstractTofersen is the first effective and approved therapy for familial ALS caused by pathogenic variants in theSOD1gene. Following treatment with tofersen, neurofilaments in patients CSF and serum display a faster response than clinical parameters, underlining their importance as a biomarker for treatment response in clinical trials. This evidence led us to hypothesize that this novel treatment might represent an opportunity to identify additional therapy-responsive biomarkers for ALS. We chose the commercial NUcleic acid Linked Immuno-Sandwich Assay (NULISA™), to investigate a predefined panel of 120 neural, glial and inflammatory markers in CSF and serum samples longitudinally collected from SOD1-ALS patients at baseline and three months after tofersen treatment. We identified a set of proteins (beyond pNfH and NfL) whose levels differed between SOD1-ALS and the matched control group and that were responsive to treatment with tofersen, including Aβ42, NPY and UCHL1. Even though our results warrant validation in larger cohorts and longer follow-up time, they may pave the way for a panel of responsive proteins solidifying biomarker endpoints in clinical trials.
The SLaM Brain Health Clinic: a remote biomarker enhanced memory clinic for patients with mild cognitive impairment within an NHS mental health trust
Authors: Venkataraman Ashwin V. , Kandangwa Pooja , Lemmen Roos , Savla Rutvi , Beigi Mazda , Hammond Devon , Harwood Daniel , Sauer Justin , Velayudhan Latha , Ballard Clive , Brem Anna-Katharine , Kalafatis Chris , Aarsland Dag 
Published: April 2024

ABSTRACTBackgroundThe novel South London and Maudsley Brain Health Clinic (SLaM BHC) leverages advances in remote consultations and biomarkers to provide a timely, cost-efficient and accurate diagnosis in mild cognitive impairment (MCI).AimsTo describe the organisation, patient cohort, and acceptability of the remote diagnostic and interventional procedures.MethodWe describe the recruitment, consultation setup, the clinical and biomarker program, and the two online group interventions for cognitive wellbeing and lifestyle change. We evaluate the acceptability of the remote consultations, lumbar puncture (LP), saliva genotyping and remote cognitive and functional assessments.ResultsWe present the results of the first 68 (mean age 73, 55% female, 43% ethnic minority) of 146 patients who enrolled for full remote clinical, cognitive, genetic, cerebrospinal fluid, and neuroimaging phenotyping. 86% were very satisfied/ satisfied with the remote service. 67% consented to LP and 95% of those were very satisfied, all having no significant complications. 93% found taking saliva genotyping very easy/easy and 93% found the cognitive assessments instructions clear. 98% were satisfied with the cognitive wellbeing groups and 90% of goals were achieved in the lifestyle intervention group.ConclusionsThe SLaM BHC provides a highly acceptable and safe clinical model for remote assessments and lumbar punctures in a representative, ethnically diverse population. This allows early and accurate diagnosis of Alzheimer’s, differentiation from other MCI causes and targets modifiable risk factors. This is crucial for future disease modification, ensuring equitable access to research, and provides precise, timely and cost-efficient diagnoses in UK mental health services.
C-reactive protein-based tuberculosis triage testing: a multi-country diagnostic accuracy study
Authors: Derendinger Brigitta , Mochizuki Tessa K. , Marcelo Danaida , Shankar Deepa , Mangeni Wilson , Nguyen Hanh , Yerikaya Seda , Worodria William , Yu Charles , Nguyen Nhung Viet , Christopher Devasahayam Jesudas , Theron Grant , Phillips Patrick P.J. , Nahid Payam , Denkinger Claudia M. , Cattamanchi Adithya , Yoon Christina 
Published: April 2024

