bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of postoperative circulating tumour DNA to predict early recurrence in patients with stage I–III right-sided colon cancer: prospective observational study
Authors: Lygre Kristin B , Forthun Rakel B , Høysæter Trude , Hjelle Sigrun M , Eide Geir E , Gjertsen Bjørn T , Pfeffer Frank , Hovland Randi 
Published: January 2024

Abstract

Background
Right-sided colon cancer (RCC) differs in mutation profile and risk of recurrence compared to distal colon cancer. Circulating tumour DNA (ctDNA) present after surgery can identify patients with residual disease after curative surgery and predict risk of early recurrence.

Methods
This is a prospective observational biomarker trial with exploration of ctDNA in 50 non-metastatic RCC patients for which oncological right-sided colectomy was performed. Blood samples were collected preoperatively, within 1 month post surgery, 3 months (not mandatory), 6 months and every 6 months thereafter. Plasma cell free DNA and/or tumour was investigated for cancer-related mutations by the next-generation sequencing (NGS) panel AVENIO surveillance specifically designed for ctDNA analysis. Detected mutations were quantified using digital droplet PCR (ddPCR) for follow-up. Recurrence-free survival was explored.

Results
50 patients were recruited. Somatic cancer-related mutations were detected in 47/50 patients. ddPCR validated results from NGS for 27/34 (plasma) and 72/72 samples (tumour). Preoperative ctDNA was detected in 31/47 of the stage I/III patients and the majority of ctDNA positive patients showed reduction of ctDNA after surgery (27/31). ctDNA-positive patients at first postoperative sample had high recurrence risk compared to patients without measurable ctDNA (adjusted hazard ratio: 172.91; 95% c.i.: 8.70 to 3437.24; P: 0.001).

Conclusion
ctDNA was detectable in most patients with non-metastatic RCC before surgery. Positive postoperative ctDNA was strongly associated with early recurrence. Detectable postoperative ctDNA is a prognostic factor with high (100%) positive predictive value for recurrence in this cohort of non-metastatic RCC.

Clinical Trial Registration
ClinicalTrials.gov ID: NCT03776591
Impact of complexity in minimally invasive liver surgery on enhanced recovery measures: prospective study
Authors: Dahlke Paul M , Benzing Christian , Lurje Georg , Malinka Thomas , Raschzok Nathanael , Kamali Can , Gül-Klein Safak , Schöning Wenzel , Hillebrandt Karl H , Pratschke Johann , Neudecker Jens , Krenzien Felix 
Published: January 2024

Abstract

Background
Adherence to enhanced recovery after surgery (ERAS) protocols is crucial for successful liver surgery. The aim of this study was to assess the impact of minimally invasive liver surgery complexity on adherence after implementing an ERAS protocol.

Methods
Between July 2018 and August 2021, a prospective observational study involving minimally invasive liver surgery patients was conducted. Perioperative treatment followed ERAS guidelines and was recorded in the ERAS interactive audit system. Kruskal–Wallis and ANOVA tests were used for analysis, and pairwise comparisons utilized Wilcoxon rank sum and Welch's t-tests, adjusted using Bonferroni correction.

Results
A total of 243 patients were enrolled and categorized into four groups based on the Iwate criteria: low (n = 17), intermediate (n = 81), advanced (n = 74) and expert difficulty (n = 71). Complexity correlated with increased overall and major morbidity rate, as well as longer length of stay (all P &lt; 0.001; standardized mean difference = 0.036, 0.451, 0.543 respectively). Adherence to ERAS measures decreased with higher complexity (P &lt; 0.001). Overall adherence was 65.4%. Medical staff-centred adherence was 79.9%, while patient-centred adherence was 38.9% (P &lt; 0.001). Complexity significantly affected patient-centred adherence (P &lt; 0.001; standardized mean difference (SMD) = 0.420), but not medical staff-centred adherence (P = 0.098; SMD = 0.315). Postoperative phase adherence showed major differences among complexity groups (P &lt; 0.001, SMD = 0.376), with mobilization measures adhered to less in higher complexity cases.

