bluuebunny/crossref_metadata_2025 huggingface dataset:
How to Precisely Update Large Language Models Knowledge While Avoiding Catastrophic Forgetting
Authors: Ding Fei
Published: July 2024

Recent advancements in Large Language Models (LLMs) have showcased their remarkable capabilities in text understanding and generation. However, even stronger LLMs are susceptible to acquiring erroneous or obsolete information from the training corpus. Direct secondary fine-tuning with data containing new knowledge may be ineffective in updating knowledge due to the conflict between old and new knowledge. In this paper, we propose a new paradigm for fine-tuning called DFT (Delicate Fine-Tuning ).This method utilizes parametric arithmetic to precisely pinpoint the location of knowledge and update only the minimal set of relevant parameters . Experimental results on two publicly available datasets demonstrate that our proposed DFT can obviously improve the knowledge updating performance of full fine-tuning , simultaneously outperforming the existing baselines in most cases.
Proof of Collatz conjecture
Authors: TAHA BEN MOHAMED ABDELKRIM
Published: July 2024

In this working paper we try to prove the Collatz conjecture also known the 3x+1 problem.
Advancements in pH-Responsive nanoparticles for osteoarthritis treatment: Opportunities and challenges
Authors: Liao Shuai , Jia Shicheng , Yue Yaohang , Zeng Hui , Lin Jianjin , Liu Peng
Published: July 2024

Osteoarthritis (OA) is a degenerative disease linked to aging and obesity. The global aging population has led to an increasing number of OA patients, imposing a significant economic burden on society. Traditional drugs treatment methods often fail to achieve satisfactory outcomes. With the rapid advancement of nanomaterial delivery systems, numerous studies have focused on utilizing nanomaterials as carriers to achieve efficient OA treatment by effectively loading and delivering bioactive ingredients (e.g., drugs, nucleic acids) tailored to the unique pathological conditions, such as the weakly acidic microenvironment of synovial fluid in OA patients. This review highlights the latest advancements in the use of pH-responsive nanoparticles for OA treatment, emphasizing the principle of targeted drug delivery leveraging the acidic microenvironment of inflamed joints. It further discusses the composition, synthesis, response mechanism, target selection, application, and recent research findings of nanoparticles, while also addressing the challenges and future directions in this promising field.
Current trends and latest developments in echocardiographic assessment of right ventricular function: load dependency perspective
Authors: Nonaka Hideaki , Rätsep Indrek , Obonyo Nchafatso G. , Suen Jacky Y. , Fraser John F. , Chan Jonathan
Published: July 2024

Right ventricle (RV) failure is a common complication of many cardiopulmonary diseases. Since it has a significant adverse impact on prognosis, precise determination of RV function is crucial to guide clinical management. However, accurate assessment of RV function remains challenging owing to the difficulties in acquiring its intricate pathophysiology and imaging its complex anatomical structure. In addition, there is historical attention focused exclusively on the left ventricle assessment, which has led to overshadowing and delayed development of RV evaluation. Echocardiography is the first-line and non-invasive bedside clinical tool for assessing RV function. Tricuspid annular plane systolic excursion (TAPSE), RV systolic tissue Doppler velocity of the tricuspid annulus (RV S'), and RV fractional area change (RV FAC) are conventional standard indices routinely used for RV function assessment, but accuracy has been subject to several limitations, such as load-dependency, angle-dependency, and localized regional assessment. Particularly, load dependency is a vexing issue, as the failing RV is always in a complex loading condition, which alters the values of echocardiographic parameters and confuses clinicians. Recently, novel echocardiographic methods for improved RV assessment have been developed. Specifically, “strain”, “RV-pulmonary arterial (PA) coupling”, and “RV myocardial work” are newly applied methods for RV function assessment, a few of which are designed to surmount the load dependency by taking into account the afterload on RV. In this narrative review, we summarize the latest data on these novel RV echocardiographic parameters and highlight their strengths and limitations. Since load independency is one of the primary advantages of these, we particularly emphasize this aspect.
Association between METS-IR and heart failure: a cross-sectional study
Authors: Su Xiaozhou , Zhao Chunli , Zhang Xianwei
Published: July 2024

Background

Prior research has indicated the importance of insulin resistance in the development of heart failure (HF). The metabolic score for insulin resistance (METS-IR), a novel measure for assessing insulin resistance, has been found to be associated with cardiovascular disease (CVD). Nevertheless, the relationship between METS-IR and heart failure remains uncertain.

Methods

This cross-sectional study collected data from the 2007–2018 National Health and Nutrition Examination Survey (NHANES). Multivariable logistic regression analysis and smoothing curve fitting were performed to explore the relationship between METS-IR and the risk of heart failure. Subgroup analysis and receiver operating characteristic (ROC) curve analysis were also conducted.

Results

A total of 14772 patients were included, of whom 485 (3.28%) had heart failure. We observed a significant positive association between METS-IR and the risk of heart failure in a fully adjusted model (per 1-unit increment in METS-IR: OR: 2.44; 95% CI: 1.38, 4.32). Subgroup analysis and interaction tests revealed no significant influence on this relationship. A saturation effect and nonlinear relationship between METS-IR and heart failure risk were found using a smoothing curve fitting analysis. The relationship was represented by a J-shaped curve with an inflection point at 40.966.

