bluuebunny/crossref_metadata_2025 huggingface dataset:
Early Solid Diet Supplementation Influences the Proteomics of Rumen Epithelium in Goat Kids
Authors: Zhuang Yimin , Lv Xiaokang , Cui Kai , Chai Jianmin , Zhang Naifeng
Published: May 2023

It is well known that solid diet supplementation in early life can significantly promote rumen development and metabolic function in young ruminants. However, the changes in the expressed proteome and related metabolism in rumen epithelium in response to a supplemented solid diet remain unclear. In this study, rumen epithelial tissue from goats in three diet regimes including milk replacer only (MRO), milk replacer supplemented concentrate (MRC), and milk replacer supplemented concentrate plus alfalfa pellets (MCA) were collected for measurement of the expression of epithelial proteins using proteomic technology (six per group). The results showed that solid diet significantly improved the growth performance of goats, enhanced the ability of rumen fermentation, and promoted the development of epithelial papilla (p < 0.05). Proteome analysis revealed the distinct difference in the expressed protein in the MRC and MCA group compared with the MRO group (42 upregulated proteins and 79 downregulated proteins in MRC; 38 upregulated proteins and 73 downregulated proteins in MCA). Functional analysis showed that solid diet supplementation activated a variety of molecular functions in the epithelium, including protein binding, ATP binding, structural constituent of muscle, etc., in the MRC and MCA groups. Meanwhile, the expression of proteins related to fatty acid metabolism, the PPAR signaling pathway, valine, leucine, and isoleucine degradation, and butanoate metabolism were upregulated, being stimulated by solid feed. In contrast, the proteins associated with carbohydrate digestion and absorption and glycosaminoglycan degradation were downregulated. In addition, the protein expression of enzymes involved in ketone body synthesis in the rumen was generally activated, which was caused by solid feed. In summary, solid feed promoted the development of rumen epithelium by changing the expression of proteins related to fatty acid metabolism, energy synthesis, and signal transduction. The ketone body synthesis pathway might be the most important activated pathway, and provides energy for rumen development.
Real-Life Advantages and Limits of Baricitinib for the Late Treatment of Adults Hospitalized with COVID-19
Authors: Poliseno Mariacristina , Lacedonia Donato , Niglio Mariangela , De Gregorio Federica , Minafra Graziano Antonio , Campanino Terence , Giganti Giulio , Scioscia Giulia , Santantonio Teresa Antonia , Foschino Barbaro Maria Pia , Lo Caputo Sergio
Published: May 2023

Baricitinib, a reversible Janus-associated kinase-inhibitor, is approved for treating COVID-19, combined with Dexamethasone and, eventually, with Remdesivir (RDV). This retrospective cohort study assesses the real-life advantages and limits of Baricitinib in the current pandemic scenario. Data of all patients consecutively hospitalized with moderate/severe COVID-19 between 1 October 2021 and 31 March 2022 were retrospectively collected and described according to the treatment received (Baricitinib, Baricitinib + RDV, none). We performed survival analyses to estimate the 21-day probability of Intensive Care Unit (ICU) admission, death, and composite. We built multivariate Cox regression models to identify ICU admission/death predictors among patients’ features. Of 111 subjects, 28 received Baricitinib, 21 received Baricitinib + RDV, and 62 could not be treated due to pre-existing conditions. Treated patients had a comparable risk of death (HR 0.50, 95% C.I. 0.20–1.26, p = 0.14) but remarkably lower risk of 21-day ICU admission (H.R., 0.10, 95% C.I., 0.01–0.86, p = 0.03), regardless of the type of treatment received. At multivariable analysis, older age was the only predictor of ICU admission/death (HR 1.14, 95% C.I. 1.03–1.26, p ≤ 0.01).Although effective, the high prevalence of elderly, co-morbid patients limits Baricitinib use in the current pandemic setting.
Association of Polymorphisms in FSHR, INHA, ESR1, and BMP15 with Recurrent Implantation Failure
Authors: Ko Eun-Ju , Shin Ji-Eun , Lee Jung-Yong , Ryu Chang-Soo , Hwang Ji-Young , Kim Young-Ran , Ahn Eun-Hee , Kim Ji-Hyang , Kim Nam-Keun
Published: May 2023

Recurrent implantation failure (RIF) refers to two or more unsuccessful in vitro fertilization embryo transfers in the same individual. Embryonic characteristics, immunological factors, and coagulation factors are known to be the causes of RIF. Genetic factors have also been reported to be involved in the occurrence of RIF, and some single nucleotide polymorphisms (SNPs) may contribute to RIF. We examined SNPs in FSHR, INHA, ESR1, and BMP15, which have been associated with primary ovarian failure. A cohort of 133 RIF patients and 317 healthy controls consisting of all Korean women was included. Genotyping was performed by Taq-Man genotyping assays to determine the frequency of the following polymorphisms: FSHR rs6165, INHA rs11893842 and rs35118453, ESR1 rs9340799 and rs2234693, and BMP15 rs17003221 and rs3810682. The differences in these SNPs were compared between the patient and control groups. Our results demonstrate a decreased prevalence of RIF in subjects with the FSHR rs6165 A>G polymorphism [AA vs. AG adjusted odds ratio (AOR) = 0.432; confidence interval (CI) = 0.206–0.908; p = 0.027, AA+AG vs. GG AOR = 0.434; CI = 0.213–0.885; p = 0.022]. Based on a genotype combination analysis, the GG/AA (FSHR rs6165/ESR1 rs9340799: OR = 0.250; CI = 0.072–0.874; p = 0.030) and GG-CC (FSHR rs6165/BMP15 rs3810682: OR = 0.466; CI = 0.220–0.987; p = 0.046) alleles were also associated with a decreased RIF risk. Additionally, the FSHR rs6165GG and BMP15 rs17003221TT+TC genotype combination was associated with a decreased RIF risk (OR = 0.430; CI = 0.210–0.877; p = 0.020) and increased FSH levels, as assessed by an analysis of variance. The FSHR rs6165 polymorphism and genotype combinations are significantly associated with RIF development in Korean women.
Chemical, Biological and Biomedical Aspects of Bioantioxidants
Authors: Saha Sarmistha , Saso Luciano , Trofimov Aleksei V. , Yablonskaya Olga I.
Published: May 2023

