bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeted degradation of oncogenic BCR-ABL by silencing the gene of NEDD8 E3 ligase RAPSYN
Authors: Sun Yanzi , Wang Yishu , Liu Chunyan , Huang Yingshuang , Long Qiulin , Ju Caoyun , Zhang Can , Chen Yijun 
Published: May 2024

AbstractTyrosine kinase inhibitors have been the standard treatment for patients with Philadelphia chromosome-positive (Ph+) leukemia. However, a series of issues, including drug resistance, relapse and intolerance, are still an unmet medical need. Here, we report the targeted siRNA-based lipid nanoparticles in Ph+ leukemic cell lines for gene therapy of Ph+ leukemia, which specifically targets a recently identified NEDD8 E3 ligase RAPSYN in Ph+ leukemic cells to disrupt the neddylation of oncogenic BCR-ABL. To achieve the specificity for Ph+ leukemia therapy, a single-chain fragment variable region (scFv) of anti-CD79B monoclonal antibody was covalently conjugated on the surface of OA2-siRAPSYN lipid nanoparticles to generate the targeted lipid nanoparticles (scFv-OA2-siRAPSYN). Through effectively silencing RAPSYN gene in leukemic cell lines by the nanoparticles, BCR-ABL was remarkably degraded accompanied by the inhibition of proliferation and the promotion of apoptosis. The specific targeting, therapeutic effects and systemic safety were further evaluated and demonstrated in cell line-derived mouse models. The present study has not only addressed the clinical need of Ph+ leukemia, but also enabled gene therapy against a less druggable target.
Graphical Abstract
Proposed diagnostic and prognostic markers of primary malignant hepatic vascular neoplasms
Authors: Yoo Youngeun , Shin Jinho , Jun Eunsung , Koh Eun-Young , Shin Hwa Jeong , Kang Hyo Jeong 
Published: May 2024

Abstract
Introduction
Primary malignant hepatic vascular tumors with various malignant potentials include epithelioid hemangioendothelioma (EHE) and angiosarcoma (AS), which may overlap pathologically. This study aimed to compare the pathological findings of hepatic EHE with those of AS, in association with patient outcomes.

Methods
Fifty-nine histologically confirmed patients with 34 EHE and 25 AS were admitted to a tertiary hospital from 2003 to 2020. Their EHE and AS pathological features were compared. Immunohistochemistry for CD31, ERG, CAMTA-1, TFE3, P53, and Ki-67 labeling was performed on paraffin-embedded blocks. Markers, along with histological findings, were analyzed for the purposes of diagnostic and prognostic significance by multivariate analysis.

Results
CAMTA-1 was 91.2% positive in EHE, but negative in AS (p = < 0.001). AS was significantly correlated to an aberrant p53 expression, high Ki-67 labeling, and high mitotic activity, compared to EHE (all, p = < 0.001). EHE can be classified as low grade (LG) and high grade (HG) using the prognostic values of mitotic activity and ki-67 labeling (sensitivity = 1, specificity = 1). Low grade-EHE showed significantly better overall survival than high grade-EHE (p = 0.020).

Conclusions
Immunohistochemistry for CAMTA-1, P53, and Ki-67 labeling may help distinguish EHE and AS in histologically ambiguous cases, especially small biopsied tissue. Moreover, the combination of mitotic activity and Ki-67 labeling can be a prognostic factor for EHE with various clinical features.
Quadrivalent Live-Attenuated Influenza Vaccine in Milan preschools: an Italian experience of school-located flu vaccination within the 2022–2023 season
Authors: Roncaglia Stefania , Amendola Antonella , Baldassarre Paola , Barilli Francesca , Bianchi Silvia , Biuso Andrea , Chillemi Claudia , Fappani Clara , Gasparini Chiara , Gori Maria , Guida Gabriella , Ripoli Francesca , Sgambetterra Laura , Tanzi Elisabetta , Zuccotti Gian Vincenzo 
Published: May 2024

Abstract
Background
In Italy, since the 2020–2021 flu season, the flu vaccine recommendation was extended to all children aged 6 months to 6 years and quadrivalent Live-Attenuated Influenza Vaccine (qLAIV) was introduced. Since school-aged children are important carriers of annual influenza epidemics, a school-based influenza vaccination program may potentially increase vaccine uptake. Recent studies, conducted in the UK and the US, show that school-based vaccination can reach higher percentage of paediatric vaccination coverage compared to children vaccinated in other settings.

