bluuebunny/crossref_metadata_2025 huggingface dataset:
Prescribing Patterns of Proton Pump Inhibitors in Germany: A Retrospective Study Including 472 146 Patients
Authors: Plehhova Kate , Haering Monika , Wray Joshua , Coyle Cathal , Ibáñez Eduardo , Kostev Karel
Published: December 2023

The aims of this study were to analyze proton pump inhibitor (PPI) users in Germany, defining and classifying them in terms of treatment appropriateness, and to analyze the PPI prescription practices of healthcare providers. The updated DGVS (Deutsche Gesellschaft für Gastroenterologie, Verdauungs-und Stoffwechselkrankheiten) gastroesophageal reflux disease (GERD) treatment guideline (published March 2023) for mild heartburn symptoms recommends carrying out a probatory treatment of mild symptoms via other medication such as antacids, alginates, and H2 blockers before escalating to PPI treatments, if the patient profile allows. This retrospective cross-sectional study was based on data from the IQVIA™ Disease Analyzer database (DA) and included adult patients (18 years or older) in 1006 general and 39 gastroenterological practices in Germany who received at least 1 PPI prescription or alginate between September 2019 and September 2021 (hereinafter referred to as the index period). Analyses included indications associated with PPI prescription, co-diagnoses, co-therapies of PPI patients, duration of PPI therapy, dosages of PPI prescriptions, and proportions of practices prescribing PPIs and alginates. A total of 472 146 patients taking PPIs and 9101 patients taking alginates were available for analysis. Very few patients (4.5%) of the total cohort were treated in complete adherence to treatment guidelines. Conditions such as gastritis and duodenitis (47.2%) and reflux diseases (38.4%) were more frequently associated with PPI prescriptions. The average PPI treatment period lasted 141 days, and 36.6% of patients were treated for >6 months. High doses were prescribed relatively often (ie, 42.8% of esomeprazole prescriptions were 40 mg, 59.1% of lansoprazole prescriptions 30 mg, 28.6% of omeprazole prescriptions 40 mg). With each practice prescribing PPIs to at least 10% of their patients; 72% of general practitioners (GPs) and 8% of GENTS (Gastroenterologists) prescribed alginates. This study highlights that discrepancies exist between clinical guidelines and real-life prescribing practices of PPIs in Germany. Particular attention should be given to the incidence of patients being prescribed high-dose or long-duration PPI with mild indications. These findings are particularly apt considering the publication (March 2023) of new guidelines on the “management of gastroesophageal reflux disease and eosinophilic esophagitis,” by the DGVS.
Risk Terrain and Multilevel Modeling of Street Robbery Distribution in Baltimore City
Authors: Ejiogu Kingsley U.
Published: December 2023

The structure and functions of neighborhoods determine the impact of measures used to estimate the distribution of street robbery across space and time. The risk of street robbery could vary between different sections of the area. Prior research has typically relied on one-dimensional analysis, which sparsely accounts for the hierarchical configuration of a neighborhood’s influence on spatial crime distribution. Much less is known about how the predictor variables moderate each other at different neighborhood levels. Data was collected from 13,789 US Census blocks ( N = 13,788) aggregated to administrative neighborhoods ( N = 278) to examine how neighborhood structure affects street robbery distribution at two spatial levels. A Risk Terrain Model was adopted to develop a physical environment risk measure—Aggregate Neighborhood Risk of Crime (ANROC), which, alongside sociodemographic risk factors, predicted the outcomes of the Negative Binomial General Linear Regression models. Study findings suggest that individual-level (block) and group (neighborhood) level predictors influenced street robbery. Both group-level physical environment and total population moderated the impact of the individual-level physical environment on street robbery incidents.
Combining Building Block Process With Computational Thinking Improves Learning Outcomes of Python Programming With Peer Assessment
Authors: Hsiao Tsung-Chih , Chuang Ya-Hsueh , Chang Chien-Yun , Chen Tzer-Long , Zhang Hong-Bo , Chang Jhih-Chung
Published: December 2023

The capability of computer programming language logic is one of the basics of technical education. How to improve students “interest in program logic design and help overcome students” fears of coding has become vital for educators. Cultivating practical talents with information technology application and basic programming development will become one of the important topics in the department of information related science. The objective of this research is to improve the ability of learning basic programming courses by using Zuvio interactive software. Zuvio employs the mathematical logic of computational thinking to analyze problems and enhance learners’ interest in learning programming skills through a graphical interface tool with building blocks. It uses innovative interactive teaching to use peer and self-assessment to study the content of the course. Zuvio improves the design ability of different groups of class learning Python programming. In line with the innovative teaching policy of the schools and the current stage of the learner’s learning model, learning effectiveness can be achieved. The research results were analyzed by midterm and final experimental group scores, and the progress of the experimental group’s scores was examined through descriptive statistics. The average and standard deviation of the assessment were used to analyze the progress of the experimental group students in the programming course. In the classroom, assessment criteria were set up as the basis for peer assessment scoring. After the midterm and final exams, the teacher assessment and peer assessment scores were analyzed for cognitive differences, and possible learning differences were analyzed. The students’ professional ability was examined to see if it met the professional standards required by the course, and whether innovative teaching methods could improve the learning outcomes of learners with different professional backgrounds in Python programming.
Consequence of Resistance to Change on AI Readiness: Mediating–Moderating Role of Task-oriented Leadership and High-Performance Work System in the Hospitality Sector
Authors: Li Cai , Ashraf Sheikh Farhan , Amin Saba , Safdar Muhammad Nabeel
Published: December 2023

