bluuebunny/crossref_metadata_2025 huggingface dataset:
Fog Intermittency and Critical Behavior
Authors: Huang Kelly Y. , Katul Gabriel G. , Hintz Thomas J. , Ruiz-Plancarte Jesus , Wang Qing , Fernando Harindra J. S.
Published: May 2023

The intermittency of fog occurrence (the switching between fog and no-fog) is a key stochastic feature that plays a role in its duration and the amount of moisture available. Here, fog intermittency is studied by using the visibility time series collected during the month of July 2022 on Sable Island, Canada. In addition to the visibility, time series of air relative humidity and turbulent kinetic energy, putative variables akin to the formation and breakup conditions of fog, respectively, are also analyzed in the same framework to establish links between fog intermittency and the underlying atmospheric variables. Intermittency in the time series is quantified with their binary telegraph approximations to isolate clustering behavior from amplitude variations. It is shown that relative humidity and turbulent kinetic energy bound many stochastic features of visibility, including its spectral exponent, clustering exponent, and the growth of its block entropy slope. Although not diagnostic, the visibility time series displays features consistent with Pomeau–Manneville Type-III intermittency in its quiescent phase duration PDF scaling (−3/2), power spectrum scaling (−1/2), and signal amplitude PDF scaling (−2). The binary fog time series exhibits properties of self-organized criticality in the relation between its power spectrum scaling and quiescent phase duration distribution.
Chemical Characterization and Source Apportionment of PM10 Using Receptor Models over the Himalayan Region of India
Authors: Choudhary Nikki , Rai Akansha , Kuniyal Jagdish Chandra , Srivastava Priyanka , Lata Renu , Dutta Monami , Ghosh Abhinandan , Dey Supriya , Sarkar Sayantan , Gupta Sakshi , Chaudhary Sheetal , Thakur Isha , Bawari Archana , Naja Manish , Vijayan Narayanasamy , Chatterjee Abhijit , Mandal Tuhin Kumar , Sharma Sudhir Kumar , Kotnala Ravindra Kumar
Published: May 2023

This study presents the source apportionment of coarse-mode particulate matter (PM10) extracted by 3 receptor models (PCA/APCS, UNMIX, and PMF) at semi-urban sites of the Indian Himalayan region (IHR) during August 2018–December 2019. In this study, water-soluble inorganic ionic species (WSIIS), water-soluble organic carbon (WSOC), carbon fractions (organic carbon (OC) and elemental carbon (EC)), and trace elements of PM10 were analyzed over the IHR. Nainital (62 ± 39 µg m−3) had the highest annual average mass concentration of PM10 (average ± standard deviation at 1 σ), followed by Mohal Kullu (58 ± 32 µg m−3) and Darjeeling (54 ± 18 µg m−3). The annual total ∑WSIIS concentration order was as follows: Darjeeling (14.02 ± 10.01 µg m−3) > Mohal-Kullu (13.75 ± 10.21 µg m−3) > Nainital (10.20 ± 6.30 µg m−3), contributing to 15–30% of the PM10 mass. The dominant secondary ions (NH4+, SO42−, and NO3−) suggest that the study sites were strongly influenced by anthropogenic sources from regional and long-range transport. Principal component analysis (PCA) with an absolute principal component score (APCS), UNMIX, and Positive Matrix Factorization (PMF) were used for source identification of PM10 at the study sites of the IHR. All three models showed relatively similar results of source profiles for all study sites except their source number and percentage contribution. Overall, soil dust (SD), secondary aerosols (SAs), combustion (biomass burning (BB) + fossil fuel combustion (FFC): BB+FFC), and vehicular emissions (VEs) are the major sources of PM10 identified by these models at all study sites. Air mass backward trajectories illustrated that PM10, mainly attributed to dust-related aerosols, was transported from the Thar Desert, Indo-Gangetic Plain (IGP), and northwestern region of India (i.e., Punjab and Haryana) and Afghanistan to the IHR. Transported agricultural or residual burning plumes from the IGP and nearby areas significantly contribute to the concentration of carbonaceous aerosols (CAs) at study sites.
Research on Promotion Pathways for Zero-Emission Medium- and Heavy-Duty Trucks: A Case Study of Hainan Island
Authors: Hao Chunxiao , Ge Yunshan , Liang Jindong , He Zhuoshi , Huang Zhihui , Dou Guangyu
Published: May 2023

Promoting the use of zero-emission vehicles is an important measure for reducing pollutant and carbon dioxide emissions from medium- and heavy-duty trucks (MHDTs). This study took Hainan Island as an example. Based on big data such as industrial layout and traffic flow, it clarified that the main channels of freight transportation on Hainan Island are concentrated in the northern region, including the surrounding areas of Haikou; the important ports of Haikou, Yangpu, and Basuo; and Chengmai and Tunchang counties. Furthermore, pathways for the promotion of zero-emission MHDTs are proposed, which can reduce exhaust emissions by 1549 tons of NOx, 62 tons of particulate matter (PM), and 3.60 million tons of CO2 by 2030. Compared with the vehicle type categorization plan, the spatial layout plan can achieve higher emission reduction benefits in the medium term (2025). In addition, in conjunction with existing policies and planning requirements, this study also puts forward policy suggestions for the promotion of zero-emission MHDTs.
Phylogenetic Triage and Risk Assessment: How to Predict Emerging Phytoplasma Diseases
Authors: Janik Katrin , Panassiti Bernd , Kerschbamer Christine , Burmeister Johannes , Trivellone Valeria
Published: May 2023

