bluuebunny/crossref_metadata_2025_split huggingface dataset:
Method, Sources, and the GaW2 Data Set
Authors: Lindström Jonas , Kardell Örjan , Ulväng Marie 
Published: January 2025

Abstract
This chapter presents the methodology behind the study and describes the source base in detail. It justifies the verb-oriented method with reference to its capacity to capture all forms of work and to do so across large swathes of time. The method also accords with how the United Nations and ILO define and measure work. The chapter acknowledges some drawbacks of the method but concludes that its benefits dominate. The sources for the extraction of verb phrases describing work activities—nearly 19,000 observations—consist of court records (62%), accounts, ego-documents, registers, and petitions. Additional sources are church records and probate inventories. The chapter points to some biases: married men are overrepresented in the data, women’s share of the observed activities decline over time, and some forms of work are underrepresented (agriculture, textile work, and domestic work). It concludes that by mapping people’s activity patterns, it is possible to identify both repertoires of practices, that is, what men and women typically did in this society, and the gender division of work within a given field.
Bridging the gap: Evaluating ChatGPT-generated, personalized, patient-centered prostate biopsy reports
Authors: Proctor Erin S , Nusbaum David J , Lee John M , Benirschke Robert C , Freedman Alexa , Raster Gregory , Glaser Alexander P , Labbate Craig V , Higgins Andrew M , Helfand Brian T , Glassy Eric F , Joseph Lija , Edelstein Robert A , Krupinski Elizabeth A , Alnajar Hussein , Kearns James T , Groth John V 
Published: January 2025

Abstract

Objective
The highly specialized language used in prostate biopsy pathology reports coupled with low rates of health literacy leave some patients unable to comprehend their medical information. Patients’ use of online search engines can lead to misinterpretation of results and emotional distress. Artificial intelligence (AI) tools such as ChatGPT (OpenAI) could simplify complex texts and help patients. This study evaluates patient-centered prostate biopsy reports generated by ChatGPT.

Methods
Thirty-five self-generated prostate biopsy reports were synthesized using National Comprehensive Cancer Network guidelines. Each report was entered into ChatGPT, version 4, with the same instructions, and the explanations were evaluated by 5 urologists and 5 pathologists.

Results
Respondents rated the AI-generated reports as mostly accurate and complete. All but 1 report was rated complete and grammatically correct by the majority of physicians. Pathologists did not rate any reports as having severe potential for harm, but 1 or more urologists rated severe concern in 20% of the reports. For 80% of the reports, all 5 pathologists felt comfortable sharing them with a patient or another clinician, but all 5 urologists reached the same consensus for only 40% of reports. Although every report required edits, all physicians agreed that they could modify the ChatGPT report faster than they could write an original report.

Conclusions
ChatGPT can save physicians substantial time by generating patient-centered reports appropriate for patient and physician audiences with low potential to cause harm. Surveyed physicians have confidence in the overall utility of ChatGPT, supporting further investigation of how AI could be integrated into physicians’ workflows.
Implantable device for intrathecal pseudodelivery of drugs: surgical protocol and proof-of-concept in a porcine model
Authors: Pérez-Martín E , Rodríguez-Cañón M , Roces-Llorián C , Álvarez G , Prado C , Tomás-Zapico C , Menéndez-González M 
Published: January 2025

Abstract

Introduction
Immunotherapy for neurodegenerative diseases often induces severe side effects due to the interaction of monoclonal antibodies (mAb) with the immune and nervous systems. We present a novel platform based on an intrathecal device that clears target molecules from cerebrospinal fluid (CSF) without releasing mAb into the organism (pseudodelivery). This non-GLP pilot study evaluates the device’s functionality and the feasibility and safety of implanting the human prototype in a porcine model.

Methods
Seven female pigs were randomly assigned to three groups: device with mAb solution (n=3), device with artificial CSF (n=3), and a naïve control (n=1). Surgery involved inserting a catheter via lumbar puncture at L4-L5 and advancing it to T7-T8. The catheter was connected to a reservoir implanted in a subcutaneous pocket. Solutions were exchanged percutaneously every 4 weeks. Device functionality was tested using ELISA and SIMOA® every 4 weeks. Daily behavioural monitoring, along with biweekly body weight, temperature, and haematology analyses, were conducted until termination at week 13.