Bioantioxidants are biologically important antioxidants, a heterogeneous variety of molecules, which are difficult to classify using commonly shared structural features [...]
Physical Training vs. Perindopril Treatment on Arterial Stiffening of Spontaneously Hypertensive Rats: A Proteomic Analysis and Possible Mechanisms
Authors: Miotto Danyelle Siqueira , Duchatsch Francine , Dionizio Aline , Buzalaf Marília Afonso Rabelo , Amaral Sandra Lia
Published: May 2023

(1) Background: Arterial stiffness is an important predictor of cardiovascular events. Perindopril and physical exercise are important in controlling hypertension and arterial stiffness, but the mechanisms are unclear. (2) Methods: Thirty-two spontaneously hypertensive rats (SHR) were evaluated for eight weeks: SHRC (sedentary); SHRP (sedentary treated with perindopril—3 mg/kg) and SHRT (trained). Pulse wave velocity (PWV) analysis was performed, and the aorta was collected for proteomic analysis. (3) Results: Both treatments determined a similar reduction in PWV (−33% for SHRP and −23% for SHRT) vs. SHRC, as well as in BP. Among the altered proteins, the proteomic analysis identified an upregulation of the EH domain-containing 2 (EHD2) protein in the SHRP group, required for nitric oxide-dependent vessel relaxation. The SHRT group showed downregulation of collagen-1 (COL1). Accordingly, SHRP showed an increase (+69%) in the e-NOS protein level and SHRT showed a lower COL1 protein level (−46%) compared with SHRC. (4) Conclusions: Both perindopril and aerobic training reduced arterial stiffness in SHR; however, the results suggest that the mechanisms can be distinct. While treatment with perindopril increased EHD2, a protein involved in vessel relaxation, aerobic training decreased COL1 protein level, an important protein of the extracellular matrix (ECM) that normally enhances vessel rigidity.
Hereditary Breast Cancer in Romania—Molecular Particularities and Genetic Counseling Challenges in an Eastern European Country
Authors: Cătană Andreea , Trifa Adrian P. , Achimas-Cadariu Patriciu A. , Bolba-Morar Gabriela , Lisencu Carmen , Kutasi Eniko , Chelaru Vlad F. , Muntean Maximilian , Martin Daniela L. , Antone Nicoleta Z. , Fetica Bogdan , Pop Florina , Militaru Mariela S.
Published: May 2023

In Romania, breast cancer (BC) is the most common malignancy in women. However, there is limited data on the prevalence of predisposing germline mutations in the population in the era of precision medicine, where molecular testing has become an indispensable tool in cancer diagnosis, prognosis, and therapeutics. Therefore, we conducted a retrospective study to determine the prevalence, mutational spectrum, and histopathological prediction factors for hereditary breast cancer (HBC) in Romania. A cohort of 411 women diagnosed with BC selected upon NCCN v.1.2020 guidelines underwent an 84-gene NGS-based panel testing for breast cancer risk assessment during 2018–2022 in the Department of Oncogenetics of the Oncological Institute of Cluj-Napoca, Romania. A total of 135 (33%) patients presented pathogenic mutations in 19 genes. The prevalence of genetic variants was determined, and demographic and clinicopathological characteristics were analyzed. We observed differences among BRCA and non-BRCA carriers regarding family history of cancer, age of onset, and histopathological subtypes. Triple-negative (TN) tumors were more often BRCA1 positive, unlike BRCA2 positive tumors, which were more often the Luminal B subtype. The most frequent non-BRCA mutations were found in CHEK2, ATM, and PALB2, and several recurrent variants were identified for each gene. Unlike other European countries, germline testing for HBC is still limited due to the high costs and is not covered by the National Health System (NSH), thus leading to significant discrepancies related to the screening and prophylaxis of cancer.
Dimethyl Fumarate as Potential Treatment for Alzheimer’s Disease: Rationale and Clinical Trial Design
Authors: Sharkus Robert , Thakkar Richa , Kolson Dennis L. , Constantinescu Cris S.
Published: May 2023

Alzheimer’s Disease (AD) is a debilitating disease that leads to severe cognitive impairment and functional decline. The role of tau hyperphosphorylation and amyloid plaque deposition in the pathophysiology of AD has been well described; however, neuroinflammation and oxidative stress related to sustained microglial activation is thought to play a significant role in the disease process as well. NRF-2 has been identified in modulating the effects of inflammation and oxidative stress in AD. Activation of NRF-2 leads to an increased production of antioxidant enzymes, including heme oxygenase, which has been shown to have protective effects in neurodegenerative disorders such as AD. Dimethyl fumarate and diroximel fumarate (DMF) have been approved for the use in relapsing–remitting multiple sclerosis. Research indicates that they can modulate the effects of neuroinflammation and oxidative stress through the NRF-2 pathway, and as such, could serve as a potential therapeutic option in AD. We propose a clinical trial design that could be used to assess DMF as a treatment option for AD.
Parnassin, a Novel Therapeutic Peptide, Alleviates Skin Lesions in a DNCB-Induced Atopic Dermatitis Mouse Model
Authors: Hwang-Bo Jeon , Veerappan Karpagam , Moon Hyunhye , Lee Tae-Hoon , Lee Kang-Woon , Park Junhyung , Chung Hoyong
Published: May 2023

