bluuebunny/crossref_metadata_2025_split huggingface dataset:
Radiomics using computed tomography to predict CD73 expression and prognosis of colorectal cancer liver metastases
Authors: Saber Ralph , Henault David , Messaoudi Nouredin , Rebolledo Rolando , Montagnon Emmanuel , Soucy Geneviève , Stagg John , Tang An , Turcotte Simon , Kadoury Samuel 
Published: July 2023

AbstractBackgroundFinding a noninvasive radiomic surrogate of tumor immune features could help identify patients more likely to respond to novel immune checkpoint inhibitors. Particularly, CD73 is an ectonucleotidase that catalyzes the breakdown of extracellular AMP into immunosuppressive adenosine, which can be blocked by therapeutic antibodies. High CD73 expression in colorectal cancer liver metastasis (CRLM) resected with curative intent is associated with early recurrence and shorter patient survival. The aim of this study was hence to evaluate whether machine learning analysis of preoperative liver CT-scan could estimate high vs low CD73 expression in CRLM and whether such radiomic score would have a prognostic significance.MethodsWe trained an Attentive Interpretable Tabular Learning (TabNet) model to predict, from preoperative CT images, stratified expression levels of CD73 (CD73Highvs. CD73Low) assessed by immunofluorescence (IF) on tissue microarrays. Radiomic features were extracted from 160 segmented CRLM of 122 patients with matched IF data, preprocessed and used to train the predictive model. We applied a five-fold cross-validation and validated the performance on a hold-out test set.ResultsTabNet provided areas under the receiver operating characteristic curve of 0.95 (95% CI 0.87 to 1.0) and 0.79 (0.65 to 0.92) on the training and hold-out test sets respectively, and outperformed other machine learning models. The TabNet-derived score, termed rad-CD73, was positively correlated with CD73 histological expression in matched CRLM (Spearman’sρ = 0.6004;P < 0.0001). The median time to recurrence (TTR) and disease-specific survival (DSS) after CRLM resection in rad-CD73Highvs rad-CD73Lowpatients was 13.0 vs 23.6 months (P = 0.0098) and 53.4 vs 126.0 months (P = 0.0222), respectively. The prognostic value of rad-CD73 was independent of the standard clinical risk score, for both TTR (HR = 2.11, 95% CI 1.30 to 3.45,P < 0.005) and DSS (HR = 1.88, 95% CI 1.11 to 3.18,P = 0.020).ConclusionsOur findings reveal promising results for non-invasive CT-scan-based prediction of CD73 expression in CRLM and warrant further validation as to whether rad-CD73 could assist oncologists as a biomarker of prognosis and response to immunotherapies targeting the adenosine pathway.
Immunostimulatory gene therapy targeting CD40, 4-1BB and IL-2R activates DCs and stimulates antigen-specific T-cell and NK-cell responses in melanoma models
Authors: Wenthe Jessica , Eriksson Emma , Hellström Ann-Charlotte , Moreno Rafael , Ullenhag Gustav , Alemany Ramon , Lövgren Tanja , Loskog Angelica 
Published: July 2023

Abstract
Background
The activation of dendritic cells (DCs) is pivotal for generating antigen-specific T-cell responses to eradicate tumor cells. Hence, immunotherapies targeting this interplay are especially intriguing. Moreover, it is of interest to modulate the tumor microenvironment (TME), as this harsh milieu often impairs adaptive immune responses. Oncolytic viral therapy presents an opportunity to overcome the immunosuppression in tumors by destroying tumor cells and thereby releasing antigens and immunostimulatory factors. These effects can be further amplified by the introduction of transgenes expressed by the virus.

Methods
Lokon oncolytic adenoviruses (LOAd) belong to a platform of chimeric serotype Ad5/35 viruses that have their replication restricted to tumor cells, but the expression of transgenes is permitted in all infected cells. LOAd732 is a novel oncolytic adenovirus that expresses three essential immunostimulatory transgenes: trimerized membrane-bound CD40L, 4-1BBL and IL-2. Transgene expression was determined with flow cytometry and ELISA and the oncolytic function was evaluated with viability assays and xenograft models. The activation profiles of DCs were investigated in co-cultures with tumor cells or in an autologous antigen-specific T cell model by flow cytometry and multiplex proteomic analysis. Statistical differences were analyzed with Kruskal–Wallis test followed by Dunn’s multiple comparison test.