Conclusions

The results of our study indicated a J-shaped association between METS-IR and HF in adults in the United States. METS-IR may be a promising novel index for predicting the risk of heart failure. More longitudinal studies are needed to further verify causal relationships and validate the results in different classifications of heart failure populations.
The frequency analytical method for regional power systems considering the emergency frequency control
Authors: Shi Zheng , Zhao Haibo , Wang Yao , Liang Yan , Yan Lu , Zhang Xiaowei , Zhang Ming
Published: July 2024

With the continuous construction of high-voltage direct-current (HVDC) transmission projects, higher requirements are placed on the frequency security of the regional power systems. In order to ensure the frequency security of regional power systems, this paper proposes a transient frequency analytical method considering the emergency frequency control (EFC). Firstly, the aggregated system frequency response (SFR) model is constructed by reducing the order of the generator governor equation, the EFC equation, and the load model equation. Then, based on the aggregation model, the analytical solution of the transient frequency nadir of the regional power system is derived. The model can quickly and accurately calculate the transient frequency nadir of the regional power system considering EFC after the HVDC block fault. Finally, based on an actual regional power system model, the accuracy and applicability of the proposed method under HVDC block fault are verified.
ROS induced pyroptosis in inflammatory disease and cancer
Authors: Wang Jingsong , Wu Ziyong , Zhu Min , Zhao Yang , Xie Jingwen
Published: July 2024

Pyroptosis, a form of caspase-1-dependent cell death, also known as inflammation-dependent death, plays a crucial role in diseases such as stroke, heart disease, or tumors. Since its elucidation, pyroptosis has attracted widespread attention from various sectors. Reactive oxygen species (ROS) can regulate numerous cellular signaling pathways. Through further research on ROS and pyroptosis, the level of ROS has been revealed to be pivotal for the occurrence of pyroptosis, establishing a close relationship between the two. This review primarily focuses on the molecular mechanisms of ROS and pyroptosis in tumors and inflammatory diseases, exploring key proteins that may serve as drug targets linking ROS and pyroptosis and emerging fields targeting pyroptosis. Additionally, the potential future development of compounds and proteins that influence ROS-regulated cell pyroptosis is anticipated, aiming to provide insights for the development of anti-tumor and anti-inflammatory drugs.
Development of the Huntington Support App (HD-eHelp study): a human-centered and co-design approach
Authors: van Lonkhuizen Pearl J. C. , Heemskerk Anne-Wil , Meijer Eline , van Duijn Erik , de Bot Susanne T. , Klempir Jiri , Landwehrmeyer G. Bernhard , Mühlbäck Alzbeta , Hoblyn Jennifer , Squitieri Ferdinando , Chavannes Niels H. , Vegt Niko J. H. ,   on behalf of the HEALTHE-RND consortium
Published: July 2024

Introduction

eHealth seems promising in addressing challenges in the provision of care for Huntington’s disease (HD) across Europe. By harnessing information and communication technologies, eHealth can partially relocate care from specialized centers to the patients’ home, thereby increasing the availability and accessibility of specialty care services beyond regional borders. Previous research on eHealth (development) in HD is however limited, especially when it comes to including eHealth services specifically designed together with HD gene expansion carriers (HDGECs) and their partners to fit their needs and expectations.

Methods

This article describes the qualitative human-centered design process and first evaluations of the Huntington Support App prototype: a web-app aimed to support the quality of life (QoL) of HDGECs and their partners in Europe. Prospective end-users, i.e., HDGECs, their partners, and healthcare providers (HCPs), from different countries were involved throughout the development process. Through interviews, we captured people’s experiences with the disease, quality of life (QoL), and eHealth. We translated their stories into design directions that were further co-designed and subsequently evaluated with the user groups.

Results

The resulting prototype centralizes clear and reliable information on the disease, HD-related news and events, as well as direct contact possibilities with HCPs via an online walk-in hour or by scheduling an appointment. The app’s prototype was positively received and rated as (very) appealing, pleasant, easy to use and helpful by both HDGECs and partners.

Discussion

By involving end-users in every step, we developed a healthcare app that meets relevant needs of individuals affected by HD and therefore may lead to high adoption and retention rates. As a result, the app provides low-threshold access to reliable information and specialized care for HD in Europe. A description of the Huntington Support App as well as implications for further development of the app’s prototype are provided.
Clinically feasible automated MRI volumetry of the brain as a prognostic marker in subjective and mild cognitive impairment
Authors: Amland Rachel , Selbæk Geir , Brækhus Anne , Edwin Trine H. , Engedal Knut , Knapskog Anne-Brita , Olsrud Ellen Regine , Persson Karin
Published: July 2024

Background/aims

The number of patients suffering from cognitive decline and dementia increases, and new possible treatments are being developed. Thus, the need for time efficient and cost-effective methods to facilitate an early diagnosis and prediction of future cognitive decline in patients with early cognitive symptoms is becoming increasingly important. The aim of this study was to evaluate whether an MRI based software, NeuroQuant® (NQ), producing volumetry of the hippocampus and whole brain volume (WBV) could predict: (1) conversion from subjective cognitive decline (SCD) at baseline to mild cognitive impairment (MCI) or dementia at follow-up, and from MCI at baseline to dementia at follow-up and (2) progression of cognitive and functional decline defined as an annual increase in the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) score.

