bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systematic in vivo candidate evaluation uncovers therapeutic targets for LMNA dilated cardiomyopathy and risk of Lamin A toxicity
Authors: Tan Chia Yee , Chan Pui Shi , Tan Hansen , Tan Sung Wei , Lee Chang Jie Mick , Wang Jiong-Wei , Ye Shu , Werner Hendrikje , Loh Ying Jie , Lee Yin Loon , Ackers-Johnson Matthew , Foo Roger S. Y. , Jiang Jianming 
Published: October 2023

Abstract
Background
Dilated cardiomyopathy (DCM) is a severe, non-ischemic heart disease which ultimately results in heart failure (HF). Decades of research on DCM have revealed diverse aetiologies. Among them, familial DCM is the major form of DCM, with pathogenic variants in LMNA being the second most common form of autosomal dominant DCM. LMNA DCM is a multifactorial and complex disease with no specific treatment thus far. Many studies have demonstrated that perturbing candidates related to various dysregulated pathways ameliorate LMNA DCM. However, it is unknown whether these candidates could serve as potential therapeutic targets especially in long term efficacy.

Methods
We evaluated 14 potential candidates including Lmna gene products (Lamin A and Lamin C), key signaling pathways (Tgfβ/Smad, mTor and Fgf/Mapk), calcium handling, proliferation regulators and modifiers of LINC complex function in a cardiac specific Lmna DCM model. Positive candidates for improved cardiac function were further assessed by survival analysis. Suppressive roles and mechanisms of these candidates in ameliorating Lmna DCM were dissected by comparing marker gene expression, Tgfβ signaling pathway activation, fibrosis, inflammation, proliferation and DNA damage. Furthermore, transcriptome profiling compared the differences between Lamin A and Lamin C treatment.

Results
Cardiac function was restored by several positive candidates (Smad3, Yy1, Bmp7, Ctgf, aYAP1, Sun1, Lamin A, and Lamin C), which significantly correlated with suppression of HF/fibrosis marker expression and cardiac fibrosis in Lmna DCM. Lamin C or Sun1 shRNA administration achieved consistent, prolonged survival which highly correlated with reduced heart inflammation and DNA damage. Importantly, Lamin A treatment improved but could not reproduce long term survival, and Lamin A administration to healthy hearts itself induced DCM. Mechanistically, we identified this lapse as caused by a dose-dependent toxicity of Lamin A, which was independent from its maturation.

Conclusions
In vivo candidate evaluation revealed that supplementation of Lamin C or knockdown of Sun1 significantly suppressed Lmna DCM and achieve prolonged survival. Conversely, Lamin A supplementation did not rescue long term survival and may impart detrimental cardiotoxicity risk. This study highlights a potential of advancing Lamin C and Sun1 as therapeutic targets for the treatment of LMNA DCM.

Graphical Abstract
Prior information guided auto-segmentation of clinical target volume of tumor bed in postoperative breast cancer radiotherapy
Authors: Xie Xin , Song Yuchun , Ye Feng , Wang Shulian , Yan Hui , Zhao Xinming , Dai Jianrong 
Published: October 2023

Abstract
Background
Accurate delineation of clinical target volume of tumor bed (CTV-TB) is important but it is also challenging due to surgical effects and soft tissue contrast. Recently a few auto-segmentation methods were developed to improve the process. However, those methods had comparatively low segmentation accuracy. In this study the prior information was introduced to aid auto-segmentation of CTV-TB based on a deep-learning model.

Methods
To aid the delineation of CTV-TB, the tumor contour on preoperative CT was transformed onto postoperative CT via deformable image registration. Both original and transformed tumor contours were used for prior information in training an auto-segmentation model. Then, the CTV-TB contour on postoperative CT was predicted by the model. 110 pairs of preoperative and postoperative CT images were used with a 5-fold cross-validation strategy. The predicted contour was compared with the clinically approved contour for accuracy evaluation using dice similarity coefficient (DSC) and Hausdorff distance.

Results
The average DSC of the deep-learning model with prior information was improved than the one without prior information (0.808 vs. 0.734, P < 0.05). The average DSC of the deep-learning model with prior information was higher than that of the traditional method (0.808 vs. 0.622, P < 0.05).

