bluuebunny/crossref_metadata_2025 huggingface dataset:
Distinguishing Healthy and Carcinoma Cell Cultures Using Fluorescence Spectra Decomposition with a Genetic-Algorithm-Based Code
Authors: Pospíšilová Marie , Kalábová Hana , Kuncová Gabriela
Published: February 2023

In this paper, we analysed the steady state fluorescence spectra of cell suspensions containing healthy and carcinoma fibroblast mouse cells, using a genetic-algorithm-spectra-decomposition software (GASpeD). In contrast to other deconvolution algorithms, such as polynomial or linear unmixing software, GASpeD takes into account light scatter. In cell suspensions, light scatter plays an important role as it depends on the number of cells, their size, shape, and coagulation. The measured fluorescence spectra were normalized, smoothed and deconvoluted into four peaks and background. The wavelengths of intensities’ maxima of lipopigments (LR), FAD, and free/bound NAD(P)H (AF/AB) of the deconvoluted spectra matched published data. In deconvoluted spectra at pH = 7, the fluorescence intensities of the AF/AB ratio in healthy cells was always higher in comparison to carcinoma cells. In addition, the AF/AB ratio in healthy and carcinoma cells were influenced differently by changes in pH. In mixtures of healthy and carcinoma cells, AF/AB decreases when more than 13% of carcinoma cells are present. Expensive instrumentation is not required, and the software is user friendly. Due to these attributes, we hope that this study will be a first step in the development of new cancer biosensors and treatments with the use of optical fibers.
Defect-Engineering of 2D Dichalcogenide VSe2 to Enhance Ammonia Sensing: Acumens from DFT Calculations
Authors: Sanyal Gopal , Kaur Surinder Pal , Rout Chandra Sekhar , Chakraborty Brahmananda
Published: February 2023

Opportune sensing of ammonia (NH3) gas is industrially important for avoiding hazards. With the advent of nanostructured 2D materials, it is felt vital to miniaturize the detector architecture so as to attain more and more efficacy with simultaneous cost reduction. Adaptation of layered transition metal dichalcogenide as the host may be a potential answer to such challenges. The current study presents a theoretical in-depth analysis regarding improvement in efficient detection of NH3 using layered vanadium di-selenide (VSe2) with the introduction of point defects. The poor affinity between VSe2 and NH3 forbids the use of the former in the nano-sensing device’s fabrications. The adsorption and electronic properties of VSe2 nanomaterials can be tuned with defect induction, which would modulate the sensing properties. The introduction of Se vacancy to pristine VSe2 was found to cause about an eight-fold increase (from −012 eV to −0.97 eV) in adsorption energy. A charge transfer from the N 2p orbital of NH3 to the V 3d orbital of VSe2 has been observed to cause appreciable NH3 detection by VSe2. In addition to that, the stability of the best-defected system has been confirmed through molecular dynamics simulation, and the possibility of repeated usability has been analyzed for calculating recovery time. Our theoretical results clearly indicate that Se-vacant layered VSe2 can be an efficient NH3 sensor if practically produced in the future. The presented results will thus potentially be useful for experimentalists in designing and developing VSe2-based NH3 sensors.
Multicenter Testing of a Simple Molecular Diagnostic System for the Diagnosis of Mycobacterium Tuberculosis
Authors: Lee Hyo Joo , Kim Nam Hun , Lee Eun Hye , Yoon Young Soon , Jeong Yun Jeong , Lee Byung Chul , Koo Bonhan , Jang Yoon Ok , Kim Sung-Han , Kang Young Ae , Lee Sei Won , Shin Yong
Published: February 2023

Mycobacterium tuberculosis (MTB) is a communicable disease and still remains a threat to common health. Thus, early diagnosis and treatment are required to prevent the spread of infection. Despite the recent advances in molecular diagnostic systems, the commonly used MTB diagnostic tools are laboratory-based assays, such as mycobacterial culture, MTB PCR, and Xpert MTB/RIF. To address this limitation, point-of-care testing (POCT)-based molecular diagnostic technologies capable of sensitive and accurate detection even in environments with limited sources are needed. In this study, we propose simple tuberculosis (TB) molecular diagnostic assay by combining sample preparation and DNA-detection steps. The sample preparation is performed using a syringe filter with amine-functionalized diatomaceous earth and homobifunctional imidoester. Subsequently, the target DNA is detected by quantitative PCR (polymerase chain reaction). The results can be obtained within 2 h from samples with large volumes, without any additional instruments. The limit of detection of this system is 10 times higher than those of conventional PCR assays. We validated the clinical utility of the proposed method in 88 sputum samples obtained from four hospitals in the Republic of Korea. Overall, the sensitivity of this system was superior to those of other assays. Therefore, the proposed system can be useful for MTB diagnosis in limited-resource settings.
Highly Sensitive Detection of Chymotrypsin Based on Metal Organic Frameworks with Peptides Sensors
Authors: Liu Lei , Liu Cheng , Gao Li
Published: February 2023

