bluuebunny/crossref_metadata_2025 huggingface dataset:
Big Data Measures of Environmental Concern
Authors: Ho Agol Wai Ming , Li Kevin Chi Keung
Published: December 2023

Environmental concern is a subjective state of society and researchers have typically relied on survey data to measure it. However, survey-based methods only capture a snapshot of it at the time and place the surveys were conducted. To overcome these problems, we develop an observable indicator that allows us to study environmental concern over time and across territories based on big data. The indicator composes of keyword groups that fit with the environmental concern measures revealed by a large-scale survey. We find that keywords associated with climate change, water pollution and waste management are the strongest predictors of environmental concern. To the best of our knowledge, our paper is the first to use online search data to capture subjective environmental concern.
Investor Behavioral Anomalies in Wartime Uncertainty: The Case of North Kivu in DRC
Authors: Mapapa Augustin Mbangala , Musay Laurent Mumbere , Mpere Seblon Mpereboye , Atangana Yves Vincent Mballa
Published: December 2023

After combining the CPT1, SARF2, and greed and grievances dynamical systems, and the overreactions models, we conducted a questionnaire survey with a sample of 921 investors from North Kivu in the DRC, of which 879 (95%) were in the service sector. The evaluation of the risk taken by investors is carried out at two levels. At the first level, it is assessed according to an informational asymmetry focused on estimating probabilities describing the outlook for results over three years (from 2014 to 2016). At the second level, the analysis describes the investors’ attitude regarding their level of profit expectation as an endogenous variable of heuristic optimization, cognitive bias, and self-expressive bias. The results show that the anomalies described in the interactive behavior of N-K investors during wartime uncertainty stem from a plurality of attitudes reflecting an ambiguity of choices dominated by a sub-reaction at the base of reluctance and a loss of opportunity in the market.
The Covid-19 Pandemic and the Consumer Staples Sector: A Test of Market Efficiency
Authors: Bacon Frank W. , George Daniel E.
Published: December 2023

On Wednesday March 11, 2020, the World Health Organization (WHO) declared the covid 19 outbreak a global pandemic (Cucinotta, 2020). How efficient is the consumer staples market reaction to the announcement of a global pandemic? The purpose of this study is to examine the risk adjusted returns on and around the pandemic announcement to test the semi-strong form market efficiency hypothesis using the standard event study methodology in the finance literature. Will returns in the consumer staples industry show larger than expected gains on and surrounding the WHO’s COVID-19 pandemic announcement? The finance literature offers little evidence supporting the link between pandemics and the stock market. The announcement of a pandemic by the WHO should significantly and quickly affect the market. According to Eugene Fama (1970), if the market is semi-strong form efficient, all public information is immediately factored into the market and no investor can use this information to achieve an above normal return when adjusted for risk. To study this relationship, data for the S&P 500 and 10 consumer staples sector firms were collected for the event period surrounding the announcement of the COVID-19 pandemic. This study tests the global pandemic announcement for semi-strong form market efficiency (Bacon &Howell 2021). Evidence here supports the expected positive signal associated with the sample of consumer staples sector firms in reaction to the announcement of the pandemic. Likewise, the study results support the semi-strong form efficient market hypothesis and suggest the possibility of trading on this information up to 15 days prior to the announcement consistent with the behavioral finance literature (Bacon & Howell 2021).
Lauchlin Currie: Lights and Shadows in the Colombian Economy 1950-2000
Authors: Gómez Jiménez Alcides
Published: December 2023

This paper explains the intellectual journey of Lauchlin Currie, Canadian by origin and Colombian by destination. His contributions were notable in the US at the time of the great world crisis of 1929-1932 in the field of monetary theory and policy and his first publication dates back to 1931, as referenced by his biographer. He directed the first World Bank mission to an underdeveloped country, Colombia, in 1949-1950. He proposed an original development theory applicable to the country and called it Operation Colombia (1961) supported by a book called “Accelerating Development: the necessity and the means”. He was the inspirer and architect of the Development Plan of the Four Strategies in the early 1970s. He made recommendations to the 1991 constituent on free central banking and stability.
Healthy Workplaces for Nurses: A Review of Lateral Violence and Evidence-Based Interventions
Authors: Desharnais Brianna , Benton Lindsay , Ramirez Bernardo , Smith Carla , DesRoches Stephanie , Ramirez Cherie Lynn
Published: December 2023

Most nurses in the United States have experienced workplace bullying, also referred to as lateral violence. Workplace bullying is serious within professional nursing practice. These behaviors are often associated with detrimental consequences for nurses, their patients, and the greater health care organization. We performed a literature review to summarize recent studies on this pervasive yet persistent problem as well as evidence-based solutions. In environments where managers, supervisors, and administrators are unable or unwilling to address lateral violence, a common pattern is that offenders continue to target new employees and cause turmoil for workers and patients in healthcare settings. This work environment also causes harm and endangers patients. Although workplace bullying cannot be fixed with just one solution, there are different initiatives healthcare settings and educational institutions can implement to help prevent and eliminate workplace bullying, such as improving leadership training and interprofessional communication. Once these initiatives are put into practice, healthcare practices can start saving money, increasing employee satisfaction, retaining workers, and providing better healthcare services for their patients.
The Interplay Between Long Memory and Bootstrap Technique in Virtual and Real Currency Markets: The Evidence on the Pre/Post-COVID Era
Authors: Kaouther Flifel
Published: December 2023