Conclusions
The introduction of prior information in deep-learning model can improve segmentation accuracy of CTV-TB. The proposed method provided an effective way to automatically delineate CTV-TB in postoperative breast cancer radiotherapy.
Use of levosimendan in hemodynamic management of heart failure in two neonates with intracranial arteriovenous shunts: a case series
Authors: Landolfo Francesca , Giliberti Paola , De Rose Domenico Umberto , Pugnaloni Flaminia , Santisi Alessandra , Columbo Claudia , Martini Ludovica , Ronchetti Maria Paola , Di Chiara Luca , Toscano Alessandra , Gandolfo Carlo , Dotta Andrea , Capolupo Irma 
Published: October 2023

Abstract
Background
The hemodynamic status of newborns with intracranial arteriovenous shunts (AVSs) may be extremely complex. Mini-invasive hemodynamic monitoring through innovative techniques such as Near-Infrared Spectroscopy (NIRS) and Pressure Recording Analytical Method (PRAM) may help in understanding hemodynamics in newborns with AVSs. Levosimendan is a calcium sensitizer and inodilator, and it is known to improve ventricular function, but its use in newborns is limited. In our cases, we evaluated the effect of levosimendan on hemodynamics through NIRS and PRAM.

Case presentation
Herein, we report the cases of two neonates with intracranial arteriovenous shunts, in whom we used levosimendan to manage cardiac failure refractory to conventional treatment. Levosimendan was used at a dosage of 0.1 mcg/kg/min for 72 h. Combined use of NIRS and PRAM helped in real-time monitoring of hemodynamic effects; in particular, levosimendan determined significant improvement in myocardium contractility as well as a reduction of heart rate.

Conclusion
In two neonatal cases of AVSs, levosimendan led to an overall hemodynamic stabilization, documented by the combination of NIRS and PRAM. Our results suggest introducing levosimendan as a second-line treatment in cases of severe cardiac dysfunction due to AVSs without improvement using standard treatment strategies. Future prospective and larger studies are highly warranted.
A CT-based radiomics approach to predict intra-tumoral tertiary lymphoid structures and recurrence of intrahepatic cholangiocarcinoma
Authors: Xu Ying , Li Zhuo , Yang Yi , Li Lu , Zhou Yanzhao , Ouyang Jingzhong , Huang Zhen , Wang Sicong , Xie Lizhi , Ye Feng , Zhou Jinxue , Ying Jianming , Zhao Hong , Zhao Xinming 
Published: October 2023

Abstract
Purpose
To predict the tertiary lymphoid structures (TLSs) status and recurrence-free survival (RFS) of intrahepatic cholangiocarcinoma (ICC) patients using preoperative CT radiomics.

Patients and methods
A total of 116 ICC patients were included (training: 86; external validation: 30). The enhanced CT images were performed for the radiomics model. The logistic regression analysis was applied for the clinical model. The combined model was based on the clinical and radiomics models.

Results
A total of 107 radiomics features were extracted, and after being eliminated and selected, six features were combined to establish a radiomics model for TLSs prediction. Arterial phase diffuse hyperenhancement and AJCC 8th stage were combined to construct a clinical model. The combined (radiomics nomogram) model outperformed both the independent radiomics model and clinical model in the training cohort (AUC, 0.85 vs. 0.82 and 0.75, respectively) and was validated in the external validation cohort (AUC, 0.88 vs. 0.86 and 0.71, respectively). Patients in the rad-score no less than −0.76 (low-risk) group showed significantly better RFS than those in the less than −0.76 (high-risk) group (p < 0.001, C-index = 0.678). Patients in the nomogram score no less than −1.16 (low-risk) group showed significantly better RFS than those of the less than −1.16 (high-risk) group (p < 0.001, C-index = 0.723).

Conclusions
CT radiomics nomogram could serve as a preoperative biomarker of intra-tumoral TLSs status, better than independent radiomics or clinical models; preoperative CT radiomics nomogram achieved accurate stratification for RFS of ICC patients, better than the postoperative pathologic TLSs status.

Critical relevance statement
The radiomics nomogram showed better performance in predicting TLSs than independent radiomics or clinical models and better prognosis stratification than postoperative pathologic TLSs status in ICC patients, which may facilitate identifying patients benefiting most from surgery and subsequent immunotherapy.

Key points
• The combined (radiomics nomogram) model consisted of the radiomics model and clinical model (arterial phase diffuse hyperenhancement and AJCC 8th stage).
• The radiomics nomogram showed better performance in predicting TLSs than independent radiomics or clinical models in ICC patients.
• Preoperative CT radiomics nomogram achieved more accurate stratification for RFS of ICC patients than the postoperative pathologic TLSs status.

