bluuebunny/crossref_metadata_2025 huggingface dataset:
A290 ILLICIT SUBSTANCE USE AND ITS IMPACT ON ALCOHOL-ASSOCIATED HEPATITIS IN LATIN AMERICA
Authors: Islam A H , Diaz L A , Idalsoaga F , Ayares G , Arnold J , Alcayaga B , Maldonado K , Arab J
Published: February 2024

Background

Concomitant substance use is frequent among patients with alcohol use disorder (AUD), but its impact on alcohol-associated hepatitis (AH) is unknown.

Aims

To assess the prevalence and impact of substance use in patients hospitalized for AH in a multinational cohort in Latin America.

Methods

Multicenter prospective cohort study including patients with AH between 2015-2022. We recorded sociodemographic and clinical information, including data on alcohol and drug use. We assessed the impact of substance consumption using competing-risk models.

Results

We included 405 patients from 24 centers in 8 countries (Argentina, Bolivia, Brazil, Chile, Colombia, Ecuador, Mexico, and Peru). The mean age was 49.6±12.2 years, 345 (85.4%) were men, 210 (57.5%) had a previous diagnosis of cirrhosis, and the median MELD at diagnosis was 25 [20–31] points. Around 74% of patients fulfilled ACLF criteria (ACLF-1: 11.1%, ACLF-2: 11.6%, ACLF-3: 49.6%). A total of 82 (20.3%) reported active substance use, while 22 (5.4%) were former substance users. The most common drugs used at admission were marijuana (11.1%), cocaine (10.4%), methamphetamine (4.4%), and heroin (0.5%). Out of the total, 35.7% died, and only 2.5% underwent liver transplantation during follow-up. Active substance use was higher in younger patients (users 44.4±16.1 years vs. non-users 51.0±10.6 years; pampersand:003C0.001) and in men compared to women (22.0% vs 10.2%, p=0.036). In a competing-risk model adjusted by age, sex, history of cirrhosis, MELD, and ACLF grade, active substance use was independently associated with mortality (subdistribution Hazard Ratio [sHR] 1.53, 95%CI:1.01–2.32; p=0.043). Also, active cocaine (sHR 1.69, 95%CI:1.07–2.70; p=0.025) and marijuana use (sHR 1.83, 95%CI:1.11–3.04; p=0.018) were independently associated with mortality in adjusted competing-risk analyses.

Conclusions

Active drug use is common in AH patients. Marijuana and cocaine were the most frequent substances and were independently associated with increased mortality. Substance use should be screened in patients with AUD, and integrated management with addiction specialists and psychiatrists could impact survival in AH.

Funding Agencies

None
A294 CHOLESTASIS SECONDARY TO XANTHOGRANULOMATOUS CHOLANGITIS: A CASE REPORT
Authors: Labib K A , Bishay K
Published: February 2024

Background

An 86-year-old female presented with four weeks of intermittent abdominal pain, postprandial nausea with an associated 10 lbs weight loss. Initial labs demonstrated a predominantly cholestatic liver enzyme elevation. Imaging revealed a thickened gallbladder with dilated CBD up to 15mm with no calculi, obstruction or pancreatic mass. EUS demonstrated a prominent ampulla with an area of hyperechogenicity, and ERCP was completed with sphincterotomy and biopsy of the ampulla. A cholangiogram showed a prominent common bile duct and a smooth distal taper without filling defects. Tumor markers, ampullary biopsy, and cytology of CBD brushings were negative for malignancy. Repeat ERCP for non-resolving symptoms with an extension of the sphincterotomy, brushings and insertion of a metal stent was completed without improvement in liver enzymes and a standard hepatitis workup returned negative. Her clinical course was further complicated by recurrent gram-negative bacteremia with CT findings of innumerable abscesses or metastasis in the liver. A US-guided targeted liver biopsy revealed large duct periductal tissue expansion by foamy macrophages with admixed neutrophils, eosinophils, plasma cells, and lymphocytes. These features were consistent with xanthogranulomatous cholangitis. We were planning to start ursodiol given the small duct disease however the patient succumbed to recurrent bacteremia and passed away.

