bluuebunny/crossref_metadata_2025_split huggingface dataset:
BTK and PLCG2 remain unmutated in one-third of patients with CLL relapsing on ibrutinib
Authors: Bonfiglio Silvia , Sutton Lesley-Ann , Ljungström Viktor , Capasso Antonella , Pandzic Tatjana , Weström Simone , Foroughi-Asl Hassan , Skaftason Aron , Gellerbring Anna , Lyander Anna , Gandini Francesca , Gaidano Gianluca , Trentin Livio , Bonello Lisa , Reda Gianluigi , Bödör Csaba , Stavroyianni Niki , Tam Constantine S. , Marasca Roberto , Forconi Francesco , Panayiotidis Panayiotis , Ringshausen Ingo , Jaksic Ozren , Frustaci Anna Maria , Iyengar Sunil , Coscia Marta , Mulligan Stephen P. , Ysebaert Loïc , Strugov Vladimir , Pavlovsky Carolina , Walewska Renata , Österborg Anders , Cortese Diego , Ranghetti Pamela , Baliakas Panagiotis , Stamatopoulos Kostas , Scarfò Lydia , Rosenquist Richard , Ghia Paolo 
Published: January 2023

Abstract
Patients with chronic lymphocytic leukemia (CLL) progressing on ibrutinib constitute an unmet need. Though Bruton tyrosine kinase (BTK) and PLCG2 mutations are associated with ibrutinib resistance, their frequency and relevance to progression are not fully understood. In this multicenter retrospective observational study, we analyzed 98 patients with CLL on ibrutinib (49 relapsing after an initial response and 49 still responding after ≥1 year of continuous treatment) using a next-generation sequencing (NGS) panel (1% sensitivity) comprising 13 CLL-relevant genes including BTK and PLCG2. BTK hotspot mutations were validated by droplet digital polymerase chain reaction (ddPCR) (0.1% sensitivity). By integrating NGS and ddPCR results, 32 of 49 relapsing cases (65%) carried at least 1 hotspot BTK and/or PLCG2 mutation(s); in 6 of 32, BTK mutations were only detected by ddPCR (variant allele frequency [VAF] 0.1% to 1.2%). BTK/PLCG2 mutations were also identified in 6 of 49 responding patients (12%; 5/6 VAF &lt;10%), of whom 2 progressed later. Among the relapsing patients, the BTK-mutated (BTKmut) group was enriched for EGR2 mutations, whereas BTK-wildtype (BTKwt) cases more frequently displayed BIRC3 and NFKBIE mutations. Using an extended capture-based panel, only BRAF and IKZF3 mutations showed a predominance in relapsing cases, who were enriched for del(8p) (n = 11; 3 BTKwt). Finally, no difference in TP53 mutation burden was observed between BTKmut and BTKwt relapsing cases, and ibrutinib treatment did not favor selection of TP53-aberrant clones. In conclusion, we show that BTK/PLCG2 mutations were absent in a substantial fraction (35%) of a real-world cohort failing ibrutinib, and propose additional mechanisms contributing to resistance.
Antibiotic resistance profile of common uropathogens during COVID-19 pandemic: hospital based epidemiologic study
Authors: Abdel Gawad Ahmed M. , Ashry Walaa Mohamed Omar , El-Ghannam Sherief , Hussein Mahmoud , Yousef Ahmed 
Published: January 2023

Abstract
Background
Antimicrobial resistance has a direct impact on the ability to treat common infections, and this was worsened during the COVID-19 pandemic. Worldwide surveillance studies are lacking and resistance rates vary spatially, so frequent local surveillance reports are required to guide antimicrobial stewardship efforts.
This study aims to report our common local uropathogens and their antibiogram profiles in our community during the COVID era.

Methods
A retrospective study included patients referred to our urology units with urine culture and sensitivity. All bacterial strains were identified, and their antibiotic susceptibilities were tested.