Atopic dermatitis (AD) is a chronic inflammatory skin disease which requires continuous treatment due to its relapsing nature. The current treatment includes steroids and nonsteroidal agents targeting inflammation but long-term administration causes various side effects such as skin atrophy, hirsutism, hypertension and diarrhea. Thus, there is an unmet need for safer and effective therapeutic agents in the treatment of AD. Peptides are small biomolecule drugs which are highly potent and remarkably have less side effects. Parnassin is a tetrapeptide with predicted anti-microbial activity curated from Parnassius bremeri transcriptome data. In this study, we confirmed the effect of parnassin on AD using a DNCB-induced AD mouse model and TNF-α/IFN-γ-stimulated HaCaT cells. In the AD mouse model, topical administration of parnassin improved skin lesions and symptoms in AD mice, such as epidermal thickening and mast cell infiltration, similar to the existing treatment, dexamethasone, and did not affect body weight, or the size and weight of spleen. In TNF-α/IFN-γ-stimulated HaCaT cells, parnassin inhibited the expression of Th2-type chemokine CCL17 and CCL22 genes by suppressing JAK2 and p38 MAPK signaling kinases and their downstream transcription factor STAT1. Parnassin also significantly reduced the gene expression of TSLP and IL-31, which are pruritus-inducing cytokines. These findings suggested that parnassin alleviates AD-like lesions via its immunomodulatory effects and can be used as a candidate drug for the prevention and treatment of AD because it is safer than existing treatments.
Estimation of Impedance Features and Classification of Carcinoma Breast Cancer Using Optimization Techniques
Authors: Asadi Majid
Published: May 2023

Breast cancer is the most prevalent form of cancer and the primary cause of cancer-related mortality among women globally. Breast cancer diagnosis involves multiple variables, making it a complex process. Therefore, the accurate estimation of features for diagnosing breast cancer is of great importance. The present study used a dataset of 21 patients with carcinoma breast cancer. Polynomial regression analysis was used to non-invasively estimate six impedance features for the diagnosis of breast cancer, including the phase angle at 500 KHz (PA500), impedance distance between spectral ends (DA), area normalized by DA (A/DA), maximum of the spectrum (Max IP), the distance between impedivity (ohm) at zero frequency and the real part of the maximum frequency point (DR), and length of the spectral curve (P). The results indicated that the polynomial degrees needed to estimate the PA500, DA, A/DA, Max IP, DR, and P features based on tumor size were 2, 2, 3, 3, 2, and 2, respectively. Additionally, we utilized a nonlinear constrained optimization (NCO) analysis to calculate the eight threshold levels for the classification of the impedance features. The deduction of eight classifications for each feature may also be an effective tool for decision-making in breast cancer. These findings may help oncologists to estimate the impedance features for breast cancer diagnosis non-invasively.
Molybdenum Disulfide/Nickel-Metal Organic Framework Hybrid Nanosheets Based Disposable Electrochemical Sensor for Determination of 4-Aminophenol in Presence of Acetaminophen
Authors: Dourandish Zahra , Sheikhshoaie Iran , Maghsoudi Shahab
Published: May 2023

The toxicity of commonly used drugs, such as acetaminophen (ACAP) and its degradation-derived metabolite of 4-aminophenol (4-AP), underscores the need to achieve an effective approach in their simultaneous electrochemical determination. Hence, the present study attempts to introduce an ultra-sensitive disposable electrochemical 4-AP and ACAP sensor based on surface modification of a screen-printed graphite electrode (SPGE) with a combination of MoS2 nanosheets and a nickel-based metal organic framework (MoS2/Ni-MOF/SPGE sensor). A simple hydrothermal protocol was implemented to fabricate MoS2/Ni-MOF hybrid nanosheets, which was subsequently tested for properties using valid techniques including X-ray diffraction (XRD), field emission-scanning electron microscopy (FE-SEM), energy dispersive X-ray spectroscopy (EDX), Fourier transformed infrared spectroscopy (FTIR), and N2 adsorption-desorption isotherm. The 4-AP detection behavior on MoS2/Ni-MOF/SPGE sensor was followed by cyclic voltammetry (CV), chronoamperometry and differential pulse voltammetry (DPV). Our experimental findings on the generated sensor confirmed a broad linear dynamic range (LDR) for 4-AP from 0.1 to 600 μM with a high sensitivity of 0.0666 μA/μM and a low limit of detection (LOD) of 0.04 μM. In addition, an analysis of real specimens such as tap water sample as well as a commercial sample (acetaminophen tablets) illuminated the successful applicability of as-developed sensor in determining ACAP and 4-AP, with an impressive recovery rate.
Concrete and Abstract Concepts in Primary Progressive Aphasia and Alzheimer’s Disease: A Scoping Review
Authors: Mancano Martina , Papagno Costanza
Published: May 2023

