bluuebunny/crossref_metadata_2025 huggingface dataset:
Improving the Salt Tolerance of “Old Limachino Tomato” by Using a New Salt-Tolerant Rootstock
Authors: Martínez Juan-Pablo , Fuentes Raúl , Badilla Danitza , Rosales Camila , Alfaro-Quezada Juan Felipe , Correa Francisco , Lizana Carolina , Sagredo Boris , Quinet Muriel , Lutts Stanley
Published: July 2024

Salinity is a major constraint limiting the yield of tomatoes. However, grafting strategies may help to overcome the salt toxicity of this important horticultural species if appropriate rootstocks are identified. The present study aimed to test a new rootstock, JUPAFORT1, obtained by crossing the glycophyte Solanum lycopersicum (cv. Poncho Negro) with the halophyte wild-related species Solanum chilense to improve the salinity tolerance of the Chilean tomato landrace Old Limachino Tomato (OLT). Intact OLT plants were exposed to 0, 80, or 160 mM of NaCl for 21 days at the vegetative stage and compared with self-grafted (L/L) and Limachino plants grafted on JUPAFORT1 rootstock (L/R) under a completely randomized design. JUPAFORT1 increased OLT scion vigor in the absence of salt but did not significantly increase fresh weight under stress conditions. However, JUPAFORT1 confers to the scion an anisohydric behavior contrasting with the isohydric behavior of L and L/L plants as indicated by measurements of stomatal conductance; L/R plants were able to maintain their metabolic status despite a slight decrease in the leaf’s relative water content. JUPAFORT1 rootstock also enabled the maintenance of photosynthetic pigment concentrations in the scion in contrast to L and L/L plants, which exhibited a decrease in photosynthetic pigments under stress conditions. L/R plants encountered oxidative stress at the highest stress intensity (160 mM of NaCl) only, while L and L/L plants suffered from oxidative damage at a lower dose (80 mM of NaCl). L/R plants behaved as includer plants and did not sequester Na+ in the root system, in contrast to L and L/L, which behaved as excluder plants retaining Na+ in the root system to avoid its translocation to the shoots. The expression of genes coding for ion transporters (HKT1.1, HKT1.2, LKT1, SKOR, SOS2, and SOS3) in the root system was not modified by salinity in L/R. In contrast, their expression varied in response to salinity in L and L/L. Overall, L/R plants exhibited higher physiological stability than L/L or L plants in response to an increasing NaCl dose and did not require additional energy investment to trigger an adaptative response to salinity. This suggests that the constitutive salinity tolerance of the halophyte S. chilense was maintained in the interspecific rootstock. JUPAFORT1 issued from S. lycopersicum x S. chilense may thus improve salt-stress resilience in OLT tomatoes. Additional studies are required to identify the molecular components involved in the root-to-shoot signaling pathway in this promising material.
Monitoring Slope Movement and Soil Hydrologic Behavior Using IoT and AI Technologies: A Systematic Review
Authors: Alam Md Jobair Bin , Manzano Luis Salgado , Debnath Rahul , Ahmed Ahmed Abdelmoamen
Published: July 2024

Landslides or slope failure pose a significant risk to human lives and infrastructures. The stability of slopes is controlled by various hydrological processes such as rainfall infiltration, soil water dynamics, and unsaturated soil behavior. Accordingly, soil hydrological monitoring and tracking the displacement of slopes become crucial to mitigate such risks by issuing early warnings to the respective authorities. In this context, there have been advancements in monitoring critical soil hydrological parameters and slope movement to ensure potential causative slope failure hazards are identified and mitigated before they escalate into disasters. With the advent of the Internet of Things (IoT), artificial intelligence, and high-speed internet, the potential to use such technologies for remotely monitoring soil hydrological parameters and slope movement is becoming increasingly important. This paper provides an overview of existing hydrological monitoring systems using IoT and AI technologies, including soil sampling, deploying on-site sensors such as capacitance, thermal dissipation, Time-Domain Reflectometers (TDRs), geophysical applications, etc. In addition, we review and compare the traditional slope movement detection systems, including topographic surveys for sophisticated applications such as terrestrial laser scanners, extensometers, tensiometers, inclinometers, GPS, synthetic aperture radar (SAR), LiDAR, and Unmanned Aerial Vehicles (UAVs). Finally, this interdisciplinary research from both Geotechnical Engineering and Computer Science perspectives provides a comprehensive state-of-the-art review of the different methodologies and solutions for monitoring landslides and slope failures, along with key challenges and prospects for potential future study.
Secular Contrasts in Physical Fitness and Athletic Skills in Japanese Elementary School Students (11-Year-Olds)
Authors: Yogi Yukitomo , Ishikawa Yasunari , Takahashi Shuichi
Published: July 2024

Since 1964, Japan has been conducting a wide fitness and athletic skills evaluation among 2000–3000 school children. This study used data made public by the Japan Sports Agency from four events that have continuously been evaluated from 1964 to 2021—grip strength, 50 meter dash, repetitive side jumps, and softball throw—to depict a secular trend over the course of 58 years. This is to statistically categorize these into generations, establishing secular contrast by identifying high and low scores for each event within the categorized generations, with the intent to examine the factors embedded within the background. The generations that had the highest average across all four events were the measurements made in 1970–1993 for males and in 1972–1994 for females. Changes made to the curriculum guidelines may have played a role in the differences found within each event. The goal of physical education and its syllabus and assigned hours in the curriculum guidelines are revised approximately every 10 years to meet social demand. Changes in the social and living environments surrounding children may be exhibited in the form of secular contrast in the measured physical fitness and athletic skills.
Recovering from COVID-19 (ReCOV): Feasibility of an Allied-Health-Led Multidisciplinary Outpatient Rehabilitation Service for People with Long COVID
Authors: D’Souza Aruska N. , Merrett Myvanwy , Griffin Hilda , Tran-Duy An , Struck Carly , Fazio Timothy N. , Juj Genevieve , Granger Catherine L. , Peiris Casey L.
Published: July 2024

