bluuebunny/crossref_metadata_2025 huggingface dataset:
Automated Restarting Fast Proximal Gradient Descent Method for Single-View Cone-Beam X-ray Luminescence Computed Tomography Based on Depth Compensation
Authors: Gao Peng , Pu Huangsheng , Liu Tianshuai , Cao Yilin , Li Wangyang , Huang Shien , Li Ruijing , Lu Hongbing , Rong Junyan
Published: January 2024

Single-view cone-beam X-ray luminescence computed tomography (CB-XLCT) has recently gained attention as a highly promising imaging technique that allows for the efficient and rapid three-dimensional visualization of nanophosphor (NP) distributions in small animals. However, the reconstruction performance is hindered by the ill-posed nature of the inverse problem and the effects of depth variation as only a single view is acquired. To tackle this issue, we present a methodology that integrates an automated restarting strategy with depth compensation to achieve reconstruction. The present study employs a fast proximal gradient descent (FPGD) method, incorporating L0 norm regularization, to achieve efficient reconstruction with accelerated convergence. The proposed approach offers the benefit of retrieving neighboring multitarget distributions without the need for CT priors. Additionally, the automated restarting strategy ensures reliable reconstructions without the need for manual intervention. Numerical simulations and physical phantom experiments were conducted using a custom CB-XLCT system to demonstrate the accuracy of the proposed method in resolving adjacent NPs. The results showed that this method had the lowest relative error compared to other few-view techniques. This study signifies a significant progression in the development of practical single-view CB-XLCT for high-resolution 3−D biomedical imaging.
Phanogracilins A–C, New Bibenzochromenones of Crinoid Phanogenia gracilis (Hartlaub, 1890)
Authors: Vasileva Elena A. , Berdyshev Dmitrii V. , Mishchenko Natalia P. , Gerasimenko Andrey V. , Menchinskaya Ekaterina S. , Pislyagin Evgeniy A. , Chingizova Ekaterina A. , Kaluzhskiy Leonid A. , Dautov Salim Sh. , Fedoreyev Sergey A.
Published: January 2024

Three new bibenzochromenones named phanogracilins A–C (1–3) were isolated from the crinoid Phanogenia gracilis. The structure of 1 was established using X-ray crystallography as 5,5′,6,6′,8,8′-hexahydroxy-2,2′-dipropyl-4H,4′H-[7,9′-bibenzo[g]chromene]-4,4′-dione. This allowed us to assign reliably 2D NMR signals for compound 1 and subsequently for its isomer 2 that differed in the connecting position of two benzochromenone moieties (7,10′ instead of 7,9′), and compound for 3 that differed in the length of the aliphatic chain of one of the fragments. Compound 4 was derived from 1 in alkaline conditions, and its structure was elucidated as 5,5′,6′,8,8′-pentahydroxy-2,2′-dipropyl-4H,4′H-[7,9′-bibenzo[g]chromene]-4,4′,6,9-tetraone. Even though compounds 1–4 did not contain stereo centers, they possessed notable optical activity due to sterical hindrances, which limited the internal rotation of two benzochromenone fragments around C(7)–C(9′/10′) bonds. Isolated bibenzochromenones 1–4 were tested for their antiradical, neuroprotective and antimicrobial activities. Compounds 1, 3 and 4 demonstrated significant antiradical properties towards ABTS radicals higher than the positive control trolox. Compounds 1 and 4 exhibited moderate neuroprotective activity, increasing the viability of rotenone-treated Neuro-2a cells at a concentration of 1 µM by 9.8% and 11.8%, respectively. Compounds 1 and 3 at concentrations from 25 to 100 μM dose-dependently inhibited the growth of Gram-positive bacteria S. aureus and yeast-like fungi C. albicans, and they also prevented the formation of their biofilms. Compounds 2 and 4 exhibited low antimicrobial activity.
Pancreatic and Hepatic Injury in COVID-19: A Worse Prognosis in NAFLD Patients?
Authors: Mengual-Moreno Edgardo , Nava Manuel , Manzano Alexander , Ariza Daniela , D’Marco Luis , Castro Ana , Marquina María A. , Hernández Marlon , Corredor-Pereira Carlos , Checa-Ros Ana , Bermúdez Valmore
Published: January 2024

The novel disease produced by SARS-CoV-2 mainly harms the respiratory tract, but it has shown the capacity to affect multiple organs. Epidemiologic evidence supports the relationship between Coronavirus Disease 2019 (COVID-19) and pancreatic and hepatic injury development, identified by alterations in these organ function markers. In this regard, it is important to ascertain how the current prevalence of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) might affect COVID-19 evolution and complications. Although it is not clear how SARS-CoV-2 affects both the pancreas and the liver, a multiplicity of potential pathophysiological mechanisms seem to be implicated; among them, a direct viral-induced injury to the organ involving liver and pancreas ACE2 expression. Additionally, immune system dysregulation, coagulopathies, and drugs used to treat the disease could be key for developing complications associated with the patient’s clinical decline. This review aims to provide an overview of the available epidemiologic evidence regarding developing liver and pancreatic alterations in patients with COVID-19, as well as the possible role that NAFLD/NASH might play in the pathophysiological mechanisms underlying some of the complications associated with COVID-19. This review employed a comprehensive search on PubMed using relevant keywords and filters. From the initial 126 articles, those aligning with the research target were selected and evaluated for their methodologies, findings, and conclusions. It sheds light on the potential pathophysiological mechanisms underlying this relationship. As a result, it emphasises the importance of monitoring pancreatic and hepatic function in individuals affected by COVID-19.
Omentin: A Key Player in Glucose Homeostasis, Atheroprotection, and Anti-Inflammatory Potential for Cardiovascular Health in Obesity and Diabetes
Authors: Sena Cristina M.
Published: January 2024