In the modern era of the fourth industrial revolution, where collaborative systems are the real innovation, people are still not prepared for the results of the third revolution, namely, artificial intelligence readiness (AIR). Hence, people didn’t have enough time to adapt to the change. This paper aimed to explore the impact of resistance to change on artificial intelligence readiness and also explores the mediating role of task-oriented leadership, moderating role of high-performance work system. The study employs a quantitative research design and collects data of 450 working employees from hospitality sector of Pakistan. SmartPLS is used to analyze structural equation modeling (SEM) to through mixed-methods approach. The study findings are consistent with the proposed study hypotheses that resistance to change has positively impacts RI readiness and task-oriented leadership. Furthermore, the findings also elaborate the mediation of task-oriented leadership between latent constructs and moderating role of high-performance work system between resistance to change and task-oriented leadership. The study concluded that the hospitality sector should focus on developing task-oriented leadership and high-performance work systems to overcome resistance to change and increase its AI readiness.
Teacher Autonomy Support Influence on Online Learning Engagement: The Mediating Roles of Self-Efficacy and Self-Regulated Learning
Authors: Miao Jia , Ma Li
Published: December 2023

Higher education faculty’s autonomous support of online teaching can promote students engagement in online context. This study collected 492 Chinese university students’ survey questionnaires and applied structural equation model to measure their teacher autonomy support, self-efficacy, self-regulated learning (SRL), and online learning engagement. This study adopted self-determination theory (SDT), systematically explored the relationship between teachers’ autonomy support and student learning engagement from the perspective of online contexts, and examined the mediating effects of students’ self-efficacy and self-regulated learning (SRL) in online contexts. This study found that teacher autonomy support had a significant effect on student engagement in online learning, and was mediated by self-efficacy. Teacher-directed support had a significant effect on student engagement in online learning mediated by SRL. Teacher-directed support had a significant impact on online learning with self-efficacy and SRL as the main mediating variables. Therefore, this study gave a fresh perspective to improve students’ online learning engagement, that is to say, teachers were encourage to improve students’ autonomy in practical teaching on the basis of giving students autonomy support. Students can promote online learning engagement by strengthening self-efficacy and self-regulation through organizational exchanges and mutual assistance and cooperation of students.
Design and Validation of Professional Development Environment Model Based on Task-Centered Approach in Medical Education
Authors: Salary Somayeh , Amin Beydokhti Ali Akbar , Karami Morteza , Layegh Parvaneh , Mahdavi Rashed Masoud , Mahmoudian Mozhgan
Published: December 2023

This study aimed to design and validate a professional development environment model based on a task-centered approach in medical education. Accordingly, a mixed research design was used, and a qualitative content analysis was performed using a synthesis research method to identify the elements and components of the proposed model. Furthermore, a descriptive survey method was employed to validate the model from the point of view of experts. For the purposeful selection of resources considering the identification of the components of the professional development environment model based on the task-centered approach, authentic scientific documents indexed in databases, such as Scopus, Science Direct, Springer, Google Scholar, ProQuest, Emerald, and PubMed from 2000 to 2022 were reviewed, and 48 documents were selected. Then, they were analyzed using open coding and axial coding. To validate the proposed model, 20 specialists in radiology, medical education, and educational sciences were selected as a sample. The data were collected through an 8-item researcher-made questionnaire the content validity of which was confirmed by calculating S-CVI and CVI. According to the analysis, 4 main components and 14 sub-components were extracted, which led to the design of the desired model. The findings in the quantitative part also showed that the presented model has high internal validity in the field of medical education. Therefore, it is suggested to use this model as an innovative strategy and guidance for medical professionals.
Evaluating the Mediating Mechanism of Perceived Trust and Risk toward Cryptocurrency: An Empirical Research
Authors: Rahardja Untung , Chen Shih-Chih , Lin Yu-Chun , Tsai Tsung-Chieh , Aini Qurotul , Khan Asif , Oganda Fitra Putri , Dewi Elisa Royani , Cho Ying-Chieh , Hsu Chung-Hao
Published: December 2023

