bluuebunny/crossref_metadata_2025_split huggingface dataset:
Best practices for the manual curation of intrinsically disordered proteins in DisProt
Authors: Quaglia Federica , Chasapi Anastasia , Nugnes Maria Victoria , Aspromonte Maria Cristina , Leonardi Emanuela , Piovesan Damiano , Tosatto Silvio C E 
Published: March 2024

Abstract
The DisProt database is a resource containing manually curated data on experimentally validated intrinsically disordered proteins (IDPs) and intrinsically disordered regions (IDRs) from the literature. Developed in 2005, its primary goal was to collect structural and functional information into proteins that lack a fixed three-dimensional structure. Today, DisProt has evolved into a major repository that not only collects experimental data but also contributes to our understanding of the IDPs/IDRs roles in various biological processes, such as autophagy or the life cycle mechanisms in viruses or their involvement in diseases (such as cancer and neurodevelopmental disorders). DisProt offers detailed information on the structural states of IDPs/IDRs, including state transitions, interactions and their functions, all provided as curated annotations. One of the central activities of DisProt is the meticulous curation of experimental data from the literature. For this reason, to ensure that every expert and volunteer curator possesses the requisite knowledge for data evaluation, collection and integration, training courses and curation materials are available. However, biocuration guidelines concur on the importance of developing robust guidelines that not only provide critical information about data consistency but also ensure data acquisition.This guideline aims to provide both biocurators and external users with best practices for manually curating IDPs and IDRs in DisProt. It describes every step of the literature curation process and provides use cases of IDP curation within DisProt.
Database URL: https://disprot.org/
Histological Outcomes and JAK-STAT Signalling in Ulcerative Colitis Patients Treated with Tofacitinib
Authors: van Gennep Sara , Fung Ivan C N , Jong Djuna C de , Ramkisoen Rishand K , Clasquin Esmé , de Jong Jitteke , de Vries Leonie C S , de Jonge Wouter J , Gecse Krisztina B , Löwenberg Mark , Woolcott John C , Mookhoek Aart , D’Haens Geert R 
Published: March 2024

Abstract

Background and aims
Histological outcomes and JAK-STAT signalling were assessed in a prospective ulcerative colitis [UC] patient cohort after 8 weeks treatment with tofacitinib, an oral Janus kinase [JAK] inhibitor.

Methods
Forty UC patients received tofacitinib 10 mg twice daily for 8 weeks. Treatment response was defined as histo-endoscopic mucosal improvement [HEMI]. Histological remission was defined as a Robarts Histopathology Index [RHI] ≤3 points and histological response as 50% decrease in RHI. Mucosal expression of JAK1-3, tyrosine kinase 2 [TYK2], and total signal transducer and activator of transcription [STAT] 1-6 were assessed using immunohistochemistry [IHC].

Results
At baseline, the median RHI was 14 (interquartile range [IQR] 10–19). Of 40 [65%] patients, 26 had severe endoscopic disease [endoscopic Mayo score 3] and 31/40 [78%] failed prior anti-tumour necrosis factor [anti-TNF] treatment. At Week 8, 15 patients [38%] had HEMI, 23 patients [58%] histological remission, and 34 [85%] histological response. RHI decreased by a median of 14 points [IQR 9-21] in responders [p &lt;0.001] and by 6 points [IQR 0-13] in non-responders [p = 0.002]. STAT1, STAT3, and STAT5 expression levels decreased significantly in the whole cohort. Responders had lower Week 8 STAT1 expression levels compared with non-responders [0.2%, IQR 0.1-2.8 vs 4.3%, IQR 1.2-11.9, p = 0.001], suggesting more profound STAT1 blockade. A trend of higher baseline JAK2 expression was observed in tofacitinib non-responders [2.7%, IQR 0.1-7.7] compared with responders [0.4%, IQR 0.1-2.1].

Conclusions
Tofacitinib treatment resulted in histological improvement in the majority of UC patients and in a substantial decrease of STAT1, STAT3, and STAT5 expression. HEMI was associated with more profound suppression of STAT1.
The challenge of advanced therapies in the contemporary era: first in Europe ECPELLA long-distance transfer—a case report
Authors: Fiorelli Francesca , Panoulas Vasileios , Riesgo Gil Fernando , Era Carl , Rosenberg Alexander 
Published: March 2024

Abstract

Background
The use of mechanical circulatory support (MCS) has markedly increased over the last decade, so have the inter-hospital transfers, with the aim of being able to offer advanced heart failure (AHF) therapies and centralizing patients to tertiary centres.