Omentin is an adipokine mainly produced by visceral fat tissue. It has two isoforms, omentin-1 and omentin-2. Omentin-1 is predominantly secreted by visceral adipose tissue, derived specifically from the stromal vascular fraction cells of white adipose tissue (WAT). Levels of omentin-1 are also expressed in other WAT depots, such as epicardial adipose tissue. Omentin-1 exerts several beneficial effects in glucose homeostasis in obesity and diabetes. In addition, research has suggested that omentin-1 may have atheroprotective (protective against the development of atherosclerosis) and anti-inflammatory effects, potentially contributing to cardiovascular health. This review highlights the potential therapeutic targets of omentin-1 in metabolic disorders.
Aggressive Primary Thyroid Mucoepidermoid Carcinoma with Extensive Pulmonary Involvement
Authors: Mitrache Marius , Terzea Dana , Sirbu Anca , Fica Simona
Published: January 2024

Mucoepidermoid carcinomas (MECs) represent the most common malignant neoplasms of the salivary glands, but they have also been described in other unusual sites. Primary MECs originating in the thyroid gland are exceedingly rare, accounting for less than 0.5% of thyroid tumors. Owing to their low to medium grade, they are usually associated with an indolent evolution and a good long-term prognosis, generally being managed surgically based on the extent of the disease. However, this does not always apply, as primary thyroid MECs may present as metastatic or locally advanced diseases. While several treatment options have been explored in such cases, no consensus currently exists on their optimal treatment plan, and they should be managed in a multidisciplinary fashion. We report the case of a 67-year-old patient with primary MEC of the thyroid, which behaved aggressively, with extensive pulmonary metastasis, ultimately leading to the rapid clinical deterioration and death of the patient.
Targeting Allosteric Site of PCSK9 Enzyme for the Identification of Small Molecule Inhibitors: An In Silico Drug Repurposing Study
Authors: Charbe Nitin Bharat , Zacconi Flavia C. , Kowthavarapu Venkata Krishna , Gupta Churni , Palakurthi Sushesh Srivatsa , Satheeshkumar Rajendran , Lokwani Deepak K. , Tambuwala Murtaza M. , Palakurthi Srinath
Published: January 2024

The primary cause of atherosclerotic cardiovascular disease (ASCVD) is elevated levels of low-density lipoprotein cholesterol (LDL-C). Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a crucial role in this process by binding to the LDL receptor (LDL-R) domain, leading to reduced influx of LDL-C and decreased LDL-R cell surface presentation on hepatocytes, resulting higher circulating levels of LDL-C. As a consequence, PCSK9 has been identified as a crucial target for drug development against dyslipidemia and hypercholesterolemia, aiming to lower plasma LDL-C levels. This research endeavors to identify promising inhibitory candidates that target the allosteric site of PCSK9 through an in silico approach. To start with, the FDA-approved Drug Library from Selleckchem was selected and virtually screened by docking studies using Glide extra-precision (XP) docking mode and Smina software (Version 1.1.2). Subsequently, rescoring of 100 drug compounds showing good average docking scores were performed using Gnina software (Version 1.0) to generate CNN Score and CNN binding affinity. Among the drug compounds, amikacin, bestatin, and natamycin were found to exhibit higher docking scores and CNN affinities against the PCSK9 enzyme. Molecular dynamics simulations further confirmed that these drug molecules established the stable protein–ligand complexes when compared to the apo structure of PCSK9 and the complex with the co-crystallized ligand structure. Moreover, the MM-GBSA calculations revealed binding free energy values ranging from −84.22 to −76.39 kcal/mol, which were found comparable to those obtained for the co-crystallized ligand structure. In conclusion, these identified drug molecules have the potential to serve as inhibitors PCSK9 enzyme and these finding could pave the way for the development of new PCSK9 inhibitory drugs in future in vitro research.
Prevention of Delayed Graft Function in Kidney Transplant Recipients through a Continuous Infusion of the Prostaglandin Analogue Iloprost: A Single-Center Prospective Study
Authors: Veroux Massimiliano , Sanfilippo Floriana , Roscitano Giuseppe , Giambra Martina , Giaquinta Alessia , Riccioli Giordana , Zerbo Domenico , Corona Daniela , Sorbello Massimiliano , Veroux Pierfrancesco
Published: January 2024

Background: Delayed graft function (DGF) is common after kidney transplantation from deceased donors and may significantly affect post-transplant outcomes. This study aimed to evaluate whether an innovative approach, based on the administration of the intravenous prostaglandin analogue iloprost, could be beneficial in reducing the incidence of DGF occurring after kidney transplantation from deceased donors. Methods: This prospective, randomized (1:1), placebo-controlled study enrolled all consecutive patients who received a kidney transplant from a deceased donor from January 2000 to December 2012 and who were treated in the peri-transplant period with the prostaglandin analogue iloprost at 0.27 μg/min through an elastomeric pump (treatment group) or with a placebo (control group). Results: A total of 476 patients were included: DGF was reported in 172 (36.1%) patients in the entire cohort. The multivariate analysis showed that the donor’s age > 70 years (OR 2.50, 95% confidence interval (CI): 1.40–3.05, p < 0.001), cold ischemia time > 24 h (OR 2.60, 95% CI: 1.50–4.51, p < 0.001), the donor’s acute kidney injury (OR 2.71, 95% CI: 1.61–4.52, p = 0.021) and, above all, the recipient’s arterial hypotension (OR 5.06, 95% CI: 2.52–10.1, p < 0.0001) were the strongest risk factors for developing post-transplant DGF. The incidence of DGF was 21.4% in the treatment group and 50.9% in the control group (p < 0.001). Interestingly, among patients who developed DGF, those who received iloprost had a shorter duration of post-transplant DGF (10.5 ± 8.3 vs. 13.4 ± 6.7, days, p = 0.016). Conclusions: This study showed that the use of a continuous infusion of iloprost could safely and effectively reduce the incidence of DGF in recipients of deceased-donor kidneys, allowing a better graft functionality as well as a better graft survival.
Post-Operational Photodynamic Therapy of the Tumor Bed: Comparative Analysis for Cold Knife and Laser Scalpel Resection
Authors: Shakhova Maria , Elagin Vadim , Plekhanov Anton , Khilov Aleksandr , Kurakina Daria , Kamensky Vladislav , Kirillin Mikhail
Published: January 2024