Results
Preliminary analyses demonstrated the device’s functionality by verifying CSF influx into the device and preventing drug outflow to the CNS. All animals exhibited a healthy status, with slight deviations that normalised after one month. Body weight remained stable over time, with minimal reduction in two animals. The main complications included pain, slight gait loss, and subcutaneous pocket infections.

Conclusion
Implantation of a human medical device for intrathecal pseudodelivery of immunotherapy is feasible and safe in pigs, and its functionality has been demonstrated. Further research is needed to refine surgical procedures and long-term implantations.
Utility of 3D Reconstruction for Surgical Planning in the Treatment of Retroperitoneal Sarcomas
Authors: Jiménez Fuertes M , Vizarreta Figueroa A , Carrillo J , Martín M , Romero Triana D , Domínguez Prieto V , Qian S , Villarejo Campos P 
Published: January 2025

Abstract

Introduction
Retroperitoneal sarcomas (RPS) are rare tumors that present significant challenges due to their location and proximity to vital structures. Accurate surgical planning is essential to optimize outcomes, and 3D reconstruction has emerged as a valuable tool for preoperative planning and intraoperative guidance.

Methods
We present our experience of 20 cases of RPS where 3D reconstruction was integrated into the surgical planning process. We retrospectively reviewed 20 patients who underwent surgery at our institution from 2021 to 2024. Preoperative CT or MRI scans were performed on all patients and used to generate 3D models of the tumors with specialized software. These 3D models facilitated the planning of surgical approaches, assessing resectability, and provided immersive visualization through virtual reality (VR) tools for enhanced surgical preparation.

Results
All 20 patients underwent curative-intent surgery using tailored surgical approaches based on 3D modeling insights. The models offered detailed visualization of the tumors and their relationships with adjacent structures, improving the precision of resection and margin assessment.

Conclusion
3D reconstruction proved to be a useful tool in the surgical treatment of RPS, improving preoperative planning and intraoperative guidance. It also provided benefits in medical education and enhanced patient understanding of their disease and treatment plan.
OP41 Duvakitug (TEV-48574), an anti-TL1a monoclonal antibody, demonstrates efficacy and favourable safety as an induction treatment in adults with moderately to severely active ulcerative colitis: Results from a phase 2b, randomised, double-blind, placebo-controlled, dose-ranging, basket trial (RELIEVE UCCD)
Authors: Reinisch W , Stepek D , Kempinski R , Danese S , Sands B E , Ratiu-Duma B , Singh R , Barkay H , Raphael G , Jairath V 
Published: January 2025

Abstract

Background
Duvakitug is a human IgG1 monoclonal antibody that inhibits TL1A binding to DR3, a key driver of inflammation and fibrosis. In comparison, it has less binding selectivity for DcR3, which regulates excess TL1A, maintaining homeostasis. Duvakitug has demonstrated reduced inflammation and fibrosis in colitis animal models.1 The efficacy and safety of duvakitug in adults with moderately to severely active ulcerative colitis (UC) and Crohn’s disease was assessed in a phase 2b basket trial (NCT05499130).2

Methods
RELIEVE UCCD was a randomised, placebo (PBO)-controlled, double-blind induction study. The UC cohort comprised of adults with moderately to severely active disease with inadequate response, loss of response or intolerance to previous conventional and/or advanced therapies (ATs). Eligible patients were randomised to receive subcutaneously a 2250 mg loading dose of duvakitug or PBO, followed by either duvakitug 450 mg, 900 mg or PBO (1:1:1; stratified by prior AT) every 2 weeks.2 The primary endpoint was clinical remission (per modified Mayo score) at week 14. Safety was assessed by adverse event (AE) reporting and laboratory monitoring.

Results
In total, 137 patients were randomised, treated and included in the UC cohort analysis (450 mg: n=47; 900 mg: n=46; PBO: n=44). Demographics and baseline characteristics were generally similar across arms (Table 1). Both duvakitug doses successfully achieved the week 14 primary endpoint of clinical remission (36% [450 mg], 48% [900 mg] versus 20% [PBO]; PBO-adjusted rates: 16% [450 mg], 27% [900 mg]). The results were statistically significant based on the prespecified Bayesian analysis, with a &gt;0.90 posterior probability that each duvakitug dose is superior to PBO. Duvakitug treatment effect was observed in both AT-experienced and -naïve patients (Table 2). AE incidence was lower for duvakitug (49% [450 mg], 43% [900 mg]) versus PBO (52%), as was incidence of AEs leading to discontinuation (0% [450 mg], 2% [900 mg] versus 5% [PBO]).