Methods
During 2022–2023 flu season in 9 preschools located in Milan healthcare personnel vaccinated children with qLAIV at the end of a school day. A Google Form questionnaire was administered to preschoolers’ parents of all preschools within the Municipality of Milan.

Results
In the preschools engaged in the vaccination program, 233 out of 1939 children were vaccinated (12%). Among these, 61 (26.2%) had never been vaccinated for influenza before. Vaccination coverage was 11.5% for Italian children and 14.3% for children coming from an immigrant background.
We collected 3659 questionnaire responses, divided according to study participation status (371 from preschools that participated in the vaccination program and 3288 from other preschools in Milan). 57% of the families who answered to the questionnaire vaccinated their children for flu. qLAIV accounted for 85.6% of vaccinations. We observed a statistically significant difference in the percentage of vaccinated children between those attending a school participating in the project (67.9%) and children attending other schools (56%) (p < 0.001). Vaccination was administered by family pediatricians (48.9%), in vaccination centers (34.8%), in vaccine hubs (11.3%), in schools (2.6%), by private pediatricians (1.6%) and in other settings (0.7%). Focusing on the responses from families whose children attend schools participating in the vaccination program, 21.8% stated that the vaccination was provided in school.

Conclusion
According to our experience, in Italy, at the moment, only the cooperation between health providers and alternative settings, including schools, may expand flu vaccination coverage. In particular, schools are to be considered a place to inform and reach out to families, useful to increase vaccination coverage.
Incidences of colorectal adenomas and cancers under colonoscopy surveillance suggest an accelerated “Big Bang” pathway to CRC in three of the four Lynch syndromes
Authors: Møller Pål , Haupt Saskia , Ahadova Aysel , Kloor Matthias , Sampson Julian R. , Sunde Lone , Seppälä Toni , Burn John , Bernstein Inge , Capella Gabriel , Evans D. Gareth , Lindblom Annika , Winship Ingrid , Macrae Finlay , Katz Lior , Laish Ido , Vainer Elez , Monahan Kevin , Half Elizabeth , Horisberger Karoline , da Silva Leandro Apolinário , Heuveline Vincent , Therkildsen Christina , Lautrup Charlotte , Klarskov Louise L , Cavestro Giulia Martina , Möslein Gabriela , Hovig Eivind , Dominguez-Valentin Mev 
Published: May 2024

Abstract
Background
Colorectal cancers (CRCs) in the Lynch syndromes have been assumed to emerge through an accelerated adenoma-carcinoma pathway. In this model adenomas with deficient mismatch repair have an increased probability of acquiring additional cancer driver mutation(s) resulting in more rapid progression to malignancy. If this model was accurate, the success of colonoscopy in preventing CRC would be a function of the intervals between colonoscopies and mean sojourn time of detectable adenomas. Contrary to expectations, colonoscopy did not decrease incidence of CRC in the Lynch syndromes and shorter colonoscopy intervals have not been effective in reducing CRC incidence. The prospective Lynch Syndrome Database (PLSD) was designed to examine these issues in carriers of pathogenic variants of the mis-match repair (path_MMR) genes.

Materials and methods
We examined the CRC and colorectal adenoma incidences in 3,574 path_MLH1, path_MSH2, path_MSH6 and path_PMS2 carriers subjected to regular colonoscopy with polypectomy, and considered the results based on sojourn times and stochastic probability paradigms.

Results
Most of the path_MMR carriers in each genetic group had no adenomas. There was no association between incidences of CRC and the presence of adenomas. There was no CRC observed in path_PMS2 carriers.

Conclusions
Colonoscopy prevented CRC in path_PMS2 carriers but not in the others. Our findings are consistent with colonoscopy surveillance blocking the adenoma-carcinoma pathway by removing identified adenomas which might otherwise become CRCs. However, in the other carriers most CRCs likely arised from dMMR cells in the crypts that have an increased mutation rate with increased stochastic chaotic probabilities for mutations. Therefore, this mechanism, that may be associated with no or only a short sojourn time of MSI tumours as adenomas, could explain the findings in our previous and current reports.
Efficacy of expanded periurethral cleansing in reducing catheter-associated urinary tract infection in comatose patients: a randomized controlled clinical trial
Authors: Qin Xingsong , Zhao He , Qin Wei , Qin Xinglei , Shen Songying , Wang Hongyu 
Published: May 2024

Abstract
Background
The effect of the periurethral cleansing range on catheter-associated urinary tract infection (CAUTI) occurrence remains unknown. The purpose of this study was to evaluate the efficacy of expanded periurethral cleansing for reducing CAUTI in comatose patients.