Phytoplasma diseases pose a substantial threat to diverse crops of agricultural importance. Management measures are usually implemented only after the disease has already occurred. Early detection of such phytopathogens, prior to disease outbreak, has rarely been attempted, but would be highly beneficial for phytosanitary risk assessment, disease prevention and mitigation. In this study, we present the implementation of a recently proposed proactive disease management protocol (DAMA: Document, Assess, Monitor, Act) for a group of vector-borne phytopathogens. We used insect samples collected during a recent biomonitoring program in southern Germany to screen for the presence of phytoplasmas. Insects were collected with malaise traps in different agricultural settings. DNA was extracted from these mass trap samples and subjected to PCR-based phytoplasma detection and mitochondrial cytochrome c oxidase subunit I (COI) metabarcoding. Phytoplasma DNA was detected in two out of the 152 insect samples analyzed. Phytoplasma identification was performed using iPhyClassifier based on 16S rRNA gene sequence and the detected phytoplasmas were assigned to ‘Candidatus Phytoplasma asteris’-related strains. Insect species in the sample were identified by DNA metabarcoding. By using established databases, checklists, and archives, we documented historical associations and records of phytoplasmas and its hosts in the study region. For the assessment in the DAMA protocol, phylogenetic triage was performed in order to determine the risk for tri-trophic interactions (plant–insect–phytoplasma) and associated disease outbreaks in the study region. A phylogenetic heat map constitutes the basis for risk assessment and was used here to identify a minimum number of seven leafhopper species suggested to be monitored by stakeholders in this region. A proactive stance in monitoring changing patterns of association between hosts and pathogens can be a cornerstone in capabilities to prevent future phytoplasma disease outbreaks. To the best of our knowledge, this is the first time that the DAMA protocol has been applied in the field of phytopathology and vector-borne plant diseases.
Importance of Magnesium Status in COVID-19
Authors: Guerrero-Romero Fernando , Micke Oliver , Simental-Mendía Luis E. , Rodríguez-Morán Martha , Vormann Juergen , Iotti Stefano , Banjanin Nikolina , Rosanoff Andrea , Baniasadi Shadi , Pourdowlat Guitti , Nechifor Mihai
Published: May 2023

A large amount of published research points to the interesting concept (hypothesis) that magnesium (Mg) status may have relevance for the outcome of COVID-19 and that Mg could be protective during the COVID disease course. As an essential element, Mg plays basic biochemical, cellular, and physiological roles required for cardiovascular, immunological, respiratory, and neurological functions. Both low serum and dietary Mg have been associated with the severity of COVID-19 outcomes, including mortality; both are also associated with COVID-19 risk factors such as older age, obesity, type 2 diabetes, kidney disease, cardiovascular disease, hypertension, and asthma. In addition, populations with high rates of COVID-19 mortality and hospitalization tend to consume diets high in modern processed foods, which are generally low in Mg. In this review, we review the research to describe and consider the possible impact of Mg and Mg status on COVID-19 showing that (1) serum Mg between 2.19 and 2.26 mg/dL and dietary Mg intakes > 329 mg/day could be protective during the disease course and (2) inhaled Mg may improve oxygenation of hypoxic COVID-19 patients. In spite of such promise, oral Mg for COVID-19 has thus far been studied only in combination with other nutrients. Mg deficiency is involved in the occurrence and aggravation of neuropsychiatric complications of COVID-19, including memory loss, cognition, loss of taste and smell, ataxia, confusion, dizziness, and headache. Potential of zinc and/or Mg as useful for increasing drug therapy effectiveness or reducing adverse effect of anti-COVID-19 drugs is reviewed. Oral Mg trials of patients with COVID-19 are warranted.
Association of Long Noncoding RNA Expression Signatures with Stress-Induced Myocardial Perfusion Defects
Authors: Chang Yu-Chieh , Liou Jun-Ting , Peng Yu-Min , Chen Guan-Jun , Lin Chien-Yu , Yang Chin-An
Published: May 2023

Stress-induced myocardial perfusion defects found in dipyridamole–thallium-201 single-photon emission computed tomography imaging may indicate vascular perfusion abnormalities and risk of obstructive or nonobstructive coronary heart disease. Besides nuclear imaging and subsequent coronary angiography (CAG), no blood test can indicate whether dysregulated homeostasis is associated with stress-induced myocardial perfusion defects. This study investigated the expression signature of long noncoding RNAs (lncRNAs) and genes involved in vascular inflammation and stress response in the blood of patients with stress-induced myocardial perfusion abnormalities (n = 27). The results revealed an expression signature consisting of the upregulation of RMRP (p < 0.01) and downregulations of THRIL (p < 0.01) and HIF1A (p < 0.01) among patients with a positive thallium stress test and no significant coronary artery stenosis within 6 months after baseline treatment. We developed a scoring system based on the expression signatures of RMRP, MIAT, NTT, MALAT1, HSPA1A, and NLRP3 to predict the need for further CAG among patients with moderate-to-significant stress-induced myocardial perfusion defects (area under the receiver operating characteristic curve = 0.963). Therefore, we identified a dysregulated expression profile of lncRNA-based genes in the blood that could be valuable for the early detection of vascular homeostasis imbalance and personalized therapy.
Endocan Knockdown Down-Regulates the Expression of Angiogenesis-Associated Genes in Il-1ß Activated Chondrocytes
Authors: Scuruchi Michele , Aliquò Federica , Avenoso Angela , Mandraffino Giuseppe , Vermiglio Giovanna , Minuti Aurelio , Campo Salvatore , Campo Giuseppe Maurizio , D’Ascola Angela
Published: May 2023