The concreteness effect (CE), namely a better performance with concrete compared to abstract concepts, is a constant feature in healthy people, and it usually increases in persons with aphasia (PWA). However, a reversal of the CE has been reported in patients affected by the semantic variant of Primary Progressive Aphasia (svPPA), a neurodegenerative disease characterized by anterior temporal lobe (ATL) atrophy. The present scoping review aims at identifying the extent of evidence regarding the abstract/concrete contrast in Alzheimer’s disease (AD) and svPPA and associated brain atrophy. Five online databases were searched up to January 2023 to identify papers where both concrete and abstract concepts were investigated. Thirty-one papers were selected and showed that while in patients with AD, concrete words were better processes than abstract ones, in most svPPA patients, there was a reversal of the CE, with five studies correlating the size of this effect with ATL atrophy. Furthermore, the reversal of CE was associated with category-specific impairments (living things) and with a selective deficit of social words. Future work is needed to disentangle the role of specific portions of the ATL in concept representation.
Oromotor Nonverbal Performance and Speech Motor Control: Theory and Review of Empirical Evidence
Authors: Weismer Gary
Published: May 2023

This position paper offers a perspective on the long-standing debate concerning the role of oromotor, nonverbal gestures in understanding typical and disordered speech motor control secondary to neurological disease. Oromotor nonverbal tasks are employed routinely in clinical and research settings, but a coherent rationale for their use is needed. The use of oromotor nonverbal performance to diagnose disease or dysarthria type, versus specific aspects of speech production deficits that contribute to loss of speech intelligibility, is argued to be an important part of the debate. Framing these issues are two models of speech motor control, the Integrative Model (IM) and Task-Dependent Model (TDM), which yield contrasting predictions of the relationship between oromotor nonverbal performance and speech motor control. Theoretical and empirical literature on task specificity in limb, hand, and eye motor control is reviewed to demonstrate its relevance to speech motor control. The IM rejects task specificity in speech motor control, whereas the TDM is defined by it. The theoretical claim of the IM proponents that the TDM requires a special, dedicated neural mechanism for speech production is rejected. Based on theoretical and empirical information, the utility of oromotor nonverbal tasks as a window into speech motor control is questionable.
Reduced Expression of Very-Long-Chain Acyl-CoA Synthetases SLC27A4 and SLC27A6 in the Glioblastoma Tumor Compared to the Peritumoral Area
Authors: Korbecki Jan , Kojder Klaudyna , Jeżewski Dariusz , Simińska Donata , Tomasiak Patrycja , Tarnowski Maciej , Chlubek Dariusz , Baranowska-Bosiacka Irena
Published: May 2023

This study aimed to analyze solute carrier family 27 (SLC27) in glioblastoma tumors. The investigation of these proteins will provide insight into how and to what extent fatty acids are taken up from the blood in glioblastoma tumors, as well as the subsequent fate of the up-taken fatty acids. Tumor samples were collected from a total of 28 patients and analyzed using quantitative real-time polymerase chain reaction (qRT–PCR). The study also sought to explore the relationship between SLC27 expression and patient characteristics (age, height, weight, body mass index (BMI), and smoking history), as well as the expression levels of enzymes responsible for fatty acid synthesis. The expression of SLC27A4 and SLC27A6 was lower in glioblastoma tumors compared to the peritumoral area. Men had a lower expression of SLC27A5. Notably, a positive correlation was observed between the expression of SLC27A4, SLC27A5, and SLC27A6 and smoking history in women, whereas men exhibited a negative correlation between these SLC27s and BMI. The expression of SLC27A1 and SLC27A3 was positively correlated with the expression of ELOVL6. In comparison to healthy brain tissue, glioblastoma tumors take up fewer fatty acids. The metabolism of fatty acids in glioblastoma is dependent on factors such as obesity and smoking.
Roles of Brand Benefits and Relationship Commitment in Consumers’ Social Media Behavior around Sustainable Fashion
Authors: Choi Tae Rang , Ahn Jisoo
Published: May 2023

As climate change continues, environmental sustainability has become a popular topic among brands and consumer groups. The fashion industry has detrimental impacts on the natural environment; however, little is known about how brand benefits can help sustainable fashion brands develop relationships with consumers and promote consumer behavior. This study focuses on Instagram to investigate how consumers’ perceived brand benefits predict relationship commitment, electronic word-of-mouth (eWOM), and purchase intention. Prior studies have overlooked the possible effects of various benefits. This study outlines five benefits of sustainable fashion brands: inner self-expression, social self-expression, warm glow, green, and economic benefits. Results from a survey of sustainable fashion brand followers on Instagram showed that eWOM positively related with economic benefits and negatively with warm glow and green benefits. Findings further indicated a mediating effect of relationship commitment between benefits and consumers’ behavior. Lastly, the level of environmental attitude influenced the mediating impact of relationship commitment. The implications of these findings are discussed, and suggestions for future research are provided.
Modelling the Construction Projects Implementation Barriers: A Structure Equation Modelling Approach
Authors: Almakayeel Naif , Buniya Mohanad Kamil , Abubakar Abdurrahman Salihu , Kamil Shahad Mohanad , Qureshi Karishma M. , Qureshi Mohamed Rafik Noor Mohamed
Published: May 2023

The construction industry significantly impacts the environment and uses natural resources that negatively impact the built environment. Conversely, green buildings can lead to several environmental, social, and economic benefits. The paper explores the barriers that impede the implementation of sustainable construction projects in Iraq. It draws on a literature review in the field of sustainable construction, as well as a survey of construction industry professionals in Iraq. A total of 17 major barriers to sustainable construction projects are identified and classified into four groups to reduce the environmental impacts of construction activities. The variance inflation factor (VIF) values of dimensions were less than 3.5, indicating that they independently contribute to the second-order constructs. Therefore, it is essential to implement green building practices, such as using energy-efficient materials and systems, adopting energy-efficient designs, and using renewable energy sources. Furthermore, the findings suggest that sustainable construction practices can also help improve quality of life.
Shaping the Architects of Tomorrow, Interplay of Teaching Philosophies and Practice Requirements: An Empirical Taxonomy of Professional Architectural Practice in the UAE
Authors: Chohan Afaq Hyder , Awad Jihad
Published: May 2023