In this paper, we report on a study regarding the efficiency of the post-operational phototherapy of the tumor bed after resection with both a cold knife and a laser scalpel in laboratory mice with CT-26 tumors. Post-operational processing included photodynamic therapy (PDT) with a topically applied chlorin-based photosensitizer (PS), performed at wavelengths of 405 or 660 nm, with a total dose of 150 J/cm2. The selected design of the tumor model yielded zero recurrence in the laser scalpel group and 92% recurrence in the cold knife group without post-processing, confirming the efficiency of the laser scalpel in oncology against the cold knife. The application of PDT after the cold knife resection decreased the recurrence rate to 70% and 42% for the 405 nm and 660 nm procedures, respectively. On the other hand, the application of PDT after the laser scalpel resection induced recurrence rates of 18% and 30%, respectively, for the considered PDT performance wavelengths. The control of the penetration of PS into the tumor bed by fluorescence confocal microscopy indicated the deeper penetration of PS in the case of the cold knife, which presumably provided deeper PDT action, while the low-dose light exposure of deeper tissues without PS, presumably, stimulated tumor recurrence, which was also confirmed by the differences in the recurrence rate in the 405 and 660 nm groups. Irradiation-only light exposures, in all cases, demonstrated higher recurrence rates compared to the corresponding PDT cases. Thus, the PDT processing of the tumor bed after resection could only be recommended for the cold knife treatment and not for the laser scalpel resection, where it could induce tumor recurrence.
Bone Turnover Markers, n-Terminal Propeptide of Type I Procollagen and Tartrate-Resistant Acid Phosphatase Type 5b, for Predicting Castration Resistance in Prostate Cancer
Authors: Kano Hiroshi , Izumi Kouji , Nakagawa Ryunosuke , Toriumi Ren , Aoyama Shuhei , Kamijima Taiki , Makino Tomoyuki , Naito Renato , Iwamoto Hiroaki , Yaegashi Hiroshi , Kawaguchi Shohei , Shigehara Kazuyoshi , Nohara Takahiro , Mizokami Atsushi
Published: January 2024

Bone is a common site of prostate cancer metastasis. Bone turnover markers n-terminal propeptide of type I procollagen (P1NP) and tartrate-resistant acid phosphatase type 5b (TRACP-5b) are highly sensitive to bone remodeling activity. However, their prognostic significance as markers of prostate cancer is unknown. This study retrospectively examined the usefulness of P1NP and TRACP-5b as prognostic biomarkers. Castration-resistant prostate cancer recurrence-free survival (CFS) was estimated using the Kaplan–Meier method. A predictive model for CFS was constructed using multivariate analysis. This study enrolled 255 patients diagnosed with prostate cancer at Kanazawa University Hospital. The median follow-up was 115.1 months. Patients with both high serum P1NP and TRACP-5b levels, defined as having a poor bone turnover category (BTC), had significantly shorter CFS. Multivariate analysis identified Gleason score, metastasis, and BTC poor as predictors for castration resistance in prostate cancer. Using these three factors, a prognostic model was established, categorizing patients into low-risk (no or one factor) and high-risk (two or three factors) groups. In the low-risk group, the median CFS was not reached, contrasting with 19.1 months in the high-risk group (hazard ratio, 32.23, p < 0.001). Combining P1NP and TRACP-5b may better predict castration resistance.
Biomimetic Design of a New Semi-Rigid Spatial Mesh Antenna Reflector
Authors: Xie Hualong , Feng Yuqing , Bi Qunfeng , Ma Xiaofei , Zhao Junfeng
Published: January 2024

The reflective surface accuracy (RSA) of traditional space mesh antennas typically ranges from 0.2 to 6 mmRMS. To improve the RSA, an active control scheme can be employed, although it presents challenges in determining the installation position of the actuator. In this study, we propose a novel design for a semi-rigid cable mesh that combines rigid members and a flexible woven mesh, drawing inspiration from both rigid ribbed antennas and biomimicry. Initially, we investigate the planar mesh topology of spider webs and determine the bionic cable surface’s mesh topology based on the existing hexagonal meshing method, with RSA serving as the evaluation criterion. Subsequently, through motion simulations and careful observation, we establish the offset angle as the key design parameter for the bionic mesh and complete the design of the bionic cable mesh accordingly. Finally, by analyzing the impact of the node quantity on RSA, we determine a layout scheme for the flexible woven mesh with a variable number of nodes, ultimately settling for 26 nodes. Our results demonstrate that the inclusion of numerous rigid components on the bionic cable mesh surface offers viable installation positions for the actuator of the space mesh antenna. The reflector accuracy achieved is 0.196 mmRMS, slightly surpassing the lower limit of reflector accuracy observed in most traditional space-space mesh antennas. This design presents a fresh research perspective on combining active control schemes with reflective surfaces, offering the potential to enhance the RSA of traditional rigid rib antennas to a certain extent.
Sleep in Healthy and Pathological Aging
Authors: Gorgoni Maurizio , De Gennaro Luigi
Published: January 2024