Endocan is a small soluble proteoglycan (PG) known to be involved in inflammation and angiogenesis. Increased endocan expression was found in the synovia of arthritic patients and chondrocytes stimulated with IL-1ß. Considering these findings, we aimed to investigate the effects of endocan knockdown on the modulation of pro-angiogenic molecules expression in a model of IL-1ß-induced inflammation in human articular chondrocytes. Endocan, VEGF-A, MMP-9, MMP-13, and VEGFR-2 expression was measured in both normal and endocan knockdown chondrocytes stimulated with IL-1ß. VEGFR-2 and NF-kB activation were also measured. Results have shown that endocan, VEGF-A, VEGFR-2, MMP-9, and MMP-13 were significantly up-regulated during IL-1ß-induced inflammation; interestingly, the expression of such pro-angiogenic molecules and NF-kB activation were significantly reduced by endocan knockdown. These data support the hypothesis that endocan released by activated chondrocytes may be involved in the mechanisms that stimulate cell migration and invasion, as well as angiogenesis, in the pannus of arthritic joints.
The Effects of Two Kinds of Dietary Interventions on Serum Metabolic Profiles in Haemodialysis Patients
Authors: Kozlowska Lucyna , Jagiello Karolina , Ciura Krzesimir , Sosnowska Anita , Zwiech Rafal , Zbrog Zbigniew , Wasowicz Wojciech , Gromadzinska Jolanta
Published: May 2023

The goal of this study was to evaluate the effects of two kinds of 24-week dietary interventions in haemodialysis patients, a traditional nutritional intervention without a meal before dialysis (HG1) and implementation of a nutritional intervention with a meal served just before dialysis (HG2), in terms of analysing the differences in the serum metabolic profiles and finding biomarkers of dietary efficacy. These studies were performed in two homogenous groups of patients (n = 35 in both groups). Among the metabolites with the highest statistical significance between HG1 and HG2 after the end of the study, 21 substances were putatively annotated, which had potential significance in both of the most relevant metabolic pathways and those related to diet. After the 24 weeks of the dietary intervention, the main differences between the metabolomic profiles in the HG2 vs. HG1 groups were related to the higher signal intensities from amino acid metabolites: indole-3-carboxaldehyde, 5-(hydroxymethyl-2-furoyl)glycine, homocitrulline, 4-(glutamylamino)butanoate, tryptophol, gamma-glutamylthreonine, and isovalerylglycine. These metabolites are intermediates in the metabolic pathways of the necessary amino acids (Trp, Tyr, Phe, Leu, Ile, Val, Liz, and amino acids of the urea cycle) and are also diet-related intermediates (4-guanidinobutanoic acid, indole-3-carboxyaldehyde, homocitrulline, and isovalerylglycine).
Patients with Disorders of Consciousness: Are They Nonconscious, Unconscious, or Subconscious? Expanding the Discussion
Authors: Fingelkurts Andrew A. , Fingelkurts Alexander A.
Published: May 2023

Unprecedented advancements in the diagnosis and treatment of patients with disorders of consciousness (DoC) have given rise to ethical questions about how to recognize and respect autonomy and a sense of agency of the personhood when those capacities are themselves disordered, as they typically are in patients with DoC. At the intersection of these questions rests the distinction between consciousness and unconsciousness. Indeed, evaluations of consciousness levels and capacity for recovery have a significant impact on decisions regarding whether to discontinue or prolong life-sustaining therapy for DoC patients. However, in the unconsciousness domain, there is the confusing array of terms that are regularly used interchangeably, making it quite challenging to comprehend what unconsciousness is and how it might be empirically grounded. In this opinion paper, we will provide a brief overview of the state of the field of unconsciousness and show how a rapidly evolving electroencephalogram (EEG) neuroimaging technique may offer empirical, theoretical, and practical tools to approach unconsciousness and to improve our ability to distinguish consciousness from unconsciousness and also nonconsciousness with greater precision, particularly in cases that are borderline (as is typical in patients with DoC). Furthermore, we will provide a clear description of three distant notions of (un)consciousness (unconsciousness, nonconsciousness, and subconsciousness) and discuss how they relate to the experiential selfhood which is essential for comprehending the moral significance of what makes life worth living.
Role of Protein Tyrosine Phosphatase 1B Inhibitor in Early Brain Injury of Subarachnoid Hemorrhage in Mice
Authors: Zhang Zhong-Hua , Zhou Xiao-Ming , Zhang Xin
Published: May 2023

Clinically, early brain injury (EBI), which refers to the acute injuries to the whole brain in the phase of the first 72 h following subarachnoid hemorrhage (SAH), is intensely investigated to improve neurological and psychological function. Additionally, it will be meaningful to explore new therapeutic approaches for EBI treatment to improve the prognosis of patients with SAH. To investigate the underlying neuroprotection mechanism in vitro, the Protein tyrosine phosphatase 1B inhibitor (PTP1B-IN-1) was put in primary neurons induced by OxyHb to observe neuroapoptosis, neuroinflammation, and ER stress. Then, one hundred forty male mice were subjected to Experiment two and Experiment three. The mice in the SAH24h + PTP1B-IN-1 group were given an intraperitoneal injection of 5 mg/kg PTP1B-IN-1 30 min before anesthesia. SAH grade, neurological score, brain water content, Western blot, PCR, and Transmission Electron Microscopy (TEM) were performed to observe the underlying neuroprotection mechanism in vivo. Overall, this study suggests that PTP1B-IN-1 could ameliorate neuroapoptosis, neuroinflammation, and ER stress in vitro and in vivo by regulating the IRS-2/AKT signaling pathway, suggesting that PTP1B-IN-1 may be a candidate drug for the treatment of early brain injury after SAH.
From Theory to Practice: Implementing the WHO 2021 Classification of Adult Diffuse Gliomas in Neuropathology Diagnosis
Authors: Martin Karina Chornenka , Ma Crystal , Yip Stephen
Published: May 2023