The UAE’s thriving real estate market has resulted in a highly diversified built environment, attracting architects from around the world. However, this has also led to a misconception within the architectural practice and its regularization, particularly concerning acceptable professional qualifications. Therefore, this study aims to address these issues and provide a blueprint for policymakers and stakeholders. This study provided a comprehensive overview of architectural practice in the UAE by identifying the services offered by professionals in the built environment and categorizing them based on their qualifications and professional titles. The study adopts a classical research method, which includes a literature review, unstructured interviews, a statistical survey, and analysis. The study identifies 13 building designs and allied services commonly provided by professionals in the built environment in the UAE. The professionals providing these services are categorized based on their qualifications and professional titles, which include registered architects, architect engineers, architectural consultants, engineering consultants, and project managers. Furthermore, the study clarifies the definition of an acceptable qualification for a principal architect, which can be used as a reference by young professionals to understand the trends in architectural qualification and practice. The results of the study can also be used by policymakers and stakeholders to address the issues in professional practice and improve the quality of architectural services in the UAE.
Fabrication of an Electrocatalyst Based on Rare Earth Manganites Incorporated with Carbon Nanofiber Hybrids: An Efficient Electrochemical Biosensor for the Detection of Anti-Inflammatory Drug Mefenamic Acid
Authors: Alagarsamy Saranvignesh , Sundaresan Ruspika , Chen Shen-Ming , Devi J. Meena , Chandrasekar Narendhar , Ramachandran Balaji
Published: May 2023

Pharmaceutical and personal care products are emerging as a new category of environmental pollution. Analytical drug detection from a biological sample for detection is still crucial today. Mefenamic acid (MA) is an anti-inflammatory drug utilized for its antipyretic and analgesic properties, which is harmful to patients at higher dosages and is also recognized as a chemical pollutant that harms the environment. In this view, Dysprosium manganite/carbon nanofiber (DMO/CNF) was prepared by hydrothermal method for the electrochemical detection of MA. DMO/CNF/GCE exhibits high selectivity, excellent anti-interference, good stability, and reproducibility toward the detection of MA. The enhanced electrochemical performance of DMO/CNF/GCE was attributed to their synergetic interaction. Under optimized conditions, DMO/CNF/GCE shows a wide linear range of 0.01–741 μM and a low LOD of 0.009 μM. Satisfactory recoveries were obtained for human blood and tablet samples. Thus, the proposed DMO/CNF nanocomposite emerges as a promising material for the detection of MA.
c-Met Mediated Cytokine Network Promotes Brain Metastasis of Breast Cancer by Remodeling Neutrophil Activities
Authors: Liu Yin , Smith Margaret R. , Wang Yuezhu , D’Agostino Ralph , Ruiz Jimmy , Lycan Thomas , Kucera Gregory L. , Miller Lance D. , Li Wencheng , Chan Michael D. , Farris Michael , Su Jing , Song Qianqian , Zhao Dawen , Chandrasekaran Arvind , Xing Fei
Published: May 2023

The brain is one of the most common metastatic sites among breast cancer patients, especially in those who have Her2-positive or triple-negative tumors. The brain microenvironment has been considered immune privileged, and the exact mechanisms of how immune cells in the brain microenvironment contribute to brain metastasis remain elusive. In this study, we found that neutrophils are recruited and influenced by c-Met high brain metastatic cells in the metastatic sites, and depletion of neutrophils significantly suppressed brain metastasis in animal models. Overexpression of c-Met in tumor cells enhances the secretion of a group of cytokines, including CXCL1/2, G-CSF, and GM-CSF, which play critical roles in neutrophil attraction, granulopoiesis, and homeostasis. Meanwhile, our transcriptomic analysis demonstrated that conditioned media from c-Met high cells significantly induced the secretion of lipocalin 2 (LCN2) from neutrophils, which in turn promotes the self-renewal of cancer stem cells. Our study unveiled the molecular and pathogenic mechanisms of how crosstalk between innate immune cells and tumor cells facilitates tumor progression in the brain, which provides novel therapeutic targets for treating brain metastasis.
Harnessing the Microbiome to Reduce Pancreatic Cancer Burden
Authors: Bastos Ana Raquel , Pereira-Marques Joana , Ferreira Rui Manuel , Figueiredo Ceu
Published: May 2023

Pancreatic cancer mortality is expected to rise in the next decades. This aggressive malignancy has a dismal prognosis due to late diagnosis and resistance to treatment. Increasing evidence indicates that host–microbiome interactions play an integral role in pancreatic cancer development, suggesting that harnessing the microbiome might offer promising opportunities for diagnostic and therapeutic interventions. Herein, we review the associations between pancreatic cancer and the intratumoral, gut and oral microbiomes. We also explore the mechanisms with which microbes influence cancer development and the response to treatment. We further discuss the potentials and limitations of using the microbiome as a target for therapeutic interventions, in order to improve pancreatic cancer patient outcomes.
The Uncomfortable Truth: Open Thoracotomy versus Minimally Invasive Surgery in Lung Cancer: A Systematic Review and Meta-Analysis
Authors: Kim Dohun , Woo Wongi , Shin Jae Il , Lee Sungsoo
Published: May 2023

