bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ablation versus Radiation Segmentectomy for Small Liver Tumors
Authors: Ozen Merve , Patel Ronak K. 
Published: January 2024

AbstractHepatocellular carcinoma (HCC) is a liver malignancy that affects more than a million people worldwide with a complex multifactorial etiology. After the diagnosis of HCC is made, physicians establish management using the Barcelona Clinic Liver Cancer (BCLC) guidelines revolving around tumor stage, liver function, performance status, and patient preferences. According to recent updates to these guidelines, thermal ablation is the second-best curative option apart from surgical resection for small HCC (< 2 cm). While thermal ablation is standard of care, recent studies have suggested that radiation segmentectomy (RS) has similar outcomes, limited hepatotoxicity, and ultimately a cost-efficient approach. Although there is limited literature on RS, this article compares ablation techniques against radiation segmentectomy for small HCC tumors.
A Review of Resection and Surgical Ablation for Primary and Secondary Liver Cancers
Authors: White McKenzie J. , Jensen Eric H. , Brauer David G. 
Published: January 2024

AbstractThe surgical management of primary and secondary liver tumors is constantly evolving. Patient selection, particularly with regard to determining resectability, is vital to the success of programs directed toward invasive treatments of liver tumors. Particular attention should be paid toward determining whether patients are best served with surgical resection or ablative therapies. A multidisciplinary approach is necessary to provide optimal care to patients with liver malignancy.
How does the new environmental protection law affect the environmental social responsibility of enterprises in Chinese heavily polluting industries?
Authors: Wu Guoyong , Sun Mengmin , Feng Yanchao 
Published: January 2024

AbstractIn the new era of seeking for cleaner production and comfortable life, it is important and necessary to improve environmental social responsibility, especially for the heavily polluting industries. Against this backdrop, the Chinese government put forward the new environmental protection law in 2015, while the effect of it on the environmental social responsibility still remains as a black box, which forms the initial motivation of this essay. Treating the implementation of the new environmental protection law (NEPL) as a quasi-natural experiment, this essay employed the difference-in-differences model to explore its impact on the environmental social responsibility (ESR) of highly polluting enterprises. The results support that implementing the NEPL can enhance the level of environmental social responsibility by strengthening the end-of-pipe governance and green office level of enterprises, in contrast, the affection on the front-end governance is not significant. The results remain unchanged after various robustness tests, such as changing the time point of the policy, placebo test, and elimination of sample selection bias. Further research finds that the scale of corporate financing and the efficiency of capital use have different moderating effects on the effectiveness of the implementation of the NEPL policy. Mechanism analysis shows that the NEPL policy affects the level of corporate environmental social responsibility through the technological innovation crowding-out effect. In addition, heterogeneity analysis reveals that environmental regulation intensity has an “inverted U-shaped” effect on the ESR of businesses. Furthermore, non-state-owned companies and companies with higher levels of executive education have higher levels of environmental social responsibility. Finally, policy implications are provided to shed light on this essay’s theoretical and practical values.
Composite of carbon dots and TiNiSn thermoelectric materials: Initial investigation on the electrical and thermal transport properties
Authors: Yong Chao , Lei Ying , Ye Fan , Wang Nan , Li Yu , Liu Yinghui , Chen Zheng , Wang Dongsheng , Zhang Shaowu 
Published: January 2024

TiNiCu0.025Sn0.99Sb0.01 is prepared using microwaves. However, an ultra-high electrical conductivity and electronic thermal conductivity are obtained by interstitial Cu and Sb doping, which could not effectively improve the ZT value. We introduce carbon dots (CDs) as a nano-second phase by ball milling to simultaneously optimize the thermoelectric properties. To our best knowledge, this is the first report on half-Heusler/CDs composites. Experimental results show that the introduction of nano-CDs optimizes the carrier concentration and mobility and dramatically improves the Seebeck coefficient through the energy filtering effect. The nano-CDs introduce more point defects, inhibit the grains growth, and form a specific carbon solid solution second phase in the matrix. The lattice thermal conductivity is reduced to the same level as TiNiSn at 1.96 W m−1 K−1 through the synergistic effect of point defects and phase and grain boundaries scattering, and the ZT value reaches a maximum of 0.63 at 873 K.
In Support of Breast-/Chestfeeding by People With HIV in High-Income Settings
Authors: Powell Anna , Agwu Allison 
Published: January 2024

