bluuebunny/crossref_metadata_2025 huggingface dataset:
The MAS4AI framework for human-centered agile and smart manufacturing
Authors: Sidorenko Aleksandr , Motsch William , van Bekkum Michael , Nikolakis Nikolaos , Alexopoulos Kosmas , Wagner Achim
Published: September 2023

Volatility and uncertainty of today's value chains along with the market's demands for low-batch customized products mandate production systems to become smarter and more resilient, dynamically and even autonomously adapting to both external and internal disturbances. Such resilient behavior can be partially enabled by highly interconnected Cyber-Physical Production Systems (CPPS) incorporating advanced Artificial Intelligence (AI) technologies. Multi-agent solutions can provide better planning and control, improving flexibility and responsiveness in production systems. Small modular parts can autonomously take intelligent decisions and react to local events. The main goal of decentralization and interconnectivity is to enable autonomous and cooperative decision-making. Nevertheless, a more efficient orchestration of various AI components and deeper human integration are required. In addition, global behaviors of coalitions of autonomous agents are not easily comprehensible by workers. Furthermore, it is challenging to implement an Industry 4.0 paradigm where a human should be in charge of decision-making and execution. This paper discusses a Multi-Agent System (MAS) where several software agents cooperate with smart workers to enable a dynamic and reconfigurable production paradigm. Asset Administration Shell (AAS) submodels hold smart workers' descriptions in machine-readable format, serving as an integration layer between various system's components. The self-description capability of the AAS supports the system's adaptability and self-configuration. The proposed concept supports the plug-and-produce functionality of the production modules and improves human-machine integration in the shared assembly tasks.
Investigating heterogeneity across autism, ADHD, and typical development using measures of cortical thickness, surface area, cortical/subcortical volume, and structural covariance
Authors: Sadat-Nejad Younes , Vandewouw Marlee M. , Cardy R. , Lerch J. , Taylor M. J. , Iaboni A. , Hammill C. , Syed B. , Brian J. A. , Kelley E. , Ayub M. , Crosbie J. , Schachar R. , Georgiades S. , Nicolson R. , Anagnostou E. , Kushki A.
Published: September 2023

Introduction

Attention-deficit/hyperactivity disorder (ADHD) and autism are multi-faceted neurodevelopmental conditions with limited biological markers. The clinical diagnoses of autism and ADHD are based on behavioural assessments and may not predict long-term outcomes or response to interventions and supports. To address this gap, data-driven methods can be used to discover groups of individuals with shared biological patterns.

Methods

In this study, we investigated measures derived from cortical/subcortical volume, surface area, cortical thickness, and structural covariance investigated of 565 participants with diagnoses of autism [n = 262, median(IQR) age = 12.2(5.9), 22% female], and ADHD [n = 171, median(IQR) age = 11.1(4.0), 21% female] as well neurotypical children [n = 132, median(IQR) age = 12.1(6.7), 43% female]. We integrated cortical thickness, surface area, and cortical/subcortical volume, with a measure of single-participant structural covariance using a graph neural network approach.

Results

Our findings suggest two large clusters, which differed in measures of adaptive functioning (χ2 = 7.8, P = 0.004), inattention (χ2 = 11.169, P < 0.001), hyperactivity (χ2 = 18.44, P < 0.001), IQ (χ2 = 9.24, P = 0.002), age (χ2 = 70.87, P < 0.001), and sex (χ2 = 105.6, P < 0.001).

Discussion

These clusters did not align with existing diagnostic labels, suggesting that brain structure is more likely to be associated with differences in adaptive functioning, IQ, and ADHD features.
6IMPOSE: bridging the reality gap in 6D pose estimation for robotic grasping
Authors: Cao Hongpeng , Dirnberger Lukas , Bernardini Daniele , Piazza Cristina , Caccamo Marco
Published: September 2023

6D pose recognition has been a crucial factor in the success of robotic grasping, and recent deep learning based approaches have achieved remarkable results on benchmarks. However, their generalization capabilities in real-world applications remain unclear. To overcome this gap, we introduce 6IMPOSE, a novel framework for sim-to-real data generation and 6D pose estimation. 6IMPOSE consists of four modules: First, a data generation pipeline that employs the 3D software suite Blender to create synthetic RGBD image datasets with 6D pose annotations. Second, an annotated RGBD dataset of five household objects was generated using the proposed pipeline. Third, a real-time two-stage 6D pose estimation approach that integrates the object detector YOLO-V4 and a streamlined, real-time version of the 6D pose estimation algorithm PVN3D optimized for time-sensitive robotics applications. Fourth, a codebase designed to facilitate the integration of the vision system into a robotic grasping experiment. Our approach demonstrates the efficient generation of large amounts of photo-realistic RGBD images and the successful transfer of the trained inference model to robotic grasping experiments, achieving an overall success rate of 87% in grasping five different household objects from cluttered backgrounds under varying lighting conditions. This is made possible by fine-tuning data generation and domain randomization techniques and optimizing the inference pipeline, overcoming the generalization and performance shortcomings of the original PVN3D algorithm. Finally, we make the code, synthetic dataset, and all the pre-trained models available on GitHub.
Total impact of electric vehicle fleet adoption in the logistics industry
Authors: Mohammed Jaby , Villegas Justin
Published: September 2023