Background: A multidisciplinary approach is required for the management of long COVID. The aim of this study was to determine the feasibility (demand, implementation, practicality, acceptability, and limited efficacy) of an allied-health-led multidisciplinary symptom management service (ReCOV) for long COVID. Methods: A single-group observational cohort feasibility study was conducted to determine demand (referrals), acceptability (survey), implementation (waitlist times, health professions seen), practicality (adverse events), and limited efficacy (admission and discharge scores from the World Health Organization Disability Assessment Scale, Brief Illness Perception Questionnaire (BIPQ), Patient Health Questionnaire, and EuroQol 5D-5L). Data are presented as median [interquartile range] or count (percentage). Results: During the study, 143 participants (aged 42.00 [32.00–51.00] years, 68% women) participated in ReCOV. Participants were waitlisted for 3.86 [2.14–9.86] weeks and engaged with 5.00 [3.00–6.00] different health professionals. No adverse events occurred. The thematic analysis revealed that ReCOV was helpful but did not fully meet the needs of all participants. Limited efficacy testing indicated that participants had improved understanding and control (p < 0.001) of symptoms (BIPQ) and a small improvement in EQ VAS score (median difference 5.50 points [0.00–25.00], p = 0.004]). Conclusions: A multidisciplinary service was safe and mostly acceptable to participants for the management of long COVID. Further research should investigate the clinical and cost effectiveness of such a service, including optimal service duration and patient outcomes.
Prevalence and Determinants of Changes in Physical Activity and Sedentary Behavior during and after the COVID-19 Pandemic: A Swedish Repeated Cross-Sectional Study
Authors: Kerstis Birgitta , Elvén Maria , Nilsson Kent W. , von Heideken Wågert Petra , Stier Jonas , Dahlen Micael , Lindberg Daniel
Published: July 2024

Physical activity (PA) and sedentary behavior (SB) changed during the COVID-19 pandemic; hence, this study examined PA and SB at four time points between December 2019 and December 2022. The participants’ PA decreased during the pandemic and did not recover afterwards. Among women, PA increased slightly in 2022 but not at all in men. From 2019 to 2020, SB increased and then decreased to near the pre-pandemic level in both sexes. Regarding age, PA decreased in the oldest age group (65–79 years) across all time points, while SB increased in all age groups during 2019–2020 and then returned close to pre-pandemic levels among the two middle age groups (30–64 years), but not among the youngest and oldest groups. Considering occupation, PA decreased from 2020 to December 2022 among retired and “other” participants, while SB decreased among nonmanual workers and retired participants. The regression models associated better self-reported health, male sex, and those born overseas with higher PA. Higher age, better self-reported health, poor education, and later survey time points were associated with lower SB. These findings highlight the need to return PA and SB to at least pre-pandemic levels and that subgroups may need different interventions.
Psychological Distress and Associated Factors among Technical Intern Trainees in Japan: A Cross-Sectional Study
Authors: Khin Ei Thinzar , Takeda Yuko , Iwata Kazunari , Nishimoto Shuhei
Published: July 2024

Japan is experiencing significant demographic shifts due to an aging and declining population. In 1993, the Japanese Government introduced the Technical Intern Training Program (TITP) to accept foreign national workers. While the number of technical intern trainees under this program has constantly increased, many of them face challenges in their daily lives, such as stress, health insecurities and limited access to healthcare. Therefore, we conducted a cross-sectional study to assess the mental well-being of technical intern trainees, focusing on psychological distress and its related factors. This study included 304 technical intern trainees from 12 prefectures in Japan, and was conducted from August 2021 to October 2021. We used self-administered questionnaires in the participants’ native languages to assess their sociodemographic conditions, health-related conditions such as health insecurities and healthcare-seeking behaviors, and psychological distress. The K6 Kessler Psychological Distress Scale was applied to evaluate the levels of psychological distress. Among the participants, 26.3% had moderate psychological distress and 2.3% had severe psychological distress. In addition, about 15% of the participants reported health insecurities and did not see a doctor despite wanting to. The multivariate model of logistic regression revealed significant associations between psychological distress and female gender (AOR 2.62, 95% CI 1.12–6.12), nationality other than Vietnamese (AOR 4.85, 95% CI 2.60–9.07), tough financial conditions (AOR 2.23, 95% CI 1.18–4.19), experiencing health insecurity (AOR 2.21, 95% CI 1.04–4.66) and the health behavior of refraining from seeking medical care (AOR 3.06, 95% CI 1.49–6.30). The top reasons for refraining from seeking medical care were the participants’ limited knowledge about the healthcare system in Japan and their worries about medical bills. These findings highlight the necessity to extend mental health support services, including counseling services, and share information about Japan’s healthcare system to supply medical services to the targeted technical intern trainee population.
Distinct Characteristic Binding Modes of Benzofuran Core Inhibitors to Diverse Genotypes of Hepatitis C Virus NS5B Polymerase: A Molecular Simulation Study
Authors: Han Di , Zhao Fang , Chen Yifan , Xue Yiwei , Bao Ke , Chang Yuxiao , Lu Jiarui , Wang Meiting , Liu Taigang , Gao Qinghe , Cui Wei , Xu Yongtao
Published: July 2024

