bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systematic review on definitions of intestinal ultrasound treatment response and remission in inflammatory bowel disease
Authors: Allocca Mariangela , D’Amico Ferdinando , Fiorino Gionata , Jairath Vipul , Kucharzik Torsten , Peyrin-Biroulet Laurent , Danese Silvio 
Published: January 2025

Abstract

Background
Intestinal ultrasound (IUS) is emerging as a valuable tool to assess treatment response in inflammatory bowel disease (IBD) clinical trials. This study details how IUS defines response and remission to evaluate treatment efficacy in IBD patients.

Methods
We conducted a comprehensive search of studies from 1984 to March 31, 2024, focusing on IUS use in assessing treatment efficacy in IBD.

Results
A total of 51 studies were included: 31 on Crohn’s disease (CD), 12 on ulcerative colitis (UC) and 8 on IBD. Ileocolonoscopy was used as a reference standard in 53% of studies. IUS-defined response was reported in 47% of studies, with the majority (71%) using changes in bowel wall thickness (BWT) and color Doppler signals (CDS) as key indicators. IUS-defined remission was reported in 53% of studies, primarily using normalization of BWT to &lt;3 mm and CDS to grades 0 or 1 as criteria. Ultrasonographic activity scores were used in 16% of studies, including the Bowel Ultrasound Score (BUSS) in two CD studies, the International Bowel Ultrasound Segmental Activity Score (IBUS-SAS) in one CD study, and the Milan Ultrasound Criteria (MUC) in one UC study The remaining four studies used unvalidated scores without clear definitions of response or remission. Assessment times varied, most commonly at weeks 8–16, and at 6, 12, and 24 months.

Conclusions
This systematic review reveals significant variability in IUS definitions of response and remission in IBD, highlighting the need to standardize eligibility criteria and outcome measures for IUS in IBD clinical trials.
Fighting for Lemons: The Balancing Effect of Private Information on Incentives in Dynamic Contests
Authors: Möller Marc 
Published: January 2025

Abstract
In a common value environment with multi-stage competition, losing a stage conveys positive news about a rival’s estimation of a contested prize, capable of balancing the discouraging effect of falling behind. We show that, due to players’ learning from stage-outcomes, aggregate incentives under private information are often greater than under public information and may even exceed the static competition benchmark. Moreover, laggards can become more motivated than leaders, giving rise to long-lasting fights. Our results have implications for the duration of R&D races, the desirability of feedback in labor- and procurement-contests, and the campaign spending and selective efficiency of presidential primaries.
Drought tolerance as an evolutionary precursor to frost and winter tolerance in grasses
Authors: Schat Laura , Schubert Marian , Fjellheim Siri , Humphreys Aelys M 
Published: January 2025

Abstract
Accumulating evidence is suggesting more frequent tropical-to-temperate transitions than previously thought. This raises the possibility that biome transitions could be facilitated by precursor traits. A wealth of ecological, genetic, and physiological evidence suggests overlap between drought and frost stress responses, but the origin of this overlap, i.e., the evolution of these responses relative to each other, is poorly known. Here, we test whether adaptation to frost and/or severe winters in grasses (Poaceae) was facilitated by ancestral adaptation to drought. We used occurrence patterns across Köppen–Geiger climate zones to classify species as drought, frost, and/or winter tolerant, followed by comparative analyses. Ancestral state reconstructions revealed different evolutionary trajectories in different clades, suggesting both drought-first and frost-first scenarios. Explicit simultaneous modelling of drought and frost/winter tolerance provided some support for correlated evolution, but suggested higher rates of gain of frost/winter tolerance in drought-sensitive rather than drought-tolerant lineages. Overall, there is limited support across grasses as a whole that drought tolerance acted as an evolutionary precursor to frost or severe winter tolerance. Different scenarios in different clades is consistent with present-day grasses being either cold or drought specialists, possibly as a consequence of trade-offs between different stress tolerance responses.
In vitro enzyme characterization and several inhibitors for monkeypox virus core protease I7L
Authors: Wei Lin , Wu Yuqi , Li Shuai , Weng Jun , Geng Miaomiao , Mei Meng , Wei Zigong 
Published: January 2025