ABSTRACTRationaleC-reactive protein (CRP)-based tuberculosis (TB) screening is recommended for people with HIV (PWH). However, its performance among people without HIV and in diverse settings is unknown.ObjectivesIn a multi-country study, we aimed to determine whether CRP meets the minimum accuracy targets (sensitivity ≥90%, specificity ≥70%) for an effective TB triage test.Methods/MeasurementsConsecutive outpatient adults with cough ≥2 weeks from five TB endemic countries in Africa and Asia had baseline blood collected for point-of-care CRP testing and HIV and diabetes screening. Sputum samples were collected for Xpert MTB/RIF Ultra (Xpert) testing and culture. CRP sensitivity and specificity (5 mg/L cut-point) was determined in reference to sputum test results and compared by country, sex, and HIV and diabetes status. Variables affecting CRP performance were identified using a multivariate receiver operating characteristic (ROC) regression model.ResultsAmong 2904 participants, of whom 613 (21%) had microbiologically-confirmed TB, CRP sensitivity was 84% (95% CI: 81-87%) and specificity was 61% (95% CI: 59-63%). CRP accuracy varied geographically, with higher sensitivity in African countries (≥91%) than Asian countries (64-82%). Sensitivity was higher among men than women (87% vs. 79%, difference +8%, 95% CI: 1-15%) and specificity was higher among people without HIV than PWH (64% vs. 45%, difference +19%, 95% CI: 13-25%). ROC regression identified country and measures of TB disease severity as predictors of CRP performance.ConclusionsOverall, CRP did not achieve the minimum accuracy targets and its performance varied by setting and in some sub-groups, likely reflecting population differences in mycobacterial load.
Culinary tourism: exploring cultural diplomacy through gastronomy festivals in Turkey and Italy
Authors: Gündüz Cemil , Rezaei Mojtaba , Quaglia Roberto , Pironti Marco 
Published: April 2024

PurposeThe primary objective of this research is to draw a comparative analysis between Turkey and Italy in terms of how festival events function as catalysts for the endorsement of regional culinary delicacies. The study endeavours to elucidate the role of these festivals in fortifying the regional gastronomic landscape of both nations.Design/methodology/approachAdopting a comprehensive comparative methodology, this study meticulously scrutinises the gastronomy festivals spanning diverse geographical locales in both Turkey and Italy. Consideration is given to the standout food and beverage items spotlighted at these events and the venues where they are hosted. The research design takes into account the extensive cultural and geographical spectrum that characterises Turkey and Italy. The primary research method comprises web content analysis techniques. This method involves analysing textual data from online sources pertaining to gastronomy festival events in both countries. Web content analysis is instrumental in evaluating how such festivals are deployed in promoting indigenous gastronomic products and exploring the intricate dynamics between brand identity and brand image.FindingsThe research outcomes underscore the pivotal role that festival events play in elevating regional gastronomic products' profile in Turkey and Italy. It highlights the top 10 festivals and the most popular local culinary items on digital platforms. Additionally, the study offers a side-by-side comparison of the most celebrated gastronomic products in Turkey versus those that receive prominence in Italy.Originality/valueThis study enriches academic understanding by dissecting the nuances of how festivals contribute to the promotion of local gastronomic treasures. By juxtaposing Turkey and Italy, this research provides valuable insights into the influence of festivals on regional culinary promotion across diverse cultural milieus. This study makes substantial contributions to the fields of gastronomy, tourism, and brand promotion.
Noble Chemical Agency – managing working capital in troubling times
Authors: Dash Ashutosh , Pramani Rahul 
Published: April 2024

Learning outcomes
The primary objectives of the case study are to get the participants exposed to the issues of working capital which even profitable companies face on a day-to-day basis; give the participants an understanding of how to balance the, at times, conflicting objectives of increasing profits and sales through favorable credit terms; and expose them to the impact of increase in inventory levels and average collection period on margins in a period of slow growth. They will also learn about the concept of factoring and its uses.

Case overview/synopsis
The case study is about a group of companies engaged in education, steel fabrication and oil businesses owned by a single proprietor. The company was based in Fatehnagar which was part of Hyderabad district in the state of Telangana, India, and the case study traces the origins of the group from 1960s to 2021. The group was invested the surplus cash flows from the oil business to initiate and expand other businesses during this period. The economic downturn due to the COVID-19 pandemic had hit the company, particularly its oldest business – Noble Chemical Agency. The oil business was facing issues related to its growth and profitability, and the uncertainty around COVID-19-related restrictions had only augmented the fears of the management. The case study looks at issues and the dilemma which the owner of the company faced. The case study highlights various issues related to working capital management, especially related to receivables management and inventory levels faced by businesses during the slow-growth phase. It demonstrates how working capital management issues, if not resolved in time, can lead to insolvency of even a successful company with a sound business model.