Case summary
In this article, we present the first in Europe long-distance air transfer of a patient supported by veno-arterial extracorporeal membrane oxygenator and Impella (ECPELLA), as a bridge to successful heart transplant. In our case report, a foreign young patient with AHF due to familiar cardiomyopathy required multiple MCS devices to achieve cardiovascular stability. After appropriate planning and multidisciplinary discussion, the patient was transferred on MCS to his country of origin via a fixed-wing airplane, in order to be assessed for heart transplantation. During take-off, the Impella flows temporarily dropped and a suction alarm was displayed; however, this rectified without intervention, and the rest of the flight was uneventful. One month after transfer, the patient underwent successful heart transplantation and remained clinically stable during the 12-month follow-up.

Discussion
Our experience links together the current challenges in the evolving AHF strategies and the increased need for inter-facility cooperation. Both these clinical and logistic challenges appear to lead to possible improved outcomes, after appropriate assessment, training, and accurate planning. Our experience provides useful information on feasibility of long-distance transport of patients supported by ECPELLA in Europe.
The evolution of the gliotoxin biosynthetic gene cluster in Penicillium fungi
Authors: Balamurugan Charu , Steenwyk Jacob L , Goldman Gustavo H , Rokas Antonis 
Published: March 2024

Abstract
Fungi biosynthesize diverse secondary metabolites, small organic bioactive molecules with key roles in fungal ecology. Fungal secondary metabolites are often encoded by physically clustered genes known as biosynthetic gene clusters (BGCs). Fungi in the genus Penicillium produce a cadre of secondary metabolites, some of which are useful (e.g. the antibiotic penicillin and the cholesterol-lowering drug mevastatin) and others harmful (e.g. the mycotoxin patulin and the immunosuppressant gliotoxin) to human affairs. Fungal genomes often also encode resistance genes that confer protection against toxic secondary metabolites. Some Penicillium species, such as Penicillium decumbens, are known to produce gliotoxin, a secondary metabolite with known immunosuppressant activity. To investigate the evolutionary conservation of homologs of the gliotoxin BGC and of genes involved in gliotoxin resistance in Penicillium, we analyzed 35 Penicillium genomes from 23 species. Homologous, lesser fragmented gliotoxin BGCs were found in 12 genomes, mostly fragmented remnants of the gliotoxin BGC were found in 21 genomes, whereas the remaining 2 Penicillium genomes lacked the gliotoxin BGC altogether. In contrast, broad conservation of homologs of resistance genes that reside outside the BGC across Penicillium genomes was observed. Evolutionary rate analysis revealed that BGCs with higher numbers of genes evolve slower than BGCs with few genes, suggestive of constraint and potential functional significance or more recent decay. Gene tree–species tree reconciliation analyses suggested that the history of homologs in the gliotoxin BGC across the genus Penicillium likely involved multiple duplications, losses, and horizontal gene transfers. Our analyses suggest that genes encoded in BGCs can have complex evolutionary histories and be retained in genomes long after the loss of secondary metabolite biosynthesis.
Genome Assembly and Annotation of the Dark-Branded Bushbrown Butterfly Mycalesis mineus (Nymphalidae: Satyrinae)
Authors: Murugesan Suriya Narayanan , Tian Shen , Monteiro Antónia 
Published: March 2024

Abstract
We report a high-quality genome draft assembly of the dark-branded bushbrown, Mycalesis mineus, a member of the Satyrinae subfamily of nymphalid butterflies. This species is emerging as a promising model organism for investigating the evolution and development of phenotypic plasticity. Using 45.99 Gb of long-read data (N50 = 11.11 kb), we assembled a genome size of 497.4 Mb for M. mineus. The assembly is highly contiguous and nearly complete (96.8% of Benchmarking Universal Single-Copy Orthologs lepidopteran genes were complete and single copy). The genome comprises 38.71% of repetitive elements and includes 20,967 predicted protein-coding genes. The assembled genome was super-scaffolded into 28 pseudo-chromosomes using a closely related species, Bicyclus anynana, with a chromosomal-level genome as a template. This valuable genomic tool will advance both ongoing and future research focused on this model organism.
Identification of CAF-related lncRNAs at the pan-cancer level represents a potential carcinogenic risk
Authors: Wang Mingwei , Jiang Minghui , Xie Aimin , Zhang Nan , Xu Yan 
Published: March 2024