Abstract
Monkeypox is a zoonotic viral disease caused by the monkeypox virus, a member of the genus Orthopoxvirus within the family Poxviridae, which also includes the variola virus. On 14 August 2024, WHO Director-General declared monkeypox outbreak a public health emergency of international concern. Similar to variola virus core protease K7L, I7L could be identified as a promising target to fight against monkeypox virus. Our work provides a solid foundation as well as specific molecular tools (protease production methods, assay design, inhibitor design) that can now be used to probe the function of I7L in vitro. Notably, in this work, various reported covalent lead compounds for COVID-19 proteases were screened and A68, shikonin, and myricetin were identified as exhibiting high inhibitory activity against I7L. This work not only sheds light on effective inhibitors for the monkeypox virus core protease but also contributes to the broader search for antiviral agents targeting this enzyme.
Reciprocal and non-reciprocal effects of clinically relevant SETBP1 protein dosage changes
Authors: Antonyan Lilit , Zhang Xin , Ni Anjie , Peng Huashan , Alsuwaidi Shaima , Fleming Peter , Zhang Ying , Semenak Amelia , Macintosh Julia , Wu Hanrong , Hettige Nuwan C , Jefri Malvin , Ernst Carl 
Published: January 2025

Abstract
Many genes in the human genome encode proteins that are dosage sensitive, meaning they require protein levels within a narrow range to properly execute function. To investigate if clinically relevant variation in protein levels impacts the same downstream pathways in human disease, we generated cell models of two SETBP1 syndromes: Schinzel-Giedion Syndrome (SGS) and SETBP1 haploinsufficiency disease (SHD), where SGS is caused by too much protein, and SHD is caused by not enough SETBP1. Using patient and sex-matched healthy first-degree relatives from both SGS and SHD SETBP1 cases, we assessed how SETBP1 protein dosage affects downstream pathways in human forebrain progenitor cells. We find that extremes of SETBP1 protein dose reciprocally influence important signalling molecules such as AKT, suggesting that the SETBP1 protein operates within a narrow dosage range and that extreme doses are detrimental. We identified SETBP1 nuclear bodies as interacting with the nuclear lamina and suggest that SETBP1 may organize higher order chromatin structure via links to the nuclear envelope. SETBP1 protein doses may exert significant influence on global gene expression patterns via these SETBP1 nuclear bodies. This work provides evidence for the importance of SETBP1 protein dose in human brain development, with implications for two neurodevelopmental disorders.
Lysine succinylome analysis of MRSA reveals critical roles in energy metabolism and virulence
Authors: Zhu Xiangqin , Min Hui , Tang Yishan , Gao Min 
Published: January 2025

Abstract
Methicillin-resistant Staphylococcus aureus’s (MRSA) resistance poses a global health challenge. This study investigates lysine succinylation in MRSA using proteomics and bioinformatics approaches to uncover metabolic and virulence mechanisms, with the goal of identifying novel therapeutic targets. Mass spectrometry and bioinformatics analyses mapped the MRSA succinylome, identifying 8048 succinylation sites on 1210 proteins. These analyses included Gene Ontology annotation, Kyoto Encyclopedia of Genes and Genomes pathway enrichment, and protein–protein interaction (PPI) network construction (e.g. using the STRING database, a widely used online tool for analyzing protein-protein interactions), providing a comprehensive functional and interactive landscape of succinylated proteins. The succinylated proteins were predominantly involved in cytoplasmic metabolic processes, with enrichment in glycolysis/gluconeogenesis and the tricarboxylic acid cycle. Both of these pathways are critical for MRSA’s energy production, growth, and virulence, supplying the necessary metabolic intermediates and energy to support bacterial survival and pathogenicity. Motif analysis revealed 13 conserved motifs, while PPI analysis highlighted fibronectin-binding protein A (FnbA) as a central virulence factor. Succinylation significantly influences MRSA’s metabolism and virulence, potentially impacting biofilm by modifying key proteins such as FnbA, bifunctional autolysin, and S-ribosylhomocysteine lyase(LuxS). These findings provide new avenues for developing antibiofilm strategies and therapeutic interventions against MRSA.
Pluripotent stem cell-based immunotherapy: advances in translational research, cell differentiation, and gene modifications
Authors: Lei Qi , Deng Hongkui , Sun Shicheng 
Published: January 2025