For decades, lung surgery in thoracic cancer has evolved in two ways: saving more parenchyma and being minimally invasive. Saving parenchyma is a fundamental principle of surgery. However, minimally invasive surgery (MIS) is a matter of approach, so it has to do with advances in surgical techniques and tools. For example, MIS has become possible with the introduction of VATS (video-assisted thoracic surgery), and the development of tools has extended the indication of MIS. Especially, RATS (robot-assisted thoracic surgery) improved the quality of life for patients and the ergonomics of doctors. However, the dichotomous idea that the MIS is new and right but the open thoracotomy is old and useless may be inappropriate. In fact, MIS is exactly the same as a classic thoracotomy in that it removes the mass/parenchyma containing cancer and mediastinal lymph nodes. Therefore, in this study, we compare randomized-controlled trials about open thoracotomy and MIS to find out which surgical method is more helpful.
Detection of Ultra-Rare ESR1 Mutations in Primary Breast Cancer Using LNA-Clamp ddPCR
Authors: Hashimoto Yoko , Masunaga Nanae , Kagara Naofumi , Abe Kaori , Yoshinami Tetsuhiro , Tsukabe Masami , Sota Yoshiaki , Miyake Tomohiro , Tanei Tomonori , Shimoda Masafumi , Shimazu Kenzo
Published: May 2023

ESR1 mutations in breast cancer are one of the mechanisms of resistance to aromatase inhibitors. These mutations are common in metastatic breast cancer; however, these are rare in primary breast cancer. However, these data have been analyzed mainly in formalin-fixed, paraffin-embedded tissue; thus, rare mutations that may be present in primary breast cancer may be overlooked. In this study, we developed a highly sensitive mutation detection method called locked nucleic acid (LNA)-clamp droplet digital PCR (ddPCR) and validated it. The mutation detection sensitivity was substantiated to 0.003%. Then, we used this method to analyze ESR1 mutations in fresh-frozen (FF) tissues of primary breast cancer. cDNA extracted from the FF tissues of 212 patients with primary breast cancers were measured. Twenty-eight ESR1 mutations were found in twenty-seven (12.7%) patients. Sixteen (7.5%) patients had Y537S mutations and twelve (5.7%) had D538G mutations. Two mutations with a variant allele frequency (VAF) of ≥0.1% and twenty-six mutations with a VAF of <0.1% were found. By using this LNA-clamp ddPCR, this study demonstrated the presence of minor clones with a VAF of <0.1% in primary breast cancer.
Prognostic Value of Erythroblastic Leukemia Viral Oncogene Homolog 2 and Neuregulin 4 in Hepatocellular Carcinoma
Authors: Rou Woo Sun , Eun Hyuk Soo , Choung Sorim , Jeon Hong Jae , Joo Jong Seok , Kang Sun Hyung , Lee Eaum Seok , Kim Seok Hyun , Kwon In Sun , Ku Bon Jeong , Lee Byung Seok
Published: May 2023

Although the roles of erythroblastic leukemia viral oncogene homolog 2 (ERBB2), neuregulin 4 (NRG4), and mitogen-inducible gene 6 (MIG6) in epidermal growth factor receptor signaling in hepatocellular carcinoma (HCC) and other malignancies have been previously investigated, the prognostic value of their serum levels in HCC remains undetermined. In the present study, correlations between serum levels and tumor characteristics, overall survival, and tumor recurrence were analyzed. Furthermore, the prognostic potential of the serum levels of these biomarkers was evaluated relative to that of alpha-fetoprotein. Both ERBB2 and NRG4 correlated with the Barcelona Clinic Liver Cancer stage, ERBB2 correlated with the tumor-maximal diameter, and NRG4 correlated with a tumor number. Cox proportional hazards regression analysis revealed that ERBB2 (hazard ratio [HR], 2.719; p = 0.007) was an independent prognostic factor for overall survival. Furthermore, ERBB2 (HR, 2.338; p = 0.002) and NRG4 (HR, 431.763; p = 0.001) were independent prognostic factors for tumor recurrence. The products of ERBB2 and NRG4 had a better area under the curve than alpha-fetoprotein for predicting 6-month, 1-year, 3-year, and 5-year mortality. Therefore, these factors could be used to evaluate prognosis and monitor treatment response in patients with HCC.
Effect on Germline Mutation Rate in a High-Risk Chinese Breast Cancer Cohort after Compliance with The National Comprehensive Cancer Network (NCCN) 2023 v.1 Testing Criteria
Authors: Kwong Ava , Ho Cecilia Y. S. , Luk Wing-Pan , Fung Ling-Hiu , Au Chun-Hang , Ma Edmond S. K.
Published: May 2023