The benzofuran core inhibitors HCV-796, BMS-929075, MK-8876, compound 2, and compound 9B exhibit good pan-genotypic activity against various genotypes of NS5B polymerase. To elucidate their mechanism of action, multiple molecular simulation methods were used to investigate the complex systems of these inhibitors binding to GT1a, 1b, 2a, and 2b NS5B polymerases. The calculation results indicated that these five inhibitors can not only interact with the residues in the palm II subdomain of NS5B polymerase, but also with the residues in the palm I subdomain or the palm I/III overlap region. Interestingly, the binding of inhibitors with longer substituents at the C5 position (BMS-929075, MK-8876, compound 2, and compound 9B) to the GT1a and 2b NS5B polymerases exhibits different binding patterns compared to the binding to the GT1b and 2a NS5B polymerases. The interactions between the para-fluorophenyl groups at the C2 positions of the inhibitors and the residues at the binding pockets, together with the interactions between the substituents at the C5 positions and the residues at the reverse β-fold (residues 441–456), play a key role in recognition and the induction of the binding. The relevant studies could provide valuable information for further research and development of novel anti-HCV benzofuran core pan-genotypic inhibitors.
Multifunctional Sr,Mg-Doped Mesoporous Bioactive Glass Nanoparticles for Simultaneous Bone Regeneration and Drug Delivery
Authors: Matic Tamara , Daou Farah , Cochis Andrea , Barac Nemanja , Ugrinovic Vukasin , Rimondini Lia , Veljovic Djordje
Published: July 2024

Mesoporous bioactive glass nanoparticles (MBGNs) doped with therapeutical ions present multifunctional systems that enable a synergistic outcome through the dual delivery of drugs and ions. The aim of this study was to evaluate influence of co-doping with strontium and magnesium ions (SrMg-MBGNs) on the properties of MBGNs. A modified microemulsion-assisted sol–gel synthesis was used to obtain particles, and their physicochemical properties, bioactivity, and drug-loading/release ability were evaluated. Indirect biological assays using 2D and 3D cell culture models on human bone marrow-derived mesenchymal stem cells (hBM-MSCs) and endothelial EA.hy926 cells, respectively, were used to determine biocompatibility of MBGNs, their influence on alkaline phosphatase (ALP) production, calcium deposition, and cytoskeletal organization. Results showed that Sr,Mg-doping increased pore volume and solubility, and changed the mesoporous structure from worm-like to radial–dendritic, which led to a slightly accelerated drug release compared to pristine MBGNs. Biological assays confirmed that particles are biocompatible, and have ability to slightly induce ALP production and calcium deposition of hBM-MSCs, as well as to significantly improve the proliferation of EA.hy926 compared to biochemical stimulation via vascular endothelial growth factor (VEGF) administration or regular media. Fluorescence staining revealed that SrMg-MBGNs had a similar effect on EA.hy926 cytoskeletal organization to the VEGF group. In conclusion, Sr,Mg-MBGNs might be considered promising biomaterial for biomedical applications.
Abiotic Stresses in Plants: From Molecules to Environment
Authors: Bartas Martin
Published: July 2024

Plants face several challenges during their growth and development, including environmental factors (mainly abiotic ones), that can lead to/induce oxidative stress—specifically, adverse temperatures (both hot and cold), drought, salinity, radiation, nutrient deficiency (or excess), toxic metals, waterlogging, air pollution, and mechanical stimuli [...]
The Regulation of Frontal Cortex Cholesterol Metabolism Abnormalities by NR3C1/NRIP1/NR1H2 Is Involved in the Occurrence of Stress-Induced Depression
Authors: Shi Rui , Li Yingmin , Zhu Weihao , Xin Hongjian , Yang Huihuang , Feng Xiaowei , Wang Zhen , Li Shujin , Cong Bin , Shi Weibo
Published: July 2024

Stress-induced alterations in central neuron metabolism and function are crucial contributors to depression onset. However, the metabolic dysfunctions of the neurons associated with depression and specific molecular mechanisms remain unclear. This study initially analyzed the relationship between cholesterol and depression using the NHANES database. We then induced depressive-like behaviors in mice via restraint stress. Applying bioinformatics, pathology, and molecular biology, we observed the pathological characteristics of brain cholesterol homeostasis and investigated the regulatory mechanisms of brain cholesterol metabolism disorders. Through the NHANES database, we initially confirmed a significant correlation between cholesterol metabolism abnormalities and depression. Furthermore, based on successful stress mouse model establishment, we discovered the number of cholesterol-related DEGs significantly increased in the brain due to stress, and exhibited regional heterogeneity. Further investigation of the frontal cortex, a brain region closely related to depression, revealed stress caused significant disruption to key genes related to cholesterol metabolism, including HMGCR, CYP46A1, ACAT1, APOE, ABCA1, and LDLR, leading to an increase in total cholesterol content and a significant decrease in synaptic proteins PSD-95 and SYN. This indicates cholesterol metabolism affects neuronal synaptic plasticity and is associated with stress-induced depressive-like behavior in mice. Adeno-associated virus interference with NR3C1 in the prefrontal cortex of mice subjected to short-term stress resulted in reduced protein levels of NRIP1, NR1H2, ABCA1, and total cholesterol content. At the same time, it increased synaptic proteins PSD95 and SYN, effectively alleviating depressive-like behavior. Therefore, these results suggest that short-term stress may induce cholesterol metabolism disorders by activating the NR3C1/NRIP1/NR1H2 signaling pathway. This impairs neuronal synaptic plasticity and consequently participates in depressive-like behavior in mice. These findings suggest that abnormal cholesterol metabolism in the brain induced by stress is a significant contributor to depression onset.
Anomaly Detection in Kuwait Construction Market Data Using Autoencoder Neural Networks
Authors: Al-Sabah Basma , Anbarjafari Gholamreza
Published: July 2024