Methods

MRI was performed in 156 patients with SCD or MCI from the memory clinic at Oslo University Hospital (OUH) that had been assessed with NQ and had a clinical follow-up examination. Logistic and linear regression analyses were performed with hippocampus volume and WBV as independent variables, and conversion or progression as dependent variables, adjusting for demographic and other relevant covariates including Mini-Mental State Examination-Norwegian Revised Version score (MMSE-NR) and Apolipoprotein E ɛ4 (APOE ɛ4) carrier status.

Results

Hippocampus volume, but not WBV, was associated with conversion to MCI or dementia, but neither were associated with conversion when adjusting for MMSE-NR. Both hippocampus volume and WBV were associated with progression as measured by the annual change in CDR-SB score in both unadjusted and adjusted analyses.

Conclusion

The results indicate that automated regional MRI volumetry of the hippocampus and WBV can be useful in predicting further cognitive decline in patients with early cognitive symptoms.
Chronic myelomonocytic leukemia with ring sideroblasts/SF3B1 mutation presents with low monocyte count and resembles myelodysplastic syndromes with-RS/SF3B1 mutation in terms of phenotype and prognosis
Authors: Xicoy Blanca , Pomares Helena , Morgades Mireia , Germing Ulrich , Arnan Montserrat , Tormo Mar , Palomo Laura , Orna Elisa , Della Porta Matteo , Schulz Felicitas , Díaz-Beya Marina , Esteban Ada , Molero Antonieta , Lanino Luca , Avendaño Alejandro , Hernández Francisca , Roldan Verónica , Ubezio Marta , Pineda Alberto , Díez-Campelo María , Zamora Lurdes
Published: July 2024

Introduction

Chronic myelomonocytic leukemia (CMML) and myelodysplastic syndromes (MDS) with ring sideroblasts (RS) or SF3B1 mutation (MDS-RS/SF3B1) differ in many clinical features, but share others, such as anemia. RS and SF3B1 mutation can also be found in CMML.

Methods

We compared CMML with and without RS/SF3B1 and MDS-RS/SF3B1 considering the criteria established by the 2022 World Health Organization classification.

Results

A total of 815 patients were included (CMML, n=319, CMML-RS/SF3B1, n=172 and MDS-RS/SF3B1, n=324). The percentage of RS was ≥15% in almost all CMML-RS/SF3B1 patients (169, 98.3%) and most (125, 72.7%) showed peripheral blood monocyte counts between 0.5 and 0.9 x109/L and low risk prognostic categories. CMML-RS/SF3B1 differed significantly from classical CMML in the main clinical characteristics, whereas it resembled MDS-RS/SF3B1. At a molecular level, CMML and CMML-RS/SF3B1 had a significantly higher frequency of mutations in TET2 (mostly multi-hit) and ASXL1 (p=0.013) and CMML had a significantly lower frequency of DNMT3A and SF3B1 mutations compared to CMML/MDS-RS/SF3B1. Differences in the median overall survival among the three groups were statistically significant: 6.75 years (95% confidence interval [CI] 5.41-8.09) for CMML-RS/SF3B1 vs. 3.17 years (95% CI 2.56-3.79) for CMML vs. 16.47 years (NA) for MDS-RS/SF3B1, p<0.001. Regarding patients with CMML and MDS, both with SF3B1 mutation, survival did not significantly differ. CMML had a higher risk of transformation to acute myeloid leukemia (24% at 8 years, 95%CI 19%-30%).

Discussion

CMML-RS/SF3B1 mutation resembles MDS-RS/SF3B1 in terms of phenotype and clearly differs from CMML. The presence of ≥15% RS and/or SF3B1 in CMML is associated with a low monocyte count. SF3B1 mutation clearly improves the prognosis of CMML.
Identification of a basement membrane-related gene signature for predicting prognosis, immune infiltration, and drug sensitivity in colorectal cancer
Authors: Shengxiao Xiang , Xinxin Sun , Yunxiang Zhu , Zhijie Tang , Xiaofei Tang
Published: July 2024

Background

Colorectal cancer (CRC) is the most common malignancy affecting the gastrointestinal tract. Extensive research indicates that basement membranes (BMs) may play a crucial role in the initiation and progression of the disease.

Methods

Data on the RNA expression patterns and clinicopathological information of patients with CRC were sourced from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. A BM-linked risk signature for the prediction of overall survival (OS) was formulated using univariate Cox regression and combined machine learning techniques. Survival outcomes, functional pathways, the tumor microenvironment (TME), and responses to both immunotherapy and chemotherapy within varying risk classifications were also investigated. The expression trends of the model genes were evaluated by reverse transcription polymerase chain reaction (RT-PCR) and the Human Protein Atlas (HPA) database.

Results

A nine-gene risk signature containing UNC5C, TINAG, TIMP1, SPOCK3, MMP1, AGRN, UNC5A, ADAMTS4, and ITGA7 was constructed for the prediction of outcomes in patients with CRC. The expression profiles of these candidate genes were verified using RT-PCR and the HPA database and were found to be consistent with the findings on differential gene expression in the TCGA dataset. The validity of the signature was confirmed using the GEO cohort. The patients were stratified into different risk groups according to differences in clinicopathological characteristics, TME features, enrichment functions, and drug sensitivities. Lastly, the prognostic nomogram model based on the risk score was found to be effective in identifying high-risk patients and predicting OS.