Background: The National Comprehensive Cancer Network (NCCN) testing criteria for the high-penetrance breast cancer susceptibility genes, specifically BRCA1, BRCA2, CDH1, PALB2, PTEN, and TP53, have been recently modified in 2023 to 2023 v.1. The following criteria have been changed: (1) from a person diagnosed with breast cancer at ≤45 to ≤50; (2) from aged 45–50 of personal breast diagnosis to any age of diagnosis with multiple breast cancers; and (3) from aged ≥51 of personal breast diagnosis to any age of diagnosis with family history listed in NCCN 2022 v.2. Methods: High-risk breast cancer patients (n = 3797) were recruited from the Hong Kong Hereditary Breast Cancer Family Registry between 2007 and 2022. Patients were grouped according to NCCN testing criteria 2023 v.1 and 2022 v.2. A 30-gene panel for hereditary breast cancer was performed. The mutation rates on high-penetrance breast cancer susceptibility genes were compared. Results: About 91.2% of the patients met the 2022 v.2 criteria, while 97.5% of the patients met the 2023 v.1 criteria. An extra 6.4% of the patients were included after the revision of the criteria, and 2.5% of the patients did not meet both testing criteria. The germline BRCA1/2 mutation rates for patients meeting the 2022 v.2 and 2023 v.1 criteria were 10.1% and 9.6%, respectively. The germline mutation rates of all 6 high-penetrance genes in these two groups were 12.2% and 11.6%, respectively. Among the additional 242 patients who were included using the new selection criteria, the mutation rates were 2.1% and 2.5% for BRCA1/2 and all 6 high-penetrance genes, respectively. Patients who did not meet both testing criteria were those with multiple personal cancers, a strong family history of cancers not listed in the NCCN, unclear pathology information, or the patient’s voluntary intention to be tested. The mutation rates of BRCA1/2 and the 6 high-penetrance genes in these patients were 5.3% and 6.4%, respectively. Conclusion: This study provided a real-world application of the revision of NCCN guidelines and its effect on the germline mutation rate in the Chinese population. Applying the updated criteria for further genetic investigation would increase the positive detection rate, and potentially more patients would benefit. The balance between the resource and outcome requires careful consideration.
Computational Optimization of Irradiance and Fluence for Interstitial Photodynamic Therapy Treatment of Patients with Malignant Central Airway Obstruction
Authors: Oakley Emily , Parilov Evgueni , Beeson Karl , Potasek Mary , Ivanick Nathaniel , Tworek Lawrence , Hutson Alan , Shafirstein Gal
Published: May 2023

There are no effective treatments for patients with extrinsic malignant central airway obstruction (MCAO). In a recent clinical study, we demonstrated that interstitial photodynamic therapy (I-PDT) is a safe and potentially effective treatment for patients with extrinsic MCAO. In previous preclinical studies, we reported that a minimum light irradiance and fluence should be maintained within a significant volume of the target tumor to obtain an effective PDT response. In this paper, we present a computational approach to personalized treatment planning of light delivery in I-PDT that simultaneously optimizes the delivered irradiance and fluence using finite element method (FEM) solvers of either Comsol Multiphysics® or Dosie™ for light propagation. The FEM simulations were validated with light dosimetry measurements in a solid phantom with tissue-like optical properties. The agreement between the treatment plans generated by two FEMs was tested using typical imaging data from four patients with extrinsic MCAO treated with I-PDT. The concordance correlation coefficient (CCC) and its 95% confidence interval (95% CI) were used to test the agreement between the simulation results and measurements, and between the two FEMs treatment plans. Dosie with CCC = 0.994 (95% CI, 0.953–0.996) and Comsol with CCC = 0.999 (95% CI, 0.985–0.999) showed excellent agreement with light measurements in the phantom. The CCC analysis showed very good agreement between Comsol and Dosie treatment plans for irradiance (95% CI, CCC: 0.996–0.999) and fluence (95% CI, CCC: 0.916–0.987) in using patients’ data. In previous preclinical work, we demonstrated that effective I-PDT is associated with a computed light dose of ≥45 J/cm2 when the irradiance is ≥8.6 mW/cm2 (i.e., the effective rate-based light dose). In this paper, we show how to use Comsol and Dosie packages to optimize rate-based light dose, and we present Dosie’s newly developed domination sub-maps method to improve the planning of the delivery of the effective rate-based light dose. We conclude that image-based treatment planning using Comsol or Dosie FEM-solvers is a valid approach to guide the light dosimetry in I-PDT of patients with MCAO.
The Cross Talk between Cellular Senescence and Melanoma: From Molecular Pathogenesis to Target Therapies
Authors: Liu Jiahua , Zheng Runzi , Zhang Yanghuan , Jia Shuting , He Yonghan , Liu Jing
Published: May 2023

Melanoma is a malignant skin tumor that originates from melanocytes. The pathogenesis of melanoma involves a complex interaction that occurs between environmental factors, ultraviolet (UV)-light damage, and genetic alterations. UV light is the primary driver of the skin aging process and development of melanoma, which can induce reactive oxygen species (ROS) production and the presence of DNA damage in the cells, and results in cell senescence. As cellular senescence plays an important role in the relationship that exists between the skin aging process and the development of melanoma, the present study provides insight into the literature concerning the topic at present and discusses the relationship between skin aging and melanoma, including the mechanisms of cellular senescence that drive melanoma progression, the microenvironment in relation to skin aging and melanoma factors, and the therapeutics concerning melanoma. This review focuses on defining the role of cellular senescence in the process of melanoma carcinogenesis and discusses the targeting of senescent cells through therapeutic approaches, highlighting the areas that require more extensive research in the field.
Correction: Sankaranarayanan et al. Auger Emitter Conjugated PARP Inhibitor for Therapy in Triple Negative Breast Cancers: A Comparative In-Vitro Study. Cancers 2022, 14, 230
Authors: Sankaranarayanan Ramya Ambur , Peil Jennifer , Vogg Andreas T. J. , Bolm Carsten , Terhorst Steven , Classen Arno , Bauwens Matthias , Maurer Jochen , Mottaghy Felix , Morgenroth Agnieszka
Published: May 2023

The authors wish to replace the ‘Author Contributions’ statement and the affiliation for Jochen Maurer of this article [...]
US Evaluation of Topical Hemostatic Agents in Post-Thyroidectomy
Authors: Dolcetti Vincenzo , Lori Eleonora , Fresilli Daniele , Del Gaudio Giovanni , Di Bella Chiara , Pacini Patrizia , D’Andrea Vito , Frattaroli Fabrizio Maria , Vallone Giulia Giordana , Liberatore Piero , Pironi Daniele , Canu Gian Luigi , Calò Pietro Giorgio , Cantisani Vito , Sorrenti Salvatore
Published: May 2023