Results
Out of 2581 urine culture results recruited, 30% showed microbiological proof of infection. The majority, 486 (63.4%), were isolated from females. The most frequent isolates were Escherichia coli (44.4%) and Staphylococcus aureus (17.8%). The resistance rates ranged from 26.9 to 79.7%. Piperacillin-tazobactam antibiotic had the lowest resistance rate. The multi-drug resistance pattern was recorded in 181 (23.9%) of the isolates; 159/597 (26.6%) Gram-negative and 22/160 (13.8%) Gram-positive isolates.

Conclusions
Alarming rates of antimicrobial resistance were detected, which stresses the significance of following infection control policies and establishing national antimicrobial stewardship standards.
Analysis of the association of sugammadex with the length of hospital stay in patients undergoing abdominal surgery: a retrospective study
Authors: Tan Jing , He Jianhua , Wang Lijun , Fang Jia , Li Pengyi , Song Zhenghuan , Bian Qingming 
Published: January 2023

AbstractBackgroundSugammadex is a newer medication used for rapid and reliable reversal of neuromuscular blockade. This study evaluated whether sugammadex could reduce the length of postoperative hospital stay in patients undergoing abdominal surgery.MethodsThis single center retrospective cohort study included patients who underwent major abdominal surgery between January 2015 and October 2019. Patients were randomized according to reversal with sugammadex or spontaneous recovery. The primary outcome was length of postoperative hospital stay. The secondary outcomes were length of post-anesthetic care unit (PACU) stay, postoperative ambulation time, time-to-first-defecation, and incidence of pulmonary complications. After 1:1 propensity score matching, univariate and multiple linear regression analyses estimated the differences in outcomes.ResultsOf the 1614 patients, 517 received sugammadex and 645 spontaneously recovered. After adjusting for potential confounders, non-linear relationship was detected between administration of sugammadex and the length of postoperative hospital stay (β = 0.29 95% confidence interval {CI}: [− 1.13, − 0.54],P = 0.4912). However, it was associated with shorter PACU stay (β = − 20.30 95% CI: [− 24.48, − 17.11],P < 0.0001), shorter time to postoperative ambulation movement (β = − 0.43 95% CI: [− 0.62, − 0.23],P < 0.0001), and reduced time-to-first-defecation (β = − 2.25 95% CI: [− 0.45, − 0.05],P = 0.0129), when compared to the spontaneously recovered group. The incidence of pneumonia in the sugammadex group was significantly lower than that in the spontaneously recovered group (18.6% [44/237] vs. 39.2% [93/237]P < 0.05).ConclusionsNeuromuscular blockade reversal with sugammadex after abdominal surgery demonstrated an excellent recovery profile and was associated with decreased risk of pneumonia, although it did not affect the length of postoperative hospital stay.
Multivariate longitudinal data for survival analysis of cardiovascular event prediction in young adults: insights from a comparative explainable study
Authors: Nguyen Hieu T. , Vasconcellos Henrique D. , Keck Kimberley , Reis Jared P. , Lewis Cora E. , Sidney Steven , Lloyd-Jones Donald M. , Schreiner Pamela J. , Guallar Eliseo , Wu Colin O. , Lima João A.C. , Ambale-Venkatesh Bharath 
Published: January 2023

Abstract
Background
Multivariate longitudinal data are under-utilized for survival analysis compared to cross-sectional data (CS - data collected once across cohort). Particularly in cardiovascular risk prediction, despite available methods of longitudinal data analysis, the value of longitudinal information has not been established in terms of improved predictive accuracy and clinical applicability.

Methods
We investigated the value of longitudinal data over and above the use of cross-sectional data via 6 distinct modeling strategies from statistics, machine learning, and deep learning that incorporate repeated measures for survival analysis of the time-to-cardiovascular event in the Coronary Artery Risk Development in Young Adults (CARDIA) cohort. We then examined and compared the use of model-specific interpretability methods (Random Survival Forest Variable Importance) and model-agnostic methods (SHapley Additive exPlanation (SHAP) and Temporal Importance Model Explanation (TIME)) in cardiovascular risk prediction using the top-performing models.