Methods
In this randomized controlled trial, eligible patients in our hospital were enrolled and allocated randomly to the experimental group (expanded periurethral cleansing protocol; n = 225) or the control group (usual periurethral cleansing protocol; n = 221). The incidence of CAUTI on days 3, 7, and 10 after catheter insertion were compared, and the pathogen results and influencing factors were analyzed.

Results
The incidences of CAUTI in the experimental and control groups on days 3, 7, and 10 were (5/225, 2.22% vs. 7/221, 3.17%, P = 0.54), (12/225, 5.33% vs. 18/221, 8.14%, P = 0.24), and (23/225, 10.22% vs. 47/221, 21.27%, P = 0.001), respectively; Escherichia coli and Candida albicans were the most common species in the two groups. The incidences of bacterial CAUTI and fungal CAUTI in the two groups were 11/225, 4.89% vs. 24/221, 10.86%, P = 0.02) and (10/225, 4.44% vs. 14/221, 6.33%, P = 0.38), respectively. The incidences of polymicrobial CAUTI in the two groups were 2/225 (0.89%) and 9/221 (4.07%), respectively (P = 0.03). The percentages of CAUTI-positive females in the two groups were 9.85% (13/132) and 29.52% (31/105), respectively (P < 0.05). The proportion of CAUTI-positive patients with diabetes in the experimental and control groups was 17.72% (14/79), which was lower than the 40.85% (29/71) in the control group (P < 0.05).

Conclusion
Expanded periurethral cleansing could reduce the incidence of CAUTI, especially those caused by bacteria and multiple pathogens, in comatose patients with short-term catheterization (≤ 10 days). Female patients and patients with diabetes benefit more from the expanded periurethral cleansing protocol for reducing CAUTI.
Organ donation after extracorporeal cardiopulmonary resuscitation: a nationwide retrospective cohort study
Authors: Yumoto Tetsuya , Tsukahara Kohei , Obara Takafumi , Hongo Takashi , Nojima Tsuyoshi , Naito Hiromichi , Nakao Atsunori 
Published: May 2024

Abstract
Background
Limited data are available on organ donation practices and recipient outcomes, particularly when comparing donors who experienced cardiac arrest and received extracorporeal cardiopulmonary resuscitation (ECPR) followed by veno-arterial extracorporeal membrane oxygenation (ECMO) decannulation, versus those who experienced cardiac arrest without receiving ECPR. This study aims to explore organ donation practices and outcomes post-ECPR to enhance our understanding of the donation potential after cardiac arrest.

Methods
We conducted a nationwide retrospective cohort study using data from the Japan Organ Transplant Network database, covering all deceased organ donors between July 17, 2010, and August 31, 2022. We included donors who experienced at least one episode of cardiac arrest. During the study period, patients undergoing ECMO treatment were not eligible for a legal diagnosis of brain death. We compared the timeframes associated with each donor’s management and the long-term graft outcomes of recipients between ECPR and non-ECPR groups.

Results
Among 370 brain death donors with an episode of cardiac arrest, 26 (7.0%) received ECPR and 344 (93.0%) did not; the majority were due to out-of-hospital cardiac arrests. The median duration of veno-arterial ECMO support after ECPR was 3 days. Patients in the ECPR group had significantly longer intervals from admission to organ procurement compared to those not receiving ECPR (13 vs. 9 days, P = 0.005). Lung graft survival rates were significantly lower in the ECPR group (log-rank test P = 0.009), with no significant differences in other organ graft survival rates. Of 160 circulatory death donors with an episode of cardiac arrest, 27 (16.9%) received ECPR and 133 (83.1%) did not. Time intervals from admission to organ procurement following circulatory death and graft survival showed no significant differences between ECPR and non-ECPR groups. The number of organs donated was similar between the ECPR and non-ECPR groups, regardless of brain or circulatory death.