Aims

Review of methods to attain diagnosis of xanthogranulomatous cholangitis.

Methods

Case Report.

Results

Diagnosis of xanthogranulomatous cholangitis can be attained from targetted US-guided biopsy, surgical excision, or EUS-guided CBD biopsy.

Conclusions

Xanthogranulomatous cholangitis is an extremely rare entity described in limited case reports, frequently mimicking neoplastic disease. Pathology is difficult to attain and historically case reports required surgical resections. One recent case reported diagnosis confirmed via EUS-guided FNA of the CBD. In our case, we attained the diagnosis through a targeted liver biopsy. Pathology of xanthogranulomatous cholangitis typically demonstrates foamy histiocytes, lipid-laden macrophages, eosinophils, lymphocytes, plasma cells, and fibrosis indicating xathogranulomas. The pathogenesis is thought to be an extension of xanthogranulomatous cholecystitis in which bile is extravasated into the gallbladder wall through Rokitansky-Aschoff sinuses or ulceration of the mucosa resulting in an inflammation caused by fibroblasts and macrophages as they phagocytose the lipids in bile, resulting in the formation of xanthoma cells. Given the rarity of the disease, there is no guideline on management and a majority of patients reported underwent surgical excision. This case demonstrates the utility of liver biopsy to establish this rare diagnosis, allowing for better detection and subsequently better-studied management.

Funding Agencies

None
A297 EXAMINING THE IMPACT OF INFLAMMATORY BOWEL DISEASE IN PRIMARY SCLEROSING CHOLANGITIS PATIENTS POST LIVER TRANSPLANTATION
Authors: Malhi G , Diaz L A , Punchhi G , Mortuza R , Khan M , Brahmania M , Jairath V , Arab J
Published: February 2024

Background

Primary sclerosing cholangitis (PSC) is an immune-mediated disease that is characterized by biliary inflammation and fibrosis. It is associated with inflammatory bowel disease (IBD) in 80% of cases. To date, the impact of IBD in liver transplantation (LT) recipients is not completely understood.

Aims

To assess the impact of IBD in individuals with PSC who underwent liver transplantation (LT) in terms of graft survival, infections, and mortality.

Methods

This was a retrospective cohort study that included individuals with PSC who received a LT between 1999–2021. Statistical analysis included Kaplan-Meier survival curves, a binary logistic regression to estimate infection risk, and a competing-risk analysis to estimate post-LT mortality (with re-transplantation being a competing risk).

Results

122 LT recipients were included. Mean age at LT was 44.9±12.6 years old. The median MELD-Na at LT was 22 [17–28]. Twenty-nine (23.8%) LT recipients died during follow-up (median 1,248 [413–3,857] days) and 5 (4.1%) required re-transplantation (median 1,460 [923–2,563] days). Estimated graft survival was 93.2% (95%CI: 86.9%–96.6%) at 1 year and 81.3% (95%CI: 72.5%–87.6%) at 5 years. An adjusted competing-risk model demonstrated that increasing age (sHR 1.05, 95%CI: 1.01–1.10; p=0.018), baseline MELD-Na (sHR 1.07, 95%CI: 1.02–1.12; p=0.005), and ERCP requirements before LT (sHR 6.33; 95%CI: 1.63–24.65; p=0.008) were associated with higher post-LT mortality, while IBD was not associated with post-LT mortality (sHR 1.02, 95%CI: 0.38–2.70; p=0.962). The incidence of infections after LT was 50.8% at 30 days. IBD was not associated with development of infections at 30 days (OR 1.01, 95%CI: 0.98–1.04; p=0.615) post-LT.