Human sleep physiology is strongly affected by age [...]
Exploring the Effect of Aspect Ratio (H/W) on Thermal Environment in Multiple Climate Zones with Open-Source Data
Authors: Rao Jifa , Zheng Bohong , Li Jiayu
Published: January 2024

For a country with multiple climate zones, analyzing the impacts of urban design in different climate zones is a prerequisite to climate adaptation policies. However, countries advanced in climate adaptation strategies are mostly located in a single climate zone, leading to a lack of research on climate adaptation policies for multiple climate countries. As China is launching the urban zoning management policy, this research takes China as an example to explore a technique to quickly distinguish the impact of urban design in multiple climate zones by combing the open-source data with the Envi-met tool, where the open-source data indicate the data that can be obtained from public platforms such as the internet and Envi-met is a microclimate simulation tool. First, the open street map tool, one of the open-source data, was used to abstract the typical models of each climate city. Then, open-source meteorological data were employed as the boundary conditions for Envi-met simulation. Lastly, after the Envi-met simulation, the impacts of aspect ratio (H/W) on multiple climate indicators in seven climate cities were analyzed with the meteorological interpolation method. The analytical results show that H/W has a stronger ability to regulate the thermal comfort of high latitude cities. In Guangzhou and Changsha, the maximum differences of PET caused by H/W are only 0.61 °C (Changsha) and 0.63 °C (Guangzhou). H/W has the strongest regulating effect on the thermal comfort in Harbin, with the highest value of 8.62 °C. The regulating effects of H/W on outdoor PET in other 4 cities are 4.37 °C in Urumqi, 3.29 °C in Xining, 1.29 °C in Xi’an, and 0.76 °C in Kunming. In addition, H/W mainly affects PET by modifying the radiant temperature. Compared with mean radiant temperature, the effects of H/W on air temperature, relative humidity, and wind speed are negligible. Longitude regulates the occurrence time of the coldest and hottest thermal environments. Among the seven climate zones in China, the difference in appearance time between the coldest and hottest reaches up to 2 h. For the implementation of urban zoning management policy, in China, high latitude cities are encouraged to high H/W to create a comfortable city. Cities whose latitude is less than 30° may not consider the impacts of H/W on thermal comfort. This method of combining open-source data with Envi-met can serve as a reference for other countries that span multiple climate zones. In addition, these results provide a decision-making basis for the management of H/W in different climate cities of China.
Analysis of Cross-Generational Co-Living Space Configuration in Residential Communities—Case Study in China and Italy Based on Space Syntax
Authors: Zhang Dongqing , Setola Nicoletta , Chen Yi
Published: January 2024

In contemporary society, a notable trend of diminishing family sizes has led to an increasing number of elderly individuals living in solitude, often facing the end of life alone. This phenomenon underscores a critical challenge: addressing the pervasive loneliness experienced by many seniors. In response to this pressing issue, the concept of “cross-generational co-living” emerges as a potential solution. By exploring and implementing cross-generational co-living models, this research contributes to the development of more inclusive, supportive, and adaptable environments. The investigation involved an extensive field study and comprehensive data analysis of twenty-four instances of cross-generational co-living spaces in China and Italy. This analysis utilized space syntax as a fundamental theoretical framework, incorporating convex graphical topological relationship extraction and visibility graph analysis models. The outcomes of the study indicate that the configuration of cross-generational co-living spaces include spatial form, type, location, and the proportion of areas. Spaces arranged in a cluster form are most effective in promoting mutual communication. Spatial types and locations characterized by elevated integration values demonstrate a heightened potential for cross-generational communication. Space possessing a higher integration value typically correlates with a reduced ratio of area discreteness. These findings are instrumental in understanding how cultural and societal variances shape the design and utilization of cross-generational co-living spaces. Consequently, this study provides valuable guidelines for improving environments that are essential for advancing the principles of age-friendly design, which aims to enhance the quality of life for the elderly and foster a more harmonious and interconnected society across all generations.
A Data-Mining-Based Novel Approach to Analyze the Impact of the Characteristics of Urban Ventilation Corridors on Cooling Effect
Authors: Shen Xiaohan , Liu Hua , Yang Xinyu , Zhou Xin , An Jingjing , Yan Da
Published: January 2024

The appropriate design of urban ventilation corridors (VCs) can improve the urban thermal environment, thereby reducing urban energy consumption and promoting sustainable urban development. However, existing research lacks a comprehensive grasp of the characteristics of VCs from multiple dimensions and quantitative analysis of its cooling effect. We propose a novel approach based on data mining to comprehensively consider the morphological and environmental characteristics of VCs and explore the correlation between VC characteristics and the cooling effect. Selecting Nanjing as an example, a comprehensive index system was constructed, the cooling effect of the VC was investigated, and the optimal range of VC index with different underlying surface types was obtained. Results revealed that the cooling effect is closely related to the underlying surface, leading to a temperature difference of up to 5.4 °C. The VC cooling range can vary from 13 to 600 m. The recommended optimal parameter intervals for different VCs were determined. Finally, targeted strategies to alleviate the heat island effect were proposed for different underlying surface types. The study output contributes to the design of VCs, which is of great significance in alleviating the urban heat island effect and promoting sustainable development of cities.
Natural Gradient Boosting for Probabilistic Prediction of Soaked CBR Values Using an Explainable Artificial Intelligence Approach
Authors: Díaz Esteban , Spagnoli Giovanni
Published: January 2024