Conclusions
This nationwide study reveals that lung graft survival was lower in recipients from ECPR-treated donors, highlighting the need for targeted research and protocol adjustments in post-ECPR organ donation.
Commonly used software tools produce conflicting and overly-optimistic AUPRC values
Authors: Chen Wenyu , Miao Chen , Zhang Zhenghao , Fung Cathy Sin-Hang , Wang Ran , Chen Yizhen , Qian Yan , Cheng Lixin , Yip Kevin Y. , Tsui Stephen Kwok-Wing , Cao Qin 
Published: May 2024

AbstractThe precision-recall curve (PRC) and the area under the precision-recall curve (AUPRC) are useful for quantifying classification performance. They are commonly used in situations with imbalanced classes, such as cancer diagnosis and cell type annotation. We evaluate 10 popular tools for plotting PRC and computing AUPRC, which were collectively used in more than 3000 published studies. We find the AUPRC values computed by the tools rank classifiers differently and some tools produce overly-optimistic results.
Identification of novel snoRNA-based biomarkers for clear cell renal cell carcinoma from urine-derived extracellular vesicles
Authors: Grützmann Konrad , Salomo Karsten , Krüger Alexander , Lohse-Fischer Andrea , Erdmann Kati , Seifert Michael , Baretton Gustavo , Aust Daniela , William Doreen , Schröck Evelin , Thomas Christian , Füssel Susanne 
Published: May 2024

Abstract
Background
Clear cell renal cell carcinoma (ccRCC) is the most common subtype of RCC with high rates of metastasis. Targeted therapies such as tyrosine kinase and checkpoint inhibitors have improved treatment success, but therapy-related side effects and tumor recurrence remain a challenge. As a result, ccRCC still have a high mortality rate. Early detection before metastasis has great potential to improve outcomes, but no suitable biomarker specific for ccRCC is available so far. Therefore, molecular biomarkers derived from body fluids have been investigated over the past decade. Among them, RNAs from urine-derived extracellular vesicles (EVs) are very promising.

Methods
RNA was extracted from urine-derived EVs from a cohort of 78 subjects (54 ccRCC patients, 24 urolithiasis controls). RNA-seq was performed on the discovery cohort, a subset of the whole cohort (47 ccRCC, 16 urolithiasis). Reads were then mapped to the genome, and expression was quantified based on 100 nt long contiguous genomic regions. Cluster analysis and differential region expression analysis were performed with adjustment for age and gender. The candidate biomarkers were validated by qPCR in the entire cohort. Receiver operating characteristic, area under the curve and odds ratios were used to evaluate the diagnostic potential of the models.

Results
An initial cluster analysis of RNA-seq expression data showed separation by the subjects’ gender, but not by tumor status. Therefore, the following analyses were done, adjusting for gender and age. The regions differentially expressed between ccRCC and urolithiasis patients mainly overlapped with small nucleolar RNAs (snoRNAs). The differential expression of four snoRNAs (SNORD99, SNORD22, SNORD26, SNORA50C) was validated by quantitative PCR. Confounder-adjusted regression models were then used to classify the validation cohort into ccRCC and tumor-free subjects. Corresponding accuracies ranged from 0.654 to 0.744. Models combining multiple genes and the risk factors obesity and hypertension showed improved diagnostic performance with an accuracy of up to 0.811 for SNORD99 and SNORA50C (p = 0.0091).

Conclusions
Our study uncovered four previously unrecognized snoRNA biomarkers from urine-derived EVs, advancing the search for a robust, easy-to-use ccRCC screening method.
Inter-season training effects on cardiovascular health in American-style football players
Authors: Hodzic Amir , Gendron Patrick , Baron Emmanuelle , Éthier Amélie , Bonnefous Odile , Saloux Eric , Milliez Paul , Normand Hervé , Tournoux François 
Published: May 2024

Abstract
Background
Recent studies on American-style football (ASF) athletes raised questions about the impact of training on the cardiovascular phenotype, particularly among linemen players who engage mostly in static exercise during competition and who exhibit concentric cardiac remodeling, often considered maladaptive. We aimed to examine the cardiovascular adaptation to the inter-season mixed-team training program among ASF players.

Methods
A prospective, longitudinal, cohort study was conducted among competitive male ASF players from the University of Montreal before and after an inter-season training, which lasted 7 months. This program includes, for all players, combined dynamic and static exercises. Clinical and echocardiographic examinations were performed at both steps. Left atrial (LA) and ventricular (LV) morphological and functional changes were assessed using a multiparametric echocardiographic approach (2D and 3D-echo, Doppler, and speckle tracking). Two-way ANOVA was performed to analyze the impacts of time and field position (linemen versus non-linemen).

