bluuebunny/crossref_metadata_2025_split huggingface dataset:
A304 EXPLORING HEPATITIS C TREATMENT COST TRENDS OVER A DECADE: A CROSS-SECTIONAL ANALYSIS WITHIN MEDICARE PART D (2012-2021)
Authors: Tsai C H , Malik G , Congly S E 
Published: February 2024

Abstract

Background
Chronic hepatitis C virus (HCV) infection negatively impacts quality and quantity of life. With the onset of direct-acting antivirals (DAAs), cure rates of HCV have increased to over 95%. Despite these advancements, chronic HCV infection continues to pose a substantial health and financial burden and without drug coverage, treatment of HCV with these DAAs is unaffordable. In the United States, Medicare Part D is a voluntary drug coverage plan predominantly for individuals covered by Medicare (typically over 65 years old) which can facilitate access to these DAAs.

Aims
This study aims to analyze the shifts in HCV treatment and spending in the USA from 2012 to 2021 for Medicare Part D and assess the impact of generic drugs on overall expenditure.

Methods
A retrospective cross-sectional study was conducted using publicly available Centers for Medicare and Medicaid Services (CMS) Medicare D drug spending data from 2012 to 2021. The total expenditure and utilization of HCV drugs was calculated, and average spending per beneficiary was utilized to estimate potential cost savings if generic DAAs were employed.

Results
The study revealed a decline in HCV claims and beneficiaries over 65 since 2015 with a peak of 134,752 beneficiaries decreasing to 35,735 in 2021. Accordingly, spending was the highest in 2015 (8.8 billion USD) and subsequently trended downwards to 1.5 billion in 2021. Over the ten-year period, the USA spent a total of 33.1 billion USD on HCV treatment. Harvoni accounted for 53% of the spending, followed by Sovaldi (17%) and Epclusa (14%). Generic drug utilization slowly increased with the introduction of generics in 2019 with 6.4% of beneficiaries treated with generic DAAs in 2019, rising to 15.3% in 2020 and 14.8% in 2021. If all prescriptions of Harvoni and Epclusa were substituted by ledipasvir/sofosbuvir and sofosbuvir/velpatasvir, respectively, there is a potential $2.7 billion cost reduction. This translates to a potential 47.3% reduction in HCV treatment expenditures from 2019 to 2021.

Conclusions
The decreasing number of beneficiaries for HCV treatment among people over the age of 65 suggests a decreasing HCV prevalence in this age group. This reflects the success of DAA treatment and low reinfection rates. However, the underutilization of generic DAAs despite their lower cost highlights a missed opportunity for substantial savings. This study emphasizes the importance of policy negotiations to ensure optimal resource management, advocating for a shift towards generic drug usage to alleviate the financial burden associated with HCV treatment.

Trends in total spending on DAAs for HCV and number of beneficiaries within Medicare Part D from 2012 to 2021. Annual percent changes in expenditure are shown within the data bars.

Funding Agencies
None
A315 A QUALITY ASSESSMENT OF THE ADEQUACY OF FLUID REPLACEMENT THERAPY FOR PATIENTS DIAGNOSED WITH ACUTE PANCREATITIS
Authors: Patel K , Niazi M , Khan S , Mathura P , Zhang J , Sandha G 
Published: February 2024

Abstract

Background
For acute pancreatitis (AP), aggressive fluid resuscitation therapy (FRT) is the cornerstone for initial management. However, results from the recent WATERFALL study show a higher incidence of fluid overload with aggressive FRT (bolus of 20 ml/kg followed by infusion of 3 ml/kg/hr of Ringer’s lactate [RL]) compared with moderate FRT (infusion of 1.5 ml/kg/hr RL preceded by a bolus of 10 ml/kg only in those with hypovolemia). Given this evidence, we conducted a study to assess whether patients with AP received appropriate fluid therapy and monitoring at our institution.

Aims
To assess whether fluid replacement therapy in patients with AP was aligned with updated clinical practice at our centre.