Conclusion
The complexity of minimally invasive liver surgery procedures impacts ERAS protocol adherence for each patient. This can be addressed using complexity-adjusted cut-offs and ‘gradual adherence’ based on the relative proportion of cut-off values achieved.
Neurodevelopmental and synaptic defects in DNAJC6 parkinsonism, amenable to gene therapy
Authors: Abela Lucia , Gianfrancesco Lorita , Tagliatti Erica , Rossignoli Giada , Barwick Katy , Zourray Clara , Reid Kimberley M , Budinger Dimitri , Ng Joanne , Counsell John , Simpson Arlo , Pearson Toni S , Edvardson Simon , Elpeleg Orly , Brodsky Frances M , Lignani Gabriele , Barral Serena , Kurian Manju A 
Published: January 2024

Abstract
DNAJC6 encodes auxilin, a co-chaperone protein involved in clathrin-mediated endocytosis (CME) at the presynaptic terminal. Biallelic mutations in DNAJC6 cause a complex, early-onset neurodegenerative disorder characterized by rapidly progressive parkinsonism-dystonia in childhood. The disease is commonly associated with additional neurodevelopmental, neurological and neuropsychiatric features. Currently, there are no disease-modifying treatments for this condition, resulting in significant morbidity and risk of premature mortality.
To investigate the underlying disease mechanisms in childhood-onset DNAJC6 parkinsonism, we generated induced pluripotent stem cells (iPSC) from three patients harbouring pathogenic loss-of-function DNAJC6 mutations and subsequently developed a midbrain dopaminergic neuronal model of disease.
When compared to age-matched and CRISPR-corrected isogenic controls, the neuronal cell model revealed disease-specific auxilin deficiency as well as disturbance of synaptic vesicle recycling and homeostasis. We also observed neurodevelopmental dysregulation affecting ventral midbrain patterning and neuronal maturation. To explore the feasibility of a viral vector-mediated gene therapy approach, iPSC-derived neuronal cultures were treated with lentiviral DNAJC6 gene transfer, which restored auxilin expression and rescued CME.
Our patient-derived neuronal model provides deeper insights into the molecular mechanisms of auxilin deficiency as well as a robust platform for the development of targeted precision therapy approaches.
In vivo calcium imaging shows that satellite glial cells have increased activity in painful states
Authors: Jager Sara E , Goodwin George , Chisholm Kim I , Denk Franziska 
Published: January 2024

Abstract
Satellite glial cells are important for proper neuronal function of primary sensory neurons for which they provide homeostatic support. Most research on satellite glial cell function has been performed with in vitro studies, but recent advances in calcium imaging and transgenic mouse models have enabled this first in vivo study of single-cell satellite glial cell function in mouse models of inflammation and neuropathic pain. We found that in naïve conditions, satellite glial cells do not respond in a time-locked fashion to neuronal firing. In painful inflammatory and neuropathic states, we detected time-locked signals in a subset of satellite glial cells, but only with suprathreshold stimulation of the sciatic nerve. Surprisingly, therefore, we conclude that most calcium signals in satellite glial cells seem to develop at arbitrary intervals not directly linked to neuronal activity patterns. More in line with expectations, our experiments also revealed that the number of active satellite glial cells was increased under conditions of inflammation or nerve injury. This could reflect the increased requirement for homeostatic support across dorsal root ganglion neuron populations, which are more active during such painful states.
Structural Elucidation of Novel Degradation Impurities of Ibrutinib in Ibrutinib Tablets Using Preparative Chromatography, LCMS, HRMS and 2D NMR Techniques
Authors: Yerla Rajender Reddy , Manubolusurya Surendrababu , Meganathan Saravanakumar , Madalapu Veerababu , Vaidyanathan Gopal 
Published: January 2024

Abstract
Ibrutinib is an orally administered compound that functions as an irreversible covalent inhibitor of the Bruton tyrosine kinase, an essential element in multiple cellular processes including B-cell differentiation, proliferation, migration, survival and apoptosis. The compound has been found to demonstrate efficacy against a range of B-cell malignancies. The drug product is available in oral tablet and capsule formulations. The drug degradation profiles of tablets dosage form were assessed in accordance with regulatory guidelines. The results indicate that the drug substance is susceptible to alkaline and oxidative stress. The oxidation degradation led to the identification of three significant unknown degradation impurities. The three compounds were isolated through the application of preparative liquid chromatography, and their structures were determined using analytical techniques such as liquid chromatography–mass spectrometry, high-resolution mass spectrometry and nuclear magnetic resonance spectroscopy. Utilizing structural elucidation data, predictions were made regarding the composition of impurities, revealing them to be novel degradation impurities that bear structural resemblance to ibrutinib. Additionally, potential pathways for the formation of the impurities were proposed.
Gold Rush vs. War: Keynes on reviving animal spirits in times of crisis
Authors: Bee Michele , Fèvre Raphaël 
Published: January 2024