The California bearing ratio (CBR) value of subgrade is the most used parameter for dimensioning flexible and rigid pavements. The test for determining the CBR value is typically conducted under soaked conditions and is costly, labour-intensive, and time-consuming. Machine learning (ML) techniques have been recently implemented in engineering practice to predict the CBR value from the soil index properties with satisfactory results. However, they provide only deterministic predictions, which do not account for the aleatoric uncertainty linked to input variables and the epistemic uncertainty inherent in the model itself. This work addresses this limitation by introducing an ML model based on the natural gradient boosting (NGBoost) algorithm, becoming the first study to estimate the soaked CBR value from this probabilistic perspective. A database of 2130 soaked CBR tests was compiled for this study. The NGBoost model showcased robust predictive performance, establishing itself as a reliable and effective algorithm for predicting the soaked CBR value. Furthermore, it produced probabilistic CBR predictions as probability density functions, facilitating the establishment of reliable confidence intervals, representing a notable improvement compared to conventional deterministic models. Finally, the Shapley additive explanations method was implemented to investigate the interpretability of the proposed model.
Trends in Anti-Tumor Effects of Pseudomonas aeruginosa Mannose-Sensitive-Hemagglutinin (PA-MSHA): An Overview of Positive and Negative Effects
Authors: Bozic Dragica , Živanović Jovana , Živančević Katarina , Baralić Katarina , Đukić-Ćosić Danijela
Published: January 2024

Cancer is a leading cause of death worldwide, for which finding the optimal therapy remains an ongoing challenge. Drug resistance, toxic side effects, and a lack of specificity pose significant difficulties in traditional cancer treatments, leading to suboptimal clinical outcomes and high mortality rates among cancer patients. The need for alternative therapies is crucial, especially for those resistant to conventional methods like chemotherapy and radiotherapy or for patients where surgery is not possible. Over the past decade, a novel approach known as bacteria-mediated cancer therapy has emerged, offering potential solutions to the limitations of conventional treatments. An increasing number of in vitro and in vivo studies suggest that the subtype of highly virulent Pseudomonas aeruginosa bacterium called Pseudomonas aeruginosa mannose-sensitive-hemagglutinin (PA-MSHA) can successfully inhibit the progression of various cancer types, such as breast, lung, and bladder cancer, as well as hepatocellular carcinoma. PA-MSHA inhibits the growth and proliferation of tumor cells and induces their apoptosis. Proposed mechanisms of action include cell-cycle arrest and activation of pro-apoptotic pathways regulated by caspase-9 and caspase-3. Moreover, clinical studies have shown that PA-MSHA improved the effectiveness of chemotherapy and promoted the activation of the immune response in cancer patients without causing severe side effects. Reported adverse reactions were fever, skin irritation, and pain, attributed to the overactivation of the immune response. This review aims to summarize the current knowledge obtained from in vitro, in vivo, and clinical studies available at PubMed, Google Scholar, and ClinicalTrials.gov regarding the use of PA-MSHA in cancer treatment in order to further elucidate its pharmacological and toxicological properties.
Correlation of Increased Soluble Tumor Necrosis Factor Receptor 1 with Mortality and Dependence on Treatment in Non-Small-Cell Lung Cancer Patients: A Longitudinal Cohort Study
Authors: Hassan Lamiaa , Bedir Ahmed , Kraus Frank Bernhard , Ostheimer Christian , Vordermark Dirk , Mikolajczyk Rafael , Seliger Barbara , Medenwald Daniel
Published: January 2024

Background: Tumor necrosis factor (TNF) is a multipotent cytokine involved in inflammation and anti-tumor activity. TNF-α exerts its function upon binding to TNF-receptor 1 (TNF-R1) and TNF-receptor 2 (TNF-R2). This study investigates the relationship of soluble (s) TNF-R1 levels in non-small-cell lung cancer (NSCLC) patients with treatment and overall survival. Methods: In total, 134 NSCLC patients treated at the Medical Faculty of Martin Luther University Halle-Wittenberg between 2017 and 2019 were included in this study. Serum levels of sTNF-R1 were measured via ELISA at baseline and during and after treatment. A linear mixed-effects model was used to assess sTNF-R1 changes over time. Linear regression was applied to investigate the association between clinical characteristics and changes in sTNF-R1. Cox regression models were used to estimate associations with overall mortality. Results: The estimated average sTNFR-1 at baseline was 2091.71 pg/mL, with a change of 6.19 pg/mL per day. Cox models revealed that the individual change in sTNF-R1 was more strongly associated with mortality than its baseline value, especially after adjusting for covariates. Conclusions: This study provides evidence that the individual change in sTNF-R1 levels during and after treatment were associated with the risk of mortality, suggesting the use of the sTNF-R1 trajectory as a prognostic marker.
Is Immunotherapy Beneficial in Patients with Oncogene-Addicted Non-Small Cell Lung Cancers? A Narrative Review
Authors: McMahon David John , McLaughlin Ronan , Naidoo Jarushka
Published: January 2024