Results
All three transgenes were expressed in infected melanoma cells and DCs and transgene expression did not impair the oncolytic activity in tumor cells. DCs were matured post LOAd732 infection and expressed a multitude of co-stimulatory molecules and pro-inflammatory cytokines crucial for T-cell responses. Furthermore, these DCs were capable of expanding and stimulating antigen-specific T cells in addition to natural killer (NK) cells. Strikingly, the addition of immunosuppressive cytokines TGF-β1 and IL-10 did not affect the ability of LOAd732-matured DCs to expand antigen-specific T cells and these cells retained an enhanced activation profile.

Conclusions
LOAd732 is a novel immunostimulatory gene therapy based on an oncolytic adenovirus that expresses three transgenes, which are essential for mediating an anti-tumor immune response by activating DCs and stimulating T and NK cells even under imunosuppressive conditions commonly present in the TME. These qualities make LOAd732 an appealing new immunotherapy approach.
Machine learning in Huntington’s disease: exploring the Enroll-HD dataset for prognosis and driving capability prediction
Authors: Ouwerkerk Jasper , Feleus Stephanie , van der Zwaan Kasper F. , Li Yunlei , Roos Marco , van Roon-Mom Willeke M. C. , de Bot Susanne T. , Wolstencroft Katherine J. , Mina Eleni 
Published: July 2023

Abstract
Background
In biomedicine, machine learning (ML) has proven beneficial for the prognosis and diagnosis of different diseases, including cancer and neurodegenerative disorders. For rare diseases, however, the requirement for large datasets often prevents this approach. Huntington’s disease (HD) is a rare neurodegenerative disorder caused by a CAG repeat expansion in the coding region of the huntingtin gene. The world’s largest observational study for HD, Enroll-HD, describes over 21,000 participants. As such, Enroll-HD is amenable to ML methods. In this study, we pre-processed and imputed Enroll-HD with ML methods to maximise the inclusion of participants and variables. With this dataset we developed models to improve the prediction of the age at onset (AAO) and compared it to the well-established Langbehn formula. In addition, we used recurrent neural networks (RNNs) to demonstrate the utility of ML methods for longitudinal datasets, assessing driving capabilities by learning from previous participant assessments.

Results
Simple pre-processing imputed around 42% of missing values in Enroll-HD. Also, 167 variables were retained as a result of imputing with ML. We found that multiple ML models were able to outperform the Langbehn formula. The best ML model (light gradient boosting machine) improved the prognosis of AAO compared to the Langbehn formula by 9.2%, based on root mean squared error in the test set. In addition, our ML model provides more accurate prognosis for a wider CAG repeat range compared to the Langbehn formula. Driving capability was predicted with an accuracy of 85.2%. The resulting pre-processing workflow and code to train the ML models are available to be used for related HD predictions at: https://github.com/JasperO98/hdml/tree/main.

Conclusions
Our pre-processing workflow made it possible to resolve the missing values and include most participants and variables in Enroll-HD. We show the added value of a ML approach, which improved AAO predictions and allowed for the development of an advisory model that can assist clinicians and participants in estimating future driving capability.
Ten years of treatment with ruxolitinib for myelofibrosis: a review of safety
Authors: Verstovsek Srdan , Mesa Ruben A. , Livingston Robert A. , Hu Wilson , Mascarenhas John 
Published: July 2023

AbstractMyelofibrosis (MF) is a chronic myeloproliferative neoplasm characterized by bone marrow fibrosis, anemia, extramedullary hematopoiesis, and splenomegaly. Patients with MF are at risk for reduced survival versus the general population and often experience burdensome signs and symptoms that reduce quality of life. The oral Janus kinase (JAK) 1/JAK2 inhibitor ruxolitinib was initially approved by the US Food and Drug Administration in 2011 for the treatment of patients with intermediate or high-risk MF, including primary MF, post-polycythemia vera MF, and post-essential thrombocythemia MF, based on efficacy and safety findings from the randomized, controlled, phase 3 COMFORT trials. Over a decade later, ruxolitinib continues to be the standard of care in higher-risk MF, and dose optimization and management remain crucial for safely maximizing clinical benefits of ruxolitinib. This review summarizes the safety profile of ruxolitinib in patients with MF in the COMFORT trials leading up to approval and in the subsequent JUMP, ROBUST, EXPAND, and REALISE trials; in pooled analyses; and in postmarketing analyses in the 10 years following approval. There is a focus on the occurrence of common hematologic and nonhematologic adverse events, with guidance provided on the management of patients with anemia or thrombocytopenia, including dosing strategies based on findings from the REALISE and EXPAND trials. Finally, to ensure a greater understanding of the safety profile of ruxolitinib, practical considerations are discussed.
Opportunistic channel estimation with LTE signals of limited bandwidth for positioning applications
Authors: Pin A. , Rinaldo R. , Tonello A. , Marshall C. , Driusso M. , Biason A. , Dalla Torre A. 
Published: July 2023