Methods
We completed a chart audit of all adult (≥ 18 years old) patients who presented to the ED from April 1, 2021 through March 31, 2022 and were diagnosed with AP. Patients were identified based on ICD-10 codes for a primary admission or discharge diagnosis of AP. Data variables collected included demographic information, cause of AP, comorbidities, laboratory tests, type and volume of fluids replaced, urine output, complications, and hospital length of stay (HLOS). Severity of AP was categorized as mild, moderate, or severe based on the revised Atlanta classification of AP. Descriptive statistics were completed.

Results
A total of 250 patients (121 F, 129 M), mean age 53±19 years (range 19-96 years) were diagnosed with AP. Body weight was not available for 4 patients and thus excluded from this analysis. FRT variables stratified for the severity of AP are below in Table 1.

Conclusions
Our quality assessment has identified a knowledge-to-practice gap in the use of FRT for patients with AP. To assist physicians in the decision-making process, we have developed an algorithm to improve FRT in AP. This will be implemented via an order set to standardize the amount of FRT and to improve monitoring of urine output. This algorithm will be tested using an improvement science approach in collaboration with healthcare professionals.
Table 1. Summary of fluid management in AP patients as stratified by severity of disease.

Funding Agencies
None
Genomic data revealed inbreeding despite a geographically connected stable effective population size since the Holocene in the protected Formosan Long-Arm Scarab beetle, Cheirotonus formosanus
Authors: Huang Jen-Pan , Wu Shu-Ping , Chen Wei-Yun , Pham Guan Jie , Kuan Yi-Hsiu 
Published: February 2024

Abstract
Biodiversity conservation is a top priority in the face of global environmental change, and the practical restoration of biodiversity has emerged as a key objective. Nevertheless, the question of how to effectively contribute to biodiversity restoration and identify suitable systems for such efforts continues to present major challenges. By using genome-wide SNP data, our study revealed that populations from different mountain ranges of the Formosan Long-Arm Scarab beetle, a flagship species that receives strict protection, exhibited a single genetic cluster with no subdivision. Additionally, our result implied an association between the demographic history and historical fluctuations in climate and environmental conditions. Furthermore, we showed that, despite a stable and moderately sized effective population over recent history, all the individuals we studied exhibited signs of genetic inbreeding. We argued that the current practice of protecting the species as one evolutionarily significant unit remains the best conservation plan and that recent habitat change may have led to the pattern of significant inbreeding. We closed by emphasizing the importance of conservation genetic studies in guiding policy decisions and highlighting the potential of genomic data for identifying ideal empirical systems for genetic rescue, or assisted gene flow studies.
Advocacy Coalitions, Policy Entrepreneurs, and Windows of Opportunity: Tobacco Control in South Africa, 1948-2018
Authors: Kusi-Ampofo Owuraku 
Published: February 2024

Abstract
This article examines the political history of tobacco control policy in South Africa from 1948 to 2018 by drawing on available historical documents, media reports, published books and articles, the grey literature, and face-to-face interviews with key policy actors. Tracing the historical evolution of tobacco control policies in South Africa reveals how embedded opposition from vested interest groups at every stage of the policy process complicates responses to the tobacco issue. This case study demonstrates how, despite such embedded difficulties, a confluence of regime change, evidence-based messaging, political will, policy entrepreneurs, and advocacy coalitions have led to the gradual transformation of tobacco control policy in South Africa over time. Understanding the historical evolution of tobacco control policy in South Africa opens up space for an in-depth inquiry that allows researchers to trace the policy-making process over the last seven decades, and to understand how those processes have facilitated a shift in the orientation of policy makers over time.
Legal research as a collective enterprise: an examination of data availability in empirical legal scholarship
Authors: Matthews Abigail A , Rantanen Jason 
Published: February 2024

Abstract
While most social sciences confronted data sharing, transparency, and reproducibility sometime in the last two decades, the legal academy has largely been absent from these discussions. In this study, we examine the degree to which the information underlying empirical studies is available. Using an original dataset of every empirical study published in top law journals from 2010 to 2022, we find that 15% have a dataset that is readily available. We compare these low rates with a dataset of every empirical article published in the top economics, political science, and interdisciplinary journals from 2018 to 2022. The vast majority of these articles (99%) make their data available. Additional analysis demonstrates that disciplinary norms enforced by journals drive when authors make their data available. Given the discrepancy between law and other social sciences, we advocate for a disciplinary and cultural shift in law that embraces data accessibility and identify concrete steps to improve data availability. (JEL K00, K1, K10)
Terrorist violence and the fuzzy frontier: national and supranational identities in Britain
Authors: Efthyvoulou Georgios , Pickard Harry , Bove Vincenzo 
Published: February 2024