Abstract
Given that HIV can be transmitted through breastfeeding, historically, breastfeeding among women with HIV in the US and other resource-rich settings was discouraged. Formula feeding was the mandated feeding option out of concern for breast-milk transmission of HIV, which occurred in 16–24% of cases pre-antiretroviral therapy (pre-ART) use. In January 2023, the US Department of Health and Human Services’ Perinatal Guidelines were revised to support shared decision-making for infant feeding choices. Updated clinical trials' data from resource-limited settings suggest the actual breastmilk HIV transmission rate in the context of maternal ART or neonatal postexposure prophylaxis is 0.3–1%. High-income countries are reporting more people with HIV breastfeeding their infants without cases of HIV transmission. We present the reasons for fully embracing breast-/chestfeeding as a viable, safe infant feeding option for HIV-exposed infants in high-income settings, while acknowledging unanswered questions and the need to continually craft more nuanced clinical guidance.
OP10 Efficacy and safety of upadacitinib in patients with moderately to severely active Crohn’s Disease: results from the U-ENDURE long-term extension
Authors: D'Haens G , Louis E , Loftus Jr. E V , Regueiro M , Jairath V , Magro F , Nakase H , Dubcenco E , Lacerda A P , Feng T , Duncan B , Wang T , Ford S , Anyanwu S I , Blumenstein I 
Published: January 2024

Abstract

Background
Upadacitinib (UPA) is an oral Janus kinase inhibitor approved for the treatment of moderately to severely active Crohn’s disease (CD).1 The U-ENDURE (NCT03345823) maintenance study and long-term extension (LTE) evaluate the long-term efficacy and safety of UPA maintenance therapy. Here, we report the results of the U-ENDURE LTE.

Methods
Patients (pts) completing the U-ENDURE 52-week (wk) maintenance study were eligible to participate in the LTE and continue their previously assigned treatment (placebo [PBO], UPA 15 mg [UPA15] once daily [QD], or UPA 30 mg [UPA30] QD; blinded until the last pt completed maintenance wk52). Clinical response, clinical remission, endoscopic response, endoscopic remission, as well as high-sensitivity C-reactive protein (hs-CRP) and faecal calprotectin (FCP) were evaluated as-observed up to wk48 of the LTE among pts (PBO [N = 89], UPA15 [N = 107], UPA30 [N = 173]); excluding pts who received open-label UPA30 rescue therapy. Safety was assessed in all pts (PBO [N = 223], UPA15 [N = 221], UPA30 [N = 229]) from wk0 of the maintenance study up to LTE wk204 (cut-off date: 01 Aug 2023).

Results
At LTE wk0, the SF/APS clinical remission rates were 73.0%, 78.3%, and 80.3% for PBO, UPA15, and UPA30, respectively (Figure 1A). Similar rates were reported at LTE wk0 for CDAI clinical remission (PBO 75.3%, UPA15 81.3%, UPA30 80.9%; Figure 1B) and clinical response (CR-100: PBO 79.5%, UPA15 84.9%, UPA30 84.4%). Rates of clinical remission were stable through wk48 of the LTE. Endoscopic response (PBO 32.9%, UPA15 59.6%, UPA30 66.5%) and remission rates (PBO 27.8%, UPA15 42.4%, UPA30 47.3%) at LTE wk0 were sustained through wk48 with UPA while decreased with PBO (Figure 1C-D). At LTE wk0, the mean [95% CI] change from induction BL in hs-CRP was 1.8 [–0.4, 4.1], –13.2 [–17.9, –8.6], and –12.8 [–16.8, –8.9] for PBO, UPA15, and UPA30, respectively; sustained through wk48. Similar results were observed with FCP (mean [95% CI] change from induction BL: PBO 126 [–103, 356], UPA15 –2946 [–4121, –1772], UPA30 –1871 [–2577, –1165]). Severe adverse events (AEs) and serious AEs were lower with UPA treatment compared with PBO (Table 1). The rates of most AEs of special interest were similar between UPA and PBO; however, numerically higher rates of herpes zoster, adjudicated gastrointestinal perforations, neutropenia, lymphopenia, creatine phosphokinase elevation, and hepatic disorders were reported in pts treated with UPA vs PBO (Table 1).

Conclusion
In pts completing wk48 of the LTE, sustained efficacy was observed in clinical and endoscopic endpoints with over 2 years of UPA treatment, while maintaining an overall positive safety profile in pts with CD.
Reference:
1. Loftus EV Jr, et al. N Engl J Med. 2023;388:1966–80
OP12 Mirikizumab improves fatigue, bowel urgency, and quality of life in patients with moderately to severely active Crohn’s Disease: Results from a phase 3 clinical trial
Authors: Travis S , Hisamatsu T , Fischer M , Dubinsky M , Jairath V , Chen M , Ferrante M , Peyrin-Biroulet L , Siegmund B , Hunter Gibble T , Lin Z , Protic M , Morris N , Ghosh S 
Published: January 2024

Abstract

Background
Mirikizumab (miri), an anti-IL-23p19 antibody, is approved for the treatment of ulcerative colitis and under development for Crohn’s disease (CD). We investigated how miri impacted fatigue, bowel urgency, and health-related quality of life (HRQoL) through 52 weeks in patients with moderately to severely active CD in the Phase 3 VIVID-1 study.