AbstractThe positioning problem is interesting in a variety of applications, especially in indoor environments or in urban canyons, where the position information obtainable with traditional Global Navigation Satellite Systems is limited. In this paper, we deal with the problem of estimating, for the purposes of positioning, the time of arrival (TOA) and the angle of arrival (AOA) by processing LTE 3GPP signals, with particular attention to the uplink signals. The main contribution of this paper is the definition of new opportunistic methods to estimate the TOA and the AOA using the upstream demodulation reference signal (DM-RS) instead of the Sounding Reference Signal. We will show that the use of DM-RS and of estimation algorithms such as the Space-Alternating Generalized Expectation-Maximization and the Iterative Adaptive Approach for Amplitude and Phase estimation (IAA-APES) allows an efficient estimate of the parameters, in spite of the small, occupied bandwidth.
Generalized UH-stability of a nonlinear fractional coupling $(\mathcalligra{p}_{1},\mathcalligra{p}_{2})$-Laplacian system concerned with nonsingular Atangana–Baleanu fractional calculus
Authors: Zhao Kaihong 
Published: July 2023

AbstractThe classical $\mathcalligra{p}$
p
-Laplace equation is one of the special and significant second-order ODEs. The fractional-order $\mathcalligra{p}$
p
-Laplace ODE is an important generalization. In this paper, we mainly treat with a nonlinear coupling $(\mathcalligra{p}_{1},\mathcalligra{p}_{2})$
(

p
1

,

p
2

)
-Laplacian systems involving the nonsingular Atangana–Baleanu (AB) fractional derivative. In accordance with the value range of parameters $\mathcalligra{p}_{1}$

p
1

and $\mathcalligra{p}_{2}$

p
2

, we obtain sufficient criteria for the existence and uniqueness of solution in four cases. By using some inequality techniques we further establish the generalized UH-stability for this system. Finally, we test the validity and practicality of the main results by an example.
On the unconstrained optimization reformulations for a class of stochastic vector variational inequality problems
Authors: Dong Dan-dan , Tang Guo-ji , Qiu Hui-ming 
Published: July 2023

AbstractIn this paper, a class of stochastic vector variational inequality (SVVI) problems are considered. By employing the idea of a D-gap function, the SVVI problem is reformulated as a deterministic model, which is an unconstrained expected residual minimization (UERM) problem, while it is reformulated as a constrained expected residual minimization problem in the work of Zhao et al. Then, the properties of the objective function are investigated and a sample average approximation approach is proposed for solving the UERM problem. Convergence of the proposed approach for global optimal solutions and stationary points is analyzed. Moreover, we consider another deterministic formulation, i.e., the expected value (EV) formulation for an SVVI problem, and the global error bound of a D-gap function based on the EV formulation is given.
Preconception education program for non-invasive prenatal testing focused on interest in genetics among female university students in Japan: a quasi-experimental study comparing pre-intervention, post-intervention, and three-month follow-up results
Authors: Katada Chihiro , Ohashi Kazutomo , Okada Kimie , Sawai Hideaki 
Published: July 2023

Abstract
Background
Non-invasive prenatal testing (NIPT) is offered as a reproductive choice in many countries. However, pregnant women, particularly those who are primipara or lack knowledge of prenatal testing, experience difficulties understanding adequate information and making decisions on NIPT. This study developed a preconception education program about NIPT, focusing on interest in genetics, and aimed to clarify the effectiveness of the program to help women make decisions on future NIPT.