Over the past 20 years, there has been a paradigm shift in the care of patients with non-small cell lung cancer (NSCLC), who now have a range of systemic treatment options including targeted therapy, chemotherapy, immunotherapy (ICI), and antibody–drug conjugates (ADCs). A proportion of these cancers have single identifiable alterations in oncogenes that drive their proliferation and cancer progression, known as “oncogene-addiction”. These “driver alterations” are identified in approximately two thirds of patients with lung adenocarcinomas, via next generation sequencing or other orthogonal tests. It was noted in the early clinical development of ICIs that patients with oncogene-addicted NSCLC may have differential responses to ICI. The toxicity signal for patients with oncogene-addicted NSCLC when treated with ICIs also seemed to differ depending on the alteration present and the specific targeted agent used. Developing a greater understanding of the underlying reasons for these clinical observations has become an important area of research in NSCLC. In this review, we analyze the efficacy and safety of ICI according to specific mutations, and consider possible future directions to mitigate safety concerns and improve the outcomes for patients with oncogene-addicted NSCLC.
Salvage Radiotherapy for Relapsed Prostate Cancer after Radical Prostatectomy Is Associated with Normal Life Expectancy
Authors: Lohm Gunnar , Knörnschild Franz , Neumann Konrad , Budach Volker , Schwartz Stefan , Burock Susen , Böhmer Dirk
Published: January 2024

In patients with prostate cancer (PCa), salvage radiotherapy (SRT) for biochemical progression (BP) after radical prostatectomy (RP) improves PCa-specific survival. However, no prospective randomized trials have compared the effect of SRT with untreated patients. In this analysis of 151 patients who received SRT for post-RP BP, we compared their overall survival (OS) with virtual, age-matched controls (n = 151,000) retrieved from government life tables. We also investigated the risk factors associated with BP and OS and compared the prostate-specific antigen (PSA) doubling times (DTs) before and after SRT for patients with BP. The median follow-up was 9.3 years for BP and 17.4 years for OS. The risk factors significantly affecting BP were Gleason score (p < 0.001), pre-SRT PSA (p = 0.003), and negative surgical margins (p = 0.003). None of these risk factors were associated with OS. In 93 patients with BP after SRT, the median PSADT was significantly prolonged compared with pre-SRT values (3.7 vs. 8.3 months, p < 0.001). The OS did not differ between patients and controls (p = 0.112), and life expectancy was similar, likely due to the survival benefit of SRT. The prolonged PSADT after SRT further supports the beneficial role of SRT in this patient population. However, subsequent treatments were not systematically recorded, which may have affected the results.
Lung Transplantation in Patients with Previous or Unknown Oncological Disease: Evaluation of Short- and Long-Term Outcomes
Authors: Catelli Chiara , Faccioli Eleonora , Silvestrin Stefano , Lorenzoni Giulia , Luzzi Luca , Bennett David , Schiavon Marco , Campisi Alessio , Bargagli Elena , Dell’Amore Andrea , Rea Federico
Published: January 2024

The accurate selection of the recipient is a crucial aspect in the field of lung transplantation (LTX), especially if patients were previously affected by oncological disease. The aim of this bicentric retrospective study was to evaluate short- and long-term outcomes in patients with previous oncological disease or unknown neoplasia found on native lungs submitted to LTX, compared to a control group. A total of 433 patients were included in the analysis, 31 with malignancies (Group 1) and 402 without neoplastic disease (Group 2). The two groups were compared in terms of short- and long-term outcomes. Patients in Group 1 were older (median age 58 years vs. 50 years, p = 0.039) and mostly affected by idiopathic pulmonary fibrosis (55% vs. 40% p = 0.002). Even though in Group 1 a lower rate of late post-operative complications was found (23% vs. 45%, p = 0.018), the median overall survival (OS) was lower compared to the control group (10 months vs. 29 months, p = 0.015). LTX represents a viable therapeutic option for patients with end-stage lung disease and a history of neoplastic disease. However, every case should be carefully debated in a multidisciplinary setting, considering oncological (histology, stage, and proper disease free-interval) and clinical factors (patient’s age and comorbidities). A scrupulous post-transplant follow-up is especially mandatory in those cases.
Machine Learning as a Tool for Early Detection: A Focus on Late-Stage Colorectal Cancer across Socioeconomic Spectrums
Authors: Galadima Hadiza , Anson-Dwamena Rexford , Johnson Ashley , Bello Ghalib , Adunlin Georges , Blando James
Published: January 2024

Purpose: To assess the efficacy of various machine learning (ML) algorithms in predicting late-stage colorectal cancer (CRC) diagnoses against the backdrop of socio-economic and regional healthcare disparities. Methods: An innovative theoretical framework was developed to integrate individual- and census tract-level social determinants of health (SDOH) with sociodemographic factors. A comparative analysis of the ML models was conducted using key performance metrics such as AUC-ROC to evaluate their predictive accuracy. Spatio-temporal analysis was used to identify disparities in late-stage CRC diagnosis probabilities. Results: Gradient boosting emerged as the superior model, with the top predictors for late-stage CRC diagnosis being anatomic site, year of diagnosis, age, proximity to superfund sites, and primary payer. Spatio-temporal clusters highlighted geographic areas with a statistically significant high probability of late-stage diagnoses, emphasizing the need for targeted healthcare interventions. Conclusions: This research underlines the potential of ML in enhancing the prognostic predictions in oncology, particularly in CRC. The gradient boosting model, with its robust performance, holds promise for deployment in healthcare systems to aid early detection and formulate localized cancer prevention strategies. The study’s methodology demonstrates a significant step toward utilizing AI in public health to mitigate disparities and improve cancer care outcomes.
Anxiety and Depression as Potential Predictors for Shorter Time to Undergo Initial Surgical Treatment for Papillary Thyroid Cancer
Authors: Vujovic Dragan , Alsen Mathilda , Vasan Vikram , Genden Eric , van Gerwen Maaike
Published: January 2024