In this study, peptides and composite nanomaterials based on copper nanoclusters (CuNCs) were used to detect chymotrypsin. The peptide was a chymotrypsin-specific cleavage peptide. The amino end of the peptide was covalently bound to CuNCs. The sulfhydryl group at the other end of the peptide can covalently combine with the composite nanomaterials. The fluorescence was quenched by fluorescence resonance energy transfer. The specific site of the peptide was cleaved by chymotrypsin. Therefore, the CuNCs were far away from the surface of the composite nanomaterials, and the intensity of fluorescence was restored. The limit of detection (LOD) using Porous Coordination Network (PCN)@graphene oxide (GO) @ gold nanoparticle (AuNP) sensor was lower than that of using PCN@AuNPs. The LOD based on PCN@GO@AuNPs was reduced from 9.57 pg mL−1 to 3.91 pg mL−1. This method was also used in a real sample. Therefore, it is a promising method in the biomedical field.
A Transgenic 5xFAD-M Line of Mice for Dendritic Spine Morphology Analysis in Alzheimer’s Disease
Authors: Ilina Anastasiia , Linkova Natalia
Published: February 2023

Cognitive impairments are closely related to synaptic loss in Alzheimer’s disease (AD). Functional changes in synaptic contacts are reflected in dendritic spine morphology. Visualization of neurons for morphological studies in vivo is complicated by the fixed brain slice staining or expensive adeno-associated virus injections. We created a transgenic 5xFAD-M line of mice with AD-associated mutations and expressed GFP protein in single neurons of the brain. This mouse model of AD is a useful tool for the simplified visualization of the hippocampal neurons’ morphology in vivo without additional staining manipulations. The progressive elimination of mushroom spines was demonstrated in 5xFAD-M mice between 4 and 5 months of age. Five-month-old 5xFAD-M male and female mice showed change both in the total density and the mushroom spines number compared to sex-matched control. We conclude 5xFAD-M mice can be a useful AD model for studying the mechanisms of synaptic pathology under neurodegenerative conditions and evaluating the effects of potential therapeutic agents on spine morphology as crucial aspect of memory loss in AD.
Neuronal Cell Types in the Spinal Trigeminal Nucleus of the Camel Brain
Authors: El-Dwairi Qasim A. , Al-Hussain Saleh M. , Banihani Ayat S. , Bataineh Ziad M. , Djouhri Laiche , Mustafa Ayman G. , Zaqout Sami
Published: February 2023

Neurons in the spinal trigeminal nucleus of a camel were morphologically studied by the Golgi impregnation method. The neurons were classified based on the size and shape of their cell bodies, the density of their dendritic trees, and the morphology and distribution of their appendages. At least 12 morphological types of neurons were found in the camel spinal trigeminal nucleus, including the following: stalked, islets, octopus-like, lobulated, boat-like, pyramidal, multipolar, round, oval, and elongated neurons. These neurons exhibited large numbers of various forms of appendages that arise not only from their dendrites but also from their cell bodies. Moreover, neurons with unique large dilatations especially at their dendritic branching points were also reported. The neurons reported in this study displayed an array of different sizes and shapes and featured various forms of appendages arising from cell bodies and dendrites. Such morphologically distinctive neuronal cell types might indicate an evolutionary adaptation to pain and temperature processing pathways at the level of the spinal trigeminal nucleus in camels, which traditionally live in a very harsh climatic environment and are frequently exposed to painful stimuli.
Schizophrenia Misdiagnosis after Capgras and Cotard Delusions in a Patient with Infantile Cystinosis, Cavum Septi Pellucidi, Cavum Vergae and Cavum Veli Interpositi
Authors: Gama Marques João
Published: February 2023