In the ambitiously evolving construction industry of Kuwait, characterised by its vision 2035 and rapid technological integration, there exists a pressing need for advanced analytical frameworks. The pressing need for advanced analytical frameworks in the Kuwait Construction Market arises from the necessity to identify inefficiencies, predict market trends, and enhance decision-making processes. For instance, these frameworks can be used to detect anomalies in investment patterns, forecast the impact of economic changes on project timelines, and optimise resource allocation by analysing labour and material supply data. By leveraging deep learning techniques, such as autoencoder neural networks, stakeholders can gain deeper insights into the market’s complexities and improve strategic planning and operational efficiency. This research paper introduces a deep learning approach utilising an autoencoder neural network to analyse the complexities of the Kuwait Construction Market and identify data irregularities. The construction sector’s significant investment influx and project expansion make it an ideal candidate for deploying sophisticated analytical techniques to detect anomalous patterns indicating inefficiencies or unveiling potential opportunities. Our approach leverages the capabilities of autoencoder architectures to delve into and understand the prevalent patterns in market behaviours. This analysis involves training the autoencoder on historical market data to learn the normal patterns and subsequently using it to identify deviations from these learned patterns. This allows for the detection of anomalies that may lead to operational or financial consequences. We elucidate the mathematical foundations of autoencoders, highlighting their proficiency in managing the complex, multidimensional data typical of the construction industry. Through training on an extensive dataset—comprising variables like market sizes, investment distributions, and project completions—our model demonstrates its ability to pinpoint subtle yet significant anomalies. The outcomes of this study enhance our understanding of deep learning’s pivotal role in construction and building management. Empirically, the model detected anomalies in transaction volumes of lands and houses, highlighting unusual spikes that correlate with specific market activities. These findings demonstrate the autoencoder’s effectiveness in anomaly detection, emphasising its importance in enhancing operational efficiency and strategic planning in the construction industry.
SINNER: A Reward-Sensitive Algorithm for Imbalanced Malware Classification Using Neural Networks with Experience Replay
Authors: Coscia Antonio , Iannacone Andrea , Maci Antonio , Stamerra Alessandro
Published: July 2024

Reports produced by popular malware analysis services showed a disparity in samples available for different malware families. The unequal distribution between such classes can be attributed to several factors, such as technological advances and the application domain that seeks to infect a computer virus. Recent studies have demonstrated the effectiveness of deep learning (DL) algorithms when learning multi-class classification tasks using imbalanced datasets. This can be achieved by updating the learning function such that correct and incorrect predictions performed on the minority class are more rewarded or penalized, respectively. This procedure can be logically implemented by leveraging the deep reinforcement learning (DRL) paradigm through a proper formulation of the Markov decision process (MDP). This paper proposes SINNER, i.e., a DRL-based multi-class classifier that approaches the data imbalance problem at the algorithmic level by exploiting a redesigned reward function, which modifies the traditional MDP model used to learn this task. Based on the experimental results, the proposed formula appears to be successful. In addition, SINNER has been compared to several DL-based models that can handle class skew without relying on data-level techniques. Using three out of four datasets sourced from the existing literature, the proposed model achieved state-of-the-art classification performance.
Electrochemically Active Copper Complexes with Pyridine-Alkoxide Ligands
Authors: Webber Christopher K. , Richardson Erica K. , Dickie Diane A. , Gunnoe T. Brent
Published: July 2024

Pyridine-alkoxide (pyalk) ligands that support transition metals have been studied for their use in electrocatalytic applications. Herein, we used the pyalk proligands diphenyl(pyridin-2-yl)methanol ([H]PhPyalk, L1), 1-(pyren-1-yl)-1-(pyridin-2-yl)ethan-1-ol ([H]PyrPyalk, L2), 1-(pyridine-2-yl)-1-(thiophen-2-yl)ethan-1-ol ([H]ThioPyalk, L3), and 1-(ferrocenyl)-1-(pyridin-2-yl)ethan-1-ol ([H]FePyalk, L4) to synthesize CuII complexes that vary in nuclearity and secondary coordination sphere. Also, the proligand 1-(ferrocenyl)-1-(5-methoxy-pyridin-2-yl)ethan-1-ol ([H]FeOMePyalk, L5) was synthesized with a methoxy substituted pyridine; however, the isolation of a CuII complex ligated by L5 was not possible. Under variable reaction conditions, the pyalk ligands reacted with CuII precursors and formed either mononuclear or dinuclear CuII complexes depending on the amount of ligand added. The resulting complexes were characterized by single crystal X-ray diffraction, elemental analysis, and cyclic voltammetry.
Ablation Parameters Predicting Pulmonary Vein Reconnection after Very High-Power Short-Duration Pulmonary Vein Isolation
Authors: Boga Márton , Orbán Gábor , Salló Zoltán , Nagy Klaudia Vivien , Osztheimer István , Ferencz Arnold Béla , Komlósi Ferenc , Tóth Patrik , Tanai Edit , Perge Péter , Merkely Béla , Gellér László , Szegedi Nándor
Published: July 2024