(1) Background: A pre-existing psychiatric condition may impact decision making by patients and/or physicians following a thyroid cancer diagnosis, such as potentially electing surgery over active surveillance, thus shortening the time to cancer removal. This is the first study to investigate the association between pre-existing anxiety and/or depression and time to receive surgical treatment for thyroid cancer. (2) Methods: Retrospective data were collected from 652 surgical thyroid cancer patients at our institution from 2018 to 2020. We investigated the time between thyroid cancer diagnosis and surgery, comparing patients with pre-existing anxiety and/or depression to those without. (3) Results: Patients with anxiety, depression, and both anxiety and depression had a significantly shorter time between diagnosis and surgery (51.6, 57, and 57.4 days, respectively) compared to patients without (111.9 days) (p = 0.002, p = 0.004, p = 0.003, respectively). (4) Conclusions: Although little is known about the impact of pre-existing psychiatric conditions in the decision-making process for thyroid cancer surgery, this present study showed that anxiety and/or depression may lead to more immediate surgical interventions. Thus, psychiatric history may be an important factor for physicians to consider when counseling patients with thyroid cancer.
Pro-Fibrotic Effects of CCL18 on Human Lung Fibroblasts Are Mediated via CCR6
Authors: Höhne Kerstin , Wagenknecht Annett , Maier Corinna , Engelhard Peggy , Goldmann Torsten , Schließmann Stephan J. , Plönes Till , Trepel Martin , Eibel Hermann , Müller-Quernheim Joachim , Zissel Gernot
Published: January 2024

Background: Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease of unknown origin, with a median patient survival time of ~3 years after diagnosis without anti-fibrotic therapy. It is characterized by progressive fibrosis indicated by increased collagen deposition and high numbers of fibroblasts in the lung. It has been demonstrated that CCL18 induces collagen and αSMA synthesis in fibroblasts. We aimed to identify the CCL18 receptor responsible for its pro-fibrotic activities. Methods: We used a random phage display library to screen for potential CCL18-binding peptides, demonstrated its expression in human lungs and fibroblast lines by PCR and immunostaining and verified its function in cell lines. Results: We identified CCR6 (CD196) as a CCL18 receptor and found its expression in fibrotic lung tissue and lung fibroblast lines derived from fibrotic lungs, but it was almost absent in control lines and tissue. CCL18 induced receptor internalization in a CCR6-overexpressing cell line. CCR6 blockade in primary human lung fibroblasts reduced CCL18-induced FGF2 release as well as collagen-1 and αSMA expression. Knockdown of CCR6 in a mouse fibroblast cell line abolished the induction of collagen and α-smooth muscle actin expression. Conclusion: Our data indicate that CCL18 triggers pro-fibrotic processes via CCR6, highlighting its role in fibrogenesis.
A Survey of the Union of European Neonatal and Perinatal Societies on Neonatal Respiratory Care in Neonatal Intensive Care Units
Authors: Moretti Corrado , Gizzi Camilla , Gagliardi Luigi , Petrillo Flavia , Ventura Maria Luisa , Trevisanuto Daniele , Lista Gianluca , Dellacà Raffaele L. , Beke Artur , Buonocore Giuseppe , Charitou Antonia , Cucerea Manuela , Filipović-Grčić Boris , Jeckova Nelly Georgieva , Koç Esin , Saldanha Joana , Sanchez-Luna Manuel , Stoniene Dalia , Varendi Heili , Vertecchi Giulia , Mosca Fabio
Published: January 2024

(1) Background: Our survey aimed to gather information on respiratory care in Neonatal Intensive Care Units (NICUs) in the European and Mediterranean region. (2) Methods: Cross-sectional electronic survey. An 89-item questionnaire focusing on the current modes, devices, and strategies employed in neonatal units in the domain of respiratory care was sent to directors/heads of 528 NICUs. The adherence to the “European consensus guidelines on the management of respiratory distress syndrome” was assessed for comparison. (3) Results: The response rate was 75% (397/528 units). In most Delivery Rooms (DRs), full resuscitation is given from 22 to 23 weeks gestational age. A T-piece device with facial masks or short binasal prongs are commonly used for respiratory stabilization. Initial FiO2 is set as per guidelines. Most units use heated humidified gases to prevent heat loss. SpO2 and ECG monitoring are largely performed. Surfactant in the DR is preferentially given through Intubation-Surfactant-Extubation (INSURE) or Less-Invasive-Surfactant-Administration (LISA) techniques. DR caffeine is widespread. In the NICUs, most of the non-invasive modes used are nasal CPAP and nasal intermittent positive-pressure ventilation. Volume-targeted, synchronized intermittent positive-pressure ventilation is the preferred invasive mode to treat acute respiratory distress. Pulmonary recruitment maneuvers are common approaches. During NICU stay, surfactant administration is primarily guided by FiO2 and SpO2/FiO2 ratio, and it is mostly performed through LISA or INSURE. Steroids are used to facilitate extubation and prevent bronchopulmonary dysplasia. (4) Conclusions: Overall, clinical practices are in line with the 2022 European Guidelines, but there are some divergences. These data will allow stakeholders to make comparisons and to identify opportunities for improvement.
Atomoxetine Treatment of Attention Deficit/Hyperactivity Disorder Symptoms in 3–6-Year-Old Children with Autism Spectrum Disorder: A Retrospective Cohort Study
Authors: Alsayouf Hamza A. , Alsarhan Osama , Khreisat Wael , Daoud Azhar
Published: January 2024