The continental United States heavily relies on land logistics with 3.8 million square miles of land and over 4 million miles of road. Additionally, the United States is committed to achieving the global goal of reaching net-zero emissions by 2050. This article examines the advantages and disadvantages of incorporating electric vehicles (EVs), specifically trucks, into the current logistics industry. This paper also provides a better understanding of what type and magnitude of impact electric trucks' uprising technology have on the logistics industry.
Do cows see the forest or the trees? A preliminary investigation of attentional scope as a potential indicator of emotional state in dairy cows housed with their calves
Authors: Neave Heather W. , Rault Jean-Loup , Bateson Melissa , Jensen Emma Hvidtfeldt , Jensen Margit Bak
Published: September 2023

A positive mood in humans tends to broaden attentional scope while negative mood narrows it. A similar effect may be present in non-human animals; therefore, attentional scope may be a novel method to assess emotional states in livestock. In this proof-of-concept exploratory study, we examined the attentional scope of dairy cows housed with their calves either full-time, part-time (during daytime only), or with no calf contact (enrolled n = 10 each). Housing conditions were previously verified to induce differences in positive and negative emotional state, where part-time was considered more negative. Cows were trained to approach or avoid hierarchical images on a screen that were consistent in local and global elements (i.e., 13 small circles or crosses arranged in an overall circle or cross). After discrimination learning (>80% correct, over two consecutive days), 14 cows proceeded to test (n = 6 each full-and part-time; n = 2 no-contact, not analyzed). Test images showed inconsistent combinations of global and local elements (i.e., the overall global shape differs from the smaller local elements, such as a global circle composed of smaller local crosses and vice versa). Over two test days, approach responses to global and local images (each presented four times) were recorded. All cows were more likely to approach the local than the global image, especially part-time cows who never approached the global image; this may reflect a narrowed attentional scope in these cows. Full-time cows approached images more often than part-time cows, but overall response rates to global and local images were low, making specific conclusions regarding attentional scope difficult. Different housing conditions have potential to affect attentional scope, and possibly emotional state, of dairy cows, but statistical comparison to no-contact treatment was not possible. Cortisol concentration did not affect responses to images; thus arousal due to treatment or test conditions could not explain test performance. Further work with refined methodology and a larger sample size is required to validate the reliability of attentional scope as an assessment method of emotional state in cattle. Beyond this, the attentional scope test revealed how cattle may process, learn and respond to different visual hierarchical images, which further our understanding of cognitive and visual processes in cattle.
Inflation Shocks and Disinflation: Stylised Facts from the Past 50 Years
Authors: Spéder Balázs , Vonnák Balázs
Published: September 2023

In our study, we examine the circumstances under which major inflation shocks lead to persistently high inflation. For our analysis, we use macroeconomic data from a broad sample of countries for the past fifty years or more. We identify several cases where inflation rises from the single-digit range to above 20 per cent, followed by successful disinflation within two years. Similarly, there are many examples where inflation remains high after an initial shock. The former cases are characterised by more pronounced increases in interest rates during inflation shocks, more disciplined fiscal policy and favourable commodity price developments. Examining the same sample, we also show that the disinflation after a period of persistently high inflation was not typically accompanied by a significant slowdown in the real economy and instead was often followed by higher economic growth. In the disinflationary episodes we identified, the size of the real cost of disinflation is negatively correlated with the central bank independence, suggesting that a disinflationary commitment played a positive role.
An Enhanced Incremental Nonlinear Dynamic Inversion Control Strategy for Advanced Unmanned Aircraft Systems
Authors: Taherinezhad Maryam , Ramirez-Serrano Alejandro
Published: September 2023

A cascade control architecture was proposed for the control of advanced unmanned aerial vehicles targeted for operation inside confined hazardous spaces. The aircraft of interest is a highly maneuverable system presenting highly coupled dynamics, enabling it to perform unique flight maneuvers that no other aircraft can. To deal with the complexities inherent to such an aircraft, a novel nonlinear control architecture was proposed. Two outer loop NDI controllers and an inner loop INDI controller were employed for position/velocity and attitude/rotation rate control, respectively. These controllers assist each other, enabling them to decouple the aircraft dynamics while coping with complex external disturbances. The obtained results demonstrate an effective control of the targeted aircraft system to accurately track complex flight maneuvers.
Research on the Performance of Slender Aircraft with Flare-Stabilized-Skirt
Authors: Pan Xueting , Yue Honghao , Liu Shufeng , Yang Fei , Lu Yifan , Chen Gang
Published: September 2023

In this paper, a morphing aircraft with a deployable flared skirt is proposed, and the influence of the flare skirt on the static stability of hypersonic aircraft is studied. The theoretical model of static stability of slender aircraft is established, and the position of the center of pressure can be used as a theoretical basis to measure static stability. Three-dimensional compressible Reynolds-averaged Navier–Stokes (RANS) solver and an SST k-ω turbulence model are used to analyze the aerodynamic characteristics of the aircraft and the influence effect of the flared skirt on the pressure distribution of the body, and the influence trend on the position of the pressure center is verified. At the same time, the reliability of the code and grid is verified by a classic example, and the results are in good agreement with the experimental data in the current literature. Finally, the static stability of an aircraft with flared skirts with different deployment angles is quantitatively measured by defining the stability derivative at the common point. The results show that the static stability of the aircraft with the same forebody is improved by more than 100% under different flight Mach numbers when the flared skirt deployment angle is 30° compared to 0°.
Distributed Robust Formation Tracking Control for Quadrotor UAVs with Unknown Parameters and Uncertain Disturbances
Authors: Xu Linxing , Li Yang
Published: September 2023