Background: Recurrences due to discontinuity in ablation lines are substantial after pulmonary vein isolation (PVI) with radiofrequency ablation for atrial fibrillation. Data are scarce regarding the durability predictors for very high-power short-duration (vHPSD, 90 W/4 s) ablation. Methods: A total of 20 patients were enrolled, who underwent 90 W PVI and a mandatory remapping procedure at 3 months. First-pass isolation (FPI) gaps, and acute pulmonary vein reconnection (PVR) sites were identified at the index procedure; and chronic PVR sites were identified at the repeated procedure. We analyzed parameters of ablation points (n = 1357), and evaluated their roles in predicting a composite endpoint of FPI gaps, acute and chronic PVR. Results: In total, 45 initial ablation points corresponding to gaps in the ablation lines were analyzed. Parameters associated with gaps were interlesion distance (ILD), baseline generator impedance, mean current, total charge, and loss of catheter–tissue contact. The optimal ILD cut-off for predicting gaps was 3.5 mm anteriorly, and 4 mm posteriorly. Conclusions: Biophysical characteristics dependent on generator impedance could affect the efficacy of vHPSD PVI. The use of smaller ILDs is required for effective and durable PVI with vHPSD compared to the consensus targets with lower power ablation, and lower ILDs for anterior applications seem necessary compared to posterior points.
An Expert-Based Review on the Relevance and Management of Type 2 Endoleaks Following Endovascular Repair of Ruptured Abdominal Aortic Aneurysms
Authors: Dueppers Philip , D’Oria Mario , Lepidi Sandro , Calvagna Cristiano , Zimmermann Alexander , Kopp Reinhard
Published: July 2024

Ruptured abdominal aortic aneurysms (rAAAs) are life-threatening and require emergent surgical therapy. Endovascular aortic repair for rupture (rEVAR) has become the leading strategy due to its minimal invasive approach with expected lower morbidity and mortality, especially in patients presenting with hemodynamic instability and relevant comorbidities. Following rEVAR, intraoperative angiography or early postinterventional computed tomography angiography have to exclude early type 1 or 3 endoleaks requiring immediate reintervention. Persistent type 2 endoleaks (T2ELs) after rEVAR, in contrast to elective cases, can cause possibly lethal situations due to continuing extravascular blood loss through the remaining aortic aneurysm rupture site. Therefore, early identification of relevant persistent T2ELs associated with continuous bleeding and hemodynamic instability and immediate management is mandatory in the acute postoperative setting following rEVAR. Different techniques and concepts for the occlusion of T2ELs after rEVAR are available, and most of them are also used for relevant T2ELs after elective EVAR. In addition to various interventional embolization procedures for persistent T2ELs, some patients require open surgical occlusion of T2EL-feeding arteries, abdominal compartment decompression or direct surgical patch occlusion of the aneurysm rupture site after rEVAR. So far, in the acute situation of rAAAs, indications for preemptive or intraoperative T2EL embolization during rEVAR have not been established. In the long term, persistent T2ELs after rEVAR can lead to continuous aneurysm expansion with the possible development of secondary proximal type I endoleaks and an increased risk of re-rupture requiring regular follow-up and early consideration for reintervention. To date, only very few studies have investigated T2ELs after rEVAR or compared outcomes with those from elective EVAR regarding the special aspects of persisting T2ELs. This narrative review is intended to present the current knowledge on the incidence, natural history, relevance and strategies for T2EL management after rEVAR.
Phenotypic Plasticity and Cancer: A System Biology Perspective
Authors: Subbalakshmi Ayalur Raghu , Ramisetty Sravani , Mohanty Atish , Pareek Siddhika , Do Dana , Shrestha Sagun , Khan Ajaz , Talwar Neel , Tan Tingting , Vishnubhotla Priya , Singhal Sharad S. , Salgia Ravi , Kulkarni Prakash
Published: July 2024

Epithelial-to-mesenchymal transition (EMT) is a major axis of phenotypic plasticity not only in diseased conditions such as cancer metastasis and fibrosis but also during normal development and wound healing. Yet-another important axis of plasticity with metastatic implications includes the cancer stem cell (CSCs) and non-CSC transitions. However, in both processes, epithelial (E) and mesenchymal (M) phenotypes are not merely binary states. Cancer cells acquire a spectrum of phenotypes with traits, properties, and markers of both E and M phenotypes, giving rise to intermediary hybrid (E/M) phenotypes. E/M cells play an important role in tumor initiation, metastasis, and disease progression in multiple cancers. Furthermore, the hybrid phenotypes also play a major role in causing therapeutic resistance in cancer. Here, we discuss how a systems biology perspective on the problem, which is implicit in the ‘Team Medicine’ approach outlined in the theme of this Special Issue of The Journal of Clinical Medicine and includes an interdisciplinary team of experts, is more likely to shed new light on EMT in cancer and help us to identify novel therapeutics and strategies to target phenotypic plasticity in cancer.
Outcomes of Liver Transplantation with Incidental Intrahepatic Cholangiocarcinoma—Own Experience and a Systematic Review
Authors: Remiszewski Piotr , Topolewski Paweł , Łaski Dariusz , Drobińska Anna
Published: July 2024

