bluuebunny/crossref_metadata_2025_split huggingface dataset:
Machine learning to improve interpretability of clinical, radiological and panel-based genomic data of glioma grade 4 patients undergoing surgical resection
Authors: Dal Bo Michele , Polano Maurizio , Ius Tamara , Di Cintio Federica , Mondello Alessia , Manini Ivana , Pegolo Enrico , Cesselli Daniela , Di Loreto Carla , Skrap Miran , Toffoli Giuseppe 
Published: July 2023

AbstractBackgroundGlioma grade 4 (GG4) tumors, including astrocytoma IDH-mutant grade 4 and the astrocytoma IDH wt are the most common and aggressive primary tumors of the central nervous system. Surgery followed by Stupp protocol still remains the first-line treatment in GG4 tumors. Although Stupp combination can prolong survival, prognosis of treated adult patients with GG4 still remains unfavorable. The introduction of innovative multi-parametric prognostic models may allow refinement of prognosis of these patients. Here, Machine Learning (ML) was applied to investigate the contribution in predicting overall survival (OS) of different available data (e.g. clinical data, radiological data, or panel-based sequencing data such as presence of somatic mutations and amplification) in a mono-institutional GG4 cohort.MethodsBy next-generation sequencing, using a panel of 523 genes, we performed analysis of copy number variations and of types and distribution of nonsynonymous mutations in 102 cases including 39 carmustine wafer (CW) treated cases. We also calculated tumor mutational burden (TMB). ML was applied using eXtreme Gradient Boosting for survival (XGBoost-Surv) to integrate clinical and radiological information with genomic data.ResultsBy ML modeling (concordance (c)- index = 0.682 for the best model), the role of predicting OS of radiological parameters including extent of resection, preoperative volume and residual volume was confirmed. An association between CW application and longer OS was also showed. Regarding gene mutations, a role in predicting OS was defined for mutations ofBRAFand of other genes involved in the PI3K-AKT-mTOR signaling pathway. Moreover, an association between high TMB and shorter OS was suggested. Consistently, when a cutoff of 1.7 mutations/megabase was applied, cases with higher TMB showed significantly shorter OS than cases with lower TMB.ConclusionsThe contribution of tumor volumetric data, somatic gene mutations and TBM in predicting OS of GG4 patients was defined by ML modeling.
Dose development in sinonasal imaging over the last decade – a retrospective patient study
Authors: Hackenbroch Carsten , Strobel Joachim Rudolf Balthasar , Lorenz Kai Johannes , Beer Meinrad , Schüle Simone 
Published: July 2023

Abstract
Background
Computed tomography (CT) has become the primary imaging modality for visualization of the paranasal sinuses. In this retrospective, single center patient study the radiation dose development in the past 12 years in CT imaging of the paranasal sinuses was assessed.

Methods
The computed tomography dose index (CTDIVol) and dose length product (DLP) of a total of 1246 patients (average age: 41 ± 18 years, 361 females, 885 males) were evaluated, who received imaging of the paranasal sinuses either for chronic sinusitis diagnostic, preoperatively or posttraumatically. Scans were performed on three different CT scanners (Somatom Definition AS, Somatom Definition AS+, Somatom Force, all from Siemens Healthineers) and on one CBCT (Morita) ranging from 2010 to 2022. Reconstruction techniques were filtered back projection and three generations of iterative reconstruction (IRIS, SAFIRE, ADMIRE, all from Siemens Healthineers). Group comparisons were performed using either parametrical (ANOVA) or non-parametrical tests (Kruskal-Wallis Test), where applicable.

Results
Over the past 12 years, there was a 73%, 54%, and 66% CTDIVol reduction and a significant (p < 0.001) 72%, 33%, and 67% DLP reduction in assessing the paranasal sinuses for chronic sinusitis, preoperatively and posttraumatically, respectively.