Conclusion
Duvakitug demonstrated statistically significant and clinically meaningful treatment responses compared to PBO in patients with UC; it was well tolerated with no emergent safety signals observed. These induction study results support further development of duvakitug as a potential treatment option for patients with moderately to severely active UC.

Funding
Duvakitug is being developed in partnership by Teva and Sanofi.

References
1. Clarke AW, et al. MAbs. 2018;10:664–77.
2. Reinisch W, et al. 19th Congress of European Crohn’s and Colitis Organization (ECCO) 2024; 21–24 February 2024; Stockholm, Sweden. Abstract P998.
DOP053 Efficacy of appendectomy in inducing remission in moderate-to-severe ulcerative colitis: preliminary one year results of a multicentre prospective cohort study (COSTA)
Authors: Visser E ,   COSTA study group
Published: January 2025

Abstract

Background
This study aimed to evaluate the efficacy of appendectomy in inducing remission in patients with moderately to severely active ulcerative colitis (UC), despite biological or small molecule therapy.

Methods
This multicentre, prospective cohort study included patients aged ≥16 years with moderately to severely active UC (total Mayo score [TMS] ≥5; endoscopic subscore of ≥2) despite optimised prior treatment with advanced medical therapy (i.e. biological/small molecule exposed). Eligible patients where those for whom the next treatment step was considered to be switching to a Janus kinase (JAK) inhibitor or undergoing (procto)colectomy. Enrolled patients were counselled (patient-preference model) to either undergo laparoscopic appendectomy (study intervention) or continue standard step-up therapy, which included: 1) switching to a JAK inhibitor or 2) undergoing staged restorative proctocolectomy with ileoanal pouch. The primary outcome was the proportion of patients achieving clinical remission (TMS≤2 with no subscore &gt;1) at 12 months without therapy failure. Therapy failure was defined as (re)start of oral corticosteroids, switch of advanced therapy, start trial medication or proctocolectomy. Patients without therapy failure and pMS≤2 at 12 months without endoscopic follow-up were considered failures for the primary outcome. Primary analyses will be conducted based on a modified intention-to-treat (mITT) principle. Patients who received the assigned intervention (appendectomy in the intervention group, proctocolectomy in the control group) or at least one dose of the assigned medication (JAK-inhibitor in the control group) will be analysed. The last patient 12-month follow-up visit was completed in September 2024.

Results
A total of 120 patients were included in the mITT analysis (appendectomy group: n=65, JAK-inhibitor group: n=50, proctocolectomy group: n=5). Numerical baseline differences across groups (appendectomy vs JAK-i vs proctocolectomy) were: male gender (35.4% vs 54.0% vs 20.0%, p=0.08), family history of IBD (33.8% vs 12.0% vs 0%, p=0.02), current smoking (13.8% vs 2.0% vs 0%, p=0.22), disease extent (E3: 41.5% vs 60.0% vs 80.0%, p=0.18), TMS (median 9 [IQR, 7-10] vs 9 [IQR, 8-10] vs 10 [0-.], p=0.16) and concomitant oral corticosteroids (26.2% vs 46.0% vs 80.0%, p=0.01). The appendectomy group had a significantly higher proportion of patients in clinical remission at 12 months without therapy failure after appendectomy, compared to the JAK inhibitor group (33.8% vs 12.0%, p=0.007, Figure 1.). Final analysis are scheduled for Q4 2024 and Q1 2025.

Conclusion
Appendectomy may be an effective treatment option for inducing clinical remission in moderately to severely active UC. Final analyses are expected in Q1 2025.
DOP082 Disease clearance prevents negative outcomes in ulcerative colitis patients and enhances the impact of independently achieving clinical, endoscopic, or histological remission.
Authors: Ramos Lopez L , De la Barreda R , Nicólas-Pérez D , Quintero E , Hernández-Guerra M 
Published: January 2025

Abstract

Background
Intestinal inflammation even without endoscopic evidence is associated with worse clinical outcomes in ulcerative colitis (UC) . However, recent advances in UC treatments have the potential to modify the disease’s natural history and improve clinical outcomes if inflammation is controlled. The emerging concept of "disease clearance" (DC) in UC aims to achieve combined clinical, endoscopic, and histological remission. Whether DC is associated with better outcomes remains unclear.

Objective
To evaluate the impact of DC during follow-up in UC patients.