In this paper, the distributed formation tracking control problem of quadrotor unmanned aerial vehicles is considered. Adaptive backstepping inherently accommodates model uncertainties and external disturbances, making it a robust choice for the dynamic and unpredictable environments in which unmanned aerial vehicles operate. This paper designs a formation flight control scheme for quadrotor unmanned aerial vehicles based on adaptive backstepping technology. The proposed control scheme is divided into two parts. For the position subsystem, a distributed robust formation tracking control scheme is developed to achieve formation flight of quadrotor unmanned aerial vehicles and track the desired flight trajectory. For the attitude subsystem, an adaptive disturbance rejection control scheme is proposed to achieve attitude stabilization during unmanned aerial vehicle flight under uncertain disturbances. Compared to existing results, the novelty of this paper lies in presenting a disturbance rejection flight control scheme for actual quadrotor unmanned aerial vehicle formations, without the need to know the model parameters of each unmanned aerial vehicle. Finally, a quadrotor unmanned aerial vehicle swarm system is used to verify the effectiveness of the proposed control scheme.
Effects of Shredded Paper Mulch on Komatsuna Spinach under Three Soil Moisture Levels
Authors: Mon May Myat , Oue Hiroki
Published: September 2023

Mulch has been considered effective for saving water and promoting plant growth. However, little has been investigated about the effect of mulch from recycled shredded paper under different soil moisture conditions on spinach growth. A pot-grown Komatsuna spinach experiment with a factorial design was conducted under two main conditions, with and without shredded paper mulch. Each of these conditions was treated with three different soil moisture levels (SWC) 20%, 25%, and 30%. The smallest evapotranspiration amount was in the mulch-only, no-plant treatment with SWC 20% (92.88 mm), and the largest was in the plant-only, no-mulch treatment (226.19 mm). All biomass yield attributions were negatively influenced by increasing the frequency of irrigation and SWC levels. SWC 20% with shredded mulch resulted in the largest dry matter, although it was statistically non-significant. But it resulted in taller plant heights and a larger leaf area index (LAI) compared to soil with no shredded mulch (p < 0.05). For SWC 25% and 30% treatments, Komatsuna spinach with no shredded mulch resulted in slightly superior plant dry matter and plant height, compared to mulched plants. These results suggest that SWC 20% with shredded paper mulch has the highest potential for saving water among all treatments for growing spinach under limited water availability.
Fretting Corrosion Performance Evaluation of Uncoated Cladding, Cr Coating Cladding and AlCrNbSiTi Coating Cladding
Authors: Liu Xin , Li Shen , Wang Hui , Tu Menghe , Zhou Bokai , Hu Yong
Published: September 2023

In pressurized water reactors (PWRs), flow-induced vibration (FIV) induces the fretting wear of fuel rods and supporting grids, and the process is accompanied by corrosion, which is called fretting corrosion. In this paper, fretting corrosion experiments were carried out in a simulated cladding service environment, and the fretting corrosion performance of AlCrNbSiTi coating cladding, Cr coating cladding and uncoated cladding with the supporting grids were investigated using a three-dimensional white light interferometer and a scanning electron microscope (SEM). The results showed that the AlCrNbSiTi coating cladding has the strongest fretting corrosion performance, the Cr coating cladding has the second best fretting corrosion performance and the uncoated cladding has the worst fretting corrosion performance. The coating also changes the wear mechanism of the cladding and improves the corrosion resistance of the cladding, which is responsible for the improvement in the fretting corrosion performance of the cladding. By comparing the AlCrNbSiTi coating with the Cr coating, it was found that the AlCrNbSiTi coating has a better fretting corrosion performance than the Cr coating due to its higher hardness and stronger corrosion resistance.
Comparison of Ultrasound-Guided Versus Anatomical Landmark-Guided Thoracolumbar Retrolaminar Techniques in Canine Cadavers
Authors: Pentsou Julia , Hoey Séamus , Vagias Michail , Guy Bethany , Huuskonen Vilhelmiina
Published: September 2023

The retrolaminar block was developed in humans as an easier and safer alternative to the thoracic paravertebral block. This study aims to describe an ultrasound-guided thoracolumbar retrolaminar injection in canine cadavers and compare the injectate distribution between a landmark-guided and an ultrasound-guided thoracolumbar retrolaminar technique using computed tomography. Ten canine cadavers were randomised to receive two injections each of 0.6 mL/kg of iodinated contrast at the level of the twelfth thoracic vertebra (T12): a landmark-guided retrolaminar injection was performed on one hemithorax (group B, n = 10) and an ultrasound-guided on the other hemithorax (group U, n = 10). Groups were compared using the Mann–Whitney U test. The median (range) spread of the contrast in the paravertebral space was 0 (0–3) and 1 (0–5) vertebrae in groups B and U, respectively (p = 0.038). The median (range) extent of the spread surrounding the interverbal foramina was 4 (0–5) in group B and 4 (3–5) in group U. The median (range) spread along the retrolaminar space cranial and caudal to T12 was 3 (0–6) retrolaminar segments in group B and 3 (3–4) in group U. The potential of the ultrasound-guided retrolaminar injection to provide analgesia for dogs suffering from thoracolumbar pain should be further investigated.
Key Findings and Experience in the Management of Juvenile Recurrent Parotitis with Sialoendoscopies—A Retrospective Study
Authors: Mohana Aladdin , Bar Ori , Porat Ben Amy Dalit , Abdelraziq Murad , Abu El-Naaj Imad
Published: September 2023