Diffuse gliomas are the most common type of primary central nervous system (CNS) neoplasm to affect the adult population. The diagnosis of adult diffuse gliomas is dependent upon the integration of morphological features of the tumour with its underlying molecular alterations, and the integrative diagnosis has become of increased importance in the fifth edition of the WHO classification of CNS neoplasms (WHO CNS5). The three major diagnostic entities of adult diffuse gliomas are as follows: (1) astrocytoma, IDH-mutant; (2) oligodendroglioma, IDH-mutant and 1p/19q-codeleted; and (3) glioblastoma, IDH-wildtype. The aim of this review is to summarize the pathophysiology, pathology, molecular characteristics, and major diagnostic updates encountered in WHO CNS5 of adult diffuse gliomas. Finally, the application of implementing the necessary molecular tests for diagnostic workup of these entities in the pathology laboratory setting is discussed.
Working-Memory-Guided Attention Competes with Exogenous Attention but Not with Endogenous Attention
Authors: Zhu Ping , Yang Qingqing , Chen Luo , Guan Chenxiao , Zhou Jifan , Shen Mowei , Chen Hui
Published: May 2023

Recent research has extensively investigated working memory (WM)-guided attention, which is the phenomenon of attention being directed towards information in the external environment that matches the content stored in WM. While prior studies have focused on the potential influencing factors of WM-guided attention, little is known about the nature of it. This attention system exhibits characteristics of two classical distinct attention systems: exogenous attention and endogenous attention, as it can operate automatically like exogenous attention yet persist for a long time and be modulated by cognitive resources like endogenous attention. Thus, the current study aimed to explore the mechanism of WM-guided attention by testing whether it competed with exogenous attention, endogenous attention, or both. Two experiments were conducted within a classic WM-guided attention paradigm. Experiment 1 included an exogenous cue and revealed an interaction between WM-guided attention and exogenous attention. Experiment 2 replaced the exogenous cue with an endogenous cue and demonstrated that endogenous attention had no impact on WM-guided attention. These findings indicate that WM-guided attention shares mechanisms with exogenous attention to some extent while operating in parallel with endogenous attention.
Predicting Alcohol-Related Memory Problems in Older Adults: A Machine Learning Study with Multi-Domain Features
Authors: Kamarajan Chella , Pandey Ashwini K. , Chorlian David B. , Meyers Jacquelyn L. , Kinreich Sivan , Pandey Gayathri , Subbie-Saenz de Viteri Stacey , Zhang Jian , Kuang Weipeng , Barr Peter B. , Aliev Fazil , Anokhin Andrey P. , Plawecki Martin H. , Kuperman Samuel , Almasy Laura , Merikangas Alison , Brislin Sarah J. , Bauer Lance , Hesselbrock Victor , Chan Grace , Kramer John , Lai Dongbing , Hartz Sarah , Bierut Laura J. , McCutcheon Vivia V. , Bucholz Kathleen K. , Dick Danielle M. , Schuckit Marc A. , Edenberg Howard J. , Porjesz Bernice
Published: May 2023

Memory problems are common among older adults with a history of alcohol use disorder (AUD). Employing a machine learning framework, the current study investigates the use of multi-domain features to classify individuals with and without alcohol-induced memory problems. A group of 94 individuals (ages 50–81 years) with alcohol-induced memory problems (the memory group) were compared with a matched control group who did not have memory problems. The random forests model identified specific features from each domain that contributed to the classification of the memory group vs. the control group (AUC = 88.29%). Specifically, individuals from the memory group manifested a predominant pattern of hyperconnectivity across the default mode network regions except for some connections involving the anterior cingulate cortex, which were predominantly hypoconnected. Other significant contributing features were: (i) polygenic risk scores for AUD, (ii) alcohol consumption and related health consequences during the past five years, such as health problems, past negative experiences, withdrawal symptoms, and the largest number of drinks in a day during the past twelve months, and (iii) elevated neuroticism and increased harm avoidance, and fewer positive “uplift” life events. At the neural systems level, hyperconnectivity across the default mode network regions, including the connections across the hippocampal hub regions, in individuals with memory problems may indicate dysregulation in neural information processing. Overall, the study outlines the importance of utilizing multidomain features, consisting of resting-state brain connectivity data collected ~18 years ago, together with personality, life experiences, polygenic risk, and alcohol consumption and related consequences, to predict the alcohol-related memory problems that arise in later life.
Nationwide Trends and the Influence of Age and Gender in the In-Patient Care of Patients with Hepatocellular Carcinoma in Germany between 2010 and 2020
Authors: Decker Josua A. , Scheurig-Muenkler Christian , Luitjens Jan H. , Kroencke Thomas
Published: May 2023