Methods
A prospective longitudinal cohort study was conducted between 2012 and 2017. Consecutive UC patients undergoing colonoscopy were included, and those with clinical follow-up longer than 18 months were analyzed. At the time of colonoscopy, clinical condition (PRO: number of stools per day and presence of blood in the stool) and endoscopic index (Mayo endoscopic score, MES) were evaluated. Histological analysis (Geboes score, GS) of biopsies from the area with the greatest macroscopic inflammation was performed. Disease clearance was defined as simultaneous clinical (PRO2 = 0; normalized stool frequency without blood), endoscopic (MES = 0), and histological (GS ≤ 2) remission. Patients were monitored every 6 months to assess negative outcomes, defined as clinical relapse requiring therapy, treatment escalation, hospitalization, or colectomy.

Results
A total of 101 UC patients were included (50 females; 44.5 ± 15 years; UC extent: E3: 32.3%, E2: 52.5%, E1: 15.2%; median time since diagnosis: 103 ± 102 months; 13.3% on anti-TNF agents). DC was present in 52 patients (51.5%) at baseline colonoscopy. During follow-up, 40 patients (39.6%) experienced a negative outcome, most commonly requiring corticosteroids (57.6%). Patients who achieved DC had a significantly lower rate of negative outcomes compared to those without DC (21.2% vs. 59.2%, p &lt; 0.0001). Kaplan-Meier curves confirmed a lower risk of clinical relapse in patients with DC (log-rank, p = 0.001) (Fig. 1). Among patients with endoscopic remission (MES = 0; n = 60), only those with DC (n = 52) had a lower risk of negative outcomes (21.2% vs. 75%, p = 0.005, log-rank, p = 0.0015) (Fig. 1A). Additionally, achieving DC reduced the risk of flare-ups even in patients with clinical remission (PRO2 = 0) (p = 0.044) (Fig.1B) or histological remission (GS ≤ 2) (p = 0.039) (Fig. 1C).

Conclusion
DC in UC patients reduces the risk of negative outcomes during follow-up, supporting its inclusion as a key composite treatment goal in UC management.
DOP129 Integrating genetic risk and omics insights to characterize the molecular alterations in inflammatory bowel disease
Authors: Mateos B , Miguel González J A , Gaite-Reguero A , Rodríguez-Lago I , M Marigorta U 
Published: January 2025

Abstract

Background
High-throughput omic technologies have enabled detailed molecular profiling of IBD patients. Traditionally, studies focus on a single molecular layer (e.g., genomics, transcriptomics, proteomics) to understand the complex interactions driving IBD. We can distinguish two strategies: 1)Genetic studies, such as genome-wide association studies (GWAS), which have identified &gt;300 SNPs linked to increased IBD risk. 2)Omic profiling of patient tissues, which identifies hundreds of genes and molecular pathways altered in disease. We performed integrative analysis to explore consistency across omic findings and to obtain a synthetic picture of the sequence of molecular events that lead to IBD.

Methods
We used three approaches to clarify the interplay between genes identified through GWAS and those identified through other omics. First, we used Mendelian Randomization to infer causality and determine the directionality of interactions between the genes identified through all strategies. We incorporated 220 additional traits using summary statistics from the GWAS Atlas to validate our findings. Second, we assessed the impact of environmental exposures, such as smoking and diet. Finally, we used polygenic risk scores (PRS) to explore if variability in genetic risk shapes the differences in omic findings observed across patients.

Results
We made four relevant findings regarding the molecular changes in IBD. First, we noted low overlap between genes involved in genetic risk and those altered in patient samples. For instance, only 7% of genes identified by GWAS are differentially expressed at the transcriptomic/proteomic levels in IBD, and only 8% of genes identified by omics are significant in GWAS results. This trend was consistent across omic technologies and disease stages. Second, we infer that genes involved in genetic risk often modulate the expression levels of genes altered in patients. This trend is not bidirectional, implying that GWAS genes are drivers of the downstream transcriptional changes that characterize patients. Third, alterations in patients do not strategy according to individual PRS, suggesting that genetic effects lead to alterations pervasively shared across patients. Finally, environmental risk exposures, such as smoking or diet, do not impact GWAS genes (p=0.91) but have ample effects on omics-identified genes (p=1.8 x10-8).