This article explores the interplay between long memory and the parametric and nonparametric bootstrap techniques in virtual and real currency markets, specifically focusing on Bitcoin and the US dollar (USD) from 2019 to late 2022. The study compares the properties of the bootstrap tests, analyzes long memory effects, and evaluates the significance using P-value plots. Additionally, the research examines the corrected size-power curves to address size distortions. The findings confirm the presence of long memory in the examined currency markets and underscore the importance of accurate bootstrap utilization for robust analysis. The study provides valuable insights for investors and decision-makers in understanding the dynamics of the pre/post-COVID era.
A Decomposition of the Relationship Between Internet Access and Earnings
Authors: Murray Sheena
Published: December 2023

Gains in internet access and quality have increased output and revenue for companies, but these gains are not uniformly distributed across regions, industries, or worker types. I examine county-level wage and income measures on time-dynamic broadband uptake rates, mobile internet access, and local education levels. Datasets from the Census and FCC are combined to construct a rich dataset of all counties in the continental US from 2010-2019. Interaction terms between internet access, duration of access, and educational levels are included to capture the heterogeneous relationship between internet access and wages across across different levels of education. Decompositions of these regressions indicate that only 25% of the differences in wages and income are driven by heterogeneous returns to internet access and education across metro densities, with the majority of the difference determined by the levels of these variables themselves.
TÜRKİYE CUMHURİYETİ’NDE GERÇEKLEŞTİRİLEN İLK REFERANDUM: 1961 REFERANDUMU’NUN ULUSAL BASINA YANSIMASI
Authors: TAŞDELEN Esra , AYDOĞAN Erdal
Published: December 2023

The first coup in the Republic of Türkiye was experienced on May 27, 1960. During the Republic period, the concept of referendum again entered the public agenda in this process. It is noteworthy that referendum, one of the most important tools of semi-direct democracy, was also used in the 1961 Constitution and the majority of the people participated in this process. This article aims to examine in detail the reflection of the 1961 Referendum, the first referendum in the history of the Republic of Türkiye, on the national press. It also evaluates the interpretation of the referendum process through cartoons and the effects of these cartoons on social consciousness. The content analysis method was used in the study. By examining materials such as news headlines, columns and cartoons, the media's approaches to the referendum process were tried to be presented from an objective perspective. In this way, the way the referendum was covered in the national press, the political atmosphere of the period and the perception created in the society were revealed through the media.

This study has revealed the historical context and importance of the 1961 Referendum. It has dealt with the political and social dynamics that led to the referendum, the people's preferences in the referendum, and the effects of the results on Turkish politics. In this context, it has analyzed in detail how the referendum results were received in the national press and how different media outlets gave meaning to these results. Examining the social reflections of the referendum process through cartoons has also constituted an important component of this study.

As a result, it has been determined that the reflections of the 1961 Referendum in the national press are an important source for understanding the political and social dynamics of the period. The press, one of the most important structural stones of the social and political equation, was used as the main source of the study. In this study, the 1961 referendum was examined as a whole by examining national newspapers. Thus, Türkiye's democratic processes, media relations and the impact of visual media were analyzed.
Özel Hukuk Cezası Kavramı ve Ceza Hukukunun Genel İlkelerinin Özel Hukuk Cezalarına Uygulanabilirliği
Authors: ÖNAY Işık , OK Orcan
Published: December 2023

Bu çalışmada ilk olarak, bir normun özel hukuk cezası içerdiği sonucuna varabilmek için normdaki yaptırımın ne gibi özelliklere sahip olması gerektiği sorgulanmaktadır. Yaptırımın özel hukuk cezası niteliğinde olduğunun kabulü için aranacak ölçütler bu çalışmada şu şekilde tespit edilmiştir: ilgili özel hukuk yaptırımının malvarlığına ilişkin olması, yaptırımın cezalandırma amacı taşıması, cezalandırma amacından daha baskın başka bir amacın mevcut olmaması ve yaptırımın kanun koyucu tarafından taraf iradelerinden bağımsız olarak öngörülmüş olması. Cezalandırma amacından söz edebilmek için tespit edilmesi gereken en önemli özellik hükmün bireylerin davranışlarını yönlendirmek suretiyle onları belli davranışlardan caydırmayı hedeflemesidir. Çalışmanın bir sonraki bölümünde bu ölçütler Türk hukukunda özel hukuk cezası olup olmadığı tartışılabilecek çeşitli hükümlere uygulanmıştır. Bu ölçütler ışığında öğretide özel hukuk cezası olduğu savunulan bazı hükümlerin aslında cezai nitelikte olmadığı sonucuna varılmaktadır. Son olarak özel hukuk cezalarına ceza hukukunun genel prensiplerinin uygulanıp uygulanamayacağı sorusu üzerinde durulmuştur. Bu soruya prensip olarak olumlu yanıt verilmiş ve kanunilik ilkesi, kusur ilkesi, cezaların şahsiliği ilkesi ve ne bis in idem ilkeleri bakımından bu yaklaşımın doğuracağı sonuçlar incelenmiştir.
Limited Şirket Müdürünün İstifası ve Ticaret Siciline Tescil
Authors: KARAMAN COŞGUN Özlem
Published: December 2023