This study analyzes nationwide trends in HCC hospitalizations focusing on interventional liver-directed treatments and the influence of age and gender. Using data from the German Federal Statistical Office all hospitalizations for HCC between 2010 and 2020 were included. Uni- and multivariable logistic regression analyses were performed to identify variables independently associated with the use of liver-directed therapies. Due to the COVID-19 pandemic, data from 2020 were analyzed separately. A total of 134,713 hospitalizations (2010–2019) were included, increasing by 3.4% annually (12,707 to 13,143). The mean in-hospital stay (−15.0% [7.2 to 6.1 days]) and mortality (−23.2% [6.8 to 5.2%]) decreased while transarterial, surgical, and percutaneous ablative interventions increased by 38.6, 31.5, and 19.3%, respectively. In-hospital mortality was 7.7% in admissions with surgical treatment, while it was 0.6 and 0.5% for transarterial and percutaneous interventions. Mortality was higher in females (6.2 vs. 5.7%). Females (OR 0.89 [0.86,0.91], p < 0.001) and patients ≥80 years (OR 0.81 [0.79,0.84], p < 0.001) were less likely to receive liver-directed treatments. Liver-directed therapies were increasingly performed while in-hospital mortality and in-hospital stay decreased. Minimally invasive approaches showed lower mortality, shorter in-hospital stay, and lower costs compared to surgery. Proportionately, more women and older patients were hospitalized, receiving fewer liver-directed treatments while their mortality was higher.
Three-Dimensional Spheroid Configurations and Cellular Metabolic Properties of Oral Squamous Carcinomas Are Possible Pharmacological and Pathological Indicators
Authors: Miyamoto Sho , Nishikiori Nami , Sato Tatsuya , Watanabe Megumi , Umetsu Araya , Tsugeno Yuri , Hikage Fumihito , Sasaya Takashi , Kato Hirotaka , Ogi Kazuhiro , Furuhashi Masato , Ohguro Hiroshi , Miyazaki Akihiro
Published: May 2023

The objective of the current study was to elucidate the clinicopathological significance and appearance of in vitro three-dimension (3D) spheroid models of oral malignant tumors that were prepared from four pathologically different squamous cell carcinoma (OSCC; low-grade; SSYP and MO-1000, intermediate-grade; LEM2) and oral adenosquamous carcinoma (OASC; high-grade; Mesimo) obtained from patients with different malignant stages. To characterize the biological significance of these cell lines themselves, two-dimensional (2D) cultured cells were subjected to cellular metabolic analysis by a Seahorse bioanalyzer alongside the measurement of the cytotoxicity of cisplatin (CDDP). The appearance of their 3D spheroids was then observed by phase contrast microscopy, and both 2D and 3D cultured cells were subject to trypsin digestion and qPCR analysis of factors related to oncogenic signaling and other related analyses. ATP-linked respiration and proton leaking were significantly different among the four cell lines, and the malignant stages of these cultures were significantly associated with increased ATP-linked respiration and decreased proton leakage. Alternatively, the appearances of these 3D spheroids were also significantly diverse among them, and their differences increased in the order of LEM2, MO-1000, SSYP, and Mesimo. Interestingly, these orders were exactly the same in that the efficacies of CDDP-induced cytotoxicity increased in the same order. qPCR analysis indicated that the levels of expression of oncogenic signaling-related factors varied among these four cell lines, and the values for fibronectin and a key regulator of mitochondrial biogenesis, PGC-1α, were prominently elevated in cultures of the worst malignant Mesimo cells. In addition, although 0.25% trypsin-induced destruction was comparable among all four 2D cultured cells, the values for the 3D spheroids were also substantially varied among these cultures. The findings reported herein indicate that cellular metabolic functions and 3D spheroid architectures may be valuable and useful indicators for estimating the pathological and drug-sensitive aspects of OSCC and OASC malignancies.
Automated Estimation of Mammary Gland Content Ratio Using Regression Deep Convolutional Neural Network and the Effectiveness in Clinical Practice as Explainable Artificial Intelligence
Authors: Kai Chiharu , Ishizuka Sachi , Otsuka Tsunehiro , Nara Miyako , Kondo Satoshi , Futamura Hitoshi , Kodama Naoki , Kasai Satoshi
Published: May 2023

Recently, breast types were categorized into four types based on the Breast Imaging Reporting and Data System (BI-RADS) atlas, and evaluating them is vital in clinical practice. A Japanese guideline, called breast composition, was developed for the breast types based on BI-RADS. The guideline is characterized using a continuous value called the mammary gland content ratio calculated to determine the breast composition, therefore allowing a more objective and visual evaluation. Although a discriminative deep convolutional neural network (DCNN) has been developed conventionally to classify the breast composition, it could encounter two-step errors or more. Hence, we propose an alternative regression DCNN based on mammary gland content ratio. We used 1476 images, evaluated by an expert physician. Our regression DCNN contained four convolution layers and three fully connected layers. Consequently, we obtained a high correlation of 0.93 (p < 0.01). Furthermore, to scrutinize the effectiveness of the regression DCNN, we categorized breast composition using the estimated ratio obtained by the regression DCNN. The agreement rates are high at 84.8%, suggesting that the breast composition can be calculated using regression DCNN with high accuracy. Moreover, the occurrence of two-step errors or more is unlikely, and the proposed method can intuitively understand the estimated results.
MR Virtual Biopsy of Solid Renal Masses: An Algorithmic Approach
Authors: Chartier Stephane , Arif-Tiwari Hina
Published: May 2023

Between 1983 and 2002, the incidence of solid renal tumors increased from 7.1 to 10.8 cases per 100,000. This is in large part due to the increase in the volume of ultrasound and cross-sectional imaging, although a majority of solid renal tumors are still found incidentally. Ultrasound and computed tomography (CT) have been the mainstay of renal mass screening and diagnosis but recent advances in magnetic resonance (MR) technology have made this the optimal choice when diagnosing and staging renal tumors. Our purpose in writing this review is to survey the modern MR imaging approach to benign and malignant solid renal tumors, consolidate the various imaging findings into an easy-to-read reference, and provide an imaging-based, algorithmic approach to renal mass characterization for clinicians. MR is at the forefront of renal mass characterization, surpassing ultrasound and CT in its ability to describe multiple tissue parameters and predict tumor biology. Cutting-edge MR protocols and the integration of diagnostic algorithms can improve patient outcomes, allowing the imager to narrow the differential and better guide oncologic and surgical management.
PSMA-PET/CT-Based Stereotactic Body Radiotherapy (SBRT) in the Treatment of Uncomplicated Non-Spinal Bone Oligometastases from Prostate Cancer
Authors: Pastorello Edoardo , Nicosia Luca , Cuccia Francesco , Olivari Laura , Fiorini Matilde , Giaj Levra Niccolò , Mazzola Rosario , Ricchetti Francesco , Rigo Michele , Ravelli Paolo , D’Alessandro Salvatore , Salgarello Matteo , Ruggieri Ruggero , Alongi Filippo
Published: May 2023