Introduction: Juvenile recurrent parotitis (JRP) is characterized by intermittent swelling of one or both parotid glands, accompanied by pain and associated with non-obstructive sialectasia. Sialoendoscopy is considered a significant treatment for JRP, being a safe and minimally invasive treatment method with good clinical outcomes. The purpose of this study was to assess the procedure of sialoendoscopy as a treatment modality for JRP and discuss the relevant literature on this topic. Methods: This study retrospectively reviewed clinical records of children diagnosed with JRP who were treated in the Maxillofacial Department of the Tzafon Medical Center, Poriya, Israel, with sialoendoscopy between May 2016 and March 2023. Data on demographics, the site of symptoms, follow-up duration, treatment outcome, and complications were collected for each patient. The inclusion criteria were patients not older than 16 years of age, with at least two episodes of swelling of the parotid gland unilaterally or bilaterally during a time period of 6 months. The exclusion criteria were patients older than 16 years of age, and patients who were diagnosed with sialolithiasis or Sjogren’s syndrome. Results: The study included 17 children, of whom 12 (70%) were boys and 5 (30%) were girls. The mean age of the children at the time of the procedure was 6.7 years and ranged from 3 to 16. The affected parotid gland was the left in 7 children (41%), right in 9 children (53%), and bilateral in 1 child (6%). The average follow-up time was 45.17 months and ranged from 5 to 81 months. A total of 15 children (88%) were deemed to have a successful treatment result regarding the frequency of episodes after therapy and subjective improvement. Full resolution was seen in 10 children (59%). The sialoendoscopy findings were avascularity in the walls of the parotid duct, strictures, and mucous plugs. Pathological findings in sialoendoscopy were found in 11 out of 12 asymptomatic contralateral glands (p-value > 0.001). Conclusions: Sialoendoscopy under general anesthesia is a worthwhile and practicable treatment method for treating JRP. Satisfactory results were seen in the vast majority of patients. It is recommended to perform bilateral sialoendoscopy also in cases of a unilateral symptomatic gland. This treatment method is effective, safe, and potentially repeatable.
Robust Sales forecasting Using Deep Learning with Static and Dynamic Covariates
Authors: Ramos Patrícia , Oliveira José Manuel
Published: September 2023

Retailers must have accurate sales forecasts to efficiently and effectively operate their businesses and remain competitive in the marketplace. Global forecasting models like RNNs can be a powerful tool for forecasting in retail settings, where multiple time series are often interrelated and influenced by a variety of external factors. By including covariates in a forecasting model, we can often better capture the various factors that can influence sales in a retail setting. This can help improve the accuracy of our forecasts and enable better decision making for inventory management, purchasing, and other operational decisions. In this study, we investigate how the accuracy of global forecasting models is affected by the inclusion of different potential demand covariates. To ensure the significance of the study’s findings, we used the M5 forecasting competition’s openly accessible and well-established dataset. The results obtained from DeepAR models trained on different combinations of features indicate that the inclusion of time-, event-, and ID-related features consistently enhances the forecast accuracy. The optimal performance is attained when all these covariates are employed together, leading to a 1.8% improvement in RMSSE and a 6.5% improvement in MASE compared to the baseline model without features. It is noteworthy that all DeepAR models, both with and without covariates, exhibit a significantly superior forecasting performance in comparison to the seasonal naïve benchmark.
Applications of Machine Learning and Neural Networks for FT-ICR Mass Measurements with SIPT
Authors: Campbell Scott E. , Bollen Georg , Hamaker Alec , Kretzer Walter , Ringle Ryan , Schwarz Stefan
Published: September 2023

The single-ion Penning trap (SIPT) at the Low-Energy Beam Ion Trapping Facility has been developed to perform precision Penning trap mass measurements of single ions, ideal for the study of exotic nuclei available only at low rates at the Facility for Rare Isotope Beams (FRIB). Single-ion signals are very weak—especially if the ion is singly charged—and the few meaningful ion signals must be disentangled from an often larger noise background. A useful approach for simulating Fourier transform ion cyclotron resonance signals is outlined and shown to be equivalent to the established yet computationally intense method. Applications of supervised machine learning algorithms for classifying background signals are discussed, and their accuracies are shown to be ≈65% for the weakest signals of interest to SIPT. Additionally, a deep neural network capable of accurately predicting important characteristics of the ions observed by their image charge signal is discussed. Signal classification on an experimental noise dataset was shown to have a false-positive classification rate of 10.5%, and 3.5% following additional filtering. The application of the deep neural network to an experimental 85Rb+ dataset is presented, suggesting that SIPT is sensitive to single-ion signals. Lastly, the implications for future experiments are discussed.
Neuropsychological Evaluation and Functional Magnetic Resonance Imaging Tasks in the Preoperative Assessment of Patients with Brain Tumors: A Systematic Review
Authors: Pertichetti Marta , Corbo Daniele , Belotti Francesco , Saviola Francesca , Gasparotti Roberto , Fontanella Marco Maria , Panciani Pier Paolo
Published: September 2023