Limited şirket müdürlerinin görevlerinin sona ermesinin ticaret siciline tescil ve ilan edilmesi gerekir. İstifa da bu sona erme sebeplerinden birisidir. Ticaret siciline tescil ve ilanda sadece şirketin değil, istifa eden müdürün de menfaati vardır. Birden çok müdürden birisinin istifası, müdürler kurulu başkanı tarafından ticaret siciline tescil ettirilir. Müdürler kurulu başkanının ihmali halinde, tescile davet usulüyle tescil gerçekleştirilir. Müdürler kurulu başkanının ya da tek müdürün veya tek ortağın müdürlük görevinden istifa etmesi ihtimalinde ticaret siciline tescili kim talep eder? Bu ihtimallerde şirketin organsız kalmaması ve gerekli tedbirlerin alınması maksadıyla istifa Ticaret Sicili’ne tescil edilmemektedir. Ancak bu durum istifa eden müdür açısından önemli sorunlara yol açmaktadır. Makalede bu sorunlar ele alınacak, çözüm yolları tartışılacaktır.
Digital Capitalism and Friendship: A Critical Analysis
Authors: Cometta Mosè
Published: December 2023

This paper starts from an understanding of friendship as a series of gradients – a definition provided firstly by Aristotle – to observe the similarities and differences between interested friendship, disinterested friendship, and market relations. Introducing the notion of surveillance capitalism, the paper discusses the advent of social media and the implicit definition of friendship that underlies it. Social media favours the quantification and bureaucratisation of friendship, transforming it into a measure of personal achievement, i.e. widely promoting instrumental friendship. This transformation raises a number of issues related to alienation, self-exploitation, and the ability to relate to otherness
Anthropization
of Goroubi forest reserve (GFR)
in North Benin, West Africa
Authors: Kpatinnon Noudossessi Rufin , Sossou Mahouénan Bédi Jonas , Mevognon Alex Vidjannangni Tobias , Orekan Prudence Adéolé , Ali Rachad Kolawolé Foumilayo Mandus
Published: December 2023

The Goroubi forest reserve (GFR) is under pressure leading to its extinction. This research aims to contribute to the restoration plans of the said forest in the district of Birni-Lafia in north Benin. In order to achieve this, questionnaire surveys and interviews were conducted with 79 people through random sampling in all of the villages of the district. The importance value index (IVI) of the pressures and the response rate were calculated. Mainly occupied by the rônier (Borassus aethiopum) originally, the GFR is particularly threatened by agriculture (IVI = 1), illegal exploitation (IVI = 0.94), grazing (IVI = 0.64), hunting (IVI = 0.51) and herbal medicine (IVI = 0.36). These pressures cause the disappearance of plant species (100 %), animal species (94 %), land degradation (89 %), etc. Today, the dominant occupation unit is a rice growing area with 327.7598 ha of cultivated territory. Therefore, it seems that the GFR is losing its forest identity. It is necessary to create new participatory management plan for the forest, initiate reforestation activities, set up a fixed co-management committee for the forest and create annual reports on the state of management of its resources in order to limit these pressures.
The Importance of Patient Safety and Risk
Authors: Tzenios Nikolaos
Published: December 2023

Presented by Professor Nikolaos Tzenios at the Massachusetts College of Pharmacy and Health Sciences on August 2, 2023, this presentation delves into the crucial aspects of patient safety and risk management within healthcare settings. It outlines the role of the presenter's employer, a healthcare management research entity, in advancing innovative healthcare solutions and policies. The presentation underscores the significance of protecting patients from harm and systemic defects, emphasizing the need for safe medical practices and the reduction of costs associated with medical errors. It also highlights the importance of creating structures for risk mitigation and ensuring compliance with healthcare laws and regulations, such as HIPAA. The presentation discusses the current landscape of the organization based on Weick and Sutcliffe's assessment of high-reliability organizations (HROs), focusing on sensitivity to operations, preoccupation with failure, deference to expertise, commitment to resilience, and reluctance to simplification. Key patient safety concerns, including diagnostic errors, healthcare-associated infections (HAIs), and emergency preparedness risks, are addressed, along with measures to mitigate these risks. The presentation concludes with personal reflections on the complexity of healthcare processes and the importance of risk management in preventing errors and safeguarding organizations against financial hardship.
Keynote presentation - Conversations with robots and AIs - Can foundation models support human wellbeing?
Authors: Lemon Oliver
Published: December 2023

Drawing on examples from several research projects at the National Robotarium and Alana AI, including SPRING (social robots for elder care), RES-Q+ (spoken dialogue to support stroke patients), and RNIB (assistive visual dialogue for partially-sighted people), I will discuss lessons learned and research directions in developing future generative AI systems to support human wellbeing.
PENGARUH REPAIR LAS GMAW TERHADAP KEKUATAN TARIK, KEKERASAN, DAN STRUKTUR MIKRO PADA MATERIAL BAJA A36
Authors: Pratama Diaz , Yuwono Indarto , Salim Alfi Tranggono Agus , Muzaki Mochamad , Suparman Suparman
Published: December 2023