Graphical Abstract
Preoperative prediction of clinical and pathological stages for patients with esophageal cancer using PET/CT radiomics
Authors: Lei Xiyao , Cao Zhuo , Wu Yibo , Lin Jie , Zhang Zhenhua , Jin Juebin , Ai Yao , Zhang Ji , Du Dexi , Tian Zhifeng , Xie Congying , Yin Weiwei , Jin Xiance 
Published: October 2023

Abstract
Background
Preoperative stratification is critical for the management of patients with esophageal cancer (EC). To investigate the feasibility and accuracy of PET-CT-based radiomics in preoperative prediction of clinical and pathological stages for patients with EC.

Methods
Histologically confirmed 100 EC patients with preoperative PET-CT images were enrolled retrospectively and randomly divided into training and validation cohorts at a ratio of 7:3. The maximum relevance minimum redundancy (mRMR) was applied to select optimal radiomics features from PET, CT, and fused PET-CT images, respectively. Logistic regression (LR) was applied to classify the T stage (T1,2 vs. T3,4), lymph node metastasis (LNM) (LNM(−) vs. LNM(+)), and pathological state (pstage) (I–II vs. III–IV) with features from CT (CT_LR_Score), PET (PET_LR_Score), fused PET/CT (Fused_LR_Score), and combined CT and PET features (CT + PET_LR_Score), respectively.

Results
Seven, 10, and 7 CT features; 7, 8, and 7 PET features; and 3, 6, and 3 fused PET/CT features were selected using mRMR for the prediction of T stage, LNM, and pstage, respectively. The area under curves (AUCs) for T stage, LNM, and pstage prediction in the validation cohorts were 0.846, 0.756, 0.665, and 0.815; 0.769, 0.760, 0.665, and 0.824; and 0.727, 0.785, 0.689, and 0.837 for models of CT_LR_Score, PET_ LR_Score, Fused_ LR_Score, and CT + PET_ LR_Score, respectively.

Conclusions
Accurate prediction ability was observed with combined PET and CT radiomics in the prediction of T stage, LNM, and pstage for EC patients.

Critical relevance statement
PET/CT radiomics is feasible and promising to stratify stages for esophageal cancer preoperatively.

Key points
• PET-CT radiomics achieved the best performance for Node and pathological stage prediction.
• CT radiomics achieved the best AUC for T stage prediction.
• PET-CT radiomics is feasible and promising to stratify stages for EC preoperatively.

Graphical Abstract
Cardiomyocyte precursors generated by direct reprogramming and molecular beacon selection attenuate ventricular remodeling after experimental myocardial infarction
Authors: Bachamanda Somesh Dipthi , Klose Kristin , Maring Janita A. , Kunkel Désirée , Jürchott Karsten , Protze Stephanie I. , Klein Oliver , Nebrich Grit , Becker Matthias , Krüger Ulrike , Nazari-Shafti Timo Z. , Falk Volkmar , Kurtz Andreas , Gossen Manfred , Stamm Christof 
Published: October 2023

Abstract
Background
Direct cardiac reprogramming is currently being investigated for the generation of cells with a true cardiomyocyte (CM) phenotype. Based on the original approach of cardiac transcription factor-induced reprogramming of fibroblasts into CM-like cells, various modifications of that strategy have been developed. However, they uniformly suffer from poor reprogramming efficacy and a lack of translational tools for target cell expansion and purification. Therefore, our group has developed a unique approach to generate proliferative cells with a pre-CM phenotype that can be expanded in vitro to yield substantial cell doses.

Methods
Cardiac fibroblasts were reprogrammed toward CM fate using lentiviral transduction of cardiac transcriptions factors (GATA4, MEF2C, TBX5, and MYOCD). The resulting cellular phenotype was analyzed by RNA sequencing and immunocytology. Live target cells were purified based on intracellular CM marker expression using molecular beacon technology and fluorescence-activated cell sorting. CM commitment was assessed using 5-azacytidine-based differentiation assays and the therapeutic effect was evaluated in a mouse model of acute myocardial infarction using echocardiography and histology. The cellular secretome was analyzed using mass spectrometry.