Conclusion
Technological developments in CT imaging, both hardware and software based, have led to a significant reduction in dose exposure in recent years. Particularly in imaging of the paranasal sinuses, the reduction of radiation exposure is of great interest due to the often young patient age and radiation-sensitive organs in the area of radiation exposure.
Technical violations and infractions are drivers of disengagement from methadone treatment among people with opioid use disorder discharged from Connecticut jails 2014–2018
Authors: Marotta Phillip , Hass Alissa , Viera Adam , Doernberg Molly , Barbour Russell , Grau Lauretta E. , Heimer Robert 
Published: July 2023

Abstract
Background
We investigated the interaction between arrests for technical violations vs. receiving new charges with receiving community-based methadone treatment on time-to reincarceration (TTR) in a cohort of men with opioid use disorder (OUD) released from custody from two Connecticut jails from 2014 to 2018.

Methods
Hazard ratios (HR) were estimated for time to reincarceration for technical violations/infractions, misdemeanors only, felonies only, and both misdemeanors and felonies after adjusting for age, race/ethnicity, and receiving methadone treatment during incarceration or in the community following release. Moderation analyses tested the hypotheses that the benefits of receiving methadone in jail or the community on TTR were significantly different for people with only technical violations and infractions compared to misdemeanor and felony charges.

Results
In the sample of 788 men who were reincarcerated, 29.4% received technical violations with no new charges (n = 232) with the remainder of the sample receiving new charges consisting of 26.9% new misdemeanor charges, 6.5% felony charges, and 37.2% both felony and misdemeanor charges. Compared to men who received new misdemeanor charges, TTR was significantly shorter among those who received technical violations and infractions with no new charges amounting to a 50% increase in TTR (334.5 days, SD = 321.3 vs. 228.1 days, SD = 308.0, p < 0.001; aHR = 1.5, 95% CI = 1.3, 1.8, p < 0.001). TTR of men who resumed methadone and were charged with a new crime was 50% longer than those who resumed methadone and received technical violations/infractions with no new charges. (230.2 days, SD = 340.2 vs. 402.3 days, SD = 231.3; aHR = 1.5, 95%CI = 1.0, 2.2, p = 0.038).

Conclusions
Reducing technical violations may enhance the benefits of providing community-based methadone following release from incarceration on extending the time between incarcerations during the vulnerable time post-incarceration and reduce the burden on correctional systems.
The impact of surgery and age on mortality with primary trachea malignant tumors: a retrospective study based on propensity-score matching analysis
Authors: Ping Chen , Liang Jia , Liu Zhi-Yuan , He Jiang , Zhou Ji-Yao , Cheng Hao , Yuan Guang-Da 
Published: July 2023

Abstract
Purpose
This study aimed to explore the survival significance of surgery and age on the prognosis of patients with primary trachea malignancies.

Methods
The entire cohort of 637 patients with primary malignant trachea tumors was used to perform the main analyses. The data of those patients were from a public database. Overall survival (OS) curves were drawn by the Kaplan-Meier method and compared by the Log-rank test. The univariable and multivariable Cox regression analyses calculated the hazard ratio (HR) and 95% confidence interval (CI) for overall mortality. The propensity-score matching analysis was used to reduce the selection bias.

Results
Age, surgery, histological type, N classification, M classification, marital status, and tumor grading were identified as independent prognostic factors after eliminating confounding factors. The results of the Kaplan-Meier method revealed that patients with age < 65 had a survival advantage over those with age ≥ 65 (HR = 1.908, 95% CI 1.549–2.348, P < 0.001). The 5-year OS rates were 28% and 8% in the group with age < 65 and age ≥ 65, respectively (P < 0.001). Cases with surgery had better survival over patients without surgery (HR = 0.372, 95% CI 0.265–0.522, P < 0.001). Compared with patients who did not undergo operations, patients with surgery had a higher median survival time (20 vs. 174 months). For patients with surgery, young age was considered a survival-promoting factor (HR 2.484; 95% CI 1.238–4.983, P = 0.010).

Conclusion
We suggested that age and surgery were the independent prognostic factors in patients with primary malignant trachea tumors. Besides, age serves as an essential indicator for evaluating the prognosis of postoperative patients.
Treatment of relapsing multiple sclerosis in Hungary – consensus recommendation from the Hungarian neuroimmunology society
Authors: Rajda Cecilia , Rózsa Csilla , Mike Andrea , Lovas Gábor , Mezei Zsolt , Jakab Gábor , Ács Péter , Rum Gábor , Simó Magdolna , Jobbágy Zita , Bíró Zita , Trauninger Anita , Imre Piroska , Mátyás Klotild , Deme István , Illés Zsolt , Csepany Tunde 
Published: July 2023