Conclusion
Genetic risk variants identified by GWAS act as upstream regulators of the main patient alterations, while environmental risk factors exert independent effects on these alterations. The model suggests that omic research does not uncover causal alterations, but reveals a convergent endpoint that characterizes IBD patients, regardless of their genetic predisposition and external exposures.
P0026 Multi-omics phenotyping characterizes perturbed molecular divergence underlying different clinical scenarios of under-treatment inflammatory bowel disease
Authors: Lee H S 
Published: January 2025

Abstract

Background
Clinically heterogeneous spectrum and molecular phenotypes of inflammatory bowel disease (IBD) remain to be comprehensively elucidated.

Methods
This study set out to explore the serum molecular profiles (I) underlying the disease subtypes, in association with (II) elevated fecal calprotectin and (III) disease activity states, (IV) upon treatment escalation, and (V) in patients who needed treatment escalation. The serum proteome, metabolome, and lipidome of 75 IBD patients were profiled. Single- and multi-omic data analysis was performed to determine differential analytes and integrative biosignatures.

Results
In (I), chronic inflammation along with tight junction disturbances promoting impaired barrier function might underly the differences between IBD subtypes. Compared to Crohn’s disease, ulcerative colitis showed a lower abundance of hypoxanthine correlating negatively with cell adhesion-related proteins of ITGB2, CD200, PRELP, and positively with lysophosphatidylcholines [LPC(16:0-SN1), LPC(O-18:1)]; and up-regulation of bile acids and FGF19. For (II), while proteins related to inflammatory-promoting signaling pathways, sphingomyelins (SMs), and LPC were increased; bile acids, amino acids, and triacylglycerols (TGs) were decreased. Not only in (II), TGs were a major class change in (III), whose abundance was consistently higher in the active state. This, along with decreased SMs levels, correlated strongly with the up-regulation of inflammatory-inducing proteins (CXCL9, CXCL1, ITGB2, IL17A). In (IV), treatment escalation promoted augmentations of signaling pathways-related proteins and triggered significant metabolome responses, especially decreased amino acids. Noticeably, the levels of TGs were consistently increased in the post-treatment escalation group, thereby suggesting treatment response with relation to (III). For (V), down-regulation of signaling pathways-related proteins and higher levels of SMs and PCs was observed. A consistent decrease of TGs in patients who needed treatment escalation along with lower level of TGs in elevated calprotectin group could imply for the inflammatory level.

Conclusion
This study provided the multi-ome profiles of IBD patients in five clinical scenarios and laid a foundation for opening new doors for disease management and treatment.

References
M. Agrawal, K.H. Allin, F. Petralia, J.-F. Colombel, T. Jess, Multiomics to elucidate inflammatory bowel disease risk factors and pathways, Nature Reviews Gastroenterology & Hepatology 19(6) (2022) 399-409.
P0037 ATF7 Deficiency Exacerbates Mitochondrial Dysfunction and Intestinal Inflammation in Ulcerative Colitis
Authors: Chen Y , Liangru Z 
Published: January 2025

Abstract

Background
Ulcerative colitis (UC), a chronic inflammatory bowel disease, is marked by sustained inflammation and excessive apoptosis of intestinal epithelial cells (IECs). Despite progress in understanding UC pathogenesis, the role of activating transcription factors (ATFs) in disease progression remains elusive. Here, we profile the expression of ATF family members (ATF1–ATF8) in the colonic mucosa of UC patients and identify ATF7 as a critical regulator of mitophagy through its control of PTEN-induced kinase 1 (PINK1).

Methods
Expression levels of ATF1–ATF8 were quantified in colonic mucosal samples from UC patients (n = 200) and healthy controls (n = 100) via quantitative PCR and immunohistochemistry. Using IEC-specific ATF7 and PINK1 knockout mouse models and human CCD 841 CoN colonic epithelial cells, we employed ChIP-seq, dual-luciferase assays, transmission electron microscopy, and immunofluorescence to elucidate their roles in mitophagy and disease progression. Clinical correlation between ATF7 expression and disease severity was assessed using the Mayo score.

Results
ATF7 expression was significantly reduced in UC patients and inversely correlated with disease severity. Mechanistically, ATF7 was identified as a direct transcriptional activator of PINK1, a key mitophagy regulator. Loss of ATF7 or PINK1 disrupted mitophagy, exacerbating mitochondrial dysfunction, IEC apoptosis, and colonic inflammation in vivo and in vitro.

Conclusion
Our findings uncover a pivotal ATF7-PINK1 axis that governs mitophagy and limits UC progression. The inverse correlation between ATF7 expression and UC severity highlights its potential as a therapeutic target, offering new avenues for intervention in this debilitating disease.