Abstract
We explore the effect of terrorism on individuals’ perceptions about national identity in the context of Great Britain, where national and supranational identities overlap. We find that exposure to terrorist attacks strengthens identification with Britain but has no effect on identification with its constituent nations. The estimated effects last for about 45 days, but subside over time as the threat fades away. We also find that exposure to terrorism leads to more positive attitudes toward the European Union, providing further support for the emergence of a supranational-unity effect. Overall, our results differ from numerous previous studies on how violence reinforces “hardline beliefs,” exacerbating nativism and “narrow” forms of solidarity (JEL D70; F50; Z10).
Effects of water extract from Cornus controversa on the expression levels of DiSOC1-b and DiCCoAOMT1 genes related with the growth of dove tree seedlings
Authors: Chen Xiaoyan , Liang Zhengchuan , Long Yun , Pan Jihong , Dong Tingfa , Liu Qinsong , Xu Xiao 
Published: February 2024

Abstract
Although characterization of plant interactions has become a research hotspot to assess the adaptability of endangered plants, the underlying molecular basis remains elusive. Dove tree (Davidia involucrata) seedlings were watered with distilled water (CK), leaf water extract (0.025 g mL−1) and branch water extract (0.1 g mL−1) from Cornus controversa, respectively. Subsequently, the morphology, biomass and gene expression levels of DiSOC1-b and DiCCoAOMT1 were analyzed. The results showed that morphological traits and biomass accumulation of D. involucrata seedlings were decreased by the addition of leaf water extracts, and increased by branch water extracts. Moreover, the gene expression level of DiSOC1-b was significantly down-regulated, while the gene expression level of DiCCoAOMT1 was significantly up-regulated in the stems and roots of D. involucrata upon treatment with leaf water extracts of C. controversa. In contrast, the gene expression level of DiSOC1-b was significantly up-regulated in the leaves and stems, while the gene expression level of DiCCoAOMT1 was significantly down-regulated in the roots of D. involucrata upon treatment with branch water extracts of C. controversa. In addition, the expression level of DiSOC1-b was positively correlated with most of morphological traits and total biomass (P &lt; 0.05), while DiCCoAOMT1 was negatively correlated with the majority of morphological traits in D. involucrata seedlings (P &lt; 0.05). Taken together, these results suggest that water extracts from the leaves and branches of the C. controversa exhibit opposite allelopathic effects and affect the expression levels of genes related to growth (DiSOC1-b) and environmental adaptability (DiCCoAOMT1) in D. involucrata seedlings.
D. R. Cox: aspects of scientific inference
Authors: Battey H S 
Published: February 2024

Abstract
The year 2022 marked 100 years since R. A. Fisher’s landmark paper on the foundations of statistics, and 50 years since D. R. Cox’s seminal work on the proportional hazards model. At a 1-day meeting in recognition of the latter, held at the London School of Hygiene and Tropical Medicine, I attempted to place some of D. R. Cox’s most influential work in its appropriate historical context, reconstructing some of his ideas from unifying principles and providing a different exposition to that of the original papers. The present article is an elaboration of that talk. Additional material includes a geometric explanation of conditional inference in models with binary outcomes, relating the logistic analysis of matched comparisons presented by Cox (1958c, Two further applications of a model for binary regression. Biometrika, 45, 562–565) to the protracted and sometimes polemical discourse over the analysis of 2×2 contingency tables.
Slipped capital femoral epiphysis in a 5-year-old boy with cerebral palsy on valproic acid and levetiracetam for epilepsy: a case report
Authors: Aldhafian Osama R 
Published: February 2024

Abstract
This study presents a rare case of unilateral slipped capital femoral epiphysis treated surgically in a 5-year-old boy with cerebral palsy who was born at 27 weeks’ gestation and developed grade III intraventricular haemorrhage and periventricular leucomalacia and was on antiepileptic drugs, including valproic acid and levetiracetam for &gt;3 years. The patient had no history of endocrine, renal, and significant familial diseases.
Laparoscopic exploration of a wandering spleen in a complex adolescent case with sigmoid volvulus and left-side portal hypertension: a case report
Authors: Rafei Ahmed , Hilal Nadir Ali 
Published: February 2024