Background: Cholangiocarcinoma, the second most common primary liver cancer, is still a contraindication for performing liver transplantation in most patients. Despite various trials being performed in large clinical centers, the results are still not satisfactory. The aim of this study was to present cases from our own cohort and perform a systematic review of the results of liver transplantation in patients with incidental intrahepatic cholangiocarcinoma. Materials and methods: We retrospectively reviewed the records of all patients who underwent liver transplantation and identified two patients with incidental intrahepatic cholangiocarcinoma via histopathological examination of the explanted liver. The results of radiological and biochemical screening performed during liver transplantation, standardized histopathological examination and follow-up data are presented. Additionally, a systematic review of PubMed and Cochrane Reviews based on the PRISMA protocol was performed, yielding 413 similar cases. Results: We present two cases of incidental intrahepatic cholangiocarcinoma found after liver transplantation. The patients were managed according to a standard protocol with no consecutive modification of immunosuppression or chemotherapy. There was no recurrence or mortality. In this systematic review, the mean reported number of lesions ranged between 1 and 2 per patient. A total of 42 recurrences were reported. The percentage of recurrences ranged between 28.6% and 80%. Conclusions: Despite not being a frequent finding, follow-up and further treatment of patients with incidental iCCA should be reported and analyzed. Extra carefulness in screening is advised in patients who are already diagnosed with oncological disease of the liver. In long-term follow-up, recurrence of the disease is rather probable.
Molecular Hydrogen for Outpatients with COVID-19 (Hydro-COVID): A Phase 3 Randomised, Triple-Blinded, Pragmatic, Placebo-Controlled, Multicentre Trial
Authors: Gaboreau Yoann , Milovančev Aleksandra , Rolland Carole , Eychenne Claire , Alcaraz Jean-Pierre , Ihl Cordelia , Mazet Roseline , Boucher François , Vermorel Celine , Ostojic Sergej M. , Borel Jean-Christian , Cinquin Philippe , Bosson Jean-Luc
Published: July 2024

Background. Due to its antioxidant, anti-inflammatory, anti-apoptosis, and anti-fatigue properties, molecular hydrogen (H2) is potentially a novel therapeutic nutrient for patients with coronavirus acute disease 2019 (COVID-19). We determined the efficacy and safety profile of hydrogen-rich water (HRW) to reduce the risk of COVID-19 progression. Methods: We also conducted a phase 3, triple-blind, randomised, placebo-controlled trial to evaluate treatment with HRW initiated within 5 days after the onset of signs or symptoms in primary care patients with mild-to-moderate, laboratory-confirmed COVID-19. Participants were randomised to receive HRW or placebo twice daily for 21 days. The incidence of clinical worsening and adverse events were the primary endpoints. Results: A total of 675 participants were followed up to day 30. HRW was not superior to placebo in preventing clinical worsening at day 14: in H2 group, 46.1% in the H2 group, 43.5% in the placebo group, hazard ratio 1.09, 90% confidence interval [0.90–1.31]. One death was reported at day 30 in the H2 group and two in the placebo group at day 30. Adverse events were reported in 91 (27%) and 89 (26.2%) participants, respectively. Conclusions: HRW taken twice daily from the onset of COVID-19 symptoms for 21 days did not reduce clinical worsening.
Effects of Robotic Postural Stand Training with Epidural Stimulation on Sitting Postural Control in Individuals with Spinal Cord Injury: A Pilot Study
Authors: Rejc Enrico , Zaccaron Simone , Bowersock Collin , Pisolkar Tanvi , Ugiliweneza Beatrice , Forrest Gail F. , Agrawal Sunil , Harkema Susan J. , Angeli Claudia A.
Published: July 2024

(1) Background. High-level spinal cord injury (SCI) disrupts trunk control, leading to an impaired performance of upright postural tasks in sitting and standing. We previously showed that a novel robotic postural stand training with spinal cord epidural stimulation targeted at facilitating standing (Stand-scES) largely improved standing trunk control in individuals with high-level motor complete SCI. Here, we aimed at assessing the effects of robotic postural stand training with Stand-scES on sitting postural control in the same population. (2) Methods. Individuals with cervical (n = 5) or high-thoracic (n = 1) motor complete SCI underwent approximately 80 sessions (1 h/day; 5 days/week) of robotic postural stand training with Stand-scES, which was performed with free hands (i.e., without using handlebars) and included periods of standing with steady trunk control, self-initiated trunk and arm movements, and trunk perturbations. Sitting postural control was assessed on a standard therapy mat, with and without scES targeted at facilitating sitting (Sit-scES), before and after robotic postural stand training. Independent sit time and trunk center of mass (CM) displacement were assessed during a 5 min time window to evaluate steady sitting control. Self-initiated antero-posterior and medial-lateral trunk movements were also attempted from a sitting position, with the goal of covering the largest distance in the respective cardinal directions. Finally, the four Neuromuscular Recovery Scale items focused on sitting trunk control (Sit, Sit-up, Trunk extension in sitting, Reverse sit-up) were assessed. (3) Results. In summary, neither statistically significant differences nor large Effect Size were promoted by robotic postural stand training for the sitting outcomes considered for analysis. (4) Conclusions. The findings of the present study, together with previous observations, may suggest that robotic postural stand training with Stand-scES promoted trunk motor learning that was posture- and/or task-specific and, by itself, was not sufficient to significantly impact sitting postural control.
Corticosteroid Treatment for Leptospirosis: A Systematic Review and Meta-Analysis
Authors: Petakh Pavlo , Oksenych Valentyn , Kamyshnyi Oleksandr
Published: July 2024