Results
In a cohort of 3539 participants, longitudinal information from 35 variables that were repeatedly collected in 6 exam visits over 15 years improved subsequent long-term (17 years after) risk prediction by up to 8.3% in C-index compared to using baseline data (0.78 vs. 0.72), and up to approximately 4% compared to using the last observed CS data (0.75). Time-varying AUC was also higher in models using longitudinal data (0.86–0.87 at 5 years, 0.79–0.81 at 10 years) than using baseline or last observed CS data (0.80–0.86 at 5 years, 0.73–0.77 at 10 years). Comparative model interpretability analysis revealed the impact of longitudinal variables on model prediction on both the individual and global scales among different modeling strategies, as well as identifying the best time windows and best timing within that window for event prediction. The best strategy to incorporate longitudinal data for accuracy was time series massive feature extraction, and the easiest interpretable strategy was trajectory clustering.

Conclusion
Our analysis demonstrates the added value of longitudinal data in predictive accuracy and epidemiological utility in cardiovascular risk survival analysis in young adults via a unified, scalable framework that compares model performance and explainability. The framework can be extended to a larger number of variables and other longitudinal modeling methods.

Trial registration
ClinicalTrials.gov Identifier: NCT00005130, Registration Date: 26/05/2000.
The utility of texture analysis based on quantitative synthetic magnetic resonance imaging in nasopharyngeal carcinoma: a preliminary study
Authors: Yang Fan , Li Yujie , Li Xiaolu , Yu Xiaoduo , Zhao Yanfeng , Li Lin , Xie Lizhi , Lin Meng 
Published: January 2023

Abstract
Background
Magnetic resonance imaging (MRI) is commonly used for the diagnosis of nasopharyngeal carcinoma (NPC) and occipital clivus (OC) invasion, but a proportion of lesions may be missed using non-enhanced MRI. The purpose of this study is to investigate the diagnostic performance of synthetic magnetic resonance imaging (SyMRI) in differentiating NPC from nasopharyngeal hyperplasia (NPH), as well as evaluating OC invasion.

Methods
Fifty-nine patients with NPC and 48 volunteers who underwent SyMRI examination were prospectively enrolled. Eighteen first-order features were extracted from VOIs (primary tumours, benign mucosa, and OC). Statistical comparisons were conducted between groups using the independent-samples t-test and the Mann–Whitney U test to select significant parameters. Multiple diagnostic models were then constructed using multivariate logistic analysis. The diagnostic performance of the models was calculated by receiver operating characteristics (ROC) curve analysis and compared using the DeLong test. Bootstrap and 5-folds cross-validation were applied to avoid overfitting.

Results
The T1, T2 and PD map-derived models had excellent diagnostic performance in the discrimination between NPC and NPH in volunteers, with area under the curves (AUCs) of 0.975, 0.972 and 0.986, respectively. Besides, SyMRI models also showed excellent performance in distinguishing OC invasion from non-invasion (AUC: 0.913–0.997). Notably, the T1 map-derived model showed the highest diagnostic performance with an AUC, sensitivity, specificity, and accuracy of 0.997, 96.9%, 97.9% and 97.5%, respectively. By using 5-folds cross-validation, the bias-corrected AUCs were 0.965–0.984 in discriminating NPC from NPH and 0.889–0.975 in discriminating OC invasion from OC non-invasion.

Conclusions
SyMRI combined with first-order parameters showed excellent performance in differentiating NPC from NPH, as well as discriminating OC invasion from non-invasion.
The comparison of diffusion tensor imaging in human hearts between 1.5 T and 3.0 T
Authors: Li Xiaodan , Chen Rui , Xu Xi , Xiao Zebin , Wei Xiaoyu , Yang Yuelong , Zhang Zhongping , Wu Zhigang , Zhu Yanjie , Liu Hui 
Published: January 2023

Abstract
Background
The aim was to compare the diffusion tensor imaging (DTI) indices derived from human hearts between 1.5 T and 3.0 T scanners. Additionally, the reproducibility of DTI indices was assessed between 1.5 T and 3.0 T scanners.