Abstract
Wandering spleen (WS) is a rare condition characterized by the hypermobility of the spleen due to the absence or abnormal flexibility of suspensory ligaments. We present a 16-year-old female presented with intermittent abdominal pain, constipation, and a palpable mass in the right iliac fossa. Imaging revealed a WS associated with sigmoid volvulus and portal hypertension. Despite a decade of symptoms, the patient remained undiagnosed. Laparoscopic splenectomy was performed successfully, addressing both WS and sigmoid volvulus. The patient’s symptoms resolved, and she was discharged in good condition. This case emphasizes the need for clinical awareness of WS in the differential diagnosis of abdominal pain. It highlights the role of imaging in prompt diagnosis and the necessity of surgical intervention. Our case sheds light on the association of WS with other conditions, providing clinicians with valuable insights for effective management.
Endovascular management of aortoiliac artery occlusive disease with pseudo-stenosis of the external iliac artery
Authors: Matsushima Hirokazu , Shintani Tsunehiro , Kita Hidenori , Hasegawa Yuto 
Published: February 2024

Abstract
In recent years, endovascular treatment has become the first-line revascularisation method for aortoiliac artery occlusive disease. Rarely, aortoiliac artery occlusive disease may be associated with stenosis of the external iliac artery (EIA) that suggested pseudo-stenosis. We describe a case of aortoiliac artery occlusive disease with EIA stenosis without calcification or atheroma. Stent grafts were inserted from the abdominal aorta to the bilateral common iliac arteries. Pre-operative computed tomography and intravascular ultrasound findings confirmed the absence of calcification or atheroma in both EIA, suggesting that the EIA had developed pseudo-stenosis. Following endovascular treatment, the EIA diameter recovered only with balloon dilation after inflow improvement. Consideration is necessary when placing an easy stent graft in the narrow EIA during endovascular treatment for aortoiliac artery occlusive disease with EIA stenosis to avoid a potential stent graft diameter mismatch.
Requests for vulvoplasty as gender-affirming surgery: a cross-sectional study in Denmark
Authors: Aaen Emma Krogsgaard , Kesmodel Ulrik Schiøler , Pop Maria Lucia , Højgaard Astrid Ditte 
Published: February 2024

Abstract

Background
Vulvoplasty, described as a promising procedure for transgender and gender diverse (TGD) persons who were assigned male at birth and who, for example, do not need a vagina or who have contraindications to vaginoplasty, is a procedure that in accordance with current guidelines is not offered as genital gender-affirming surgery in Denmark.

Aim
In this study we sought to quantify the need for offering vulvoplasty in Denmark.

Materials and methods
An online questionnaire was developed. The target group included TGD persons who were assigned male at birth and a minimum of 18 years old. Prior to data collection, the questionnaire was tested with stakeholders from the target group and was subsequently distributed exclusively in closed groups and online fora for TGD persons. Data collection took place from September 1 to October 31, 2022.

Outcomes
Primary outcomes were type of bottom surgery respondents preferred, when vulvoplasty was chosen, the reason(s) for choosing it.

Results
A total of 152 responses were included for data analysis, and 134 records were complete responses. Out of 134 respondents, 35 (26.1%) preferred vulvoplasty. The reasons for preferring vulvoplasty were the belief that there is less risk with the procedure (71%), followed by not wanting to dilate (54%), no need for a vagina (48%), and no need for vaginal penetration (40%). Health issues or other reasons were infrequent (5%). Out of 122 respondents who had not had prior bottom surgery, 106 (86.9%) wanted it in the future.

Clinical implications
Some TGD individuals in Denmark could benefit from vulvoplasty and would choose it if offered.

Strengths and limitations
Strengths of this study were that the questionnaire was thoroughly tested prior to application and that the survey could only be accessed via closed fora and groups for TDG persons. Limitations were that the sample size was small, and that the response rate could not be estimated.