Background and purpose: Stereotactic body radiotherapy (SBRT) has a consolidated role in the treatment of bone oligometastases from prostate cancer (PCa). While the evidence for spinal oligometastases SBRT was robust, its role in non-spinal-bone metastases (NSBM) is not standardized. In fact, there was no clear consensus about dose and target definition in this setting. The aim of our study was to evaluate efficacy, toxicity, and the pattern of relapse in SBRT delivered to NSBM from PCa. Materials and methods: From 2016 to 2021, we treated a series of oligo-NSBM from PCa with 68Ga-PSMA PET/CT-guided SBRT. The primary endpoint was local progression-free survival (LPFS). The secondary endpoints were toxicity, the pattern of intraosseous relapse, distant progression-free survival (DPFS), polimetastases-free survival (PMFS), and overall survival (OS). Results: a total of 150 NSBM in 95 patients were treated with 30–35 Gy in five fractions. With a median follow-up of 26 months, 1- and 3 years LPFS was 96.3% and 89%, respectively. A biologically effective dose (BED) ≥ 198 Gy was correlated with improved LPFS (p = 0.007). Intraosseous relapse occurred in eight (5.3%) cases. Oligorecurrent disease was associated with a better PMFS compared to de novo oligometastatic disease (p = 0.001) and oligoprogressive patients (p = 0.007). No grade ≥ 3 toxicity occurred. Conclusion: SBRT is a safe and effective tool for NSBM from PCa in the oligometastatic setting. Intraosseous relapse was a relatively rare event. Predictive factors of the improved outcomes were defined.
Multi-Omic Analysis of CIC’s Functional Networks Reveals Novel Interaction Partners and a Potential Role in Mitotic Fidelity
Authors: Takemon Yuka , LeBlanc Véronique G. , Song Jungeun , Chan Susanna Y. , Lee Stephen Dongsoo , Trinh Diane L. , Ahmad Shiekh Tanveer , Brothers William R. , Corbett Richard D. , Gagliardi Alessia , Moradian Annie , Cairncross J. Gregory , Yip Stephen , Aparicio Samuel A. J. R. , Chan Jennifer A. , Hughes Christopher S. , Morin Gregg B. , Gorski Sharon M. , Chittaranjan Suganthi , Marra Marco A.
Published: May 2023

CIC encodes a transcriptional repressor and MAPK signalling effector that is inactivated by loss-of-function mutations in several cancer types, consistent with a role as a tumour suppressor. Here, we used bioinformatic, genomic, and proteomic approaches to investigate CIC’s interaction networks. We observed both previously identified and novel candidate interactions between CIC and SWI/SNF complex members, as well as novel interactions between CIC and cell cycle regulators and RNA processing factors. We found that CIC loss is associated with an increased frequency of mitotic defects in human cell lines and an in vivo mouse model and with dysregulated expression of mitotic regulators. We also observed aberrant splicing in CIC-deficient cell lines, predominantly at 3′ and 5′ untranslated regions of genes, including genes involved in MAPK signalling, DNA repair, and cell cycle regulation. Our study thus characterises the complexity of CIC’s functional network and describes the effect of its loss on cell cycle regulation, mitotic integrity, and transcriptional splicing, thereby expanding our understanding of CIC’s potential roles in cancer. In addition, our work exemplifies how multi-omic, network-based analyses can be used to uncover novel insights into the interconnected functions of pleiotropic genes/proteins across cellular contexts.
Beyond Corticoresistance, A Paradoxical Corticosensitivity Induced by Corticosteroid Therapy in Pediatric Acute Lymphoblastic Leukemias
Authors: Angot Laure , Schneider Pascale , Vannier Jean-Pierre , Abdoul-Azize Souleymane
Published: May 2023

Known as a key effector in relapse of acute lymphoblastic leukemia (ALL), resistance to drug-induced apoptosis, is tightly considered one of the main prognostic factors for the disease. ALL cells are constantly developing cellular strategies to survive and resist therapeutic drugs. Glucocorticoids (GCs) are one of the most important agents used in the treatment of ALL due to their ability to induce cell death. The mechanisms of GC resistance of ALL cells are largely unknown and intense research is currently focused on this topic. Such resistance can involve different cellular and molecular mechanisms, including the modulation of signaling pathways involved in the regulation of proliferation, apoptosis, autophagy, metabolism, epigenetic modifications and tumor suppressors. Recently, several studies point to the paradoxical role of GCs in many survival processes that may lead to therapy-induced resistance in ALL cells, which we called “paradoxical corticosensitivity”. In this review, we aim to summarize all findings on cell survival pathways paradoxically activated by GCs with an emphasis on previous and current knowledge on gene expression and signaling pathways.
Netrin Family Genes as Prognostic Markers and Therapeutic Targets for Clear Cell Renal Cell Carcinoma: Netrin-4 Acts through the Wnt/β-Catenin Signaling Pathway
Authors: Ke Shuai , Guo Jiayu , Wang Qinghua , Shao Haoren , He Mu , Li Tao , Qiu Tao , Guo Jia
Published: May 2023