Methods
A total of 18 ex-vivo hearts were derived from patients who underwent heart transplantation. The DTI schemes were performed at 1.5 T and 3.0 T, respectively. Then, the same slices from each ex-vivo heart were selected for image analysis. The student’s t-test or Wilcoxon-rank test was used to compare the statistical differences. The agreement of DTI indices was mainly reported as the interclass correlation coefficient (ICC).

Results
No significant differences (all P > 0.05) were found in the DTI indices between 1.5 T and 3.0 T scanners. Interestingly, the ICC of all DTI indices was relatively lower with a low b-value. The reproducibility of the helix angle (HA) was relatively lower when compared to the other DTI indices.

Conclusion
The DTI indices of ex-vivo human hearts between 1.5 T and 3.0 T scanners had no significant differences. The consistency of DTI indices needed caution using a low b-value with different field strengths, and the relatively low reproducibility of HA should be considered.
Elevated RANTES levels are associated with increased risk of cerebral atherosclerotic stenosis
Authors: Guo Yinping , Kong Qianqian , Zhang Yi , Zhao Jing , Yu Zhiyuan , He Dan , Huang Hao , Luo Xiang 
Published: January 2023

AbstractBackgroundCerebral atherosclerotic stenosis (CAS) is a significant factor in the development of acute ischemic stroke (AIS). Previous studies have reported that cytokines are involved in atherosclerotic diseases, although the relationship between serum levels of the chemokine RANTES (regulated on activation, normal T-cell expressed and secreted) and the presence of CAS remains unclear.MethodsIn total, 127 participants (65 non-AIS controls and 62 patients with AIS) were involved in this study. CAS was defined as the presence of ≥ 50% stenosis in major intracranial or extracranial artery by a Digital Substraction Angiography (DSA) examination, and we classified all participants into four groups according to stroke and CAS status. Serum concentrations of 8 cytokines, including RANTES, were measured by the Human ProcartaPlex Multiplex Immunoassay Kit.ResultsSeventy-eight participants (61.41%) had CAS, of which 39 cases with AIS and 39 case with non-AIS. Patients with CAS had higher RANTES levels compared to non-CAS patients in both the non-AIS group (10.54 ± 0.80 vs. 13.20 ± 0.71,p = 0.016) and stroke group (11.96 ± 0.87 vs. 15.03 ± 0.75,p = 0.011), and multivariate logistic regression analysis showed that the RANTES level is independently associated with CAS in both the non-AIS group (adjusted odds ratio (OR), 1.07; 95% CI, 1.02–1.12,P = 0.004) and stroke group (adjusted OR, 1.32; 95% CI, 1.10–1.58,P = 0.003).ConclusionPatients with CAS have higher levels of serum RANTES than non-CAS patients regardless of stroke status suggesting that RANTES may play an important role in the formation of CAS.
Tumor micronecrosis predicts poor prognosis of patients with hepatocellular carcinoma after liver transplantation
Authors: Wang Yangyang , Zhang Wei , Ge Hongbin , Han Xu , Wu Jiangchao , Sun Xuqi , Sun Ke , Cao Wanyue , Huang Chao , Li Jingsong , Zhang Qi , Liang Tingbo 
Published: January 2023

Abstract
Background
Tumor micronecrosis is a histopathological feature predicting poor prognosis in patients with hepatocellular carcinoma (HCC) who underwent liver resection. However, the role of tumor micronecrosis in liver transplantation remains unclear.