Methods
In the treat-through VIVID-1 (NCT03926130) study, patients (N=1065) with moderately to severely active CD and a Simple Endoscopic Score for CD (SES-CD) score ≥7 (or ≥4 for patients with isolated ileal disease) and failure to biologic and/or conventional therapy were randomized in a 6:3:2 ratio to receive miri (N=579) (a single 900mg intravenous (IV) dose at W0, W4, and W8 followed by a subcutaneous (SC) dose of 300 mg at W12 and then every 4 weeks), ustekinumab (N=287) (6mg/kg IV at W0 and SC dose of 90mg at W8 and then every 8 weeks), or PBO (N=199). At W12 PBO responders continued PBO to W52; PBO-non-responders received the same blinded miri regimen as described above. This analysis focuses on results in patients randomized to either miri or PBO. The change from baseline for Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Urgency Numeric Rating Scale (UNRS), and Inflammatory Bowel Disease Questionnaire (IBDQ) total and domain scores (bowel symptoms, systemic symptoms, emotional function, social function) were analyzed through W52. IBDQ response (≥16-point improvement from baseline) and remission (total score ≥ 170) rates were also analyzed at W12 and W52. For binary variables, adjusted risk differences were compared between miri and PBO using the Cochran-Mantel-Haenszel (CMH) test. For continuous variables, least squares mean changes from baseline were compared between treatment groups using ANCOVA.

Results
Significant improvement in mean change from baseline to W12 and W52 were observed with miri for FACIT-F, UNRS, and IBDQ total and domain scores (all p&lt;0.000001 at W52) (Figure 1&2). Miri-treated patients showed improved UNRS scores versus PBO as early as W8 with statistical significance sustained to W52 (Figure 1B). At W12 and W52, a greater percentage of miri-treated patients achieved IBDQ response (W12: p&lt;0.000001; W52: p&lt;0.000001) and remission (W12: p&lt;0.000001; W52: p&lt;0.000001) compared to PBO (Figure 2A&B).

Conclusion
Treatment with miri resulted in improvements in fatigue, bowel urgency, and HRQoL at W12 and W52 in patients with moderately to severely active CD.
OP25 Dual activation of GCGR/GLP1R signaling ameliorates intestinal fibrosis via metabolic regulation of histone H3K9 lactylation in epithelial cells
Authors: Liu H , Hong Y , Wang X , Dong J , Li X , Shi Z , Wang J , Zhou L , Rieder F , Chen B , Chen M , Zhang Y , Mao R , Jiang X 
Published: January 2024

Abstract

Background
Intestinal fibrosis is a significant clinical challenge in inflammatory bowel diseases, but no effective anti-fibrotic therapy is currently available. GCGR and GLP1R are both peptide hormone receptors involved in energy metabolism of epithelial cells. However, their role in intestinal fibrosis and the underlying mechanisms remain largely unexplored.

Methods
Intestinal tissues from patients with Crohn’s Disease (CD) (n=20) were obtained. AAV9-Glp1r-shRNA, AAV9-Gcgr-shRNA or AAV9-NC-shRNA were used to transfect mice. Murine colons were analyzed by single-cell RNA sequencing (seq) and metabonomics. Glycolytic metabolism of epithelial cells was analyzed with bulk RNAseq and seahorse-XF technology, while lactylation levels were verified using antibodies against diverse forms of lactylated histones. Then a range of GCGR/GLP1R dual-target ultralong-acting peptides were synthesized, and their agonistic activities were assessed in HEK293 cells that stably expressed either human GLP1R or GCGR, using a cAMP response element-driven luciferase reporter. The antifibrotic activity of the leading peptide 1907B was functionally evaluated in vitro and in vivo.