Results
We found that proliferative CM precursor-like cells were part of the phenotype spectrum arising during direct reprogramming of fibroblasts toward CMs. These induced CM precursors (iCMPs) expressed CPC- and CM-specific proteins and were selectable via hairpin-shaped oligonucleotide hybridization probes targeting Myh6/7-mRNA–expressing cells. After purification, iCMPs were capable of extensive expansion, with preserved phenotype when under ascorbic acid supplementation, and gave rise to CM-like cells with organized sarcomeres in differentiation assays. When transplanted into infarcted mouse hearts, iCMPs prevented CM loss, attenuated fibrotic scarring, and preserved ventricular function, which can in part be attributed to their substantial secretion of factors with documented beneficial effect on cardiac repair.

Conclusions
Fibroblast reprogramming combined with molecular beacon-based cell selection yields an iCMP-like cell population with cardioprotective potential. Further studies are needed to elucidate mechanism-of-action and translational potential.

Graphical Abstract
Examining students’ course trajectories using data mining and visualization approaches
Authors: Maqsood Rabia , Ceravolo Paolo , Ahmad Muhammad , Sarfraz Muhammad Shahzad 
Published: October 2023

AbstractThe heterogeneous data acquired by educational institutes about students’ careers (e.g., performance scores, course preferences, attendance record, demographics, etc.) has been a source of investigation for Educational Data Mining (EDM) researchers for over two decades. EDM researchers have primarily focused on course-specific data analyses of students’ performances, and rare attempts are made at the domain level that may benefit the educational institutes at large to gauge and improve their institutional effectiveness. Our work aims to fill this gap by examining students’ transcripts data for identifying similar groups of students and patterns that might associate with these different cohorts of students based on: (a) difficulty level of a course category, (b) formation of course trajectories, and, (c) transitioning of students between different performance groups. We have exploited descriptive data mining and visualization methods to analyze transcript data of 1398 undergraduate Computer Science students of a private university in Pakistan. The dataset includes students’ transcript data of 124 courses from nine distinct course categories. In the end, we have discussed our findings in detail, challenges, and, future work directions.
Impact of a digital and conventional prevention program on work ability, physical health, and mental health among employees with initial impairments
Authors: Schmidt Detlef , Fritsch Julian , Feil Katharina , Weyland Susanne , Jekauc Darko 
Published: October 2023

Abstract
Background
This quasi-experimental study aimed to compare the effectiveness of a digital prevention intervention on work ability, physical health, and mental health with a conventional prevention program for employees with initial impairments. The study recruited 245 participants, of whom 173 completed the study, 98 (65 female, 66.3%) in the intervention group and 75 (55 female, 73.3%) in the control group. Both groups received prevention programs, with the intervention group using the Caspar digital platform and the control group using the conventional BETSI/RV Fit program. There were three measurement points in the study: T0 before the intervention, T1 in the middle of the intervention, and T2 at the end of the intervention. Participants’ health was assessed using the SF-12 health status questionnaire, while their work ability was measured using the short version of the Work Ability Index.

Results
Repeated-measures analyses of variance indicated that both prevention programs were effective in improving work ability and mental health, while physical health did not show any significant improvement. Additionally, the results of the study suggest that younger individuals benefited more from the digital prevention intervention, while older individuals benefited more from the conventional prevention program.

Conclusion
The study emphasizes the need for further research and improvements in both research and practice. Future studies should include larger sample sizes, randomized controlled trials, and follow-up assessments to enhance understanding of the effectiveness and the durability of effects of prevention programs.
The Impact of Mental Fatigue on a Strength Endurance Task: Is there a Role for the Movement-Related Cortical Potential?
Authors: Proost Matthias , Habay Jelle , De Wachter Jonas , De Pauw Kevin , Marusic Uros , Meeusen Romain , De Bock Sander , Roelands Bart , Van Cutsem Jeroen 
Published: October 2023

ABSTRACT

Purpose
Several mechanisms have been proposed to explain how mental fatigue degrades sport performance. In terms of endurance performance, a role for an increased perceived exertion has been demonstrated. Utilizing electroencephalography (EEG) and, more specifically, the movement-related cortical potential (MRCP), the present study explored the neural mechanisms that could underly the mental fatigue-associated increase in perceived exertion.