Background: Current surgical treatment of gliomas relies on a function-preserving, maximally safe resection approach. Functional Magnetic Resonance Imaging (fMRI) is a widely employed technology for this purpose. A preoperative neuropsychological evaluation should accompany this exam. However, only a few studies have reported both neuropsychological tests and fMRI tasks for preoperative planning—the current study aimed to systematically review the scientific literature on the topic. Methods: PRISMA guidelines were followed. We included studies that reported both neuropsychological tests and fMRI. Exclusion criteria were: no brain tumors, underage patients, no preoperative assessment, resting-state fMRI only, or healthy sample population/preclinical studies. Results: We identified 123 papers, but only 15 articles were included. Eight articles focused on language; three evaluated cognitive performance; single papers studied sensorimotor cortex, prefrontal functions, insular cortex, and cerebellar activation. Two qualitative studies focused on visuomotor function and language. According to some authors, there was a strong correlation between performance in presurgical neuropsychological tests and fMRI. Several papers suggested that selecting well-adjusted and individualized neuropsychological tasks may enable the development of personalized and more efficient protocols. The fMRI findings may also help identify plasticity phenomena to avoid unintentional damage during neurosurgery. Conclusions: Most studies have focused on language, the most commonly evaluated cognitive function. The correlation between neuropsychological and fMRI results suggests that altered functions during the neuropsychological assessment may help identify patients who could benefit from an fMRI and, possibly, functions that should be tested. Neuropsychological evaluation and fMRI have complementary roles in the preoperative assessment.
Trends in Outcome of Hematopoietic Stem Cell Transplantation: 5000 Transplantations and 30 Years of Single-Center Experience
Authors: Zubarovskaya Ludmila Stepanovna , Moiseev Ivan Sergeevich , Vladovskaya Maria Dmidrievna , Mikhailova Natalia Borisovna , Morozova Elena Vladislavovna , Bykova Tatyana Alexandrovna , Vlasova Yulia Yurievna , Paina Olesya Vladimirovna , Kazantsev Ilya Viktorovich , Slesarchuk Olga Alexandrovna , Smirnova Anna Gennadyevna , Osipova Anna Alekseevna , Stelmakh Liliya Vladimirovna , Polushin Alexey Yurievich , Goloshchapov Oleg Valerievich , Bogomolny Maxim Pavlovich , Estrina Maria Arkadievna , Popova Marina Olegovna , Kucher Maxim Anatolievich , Volkova Alisa Georgievna , Alyansky Alexander Leonidovich , Pevtcov Dmitrii Eduardovich , Ivanova Natalia Evgenievna , Babenko Elena Vitalievna , Mamaev Nikolai Nikolaevich , Gindina Tatiana Leonidovna , Vitrishchak Alina Alexandrovna , Chukhlovin Alexei Borisovich , Semenova Elena Vladimirovna , Bondarenko Sergei Nicolaevich , Kulagin Alexander Dmitrievich , Afanasyev Boris Vladimirovich
Published: September 2023

In this single-center analysis, we evaluated the trends in 5185 hematopoietic cell transplantations performed between 1990 and 2022. The study group comprised 3237 allogeneic (alloHCT) and 1948 autologous (autoHCT) hematopoietic cell transplantations. In the multivariate analysis, there was an improvement in event-free-survival (EFS) after autoHCT (HR 0.6, 95% CI 0.4–0.7, p < 0.0001) due to reduced cumulative incidence of relapse in the last five years (56% in 2010–2014 vs. 38% in 2015–2022). An improvement in EFS after alloHCT over time was observed (HR 0.33, 95% CI 0.23–0.48, p < 0.0001), which was due to reduced non-relapse mortality. No difference in cumulative relapse incidence was observed over the last decade for allografted patients. Survival after autoHCT improved in Hodgkin’s disease (HR 0.1, 95% CI 0.1–0.3), multiple myeloma (HR 0.4, 95% CI 0.2–0.7) and solid tumors (HR 0.2, 95% CI 0.2–0.4), while after alloHCT, improvement was observed in acute myeloid leukemia (HR 0.3, 95% CI 0.1–0.5), acute lymphoblastic leukemia (HR 0.2, 95% CI 0.1–0.5), Hodgkin’s disease (HR 0.1, 95% CI 0.0–0.4), non-Hodgkin’s lymphomas and chronic lymphocytic leukemia (HR 0.2, 95% CI 0.0–0.6), inborn diseases (HR 0.2, 95% CI 0.2–0.4) and acquired aplastic anemia with matched related donors and matched unrelated donors (HR 0.3, 95% CI 0.2–0.8).
Up-Front ASCT Overcomes the Survival Benefit Provided by HDAC-Based Induction Regimens in Mantle Cell Lymphoma: Data from a Real-Life and Long-Term Cohort
Authors: de Pádua Covas Lage Luís Alberto , Elias Marcela do Vale , Reichert Cadiele Oliana , Culler Hebert Fabrício , de Freitas Fábio Alessandro , de Oliveira Costa Renata , Rocha Vanderson , da Siqueira Sheila Aparecida Coelho , Pereira Juliana
Published: September 2023