Results
Fifty-nine players (20 linemen and 39 non-linemen) were included. At baseline, linemen had higher blood pressure (65% were prehypertensive and 10% were hypertensive), thicker LV walls, lower LV systolic and diastolic functions, lower LA-reservoir and conduit functions than non-linemen. After training, linemen significantly reduced weight (Δ-3.4%, P < 0.001) and systolic blood pressure (Δ-4.5%, P < 0.001), whereas non-linemen maintained their weight and significantly increased their systolic (Δ+4.2%, P = 0.037) and diastolic (Δ+16%, P < 0.001) blood pressure ). Mixed training was associated with significant increases in 2D-LA volume (P < 0.001), 3D-LV end-diastolic volume (P < 0.001), 3D-LV mass (P < 0.001), and an improvement in LV systolic function, independently of the field position. Non-linemen remodeled their LV in a more concentric fashion and showed reductions in LV diastolic and LA reservoir functions.

Conclusions
Our study underscored the influence of field position on cardiovascular adaptation among university-level ASF players, and emphasized the potential of inter-season training to modulate cardiovascular risk factors, particularly among linemen.
One chiral fingerprint to find them all
Authors: Orsi Markus , Reymond Jean-Louis 
Published: May 2024

Abstract
Molecular fingerprints are indispensable tools in cheminformatics. However, stereochemistry is generally not considered, which is problematic for large molecules which are almost all chiral.
Herein we report MAP4C, a chiral version of our previously reported fingerprint MAP4, which lists MinHashes computed from character strings containing the SMILES of all pairs of circular substructures up to a diameter of four bonds and the shortest topological distance between their central atoms. MAP4C includes the Cahn-Ingold-Prelog (CIP) annotation (R, S, r or s) whenever the chiral atom is the center of a circular substructure, a question mark for undefined stereocenters, and double bond cis–trans information if specified. MAP4C performs slightly better than the achiral MAP4, ECFP and AP fingerprints in non-stereoselective virtual screening benchmarks. Furthermore, MAP4C distinguishes between stereoisomers in chiral molecules from small molecule drugs to large natural products and peptides comprising thousands of diastereomers, with a degree of distinction smaller than between structural isomers and proportional to the number of chirality changes. Due to its excellent performance across diverse molecular classes and its ability to handle stereochemistry, MAP4C is recommended as a generally applicable chiral molecular fingerprint.

Scientific contribution
The ability of our chiral fingerprint MAP4C to handle stereoisomers from small molecules to large natural products and peptides is unprecedented and opens the way for cheminformatics to include stereochemistry as an important molecular parameter across all fields of molecular design.

Graphical Abstract
Evaluating the predictions of an interoceptive inference model of bulimia nervosa
Authors: Chester Maia A. , Viranda Thalia , Kaye Walter H. , Berner Laura A. 
Published: May 2024

Abstract
Objective
Bulimia nervosa (BN) is associated with loss-of-control (LOC) eating episodes that frequently occur in response to negative emotions. According to recent neurocomputational models, this link could be explained by a failure to accurately update beliefs about the body in states of high arousal. Specifically, these interoceptive inference models suggest that under-relying on signals from one’s body about sensory experience (“low sensory precision”) and/or over-relying on previously held beliefs (“excessively precise priors”) lead to inaccurate perception and maladaptive behaviors. We conducted an initial test of these core predictions of the interoceptive inference model in BN using self-report measures.

Methods
We compared women with BN (n = 30) and age-, BMI-, and full-scale IQ-matched controls (n = 31) on trust in sensory information from the body and two types of beliefs about what can be done to regulate high negative affect. Within the BN group, we tested interrelations among these measures and explored their associations with LOC eating frequency.

Results
Compared with healthy controls, the BN group reported lower levels of trust in sensory information and stronger beliefs that once upset, there is little one can do, apart from eating, to self-regulate. These beliefs were associated with each other and with lower body trust. Beliefs about the uncontrollability of emotion were associated with more frequent subjective binge-eating episodes.

Conclusions
Findings provide initial support for the core predictions of an interoceptive inference account of BN: low trust in sensory information (“sensory precision”) may promote an overreliance on maladaptive “prior beliefs” about the effects of eating on negative emotions, ultimately interfering with accurate updating of beliefs about other strategies that could regulate emotions and maintain LOC eating. Low body trust, strong expectations about emotions, and their neurocomputational underpinnings could be promising combined treatment targets for BN.