Methods
This was a one-group, quasi-experimental, pre-post-test study. The study population was female undergraduate students in Japan who participated in the education program. This program included two games and was based on the Attention, Relevance, Confidence, and Satisfaction (ARCS) model, which is an instructional design that stimulates learning interest and motivation. The data of 73 pre-pregnant women who completed all three questionnaires—before, immediately after, and three months after the intervention—were analyzed to clarify the time effects. Moreover, all variables were analyzed using logistic regression analysis to investigate factors related to decisional conflict.

Results
Interest in genetics, knowledge of genetics and prenatal testing, and indecisive attitudes toward NIPT significantly improved immediately after the intervention, and consequently, these changes and reduction of decisional conflict were maintained at three months. Moreover, low decisional conflict at follow-up was significantly associated with a high interest in genetics (adjusted odds ratio, 3.42).

Conclusions
These findings provide preliminary evidence that this preconception education program, which focused on facilitating interest in genetics, assists pre-pregnant women to reduce decisional conflict about future NIPT.

Trial registration
The trial was registered at the UMIN-CTR registry (January 16, 2023), registration number UMIN000050047.
A microbial causal mediation analytic tool for health disparity and applications in body mass index
Authors: Wang Chan , Ahn Jiyoung , Tarpey Thaddeus , Yi Stella S. , Hayes Richard B. , Li Huilin 
Published: July 2023

Abstract
Background
Emerging evidence suggests the potential mediating role of microbiome in health disparities. However, no analytic framework can be directly used to analyze microbiome as a mediator between health disparity and clinical outcome, due to the non-manipulable nature of the exposure and the unique structure of microbiome data, including high dimensionality, sparsity, and compositionality.

Methods
Considering the modifiable and quantitative features of the microbiome, we propose a microbial causal mediation model framework, SparseMCMM_HD, to uncover the mediating role of microbiome in health disparities, by depicting a plausible path from a non-manipulable exposure (e.g., ethnicity or region) to the outcome through the microbiome. The proposed SparseMCMM_HD rigorously defines and quantifies the manipulable disparity measure that would be eliminated by equalizing microbiome profiles between comparison and reference groups and innovatively and successfully extends the existing microbial mediation methods, which are originally proposed under potential outcome or counterfactual outcome study design, to address health disparities.

Results
Through three body mass index (BMI) studies selected from the curatedMetagenomicData 3.4.2 package and the American gut project: China vs. USA, China vs. UK, and Asian or Pacific Islander (API) vs. Caucasian, we exhibit the utility of the proposed SparseMCMM_HD framework for investigating the microbiome’s contributions in health disparities. Specifically, BMI exhibits disparities and microbial community diversities are significantly distinctive between reference and comparison groups in all three applications. By employing SparseMCMM_HD, we illustrate that microbiome plays a crucial role in explaining the disparities in BMI between ethnicities or regions. 20.63%, 33.09%, and 25.71% of the overall disparity in BMI in China-USA, China-UK, and API-Caucasian comparisons, respectively, would be eliminated if the between-group microbiome profiles were equalized; and 15, 18, and 16 species are identified to play the mediating role respectively.

Conclusions
The proposed SparseMCMM_HD is an effective and validated tool to elucidate the mediating role of microbiome in health disparity. Three BMI applications shed light on the utility of microbiome in reducing BMI disparity by manipulating microbial profiles.
Developing an in-house colorimetric method for detecting organophosphate and carbamate residue using cricket cholinesterase
Authors: Wongta Anurak , Hongsibsong Surat , Anand Priyanshi , Jaitum Udomsurb , Sawarng Nootchakarn , Wongwilai Wasin , Dhumtanom Pongsathorn 
Published: July 2023

Abstract
Background
Pesticides such as organophosphates and carbamates are used to control pests, leaving residues on fruits and vegetables. The assessment of residues in food materials is required for consumer and agricultural worker health protection. The purpose of this study was to develop an in-house colorimetric method for detecting organophosphate and carbamate residues using cricket cholinesterase that can be used as a low-cost, simple-to-use, and widely used test.