Background: the aim of this study was to describe the ultrasound appearance of topical hemostatics after thyroidectomy. Methods: we enrolled 84 patients who were undergoing thyroid surgery and were treated with two types of topical hemostats, 49 with an absorbable hemostat of oxidized regenerated cellulose (Oxitamp®) and 35 with a fibrin glue-based hemostat (Tisseel®). All patients were examined using B-mode ultrasound. Results: In 39 patients of the first group (approximately 80%), a hemostatic residue was detected and in some cases confused with a native gland residue, or with cancer recurrence in oncological patients. No residue was detected in patients in the second group. The main ultrasound characteristics of the tampon were analyzed and arranged according to predefined patterns, and suggestions to recognize it and avoid wrong diagnoses were provided. A part of the group of patients with tampon residue was re-evaluated after 6–12 months, ensuring that the swab remained for months after the maximum resorption time declared by the manufacturer. Conclusions: with equal hemostatic effectiveness, the fibrin glue pad is more favorable in the ultrasound follow-up because it creates reduced surgical outcomes. It is also important to know and recognize the ultrasound characteristics of oxidized cellulose-based hemostats in order to reduce the number of diagnostic errors and inappropriate diagnostic investigations.
Complement Activation and Up-Regulated Expression of Anaphylatoxin C3a/C3aR in Glioblastoma: Deciphering the Links with TGF-β and VEGF
Authors: Ah-Pine Franck , Malaterre-Septembre Axelle , Bedoui Yosra , Khettab Mohamed , Neal James W. , Freppel Sébastien , Gasque Philippe
Published: May 2023

The complement (C) innate immune system has been shown to be activated in the tumor microenvironment of various cancers. The C may support tumor growth by modulating the immune response and promoting angiogenesis through the actions of C anaphylatoxins (e.g., C5a, C3a). The C has important double-edged sword functions in the brain, but little is known about its role in brain tumors. Hence, we analyzed the distribution and the regulated expression of C3a and its receptor C3aR in various primary and secondary brain tumors. We found that C3aR was dramatically upregulated in Grade 4 diffuse gliomas, i.e., glioblastoma multiforme, IDH-wildtype (GBM) and astrocytoma, IDH-mutant, Grade 4, and was much less expressed in other brain tumors. C3aR was observed in tumor-associated macrophages (TAM) expressing CD68, CD18, CD163, and the proangiogenic VEGF. Robust levels of C3a were detected in the parenchyma of GBM as a possible result of Bb-dependent C activation of the alternative C pathway. Interestingly, in vitro models identified TGF-β1 as one of the most potent growth factors that upregulate VEGF, C3, and C3aR in TAM (PMA-differentiated THP1) cell lines. Further studies should help to delineate the functions of C3a/C3aR on TAMs that promote chemotaxis/angiogenesis in gliomas and to explore the therapeutic applications of C3aR antagonists for brain tumors.
Role of PSA Density and MRI in PSA Interpretation. Comment on Lumbreras et al. Variables Associated with False-Positive PSA Results: A Cohort Study with Real-World Data. Cancers 2023, 15, 261
Authors: Jue Joshua S. , Alameddine Mahmoud
Published: May 2023

Prostate-specific antigen (PSA) has been utilized as a prostate cancer screening test for its high sensitivity for prostate cancer but is often criticized for its low specificity [...]
Photocatalytic Technologies for Transformation and Degradation of Microplastics in the Environment: Current Achievements and Future Prospects
Authors: Xie Anyou , Jin Meiqing , Zhu Jiangwei , Zhou Qingwei , Fu Li , Wu Weihong
Published: May 2023

Microplastic (MP) pollution has emerged as a significant environmental concern, with exposure to it linked to numerous negative consequences for both ecosystems and humans. To tackle this complex issue, innovative technologies that are capable of effectively eliminating MPs from the environment are necessary. In this review, we examined a variety of bare and composite photocatalysts employed in the degradation process. An in-depth assessment of the benefits and drawbacks of each catalyst was presented. Additionally, we explored the photocatalytic mechanisms and factors influencing degradation. The review concludes by addressing the current challenges and outlining future research priorities, which will help guide efforts to mitigate MP contamination.
Embryonic Ethanol but Not Cannabinoid Exposure Affects Zebrafish Cardiac Development via Agrin and Sonic Hedgehog Interaction
Authors: Zhang Chengjin , Ezem Natalie , Mackinnon Shanta , Cole Gregory J.
Published: May 2023

Recent studies demonstrate the adverse effects of cannabinoids on development, including via pathways shared with ethanol exposure. Our laboratory has shown that both the nervous system and cardiac development are dependent on agrin modulation of sonic hedgehog (shh) and fibroblast growth factor (Fgf) signaling pathways. As both ethanol and cannabinoids impact these signaling molecules, we examined their role on zebrafish heart development. Zebrafish embryos were exposed to a range of ethanol and/or cannabinoid receptor 1 and 2 agonist concentrations in the absence or presence of morpholino oligonucleotides that disrupt agrin or shh expression. In situ hybridization was employed to analyze cardiac marker gene expression. Exposure to cannabinoid receptor agonists disrupted midbrain–hindbrain boundary development, but had no effect on heart development, as assessed by the presence of cardiac edema or the altered expression of cardiac marker genes. In contrast, exposure to 1.5% ethanol induced cardiac edema and the altered expression of cardiac marker genes. Combined exposure to agrin or shh morpholino and 0.5% ethanol disrupted the cmlc2 gene expression pattern, with the restoration of the normal expression following shh mRNA overexpression. These studies provide evidence that signaling pathways critical to heart development are sensitive to ethanol exposure, but not cannabinoids, during early zebrafish embryogenesis.