Conclusion
The results of this study imply that there is an unmet need for vulvoplasty, and bottom surgery in general, in Denmark.
Introduction of a terminal electron sink in chloroplasts decreases leaf cell expansion associated with higher proteasome activity and lower endoreduplication
Authors: Arce Rocío C , Mayta Martín L , Melzer Michael , Hajirezaei Mohammad-Reza , Lodeyro Anabella F , Carrillo Néstor 
Published: February 2024

Abstract
Foliar development involves successive phases of cell proliferation and expansion that determine the final leaf size, and is characterized by an early burst of reactive oxygen species generated in the photosynthetic electron transport chain (PETC). Introduction of the alternative PETC acceptor flavodoxin in tobacco chloroplasts led to a reduction in leaf size associated to lower cell expansion, without affecting cell number per leaf. Proteomic analysis showed that the biogenesis of the PETC proceeded stepwise in wild-type leaves, with accumulation of light-harvesting proteins preceding that of electron transport components, which might explain the increased energy and electron transfer to oxygen and reactive oxygen species build-up at this stage. Flavodoxin expression did not affect biogenesis of the PETC but prevented hydroperoxide formation through its function as electron sink. Mature leaves from flavodoxin-expressing plants were shown to contain higher levels of transcripts encoding components of the proteasome, a key negative modulator of organ size. Proteome profiling revealed that this differential accumulation was initiated during expansion and led to increased proteasomal activity, whereas a proteasome inhibitor reverted the flavodoxin-dependent size phenotype. Cells expressing plastid-targeted flavodoxin displayed lower endoreduplication, also associated to decreased organ size. These results provide novel insights into the regulation of leaf growth by chloroplast-generated redox signals, and highlight the potential of alternative electron shuttles to investigate the link(s) between photosynthesis and plant development.
Physiological function and regulation of ascorbate peroxidase isoforms
Authors: Yoshimura Kazuya , Ishikawa Takahiro 
Published: February 2024

AbstractAscorbate peroxidase (APX) reduces H2O2 to H2O by utilizing ascorbate as a specific electron donor and constitutes the ascorbate–glutathione cycle in organelles of plants including chloroplasts, cytosol, mitochondria, and peroxisomes. It has been almost 40 years since APX was discovered as an important plant-specific H2O2-scavenging enzyme, during which time many research groups have conducted molecular physiological analyses. It is now clear that APX isoforms function not only just as antioxidant enzymes but also as important factors in intracellular redox regulation through the metabolism of reactive oxygen species. The function of APX isoforms is regulated at multiple steps, from the transcriptional level to post-translational modifications of enzymes, thereby allowing them to respond flexibly to ever-changing environmental factors and physiological phenomena such as cell growth and signal transduction. In this review, we summarize the physiological functions and regulation mechanisms of expression of each APX isoform.
Autoantibodies in laryngeal cancer: detection and role as a biomarker
Authors: Gunasekera Thashani , Rajagopalan Umapriyatharshini , Herath Samith , Samarakoon Sameera , Sakkaff Rizny , Jalaldeen Roshan 
Published: February 2024

Abstract

Objective
Diagnostic role of autoantibodies (AAb) as serological biomarkers has not been specifically investigated in laryngeal cancer (LC) previously. The study investigates the presence of anti-LC AAbs and their potential as a biomarker for early diagnosis of LC, to improve patient outcome.

Method
Anti-LC AAb levels were investigated in LC patients (n = 30) and healthy individuals (n = 30) by indirect enzyme-linked immunosorbent assay (ELISA). Patient AAb levels were analyzed with various clinical factors, primarily tumor stage.

Results
AAb levels were significantly higher in LC patients than in the control group (P = .019). The diagnostic performance of AAb-level testing for LC detection presented a sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of 70% each. The positive likelihood (LR+) and negative likelihood (LR−) ratios were 2.33 and 0.43, respectively. AAb levels were independent of cancer stage (P = .708), duration since first appearance of symptoms (P = .228), duration of medical attention (P = .231), and degree of risk-factor exposure (P = .478).

Conclusion
Significant level of AAbs could be detected among LC patients with good diagnostic performance, irrespective of stage. Thus, anti-LC AAbs reflect potential to be utilized as predictive biomarkers in early diagnostics of LC.