Welding is a technique of joining metal materials that has a detrimental impact in the form of defects in the material, especially welded joints, in the weld joint area with improper welding procedures resulting in weld defects in the material, changes in the crystal structure and mechanical properties of material. This research method is carried out by re-welding or repairing the defective material. The purpose of this study is to analyze and compare the mechanical properties of repair results with welded joints without repair. The repair process uses a variety of repair 2 times, repair 3 times, and repair 4 times by welding GMAW on A36 steel material. The results of the study were mechanical properties of the material in the form of the crystal structure of the specimen, the value of the hardness test and the ultimate tensile strength, microstructure testing there is a crystal structure of perlite and ferrite. The highest hardness test value is repair 2 times 170 HV, without repair 166 HV, repair 3 times 163.3 HV, and repair 4 times 162.8 HV on weld metal. The result of ultimate strength variation without repair 485 N/mm2, repair 2 times 466.5 N/mm2, repair 3 times 466.5 N/mm2, repair 4 times 468 N/mm2 with tensile test fracture located in the base metal area, the result of ultimate tensile strength repair 2 times, repair 3 times, repair 4 times is still within the minimum tensile provision of ASTM A36 steel material of 452 N/mm2 so that welded joints that are made up to 4 times repair can be used.
Evaluasi Kekuatan Tarik Printer 3D dengan Variasi Suhu dan Ketebalan Layer pada Material PLA berdasarkan Standar ASTM D-638
Authors: Hadi Susilo Sugeng , Setiawan Agus , Yudiyanto Eko
Published: December 2023

In the context of modern developments, 3D printers are an important necessity in a world that is constantly developing. Although there is limited information about the strength of products produced by 3D printers, this tool is very suitable for realizing one's imagination in creating various kinds of products, such as coffee cups, children's toys, and metal tools. This research is focused on 3D printers that use plastic materials, especially PLA, and aims to evaluate the tensile strength of 3D printer products with ASTM D-638 type 1 standards. This research method involves two independent variables, namely temperature with a variation of 200˚ C, 220˚ C, and 240˚ C, as well as different layer thickness with a thickness of 0.1 mm, 0.2 mm, and 0.3 mm. Based on the research results, it was found that a temperature of 200˚C with a layer thickness of 0.1 mm had the highest average stress of 35.90 N/mm².
Supervised exercise training in patients with cancer during anthracycline-based chemotherapy to mitigate cardiotoxicity: a randomized-controlled-trial
Authors: Schneider Caroline , Ryffel Christoph , Stütz Laura , Rabaglio Manuela , Suter Thomas M. , Campbell Kristin L. , Eser Prisca , Wilhelm Matthias
Published: December 2023

Background

Exercise training (ET) has been shown to mitigate cardiotoxicity of anthracycline-based chemotherapies (AC) in animal models. Data from randomized controlled trials in patients with cancer are sparse.

Methods

Patients with breast cancer or lymphoma receiving AC were recruited from four cancer centres and randomly assigned to 3 months supervised ET. Primary outcome was change in left ventricular global longitudinal strain (GLS) from baseline (before AC) to post AC (AC-end) compared between the EXduringAC group, who participated in an exercise intervention during AC including the provision of an activity tracker, and the control group EXpostAC, who received an activity tracker only. Secondary outcome parameters were changes in high sensitivity Troponin T (hsTnT), NT-pro-brain natriuretic peptide (NT-proBNP), peak oxygen consumption (peak VO2) and objectively measured physical activity (PA) during this same time-period. All assessments were repeated at a 12-week follow-up from AC-end, when also the EXpostAC group had completed the ET, that started after AC. In exploratory analyses, robust linear models were performed to assess the association of PA with changes in echocardiographic parameters and biomarkers of LV function.

Results

Fifty-seven patients (median age 47 years; 95% women) were randomized to EXduringAC (n = 28) and EXpostAC (n = 29) group. At AC-end, GLS deteriorated in both study groups (albeit insignificantly) with 7.4% and 1.0% in EXduringAC (n = 18) and EXpostAC (n = 18), respectively, and hsTnT and NT-proBNP significantly increased in both groups, without difference between groups for any parameter. Change in peak VO2 (−1.0 and −1.1 ml/kg/min) at AC-end was also similar between groups as was duration of moderate-to-vigorous PA (MVPA) with a median of 33 [26, 47] min/day and 32 [21, 59] min/day in the EXduringAC and EXpostAC group, respectively. In the robust linear model including the pooled patient population, MVPA was significantly associated with a more negative GLS and lesser increase in hsTnT at AC-end.

Conclusion

In this small scale RCT, supervised ET during AC was not superior to wearing a PA tracker to mitigate cardiotoxicity. The dose-response relationship between PA and cardioprotective effects during AC found in our and previous data supports the notion that PA should be recommended to patients undergoing AC.