Conclusion

A basement membrane-related risk signature was constructed and found to be effective for predicting the prognosis of patients with CRC.
Long-term follow-up in pediatric intensive care—a narrative review
Authors: Quadir Ashfaque , Festa Marino , Gilchrist Michelle , Thompson Kate , Pride Natalie , Basu Shreerupa
Published: July 2024

Pediatric intensive care is a rapidly developing medical specialty and with evolving understanding of pediatric pathophysiology and advances in technology, most children in the developed world are now surviving to intensive care and hospital discharge. As mortality rates for children with critical illness continue to improve, increasing PICU survivorship is resulting in significant long-term consequences of intensive care in these vulnerable patients. Although impairments in physical, psychosocial and cognitive function are well documented in the literature and the importance of establishing follow-up programs is acknowledged, no standardized or evidence-based approach to long-term follow-up in the PICU exists. This narrative review explores pediatric post-intensive care syndrome and summarizes the multifactorial deficits and morbidity that can occur in these patients following recovery from critical illness and subsequent discharge from hospital. Current practices around long-term follow-up are explored with discussion focusing on gaps in research and understanding with suggested ways forward and future directions.
Intrinsic organization of the corpus callosum
Authors: Barbaresi Paolo , Fabri Mara , Lorenzi Teresa , Sagrati Andrea , Morroni Manrico
Published: July 2024

The corpus callosum—the largest commissural fiber system connecting the two cerebral hemispheres—is considered essential for bilateral sensory integration and higher cognitive functions. Most studies exploring the corpus callosum have examined either the anatomical, physiological, and neurochemical organization of callosal projections or the functional and/or behavioral aspects of the callosal connections after complete/partial callosotomy or callosal lesion. There are no works that address the intrinsic organization of the corpus callosum. We review the existing information on the activities that take place in the commissure in three sections: I) the topographical and neurochemical organization of the intracallosal fibers, II) the role of glia in the corpus callosum, and III) the role of the intracallosal neurons.
Real-time citrus variety detection in orchards based on complex scenarios of improved YOLOv7
Authors: Deng Fuqin , Chen Jianle , Fu Lanhui , Zhong Jiaming , Qiaoi Weilai , Luo Jialong , Li Junwei , Li Nannan
Published: July 2024

Variety detection provides technical support for selecting XinHui citrus for use in the production of XinHui dried tangerine peel. Simultaneously, the mutual occlusion between tree leaves and fruits is one of the challenges in object detection. In order to improve screening efficiency, this paper introduces a YOLO(You Only Look Once)v7-BiGS(BiFormer&GSConv) citrus variety detection method capable of identifying different citrus varieties efficiently. In the YOLOv7-BiGS network model, initially, the BiFormer attention mechanism in the backbone of the YOLOv7-based network strengthens the model’s ability to extract citrus’ features. In addition, the introduction of the lightweight GSConv convolution in place of the original convolution within the ELAN of the head component effectively streamlines model complexity while maintaining performance integrity. To environment challenge validate the effectiveness of the method, the proposed YOLOv7-BiGS was compared with YOLOv5, YOLOv7, and YOLOv8. In the comparison of YOLOv7-BiGS with YOLOv5, YOLOv7, and YOLOv8, the experimental results show that the precision, mAP and recell of YOLOv7-BiGS are 91%, 93.7% and 87.3% respectively. Notably, compared to baseline methods, the proposed approach exhibited significant enhancements in precision, mAP, and recall by 5.8%, 4.8%, and 5.2%, respectively. To evaluate the efficacy of the YOLOv7-BiGS in addressing challenges posed by complex environmental conditions, we collected occluded images of Xinhui citrus fruits from the Xinhui orchard base for model detection. This research aims to fulfill performance criteria for citrus variety identification, offering vital technical backing for variety detection endeavors.
Working with the inner critic in patients with depression using chairwork: a pilot study
Authors: Kroener Julia , Mahler Jacqueline , Sosic-Vasic Zrinka
Published: July 2024

Introduction

Individuals diagnosed with depression frequently experience self-criticism, leading to considerable psychological distress. Despite the availability of cognitive-behavioral treatments, a notable proportion of patients indicate that they solely experience cognitive improvements, without the corresponding emotional changes, following therapy. As a result, their psychological symptoms persist. Interventions that specifically target emotional experiencing, such as the chairwork technique, are exclusively included within long-term therapeutic procedures. Hence, the objective of this study is to assess the efficacy as well as the acceptability, feasibility, and safety of a brief intervention utilizing emotion-focused chairwork to treat self-criticism in individuals diagnosed with depression.

Methods

A pre-post A-B design with two post-treatment assessments (one week- and one month post-intervention) was implemented. Seven patients received three sessions of manualized emotion focused chairwork. Symptomatic change was evaluated using the Beck Depression Inventory II (BDI-II), the emotion regulation questionnaire (SEK-27), the Forms of Self-Criticizing/Reassuring Scale (FSCRS), the Self-Compassion Scale (SCS-D), as well as the Rosenberg Self-Esteem Scale (RSES). Patient satisfaction was evaluated using a self-developed questionnaire. Safety was assessed by the Beck Suicidality Inventory (BSI).