Methods
We retrospectively reviewed patients with HCC who underwent liver transplantation between January 2015 and December 2021 at our center. We then classified them into micronecrosis(−) and micronecrosis(+) groups and compared their recurrence-free survival (RFS) and overall survival (OS). We identified independent prognostic factors using Cox regression analysis and calculated the area under the receiver operating characteristic curve (AUC) to evaluate the predictive value of RFS for patients with HCC after liver transplantation.

Results
A total of 370 cases with evaluable histological sections were included. Patients of the micronecrosis(+) group had a significantly shorter RFS than those of the micronecrosis(−) group (P = 0.037). Shorter RFS and OS were observed in micronecrosis(+) patients without bridging treatments before liver transplantation (P = 0.002 and P = 0.007), while no differences were detected in those with preoperative antitumor therapies that could cause iatrogenic tumor necrosis. Tumor micronecrosis improved the AUC of Milan criteria (0.77–0.79), the model for end-stage liver disease score (0.70–0.76), and serum alpha-fetoprotein (0.63–0.71) for the prediction of prognosis after liver transplantation.

Conclusion
Patients with HCC with tumor micronecrosis suffer from a worse prognosis than those without this feature. Tumor micronecrosis can help predict RFS after liver transplantation. Therefore, patients with HCC with tumor micronecrosis should be treated with adjuvant therapy and closely followed after liver transplantation.

Clinical trials registration
Not Applicable.
Risk stratification and prognostic value of multi-modal MRI-based radiomics for extranodal nasal-type NK/T-cell lymphoma
Authors: Zhao Yu-Ting , Chen Si-Ye , Liu Xin , Yang Yong , Chen Bo , Song Yong-Wen , Fang Hui , Jin Jing , Liu Yue-Ping , Jing Hao , Tang Yuan , Li Ning , Lu Ning-Ning , Wang Shu-Lian , Ouyang Han , Hu Chen , Liu Jin , Wang Zhi , Chen Fan , Yin Lin , Zhong Qiu-Zi , Men Kuo , Dai Jian-Rong , Qi Shu-Nan , Li Ye-Xiong 
Published: January 2023

AbstractBackgroundMagnetic resonance imaging (MRI) performs well in the locoregional assessment of extranodal nasal-type NK/T-cell lymphoma (ENKTCL). It’s important to assess the value of multi-modal MRI-based radiomics for estimating overall survival (OS) in patients with ENKTCL.MethodsPatients with ENKTCL in a prospectively cohort were systemically reviewed and all the pretreatment MRI were acquisitioned. An unsupervised spectral clustering method was used to identify risk groups of patients and radiomic features. A nomogram-revised risk index (NRI) plus MRI radiomics signature (NRI-M) was developed, and compared with the NRI.ResultsThe 2 distinct type I and II groups of the MRI radiomics signatures were identified. The 5-year OS rates between the type I and type II groups were 87.2% versus 67.3% (P = 0.002) in all patients, and 88.8% versus 69.2% (P = 0.003) in early-stage patients. The discrimination and calibration of the NRI-M for OS prediction demonstrated a better performance than that of either MRI radiomics or NRI, with a mean area under curve (AUC) of 0.748 and 0.717 for predicting the 5-year OS in all-stages and early-stage patients.ConclusionsThe NRI-M model has good performance for predicting the prognosis of ENKTCL and may help design clinical trials and improve clinical decision making.
IGF-1R down regulates the sensitivity of hepatocellular carcinoma to sorafenib through the PI3K / akt and RAS / raf / ERK signaling pathways
Authors: Cai Wenpeng , Ma Yongfang , Song Li , Cao Niandie , Gao Jiafeng , Zhou Shuping , Tang Xiaolong 
Published: January 2023

Abstract
Background
Insulin-like growth factor-1 receptor (IGF-1R) promotes cell proliferation and migration and inhibitsapoptosis, all of which can contribute to the development of cancers.

Method
This study investigated the effect and mechanism of IGF-1R in mediating the desensitization of hepatocellular carcinoma (HCC) to sorafenib.