Clear cell renal cell carcinoma (ccRCC, or KIRC) is the most common type of kidney cancer, originating within the renal cortex. The current outcomes for early diagnosis and late treatment of ccRCC are unsatisfactory. Therefore, it is important to explore tumor biomarkers and therapeutic opportunities for ccRCC. In this study, we used bioinformatics methods to systematically evaluate the expression and prognostic value of Netrin family genes in ccRCC. Through our analysis, three potential biomarkers for ccRCC were identified, namely NTNG1, NTNG2, and NTN4. Moreover, we performed in vitro and in vivo experiments to explore the possible biological roles of NTN4 and found that NTN4 could regulate ccRCC development through Wnt/β-catenin signaling. We elucidate the molecular mechanism by which NTN4 modulates β-catenin expression and nuclear translocation to inhibit ccRCC progression, providing a new theoretical basis for developing therapeutic targets for ccRCC. Thus, we suggest that Netrin-related studies may offer new directions for the diagnosis, treatment, and prognosis of ccRCC patients.
Targeting the Divergent Roles of STK3 Inhibits Breast Cancer Cell Growth and Opposes Doxorubicin-Induced Cardiotoxicity In Vitro
Authors: Nam Jiung , Schirmer Amelia U. , Loh Chelsea , Drewry David H. , Macias Everardo
Published: May 2023

Breast cancer (BCa) is the most prevalent type of cancer in women. Several therapies used in the treatment of breast cancer are associated with clinically important rates of cardiovascular toxicity during or after treatment exposure, including anthracyclines. There is a need for new BCa therapeutics and treatments that mitigate chemotherapy-induced cardiotoxicity in BCa. In this study, we examine the effects of Serine/Threonine Kinase 3 (STK3) inhibition in the context of BCa therapy and cardioprotection from doxorubicin. STK3 (also known as MST2) is a key member of the Hippo Tumor-Suppressor Pathway, which regulates cell growth and proliferation by inhibiting YAP/TAZ co-transcription factors. Canonically, STK3 should restrict BCa growth; however, we observed that STK3 is amplified in BCa and associated with worse patient outcomes, suggesting a noncanonical pro-tumorigenic role. We found BCa cell lines have varying dependence on STK3. SUM52PE cells had the highest expression and dependence on STK3 in genetic and pharmacological assays. MCF-7 and MDA-MB-231 were less sensitive to STK3 targeting in standard proliferation assays, but were STK3 dependent in colony formation and matrigel invasion assays. In contrast, STK3 inhibition mitigated the toxic effects of doxorubicin in H9C2 rat cardiomyocytes by increasing YAP expression. Importantly, STK3 inhibition in BCa cells did not interfere with the therapeutic effects of doxorubicin. Our studies highlight STK3 is a potential molecular target for BCa with dual therapeutic effects: suppression of BCa growth and progression, and chemoprotection in cardiomyocytes.
Diagnostic Utility and Tendency of Bronchial and Serum Soluble Receptor for Advanced Glycation EndProducts (sRAGE) in Lung Cancer
Authors: Kim Taehee , Kim Soo Jung , Choi Hayoung , Shin Tae Rim , Sim Yun Su
Published: May 2023

The receptor for advanced glycation end-products (RAGE) may serve as a diagnostic and prognostic biomarker of lung cancer and lung injury. We explored whether the serum and bronchial levels of soluble RAGE (sRAGE) distinguished infectious lung diseases from lung cancer. We collected serum and bronchial washing fluids (BWFs) from patients diagnosed with pneumonia, tuberculosis, or preoperative lung cancer from April 2016 to March 2022. sRAGE levels were measured using an enzyme-linked immunosorbent assay and we drew receiver operating characteristic (1) curves to determine the cut-off values affording the best diagnostic sensitivities. We enrolled 81 patients including 20 with tuberculosis, 30 with pneumonia, and 31 with lung cancer. Of the 81, 61% were males and the median age was 66 years. The median serum level of sRAGE was 822 (678–1168 pg/mL) and did not differ significantly between the three groups. The median bronchial sRAGE level was 167 (83–529 pg/mL) but 231 (108–649 pg/mL) for tuberculosis, 366 (106–706 pg/mL) for pneumonia, and 103 (32–254 pg/mL) for lung cancer patients (p = 0.018). The ROC curve for the bronchial sRAGE values of lung cancer patients revealed that the optimal cut-off was 118.9 pg/mL. This afforded a sensitivity of 76%, a specificity of 58%, and an area under the ROC curve of 0.695 (p = 0.005). The level of bronchial sRAGE differed significantly between patients with lung cancer and other respiratory diseases; that level may serve as an auxiliary diagnostic biomarker.
The Management of Metastatic Spinal Cord Compression in Routine Clinical Practice
Authors: Pérez-Romasanta Luis Alberto , Arana Estanislao , Kovacs Francisco M. , Royuela Ana
Published: May 2023

(1) Background: Whether clinical management of spinal metastatic disease (SMD) matches evidence-based recommendations is largely unknown. (2) Patients and Methods: A questionnaire was distributed through Spanish Medical Societies, exploring routine practice, interpretation of the SINS and ESCC scores and agreement with items in the Tokuhashi and SINS scales, and NICE guideline recommendations. Questionnaires were completed voluntarily and anonymously, without compensation. (3) Results: Eighty specialists participated in the study. A protocol for patients with SMD existed in 33.7% of the hospitals, a specific multidisciplinary board in 33.7%, 40% of radiological reports included the ESCC score, and a prognostic scoring method was used in 73.7%. While 77.5% of the participants were familiar with SINS, only 60% used it. The different SINS and ESCC scores were interpreted correctly by 57.5–70.0% and 30.0–37.5% of the participants, respectively. Over 70% agreed with the items included in the SINS and Tokuhashi scores and with the recommendations from the NICE guideline. Differences were found across private/public sectors, hospital complexity, number of years of experience, number of patients with SMD seen annually and especially across specialties. (4) Conclusions: Most specialists know and agree with features defining the gold standard treatment for patients with SCC, but many do not apply them.
Sustainable Biorefineries Based on Catalytic Biomass Conversion: A Review
Authors: Solarte-Toro Juan Camilo , Ortiz-Sanchez Mariana , Inocencio-García Pablo-José , Cardona Alzate Carlos Ariel
Published: May 2023