How many patients with psychosis secondary to genetic conditions or congenital brain malformation have been diagnosed with schizophrenia, since its initial conception more than one hundred years ago? A case report of a young man, with antecedents of Capgras and Cotard syndromes, sent to a schizophrenia treatment-resistant outpatient clinic is presented. Instead of true, primary, idiopathic schizophrenia, a diagnosis of secondary schizophrenia (pseudo-schizophrenia or schizophrenia-like psychosis) was made, corresponding to a secondary psychotic syndrome, with hallucinations and delusions due to congenital cavum septi pellucidi, cavum vergae, cavum veli interpositi and progressive brain atrophy due to cystinosis. Extreme caution is recommended when diagnosing schizophrenia in severely psychotic patients independent of their acute or chronic condition. Schizophrenia shall never be forgotten as the great imitated of medicine.
Design and Parameter Optimization of the Reduction-Isolation Control System for Building Structures Based on Negative Stiffness
Authors: Kang Xiaofang , Li Shuai , Hu Jun
Published: February 2023

In order to improve the damping capacity of building isolation system, this paper studies the damping isolation control system of the building structure based on negative stiffness. In this paper, the dynamic equation of the damping isolation control system is derived and its parameters are optimized by H2 norm theory and Monte Carlo pattern search method. Taking the 5-story building structure as an example, this paper analyzes and evaluates the damping performance of the damping isolation control system of the building structure under the actual earthquake. The results show that negative stiffness can improve the damping capacity of traditional isolation system. Additionally, the negative stiffness ratio under the condition of stability, the smaller the negative stiffness ratio, the stronger the vibration reduction ability of the negative stiffness. The damping isolation control system of building structure based on negative stiffness shows good damping effect under the actual earthquake.
Retention over Attraction: A Review of Women’s Experiences in the Australian Construction Industry; Challenges and Solutions
Authors: Ghanbaripour Amir Naser , Tumpa Roksana Jahan , Sunindijo Riza Yosia , Zhang Weiwei , Yousefian Parinaz , Camozzi Ranka Novak , Hon Carol , Talebian Nima , Liu Tingting , Hemmati Mina
Published: February 2023

Despite substantial investments and efforts by governments, construction organisations, and researchers, the construction industry remains one of the most male-dominated industries in Australia, with women being underrepresented numerically and hierarchically. Efforts to attract and retain women in construction have been implemented inconsistently on an ad hoc basis. As part of a larger research project that focuses on retaining women in the Australian construction industry, this research conducts a systematic literature review (SLR) in accordance with the PRISMA guidelines. The objective is to explore the factors that influence women’s careers and their experiences in the Australian construction industry that have been identified in the literature over the past three decades. Additionally, the findings are anticipated to inform future efforts to evaluate the effectiveness of current initiatives to retain women and develop a framework for enhancing women’s experiences and retaining them in this profession. This SLR revealed that excessive and rigid work hours, gendered culture and informal rules, limited career development opportunities, and negative perceptions of women’s abilities are the main factors and issues that cause women to leave the industry. Among these, rigid and long work hours seem to be the foremost factor to be prioritised. Understanding the roles of key variables in driving this cultural change is important to ensure that concrete progress is made. The paper draws three major aspects from the literature in which solutions and policies can be researched, designed and implemented.
Numerical Simulation of Anchorage Performance of GFRP Bolt and Concrete
Authors: Sun Gan , Bai Xiaoyu , Sang Songkui , Zeng Ling , Yin Jichao , Jing Desheng , Zhang Mingyi , Yan Nan
Published: February 2023

We conducted anchoring performance, stress distribution, and full-scale indoor pulling tests on glass-fiber-reinforced polymer (GFRP) bolts. The tests were conducted using finite element software while considering the multi-interface contact and BK criterion by using the cohesive element to simulate the contact relations between the anchor rod body and concrete and building an axial symmetry calculation model of the GRFP bolt and concrete. The results indicated that the finite element model based on cohesive element accurately represents the load–displacement relationship of the GFRP bolt and the distribution law of axial stress along the anchoring length. In addition, the simulation outcomes of the load–displacement relationship were in good agreement with the measured test values. Under the same load, the axial-force-transferred depth of the bolt body was identical regardless of the anchorage length. As anchoring length increases, the pull load on the bolt and the decay rate of axial stress along the anchoring length rises gradually. There is a critical value for the anchorage length of the bolt.
Dynamic Response and Impact Force Calculation of PC Box Girder Bridge Subjected to Over-Height Vehicle Collision
Authors: Jing Yuan , Zhang Xu , Zhou Yongjun , Zhao Yu , Li Wenchao
Published: February 2023