Conclusions

Based on this retrospective review, an older age, higher MELD-Na at LT and prior ERCP requirements were independently associated with a higher mortality post-LT in PSC patients. However, a background history of IBD was not associated with higher mortality or with infections post-LT.

Table 1: Baseline Demographics

Funding Agencies

None
A298 HIGH MORTALITY NOTED AMONG PATIENTS ADMITTED WITH ALCOHOL ASSOCIATED HEPATITIS: A DESCRIPTIVE STUDY
Authors: Malhi G , McChesney C , Hudson D , Stephenson E , Almahanna Y , Arab J
Published: February 2024

Background

Alcohol associated hepatitis is a syndrome related to alcohol use disorder characterized by jaundice, malaise, decompensated liver disease, and coagulopathy. This is associated with bacterial infections, the development of chronic liver failure, and high short-term mortality. However, the rates at which these events occur is less understood, with a broad range of estimates reported.

Aims

To understand the demographic profile of those admitted with alcohol associated hepatitis assess its impact on resource utilization, complications in hospital, and mortality.

Methods

This study examined a subset of individuals with alcohol associated hepatitis who were admitted to the GI and Medicine Wards between 2010 and 2023.

Results

70 encounters were identified and interpreted. The average age at admission was 48.3 ± 11.4 years old. 62.8% were male and 22% reported cannabis use. 54% had a previous reported history of alcohol use disorder. The average MELD-Na score at the time of admission was 25.9 ± 7.7.

The Median length of stay was 8.5 days (IQR 4.5,15). 63% were provided steroids in hospital and 33.3% developed infectious complications. 36.3% of patients had a GI bleed reported during admission. 4% of patients underwent a transplantation during follow-up. Approximately 44.3% experienced mortality with a 30-day mortality rate found to be 28.6%.

Conclusions

Alcohol associated hepatitis patients are prone to developing infections and bleeding during admission. This diagnosis also carries a high mortality rate, particularly within the first 30 days. Further studies examining the global impact of alcohol associated hepatitis should be considered.

Table 1: Baseline Demographics

Funding Agencies

None
A301 RELATIONSHIP BETWEEN INTRAHEPATIC IMMUNE CELL PROFILE AND MICROBIOME ACCORDING TO DISEASE SEVERITY IN OBESE PATIENTS WITH NON-ALCOHOLIC FATTY LIVER DISEASE
Authors: Schwenger K J , Ghorbani Y , Chen L , Fischer S , Jackson T
Published: February 2024

Background

Non-alcoholic fatty liver disease (NAFLD) includes histology ranging from simple steatosis (SS) to non-alcoholic steatohepatitis (NASH), fibrosis and cirrhosis. The pathogenesis of NAFLD is multifactorial and includes several immune cell-mediated inflammatory processes. Recent research suggests a potential relationship between NAFLD, disease severity and the intestinal microbiome (IM). In particular, our previous work in NAFLD showed that lower abundance of fecal Faecalibacterium prausnitzii was associated with liver histology and gene expression. In addition, we found that Kupffer cell markers, hematopoietic cell marker cluster of differentiation and B cells were associated with liver histology.

Aims

Knowing that F prausnitzii may have anti-inflammatory effect, we seek to determine if there was any association between fecal F prausnitzii and hepatic immune cells.

Methods

Biochemical and anthropometric measurements as well fecal samples for IM analysis were collected in those with obesity undergoing bariatric surgery. Fecal shotgun metagenome sequencing to profile the intestinal microbiome Liver histology was assessed using Brunt scoring system. The frequency, location and phenotype of 8 immune cell subtypes were analyzed by multiplex immunofluorescence. Spearman correlation coefficients and partial Spearman correlation coefficients were used to evaluate the association between significant hepatic immune cells and fecal F. prausnitzii.