Abstract
Cell-based immunotherapy, recognized as living drugs, is revolutionizing clinical treatment to advanced cancer and shaping the landscape of biomedical research for complex diseases. The differentiation of human pluripotent stem cells (PSCs) emerges as a novel platform with the potential to generate an unlimited supply of therapeutic immune cells, especially when coupled with gene modification techniques. PSC-based immunotherapy is expected to meet the vast clinical demand for living drugs. Here, we examine recent preclinical and clinical advances in PSC-based immunotherapy, focusing on PSC gene modification strategies and differentiation methods for producing therapeutic immune cells. We also discuss opportunities in this field and challenges in cell quality and safety, and stresses the need for further research and transparency to unlock the full potential of PSC immunotherapies.
Lineage-dependence of the neuroblastoma surfaceome defines tumor cell state-dependent and independent immunotherapeutic targets
Authors: Kendsersky Nathan M , Odrobina Michal , Mabe Nathaniel W , Farrel Alvin , Grossmann Liron , Tsang Matthew , Groff David , Wolpaw Adam J , Narch Alaa , Zammarchi Francesca , van Berkel Patrick H , Dang Chi V , Mossé Yaël P , Stegmaier Kimberly , Maris John M 
Published: January 2025

Abstract

Background
Neuroblastoma is a heterogeneous disease with adrenergic (ADRN)- and therapy resistant mesenchymal (MES)-like cells driven by distinct transcription factor networks. Here, we investigate the expression of immunotherapeutic targets in each neuroblastoma subtype and propose pan-neuroblastoma and cell state specific targetable cell-surface proteins.

Methods
We characterized cell lines, patient-derived xenografts, and patient samples as ADRN-dominant or MES-dominant to define subtype-specific and pan-neuroblastoma gene sets. Targets were validated with ChIP-sequencing, immunoblotting, and flow cytometry in neuroblastoma cell lines and isogenic ADRN-to-MES transition cell line models. Finally, we evaluated the activity of MES-specific agents in vivo and in vitro.

Results
Most immunotherapeutic targets being developed for neuroblastoma showed significantly higher expression in the ADRN subtype with limited expression in MES-like tumor cells. In contrast, CD276 (B7-H3) and L1CAM maintained expression across both ADRN and MES states. We identified several receptor tyrosine kinases (RTKs) enriched in MES-dominant samples and showed that AXL targeting with ADCT-601 was potently cytotoxic in MES-dominant cell lines and showed specific anti-tumor activity in a MES cell line-derived xenograft.

Conclusions
Immunotherapeutic strategies for neuroblastoma must address the potential of epigenetic downregulation of antigen density as a mechanism for immune evasion. We identified several RTKs as candidate MES-specific immunotherapeutic target proteins for the elimination of therapy-resistant cells. We hypothesize that the phenomena of immune escape will be less likely when targeting pan-neuroblastoma cell surface proteins such as B7-H3 and L1CAM, and/or dual targeting strategies that consider both the ADRN- and MES-cell states.
Kikuchi-Fujimoto disease: 6 years old boy rare case in Syria
Authors: Daoo Baseel Tawfik , Alhayek Shahd , Alakhrass Dana , Shibani Mosa , Khallouf Mohammad Samih 
Published: January 2025