Results
GCGR and GLP1R were reduced in the stenotic ileum of patients with CD as well as in the fibrotic colon of mice with chronic colitis. In the chronic model, Gcgr/Glp1r dual knockdown worsened the degree of fibrosis in mice, and increased glycolysis-related metabolites, with lactate exhibiting the most prominent alterations. In the TGFβ1-induced epithelial cell model, exogenous and endogenous lactate induced fibrotic genes expression and overwhelming histone lactylation in H3K9 (H3K9la). Further, cells overexpressing H3.1 (K9R) exhibited lower levels of fibrotic genes and proteins after treatment with lactate compared with the H3.1 WT group. Then 1907B, the leading GCGR/GLP1R dual-target peptide, normalized the ATP production rate of glycolysis, extracellular lactate, H3K9la levels of promoters related to fibrosis genes, and further ameliorated intestinal fibrosis in vivo.

Conclusion
We uncovered the role of GCGR/GLP1R in regulating EMT involved in intestinal fibrosis via histone lactylation. Simultaneously activating GCGR/GLP1R with the novel dual agonist 1907B holds promise as a treatment strategy for alleviating intestinal fibrosis.
OP32 TWIST1-mediated fibroblast activation protein (FAP)-expressing fibroblasts drives fibrosis in Crohn’s Disease
Authors: Ke B J , Abdurahiman S , Verstockt B , Biscu F , Zanella G , Zouzaf A , van Baarle L , De Simone V , Stakenborg M , Santhosh S , Verstockt S , De Hertogh G , Vermeire S , Matteoli G 
Published: January 2024

Abstract

Background
Stricturing Crohn’s disease (CD) is a distinct clinical phenotype, characterised by the development of fibrotic strictures within the GI tract. These strictures result from chronic inflammation, leading to the accumulation of collagen and scar tissue, causing narrowing of the affected intestinal segments. Due to a lack of anti-fibrotic medication, up to 70% of patients with CD will require surgery in their lifetime, while up to 40% of patients need repetitive resections within 10 years.

Methods
To understand inflammation-induced fibrosis, full-thickness ileal punch biopsies from CD patients (n=10) and colorectal cancer (CRC) patients (n=5) undergoing ileocecal resection (ICR), were profiled using single-cell RNA sequencing (scRNA-seq) on the 10x Genomics platform. Flow cytometry was performed to confirm scRNA-seq findings. Intestinal fibroblasts were cultured in the presence of NicheNet-predicted cytokines or supernatant of FACS-sorted myeloid cells. To confirm the pro-fibrotic role of TWIST1 in fibroblasts, both Harmine (TWIST1 inhibitor)-treated wild-type mice and COL1A2CrexTWIST1fl/fl mice were subjected to chronic dextran sulphate sodium (DSS)-induced colitis.

Results
Using scRNA-seq, we identified a specific subset of FAP-expressing fibroblasts enriched in fibrotic surgical CD specimens. Flow cytometry confirmed a significant increase of these cells in the inflamed and stenotic ileum, compared to proximal uninflamed ileum and unaffected control ileum from CRC patients undergoing ICR. Computational methods identified TWIST1 as a key transcription factor, mediating fibroblast activation and extracellular matrix (ECM)-regulatory phenotypes. Myeloid cell-derived inflammatory signals were predicted to induce this specific fibroblast activation, resulting in collagen deposition and tissue fibrosis. Intestinal fibroblasts cultured with inflammatory monocyte supernatant or pro-inflammatory cues expressed higher levels of TWIST1, FAP, and COL3A1. After inhibiting TWIST1 with Harmine, collagen expression and ECM accumulation were decreased in fibroblasts. In addition, in chronic DSS colitis, wild-type mice treated with Harmine showed a reduction in collagen deposition. COL1A2CrexTWIST1fl/fl mice showed improved disease activity, compared to their littermate controls.

Conclusion
Our findings suggest that TWIST1 serves as a central mediator in the activation of fibroblasts, promoting excessive collagen deposition in ileal CD. Targeting TWIST1 may reduce tissue remodelling and prevent fibrosis in CD.
DOP33 Distinct perturbances in metabolic pathways associate with disease progression in patients with Inflammatory Bowel Disease
Authors: Bourgonje A R , Ibing S , Argmann C , Sands B E , Dubinsky M , Jacobsen H A , Suarez-Farinas M , Mehandru S , Colombel J F , Ungaro R C 
Published: January 2024

Abstract

Background
Patients with inflammatory bowel diseases (IBD) exhibit distinct shifts in circulating metabolite levels that have been associated with clinical disease activity and disease phenotype. However, there are limited data on the impact of metabolomic changes on disease progression in IBD. We aimed to understand the association of circulating metabolite levels and related pathways with the risk of disease progression in patients with IBD.