Background: Leptospirosis, a zoonotic disease prevalent in tropical regions, often leads to severe complications such as Weil’s disease and acute respiratory distress syndrome (ARDS). This pioneering meta-analysis investigated the role of corticosteroids in treating severe leptospirosis, addressing a critical gap in the current clinical knowledge. Methods: We systematically reviewed studies from PubMed and Scopus, focusing on randomized controlled trials and observational cohort studies involving adult patients diagnosed with leptospirosis. Five studies comprising 279 participants met the inclusion criteria. Results: Although some studies suggest potential benefits, particularly for pulmonary complications, the evidence remains inconclusive due to the limited number of studies and their methodological limitations. Notably, while four of the five reviewed studies indicated a possible positive role of corticosteroids, the single randomized controlled trial showed no significant benefit, highlighting the need for more robust research. Conclusions: While the current evidence provides a basis for potential benefits, it is not sufficient to make definitive clinical recommendations. Further research is essential to clarify the role of corticosteroids in the treatment of severe leptospirosis, with the aim of improving patient outcomes and guiding clinical practices effectively.
Ultrasonic Scalpel vs. Polymeric Clip Laparoscopic Varicocelectomy in Adolescents with Symptomatic Varicocele
Authors: Pogorelić Zenon , Poljak Karlo , Jukić Miro , Vukojević Katarina
Published: July 2024

Background: The aim of this study was to investigate treatment outcomes in adolescents who underwent laparoscopic surgery with an ultrasonic scalpel for symptomatic varicocele compared with adolescents who underwent surgery with a polymer clip. Methods: A total of 270 adolescents with a median age of 16 (interquartile range, IQR 13–17) years were included in the study. Taking into account the laparoscopic varicocelectomy technique used, the patients were divided into two groups. In the first group (n = 151), a polymer clip was used, while in the second group (n = 119), an ultrasonic scalpel was used to resect the spermatic vessels. The primary outcome measure was the effect of the laparoscopic technique used on treatment outcomes (postoperative complications and recurrence rates). Secondary outcomes were the duration of surgery and anesthesia and the length of hospital stay. Results: The duration of the surgical procedure (12 min (IQR 11, 15) versus 15 min (12, 19), p = 0.029) and anesthesia (21.5 min (16, 29.5) versus 28 min (23, 34), p = 0.003) was shorter in the group of adolescents in whom laparoscopic varicocelectomy was performed with an ultrasonic scalpel than in the group in which a polymer clip was used. No statistically significant difference was found between the groups studied in terms of length of hospital stay, recurrence rate (p >0.999), and complications (p = 0.703). There were no cases of testicular atrophy in either group. In the group of patients who underwent laparoscopic varicocelectomy with an ultrasonic scalpel, a slightly higher incidence of hydroceles was found (n = 4, 3.4%) than in the group in which a polymer clip was used (n = 2, 1.3%) (p = 0.410). At six-month follow-up, it was found that the majority of patients showed moderate or significant improvement in the spermogram after laparoscopic varicocelectomy (n = 85, 89.5%). In addition, the subjective discomfort or pain disappeared in the majority of patients (n = 71, 93.4%). The testicular volume increased significantly in 132 adolescents (89.8%). Conclusions: Laparoscopic varicocelectomy with a polymer clip or ultrasonic scalpel is safe and effective in adolescents with symptomatic varicocele. Treatment outcomes after laparoscopic varicocelectomy are the same regardless of whether a polymer clip or an ultrasonic scalpel is used to resect the spermatic vessels. The use of an ultrasonic scalpel for resection of the spermatic vessels shortens the overall duration of surgery and anesthesia.
A Five-Year Retrospective Study from a Single Center on the Location, Presentation, Diagnosis, and Management of 110 Patients with Aneurysms of the Femoral and Popliteal Arteries of the Lower Limb
Authors: Serafin Michał , Łyko-Morawska Dorota , Szostek Julia , Stańczyk Dariusz , Mąka Magdalena , Kania Iga , Kuczmik Wacław
Published: July 2024

Background: Peripheral aneurysms, although known about for centuries, are challenging to monitor due to their asymptomatic nature. Advanced imaging has improved detection, which is crucial for preventing emergent complications. This five-year retrospective study from a single center aimed to evaluate the location, presentation, diagnosis, and management of 110 patients with aneurysms of the femoral and popliteal arteries of the lower limb. Materials and methods: The study included 71 true aneurysms and 39 pseudoaneurysms patients treated between 2018–2023. Treatment methods were based on aneurysm size, atherosclerosis severity, and operation risk. The study assessed patient demographics, surgical details, postoperative complications, and aneurysm characteristics. Results: Acute limb ischemia was more prevalent in true aneurysms (25.4% vs. 7.7%; p = 0.02). Aneurysmectomy was performed more frequently in pseudoaneurysms (87.2% vs. 54.9%; p < 0.001), while endovascular treatment and surgical bypass were more common in true aneurysms (Endovascular: 22.5% vs. 2.6%; p = 0.01; bypass: 21.1% vs. 0%; p < 0.001). Early postoperative complications occurred in 22.7% of patients. The 12-month freedom from reoperations (73.7% vs. 87%; p = 0.07), amputations (97.7% vs. 93.8%; p = 0.2), and graft stenosis (78.7% vs. 86.87%; p = 0.06) showed no significant differences between groups. Conclusions: Lower limb aneurysms often present with non-specific symptoms, leading to late diagnosis and life-threatening complications. Both open and endovascular treatments are feasible, though more research is needed for pseudoaneurysms. Vigilant follow-up is crucial due to potential adverse events, though overall mortality and morbidity remain low.
Image-Based 3D Reconstruction in Laparoscopy: A Review Focusing on the Quantitative Evaluation by Applying the Reconstruction Error
Authors: Göbel Birthe , Reiterer Alexander , Möller Knut
Published: July 2024