Clinical Trial Registration

ClinicalTrials.gov, identifier NCT03850171.
Disproportionate impacts of the COVID-19 pandemic on early career researchers and disabled researchers in volcanology
Authors: Chim Man Mei , Maters Elena C. , Morin Julie , Kavanagh Janine L. , Donovan Amy , Aubry Thomas J. , Schmidt Anja
Published: December 2023

The COVID-19 pandemic has brought unprecedented challenges to researchers worldwide, and extensive studies have demonstrated that its impacts since March 2020 have been unequal, including across research discipline, gender, and career status. In 2023, as we navigate the post-pandemic times, questions persist regarding potential disparities and enduring effects faced by volcanology researchers, whose activities range from field work in remote areas to laboratory experiments and numerical modelling. In this study, we explore the multifaceted impacts of the pandemic on volcanology researchers through an online survey distributed globally from January to March 2023. Our survey findings reveal that a considerable fraction of volcanology researchers (44%–62%) face longer-term challenges from the pandemic that continue to impact their research, with a notably higher proportion among early career researchers (62%) and researchers with disabilities (76%). In addition, over half (52%) of all surveyed researchers indicated that they had left or considered leaving academia due to pandemic-related factors. A significantly higher proportion of disabled researchers (56%–70%) had left or considered leaving academia compared to researchers without disabilities (42%). Our findings underscore the pandemic’s long-lasting and disproportionate impacts on early career and disabled volcanology researchers. We emphasis the need for concerted efforts by research organisations and funding bodies to mitigate the pandemic’s enduring impacts, and stress the importance of making conferences accessible to support disabled researchers’ participation. As the pandemic’s long-lasting impacts ripple across the broader scientific community, the insights from this research can be used for fostering equitable practices and shaping policies beyond volcanology to other research disciplines.
Elucidating fault-related fold mechanics: a 2D finite element analysis of bending, slip, and buckling mechanisms
Authors: Khalifeh-Soltani Anis , Alavi Seyed Ahmad , Ghassemi Mohammad Reza , Ganjiani Mehdi , Derakhshani Reza
Published: December 2023

Fault-related folds are present in most tectonic settings and may serve as structural traps for hydrocarbons. Due to their economic importance, many kinematic models present for them. Unfortunately, most of them have predominantly concentrated on the sliding mechanism parallel to the layering and often ignore the integral role of buckling in folding processes. This study is at the forefront of exploring the interplay among, sliding, buckling, and bending in the formation of the three fundamental types of fault-related folds: detachment, fault-propagation, and fault-bend folds. To this end, we developed five sets of two-dimensional (2D) finite element models, embodying both elastic and elastic-plastic behaviors. Our results indicate that sliding parallel to layering and faults, in conjunction with buckling, are the predominant mechanisms in fault-related folding. The strain ellipse patterns in our models are consistent with those observed in buckling models, thus affirming the significance of buckling in these geological structures. Furthermore, our models demonstrate that fault slip diminishes from the periphery towards the center in all three types of fault-related folds, in contrast to interlayer slip, which intensifies from the edge towards the center. In essence, a diminution in fault slip at the center is balanced by an augmentation in interlayer slip, leading to thickening and buckling. The genesis of all three fault-related fold types is attributed to the reduction in fault slip, with their distinctiveness defined by the location of this reduction: at the detachment fault tip for detachment folds, at the ramp tip for fault-propagation folds, and at the upper flat for fault-bend folds.
Prevention before intervention: introducing mindfulness-based social-emotional learning in higher education institutions across the United Arab Emirates
Authors: Kassie Seada A.
Published: December 2023

In recent years, several studies have indicated that there is a considerable mismatch between the specific set of skills that employers require and the ones that university graduates have to offer. The 2023 report from the World Economic Forum lists 10 core skills that are sought after by global organizations, six of which are categorized under social-emotional learning. As part of its National Employment Strategy 2031, the United Arab Emirates (UAE) aims to build a knowledge-based economy and increase labor productivity. This communicative piece proposes a policy reform across higher education institutions in the United Arab Emirates, seizing as an opportunity the country’s growing commitment to increase talent attraction and retention in the rapidly evolving workplace. Seeing the significant association between social-emotional competencies and thriving in dynamic professional settings, the article highlights the prevalence of mental health disorders among the general youth in the UAE, the government’s commitment towards awareness and prevention of mental health disorders, the relevance of social-emotional competencies for employability and adaptability in the rapidly evolving workplace, the importance of introducing lessons and training in mindfulness-based social-emotional learning (MBSEL) to build the youth’s adaptability in an ever-changing job landscape, and practical measures that can be taken at the institutional level within the UAE context.
Case report: Genetic analysis of a novel intronic inversion variant in the SPTB gene associated with hereditary spherocytosis
Authors: Xi Bixin , Liu Siying , Zhu Yongbing , Zhang Dedong , Zhang Yu , Liu Aiguo
Published: December 2023

Background: Hereditary spherocytosis (HS) is a congenital haemolytic anaemia attributed to dysregulation or abnormal quantities of erythrocyte membrane proteins. Currently, the most common erythrocytic gene, spectrin β (SPTB), variants are located in exons and give rise to mRNA defects. However, the genetic characteristics and pathogenic mechanisms of SPTB intronic variants are not completely understood. This study aimed to analyse a rare intronic inversion variant in the SPTB gene associated with HS, and explore the impact of the variant on SPTB mRNA splicing.

Method: The clinical manifestations of the patient were summarised and analysed for spherocytosis phenotype diagnosis. The pathogenic variant was identified in the proband using targeted next-generation and Sanger sequencing. RNA sequencing was performed to analyse whether SPTB gene splicing and expression were affected.

Results: Targeted next-generation sequencing identified a novel disease-associated intronic inversion variant of the SPTB gene in the proband. The inversion variant was located between intron 19 and 20, and contained the entire exon 20 and partial sequences of adjacent introns. Sanger sequencing confirmed that the intronic inversion variant only appeared in the genome of the proband, not in his parents. RNA sequencing revealed that the variant could result in the skipping of exon 20 and reduced expression of SPTB mRNA.