Background: Mantle cell lymphoma (MCL) is a rare malignancy with heterogeneous behavior. Despite the therapeutic advances recently achieved, MCL remains incurable. Currently, the standard of care for young and fit patients involves induction immunochemotherapy followed by up-front autologous stem cell transplantation (ASCT). However, the role of more intensive induction regimens, such as those based on high doses of cytarabine (HDAC), remains controversial in the management of ASCT-eligible patients. Methods: This retrospective, observational, and single-center study involved 165 MCL patients treated at the largest oncology center in Latin America from 2010 to 2022. We aimed to assess outcomes, determine survival predictors, and compare responses between different primary therapeutic strategies, with a focus on assessing the impact of HDAC-based regimens on outcomes in ASCT-eligible patients. Results: The median age at diagnosis was 65 years (38–89 years), and 73.9% were male. More than 90% of the cases had a classic nodal form (cnMCL), 76.4% had BM infiltration, and 56.4% presented splenomegaly. Bulky ≥ 7 cm, B-symptoms, ECOG ≥ 2, and advanced-stage III/IV were observed in 32.7%, 64.8%, 32.1%, and 95.8%, respectively. Sixty-four percent of patients were categorized as having high-risk MIPI. With a median follow-up of 71.1 months, the estimated 2-year OS and EFS were 64.1% and 31.8%, respectively. Patients treated with (R)-HDAC-based regimens had a higher ORR (85.9% vs. 65.7%, p = 0.007) compared to those receiving (R)-CHOP, as well as lower POD-24 rates (61.9% vs. 80.4%, p = 0.043) and lower mortality (43.9% vs. 68.6%, p = 0.004). However, intensified induction regimens with (R)-HDAC were not associated with a real OS benefit in MCL patients undergoing up-front consolidation with ASCT (2-year OS: 88.7% vs. 78.8%, p = 0.289). Up-front ASCT was independently associated with increased OS (p < 0.001), EFS (p = 0.005), and lower POD-24 rates (p < 0.001) in MCL. Additionally, CNS infiltration, TLS, hypoalbuminemia, and the absence of remission after induction were predictors of poor OS. Conclusions: In the largest Latin American cohort of MCL patients, we confirmed the OS benefit promoted by up-front consolidation with ASCT in young and fit patients, regardless of the intensity of the immunochemotherapy regimen used in the pre-ASCT induction. Although HDAC-based regimens were not associated with an unequivocal increase in OS for ASCT-eligible patients, it was associated with higher ORR and lower rates of early relapses for the whole cohort.
Thyroid Cancer: Focus on Invasion and Metastasis Mechanisms, Therapeutic Target and Drug Treatment
Authors: Vasko Vasyl
Published: September 2023

Understanding the molecular processes driving thyroid cancer invasion, metastasis, and resistance to therapy is essential for the advancement of novel treatment approaches [...]
Hemoptysis in Cancer Patients
Authors: Singer Emad D. , Faiz Saadia A. , Qdaisat Aiham , Abdeldaem Karim , Dagher Jim , Chaftari Patrick , Yeung Sai-Ching J.
Published: September 2023

Hemoptysis in cancer patients can occur for various reasons, including infections, tumors, blood vessel abnormalities and inflammatory conditions. The degree of hemoptysis is commonly classified according to the quantity of blood expelled. However, volume-based definitions may not accurately reflect the clinical impact of bleeding. This review explores a more comprehensive approach to evaluating hemoptysis by considering its risk factors, epidemiology and clinical consequences. In particular, this review provides insight into the risk factors, identifies mortality rates associated with hemoptysis in cancer patients and highlights the need for developing a mortality prediction score specific for cancer patients. The use of hemoptysis-related variables may help stratify patients into risk categories; optimize the control of bleeding with critical care; implement the use of tracheobronchial or vascular interventions; and aid in treatment planning. Effective management of hemoptysis in cancer patients must address the underlying cause while also providing supportive care to improve patients’ quality of life.
Differentiation Syndrome in Acute Leukemia: APL and Beyond
Authors: Woods Ashley C. , Norsworthy Kelly J.
Published: September 2023

Differentiation syndrome (DS) is a frequent and potentially life-threatening clinical syndrome first recognized with the advent of targeted therapeutics for acute promyelocytic leukemia (APL). DS was subsequently observed more broadly with targeted therapeutics for acute myeloid leukemia (AML). DS is typically characterized by fever, dyspnea, hypotension, weight gain, pleural or pericardial effusions, and acute renal failure. The incidence in patients with APL ranges from 2 to 37%, with the wide variation likely attributed to different diagnostic criteria, use of prophylactic treatment, and different treatment regimens. Treatment with corticosteroids +/- cytoreductive therapy should commence as soon as DS is suspected to reduce DS-related morbidity and mortality. The targeted anti-leukemic therapy should be discontinued in patients with severe DS. Here, we discuss the pathogenesis of DS, clinical presentations, diagnostic criteria, management strategies, and implementation of prospective tracking on clinical trials.
Exploring the Potential of Non-Coding RNAs as Liquid Biopsy Biomarkers for Lung Cancer Screening: A Literature Review
Authors: Garbo Edoardo , Del Rio Benedetta , Ferrari Giorgia , Cani Massimiliano , Napoli Valerio Maria , Bertaglia Valentina , Capelletto Enrica , Rolfo Christian , Novello Silvia , Passiglia Francesco
Published: September 2023