Results
The method’s parameters, including substrate specificity, kinetics, and incubation time, were optimized. The results indicated that acetylthiocholine iodide was more active than butyrylthiocholine iodide. Using a buffer with a pH of 8.0 resulted in the greatest activity after 5 min. The same enzyme activity was observed at 25 °C and 30 °C, which was greater than at 35 °C and 40 °C. In this study, the Km and Vmax values for cricket cholinesterase were 3.75 mM and 35 µM/min, respectively. The specificity and purification factor of the produced ChE were 1.54 µM/min/mg and 1.43-fold, respectively. The limit of detection for detecting organophosphates and carbamates was in the range of 0.002–0.877 ppm. The validity of the method yielded the following results: relative sensitivity of 95%, relative specificity of 90%, relative accuracy of 93%, positive predictive value of 95%, and negative predictive value of 90%.

Conclusions
The developed method is simple and inexpensive, and it can analyze organophosphates and carbamates in a variety of vegetables at an appropriate detection level. Cholinesterase from cricket has the potential to be used for the development of a variety of methods for detecting residues, and the sensitivity could be enhanced using new techniques in the future.

Graphical Abstract
Hematoma expansion in intracerebral hemorrhage – the right target?
Authors: Haupenthal David , Schwab Stefan , Kuramatsu Joji B. 
Published: July 2023

Abstract
Background
The avoidance of hematoma expansion is the most important therapeutic goal during acute care of patients with intracerebral hemorrhage. Hematoma expansion occurs in up to 20–40% of patients and leads to poorer patient outcome in one of the most severe sub-types of stroke.

Main text
At current, randomized controlled trials have failed to provide evidence for interventions that effectively improve functional outcome in patients with intracerebral hemorrhage. Hence, hematoma expansion may serve as important surrogate target that appears causally linked with a poorer prognosis. Therefore, reduction of hematoma expansion rates will eventually translate to improved patient outcome overall. Recent years have shed light on the importance of early and aggressive treatment in order to reduce the risk for hematoma expansion in these patients. Time measures and imaging markers have been identified that may allow patient selection at very high risk for hematoma expansion.

Conclusions
Refinements in patient selection may increase chance for randomized trials to show true benefit. Therefore, this current review article will critically evaluate and discuss available evidence associated with hematoma expansion in patients with intracerebral hemorrhage.
Clinical Outcomes and Health Care Utilization in Patients With Burkitt Lymphoma
Authors: Johnson P. Connor , Markovitz Netana H. , Yi Alisha , Horick Nora , Newcomb Richard A. , Cronin Katherine , Schneider David , Nipp Ryan D. , El-Jawahri Areej 
Published: July 2023

PURPOSE Burkitt lymphoma is an aggressive B-cell lymphoma requiring intensive therapy, which places patients at risk for severe toxicity. However, few studies have described these patients' clinical outcomes and health care utilization, particularly among older adults. METHODS We conducted a retrospective analysis of adults 40 years and older with Burkitt lymphoma at Massachusetts General Hospital and Dana-Farber Cancer Institute from February 1999 to December 2020 (N = 97). We abstracted patient characteristics, clinical outcomes, and health care utilization (unplanned hospitalizations, intensive care unit [ICU] admissions) during therapy from the electronic health record. Using univariate logistic regression, we examined factors associated with rates of unplanned hospitalization and ICU admission during therapy. RESULTS Among evaluable patients (median age, 69 years; 23.7% female; 19.3% with bone marrow involvement), 45.8% (38 of 83) experienced unplanned hospitalization and 23.2% (19 of 82) experienced ICU admission during therapy. Among those 70 years and older, rates of unplanned hospitalization and ICU admission were 36.8% (14 of 38) and 29.0% (11 of 38), respectively. Bone marrow involvement (odds ratio [OR], 3.00; P = .069) was associated with a nonsignificantly greater likelihood of unplanned hospitalization. Older age (OR, 1.06; P = .039), Charlson comorbidity index >0 (OR, 3.14; P = .038), and hypoalbuminemia (OR, 3.22; P = .035) were associated with greater likelihood of ICU admission. Overall, 8.7% (8 of 92) of patients died during treatment, all of whom were 70 years and older. CONCLUSION Adults with Burkitt lymphoma experience substantial rates of unplanned hospitalizations and ICU admissions, with older adults at especially high risk for ICU admission and death during treatment. Our findings underscore the need to develop supportive care interventions for patients with Burkitt lymphoma to help improve clinical outcomes and health care utilization.