Results

There was a significant improvement in depressive symptoms and self-compassion at both follow-up assessment time-points. Moreover, emotion regulation as well as self-esteem improved significantly. Self-criticizing decreased significantly, while self-reassuring increased. Patients were very satisfied with the intervention. Intervention safety was given at all time-points. There were no drop-outs.

Conclusion

The implemented chairwork short-intervention is a feasible and safe therapeutic technique. The treatment was highly accepted revealing significant symptomatic improvements. Large-scale randomized controlled trials (RCTs) are necessary to investigate the treatment’s effectiveness.
Short-term changes in chest CT images among individuals at low altitude after entering high-altitude environments
Authors: Wang Peng , Zuo Zhiwei , Wu Jie , Wang Jianxiong , Jiang Rui , Du Feizhou
Published: July 2024

Objective

To investigate the short-term changes in chest CT images of low-altitude populations after entering a high-altitude environment.

Methods

Chest CT images of 3,587 people from low-altitude areas were obtained within one month of entering a high-altitude environment. Abnormal CT features and clinical symptoms were analyzed.

Results

Besides acute high-altitude pulmonary edema, the incidence of soft tissue space pneumatosis was significantly higher than that in low-altitude areas. Pneumatosis was observed in the mediastinum, cervical muscle space, abdominal cavity, and spinal cord epidural space, especially the mediastinum.

Conclusion

In addition to acute high-altitude pulmonary edema, spontaneous mediastinal emphysema often occurs when individuals in low-altitude areas adapt to the high-altitude environment of cold, low-pressure, and hypoxia. When the gas escapes to the abdominal cavity, it is easy to be misdiagnosed as gastrointestinal perforation. It is also not uncommon for gas accumulation to escape into the epidural space of the spinal cord. The phenomenon of gas diffusion into distant tissue space and the mechanism of gas escape needs to be further studied.
Perceived satisfaction and household fuel transition: evidence from Ugandan households
Authors: Elasu Joseph , Ntayi Joseph Mpeera , Adaramola Muyiwa S. , Buyinza Faisal , Atukunda Ronnette , Ngoma Muhamad
Published: July 2024

Introduction

The dominance of biomass for cooking has implications for the country. For instance, biomass conversion using traditional technologies (three stone) in poorly ventilated kitchens produce smoke that influences the reproductive health outcomes for expectant mother. Beyond health outcomes, uncontrollable harvesting of biomass for cooking contributes to environmental degradation. Unfortunately, biomass in form of firewood, charcoal, plant and animal wastes is widely consumed by more than 94% of Ugandan households for cooking. This paper examined whether perceived satisfaction plays a significant role in household energy transition in Uganda.

Methods

The study adopted a panel data methodology employing an ordered logit model with random effects to estimate the effect of perceived satisfaction on household fuel transition from high to low pollutant cooking fuels in Uganda. The data used was obtained from Uganda Bureau of Statistics (UBoS) which is mandated by an Act of parliament to develop and maintain a national statistics system to ensure collection, analysis and publication of integrated, relevant, reliable and timely statistical information.

Findings and discussion

Our findings demonstrate that perceived satisfaction influences household fuel transition decisions in Uganda. The study concluded by suggesting policy recommendations for government action.
Gradual rewarming with a hemoglobin-based oxygen carrier improves viability of donation after circulatory death in rat livers
Authors: Mahboub Paria , Aburawi Mohamed , Ozgur O. Sila , Pendexter Casie , Cronin Stephanie , Lin Florence Min , Jain Rohil , Karabacak Murat N. , Karimian Negin , Tessier Shannon N. , Markmann James F. , Yeh Heidi , Uygun Korkut
Published: July 2024

Background

Donation after circulatory death (DCD) grafts are vital for increasing available donor organs. Gradual rewarming during machine perfusion has proven effective in mitigating reperfusion injury and enhancing graft quality. Limited data exist on artificial oxygen carriers as an effective solution to meet the increasing metabolic demand with temperature changes. The aim of the present study was to assess the efficacy and safety of utilizing a hemoglobin-based oxygen carrier (HBOC) during the gradual rewarming of DCD rat livers.

Methods

Liver grafts were procured after 30 min of warm ischemia. The effect of 90 min of oxygenated rewarming perfusion from ice cold temperatures (4 °C) to 37 °C with HBOC after cold storage was evaluated and the results were compared with cold storage alone. Reperfusion at 37 °C was performed to assess the post-preservation recovery.

Results

Gradual rewarming with HBOC significantly enhanced recovery, demonstrated by markedly lower lactate levels and reduced vascular resistance compared to cold-stored liver grafts. Increased bile production in the HBOC group was noted, indicating improved liver function and bile synthesis capacity. Histological examination showed reduced cellular damage and better tissue preservation in the HBOC-treated livers compared to those subjected to cold storage alone.