Methods
Fourteen participants (age: 23 ± 2 y, 5 females, 9 males) performed one familiarisation and two experimental trials in a randomised, blinded, cross-over study design. Participants had to complete a submaximal leg extension task after a mentally fatiguing task (EXP; individualized 60-min Stroop task) or control task (CON; documentary). The leg extension task consisted of performing 100 extensions at 35% of 1RM, during which multiple physiological (heart rate, EEG, ratings of perceived exertion) and psychological measures (self-reported feeling of mental fatigue, cognitive load, motivation) were assessed.

Results
Self-reported feeling of mental fatigue was higher in EXP (72 ± 18) compared to CON (37 ± 17; p < 0.001). A decrease in flanker accuracy was detected only in EXP (from 0.96 ± 0.03 to 0.94 ± 0.03; p < 0.05). No significant differences between conditions were found in MRCP characteristics and perceived exertion. Specifically in EXP, alpha wave power increased during the leg extension task (p < 0.01).

Conclusions
Mental fatigue did not impact the perceived exertion or MRCP characteristics during the leg extension task. This could be related to low perceived exertion and/or the absence of a performance outcome during the leg extension task. The increase in alpha power during the leg extension task in EXP, suggests participants may engage a focused internal attention mechanism to maintain performance and mitigate feelings of fatigue.
A Somatosensory Computation That Unifies Limbs and Tools
Authors: Miller Luke E. , Fabio Cécile , de Vignemont Frédérique , Roy Alice , Medendorp W. Pieter , Farnè Alessandro 
Published: October 2023

AbstractIt is often claimed that tools are embodied by their user, but whether the brain actually repurposes its body-based computations to perform similar tasks with tools is not known. A fundamental computation for localizing touch on the body is trilateration. Here, the location of touch on a limb is computed by integrating estimates of the distance between sensory input and its boundaries (e.g., elbow and wrist of the forearm). As evidence of this computational mechanism, tactile localization on a limb is most precise near its boundaries and lowest in the middle. Here, we show that the brain repurposes trilateration to localize touch on a tool, despite large differences in initial sensory input compared with touch on the body. In a large sample of participants, we found that localizing touch on a tool produced the signature of trilateration, with highest precision close to the base and tip of the tool. A computational model of trilateration provided a good fit to the observed localization behavior. To further demonstrate the computational plausibility of repurposing trilateration, we implemented it in a three-layer neural network that was based on principles of probabilistic population coding. This network determined hit location in tool-centered coordinates by using a tool’s unique pattern of vibrations when contacting an object. Simulations demonstrated the expected signature of trilateration, in line with the behavioral patterns. Our results have important implications for how trilateration may be implemented by somatosensory neural populations. We conclude that trilateration is likely a fundamental spatial computation that unifies limbs and tools.
Characterization of integrons, extended spectrum beta lactamases and genetic diversity among uropathogenic Escherichia coli isolates from Kerman, south east of Iran
Authors: Mohebi Samane , Golestani-Hotkani Zahra , Foulad-Pour Maryam , Nazeri Peivand , Mohseni Fahimeh , Hashemizadeh Zahra , Moghani-Bashi Zahra , Niksefat Naser , Rastegar Sanaz , Khajedadian Maryam , Lotfian Zahra , Hosseini-Nave Hossein 
Published: October 2023

Background and Objectives: The study aimed to investigate the distribution of genes encoding integrons, extended spec- trum beta-lactamase (ESBL) in E. coli isolated from UTIs, as well as the genetic diversity among the isolates.
Materials and Methods: E. coli isolates were recovered from the patients with UTI in Kerman Iran. Antibiotic susceptibility was done according to CLSI guidelines. The presence of ESBL genes and integrons was evaluated using PCR. PCR and sequencing were applied for the evaluation of cassette content of integrons. Genotyping of the isolates was performed by multiple-locus variable-number tandem repeat analysis (MLVA).
Results: Imipenem was the most effective antibiotic, while the highest resistance was observed to streptomycin. In total 40.2% of isolates were ESBL producers. Of 69 integron-positive isolates, 59 only had class I integrons, 4 only had class II integrons and 6 had both types. The most common gene cassette found within class I integrons was dfrA17-aadA5 (n=27). The E. coli isolates were divided into 16 MLVA clusters.
Conclusion: The current study demonstrated the simultaneous presence of class I integrons and ESBLs involved in the resistance of UPEC isolates to antibacterial agents. Our finding also revealed that the E. coli isolates belonged to diverse clones.