Abstract
Cancer-associated fibroblasts (CAFs) are increasingly recognized as playing a crucial role in regulating cancer progression and metastasis. These cells can be activated by long non-coding RNAs (lncRNAs), promoting the malignant biological processes of tumor cells. Therefore, it is essential to understand the regulatory relationship between CAFs and lncRNAs in cancers. Here, we identified CAF-related lncRNAs at the pan-cancer level to systematically predict their potential regulatory functions. The identified lncRNAs were also validated using various external data at both tissue and cellular levels. This study has revealed that these CAF-related lncRNAs exhibit expression perturbations in cancers and are highly correlated with the infiltration of stromal cells, particularly fibroblasts and endothelial cells. By prioritizing a list of CAF-related lncRNAs, we can further distinguish patient subtypes that show survival and molecular differences. In addition, we have developed a web server, CAFLnc (https://46906u5t63.zicp.fun/CAFLnc/), to visualize our results. In conclusion, CAF-related lncRNAs hold great potential as a valuable resource for comprehending lncRNA functions and advancing the identification of biomarkers for cancer progression and therapeutic targets in cancer treatment.
Clinical Pharmacist Counselling Improves Long-term Medication Safety and Patient-reported Outcomes in Anti-TNF-treated Patients With Inflammatory Bowel Diseases: The Prospective, Randomized AdPhaNCED Trial
Authors: Plechschmidt Johannes , Fietkau Konstantin , Hepp Tobias , Dietrich Peter , Fischer Sarah , Krebs Sabine , Neurath Markus F , Dörje Frank , Atreya Raja 
Published: March 2024

Abstract

Background
Antitumor necrosis factor (anti-TNF) antibody treatment has led to marked improvements in the management of patients with inflammatory bowel diseases (IBDs). Nevertheless, anti-TNF therapy is associated with potential adverse drug reactions (ADRs). Our prospective, randomized trial investigated the effect of intensified clinical pharmacist counselling in a multidisciplinary team on medication safety in anti-TNF-treated IBD patients.

Methods
Patients with IBD with ongoing anti-TNF treatment were enrolled in our tertiary center AdPhaNCED trial and randomized to either receive conventional standard of care (control group) or additional clinical pharmacist counselling (intervention group) over 12 months. The primary end point consisted of the number and severity of ADRs associated with anti-TNF therapy. Secondary end points included patient satisfaction with medication information and medication safety.

Results
One hundred twenty-seven IBD patients were included in this study. Anti-TNF-related ADRs were significantly lower in the intervention compared with the control group (0.20 vs 0.32 [mean] ADR/patient/month, P = .006) after 12 months. The risk of more severe ADRs (Common Terminology Criteria for Adverse Events [CTCAE] grade ≥2) was significantly higher in the control compared with the intervention group (hazard ratio, 0.34; P = .001). The probability of ADR resolution (hazard ratio, 2.02; P &lt; .001) and patient satisfaction with medication information (14.82 vs 11.60; P &lt; .001) were significantly higher in the intervention group compared with the control group.

Conclusions
Our study results demonstrate that intensified pharmacist counselling significantly reduces the occurrence and severity of therapy-related ADRs and improves patient satisfaction. Clinical pharmacists should therefore be part of a holistic approach to IBD care delivered by a multidisciplinary team.
Children and Adolescents Diagnosed With Inflammatory Bowel Disease Are at Increased Risk of Developing Diseases With a Possible Autoimmune Pathogenesis
Authors: Jølving Line Riis , Zegers Floor Dijkstra , Lund Ken , Wod Mette , Nielsen Jan , Qvist Niels , Nielsen Rasmus Gaardskær , Nørgård Bente Mertz 
Published: March 2024

Abstract

Background
The development of diseases with a possible autoimmune pathogenesis is common in adults with inflammatory bowel disease (IBD). In early onset IBD, it may differ but the evidence is sparse. We aimed to investigate the risk and time span from IBD diagnosis to outcomes with different associated disorders with possible autoimmune pathogenesis.