Conclusion

This study suggests the safety of using HBOC during rewarming perfusion of rat livers as no harmful effect was detected. Furthermore, the viability assessment indicated improvement in graft function.
Norwegian male U14 soccer players have superior running capacity compared to Icelandic players
Authors: Benediktsson Sigurður , Johannsson Erlingur , Rygh Cecilie Brekke , Gundersen Hilde
Published: July 2024

The organisation and development strategies of youth soccer differ between Norway and Iceland. Whether this affect physical capacity is unknown. Thus, the first aim of the present study is to compare physical capacity between players from Iceland and Norway. Secondary aim is to assess associations between biological maturity and physical capacity in the Icelandic players since an association previously has been shown among the Norwegians. There were 48 U14 players from Iceland included and 103 players from Norway. Bone age (BA), measured with left-wrist x-ray, was used as an indicator of biological maturity. To measure physical capacity, 40 metre (m) linear sprint, standing long jump (SLJ), countermovement jump (CMJ), the Yo-Yo intermittent recovery test (IR1-test) and a maximal oxygen uptake test (VO2max) were used. Training load was assessed by questionnaire. The results showed that the Norwegian players ran faster (5.90 ± 0.38 vs. 6.37 ± 0.44 s, p < .001), had better intermittent endurance capacity (1,235 ± 461 vs. 960 ± 423 m, p < .001) and higher VO2max, (60.3 ± 6.5 vs. 54.8 ± 5.3 ml·kg−1·min−1, p < .001) than the Icelandic players. The players from Norway reported a higher number of weekly organised soccer training hours than the Icelandic. We also found significant correlations between BA and performance on 40 m linear sprint (r = −.566, p < .001), SLJ (r = .380, p = .008) and CMJ (r = .354, p = .014) among the Icelandic players. Moreover, no correlations were found between BA and VO2max or intermittent endurance capacity. In conclusion, the Norwegian players ran faster and had better VO2max and intermittent endurance capacity than the Icelandic players. Biological maturity level was associated with speed and jumping performance in U14 soccer players in Iceland, but not with VO2max or intermittent endurance capacity. Findings indicate that more research is needed to investigate the influence of different organisation and structure of youth soccer between the two countries on physical capacity.
Maximizing the Average Environmental Benefit of a Fleet of Drones under a Periodic Schedule of Tasks
Authors: Kats Vladimir , Levner Eugene
Published: July 2024

Unmanned aerial vehicles (UAVs, drones) are not just a technological achievement based on modern ideas of artificial intelligence; they also provide a sustainable solution for green technologies in logistics, transport, and material handling. In particular, using battery-powered UAVs to transport products can significantly decrease energy and fuel expenses, reduce environmental pollution, and improve the efficiency of clean technologies through improved energy-saving efficiency. We consider the problem of maximizing the average environmental benefit of a fleet of drones given a periodic schedule of tasks performed by the fleet of vehicles. To solve the problem efficiently, we formulate it as an optimization problem on an infinite periodic graph and reduce it to a special type of parametric assignment problem. We exactly solve the problem under consideration in O(n3) time, where n is the number of flights performed by UAVs.
Enhancing Program Synthesis with Large Language Models Using Many-Objective Grammar-Guided Genetic Programming
Authors: Tao Ning , Ventresque Anthony , Nallur Vivek , Saber Takfarinas
Published: July 2024

The ability to automatically generate code, i.e., program synthesis, is one of the most important applications of artificial intelligence (AI). Currently, two AI techniques are leading the way: large language models (LLMs) and genetic programming (GP) methods—each with its strengths and weaknesses. While LLMs have shown success in program synthesis from a task description, they often struggle to generate the correct code due to ambiguity in task specifications, complex programming syntax, and lack of reliability in the generated code. Furthermore, their generative nature limits their ability to fix erroneous code with iterative LLM prompting. Grammar-guided genetic programming (G3P, i.e., one of the top GP methods) has been shown capable of evolving programs that fit a defined Backus–Naur-form (BNF) grammar based on a set of input/output tests that help guide the search process while ensuring that the generated code does not include calls to untrustworthy libraries or poorly structured snippets. However, G3P still faces issues generating code for complex tasks. A recent study attempting to combine both approaches (G3P and LLMs) by seeding an LLM-generated program into the initial population of the G3P has shown promising results. However, the approach rapidly loses the seeded information over the evolutionary process, which hinders its performance. In this work, we propose combining an LLM (specifically ChatGPT) with a many-objective G3P (MaOG3P) framework in two parts: (i) provide the LLM-generated code as a seed to the evolutionary process following a grammar-mapping phase that creates an avenue for program evolution and error correction; and (ii) leverage many-objective similarity measures towards the LLM-generated code to guide the search process throughout the evolution. The idea behind using the similarity measures is that the LLM-generated code is likely to be close to the correct fitting code. Our approach compels any generated program to adhere to the BNF grammar, ultimately mitigating security risks and improving code quality. Experiments on a well-known and widely used program synthesis dataset show that our approach successfully improves the synthesis of grammar-fitting code for several tasks.
Design and Test of Discrete Element-Based Separation Roller Potato–Soil Separation Device
Authors: Du Xinwu , Liu Jin , Zhao Yueyun , Zhang Chenglin , Zhang Xiaoxuan , Wang Yanshuai
Published: July 2024