In recent years, investing in cryptocurrencies has become a fad worldwide. However, fewer studies have explored the intention of using cryptocurrencies. Different from traditional financial commodities, cryptocurrencies have a unique appeal. Therefore, this study uses technology mindfulness, technology readiness, and financial literacy, and through perceived trust and perceived risk, to understand users’ intentions to use cryptocurrencies. The respondents to this study were cryptocurrency owners or those having financial investment experience. A total of 337 valid samples were obtained and analyzed by the partial least square-structural equation model (PLS-SEM) method. The results showed that technology mindfulness and negative technology readiness significantly impacted perceived trust and perceived risk. On the other hand, perceived trust and perceived risk significantly impacted the intention to use. Finally, this study proposes theoretical and practical implications which can help cryptocurrency trading platforms understand the motivations of potential and existing users. Finally, this study can also serve as a reference for cryptocurrency trading service providers to develop marketing strategies.
The Interaction Between Financial Development and Economic Growth: A Novel Application of Transfer Entropy and Nonlinear Approach in Algeria
Authors: Al khatib Abdullah Mohammad Ghazi , Alshaib Bayan Mohamad , Kanaan Ali Mohamad
Published: December 2023

This study examines the complex interaction between Financial Development (FD) and Economic Growth (EG) in Algeria from 1980 to 2020 using nonlinear modeling techniques. We apply the Non-Linear Causality test with Transfer Entropy, a novel method in this literature, to confirm the nonlinear causality from FD to EG. We also use the Nonlinear Autoregressive Distributed Lag (NARDL) model and the Cumulative Dynamic Multiplier (CDM) to establish the long-run equilibrium and the short-run dynamic relationship between FD and EG. The NARDL results support the Transfer Entropy findings and show that FD has a symmetric impact on EG in both the short and long term. Positive and negative shocks on FD affect EG similarly and the imbalance is corrected in about 6 years. This study provides useful information for policymakers and stakeholders to design policies that promote (EG) and development in Algeria by enhancing FD and mitigating shocks.

JEL Codes: C45, C32, E44, O16, O53
Relieving Social Anxiety Disorder: The Impact of Traveling Abroad on Improving English Listening Skills From Students’ Perspectives
Authors: Al Abiky Waleed B.
Published: December 2023

The current study aimed to investigate the underlying effects of short-term traveling abroad on relieving social anxiety disorder (SAD) and improving English listening skills based on students’ perspectives. The study examined the effects of two independent variables: (1) the duration of traveling abroad and (2) the type of listening sources. Mixed-method approaches with a purposive sample were used consisting of 112 students with (SAD) majoring in English at Qassim University, Saudi Arabia. All participants enrolled in the fall 2018 semester and had traveled abroad to an English-speaking country for a period ranging from 1 to 8 weeks. Surveys were distributed, and five participants were semi-structurally interviewed. The study found that: (1) with alpha set at (α ≤ .05), traveling abroad was a significant factor in relieving the (SAD), and statistically significant differences were observed for the duration of travel abroad for those who stayed abroad longer; (2) there were three effective listening sources on relieving the (SAD) during traveling abroad: (a) living with a host family or a roommate, (b) solo listening to TV channels or movies, and (c) social gatherings and events; and (3) formal listening situations such as the ones occurred at banks, airports and police stations, were the most confusing and least effective. In addition, for the variation of the effective listening sources, one-way ANOVA was used, and the results showed no statistically significant differences. More traveling or study abroad opportunities should be encouraged as the study opens doors for further academic investigations.
How Can Pairing Quantitative With Qualitative Data Collection Methods Better Elicit Rice Varietal Selection? Evidence From Burundi
Authors: Ng’endo Mary , Nduwimana Julien , Villanueva Donald , Demont Matty
Published: December 2023

Participatory Varietal Selection (PVS) is the selection by stakeholders of varieties in advanced testing stages by plant breeding programs. With Burundi as a case example, this study incorporated qualitative Focus Group Discussions (FGDs) into the quantitative PVS structure so as to elicit deeper insights into rice trait preferences and illuminate broader issues affecting rice farmers. During two consecutive years, this study surveyed 174 participants across six stakeholder groups (administrators, farmers, custom millers, researchers, seed producers, and traders) in three locations. There were statistically significant associations in rice trait preferences across locations, participating stakeholders, and genders, highlighting preference alignment. Moreover, multiple traits were desired simultaneously, beyond productivity-related traits, and sometimes contradicting researchers’ preferences, especially in rainfed systems. By moving beyond quantitative PVS preference scores as being the only way of gathering trait preference data, this study has shown how the incorporation of qualitative FGDs into the PVS structure can elicit deeper insights on trait preferences and illuminate broader issues affecting rice farmers, which when solved can accelerate the momentum in widespread adoption of new rice varieties.
Macroeconomic Announcements: How Announcements Shape Trading Strategies
Authors: Cui Qi , Zhao Tianhong , Cui Tingyue
Published: December 2023