Biorefineries have been profiled as potential alternatives to increase biomass use at the industrial level. However, more efforts are required to improve the sustainability of these facilities through process improvement and product portfolio increase. The catalytic conversion of biomass to chemicals and energy vectors is one of the most studied research lines today. The open literature has described catalytic pathways for producing biofuels and platform molecules using this renewable resource. Nevertheless, few literature reviews have aimed to analyze the role of the catalytic conversion of biomass in biorefineries while considering the following items: (i) biocatalysis, (ii) carbon dioxide conversion, (iii) design based on catalytic biomass upgrading, and (iv) sustainability metrics. This paper reviews several processes where catalysis has been applied to improve yields and conversion to elucidate the potential of this research field to boost biomass implementation in different productive sectors. This paper provides an overview of the catalytic conversion of biomass into a series of biofuels and high-value-added products, involving key topics related to catalyst performance, use, applications, and recent trends. In addition, several research gaps and ideas are highlighted based on previous studies. In conclusion, the catalytic conversion of biomass has the potential to increase biorefineries’ sustainability. Nevertheless, more studies focused on (i) the production of new catalysts using renewable resources, (ii) the techno-economic and environmental assessment of processes involving catalysis, and (iii) the influence of involving biomass valorization via heterogeneous catalysis in existing facilities are required to obtain a real understanding of catalytic upgrades’ benefits.
Tissue-Specific Vulnerability to Apoptosis in Machado-Joseph Disease
Authors: Ferreira Ana F. , Raposo Mafalda , Shaw Emily D. , Ashraf Naila S. , Medeiros Filipa , Brilhante Maria de Fátima , Perkins Matthew , Vasconcelos João , Kay Teresa , Costa Maria do Carmo , Lima Manuela
Published: May 2023

Machado-Joseph disease (MJD) is a dominant neurodegenerative disease caused by an expanded CAG repeat in the ATXN3 gene encoding the ataxin-3 protein. Several cellular processes, including transcription and apoptosis, are disrupted in MJD. To gain further insights into the extent of dysregulation of mitochondrial apoptosis in MJD and to evaluate if expression alterations of specific apoptosis genes/proteins can be used as transcriptional biomarkers of disease, the expression levels of BCL2, BAX and TP53 and the BCL2/BAX ratio (an indicator of susceptibility to apoptosis) were assessed in blood and post-mortem brain samples from MJD subjects and MJD transgenic mice and controls. While patients show reduced levels of blood BCL2 transcripts, this measurement displays low accuracy to discriminate patients from matched controls. However, increased levels of blood BAX transcripts and decreased BCL2/BAX ratio are associated with earlier onset of disease, indicating a possible association with MJD pathogenesis. Post-mortem MJD brains show increased BCL2/BAX transcript ratio in the dentate cerebellar nucleus (DCN) and increased BCL2/BAX insoluble protein ratio in the DCN and pons, suggesting that in these regions, severely affected by degeneration in MJD, cells show signs of apoptosis resistance. Interestingly, a follow-up study of 18 patients further shows that blood BCL2 and TP53 transcript levels increase over time in MJD patients. Furthermore, while the similar levels of blood BCL2, BAX, and TP53 transcripts observed in preclinical subjects and controls is mimicked by pre-symptomatic MJD mice, the expression profile of these genes in patient brains is partially replicated by symptomatic MJD mice. Globally, our findings indicate that there is tissue-specific vulnerability to apoptosis in MJD subjects and that this tissue-dependent behavior is partially replicated in a MJD mouse model.
The Clinical Significance and Role of CXCL1 Chemokine in Gastrointestinal Cancers
Authors: Korbecki Jan , Bosiacki Mateusz , Barczak Katarzyna , Łagocka Ryta , Chlubek Dariusz , Baranowska-Bosiacka Irena
Published: May 2023

One area of cancer research is the interaction between cancer cells and immune cells, in which chemokines play a vital role. Despite this, a comprehensive summary of the involvement of C-X-C motif ligand 1 (CXCL1) chemokine (also known as growth-regulated gene-α (GRO-α), melanoma growth-stimulatory activity (MGSA)) in cancer processes is lacking. To address this gap, this review provides a detailed analysis of CXCL1’s role in gastrointestinal cancers, including head and neck cancer, esophageal cancer, gastric cancer, liver cancer (hepatocellular carcinoma (HCC)), cholangiocarcinoma, pancreatic cancer (pancreatic ductal adenocarcinoma), and colorectal cancer (colon cancer and rectal cancer). This paper presents the impact of CXCL1 on various molecular cancer processes, such as cancer cell proliferation, migration, and invasion, lymph node metastasis, angiogenesis, recruitment to the tumor microenvironment, and its effect on immune system cells, such as tumor-associated neutrophils (TAN), regulatory T (Treg) cells, myeloid-derived suppressor cells (MDSCs), and macrophages. Furthermore, this review discusses the association of CXCL1 with clinical aspects of gastrointestinal cancers, including its correlation with tumor size, cancer grade, tumor–node–metastasis (TNM) stage, and patient prognosis. This paper concludes by exploring CXCL1’s potential as a therapeutic target in anticancer therapy.