Image-based 3D reconstruction enables laparoscopic applications as image-guided navigation and (autonomous) robot-assisted interventions, which require a high accuracy. The review’s purpose is to present the accuracy of different techniques to label the most promising. A systematic literature search with PubMed and google scholar from 2015 to 2023 was applied by following the framework of “Review articles: purpose, process, and structure”. Articles were considered when presenting a quantitative evaluation (root mean squared error and mean absolute error) of the reconstruction error (Euclidean distance between real and reconstructed surface). The search provides 995 articles, which were reduced to 48 articles after applying exclusion criteria. From these, a reconstruction error data set could be generated for the techniques of stereo vision, Shape-from-Motion, Simultaneous Localization and Mapping, deep-learning, and structured light. The reconstruction error varies from below one millimeter to higher than ten millimeters—with deep-learning and Simultaneous Localization and Mapping delivering the best results under intraoperative conditions. The high variance emerges from different experimental conditions. In conclusion, submillimeter accuracy is challenging, but promising image-based 3D reconstruction techniques could be identified. For future research, we recommend computing the reconstruction error for comparison purposes and use ex/in vivo organs as reference objects for realistic experiments.
Ship Autonomous Berthing Strategy Based on Improved Linear-Quadratic Regulator
Authors: Yin Jian , Chen Guoquan , Yang Shenhua , Huang Zeyang , Suo Yongfeng
Published: July 2024

There has been significant interest in the research field of ship automatic navigation, particularly in the area of autonomous berthing. To address the key challenges of path planning and control during ship berthing, we propose an enhanced Linear−Quadratic Regulator (LQR) control approach, reinforced by the Covariance Matrix Adaptation Evolution Strategy (CMA−ES), along with an adaptive berthing strategy decision model. This integrated framework encompasses ship motion control, path planning, and berthing strategy selection to facilitate adaptive and autonomous ship berthing. Initially, a dynamic mathematical model of ship motion is established, taking into account wind and current interference effects. Subsequently, an adaptive environment−aware berthing strategy model is introduced to enable automatic selection of berthing strategies based on spatial relationships between environmental factors and the berth. By utilizing the refined LQR method, autonomous motion control for ship berthing is achieved. To validate the effectiveness of our controller, comprehensive simulation analyses are conducted under varying operating conditions to encompass crucial factors such as large drift angle characteristics of ships, shallow water effects, and bank effects across seven diverse working conditions. The simulation results underscore the robustness of our proposed method in responding to environmental interference while demonstrating its capability to select appropriate berthing strategies based on varying operational scenarios.
Enhancement of Biodegradation and Detoxification of Methylene Blue by Preformed Biofilm of Thermophilic Bacilli on Polypropylene Perforated Balls
Authors: Zammuto Vincenzo , Macrì Angela , Agostino Eleonora , Ruggeri Lorenzo Maria , Caccamo Maria Teresa , Magazù Salvatore , Campos Victor L. , Aguayo Paulina , Guglielmino Salvatore , Gugliandolo Concetta
Published: July 2024

Microbial degradation represents an eco-friendly alternative to traditional physicochemical treatments in removing persistent and toxic environmental pollutants, including synthetic dyes (i.e., methylene blue, MB) employed in different industries. The exploitation of thermophilic bacilli, such as those isolated from the shallow hydrothermal vents of the Eolian Islands (Italy), could provide valuable resources for the treatment of warm, dye-containing wastewater. In this study, we evaluated the ability of preformed biofilms on polypropylene perforated balls (BBs) of fifteen thermophilic bacilli, to decolor, degrade, and detoxify MB in aqueous solutions. Among them, BBs of Bacillus licheniformis B3-15 and Bacillus sp. s7s-1 were able to decolorize MB more than 50% in saline solution (NaCl 2%), incubated in static conditions at 45 °C for 48 h. At optimized initial conditions (10 mg L−1 MB, pH 5.2 for B3-15 or pH 4 for s7s-1), the two strains enhanced their decolorization potential, reaching 96% and 67%, respectively. As indicated by ATR-FTIR spectroscopy, the treatment with BB B3-15 was the most efficient in degrading the Cl–C and –NH groups of MB. This degraded solution was 40% less toxic than undegraded MB, and it has no impact on the bioluminescence of Vibrio harveyi, nor the growth of the marine diatom Phaeodactylum tricornutum. Biofilm formed by strain B3-15 on polypropylene perforated balls could be proposed as a component of bioreactors in the treatment of warm, dye-containing wastewater to concomitantly remediate MB pollution and simultaneously counteract harmful effects in aquatic environments.