Results
IGF-1R, highly expressed in the HCC cell lines SK-Hep1 and HepG2, promotes cell proliferation, migration, and anti-apoptosis through PI3K / Akt and RAS / Raf / ERK signaling pathways, resulting in HCC resistance to sorafenib. Knockdown of IGF-1R by RNA interference decreased proliferation and cell migration and upregulation of sorafenib-induced apoptosis of HCC cells. In vivo studies demonstrated that IGF-1R knockdown inhibited the growth of SK-Hep1 xenografts.

Conclusion
These data are evidence that IGF-1R participates in regulating the survival and cell growth of HCC through the PI3K / Akt and RAS / Raf / ERK signaling pathways. Intervention in the expression of IGF-1R may increase the inhibitory effect of sorafenib on HCC.
The characteristics of dome-shaped macula in Chinese children aged 4–6 years using optical coherence tomography angiography
Authors: Xiang Lu , Zhou Yingming , Zhang Xuan , Li Kai , Fei Chunli , Wang Yangyang , Bai Yang , Xie Bing , Shen Xi 
Published: January 2023

Abstract
Purpose:
To evaluate the characteristics of dome-shaped macula (DSM) in children aged 4–6 years with normal visual acuity using optical coherence tomography angiography.

Method:
This is a cross-sectional study. A total of 19 children aged 4–6 years were included. The results of optical coherence tomography angiography images were analysed to identify and quantify retinal structural and vascular parameters in DSM children. The dome height, dome base, and sub-dome choroidal thickness were manually measured. Participants with DSM and those without DSM from our previous study were compared on these parameters.

Results:
Nineteen eyes of the preschool subjects with normal visual acuity showed horizontal DSM on optical coherence tomography (OCT). The DSM was significantly smooth and low in the children, and we did not observe differences between sex and age. Compared to the children without DSM, the average axial length was longer, and the average macular vessel density was lower in the DSM group, especially in the deep retinal vascular density. Additionally, the dome height was positively correlated with the sub-dome choroidal thickness. When the dome base/height was increased, the fovea avascular zone (FAZ) area was larger.

Conclusion:
Dome-shaped macula was detected in the preschool children in the process of the emmetropization with normal visual acuity. The changes in macular structure and vasculature provide new ideas for further investigation into the characteristics of DSM formation.
Quantifying side effects and caregiver burdens of pediatric pulmonary hypertension therapies
Authors: Nelson Erik J. , Cook Ella , Nelson Samara , Brown Rebecca , Pierce Megan , Seelos Ashley Bangerter , Stickle Heather , Johansen Michael 
Published: January 2023

Abstract
Background and objectives
Pulmonary hypertension (PH) is a rare, but serious disease among children. However, PH has been primarily evaluated among adults. Consequently, treatment therapies have not been fully evaluated among pediatric populations and are used in an ‘off label’ manner. The purpose of this study was to estimate the side effect profiles of the most commonly prescribed pediatric PH therapies and to understand the burdens placed upon families caring for children living with PH.

Methods
Participants were recruited online through the “Families of children with pulmonary hypertension” Facebook group and asked to complete a survey about PH treatments.

Results
A total of 139 parents of a child living with PH completed the survey. Almost all children used ≥ 1 medication to treat PH, with 52% using ≥ 3 medications. The highest average number of side effects was reported by users of Treprostinil, Selexipag and type-5 phosphodiesterase (PDE5) inhibitors. The most common side effects were skin flushing, headache, nasal congestion, joint/muscle pain, and nausea. In terms of accessing care, 81% travel ≥ 20 miles and 68% travel for ≥ 60 min to receive care.

Conclusions
We found an array of treatment combinations employed to mitigate symptoms of PH in children, with a wide range of side effects. We also found a large, unseen economic, emotional, and time burden of caring for a child living with PH. Further research is warranted to understand the clinical implications of these side effects to move towards labeled usage of these therapies rather than post-hoc off-label usage.