Lung cancer represent the leading cause of cancer mortality, so several efforts have been focused on the development of a screening program. To address the issue of high overdiagnosis and false positive rates associated to LDCT-based screening, there is a need for new diagnostic biomarkers, with liquid biopsy ncRNAs detection emerging as a promising approach. In this scenario, this work provides an updated summary of the literature evidence about the role of non-coding RNAs in lung cancer screening. A literature search on PubMed was performed including studies which investigated liquid biopsy non-coding RNAs biomarker lung cancer patients and a control cohort. Micro RNAs were the most widely studied biomarkers in this setting but some preliminary evidence was found also for other non-coding RNAs, suggesting that a multi-biomarker based liquid biopsy approach could enhance their efficacy in the screening context. However, further studies are needed in order to optimize detection techniques as well as diagnostic accuracy before introducing novel biomarkers in the early diagnosis setting.
αV-Integrin-Dependent Inhibition of Glioblastoma Cell Migration, Invasion and Vasculogenic Mimicry by the uPAcyclin Decapeptide
Authors: Franco Paola , Camerino Iolanda , Merlino Francesco , D’Angelo Margherita , Cimmino Amelia , Carotenuto Alfonso , Colucci-D’Amato Luca , Stoppelli Maria Patrizia
Published: September 2023

Among the deadliest human cancers is glioblastoma (GBM) for which new treatment approaches are urgently needed. Here, the effects of the cyclic decapeptide, uPAcyclin, are investigated using the U87-MG, U251-MG, and U138-MG human GBM and C6 rat cell models. All GBM cells express the αV-integrin subunit, the target of uPAcyclin, and bind specifically to nanomolar concentrations of the decapeptide. Although peptide exposure affects neither viability nor cell proliferation rate, nanomolar concentrations of uPAcyclin markedly inhibit the directional migration and matrix invasion of all GBM cells, in a concentration- and αV-dependent manner. Moreover, wound healing rate closure of U87-MG and C6 rat glioma cells is reduced by 50% and time-lapse videomicroscopy studies show that the formation of vascular-like structures by U87-MG in three-dimensional matrix cultures is markedly inhibited by uPAcyclin. A strong reduction in the branching point numbers of the U87-MG, C6, and U251-MG cell lines undergoing vasculogenic mimicry, in the presence of nanomolar peptide concentrations, was observed. Lysates from matrix-recovered uPAcyclin-exposed cells exhibit a reduced expression of VE-cadherin, a prominent factor in the acquisition of vascular-like structures. In conclusion, these results indicate that uPAcyclin is a promising candidate to counteract the formation of new vessels in novel targeted anti-GBM therapies.
Endoscopic Management of Dysplastic Barrett’s Oesophagus and Early Oesophageal Adenocarcinoma
Authors: Eusebi Leonardo Henry , Telese Andrea , Castellana Chiara , Engin Rengin Melis , Norton Benjamin , Papaefthymiou Apostolis , Zagari Rocco Maurizio , Haidry Rehan
Published: September 2023

Barrett’s oesophagus is a pathological condition whereby the normal oesophageal squamous mucosa is replaced by specialised, intestinal-type metaplasia, which is strongly linked to chronic gastro-oesophageal reflux. A correct endoscopic and histological diagnosis is pivotal in the management of Barrett’s oesophagus to identify patients who are at high risk of progression to neoplasia. The presence and grade of dysplasia and the characteristics of visible lesions within the mucosa of Barrett’s oesophagus are both important to guide the most appropriate endoscopic therapy. In this review, we provide an overview on the management of Barrett’s oesophagus, with a particular focus on recent advances in the diagnosis and recommendations for endoscopic therapy to reduce the risk of developing oesophageal adenocarcinoma.
Novel In Vitro Models for Cell Differentiation and Drug Transport Studies of the Human Intestine
Authors: Przybylla Randy , Krohn Mathias , Sellin Marie-Luise , Frank Marcus , Oswald Stefan , Linnebacher Michael
Published: September 2023

The most common in vitro model for absorption, distribution, metabolism, and excretion (ADME) purposes is currently the Caco-2 cell line. However, clear differences in gene and protein expression towards the small intestine and an, at best, fair prediction accuracy of intestinal drug absorption restrict the usefulness of a model for intestinal epithelial cells. To overcome these limitations, we evaluated a panel of low-passaged patient-derived colorectal cancer cell lines of the HROC collection concerning similarities to small intestinal epithelial cells and their potential to predict intestinal drug absorption. After initial screening of a larger panel, ten cell lines with confluent outgrowth and long-lasting barrier-forming potential were further characterized in close detail. Tight junctional complexes and microvilli structures were detected in all lines, anda higher degree of differentiation was observed in 5/10 cell lines. All lines expressed multiple transporter molecules, with the expression levels in three lines being close to those of small intestinal epithelial cells. Compared with the Caco-2 model, three HROC lines demonstrated both higher similarity to jejunal epithelial tissue cells and higher regulatory potential of relevant drug transporters. In summary, these lines would be better-suited human small intestinal epithelium models for basic and translational research, especially for ADME studies.
The Neutrophil-to-Lymphocyte Ratio (NLR) Can Predict Sepsis’s Presence and Severity in Malnourished Infants—A Single Center Experience
Authors: Domnicu Alina Emilia , Boia Eugen Radu , Mogoi Mirela , Manea Aniko-Maria , Marcovici Tamara Marcela , Mărginean Otilia , Boia Marioara
Published: September 2023