Methods
A register-based study included all Danish patients with early onset of IBD (≤18 years) between 1980 and 2021 and 50 matched references without IBD for each case. We examined the risk of type 1 and type 2 diabetes, celiac disease, thyroid disease, rheumatoid arthritis, psoriatic arthritis, and spondyloarthritis in Cox regression models.

Results
In total, 6822 patients with IBD were identified, and 337 728 matched references. The median age at the time of IBD diagnosis or index date for the matched references was 16 years (25-75 percentile: 13-18 years), and the median age at the time of an outcome or at the end of follow-up was 28.1 years (25-75 percentile: 21.5-37.0 years). According to the cumulative incidence plots psoriatic arthritis, and spondyloarthritis was diagnosed approximately 10 years after the IBD onset, and the remaining outcomes later. The adjusted hazard ratio after full follow-up was 4.72 (95% CI, 3.85-5.80) for psoriatic arthritis, 5.21 (95% CI, 4.17-6.50) for spondyloarthritis, 2.77 (95% CI, 1.92-4.00) for celiac disease, 2.15 (95% CI, 1.54-3.01) for rheumatoid arthritis, 1.69 (95% CI, 1.23-2.32) and 1.64 (95% CI, 1.21-2.21) for type 1 and type 2 diabetes, respectively. For thyroid disease, it was 1.16 (95% CI, 0.97-1.40).

Conclusions
The risk estimates were significantly increased for all outcomes at the end of follow-up, except for thyroid disease, but according to the cumulative incidence plots, only psoriatic arthritis and spondyloarthritis occurred earlier in the IBD cohort than in the matched references.
Maximality Properties of Generalized Springer Representations of SO (N, ℂ)
Authors: La Ruben 
Published: March 2024

Abstract
Let $C$ be a unipotent class of $G=\textrm{SO}(N,\mathbb{C})$, $\mathcal{E}$ an irreducible $G$-equivariant local system on $C$. The generalized Springer representation $\rho (C,\mathcal{E})$ appears in the top cohomology of some variety. Let $\bar \rho (C,\mathcal{E})$ be the representation obtained by summing over all cohomology groups of this variety. It is well known that $\rho (C,\mathcal{E})$ appears in $\bar \rho (C,\mathcal{E})$ with multiplicity $1$ and that its Springer support $C$ is strictly minimal in the closure ordering among the Springer supports of the irreducbile subrepresentations of $\bar \rho (C,\mathcal{E})$. Suppose $C$ is parametrized by an orthogonal partition with only odd parts. We prove that $\bar \rho (C,\mathcal{E})$ (resp. $\textrm{sgn}\otimes \bar \rho (C,\mathcal{E})$) has a unique multiplicity 1 “maximal” subrepresentation $\rho ^{\textrm{max}}$ (resp. “minimal” subrepresentation $\textrm{sgn}\otimes \rho ^{\textrm{max}}$), where $\textrm{sgn}$ is the sign representation. These are analogues of results for $\textrm{Sp}(2n,\mathbb{C})$ by Waldspurger.
Animal models of eosinophilic esophagitis
Authors: Pilat Jennifer M , Jacobse Justin , Buendia Matthew A , Choksi Yash A 
Published: March 2024

Abstract
Eosinophilic esophagitis is a chronic inflammatory disorder of the esophagus. Over the past 25 yr, great strides have been made toward understanding its pathogenesis, in part due to studies in several types of animal models. The vast majority of these models have been characterized in mice. In this review, we summarize the histopathological features of eosinophilic esophagitis recapitulated by these animal models, as well as discuss their strengths and weaknesses.
Diurnal activity in an insectivorous bat during migration period
Authors: Lučan Radek K , Bartonička Tomáš 
Published: March 2024