Results

113 patients had both hepatic immune and IM data. Of the 113 patients, 30 had normal liver obese (NLO), 41 had SS and 42 had NASH. With regards to hepatic immune cells, those with NAFLD (SS and NASH) or NASH had significantly higher Helper T, CD4 and B cells and lower activated macrophages compared to NLO. In those with NAFLD or NASH, F. prausnitzii was significantly negatively correlated with Helper T cells (NAFLD, R= -0.25, p-value 0.009; NASH, R= -0.25, p-value 0.038). In those with NASH, F. prausnitzii was also significantly negatively correlated with CD4 cells (R= -0.31, p-value 0.009).

Conclusions

Specific hepatic immune cells were associated with NAFLD and NASH with Helper T and CD4 cells being negatively correlated with F. prausnitzii. Knowing that these immune cells contribute to NAFLD pathogenesis, the relationship between fecal IM, hepatic immune cells and NAFLD require further exploration.

Funding Agencies

CIHRCanadian Liver Foundation
A302 NON-INVASIVE BIOMARKERS PREDICTING THE PROGRESSION OF MASLD TO ADVANCED FIBROSIS: A PROSPECTIVE COHORT STUDY
Authors: Song Y , Mortuza R , Arab J , Khan M
Published: February 2024

Background

Metabolic dysfunction-associated steatotic liver disease (MASLD) affects around 30% of the global population and is one of the most prevalent non-communicable diseases. Due to its high prevalence, it is becoming the most common cause of liver-related mortality in all populations worldwide. Current standards of care for the treatment of MASLD encompass mostly lifestyle measures that are nonspecific and difficult for clinicians to ensure compliance. Although not all patients with MASLD progress to more advanced disease, the high prevalence of MASLD in the general population means the absolute number of “at risk” individuals are substantial and places a significant burden on the healthcare system. As a result, MASLD is currently viewed as a heterogeneous disease with varying rates of disease progression.

Aims

We aim to elucidate the predictors of disease progression in MASLD to develop and guide interventions while the disease is reversible.

Methods

Prospective chart review on patients seen in MASLD clinic at LHSC on CERNER from Sept. 2021 – Apr. 30, 2023. A REDCap database was constructed pertaining to a) basic patient information b) basic medical history c) patient lifestyle habits d) InBody bioimpedance analysis if available f) laboratory data g) elastography, including liver stiffness measurement (LSM) and controlled attenuation parameter (CAP). Collected data were exported into a spreadsheet to allow for analysis. IBM SPSS was used to analyze descriptive statistics and regression analyses.

Results

A total of 116 encounters were reviewed, including both enrolment and follow-ups. HbA1c percent is positively correlated with LSM (r=0.28, pampersand:003C0.05). The longer that the patient has been diagnosed with NAFLD (current age minus age of initial diagnosis), the more likely the patient has higher LSM scores (r= 0.23, pampersand:003C0.05). Platelet levels are negatively correlated with LSM (r=-0.28, pampersand:003C0.05). There is no difference between cannabis users and non-users in the degree of CAP or LSM. Only n=15 InBody bioimpedance analyses were included; preliminary results showed Trunk Reactance at 250kHz is correlated with LSM with (r=0.593 pampersand:003C0.05).

Conclusions

Patients with higher HbA1c, lower platelets and longer duration of disease are at higher risk for developing advanced fibrosis. This can allow the development of a better predictive model to find F2-F3 patients without using FibroScan or a liver biopsy, which is helpful in the primary care setting, given the prevalence of MASLD. InBody bioimpedance studies are a useful tool to predict LSM, although more data is needed to ensure the correlation is sufficiently powered. Phenotyping patients would lead to more accurate prognostication, facilitate better monitoring to prevent decompensation and allow for the development of precision-based, personalized management plans.