The Capital Asset Pricing Model (CAPM) is a widely used and tractable model relating financial risk and return. However, it has been less successful when taken to the data. In their seminal paper, Frazzini and Pedersen propose a Betting Against Beta (BAB) factor to take advantage of this fact. In their construction, the BAB factor is a portfolio which longs low-beta stocks and shorts high-beta stocks. Since its construction, the BAB factor has been widely cited and used both in financial academics and in industry. This paper proposes a novel betting on and against beta (BOAB) strategy, which bets on beta on days with macroeconomic announcements and bets against beta on days without. Here, macroeconomic announcement days are defined as days when inflation, unemployment, or interest rate decisions are released. Our findings confirm the persistent positive beta-return relationship observed on macroeconomic announcement days. We show that compared to the BAB strategy, BOAB delivers higher average daily excess returns over the time period 1964 to 2021 when applied to the U.S. stock market. This outperformance of the BOAB strategy is robust to different constructions of the BAB factor and is economically and statistically significant when compared with the usual asset pricing factors such as value, size, and momentum. The outperformance of the BOAB strategy could be used to inform agents’ portfolio allocation choices. Limitations are also discussed.
Like Performance, Perfect Match: Role of Past Performance in Venture Capital Syndication
Authors: Qiu Zhiyi , Liu Bingyi , Yang Ye
Published: December 2023

Syndication among venture capital firms (VCFs) is increasingly prevailing in recent years, especially in emerging markets like China. Some of the VCFs have to syndicate with “worse performers” despite the “better performer preference.” The primary aim of this article is to contribute to our understanding of the impact performance gap among syndicated VCFs on formulation and duration of syndicate. The data consist of over 295,000 pair of VCFs syndicated in China mainland from 2000 to 2020. We find the negative effect of performance gap on the propensity of syndication with self-categorization of VCFs as the moderator. The key contribution of this paper is to test the significance of homogenous performance in syndication. This study advances the knowledge of agency in collaboration and sheds new light on organizational performance feedback in venture capital markets.
Pre-Service Teachers’ Instructional Innovation Capabilities: A Many-Faceted Rasch Model Analysis
Authors: Liu Jun , Sun Meng , Liu Zile , Xu Yanhua
Published: December 2023

Innovation capability has become a necessary requirement for qualified teachers in the context of informatization. However, the validity and objectivity of existing assessments are unclear. Therefore, this study selected nine researchers to evaluate the instructional innovation capabilities of 60 pre-service teachers from a Chinese normal university. The Many-Faceted Rasch Model (MFRM) was used to measure and analyze the rater severity, difficulty of evaluation criteria, and instructional innovation capability of pre-service teachers. Combined with qualitative analysis, the results showed that most participants had moderate instructional innovation capability, and only certain individuals demonstrated a high level. In addition, innovation related to teaching content and learning activities was easier than innovation related to instructional and evaluation strategies. These results suggest directions for fostering pre-service teachers’ instructional innovation capabilities.
Relationships Between Achievement Goals, Motivation Instability, and Learning Persistence in Asynchronous Distance Classes
Authors: Umemoto Takatoyo , Inagaki Tsutomu
Published: December 2023

This study examined the relationships between achievement goals, motivation instability, and learning persistence in asynchronous distance classes by focusing on mastery goals and performance-avoidance goals. A longitudinal online survey was conducted among university students in Japan at two time points. The first survey had 171 respondents. Out of them, 91 responded to the second survey. The data of the 91 students were analyzed. The results of partial correlation analysis indicated that mastery goals were negatively related to motivation instability and lack of persistence, while performance-avoidance goals were positively related to lack of persistence and unrelated to motivation instability. Mediation analysis indicated that the negative indirect effect of mastery goals on lack of persistence via motivation instability was found, and that the direct effect of mastery goals on lack of persistence was not found. The results highlight the vital role that mastery goals play in learning during asynchronous distance classes.
Inflation Differential Pass-Through to Exchange Rate: Some Evidence From Pakistan
Authors: Zakaria Muhammad , Tanveer Seemab , Fida Bashir Ahmad , Iftikhar ul Husnain Muhammad
Published: December 2023

Using regression and wavelet coherence techniques this paper tries to probe the validity of purchasing power parity (PPP) in Pakistan. For this purpose, monthly data is collected for nominal exchange rate and consumer prices of Pakistan and its 23 major trading partners for the flexible exchange rate period 1982M1 to 2020M12. The regression results show that in 12 countries inflation differential significantly positively affect exchange rate. Similarly, Granger causality results reveal that inflation differential causes exchange rates in 12 countries. Wavelet coherency results indicate that there is significant co-movements between inflation differentials and exchange rates in varying time and frequency domains in all countries. These results indicate the partial validity of PPP in Pakistan. These results suggest that by reducing its inflation Pakistan can stabilize its exchange rates.

JEL Classifications: C14, E31, F31
Shopping Companions and Their Diverse Impacts: A Systematic Annotated Bibliography
Authors: Scholz Tobias Benjamin , Pagel Sven , Henseler Jörg
Published: December 2023

Research studies of shopping with companions, or “co-shopping,” have investigated different "types of companion" (e.g., children, spouses, parents, friends) and the nature of their influence on shoppers’ retail experience. By means of a systematic literature review guided by the standard review protocol PRISMA and qualitative content analysis, this paper offers a state-of-the-art overview of 66 studies and their findings, through the middle of 2023. It finds that sparse attention has been paid to shopping companions’ behaviors and personalities and that it is so far impossible to attribute their impacts on shoppers specifically to one or more types of companion. It also finds that the various factors that could facilitate understanding of how companions’ influences work in practice remain largely unexplored. In short, too little is known about how companions exert their influence and how shoppers process it and there remains much to be investigated about the interplay between shoppers, their companions, and an interacting salesperson. Our detailed findings and their implications could therefore usefully shape the agenda for future research into accompanied shopping.
Commuting and Acceptance of Worksite Physical Activity Opportunities: Insights From a French University Hospital
Authors: Da Silva Baptiste , Constant Aymery , Brière Marie , Schnebelen Celine
Published: December 2023

Background:

Recent research suggests a need for worksite programs that promote structured physical activity (PA) among hospital staff. The objectives of this study were to assess the hospital employees’ acceptance of PA opportunities that could be implemented at the worksite, and the association between worksite PA and commuting and other sociocognitive factors.