Conclusion: This study identifies a rare intronic inversion variant in the SPTB gene associated with hereditary spherocytosis. The pathogenic variant can lead to exon 20 skipping and decreased SPTB gene expression. This finding has not been previously reported in any literature. This study can expand the intronic variant spectrum of the SPTB gene, deepen our understanding of HS pathogenesis, and contribute to the genetic diagnosis and clinical management of patients.
Single-cell and bulk RNA sequencing analysis of B cell marker genes in TNBC TME landscape and immunotherapy
Authors: Zhao Fangrui , Zhao Chen , Xu Tangpeng , Lan Yanfang , Lin Huiqing , Wu Xiaofei , Li Xiangpan
Published: December 2023

Objective

This study amied to investigate the prognostic characteristics of triple negative breast cancer (TNBC) patients by analyzing B cell marker genes based on single-cell and bulk RNA sequencing.

Methods

Utilizing single-cell sequencing data from TNBC patients, we examined tumor-associated B cell marker genes. Transcriptomic data from The Cancer Genome Atlas (TCGA) database were used as the foundation for predictive modeling. Independent validation set was conducted using the GSE58812 dataset. Immune cell infiltration into the tumor was assessed through various, including XCELL, TIMER, QUANTISEQ, CIBERSORT, CIBERSORT-ABS, and ssGSEA. The TIDE score was utilized to predict immunotherapy outcomes. Additional investigations were conducted on the immune checkpoint blockade gene, tumor mutational load, and the GSEA enrichment analysis.

Results

Our analysis encompassed 22,106 cells and 20,556 genes in cancerous tissue samples from four TNBC patients, resulting in the identification of 116 B cell marker genes. A B cell marker gene score (BCMG score) involving nine B cell marker genes (ZBP1, SEL1L3, CCND2, TNFRSF13C, HSPA6, PLPP5, CXCR4, GZMB, and CCDC50) was developed using TCGA transcriptomic data, revealing statistically significant differences in survival analysis (P<0.05). Functional analysis demonstrated that marker genes were predominantly associated with immune-related pathways. Notably, substantial differences between the higher and lower- BCMG score groups were observed in terms of immune cell infiltration, immune cell activity, tumor mutational burden, TIDE score, and the expression of immune checkpoint blockade genes.

Conclusion

This study has established a robust model based on B-cell marker genes in TNBC, which holds significant potential for predicting prognosis and response to immunotherapy in TNBC patients.
Bispecific antibodies revolutionizing breast cancer treatment: a comprehensive overview
Authors: Lan Huan-Rong , Chen Min , Yao Shi-Ya , Chen Jun-Xia , Jin Ke-Tao
Published: December 2023

Breast cancer (BCa) is known as a complex and prevalent disease requiring the development of novel anticancer therapeutic approaches. Bispecific antibodies (BsAbs) have emerged as a favorable strategy for BCa treatment due to their unique ability to target two different antigens simultaneously. By targeting tumor-associated antigens (TAAs) on cancer cells, engaging immune effector cells, or blocking critical signaling pathways, BsAbs offer enhanced tumor specificity and immune system involvement, improving anti-cancer activity. Preclinical and clinical studies have demonstrated the potential of BsAbs in BCa. For example, BsAbs targeting human epidermal growth factor receptor 2 (HER2) have shown the ability to redirect immune cells to HER2-positive BCa cells, resulting in effective tumor cell killing. Moreover, targeting the PD-1/PD-L1 pathway by BsAbs has demonstrated promising outcomes in overcoming immunosuppression and enhancing immune-mediated tumor clearance. Combining BsAbs with existing therapeutic approaches, such as chemotherapy, targeted therapies, or immune checkpoint inhibitors (ICIs), has also revealed synergistic effects in preclinical models and early clinical trials, emphasizing the usefulness and potential of BsAbs in BCa treatment. This review summarizes the latest evidence about BsAbs in treating BCa and the challenges and opportunities of their use in BCa.
Serum sulfatide level is associated with severe systemic vasculitis with kidney involvement
Authors: Aomura Daiki , Harada Makoto , Nakajima Takero , Nimura Takayuki , Yamaka Kosuke , Yamada Yosuke , Hashimoto Koji , Tanaka Naoki , Kamijo Yuji
Published: December 2023