Funding Agencies

None
A303 SAFETY AND EFFICACY OF DIRECT ORAL ANTICOAGULANTS IN PATIENTS WITH LIVER CIRRHOSIS: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Tham D , Yu W , Zhao L , Kou R , Kherani J , Li P , Sreeraman S , Eshaghpour A , Li A , Crowther M
Published: February 2024

Background

Direct oral anticoagulants (DOACs) are widely used for treatment of venous thromboembolism (VTE) and stroke prophylaxis in patients with atrial fibrillation. Liver cirrhosis increases the risk of conditions necessitating anticoagulation, but also increases bleeding risks, complicating anticoagulation use. DOACs may be suitable for chirrotic patients as their reliance on hepatic elimination is reduced compared to traditionally used anticoagulants such as low molecular weight heparin (LMWH) or vitamin K antagonists (VKAs). However, safety data on DOACs in cirrhosis patients is limited as severe Child-Pugh (CP) classes are historically underrepresented in major trials. Various guidelines currently classify severe CP classes as contraindications to DOACs.

Aims

To synthesize primary evidence on the safety profile of DOACs in patients with severe liver cirrhosis.

Methods

A literature search of MEDLINE and Embase from inception to Jan 2023 identified randomized controlled trials (RCTs) and cohort studies comparing DOACs to LMWH or VKAs in cirrhosis patients. Two reviewers screened and extracted data at title/abstract, and full-text levels. Baseline patient characteristics, CP class, and anticoagulation regimens were extracted. The primary outcome was major bleeding per ISTH criteria, stratified by CP B&C, and CP Unspecified (primary study did not report/stratify by CP class) subgroups. Data were meta-analyzed using the Mantel-Haenszel random-effects model and presented as odds ratios with corresponding 95% confidence intervals.

Results

Of 794 articles screened, 17 articles (2 RCTs, 15 cohorts) were included for analysis (n = 5046). Overall, DOACs were associated with a lower risk of major bleeding compared to controls (OR=0.63 [0.45, 0.89]). This result was consistent in the CP B&C Exclusive subgroup (OR=0.42 [0.29, 0.62], 5 studies) but not in the CP Unspecified subgroup (OR=0.71 [0.48, 1.08], 12 studies). One large study (n=3213), Lawal 2023, in the CP B&C group, favored DOACs in reduction of major bleeding (OR=0.37, 95%CI [0.24,0.57]). Removal of this study in post-hoc sensitivity analysis led to no significant differences in major bleeding overall or in any subgroup.

Conclusions

In this analysis comparing DOACs to LMWH/VKAs in patients with liver cirrhosis, DOACs were associated with a statistically significant reduction in the risk of major bleeding overall and in more advanced subgroups (CP B&C). Future analysis will stratify by DOAC agent, duration, dosage, and include secondary efficacy outcomes.

Table 1. Summary of the major bleeding effect size in all subgroups.

Figure 1. Major bleeding in Child-Pugh B&C and Child-Pugh Unspecified groups with DOAC vs VKA

Funding Agencies

None
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

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

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

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

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

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

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

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 < 0.05), while DiCCoAOMT1 was negatively correlated with the majority of morphological traits in D. involucrata seedlings (P < 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

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

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 >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

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

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

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

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

Ascorbate 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

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.
Examining the self-interaction of dark matter through central cluster galaxy offsets
Authors: Cross D , Thoron G , Jeltema T E , Swart A , Hollowood D L , Adhikari S , Bocquet S , Eiger O , Everett S , Jobel J , Laubner D , McDaniel A , Aguena M , Alves O , Andrade-Oliveira F , Bacon D , Bertin E , Brooks D , Burke D L , Carnero Rosell A , Carrasco Kind M , Cawthon R , Costanzi M , da Costa L N , Pereira M E S , Davis T M , Desai S , Doel P , Ferrero I , Frieman J , García-Bellido J , Giannini G , Gruen D , Gruendl R A , Hinton S R , Honscheid K , James D J , Kuehn K , Marshall J L , Mena-Fernández J , Menanteau F , Miquel R , Ogando R L C , Pieres A , Plazas Malagón A A , Raveri M , Romer A K , Sanchez E , Sevilla-Noarbe I , Smith M , Soares-Santos M , Sobreira F , Suchyta E , Swanson M E C , Tarle G , To C , Weaverdyck N , Weller J , Wiseman P ,   (DES Collaboration)
Published: February 2024