Method:

Acceptance of seven PA opportunities from the WHO guidelines was correlated with commuting and socio-cognitive factors through an online survey conducted among the workforce of the University Hospital of Angers, France ( N = 6874) between April 25 and May 22, 2022.

Results:

Only three PA opportunities in the seven proposed reached high approval rates among at least 50% of the 1,427 participants, namely, provide cycle facilities onsite, create a fitness room onsite, and establish partnerships with private associations or sports clubs, albeit rates decreased significantly with commuting distance for the first and the last proposals. The number of approved PA opportunities was positively related to the perceived negative influence of commuting on well-being and self-rated concerns with current PA level. It was negatively related to older age, long commuting, and flexible rest days.

Conclusion:

Based on these results, we recommend raising PA awareness and self-efficacy before implementing an easily accessible fitness center for employees. Providing cycle facilities and a more walkable environment in the hospital setting while encouraging active traveling between home and work for short commuters could additionally increase the level of physical activity on an equitable and sustainable basis.
Not So Benign Chest Pain in the Young: A Story of Spontaneous Coronary Artery Dissection and Fibromuscular Dysplasia
Authors: Dah Kingsley , Desai Rohan , Patel Divyank , Patel Amar , Lopes Jan , Borges Jorge Chiquie
Published: December 2023

Spontaneous coronary artery dissection (SCAD) is a rare clinical entity, often presenting similar to atherosclerotic acute coronary syndrome (ACS), although it is a non-atherosclerotic, non-traumatic, and non-iatrogenic coronary artery pathology. We report the case of a 36-year-old woman who presented with substernal, pressure-like chest pain without aggravating, alleviating, or associated symptoms. Initial evaluation revealed elevated troponin levels which peaked at 8.71 ng/mL. Electrocardiogram showed borderline J point elevation in the lateral leads. A transthoracic echocardiography revealed mild left ventricular dysfunction with an estimated ejection fraction of 45% to 50%, an akinetic apex with hyperdynamic basal segments, suggestive of stress cardiomyopathy. However, a left anterior descending artery (LAD) infarction could not be excluded. Emergent coronary angiography revealed SCAD of the LAD. No coronary interventions were performed. The patient was managed medically with dual antiplatelet therapy and beta-blockers. Given the high suspicion for fibromuscular dysplasia (FMD), computed tomographic angiography (CTA) of the head to pelvis was performed. The CTA neck showed bilateral focal areas of mild stenosis and dilation of the distal cervical internal carotid artery, and CTA abdomen revealed multiple splenic artery aneurysms, diagnostic of FMD. Unlike atherosclerotic ACS, our patient was managed medically without percutaneous intervention. This case illustrates the rare occurrence of myocardial injury due to SCAD which results in spontaneous intramural hematoma formation rather than atherosclerotic plaque rupture typically seen in ACS. FMD remains the most commonly associated condition with SCAD.
Social Justice and Social Order: Moral Intuitions and Endorsements of Antiblack and Antiwhite Stereotypes
Authors: Silver Eric , Goff Kerby , Iceland John
Published: December 2023

Few topics are as heavily studied as Americans’ beliefs about racial disparities. Most of this research examines white people’s endorsements of stereotypes that blame black people for their unequal position in society. Research in the racial resentment and symbolic racism traditions is perhaps the best-known example of this approach. This research, however, is incomplete and is becoming more so as contemporary U.S. discourse expands to incorporate systemic racism as a fundamental cause of racial disparities. Within this discourse, negative stereotypes of whites—as racially insensitive, biased, and complicit in maintaining systemic racism—are increasingly common. This raises the question, Why do some Americans attempt to make sense of racial disparities by endorsing antiblack stereotypes while others do so by endorsing antiwhite stereotypes? Building on recent work by Silver and colleagues, the authors examine a novel explanation: the strength of people’s moral intuitions regarding social justice and social order. Using a YouGov sample of 1,125 U.S. adults, the authors find that social justice intuitions decrease antiblack stereotypes but increase antiwhite stereotypes, whereas social order intuitions do the opposite. These results suggest that future studies of Americans’ beliefs about racial disparities would benefit from measuring antiblack and antiwhite stereotypes and from measuring people’s social justice and social order intuitions.
Patterns of Global Democracy Promotion: Centrality in DINGO Networks, 1981–2015
Authors: Kim Jessica , Collins Andrew
Published: December 2023