Abstract
Kikuchi-Fujimoto disease (KFD) is a rare condition first identified in Japan in 1972. It typically presents with high fever and lymph node swelling, and may be linked to autoimmune conditions or viral infections. A 6-year-old boy presented with cervical enlargement and recurrent high fever. Physical examination revealed enlarged lymph nodes in the neck, axillary, and inguinal regions, along with hepatosplenomegaly. CT scans confirmed widespread lymphadenopathy, and blood tests showed elevated white blood cell count and C-reactive protein levels. Although lymphoma was suspected, biopsies indicated atypical lymphadenitis. Despite a positive Epstein–Barr virus test, no treatment was effective. Further lymph node biopsies ruled out lymphoma, EBV, and TB, ultimately confirming Kikuchi-Fujimoto Disease.
Disseminated fungal infection with Saprochaete capitata in acute myeloid leukemia patient: a case report from a developing country
Authors: Sweileh Mamoun W , Dawoud Ayman , Malhis Razan , Aiesh Banan M 
Published: January 2025

Abstract
Background: Saprochaete capitata may cause fatal infections in immunocompromised patients. This is the first case report of invasive Saprochaete capitate infection at an academic-tertiary care center in Palestine. Case presentation: We report a 36—year—old woman who presented with fever and severe neutropenia and was found to have AML/Non M3. While receiving her initial chemotherapy treatment, she encountered a rare fungal infection (Saprochaete capitata) that spread throughout her lungs, stomach, spleen, liver, and kidneys, presenting difficulties in both diagnosing and treatment. In addition to being treated with both voriconazole and amphotericin B, the patient underwent surgery to remove the infection source, resulting in a cure. Conclusion: In immunocompromised patients, Saprochaete capitata infection is frequently overlooked. It is essential to give antifungal combinations and to control the source of infection to enhance the outcome for patients.
Arising of autoimmune gastritis after helicobacter pylori eradication in an elderly female patient
Authors: Kiba Takayoshi , Nose Soichiro 
Published: January 2025

Abstract
Autoimmune gastritis (AIG) is a chronic condition in which the body’s immune system mistakenly attacks the stomach lining, specifically targeting parietal cells that produce stomach acid and intrinsic factors. After the H. pylori infection was eradicated, AIG developed in an elderly woman with symptoms of the disease. 1.5 years after eradication, esophagogastroduodenoscopy revealed remnants of the oxyntic mucosa sticky adherent dense mucus and scattered minute whitish protrusions at the greater curvature of the gastric corpus. Biopsy specimens from the greater curvature site of the gastric corpus before H. pylori eradication revealed neutrophilic cells in the superficial mucosa of the stomach that were mildly inflammatory and infiltrating. With the removal of H. pylori, the number of infiltrating inflammatory neutrophilic cells in the superficial mucosa decreased, whereas that of infiltrating lymphocytes increased in the sub-superficial mucosa. This case suggests that further studies regarding the detailed time course of AIG are required.
A single giant frontoparietal intraaxial hydatid cyst in a 5-year-old female: a case report and review of literature
Authors: AL-Ihribat Alaa R , Qunaibi Yaman N , Amro Rawand B , Ahmed Jamal , Rije Rama F , Shalalfeh Husam , Ibedo Falah , Itkaidek Saeed 
Published: January 2025

Abstract
Echinococcus larval stage or a hydatid cyst, a parasitic disease that passes from animals to humans. Echinococcus granulosus and, less commonly, Echinococcus multilocularis species cause the disease. Intracranial echinococcosis is rare, with an incidence of approximately 1%–2%. Primary and secondary intracranial hydatid cysts can be found. A primary one, the most common type, is always solitary. CT and MRI have significantly contributed to the accurate diagnosis of hydatids. Surgical removal of the cyst is the treatment of choice, resulting in most cases in a complete recovery. In this report, we aim to emphasize the presentation of such an isolated primary cerebral hydatid cyst in a 5-year-old girl with neurological symptoms of a space-occupying lesion. Radiology revealed a giant left frontoparietal hydatid cyst. A cerebral hydatid cyst was operated on. The patient showed an uneventful recovery and was discharged. There was no recurrence at follow-up.
Circadian Misalignment Impacts Cardiac Autonomic Modulation in Adolescence
Authors: Morales-Ghinaglia Natasha , He Fan , Calhoun Susan L , Vgontzas Alexandros N , Liao Jiangang , Liao Duanping , Bixler Edward O , Fernandez-Mendoza Julio 
Published: January 2025

Abstract

Study Objectives
Although heart rate variability (HRV), a marker of cardiac autonomic modulation (CAM), is known to predict cardiovascular morbidity, the circadian timing of sleep (CTS) is also involved in autonomic modulation. We examined whether circadian misalignment is associated with blunted HRV in adolescents as a function of entrainment to school or on-breaks.