While collisionless cold dark matter models have been largely successful in explaining a wide range of observational data, some tensions still exist, and it remains possible that dark matter possesses a non-negligible level of self-interactions. In this paper, we investigate a possible observable consequence of self-interacting dark matter: offsets between the central galaxy and the centre of mass of its parent halo. We examine 23 relaxed galaxy clusters in a redshift range of 0.1–0.3 drawn from clusters in the Dark Energy Survey and the Sloan Digital Sky Survey which have archival Chandra X-ray data of sufficient depth for centre and relaxation determination. We find that most clusters in our sample show non-zero offsets between the X-ray centre, taken to be the centroid within the cluster core, and the central galaxy position. All of the measured offsets are larger, typically by an order of magnitude, than the uncertainty in the X-ray position due to Poisson noise. In all but six clusters, the measured offsets are also larger than the estimated, combined astrometric uncertainties in the X-ray and optical positions. A more conservative cut on concentration to select relaxed clusters marginally reduces but does not eliminate the observed offset. With our more conservative sample, we find an estimated median X-ray to central galaxy offset of $\mu = 6.0 ^{+ 1.4}_{- 1.5}$ kpc. Comparing to recent simulations, this distribution of offsets is consistent with some level of dark matter self-interaction, though further simulation work is needed to place constraints.
Classical Cepheid pulsation properties in the Rubin-LSST filters
Authors: De Somma Giulia , Marconi Marcella , Cassisi Santi , Molinaro Roberto , Bhardwaj Anupam , Ripepi Vincenzo , Musella Ilaria , Pietrinferni Adriano , Sicignano Teresa , Trentin Erasmo , Leccia Silvio
Published: February 2024

Homogeneous multiwavelength observations of classical Cepheids from the forthcoming Rubin-LSST have the potential to significantly contribute to our understanding of the evolutionary and pulsation properties of these pulsating stars. Updated pulsation models for classical Cepheid stars have been computed under various assumptions about chemical compositions, including relatively low metallicity (Z = 0.004 with Y = 0.25 and Z = 0.008 with Y = 0.25), solar metallicity (Z = 0.02 with Y = 0.28), and supersolar metallicity environments (Z = 0.03 with Y = 0.28). From the predicted periods, intensity-weighted mean magnitudes, and colours, we have derived the first theoretical pulsation relations in the Rubin-LSST filters (ugrizy), including period–luminosity–colour, period–Wesenheit, and period–age–colour relations. We find that the coefficients of these relations are almost insensitive to the efficiency of superadiabatic convection but are significantly affected by the assumption of the mass–luminosity relation and the adopted chemical composition. Metal-dependent versions of these relations are also derived, representing valuable tools for individual distance determinations and correction for metallicity effects on the cosmic distance scale.
The Kormendy relation of cluster galaxies in PPS regions
Authors: Ribeiro A L B , Lopes P A A , Morell D F , Dantas C C , Fonseca M H S , Amarante B G , Morais-Neto F R
Published: February 2024

We study a sample of 936 early-type galaxies located in 48 low-z regular galaxy clusters with M200 ≥ 1014 M⊙ at z < 0.1. We examine variations in the Kormendy relation (KR) according to their location in the projected phase space (PPS) of the clusters. We have used a combination of Bayesian statistical methods to identify possible differences between the fitted relations. Our results indicate that the overall KR is better fitted when we take into account the information about PPS regions. We also find that objects with time since infall ≥6.5 Gyr have a significant statistical difference of the KR coefficients relative to objects that are more recent in the cluster environment. We show that giant central ellipticals are responsible for tilting the KR towards smaller slopes. These galaxies present a late growth probably due to cumulative preprocessing during infall, plus cannibalism and accretion of smaller stripped objects near the centre of the clusters.