Methods
We conducted an observational cohort study using the Mount Sinai Crohn’s and Colitis Registry (MSCCR). Patients were prospectively enrolled with baseline questionnaires and biospecimens that were then linked to longitudinal electronic health record data. A total of 1,456 serum metabolites were measured in 277 patients with UC and 375 patients with CD using untargeted metabolomics. Disease progression was defined as any new steroid or biological prescriptions, IBD-related hospitalizations, or surgery. Multivariable Cox proportional hazards regression models, adjusted for age, sex, smoking, biologic use, and surgery were used to explore metabolite associations with risk of disease progression. Metabolite set enrichment analysis (MSEA) was performed to identify underlying metabolic pathways associated with disease progression.

Results
During a median 2-year follow-up time (IQR 0.3-5.1 years), 375 patients (57.5%) had a disease progression event. Among CD, 151 metabolites significantly correlated with the composite outcome (FDR&lt;0.1). Of these, 81 (53.6%) were linked to higher risk, mainly enriched in amino acids, purine, and pyrimidine metabolism, fibrinogen cleavage peptides, and bile acid pathways. Additionally, 70 (46.4%) metabolites associated with lower risk with enrichment in fatty acid metabolism, steroid biosynthesis, histidine, tryptophan, and antioxidant pathways. In CD, aspartate metabolism was most significantly associated with increased risk and linoleic metabolism with decreased risk. In UC, 84 metabolites were significantly associated with disease progression (FDR&lt;0.1), with 29 (34.5%) associated with increased and 55 (65.5%) with decreased risk. Metabolic pathways linked to higher risk were sphingolipid, benzoate, hydrogen sulfide, polyamine, and tyrosine metabolism, while protective metabolites were enriched in branched-chain amino acid (BCAA), steroid biosynthesis, histidine, and phenylalanine pathways. In UC, sphingolipid metabolism was prominently associated with increased risk and BCAA metabolism with decreased risk.

Conclusion
Specific metabolites and metabolic pathways are associated with risk of disease progression in patients with IBD, highlighting potential prognostic metabolite biomarkers and pathways that may be important in modulating risk of disease progression.
DOP39 Constructing butyrate-producing yeast as a cell-dependent treatment option for Inflammatory Bowel Disease
Authors: Wu J , Kang G , Wang L , Gao M , Meng S , Cao X , Li B , Huang H 
Published: January 2024

Abstract

Background
Intestinal microbiota dysbiosis and metabolic disruption are essential characteristics of inflammatory bowel disorders (IBD). Butyrate has been proven to regulate immune response and gut microbiota. It has been confirmed that the butyrate content in the intestinal cavity of IBD patients decreases (Fig. 1A).

Methods
In this study, gene editing was used to reconstruct the butyrate synthesis pathway and regulate related metabolic pathways in Saccharomyces cerevisiae to produce butyrate and enrich its synthesis in anaerobic environments to cope with complex intestinal conditions. A series of engineered strains were co-cultured with gut microbiota samples from six patients with mild-to-moderate ulcerative colitis and 16S ribosomal RNA sequencing was used to analyze the regulatory effect of engineered strains on intestinal microbiota in vitro. The TNBS-induced IBD mice model was used to explore the protective effect of butyrate-engineered yeasts in vivo.

Results
A series of engineered strains with different butyrate synthesis abilities was constructed to meet the needs of different patients. S. cerevisiae was engineered by introducing an exogenous butyrate synthesis pathway and regulating yeast metabolism to increase the availability of the precursors. Engineered yeast can produce up to 1.8 g/L butyrate (Fig. 1B). The modification of related metabolic pathways also focused on enhancing the synthesis of butyrate under anaerobic conditions to enable engineered yeasts to adapt to the intestinal environment. This series of engineered yeasts with different butyrate synthesis abilities regulated the intestinal microbiota of IBD patients to varying degrees, enhancing the abundance of related probiotics such as Lactobacillus and Bifidobacterium and reducing the abundance of harmful bacteria like Candidatus Bacilloplasma (Fig. 1C). Meanwhile, strains improved TNBS-induced colitis in mice by restoring butyrate content. Remarkably, the engineered strain with the second-highest butyrate yield showed the most significant therapeutic effect (Fig. 1D).

Conclusion
This study realized butyrate synthesis in S. cerevisiae and regulated related metabolic modules to adjust the butyrate production to achieve the best therapeutic effect on colitis in vivo and in vitro. In addition, the strain with the second-highest butyrate production has the best therapeutic effect. This highlights the dual role of butyrate in epithelial cell repair and suggests a therapeutic window for IBD treatment through butyrate supplementation. Selecting the most suitable strain for each patient's condition is essential for restoring butyrate levels, regulating microbiota, and promoting mucosal repair.