AbstractMultiple sclerosis (MS) may impact quality of life, careers and family plans of the affected individuals. The current treatments with disease modifying therapies aim to prevent people with MS (pwMS) from disability accumulation and progression. Different countries have different reimbursement policies resulting in inequalities in patient care among geographical regions. Access to anti-CD20 therapies for relapsing MS is restricted in Hungary because therapy of individual cases only is reimbursed. In the light of the latest research and national guidelines, 17 Hungarian MS experts agreed on 8 recommendations regarding relapsing pwMS using the Delphi round method. Strong agreement (> 80%) was achieved in all except one recommendation after three rounds, which generated a fourth Delphi round. The experts agreed on treatment initiation, switch, follow-up and discontinuation, as well as on special issues such as pregnancy, lactation, elderly population, and vaccination. Well-defined national consensus protocols may facilitate dialogue between policymakers and healthcare professionals and thus contribute to better patient care in the long run.
Mutation-Attention (MuAt): deep representation learning of somatic mutations for tumour typing and subtyping
Authors: Sanjaya Prima , Maljanen Katri , Katainen Riku , Waszak Sebastian M. ,   Genomics England Research Consortium, Ambrose J. C. , Arumugam P. , Bevers R. , Bleda M. , Boardman-Pretty F. , Boustred C. R. , Brittain H. , Brown M. A. , Caulfield M. J. , Chan G. C. , Giess A. , Griffin J. N. , Hamblin A. , Henderson S. , Hubbard T. J. P. , Jackson R. , Jones L. J. , Kasperaviciute D. , Kayikci M. , Kousathanas A. , Lahnstein L. , Lakey A. , Leigh S. E. A. , Leong I. U. S. , Leong F. J. , Maleady-Crowe F. , McEntagart M. , Minneci F. , Mitchell J. , Moutsianas L. , Mueller M. , Murugaesu N. , Need A. C. , O’Donovan P. , Odhams C. A. , Patch C. , Perez-Gil D. , Perez-Gil M. B. , Pullinger J. , Rahim T. , Rendon A. , Rogers T. , Savage K. , Sawant K. , Scott R. H. , Siddiq A. , Siddiq A. , Smith S. C. , Sosinsky A. , Stuckey A. , Tanguy M. , Taylor Tavares A. L. , Thomas E. R. A. , Thompson S. R. , Tucci A. , Welland M. J. , Williams E. , Witkowska K. , Wood S. M. , Zarowiecki M. , Aaltonen Lauri A. , Stegle Oliver , Korbel Jan O. , Pitkänen Esa 
Published: July 2023

Abstract
Background
Cancer genome sequencing enables accurate classification of tumours and tumour subtypes. However, prediction performance is still limited using exome-only sequencing and for tumour types with low somatic mutation burden such as many paediatric tumours. Moreover, the ability to leverage deep representation learning in discovery of tumour entities remains unknown.

Methods
We introduce here Mutation-Attention (MuAt), a deep neural network to learn representations of simple and complex somatic alterations for prediction of tumour types and subtypes. In contrast to many previous methods, MuAt utilizes the attention mechanism on individual mutations instead of aggregated mutation counts.

Results
We trained MuAt models on 2587 whole cancer genomes (24 tumour types) from the Pan-Cancer Analysis of Whole Genomes (PCAWG) and 7352 cancer exomes (20 types) from the Cancer Genome Atlas (TCGA). MuAt achieved prediction accuracy of 89% for whole genomes and 64% for whole exomes, and a top-5 accuracy of 97% and 90%, respectively. MuAt models were found to be well-calibrated and perform well in three independent whole cancer genome cohorts with 10,361 tumours in total. We show MuAt to be able to learn clinically and biologically relevant tumour entities including acral melanoma, SHH-activated medulloblastoma, SPOP-associated prostate cancer, microsatellite instability, POLE proofreading deficiency, and MUTYH-associated pancreatic endocrine tumours without these tumour subtypes and subgroups being provided as training labels. Finally, scrunity of MuAt attention matrices revealed both ubiquitous and tumour-type specific patterns of simple and complex somatic mutations.