Atomoxetine is indicated for the management of attention deficit/hyperactivity disorder (ADHD) in children and adolescents aged 6 to 18 years. Few studies have assessed the safety and tolerability of atomoxetine in younger patients. This retrospective cohort study included 133 children aged 3–6 years who were diagnosed with ADHD comorbid with autism spectrum disorder (ASD). The primary endpoint was the evaluation of the safety profile of atomoxetine. In total, 50 patients (37.6%) experienced adverse events (AEs), which led to treatment discontinuation in 23 patients (17.3%). The most common AEs were gastrointestinal (24.1%), aggression or hostility (12.8%), and increased hyperactivity (9.0%). In the 23 patients who discontinued treatment, all the AEs resolved after treatment ceased. Among the 110 patients who completed at least 6 months’ treatment, atomoxetine titrated to a dose of 1.2–1.8 mg/kg/day appeared to be well tolerated and effective. The Clinical Global Impression—Improvement score improved to 1 (“very much improved”) and 2 (“much improved”) in 62.4% and 20.3% of children, respectively, at their last visit. Overall, atomoxetine appeared to be well tolerated in younger children with comorbid ADHD and ASD. Nevertheless, close patient monitoring remains essential, and the study limitations necessitate caution in generalizing these findings to broader populations. Long-term prospective studies are required.
Experimental and Numerical Investigation of the Thermal and Force Regulation Mechanism of Bypass Coupling Double-Sided Arc Welding Based on 6061 Aluminum Alloy
Authors: Zhang Zheng , Wang Ziran , Miao Yugang , Hu Guangxu , Zhao Yuyang , Liu Ji , Wu Yifan , Deng Qingwen
Published: January 2024

In this study, 6061 aluminum alloy was proposed for welding using bypass coupling double-sided arc welding (BCO-DASW) to further improve its welding quality and efficiency. To gain insight into the thermal and force regulation mechanism of the BCO-DASW of 6061 aluminum alloy, the dynamic effects of the high-temperature plasma inside the arc with various parameters were fully compared and investigated through the combined method of the physical experiment and the numerical simulation. The thermal flow field of the hybrid arc was analyzed numerically. Furthermore, its working adaptability and mechanical behaviors were studied experimentally. The results show that a single penetration of the 6 mm sheets can be achieved without visible defects when the center offset of the arcs is within 3 mm on both sides of the base metal during BCO-DASW. Through the thermal analysis, it was found that, compared with the MIG process, the introduction of the bypass arc lead to a temperature decrease at the bottom of the hybrid arc due to energy redistribution. Furthermore, through the kinetic analysis, it was found that not only could the level of arc pressure be reduced, but also the action range of the arc pressure could be regulated up to 4.6 mm. The thermal force regulation mechanism worked together to enhance the stability of the molten pool and achieves good joint strength during the BCO-DASW of 6061 aluminum alloy. This research not only has great significance in further improving the welding quality and efficiency of aluminum alloy, but also deeper understanding of the energy regulation mechanism during aluminum alloy welding.
Synergistic Defect Management for Boosting the Efficiency of Cu(In,Ga)Se2 Solar Cells
Authors: Dai Wanlei , Jiang Zhaoyi , Sun Yali , Wang Juhua , Gao Zeran , Xu Haoyu , Wang Xinzhan , Gao Chao , Ma Qiang , Wang Yinglong , Yu Wei
Published: January 2024

In this study, a feasible strategy is proposed for directly depositing high-quality Cu(In,Ga)Se2 (CIGS) films using Na-doped targets in a selenium-free atmosphere to boost the power conversion efficiency (PCE) of CIGS solar cells. Introducing a small amount of sodium dopant effectively promoted the textured growth of CIGS crystals in the prepared films, resulting in larger grain sizes and a smoother interface. The higher MoSe2 content at the CIGS/Mo interface increased the carrier lifetime in the films. In addition, sodium doping increased the proportion of Se atoms on the film surface and reduced the concentration of defects caused by the direct sputtering of the films in the selenium-free atmosphere. Therefore, the separation and transportation of photo-generated carriers in the devices were effectively enhanced. Using the optimized parameters, a record-high PCE of 17.26% was achieved for the 7.5% Na-doped devices, which represents an improvement of nearly 63%.
Phase Transitions under the Electric Field in Ternary Ferroelectric Solid Solutions of Pb(In1/2Nb1/2)O3–Pb(Mg1/3Nb2/3)O3–PbTiO3 near the Morphotropic Phase Boundary: Electric Approach
Authors: Iwata Makoto , Suzuki Soma , Takikawa Yoshinori , Nakamura Keiichiro , Echizenya Kazuhiko
Published: January 2024

Temperature–field phase diagrams in the [001]c and [011]c directions in the cubic coordinate in 24%Pb(In1/2Nb1/2)O3–46%Pb(Mg1/3Nb2/3)O3–30%PbTiO3 (24PIN–46PMN–30PT) and 31PIN–43PMN–26PT near the morphotropic phase boundary have been clarified by measuring the temperature dependences of permittivity under an electric field. Field-induced intermediate orthorhombic and tetragonal phases have been newly found in 24PIN–46PMN–30PT and 31PIN–43PMN–26PT, respectively. The temperature dependences of the remanent polarization have also been determined by polarization–electric field (P–E) hysteresis loop evaluation. On the basis of our experimental results, the phase transition and dielectric anisotropy in PIN–PMN–PT have been discussed.