Methods
We evaluated 360 subjects from the Penn State Child Cohort (median 16y) who had at least 3-night at-home actigraphy (ACT), in-lab 9-h polysomnography (PSG) and 24-h Holter-monitoring heart rate variability (HRV) data. ACT-measured metrics of circadian misalignment included sleep midpoint (SM), sleep irregularity (SI), and social jetlag (SJL). Five 24-h, daytime and nighttime frequency- and time-domain HRV indices were the primary outcomes. Linear regression models adjusted for sex, race/ethnicity, age, body mass index, apnea/hypopnea index, sleep duration and its variability. These associations were also examined as a function of being in-school or on-break.

Results
While on-break, a later SM on weekends was significantly associated with all five nighttime HRV indices. While in-school, greater SI on weekdays was significantly associated with three daytime and three nighttime HRV indices. Greater SJL was not associated with any HRV index. Longitudinal analyses confirmed the association of adolescent SM, SI and SJL with change in nighttime HRV since childhood.

Conclusions
An irregular sleep phase during days of entrainment to social demands and a delayed sleep phase during ad-libitum days are associated with blunted HRV in adolescents. Circadian misalignment contributes to increased cardiovascular risk via an altered CAM in youth.
Didactic transposition of loan repayments in economics and the place of the discrete-continuous interplay
Authors: Milin Šipuš Željka , González-Martín Alejandro S , Bašić Matija 
Published: January 2025

Abstract
The study reported in this paper is motivated by an article published on a financial portal that presented loan repayments with a continuous approach, as opposed to the discrete approach of addressing loan repayments applied in mathematics courses for economists. Using the Anthropological Theory of the Didactic, we analyse the current didactic transposition of this content, based on a textbook for mathematics in economics and five interviews with teachers of mathematics and of economics, inquiring about their practices in teaching related to loan repayments in economics. The interviewed teachers indicated that this content is presented in a discrete way in mathematics courses for economics, although for reasons that do not seem directly connected to the content itself. Additionally, although the participants see the interest of considering the use of continuous variables and graphs, several constraints prevent them from their use in the context of loan repayments.
Quantifying protein unfolding kinetics with a high-throughput microfluidic platform
Authors: Atsavapranee B. , Sunden F. , Herschlag D. , Fordyce P.M. 
Published: January 2025

AbstractEven after folding, proteins transiently sample unfolded or partially unfolded intermediates, and these species are often at risk of irreversible alteration (e.g.via proteolysis, aggregation, or post-translational modification). Kinetic stability, in addition to thermodynamic stability, can directly impact protein lifetime, abundance, and the formation of alternative, sometimes disruptive states. However, we have very few measurements of protein unfolding rates or how mutations alter these rates, largely due to technical challenges associated with their measurement. To address this need, we developed SPARKfold (Simultaneous Proteolysis Assay Revealing Kinetics of Folding), a microfluidic platform to express, purify, and measure unfolding rate constants for >1000 protein variants in parallel via on-chip native proteolysis. To demonstrate the power and potential of SPARKfold, we determined unfolding rate constants for 1,104 protein samples in parallel. We built a library of 31 dihydrofolate reductase (DHFR) orthologs with up to 78 chamber replicates per variant to provide the statistical power required to evaluate the system’s ability to resolve subtle effects. SPARKfold rate constants for 5 constructs agreed with those obtained using traditional techniques across a 150-fold range, validating the accuracy of the technique. Comparisons of mutant kinetic effects via SPARKfold with previously published measurements impacts on folding thermodynamics provided information about the folding transition state and pathways via φ analysis. Overall, SPARKfold enables rapid characterization of protein variants to dissect the nature of the unfolding transition state. In future work, SPARKfold can reveal mutations that drive misfolding and aggregation and enable rational design of kinetically hyperstable variants for industrial use in harsh environments.