Conclusions
Integrated representations of somatic alterations learnt by MuAt were able to accurately identify histological tumour types and identify tumour entities, with potential to impact precision cancer medicine.
Aberrant mechanical loading induces annulus fibrosus cells apoptosis in intervertebral disc degeneration via mechanosensitive ion channel Piezo1
Authors: Liu Chenhao , Gao Xiaoxin , Lou Jinhui , Li Haiyin , Chen Yuxuan , Chen Molong , Zhang Yuyao , Hu Zhilei , Chang Xian , Luo Menglin , Zhai Yu , Li Changqing 
Published: July 2023

AbstractBackgroundIntervertebral disc degeneration (IVDD) is closely associated with the structural damage in the annulus fibrosus (AF). Aberrant mechanical loading is an important inducement of annulus fibrosus cells (AFCs) apoptosis, which contributes to the AF structural damage and aggravates IVDD, but the underlying mechanism is still unclear. This study aims to investigate the mechanism of a mechanosensitive ion channel protein Piezo1 in aberrant mechanical loading-induced AFCs apoptosis and IVDD.MethodsRats were subjected to lumbar instability surgery to induce the unbalanced dynamic and static forces to establish the lumbar instability model. MRI and histological staining were used to evaluate the IVDD degree. A cyclic mechanical stretch (CMS)-stimulated AFCs apoptosis model was established by a Flexcell system in vitro. Tunel staining, mitochondrial membrane potential (MMP) detection, and flow cytometry were used to evaluate the apoptosis level. The activation of Piezo1 was detected using western blot and calcium fluorescent probes. Chemical activator Yoda1, chemical inhibitor GSMTx4, and a lentiviral shRNA-Piezo1 system (Lv-Piezo1) were utilized to regulate the function of Piezo1. High-throughput RNA sequencing (RNA-seq) was used to explore the mechanism of Piezo1-induced AFCs apoptosis. The Calpain activity and the activation of Calpain2/Bax/Caspase3 axis were evaluated by the Calpain activity kit and western blot with the siRNA-mediated Calapin1 or Calpain2 knockdown. Intradiscal administration of Lv-Piezo1 was utilized to evaluate the therapeutic effect of Piezo1 silencing in IVDD rats.ResultsLumbar instability surgery promoted the expression of Piezo1 in AFCs and stimulated IVDD in rats 4 weeks after surgery. CMS elicited distinct apoptosis of AFCs, with enhanced Piezo1 activation. Yoda1 further promoted CMS-induced apoptosis of AFCs, while GSMTx4 and Lv-Piezo1 exhibited opposite effects. RNA-seq showed that knocking down Piezo1 inhibited the calcium signaling pathway. CMS enhanced Calpain activity and elevated the expression of BAX and cleaved-Caspase3. Calpain2, but not Calpain1 knockdown, inhibited the expression of BAX and cleaved-Caspase3 and alleviated AFCs apoptosis. Lv-Piezo1 significantly alleviated the progress of IVDD in rats after lumbar instability surgery.ConclusionsAberrant mechanical loading induces AFCs apoptosis to promote IVDD by activating Piezo1 and downstream Calpain2/BAX/Caspase3 pathway. Piezo1 is expected to be a potential therapeutic target in treating IVDD.
Sex- and age-specific effects on the development of addiction and compulsive-like drinking in rats
Authors: Foo Jerome C. , Skorodumov Ivan , Spanagel Rainer , Meinhardt Marcus W. 
Published: July 2023

Abstract
Background
Biological factors are known to influence disease trajectories and treatment effectiveness in alcohol addiction and preclinical and clinical evidence suggests that sex is an important factor influencing disease dynamics in alcohol dependence. Another critical factor is age at first intoxicating drink, which has been identified as a risk factor for later alcohol binging. Preclinical research allows prospective monitoring of rodents throughout the lifespan, providing very detailed information that cannot be acquired in humans. Lifetime monitoring in rodents can be conducted under highly controlled conditions, during which one can systematically introduce multiple biological and environmental factors that impact behaviors of interest.

Methods
Here, we used the alcohol deprivation effect (ADE) rat model of alcohol addiction in a computerized drinkometer system, acquiring high-resolution data to study changes over the course of addictive behavior as well as compulsive-like drinking in cohorts of adolescent vs. adult as well as male vs. female rats.