To address the problems of low bright rates and high rates of potato injuries, a left and right-hand rotation combination of potato–soil separation devices was developed. Its overall structure and working principle were introduced. A Texture Analyzer and pressure sensor were used to measure the force threshold of different varieties of potatoes. A discrete element model of separation rollers and potatoes was established. The collision characteristics of potatoes were analyzed using the device inclination angle, rotational speed, and the center distance of the separation rollers as test factors. A field trial was carried out to optimize the best combination of factors by taking the rate of injured potatoes, bright potatoes, and skin-breaking rate as the test indexes. The force threshold for skin-breaking injury in potatoes was found to be 190–195 N. When the inclination angle of the device was 6°, the rotation speed of the separation roller was 100 r/min, and the distance between the centers of the separation rollers was 79 mm. The rate of injury was 1.25%, the rate of bright potatoes was 99.01%, and the rate of skin-breaking was 1.58%. When the inclination angle of the device was 8°, the rotational speed of the separating roller was 80 r/min, and the center distance of the separating roller was 79 mm, the rate of injured potato was 1.43%, the rate of bright potato was 98.64%, and the rate of broken skin was 1.77%. This paper offers an optimized reference for the effectual removal of sticky soil.
Bioindicators for Assessing Soil Quality in Ecuador’s Jun Jun Micro-Watershed
Authors: Meneses Quelal Orlando , Yánez Yánez Wilfrido , Aranguren Carrera Jesús
Published: July 2024

The evaluation of soil quality in different altitudinal gradients, with vegetative and non-vegetative subareas, is crucial for proper soil functioning and optimal crop growth, thus contributing to the sustainability of agroecosystems. Although the altitudinal gradient significantly influences soil quality, the ability to predict this quality, expressed through an index, in soils with and without vegetative cover, is still insufficiently explored. This study employed the simple additive index (SQI) method to evaluate soil quality in Ecuador’s Jun Jun micro-watershed, Tungurahua region. Three altitude categories (<2800, 2800–2900, >2900 masl) were investigated, with 24 soil samples collected across both vegetated and non-vegetated areas. The indicators used included chemical and biological parameters such as soil organic carbon (OC), earthworm density (WD), earthworm biomass (WB), organic matter (OM), pH, and total nitrogen (TN). The results revealed that in areas with altitudinal gradients below 2800 masl, the soil quality index values were higher compared to other altitudes. In vegetated areas, a decrease in index values was observed as the altitudinal gradient increased, indicating a deterioration in soil quality with increasing altitude. These findings are significant in providing a quantitative assessment of the effects of altitudinal gradient and vegetative cover influence on soil quality.
The Target Therapy Hyperbole: “KRAS (p.G12C)”—The Simplification of a Complex Biological Problem
Authors: Chetta Massimiliano , Basile Anna , Tarsitano Marina , Rivieccio Maria , Oro Maria , Capitanio Nazzareno , Bukvic Nenad , Priolo Manuela , Rosati Alessandra
Published: July 2024

Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) gene variations are linked to the development of numerous cancers, including non-small cell lung cancer (NSCLC), colorectal cancer (CRC), and pancreatic ductal adenocarcinoma (PDAC). The lack of typical drug-binding sites has long hampered the discovery of therapeutic drugs targeting KRAS. Since “CodeBreaK 100” demonstrated Sotorasib’s early safety and efficacy and led to its approval, especially in the treatment of non-small cell lung cancer (NSCLC), the subsequent identification of specific inhibitors for the p.G12C mutation has offered hope. However, the CodeBreaK 200 study found no significant difference in overall survival (OS) between patients treated with Docetaxel and Sotorasib (AMG 510), adding another degree of complexity to this ongoing challenge. The current study compares the three-dimensional structures of the two major KRAS isoforms, KRAS4A and KRAS4B. It also investigates the probable structural changes caused by the three major mutations (p.G12C, p.G12D, and p.G12V) within Sotorasib’s pocket domain. The computational analysis demonstrates that the wild-type and mutant isoforms have distinct aggregation propensities, resulting in the creation of alternate oligomeric configurations. This study highlights the increased complexity of the biological issue of using KRAS as a therapeutic target. The present study stresses the need for a better understanding of the structural dynamics of KRAS and its mutations to design more effective therapeutic approaches. It also emphasizes the potential of computational approaches to shed light on the complicated molecular pathways that drive KRAS-mediated oncogenesis. This study adds to the ongoing efforts to address the therapeutic hurdles presented by KRAS in cancer treatment.
Characteristics and Outcomes of Colorectal Cancer Patients Cared for by the Multidisciplinary Team in the Reggio Emilia Province, Italy
Authors: Mangone Lucia , Marinelli Francesco , Bisceglia Isabella , Braghiroli Maria Barbara , Banzi Maria , Damato Angela , Iori Veronica , Pinto Carmine , Cerullo Loredana , Pellegri Carlotta , Zizzo Maurizio , Morabito Fortunato , Neri Antonino , Giorgi Rossi Paolo
Published: July 2024

Colorectal cancer emerged as the third most prevalent malignancy worldwide, affecting nearly 2 million individuals in the year 2020. This study elucidates the pivotal role of a multidisciplinary team (MDT) in influencing the prognosis, as measured by relative survival rates, depending upon the stage and age. Cases recorded in an Italian Cancer Registry between 2017 and 2018 were included. Relative survival was reported at 1 and 3 years after diagnosis comparing MDT vs. no-MDT approaches. During the study period, 605 CRCs were recorded while 361 (59.7%) were taken care of by an MDT. Compared to no-MDT, MDT patients were younger with earlier stages and received more surgery. One year after diagnosis, survival was 78.7% (90% in MDT vs. 62% in no-MDT); stratifying by stage, in the MDT group there was no survival advantage for stage I (97.2% vs. 89.9%) and II (96.8% vs. 89.4%), but an advantage was observed for stage III (86.4% vs. 56.9%) and stage IV (63.7% vs. 27.4%). Similar values were observed at 3 years where a marked advantage was observed for stages III (69.9% vs. 35.1%) and IV (29.2% vs. 5.1%). The univariable analysis confirmed an excess risk in the no-MDT group (HR 2.6; 95% CI 2.0–3.3), also confirmed in the multivariable regression analysis (HR 2.0; 95% CI 1.5–2.5). Despite the increase in the number of MDT patients in 2018 (from 50% to 69%), this does not correspond to an improvement in outcome.
The Paradox of Ribosomal Insufficiency Coupled with Increased Cancer: Shifting the Perspective from the Cancer Cell to the Microenvironment
Authors: D’Andrea Giacomo , Deroma Giorgia , Miluzio Annarita , Biffo Stefano
Published: July 2024