Sulfatides are a type of sulfated glycosphingolipid that are secreted with lipoproteins into the serum. These molecules are involved in the inflammatory pathway of vessels in addition to coagulation and platelet aggregation. Previous studies have proposed that sulfatides play a pivotal role in regulating inflammation-related disorders. Systemic vasculitis (SV) diseases are generally caused by autoimmune diseases and often involve kidney vasculitis, which may lead to rapidly progressive kidney dysfunction and end-stage kidney disease. Our earlier pilot study revealed that the level of serum sulfatides (SSs) was significantly decreased in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV), a representative disease-causing SV with kidney involvement (SVKI), especially in patients exhibiting active crescentic findings on kidney biopsy. To further explore the clinical significance of an association between SS and SVKI, we analyzed and compared the SS level of patients with various SVKI diseases in this retrospective cohort study. Among patients admitted to our hospital between 2008 and 2021, we ultimately enrolled 26 patients with IgA vasculitis (IgAV), 62 patients with AAV, and 10 patients with anti-glomerular basement membrane disease (GBM) as examples of SVKI diseases, as well as 50 patients with IgA nephropathy (IgAN) and 23 donors for living kidney transplantation as controls. The mean ± standard deviation SS level in the donor, IgAN, IgAV, AAV, and GBM groups was 8.26 ± 1.72, 8.01 ± 2.21, 6.01 ± 1.73, 5.37 ± 1.97, and 2.73 ± 0.99 nmol/mL, respectively. Analysis of patients in the SVKI disease group showed that those with the crescentic class kidney biopsy finding exhibited a significantly lower SS level than did those with other class biopsy features. Additionally, the SS level had a higher detection ability for SVKI patients with crescentic class kidney biopsy findings (area under the receiver operating characteristic curve 0.90, 95% confidence interval 0.82–0.99) than did several other predictor candidates. Our results indicate that the SS level is decreased in more severe SVKI diseases and may be associated with active glomerular lesions in SVKI kidney biopsy samples.
Efficacy of pegylated interferon α-2b plus entecavir therapy and predictors of treatment success in children with chronic hepatitis B
Authors: Huang Liang , Zhang Hong , Kang Xintong , Chen Zhu , Wang Lin , Zeng Yilan
Published: December 2023

Introduction

Interferon therapy, used in the treatment of chronic hepatitis B (CHB), is one of the means by which patients can achieve a functional cure. Pegylated interferon is currently used in the treatment of CHB. There are two main types of pegylated interferon: α-2b and α-2a.

Methods

This study explored the efficacy, safety, and predictors of treatment response for α-2b plus entecavir among children in a real-world setting.

Results

The study included 76 patients aged 3–18 years, all of whom were treated with interferon α-2b plus entecavir. The mean duration of treatment was 401.99 days, and 31.6% (24/76) of patients achieved HBsAg clearance. Competing risk model analyses showed that children with baseline HBsAg <1500 IU/mL (subdistribution hazard ratio [sHR]=2.643, P=0.022) and a higher baseline alanine aminotransferase (ALT) level (sHR=1.005, P=0.000) had a higher probability of achieving HBsAg clearance during treatment. Conversely, children with a higher hepatitis B virus loading level (sHR=0.835, P=0.043) and age ≥10 years (sHR=0.243, P=0.002) had a lower probability of achieving HBsAg clearance during treatment. A decrease of >1 log10 in HBsAg level (sHR=3.479, P=0.001) at 12 weeks of treatment was associated with a higher probability of achieving surface antigen clearance.

Discussion

These results indicated that interferon plus entecavir therapy is a promising means of achieving HBsAg clearance in children with CHB. Moreover, HBsAg, ALT, virus loading, and age are indicators of treatment success probability.
Redox and proteolytic regulation of cardiomyocyte β1-adrenergic receptors – a novel paradigm for the regulation of catecholamine responsiveness in the heart
Authors: Steinberg Susan F.
Published: December 2023

Conventional models view β1-adrenergic receptors (β1ARs) as full-length proteins that activate signaling pathways that influence contractile function and ventricular remodeling - and are susceptible to agonist-dependent desensitization. This perspective summarizes recent studies from my laboratory showing that post-translational processing of the β1-adrenergic receptor N-terminus results in the accumulation of both full-length and N-terminally truncated forms of the β1AR that differ in their signaling properties. We also implicate oxidative stress and β1AR cleavage by elastase as two novel mechanisms that would (in the setting of cardiac injury or inflammation) lead to altered or decreased β1AR responsiveness.
Scenarios of temporal environmental alterations and phytoplankton diversity in a changing bay in the East China Sea
Authors: Wang Yu , Wang Weibo , Huang Yaqin , Chang Lin , Tang Xiaoming , He Xuebao , Lin Hui
Published: December 2023

In the context of global change, the stressors of warming and eutrophication have significant ecological implications in coastal waters. In order to examine the diversity of phytoplankton and its relationship with water quality, we conducted a survey of phytoplankton community compositions and their correlation with environmental changes over four seasons in a eutrophic bay located in the East China Sea. Through a systematic analysis, we identified diatoms and dinoflagellates as the primary dominant groups, with the species Skeletonema costatum, Skeletonema marinoi, Biddulphia sinensis, Thalassiosira eccentrica, Leptocylindrus danicus, Coscinodiscus oculus-iridis, Coscinodiscus jonesianus, and Chaetoceros knipowitschi as the most abundant species in all seasons. Significant seasonal alterations were observed in both environmental settings and phytoplankton species richness, dominance, and abundance. The phytoplankton community varied in its response to diverse aquatic environments and was principally affected by temperature, silicic acid concentrations, and suspended solids. Elevated temperatures were found to promote an increase in phytoplankton abundance. However, no clear evidence of diatom and dinoflagellate succession in relation to N:P ratio was observed across seasons. Water quality analysis illustrated that the majority of the study area exhibited a mid-eutrophic with severe organic pollution. The abundance of phytoplankton was significantly influenced by eutrophication and organic pollution. The accelerated warming process related to coastal nuclear power plants and nutrient regime alterations significantly affect the temporal shift of the phytoplankton community. These findings contribute valuable insights into the effects of eutrophic environments on the structure of phytoplankton communities in coastal aquatic systems.
Altered dietary behaviour during pregnancy impacts systemic metabolic phenotypes
Authors: Rowley Charlotte E. , Lodge Samantha , Egan Siobhon , Itsiopoulos Catherine , Christophersen Claus T. , Silva Desiree , Kicic-Starcevich Elizabeth , O’Sullivan Therese A. , Wist Julien , Nicholson Jeremy , Frost Gary , Holmes Elaine , D’Vaz Nina
Published: December 2023