Sepsis represents one of the leading causes of death in newborns and infants, and prompt diagnosis is essential for achieving favorable outcomes. Regarding malnourished children with concurrent infection, most studies have focused, besides blood culture, on C-reactive protein and procalcitonin. Because malnutrition has a deleterious effect on cellular immune competence, the present study characterized the acute-phase response, including hematological indices, in response to sepsis. Among the examined laboratory biomarkers, procalcitonin and neutrophil-to-lymphocyte ratio were the most accurate discriminators between sepsis patients and those with bacterial infection. Moreover, these two parameters showed a gradual increase between sepsis, severe sepsis, and septic shock patients (p < 0.001). Subgroup analysis of the sepsis group revealed positive correlations of NLR with prolonged ICU stay (<0.001), acute organ dysfunction (0.038), mechanical ventilation (<0.001), and fatality (<0.001). In summary, our results suggest that the neutrophil-to-lymphocyte ratio can be used as an auxiliary diagnostic index in discriminating the presence and severity of bacterial sepsis in malnourished infants.
Full-Thickness Rectal Biopsy in Children Suspected of Having Hirschsprung’s Disease: The Inconclusive Biopsy
Authors: Korsager Leise Elisabeth Hviid , Bjørn Niels , Ellebæk Mark Bremholm , Christensen Lene Gaardsmand , Qvist Niels
Published: September 2023

The diagnosis of Hirschsprung’s disease relies on histologically proven aganglionosis and nerve trunk hypertrophy in rectal biopsies. Although the frequency of inconclusive biopsies is relatively low, it is a relevant clinical problem. The aim of the present study was to investigate whether a re-evaluation of archived full-thickness biopsies (FTBs) stained with hematoxylin and eosin (HE), together with immune histochemical (IHC) staining, would be diagnostic in biopsies otherwise deemed inconclusive at initial examination with HE only. A total of 34 inconclusive biopsies in 31 patients were identified. From each tissue block, three slices were cut and stained with HE, S100 and calretinin. A blinded pathologist examined the tissue samples. At re-evaluation, one patient was found positive for HD and 11 negative for HD with both HE and IHC staining, respectively. In all 12 cases, the result was confirmed by the final diagnosis at a 5-year follow-up. The rest of the cases were deemed inconclusive. A re-evaluation of the remaining tissue from the biobank might have saved one third of the children from a re-biopsy. The value of adding IHC to conventional HE staining is dubious.
Exploring the Functional Basis of Epigenetic Aging in Relation to Body Fat Phenotypes in the Norfolk Island Cohort
Authors: Cao Thao Van , Sutherland Heidi G. , Benton Miles C. , Haupt Larisa M. , Lea Rodney A. , Griffiths Lyn R.
Published: September 2023

DNA methylation is an epigenetic factor that is modifiable and can change over a lifespan. While many studies have identified methylation sites (CpGs) related to aging, the relationship of these to gene function and age-related disease phenotypes remains unclear. This research explores this question by testing for the conjoint association of age-related CpGs with gene expression and the relation of these to body fat phenotypes. The study included blood-based gene transcripts and intragenic CpG methylation data from Illumina 450 K arrays in 74 healthy adults from the Norfolk Island population. First, a series of regression analyses were performed to detect associations between gene transcript level and intragenic CpGs and their conjoint relationship with age. Second, we explored how these age-related expression CpGs (eCpGs) correlated with obesity-related phenotypes, including body fat percentage, body mass index, and waist-to-hip ratio. We identified 35 age-related eCpGs associated with age. Of these, ten eCpGs were associated with at least one body fat phenotype. Collagen Type XI Alpha 2 Chain (COL11A2), Complement C1s (C1s), and four and a half LIM domains 2 (FHL2) genes were among the most significant genes with multiple eCpGs associated with both age and multiple body fat phenotypes. The COL11A2 gene contributes to the correct assembly of the extracellular matrix in maintaining the healthy structural arrangement of various components, with the C1s gene part of complement systems functioning in inflammation. Moreover, FHL2 expression was upregulated under hypermethylation in both blood and adipose tissue with aging. These results suggest new targets for future studies and require further validation to confirm the specific function of these genes on body fat regulation.
Interferon-Free Regimens and Direct-Acting Antiviral Agents for Delta Hepatitis: Are We There Yet?
Authors: Nemteanu Roxana , Clim Andreea , Hincu Corina Elena , Gheorghe Liliana , Ciortescu Irina , Plesa Alina
Published: September 2023

Chronic delta hepatitis is a global health problem. Although a smaller percentage of chronic HBV-infected patients are coinfected with the hepatitis delta virus, these patients have a higher risk of an accelerated progression to fulminant “delta hepatitis”, cirrhosis, hepatic decompensation, and hepatocellular carcinoma, putting a financial strain on the healthcare system and increasing the need for a liver transplant. Since its discovery, tremendous efforts have been directed toward understanding the intricate pathogenic mechanisms, discovering the complex viral replication process, the essential replicative intermediates, and cell division-mediated viral spread, which enables virion viability. The consideration of the interaction between HBV and HDV is crucial in the process of developing novel pharmaceuticals. Until just recently, interferon-based therapy was the only treatment available worldwide. This review aims to present the recent advancements in understanding the life cycle of HDV, which have consequently facilitated the development of innovative drug classes. Additionally, we will examine the antiviral strategies currently in phases II and III of development, including bulevirtide (an entry inhibitor), lonafarnib (a prenylation inhibitor), and REP 2139 (an HBsAg release inhibitor).