Complexity academic level
The case study is meant for teaching in postgraduate management programs (Master of Business Administration and Postgraduate Diploma in Management) in the following courses: corporate finance/financial management course in the first year (the case study should be taught towards the end of the course); and management accounting courses in first year (the case study should be positioned in the middle of these courses). The case study can also be used to highlight issues related to working capital and small business management in a Management Development Programme (MDP) course for “Finance fundamentals for non-finance executives”.

Supplementary materials
Teaching notes are available for educators only.

Subject code
CSS 1: Accounting and finance.
Learning generatively to facilitate marketing innovation of international joint ventures in emerging markets
Authors: Do Truong Quang , Tho Nguyen Dinh , Le Nguyen-Hau 
Published: April 2024

PurposeThis study aims to investigate a mediation model in which generative learning positively affects marketing innovation and both organizational control and relationship openness mediate the relationship between learning intent and generative learning of international joint ventures (IJVs) in emerging markets. We also decipher the degree of necessity of these factors for generative learning and of generative learning for marketing innovation.Design/methodology/approachA sample of 181 marketing managers of IJVs in Vietnam, an emerging market, was surveyed to collect data. Partial least squares structural equation modeling (PLS-SEM) was employed to test the net effect, and necessary condition analysis (NCA) was used to decipher the degree of necessity.FindingsThe PLS-SEM results demonstrate that the effect of learning intent on generative learning is fully mediated by organizational control and relationship openness, which in turn leads to marketing innovation. The NCA findings reveal that all three factors, namely learning intent, organizational control and relationship openness, serve as necessary conditions for generative learning. However, generative learning does not play the role of a necessary condition for marketing innovation.Practical implicationsThe study findings suggest that IJVs in emerging markets should pay attention not only to the net effects of those factors but also to their degrees of necessity for generative learning in order to achieve marketing innovation.Originality/valueThe study contributes to the literature by confirming the mediating roles of organizational control and relationship openness in the relationship between learning intent and generative learning. Furthermore, it is among the first to decipher the degrees of necessity of these factors for generative learning and of generative learning for the marketing innovation of IJVs in emerging markets.
The dynamics of the financial inclusion index for developing countries: lessons learned
Authors: Ayayi Ayi Gavriel , Dout Hamitande 
Published: April 2024

Purpose
The purpose of this paper is to calculate the financial inclusion index and analyze its dynamics in developing countries.

Design/methodology/approach
The authors use the two-stage principal component analysis (PCA) method and consider financial technology innovations to improve the accuracy of the financial inclusion index.

Findings
The authors found a downward trend in the financial inclusion index in most developing countries over the study period. The authors also found that a high financial inclusion index is linked to high scores in the Doing Business and high business climate regulation ranking. In addition, the authors observed that the rates of low financial inclusion in developing countries are due to low utilization of and unequal access to financial services.

Practical implications
The analysis suggests that policymakers in developing countries could invest in digital infrastructure to extend access to financial services in remote areas. They could also encourage financial innovation, particularly in financial technologies, by adopting flexible regulatory frameworks. Promoting the financial inclusion of marginalized groups through targeted initiatives tailored to their needs is another solution. They could also encourage the use of financial services by raising awareness and educating populations through training programs. Finally, to improve the business climate, governments could simplify administrative procedures and promote transparency and legal stability.

Originality/value
Unlike previous studies, the use of the two-stage PCA method and the consideration of financial technology (Fintech) innovations such as mobile money in the determinants of the financial inclusion index improve the accuracy of the index.
Interconnectedness of European insurers and cat shocks contagion effects
Authors: Srbinoski Bojan , Poposki Klime , Bogdanovski Vasko 
Published: April 2024

Purpose
The purpose of this paper is to examine the evolution of interconnectedness of European insurers among themselves, as well as with other non-financial firms, for the period 2000–2021 and to analyze the stock return movements around the costliest catastrophic events (hurricanes) in the past two decades.

Design/methodology/approach
This paper follows the “simple” approach of Patro et al.(2013) and examines the daily stock return correlations of the largest 30 insurers and the largest 30 non-financial firms headquartered in Europe. In addition, the study uses event study methodology to examine stock return movements around the costliest hurricanes.