Despite the long-recognized role of international organizational networks in spreading global norms, including democracy, democracy-promoting international nongovernmental organizations (DINGOs) remain understudied. This visualization addresses this gap by plotting nations’ degree centrality within various DINGO networks over time from 1981 to 2015, thereby quantifying, for the first time, the configuration of nonstate democracy promotion networks. The results indicate that all networks are extremely dense, and nations’ mean centrality increases over time. Although dispersion tends to decrease over time, particularly after 2000, relatively high dispersion persists for one network: civil liberties. Thus, although more nations are increasingly integrated within DINGO networks overall, this trend is not uniform. The authors suspect that this difference reflects nations’ growing disillusionment with an enterprise that condemns civil liberties only when geopolitics allow and the subsequently declining traction of civil liberties norms. The results suggest a pivotal yet potentially controversial role of DINGO networks and motivate further research exploring their effects.
Outcomes of Pars Plana Vitrectomy With Membrane Peel for Lamellar Macular Holes and Related Conditions Using a New Optical Coherence Tomography Consensus Definition
Authors: Mohammed Taariq K. , Thompson John T.
Published: December 2023

Purpose: To characterize the change in visual acuity (VA) in eyes treated with vitrectomy using the 2020 international consensus-based optical coherence tomography (OCT) definition of lamellar macular hole (LMH), macular pseudohole (MPH), and epiretinal membrane with foveoschisis (ERMF). Methods: A retrospective chart review was performed from 2000 to 2022 of patients who had vitrectomy for symptomatic decreased VA from LMH, MPH, or ERMF performed by the same surgeon at a community hospital. Preoperative spectral domain (SD-OCT) was reviewed to classify patients using the consensus guidelines. Primary outcomes were the mean change in best-corrected VA at 3 months, 1 year, and the final postoperative examination. Results: Fifty-one patients were included, 30 with LMH, 14 with MPH, and 7 with ERMF. The VA was 20/63 at baseline, 20/62 ( P = .79) 3 months postoperatively, 20/40 ( P = .003) at 1 year, and 20/52 ( P = .10) at the final examination for LMH; 20/64, 20/50 ( P = .16), 20/40 ( P = .040), and 20/40 ( P = .02), respectively, for MPH; and 20/53, 20/50 ( P = .42), 20/30 ( P = .03), and 20/38 ( P = .04), respectively, for ERMF. Subgroup analysis showed that eyes with LMH without ellipsoid zone (EZ) disruption on SD-OCT improved from 20/57 at baseline to 20/39 ( P = .01) at the final examination. Conclusions: There was no significant improvement in VA at the final postvitrectomy examination in eyes with LMH, while there was significant improvement in eyes with MPH and ERMF. This supports surgery in selected eyes with MPH and ERMF but possibly not in eyes with LMH, unless OCT shows no EZ disruption.
Dozing Off With Drosophila: The Effect of Disrupted Circadian Rhythms and Sleep Disturbance on Mortality, Mood, and Addiction
Authors: Lateef Rania S , Pokharel Bibhaw , Shafin Tasnuva Nuhat
Published: December 2023

Many environmental factors can disrupt sleep and circadian rhythms, yet the consequences of such disruptions are poorly understood. The main goals of this project were to study the effects of disrupted circadian rhythms and sleep disturbance on Drosophila melanogaster’s: (1) lifespan, (2) depression-like behaviors, and (3) propensity to consume caffeine-containing media. Three experimental groups were used: controls, Circadian Dysfunction (CD), and Sleep Disturbance (SD). Circadian disruption (CD): used flies with Tim01 mutation, which eliminates circadian behavioral rhythms. Sleep disturbance (SD): used flies subjected to hourly light exposure and manual mechanical disruption, for 48 hours. To assess the effect on lifespan, the percent of flies surviving over time, within each group, was calculated. Impaired geotaxis, or loss of climbing motivation, was assessed as a measure of a depression-like state. Preference for caffeine-containing food was evaluated using a choice chamber where caffeine enriched, and regular media were presented to flies. Group differences were analyzed with survival curves. Chi-square tests were used for the categorical variables. Survival curve analysis showed that Flies with the timeless gene mutation ( tim01) have a significantly shorter lifespan than controls. Geotaxis was not significantly impaired by sleep disturbance, but it was negatively affected by circadian dysfunction. Both the Circadian Dysfunction and Sleep Disturbance groups showed a preference for caffeine-containing food, after 72 hours of exposure to it, although the Circadian Dysfunction group was much more affected than the Sleep Disturbance group. Sleep and circadian disturbances can negatively influence physical and mental wellbeing and the accompanying molecular mechanisms, as well as disrupted brain physiology, must be studied. It is critical to identify and minimize social and environmental disruptors of such biological rhythms.
A Comprehensive Review on the Regulatory Action of TRP Channels: A Potential Therapeutic Target for Nociceptive Pain
Authors: Anand Santosh , Rajagopal Senthilkumar
Published: December 2023