The dynamic response of a prestressed concrete box girder bridge under the impact of an over-height vehicle is studied using the numerical simulation method. The finite element analysis software LS-DYNA is used to simulate the collision between the bridge superstructure and an over-height truck. Further, a parametric analysis is carried out to investigate the influence of six factors, i.e., girder configuration, vehicle speed, vehicle mass, impact angle, concrete strength and strand prestress, on both local damage and overall performance of the bridge. The numerical analysis results show that the girder configuration, vehicle speed, vehicle mass and impact angle have obvious effects on both local damage and the overall behavior of the PC box girder bridge. Whereas, the concrete strength and strand prestress only have a certain effect on the local damage at the impact area with very limited influence on the overall behavior of the bridge. In addition, based on the results obtained from the numerical simulation and parametric analysis, a formula for predicting the peak and average impact force of the prestressed concrete box girder bridge under the over-height vehicle impact is developed. The proposed impact force formula comprehensively accounts for the influence of the vehicle speed, vehicle mass and impact angle and can accurately predict the impact force generated under different working conditions, which confirms the promising prospect of the proposed formula in practical applications.
Design for Seismic Resilient Cross Laminated Timber (CLT) Structures: A Review of Research, Novel Connections, Challenges and Opportunities
Authors: Li Zhengyao , Tsavdaridis Konstantinos Daniel
Published: February 2023

As a sustainable alternative to steel and concrete, cross laminated timber (CLT) shear wall systems are getting increasingly popular in mid-rise and high-rise construction, and that imposes new challenges on their seismic performance. The conventional connections used in this system, such as steel hold-downs and angle brackets, are, however, susceptible to brittle failures, thus being inappropriate for use in structures in seismic regions. A series of innovative connections have therefore been proposed in recent years for achieving better seismic behaviours in CLT structures, characterised by an adequate capacity, significantly improved ductility and dissipative capacity, as well as more controllable ductile failure modes. This paper first reviews the recent studies of CLT shear wall systems and conventional connections. Connection systems and shear wall reinforcement methods that have been recently proposed for seismic resilient CLT structures are then introduced, with their design strategies being summarised accordingly. The connections are then discussed comprehensively in terms of structural performance, manufacturability and constructability, employing similar criteria that have previously been proposed for steel modular connections. It is found that much improved ductility along with more predictable, ductile, timber damage-free deformation modes are achieved in most of the new connections. Some new connectors are designed with additional functionalities for optimised seismic performance or for easing the construction process, which, however, lead to complex designs that may add difficulties to the mass production. Therefore, comprehensive considerations are needed in connection design, and the discussion of this paper aims to assist in the future development of connection systems for seismic resilient multi-storey CLT buildings.
Potential Role of the Fragile Histidine Triad in Cancer Evo-Dev
Authors: Niu Zheyun , Jiang Dongming , Shen Jiaying , Liu Wenbin , Tan Xiaojie , Cao Guangwen
Published: February 2023

Cancer development follows an evolutionary pattern of “mutation-selection-adaptation” detailed by Cancer Evolution and Development (Cancer Evo-Dev), a theory that represents a process of accumulating somatic mutations due to the imbalance between the mutation-promoting force and the mutation-repairing force and retro-differentiation of the mutant cells to cancer initiation cells in a chronic inflammatory microenvironment. The fragile histidine triad (FHIT) gene is a tumor suppressor gene whose expression is often reduced or inactivated in precancerous lesions during chronic inflammation or virus-induced replicative stress. Here, we summarize evidence regarding the mechanisms by which the FHIT is inactivated in cancer, including the loss of heterozygosity and the promoter methylation, and characterizes the role of the FHIT in bridging macroevolution and microevolution and in facilitating retro-differentiation during cancer evolution and development. It is suggested that decreased FHIT expression is involved in several critical steps of Cancer Evo-Dev. Future research needs to focus on the role and mechanisms of the FHIT in promoting the transformation of pre-cancerous lesions into cancer.
Prognoses of Patients with Hormone Receptor-Positive and Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer Receiving Neoadjuvant Chemotherapy before Surgery: A Retrospective Analysis
Authors: Zhang Shichao , Liu Yan , Liu Xu , Liu Yingxue , Zhang Jin
Published: February 2023