Abstract
This paper aims to exploit fully the heuristic virtues of Keynes’ famous ‘old bottles’ story, deploying a multi-layered argument and drawing out its broadest implications. In essence, we show that through this story Keynes was making a very serious point about anti-crisis policies: the need for authorities to stimulate animal spirits by relying on people’s natural impulse to action. Rather than taking the place of entrepreneurs and paying people to dig holes, Keynes seems to be arguing that public authorities should put entrepreneurs in a situation where they are so enthusiastic that they go into debt to dig holes, just like during a gold rush. At the same time, it is a question of restoring the banks’ willingness to lend for these overoptimistic projects in a period of total depression. This article explores the conditions that make public intervention as effective as possible through the enthusiasm and individual initiative that can be generated by an artificial gold rush. Such intervention therefore can be as minimal as possible, without having to resort to the opposite authoritarian solution of war. Since the gold rush builds cities and war destroys them, Keynes spent considerable energy convincing his contemporaries that liberal-democratic countries would have to take the former path if they wanted to avoid the latter.
Conceptualizing embeddedness as a key dimension for analyzing journalistic cultures
Authors: Vos Tim P , Hanusch Folker 
Published: January 2024

Abstract
The study of journalistic cultures has a long history in communication research. Yet, much scholarship has been criticized for emanating too much from normative and—particularly in the case of comparative work—ethnocentric assumptions. While much progress has been made, the field arguably still suffers from these imbalances, restricting a more holistic understanding of journalistic cultures. This article aims to address this gap by proposing a repurposed concept for the study of journalistic cultures that focuses on the extent to which journalists are embedded in communities’ experiences, values, histories, places, and languages. Following an overview and explication of how embeddedness has been used in journalism scholarship, but also in other disciplines, we argue that the term provides an opportunity to better contextualize journalistic cultures, contributing to a less normatively dismissive and more explanatory approach to analyzing journalism and comparing journalistic cultures.
Vasostatins: new molecular targets for atherosclerosis, post-ischaemic angiogenesis, and arteriogenesis
Authors: Madonna Rosalinda , Barachini Serena , Ghelardoni Sandra , Lu Lin , Shen Wei-Feng , De Caterina Raffaele 
Published: January 2024

Abstract
The chromogranin–secretogranin secretory proteins—granins—are acidic proteins localized in granules of endocrine cells and neurons. The chromogranin family includes chromogranins A (CgA) and B, as well as secretogranin II (once called chromogranin C). Members of this family undergo catalytic proteolysis to produce active peptides. The CgA-derived peptides vasostatin-1 and vasostatin-2, in particular, appear to protect against atherosclerosis, suppressing the expression of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1, as well as exerting vasodilatory effects by enhancing nitric oxide bioavailability. Vasostatin-1 also suppresses vasoconstriction and abnormal angiogenesis. Vasostatin-1 and vasostatin-2 may be novel therapeutic targets for atherosclerosis and coronary heart disease, also protecting the myocardium against ischaemic damage.
“Stuckness” and the Fraying Promise of Postfeminism in Contemporary Women’s Short Stories
Authors: Appleton Marni 
Published: January 2024

Abstract
While postfeminism is typically associated with upbeat feelings, such as confidence and resilience, scholars have begun to examine the emergence of less positive feelings alongside the compulsory outward presentation of enthusiasm. This essay examines feelings of “stuckness” in two short stories—“Would Like to Meet” (2014) by May-Lan Tan and “Los Angeles” (2020) by Emma Cline—and how these feelings illuminate the affective regulation of postfeminism. It also makes the case that the short story is an adept form through which to explore the contradictions of neoliberal femininity and that women short story writers are utilizing the tendencies of the form—particularly in regard to the short story’s ending—to re-create the lingering, non-cathartic feelings produced by the deteriorating promise of postfeminist culture.
DAPredict: a database for drug action phenotype prediction
Authors: Meng Qingkang , Cai Yiyang , Zhou Kun , Xu Fei , Huo Diwei , Xie Hongbo , Yu Meini , Zhang Denan , Chen Xiujie 
Published: January 2024