Ribosomopathies are defined as inherited diseases in which ribosomal factors are mutated. In general, they present multiorgan symptoms. In spite of the fact that in cellular models, ribosomal insufficiency leads to a reduced rate of oncogenic transformation, patients affected by ribosomopathies present a paradoxical increase in cancer incidence. Several hypotheses that explain this paradox have been formulated, mostly on the assumption that altered ribosomes in a stem cell induce compensatory changes that lead to a cancer cell. For instance, the lack of a specific ribosomal protein can lead to the generation of an abnormal ribosome, an oncoribosome, that itself leads to altered translation and increased tumorigenesis. Alternatively, the presence of ribosomal stress may induce compensatory proliferation that in turns selects the loss of tumor suppressors such as p53. However, modern views on cancer have shifted the focus from the cancer cell to the tumor microenvironment. In particular, it is evident that human lymphocytes are able to eliminate mutant cells and contribute to the maintenance of cancer-free tissues. Indeed, many tumors develop in conditions of reduced immune surveillance. In this review, we summarize the current evidence and attempt to explain cancer and ribosomopathies from the perspective of the microenvironment.
Pre-Existing Immunity Predicts Response to First-Line Immunotherapy in Non-Small Cell Lung Cancer Patients
Authors: Xagara Anastasia , Goulielmaki Maria , Fortis Sotirios P. , Kokkalis Alexandros , Chantzara Evangelia , Christodoulopoulos George , Samaras Ioannis , Saloustros Emmanouil , Tsapakidis Konstantinos , Papadopoulos Vasileios , Pateras Ioannis S. , Georgoulias Vasilis , Baxevanis Constantin N. , Kotsakis Athanasios
Published: July 2024

T-cell-mediated anti-tumoral responses may have significant clinical relevance as a biomarker for response to immunotherapy. The value of peripheral blood pre-existing tumor antigen-specific T cells (PreI+) as a predictive immunotherapy biomarker in NSCLC patients was investigated, along with the frequency of various circulating immune cells. Fifty-two treatment-naïve, stage III/IV NSCLC patients, treated with front-line immune checkpoint inhibitors (ICI)-containing regimens were enrolled. PreI was calculated as the percentages of CD3+IFNγ+ cells after in vitro co-cultures of PBMCs with peptides against four different Tumor-Associated Antigens (TAA). Immunophenotyping of peripheral blood immune cells was performed using multicolor flow cytometry. PreI+ T cells were detected in 44% of patients. Median overall survival (OS) was significantly higher in PreI+ patients compared to PreI– patients (not reached vs. 321 days, respectively; p = 0.014). PreI+ patients had significantly higher numbers of possible exhausted CD3+CD8+PD-1+ cells and lower percentages of immunosuppressive Tregs compared to PreI− patients. Additionally, patients with PreI+ and low numbers of peripheral blood M-MDSCs had a significant survival advantage compared to the rest of the patients. Thus, combining pre-existing tumor antigen-specific immunity before initiation of ICI in NSCLC patients with selected immune-suppressive cells could identify patients who have a favorable clinical outcome when treated with ICI-containing regimens.
Dutch Translation of the Yost Self-Report Lower Extremity Lymphedema Screening Questionnaire in Women
Authors: Decorte Tina , Van Calster Charlotte , Randon Caren , Van Besien Vickie , Ketels Mathilde , Vanden Bossche Luc , De Schryver Mieke , Monten Chris
Published: July 2024

Background: Validated questionnaires of self-reported LEL are important in the assessment and diagnosis of LEL. The aim of this study was to validate and translate a Dutch version of the screening questionnaire, the LELSQ developed and validated by Yost et al. Methods: We tested the questionnaire on a group of healthy women and a group of patients diagnosed with LEL. The translation was carried out using the forward and backward method from English to Dutch. Statistical analyses: SPSS (IBM corp, Armonk, New York, NY, USA) version 28.0.1.0 (001) was used for statistical analysis in the process of validation. The internal consistency was assessed by determining Cronbach’s alpha. The reliability was tested by test–retest reliability. The validity was determined by ROC analysis, and content and face validity were evaluated. Results: The internal consistency score in both groups had a strong value (0.83 to 0.90). The test–retest reliability was also strong in both groups. Face and content validity showed the LELSQ is an easy, understandable questionnaire that is not too time-consuming in the early detection of LEL. The ROC analysis showed an AUC value of 0.93, indicating strong validity. Conclusions: The validated Dutch translation showed high values for internal consistency, test–retest reliability, and validity, which allows us to implement the questionnaire in the early detection of LEL after gynecological cancer treatment.