Findings
We find that the European insurance sector has become highly interconnected during the past two decades; however, its increasing connectedness with non-financial firms is limited to a few firms. In addition, we find weak evidence of the destabilizing effects of catastrophic events on European insurers and non-financial firms; however, the potential for cat risk contagion effects exists as the insurance industry becomes heavily interconnected.

Originality/value
The extant literature is largely concerned with the contribution of the insurance sector to the systemic risk of the financial sector. We focus on a specific region (Europe) and analyze the evolution of interconnectedness of the largest insurers within the insurance sector as well as with the largest non-financial firms encapsulating important crisis periods. In addition, we relate to the literature that examines the market reactions around catastrophic events to test the relevance of traditional insurance activities in instigating potential contagion shocks.
Can the text features of regulatory inquiry letters predict companies’ financial restatements? Evidence from China
Authors: Zhang Chao , Cao Zenghao , Li Zhimin , Zhu Weidong , Wu Yong 
Published: April 2024

PurposeSince the implementation of the regulatory inquiry system, research on its impact on information disclosure in the capital market has been increasing. This article focuses on a specific area of study using Chinese annual report inquiry letters as the basis. From a text mining perspective, we explore whether the textual information contained in these inquiry letters can help predict financial restatement behavior of the inquired companies.Design/methodology/approachPython was used to process the data, nonparametric tests were conducted for hypothesis testing and indicator selection, and six machine learning models were employed to predict financial restatements.FindingsSome text feature indicators in the models that exhibit significant differences are useful for predicting financial restatements, particularly the proportion of formal positive words and stopwords, readability, total word count and certain textual topics. Securities regulatory authorities are increasingly focusing on the accounting and financial aspects of companies' annual reports.Research limitations/implicationsThis study explores the textual information in annual report inquiry letters, which can provide insights for other scholars into research methods and content. Besides, it can assist with decision making for participants in the capital market.Originality/valueWe use information technology to study the textual information in annual report inquiry letters and apply it to forecast financial restatements, which enriches the research in the field of regulatory inquiries.
Research on the trajectory planning and global optimization strategy of cold spraying technique for complex products coating preparation
Authors: Yang Xu , Yue Xin , Cai Zhenhua , Zhong Shengshi 
Published: April 2024

Purpose
This paper aims to present a set of processes for obtaining the global spraying trajectory of a cold spraying robot on a complex surface.

Design/methodology/approach
The complex workpiece surfaces in the project are first divided by triangular meshing. Then, the geodesic curve method is applied for local path planning. Finally, the subsurface trajectory combination optimization problem is modeled as a GTSP problem and solved by the ant colony algorithm, where the evaluation scores and the uniform design method are used to determine the optimal parameter combination of the algorithm. A global optimized spraying trajectory is thus obtained.

Findings
The simulation results show that the proposed processes can achieve the shortest global spraying trajectory. Moreover, the cold spraying experiment on the IRB4600 six-joint robot verifies that the spraying trajectory obtained by the processes can ensure a uniform coating thickness.

Originality/value
The proposed processes address the issue of different parameter combinations, leading to different results when using the ant colony algorithm. The two methods for obtaining the optimal parameter combinations can solve this problem quickly and effectively, and guarantee that the processes obtain the optimal global spraying trajectory.
Path planning for robot search task using belief criteria decision-making
Authors: Zhao Long , Liu Xiaoye , Li Linxiang , Guo Run , Chen Yang 
Published: April 2024

Purpose
This study aims to realize efficient, fast and safe robot search task, the belief criteria decision-making approach is proposed to solve the object search task with an uncertain location.

Design/methodology/approach
The study formulates the robot search task as a partially observable Markov decision process, uses the semantic information to evaluate the belief state and designs the belief criteria decision-making approach. A cost function considering a trade-off among belief state, path length and movement effort is modelled to select the next best location in path planning.

Findings
The semantic information is successfully modelled and propagated, which can represent the belief of finding object. The belief criteria decision-making (BCDM) approach is evaluated in both Gazebo simulation platform and physical experiments. Compared to greedy, uniform and random methods, the performance index of path length and execution time is superior by BCDM approach.

Originality/value
The prior knowledge of robot working environment, especially semantic information, can be used for path planning to achieve efficient task execution in path length and execution time. The modelling and updating of environment information can lead a promising research topic to realize a more intelligent decision-making method for object search task.