Abstract
The phenotypes of drug action, including therapeutic actions and adverse drug reactions (ADRs), are important indicators for evaluating the druggability of new drugs and repositioning the approved drugs. Here, we provide a user-friendly database, DAPredict (http://bio-bigdata.hrbmu.edu.cn/DAPredict), in which our novel original drug action phenotypes prediction algorithm (Yang,J., Zhang,D., Liu,L. et al. (2021) Computational drug repositioning based on the relationships between substructure-indication. Brief. Bioinformatics, 22, bbaa348) was embedded. Our algorithm integrates characteristics of chemical genomics and pharmacogenomics, breaking through the limitations that traditional drug development process based on phenotype cannot analyze the mechanism of drug action. Predicting phenotypes of drug action based on the local active structures of drugs and proteins can achieve more innovative drug discovery across drug categories and simultaneously evaluate drug efficacy and safety, rather than traditional one-by-one evaluation. DAPredict contains 305 981 predicted relationships between 1748 approved drugs and 454 ADRs, 83 117 predicted relationships between 1478 approved drugs and 178 Anatomical Therapeutic Chemicals (ATC). More importantly, DAPredict provides an online prediction tool, which researchers can use to predict the action phenotypic spectrum of more than 110 000 000 compounds (including about 168 000 natural products) and corresponding proteins to analyze their potential effect mechanisms. DAPredict can also help researchers obtain the phenotype-corresponding active structures for structural optimization of new drug candidates, making it easier to evaluate the druggability of new drug candidates and develop more innovative drugs across drug categories.
Database URL: http://bio-bigdata.hrbmu.edu.cn/DAPredict/
Hospital Surgical Volume–Outcome Relationship of Postoperative Morbidity for Ileocolic Resection in Crohn’s Disease: A French Nationwide Study of 4205 Patients
Authors: Bitterlin Thibaut , Valibouze Caroline , Lenne Xavier , Bruandet Amélie , Desreumaux Pierre , Zerbib Philippe 
Published: January 2024

Abstract

Background and Aims
Despite the development of medical therapy, nearly 50% of patients with Crohn’s disease [CD] undergo surgery during their lifetime. Several studies have suggested some risk factors for postoperative morbidity [POM] after ileocolic resection [ICR]. However, the impact of surgical hospital volume on POM in CD has not been extensively studied. This study aimed to assess the impact of surgical hospital volume on POM after ICR for CD.

Methods
All patients with CD who underwent ICR in France between 2013 and 2022 were identified in the French Database, Programme de Médicalisation des Systèmes d’Information. Using the Chi-square automatic interaction detector, we determined the cut-off value to split high-surgical-volume [≥6 ICRs/year] and low-surgical-volume centres [&lt;6 ICRs/year]. The primary outcome was the evaluation of major POM during hospitalization. POM was evaluated according to the surgical volume centre. The Elixhauser comorbidity index [ECI] was used to categorize the comorbidities of patients.

Results
A total of 4205 patients were identified, and the major POM during hospitalization was significantly [p = 0.0004] lower in the high-surgical-volume [6.2%] compared to low-surgical-volume centres [9.1%]. After multivariate analysis, independent factors associated with major POM were surgical hospital volume [p = 0.024], male sex [p = 0.029], ECI ≥ 1 [p &lt; 0.001], and minor POM [p &lt; 0.001].

Conclusion
Major POM after ICR for CD is closely associated with surgical hospital volume. Centralization of surgery for CD is desirable, especially in patients with major comorbidities.
Prophylactic Versus Endoscopy-driven Treatment of Crohn’s Postoperative Recurrence: A Retrospective, Multicentric, European Study [PORCSE Study]
Authors: Geldof Jeroen , Truyens Marie , Hanssens Michiel , Van Gucht Emily , Holvoet Tom , Elorza Ainara , Bouillon Vincent , Barros Sónia , Martins Viviana , Argyriou Konstantinos , Potamianos Spyridon , Diculescu Mircea , Stroie Tudor , Bossuyt Peter , Moens Annick , Theodoraki Eirini , Koutroubakis Ioannis E , Pedro Juliana , Fernandes Samuel , Nikolaou Pinelopi , Karmiris Konstantinos , Baert Filip J , Ferreiro-Iglesias Rocio , Peeters Harald , Claeys Sophie , Casanova Maria José , Eder Piotr , Porter Ross J , Arnott Ian , Karakan Tarkan , Mesonero Francisco , Revés Joana , Van Dyck Evi , Jauregui-Amezaga Aranzazu , Mañosa Míriam , Rivière Pauline , Marquez Mosquera Lucia , Portela Francisco , Pimentel Raquel , Lobaton Triana 
Published: January 2024