The transient receptor potential (TRP) superfamily of ion channels in humans comprises voltage-gated, non-selective cation channels expressed both in excitable as well as non-excitable cells. Four TRP channel subunits associate to create functional homo- or heterotetramers that allow the influx of calcium, sodium, and/or potassium. These channels are highly abundant in the brain and kidney and are important mediators of diverse biological functions including thermosensation, vascular tone, flow sensing in the kidney and irritant stimuli sensing. Inherited or acquired dysfunction of TRP channels influences cellular functions and signaling pathways resulting in multifaceted disorders affecting skeletal, renal, cardiovascular, and nervous systems. Studies have demonstrated the involvement of these channels in the generation and transduction of pain. Based on the multifaceted role orchestrated by these TRP channels, modulation of the activity of these channels presents an important strategy to influence cellular function by regulating intracellular calcium levels as well as membrane excitability. Therefore, there has been a remarkable pharmaceutical inclination toward TRP channels as therapeutic interventions. Several candidate drugs influencing the activity of these channels are already in the clinical trials pipeline. The present review encompasses the current understanding of TRP channels and TRP modulators in pain and pain management.
Salvage Esophagectomy: Why it Makes Sense to Selectively Resect Squamous Cell Carcinoma
Authors: Zhou Nicolas , Hofstetter Wayne L.
Published: December 2023

Previous clinical trials have concluded that trimodality and bimodality therapy are equivalent for treating locally advanced esophageal squamous cell carcinoma (ESCC). However, the use of chemoradiation alone achieves only a 45% to 50% complete response rate. Surgery remains crucial for locoregional control. In ESCC, salvage esophagectomy for locoregional recurrence has increased morbidity compared to planned esophagectomy. Retrospective data suggest that patients requiring cervical/upper chest anastomosis are more likely to undergo salvage esophagectomy rather than completing trimodality therapy. It’s unclear if selective surgery versus an operative approach on all patients after chemoradiation leads to differences in overall outcomes.
Physiological Archetypes of de novo Gastroesophageal Reflux Disease After Laparoscopic Sleeve Gastrectomy
Authors: Ottoboni Brunaldi Vitor , Ghanem Omar M. , Abu Dayyeh Barham K.
Published: December 2023

Laparoscopic Sleeve Gastrectomy (LSG) is the most common bariatric surgery in the world. While clinically effective, recent studies have shown increasingly higher rates of gastroesophageal reflux disease (GERD) and esophageal motility disorders. We reviewed all the literature and unraveled the underlying mechanism of post-LSG GERD. Finally, we propose a new classification to help us understand the disease and guide work-up, treatment, and future refinements in the surgical technique.
Tumor necrosis factor α promotes clonal dominance of KIT D816V+ cells in mastocytosis: role of survivin and impact on prognosis
Authors: Greiner Georg , Witzeneder Nadine , Klein Klara , Tangermann Simone , Kodajova Petra , Jaeger Eva , Ratzinger Franz , Gerner Marlene C. , Jawhar Mohamad , Baumgartner Sigrid , Fruehwirth Karin , Schmetterer Klaus G. , Zuber Johannes , Gleixner Karoline V. , Mayerhofer Matthias , Schwarzinger Ilse , Simonitsch-Klupp Ingrid , Esterbauer Harald , Baer Constance , Walter Wencke , Meggendorfer Manja , Strassl Robert , Haferlach Torsten , Hartmann Karin , Kenner Lukas , Sperr Wolfgang R. , Reiter Andreas , Sexl Veronika , Arock Michel , Valent Peter , Hoermann Gregor
Published: December 2023

Systemic mastocytosis (SM) is defined by the expansion and accumulation of neoplastic mast cells (MCs) in the bone marrow (BM) and extracutaneous organs. Most patients harbor a somatic KIT D816V mutation, which leads to growth factor–independent KIT activation and accumulation of MC. Tumor necrosis factor α (TNF) is a proapoptotic and inflammatory cytokine that has been implicated in the clonal selection of neoplastic cells. We found that KIT D816V increases the expression and secretion of TNF. TNF expression in neoplastic MCs is reduced by KIT-targeting drugs. Similarly, knockdown of KIT or targeting the downstream signaling cascade of MAPK and NF-κB signaling reduced TNF expression levels. TNF reduces colony formation in human BM cells, whereas KIT D816V+ cells are less susceptible to the cytokine, potentially contributing to clonal selection. In line, knockout of TNF in neoplastic MC prolonged survival and reduced myelosuppression in a murine xenotransplantation model. Mechanistic studies revealed that the relative resistance of KIT D816V+ cells to TNF is mediated by the apoptosis-regulator BIRC5 (survivin). Expression of BIRC5 in neoplastic MC was confirmed by immunohistochemistry of samples from patients with SM. TNF serum levels are significantly elevated in patients with SM and high TNF levels were identified as a biomarker associated with inferior survival. We here characterized TNF as a KIT D816V-dependent cytokine that promotes clonal dominance. We propose TNF and apoptosis-associated proteins as potential therapeutic targets in SM.
Peripheral T-cell lymphoma: are all patients high risk?
Authors: Shea Lauren , Mehta-Shah Neha
Published: December 2023

Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of mature T-cell neoplasms that represent ∼10% of all non-Hodgkin lymphoma. Outcomes for the majority of patients with PTCL are poor, and treatment approaches have been relatively uniform using cyclophosphamide, doxorubicin, vincristine, and prednisone–based therapy. For example, large registry studies consistently demonstrate 5-year overall survival of ∼30% to 40%. However, as our understanding of the biology underpinning the heterogeneity of PTCL improves and as treatments specifically for PTCL are developed, risk stratification has become a more relevant question. Tools including positron emission tomography–computed tomography and minimal residual disease (MRD) monitoring offer the potential for dynamic risk stratification. In this review, we first summarize registry data describing outcomes in the most common subtypes of PTCL: PTCL not otherwise specified, nodal T-follicular helper cell lymphoma including angioimmunoblastic T-cell lymphoma, and anaplastic large cell lymphoma. We describe current clinically based prognostic indices validated for PTCL and highlight emerging tools for prognostication including novel molecular biomarkers, imaging-based metrics, and MRD dynamics.
Whole-genome CRISPR screening identifies molecular mechanisms of PD-L1 expression in adult T-cell leukemia/lymphoma
Authors: Chiba Masahiro , Shimono Joji , Suto Keito , Ishio Takashi , Endo Tomoyuki , Goto Hideki , Hasegawa Hiroo , Maeda Michiyuki , Teshima Takanori , Yang Yibin , Nakagawa Masao
Published: December 2023

Adult T-cell leukemia/lymphoma (ATLL) is an aggressive T-cell malignancy with a poor prognosis and limited treatment options. Programmed cell death ligand 1(PD-L1) is recognized to be involved in the pathobiology of ATLL. However, what molecules control PD-L1 expression and whether genetic or pharmacological intervention might modify PD-L1 expression in ATLL cells are still unknown. To comprehend the regulatory mechanisms of PD-L1 expression in ATLL cells, we performed unbiased genome-wide clustered regularly interspaced short palindromic repeat (CRISPR) screening in this work. In ATLL cells, we discovered that the neddylation-associated genes NEDD8, NAE1, UBA3, and CUL3 negatively regulated PD-L1 expression, whereas STAT3 positively did so. We verified, in line with the genetic results, that treatment with the JAK1/2 inhibitor ruxolitinib or the neddylation pathway inhibitor pevonedistat resulted in a decrease in PD-L1 expression in ATLL cells or an increase in it, respectively. It is significant that these results held true regardless of whether ATLL cells had the PD-L1 3' structural variant, a known genetic anomaly that promotes PD-L1 overexpression in certain patients with primary ATLL. Pevonedistat alone showed cytotoxicity for ATLL cells, but compared with each single modality, pevonedistat improved the cytotoxic effects of the anti–PD-L1 monoclonal antibody avelumab and chimeric antigen receptor (CAR) T cells targeting PD-L1 in vitro. As a result, our work provided insight into a portion of the complex regulatory mechanisms governing PD-L1 expression in ATLL cells and demonstrated the in vitro preliminary preclinical efficacy of PD-L1–directed immunotherapies by using pevonedistat to upregulate PD-L1 in ATLL cells.
Treatment outcomes of complement protein C5 inhibition in 509 UK patients with paroxysmal nocturnal hemoglobinuria
Authors: Kelly Richard J. , Holt Matthew , Vidler Jennifer , Arnold Louise M. , Large Joanna , Forrest Briony , Barnfield Catherine , Pike Alexandra , Griffin Morag , Munir Talha , Muus Petra , Nagumantry Sateesh K. , Varghese Abraham , Davies John R. , Trikha Roochi , Kulasekararaj Austin G. , Mitchell Lindsay , Gandhi Shreyans
Published: December 2023

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal hematopoietic disorder that occurs on a background of bone marrow failure (BMF). In PNH, chronic intravascular hemolysis causes an increase in morbidity and mortality, mainly because of thromboses. Over the last 20 years, treatment of PNH has focused on the complement protein C5 to prevent intravascular hemolysis using the monoclonal antibody eculizumab and more recently ravulizumab. In the United Kingdom, all patients are under review at 1 of 2 reference centers. We report on all 509 UK patients with PNH treated with eculizumab and/or ravulizumab between May 2002 and July 2022. The survival of patients with eculizumab and ravulizumab was significantly lower than that of age- and sex-matched controls (P = .001). Only 4 patients died of thromboses. The survival of patients with PNH (n = 389), when those requiring treatment for BMF (clonal evolution to myelodysplastic syndrome or acute leukemia or had progressive unresponsive aplastic anemia) were excluded, was not significantly different from that of age- and sex-matched controls (P = .12). There were 11 cases of meningococcal sepsis (0.35 events per 100 patient-years). Extravascular hemolysis was evident in patients who received treatment, with 26.7% of patients requiring transfusions in the most recent 12 months on therapy. Eculizumab and ravulizumab are safe and effective therapies that reduce mortality and morbidity in PNH, but further work is needed to reduce mortality in those with concomitant BMF.