Rationale

Evidence suggests consumption of a Mediterranean diet (MD) can positively impact both maternal and offspring health, potentially mediated by a beneficial effect on inflammatory pathways. We aimed to apply metabolic profiling of serum and urine samples to assess differences between women who were stratified into high and low alignment to a MD throughout pregnancy and investigate the relationship of the diet to inflammatory markers.

Methods

From the ORIGINS cohort, 51 pregnant women were stratified for persistent high and low alignment to a MD, based on validated MD questionnaires. 1H Nuclear Magnetic Resonance (NMR) spectroscopy was used to investigate the urine and serum metabolite profiles of these women at 36 weeks of pregnancy. The relationship between diet, metabolite profile and inflammatory status was investigated.

Results

There were clear differences in both the food choice and metabolic profiles of women who self-reported concordance to a high (HMDA) and low (LMDA) Mediterranean diet, indicating that alignment with the MD was associated with a specific metabolic phenotype during pregnancy. Reduced meat intake and higher vegetable intake in the HMDA group was supported by increased levels of urinary hippurate (p = 0.044) and lower creatine (p = 0.047) levels. Serum concentrations of the NMR spectroscopic inflammatory biomarkers GlycA (p = 0.020) and GlycB (p = 0.016) were significantly lower in the HDMA group and were negatively associated with serum acetate, histidine and isoleucine (p < 0.05) suggesting a greater level of plant-based nutrients in the diet. Serum branched chain and aromatic amino acids were positively associated with the HMDA group while both urinary and serum creatine, urine creatinine and dimethylamine were positively associated with the LMDA group.

Conclusion

Metabolic phenotypes of pregnant women who had a high alignment with the MD were significantly different from pregnant women who had a poor alignment with the MD. The metabolite profiles aligned with reported food intake. Differences were most significant biomarkers of systemic inflammation and selected gut-microbial metabolites. This research expands our understanding of the mechanisms driving health outcomes during the perinatal period and provides additional biomarkers for investigation in pregnant women to assess potential health risks.
Case Report: The first report of PPP2R1A mutations in mesonephric-like adenocarcinoma of endometrial carcinoma
Authors: Cai Lei , Yang Chenmin , Gu Yijin , Dong Lei , Feng Weiwei
Published: December 2023

We performed clinical treatment, histopathology, immunohistochemistry and molecular analyses. To compare with the published literature and have a reference overview. A 57-year-old woman and a 77-year-old woman presented with mesonephric-like adenocarcinoma of endometrium at an early clinical stage. The former had no deep myometrial infiltration and no regional lymph node involvement. The latter had deep myometrial infiltration, presence of LVSI and no regional lymph node involvement. Both of the tumor cells were positive for PAX8, GATA-3,CD-10,TTF-1,AE1/AEs,Ki67,P53 and P16 in immunohistochemical staining (IHC)Test. Primary tumors were examined for gene mutations by next generation sequencing. The former was identified KRAS mutation. The latter had KRAS,PIKCA and PPP2R1A mutations. To our knowledge, it is the first time that PPP2R1A(protein phosphatase 2,regulatory subunit A,α) mutation in MLA is reported in English literature.
Extended long-term follow-up of metastatic melanoma patients treated with immunotherapy: late relapses and second primary melanomas
Authors: Minor David R. , Kim Kevin B. , Karuturi R. Krishna M. , Kashani-Sabet Mohammed
Published: December 2023

Background

Immunotherapy has revolutionized the treatment of patients with advanced melanoma as well as other cancers. Most studies, whether of interleukin-2 or checkpoint inhibitor therapies, have limited follow-up after 5 years, making the incidence of late relapses uncertain. In addition, the incidence of second primary melanomas in patients with stage IV melanoma treated with immunotherapy has rarely been reported.

Methods

We performed a single-institution retrospective study of stage IV melanoma patients treated with interleukin-2 or checkpoint inhibitors over the period from 1992 to 2013. We found 59 patients alive and in remission 5 years after the beginning of immunotherapy and reviewed their subsequent clinical course.

Results

This 59-patient cohort had a median follow-up of 13.1 years, with 36 patients followed up for at least 10 years. Four patients (6.8%) had relapses of their metastatic melanoma at 5, 8, 15, and 17 years after starting the successful immunotherapy. Three of the four are still alive. Only one patient in 690 patient-years of observation had a second primary invasive melanoma.

Conclusion

Although late relapses after immunotherapy for melanoma do occur, we can conclude that the prognosis of stage IV melanoma patients in continuous remission 5 years after starting immunotherapy is excellent, with a progression-free survival of approximately 85% and a melanoma-specific survival of approximately 95% at 20 years in our series. Our incidence of second primary melanomas is lower than usually reported. These results have important implications regarding the follow-up of stage IV melanoma patients successfully treated with immunotherapy.