Abstract

Background and Aims
No consensus exists on optimal strategy to prevent postoperative recurrence [POR] after ileocaecal resection [ICR] for Crohn’s disease [CD]. We compared early medical prophylaxis versus expectant management with treatment driven by findings at elective endoscopy 6–12 months after ICR.

Methods
A retrospective, multicentric, observational study was performed. CD patients undergoing first ICR were assigned to Cohort 1 if a biologic or immunomodulator was [re]started prophylactically after ICR, or to Cohort 2 if no postoperative prophylaxis was given and treatment was started as reaction to elective endoscopic findings. Primary endpoint was rate of endoscopic POR [Rutgeerts &gt;i1]. Secondary endpoints were severe endoscopic POR [Rutgeerts i3/i4], clinical POR, surgical POR, and treatment burden during follow-up.

Results
Of 346 included patients, 47.4% received prophylactic postoperative treatment [proactive/Cohort 1] and 52.6% did not [reactive/Cohort 2]. Endoscopic POR [Rutgeerts &gt;i1] rate was significantly higher in Cohort 2 [41.5% vs 53.8%, OR 1.81, p = 0.039] at endoscopy 6–12 months after surgery. No significant difference in severe endoscopic POR was found [OR 1.29, p = 0.517]. Cohort 2 had significantly higher clinical POR rates [17.7% vs 35.7%, OR 3.05, p = 0.002] and numerically higher surgical recurrence rates [6.7% vs 13.2%, OR 2.59, p = 0.051]. Cox proportional hazards regression analysis showed no significant difference in time to surgical POR of proactive versus expectant/reactive approach [HR 2.50, p = 0.057]. Quasi-Poisson regression revealed a significantly lower treatment burden for immunomodulator use in Cohort 2 [mean ratio 0.53, p = 0.002], but no difference in burden of biologics or combination treatment.

Conclusions
The PORCSE study showed lower rates of endoscopic POR with early postoperative medical treatment compared with expectant management after first ileocaecal resection for Crohn’s disease.
Blocking GPR15 Counteracts Integrin-dependent T Cell Gut Homing in Vivo
Authors: Schramm Sebastian , Liu Li-Juan , Saad Marek , Dietz Lisa , Dedden Mark , Müller Tanja M , Atreya Imke , Voskens Caroline J , Atreya Raja , Neurath Markus F , Zundler Sebastian 
Published: January 2024

Abstract

Background and Aims
The G protein coupled receptor GPR15 is expressed on and functionally important for T cells homing to the large intestine. However, the precise mechanisms by which GPR15 controls gut homing have been unclear. Thus, we aimed to elucidate these mechanisms as well as to explore the potential of targeting GPR15 for interfering with T cell recruitment to the colon in inflammatory bowel disease [IBD].

Methods
We used dynamic adhesion and transmigration assays, as well as a humanised in vivo model of intestinal cell trafficking, to study GPR15-dependent effects on gut homing. Moreover, we analysed GPR15 and integrin expression in patients with and without IBD, cross-sectionally and longitudinally.

Results
GPR15 controlled T cell adhesion to MAdCAM-1 and VCAM-1 upstream of α4β7 and α4β1 integrin, respectively. Consistently, high co-expression of these integrins with GPR15 was found on T cells from patients with IBD, and GPR15 also promoted T cell recruitment to the colon in humanised mice. Anti-GPR15 antibodies effectively blocked T cell gut homing in vitro and in vivo. In vitro data, as well as observations in a cohort of patients treated with vedolizumab, suggest that this might be more effective than inhibiting α4β7.

Conclusions
GPR15 seems to have a broad, but organ-selective, impact on T cell trafficking and is therefore a promising target for future therapy of IBD. Further studies are needed.