Abstract
Diurnal flight activity in otherwise strictly nocturnal bats has typically been linked to random disturbance from day roosts, an urgent need to balance food shortage caused by adverse weather during nighttime, or the absence of diurnal predators. However, migration may be another reason why bats fly during daylight, at least in some areas. Using community-science data collection, we obtained more than 500 records of over 15,000 bats displaying diurnal flight activity, suggesting that it is relatively common in Central Europe. The vast majority of sightings were of common noctules (Nyctalus noctula), with most records concentrated in spring and autumn. The seasonal dynamics of diurnal flights exactly coincided with migratory periods, and directional movements in autumn—when diurnal activity was most frequent and included highest numbers of observed bats—suggest that the behavior may ultimately be linked to migration ecology. The highest frequency of diurnal flights in autumn coincided with highest body mass in the studied territory, thereby refuting the hypothesis of early roost emergence due to poor body condition or decreased predation risk related to increased maneuverability. A shift from strictly nocturnal to partly diurnal activity may balance increased energetic demands imposed by migration, which is temporally synchronized with periods of cold nights when prey density is limited. Common noctule diurnal activity during the migratory period may be beneficial as they can acquire energy by foraging on daily abundant prey while saving nighttime for long endurance flights—alternatively, they may forage on the way to their migratory destination, thereby saving time. Predation risk from diurnal predators may be significantly decreased by choosing high flight altitudes, as observed particularly during autumn. We suggest that observations on the geographic distribution of diurnally flying noctules may help identify migration corridors.
Economic Principles for the Enforcement of Abuse of Dominance Provisions
Authors: Fumagalli Chiara , Motta Massimo 
Published: March 2024

Abstract
The European Commission (EC) has recently announced its intention to issue Guidelines on exclusionary abuses. In this paper, we explain how economics can and should be used to inform a sound and effects-based approach in the enforcement of Article 102 TFEU. In particular, the EC should be guided only by a consumer welfare standard; exclusive dealing and exclusivity rebates should be subject to a (rebuttable) presumption of harm; price–cost tests are meaningful only for predation and other practices that do not reference rivals; essentiality of the input should not be a requirement for vertical foreclosure cases of any type, but such cases should be limited only to dominant firms that satisfy certain criteria.
Phillyrin alleviates high glucose-induced oxidative stress and inflammation in HBZY-1 cells through inhibition of the PI3K/Akt signaling pathway
Authors: Yang Chunjing , Bao Li , Shi Zhengyuan , Xv Xiqiao , Jiang Dechun , You Longtai 
Published: March 2024

Abstract

Background
Phillyrin, the major lignin compound of Forsythia suspense (Thunb.) Vahl, has been shown the effects of anti-inflammatory and antioxidant. Our study was aimed to explore the protective effect of phillyrin on glomerular mesangial cells (HBZY-1) and the potential mechanism.

Methods
Cell viability, cytokine production, levels of reactive oxygen radicals (ROS), glutathione (GSH), malondialdehyde (MDA), and superoxide dismutase (SOD), as well as autophagy and apoptosis levels were determined to verify the mechanism of phillyrin on HBZY-1 cells.

Results
Our result indicated that phillyrin significantly inhibited HG-induced HBZY-1 proliferation by inhibiting Bcl-2 expression and upregulating Bad, cleaved caspase-3, and -9 expression. Also, phillyrin suppressed HG-induced mesangial extracellular matrix accumulation by inhibiting the expression of fibronectin and transforming growth factor-β1. Further, phillyrin inhibited oxidative stress and inflammation by decreasing ROS, MDA, TNF-α, IL-1β, and IL-6 contents and increasing SOD and GSH expression. Phillyrin also promoted autophagy by increasing LC3-II/LC3-I ratio and down-regulating p62 expression. Furthermore, WB assay showed that phillyrin inhibited oxidative stress caused by HG via activating Nrf2 signaling pathway, while attenuated proliferation and inflammation in HBZY-1 cells through inactivating PI3K/Akt/mTOR and NF-κB pathways.

Conclusion
All results showed that phillyrin might be a promising therapeutic agent for the treatment of DN.
Proximity ascertainment bias in early COVID case locations
Authors: Weissman Michael B 
Published: March 2024

Abstract
A comparison of the distances to the Huanan Seafood Market of early COVID cases with known links to the market versus cases without known links shows results apparently incompatible with a location model lacking proximity ascertainment bias. The sign of the difference instead agrees with a model in which such ascertainment bias is large. In the presence of such bias inferences based on the clustering of case locations become unreliable.