Results
Female rats drank more alcohol than male rats during the whole experiment, drinking much more weak alcohol (5%) and similar amounts of stronger alcohol solutions (10%, 20%); female rats also consumed more alcohol than male rats during quinine taste adulteration. Increased consumption in females compared to males was driven by larger access sizes of alcohol. Differences in circadian patterns of movement were observed between groups. Early age of onset of drinking (postnatal day 40) in male rats had surprisingly little impact on the development of drinking behavior and compulsivity (quinine taste adulteration) when compared to rats that started drinking during early adulthood (postnatal day 72).

Conclusions
Our results suggest that there are sex-specific drinking patterns, not only in terms of total amount consumed, but specifically in terms of solution preference and access size. These findings provide a better understanding of sex and age factors involved in the development of drinking behavior, and can inform the preclinical development of models of addiction, drug development and exploration of options for new treatments.
RETRACTED ARTICLE: A novel energy-efficient scheduling method for three-dimensional heterogeneous wireless sensor networks based on improved memetic algorithm and node cooperation strategy
Authors: Gou Pingzhang , Guo Baoyong , Guo Miao 
Published: July 2023

AbstractNodes in performance heterogeneous wireless sensor networks (HWSNs) often have varying levels of available energy, storage space, and processing power due to the network’s limited resources. Additionally, coverage redundancy and channel conflicts may adversely influence the quality of service in a network when many nodes have been deployed at once. Energy as a major constrained resource requires an effective energy-efficient scheduling mechanism to balance node energy consumption to extend the network lifespan. Therefore, this research proposes an energy-efficient scheduling technique, IMA–NCS-3D for three-dimensional HWSNs on the basis of an improved memetic algorithm and node cooperation strategy. A multi-objective fitness function is created to encode the active and inactive states of nodes as genes, and the optimal scheduling set of the network is built via selection, crossover, variation, and local search. This phase of the process is known as node scheduling. Node-to-node cooperation solutions are offered during data transmission to deal with unforeseen traffic abnormalities and reduce congestion and channel conflicts when traffic volumes are high. Simulation results show that IMA–NCS-3D has superior scheduling capability, cross-network load balancing capability, and a longer network lifespan than other current coverage optimization approaches.
The impact of ABCB1, CYP3A4/5 and ABCG2 gene polymorphisms on rivaroxaban trough concentrations and bleeding events in patients with non-valvular atrial fibrillation
Authors: Wu Tingting , Wu Shuyi , Li Li , Xiang Jing , Wang Na , Chen Wenjun , Zhang Jinhua 
Published: July 2023

Abstract
Background
The influence of genetic factors on the pharmacokinetics and clinical outcomes of rivaroxaban in patients with non-valvular atrial fibrillation (NVAF) is poorly understood. This study aimed to explore the effects of CYP3A4/5, ABCB1, and ABCG2 gene polymorphisms on the trough concentrations and the bleeding risk of rivaroxaban in NVAF patients.

Patients and methods
This study is a prospective multicenter study. The patient's blood samples were collected to detect the steady-state trough concentrations of rivaroxaban and gene polymorphisms. We visited the patients regularly at month 1, 3, 6, and 12 to record bleeding events and medications.

Results
A total of 95 patients were enrolled in this study, and 9 gene loci were detected. For the dose-adjusted trough concentration ratio (Ctrough/D) of rivaroxaban, the homozygous mutant type was significantly lower than wild type at ABCB1 rs4148738 locus (TT vs. CC, P = 0.033), and the mutant type was significantly lower than the wild type at ABCB1 rs4728709 locus (AA + GA vs. GG, P = 0.008). ABCB1 (rs1045642, rs1128503), CYP3A4 (rs2242480, rs4646437), CYP3A5 (rs776746), and ABCG2 (rs2231137, rs2231142) gene polymorphisms had no significant effect on the Ctrough/D of rivaroxaban. For the bleeding events, we found that there were no significant differences among genotypes of all gene loci.

Conclusion
This study found for the first time that ABCB1 rs4148738 and rs4728709 gene polymorphisms had a significant impact on the Ctrough/D of rivaroxaban in NVAF patients. CYP3A4/5, ABCB1, and ABCG2 gene polymorphisms were not associated with the bleeding risk of rivaroxaban.