Purpose: To evaluate the clinical characteristics, pathological response, and prognostic significance of hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR+/HER2−) breast cancer (BC) after neoadjuvant chemotherapy (NAC). Methods: A survival analysis was performed to detect the factors related to recurrence and death in 3070 consecutive patients with HR+/HER2− BC who received NAC from 2011 to 2022. All patients received current “standard of care” following neoadjuvant therapy based on guidelines, including surgery and adjuvant endocrine therapy. HER2-low was defined as immunohistochemistry (IHC) 1+ or IHC 2+ and fluorescence in-situ hybridization-negative. Results: The complete pathological response (pCR) (ypT0/is ypN0) rate was 14.5%. The clinical tumor size (cT), ER scores, PR status, and Ki67 levels were related to pCR. The 5-year disease-free survival (DFS) and overall survival (OS) rates were 82.6% and 90.4%, respectively. PR, Ki67 levels, and postmastectomy radiotherapy were independent factors for DFS and OS, and the extranodal extension (ENE) correlated with DFS. However, pCR and HER2 status were related to OS. The pCR rate in PR negativity BC was significantly higher than that in PR positivity BC (21.1% vs. 12.2%, p = 0.000), but PR negativity BC had a poorer prognosis than PR positivity BC. HER2-low BC showed high ER scores (over 50%), PR positivity, large ypT, ENE, and lymphovascular invasion but a lower pCR rate than HER2-zero BC. Patients with HER2-low BC had shorter OS than those with HER2-zero BC (p = 0.037). However, there was no difference in DFS. Conclusions: Depending on PR status and HER2 status, patients with ER positivity and HER2 negativity exhibit different pathologic complete response rates to neoadjuvant chemotherapy and long-term outcomes, especially patients with PR negativity or HER2-low status.
Unique Metabolic Contexts Sensitize Cancer Cells and Discriminate between Glycolytic Tumor Types
Authors: Chacon-Barahona Jonathan A. , MacKeigan Jeffrey P. , Lanning Nathan J.
Published: February 2023

Cancer cells utilize variable metabolic programs in order to maintain homeostasis in response to environmental challenges. To interrogate cancer cell reliance on glycolytic programs under different nutrient availabilities, we analyzed a gene panel containing all glycolytic genes as well as pathways associated with glycolysis. Using this gene panel, we analyzed the impact of an siRNA library on cellular viability in cells containing only glucose or only pyruvate as the major bioenergetic nutrient source. From these panels, we aimed to identify genes that elicited conserved and glycolysis-dependent changes in cellular bioenergetics across glycolysis-promoting and OXPHOS-promoting conditions. To further characterize gene sets within this panel and identify similarities and differences amongst glycolytic tumor RNA-seq profiles across a pan-cancer cohort, we then used unsupervised statistical classification of RNA-seq profiles for glycolytic cancers and non-glycolytic cancer types. Here, Kidney renal clear cell carcinoma (KIRC); Head and Neck squamous cell carcinoma (HNSC); and Lung squamous cell carcinoma (LUSC) defined the glycolytic cancer group, while Prostate adenocarcinoma (PRAD), Thyroid carcinoma (THCA), and Thymoma (THYM) defined the non-glycolytic cancer group. These groups were defined based on glycolysis scoring from previous studies, where KIRC, HNSC, and LUSC had the highest glycolysis scores, meanwhile, PRAD, THCA, and THYM had the lowest. Collectively, these results aimed to identify multi-omic profiles across cancer types with demonstrated variably glycolytic rates. Our analyses provide further support for strategies aiming to classify tumors by metabolic phenotypes in order to therapeutically target tumor-specific vulnerabilities.
c-MYC-Induced AP4 Attenuates DREAM-Mediated Repression by p53
Authors: Kaller Markus , Shi Wenjing , Hermeking Heiko
Published: February 2023

Background: The deregulated expression of the c-MYC oncogene activates p53, which is presumably mediated by ARF/INK4, as well as replication-stress-induced DNA damage. Here, we aimed to determine whether the c-MYC-inducible AP4 transcription factor plays a role in this context using a genetic approach. Methods: We used a CRISPR/Cas9 approach to generate AP4- and/or p53-deficient derivatives of MCF-7 breast cancer cells harboring an ectopic, inducible c-MYC allele. Cell proliferation, senescence, DNA damage, and comprehensive RNA expression profiles were determined after activation of c-MYC. In addition, we analyzed the expression data from primary breast cancer samples. Results: Loss of AP4 resulted in elevated levels of both spontaneous and c-MYC-induced DNA damage, senescence, and diminished cell proliferation. Deletion of p53 in AP4-deficient cells reverted senescence and proliferation defects without affecting DNA damage levels. RNA-Seq analyses showed that loss of AP4 enhanced repression of DREAM and E2F target genes after p53 activation by c-MYC. Depletion of p21 or the DREAM complex component LIN37 abrogated this effect. These p53-dependent effects were conserved on the level of clinical and gene expression associations found in primary breast cancer tumors. Conclusions: Our results establish AP4 as a pivotal factor at the crossroads of c-MYC, E2F, and p53 target gene regulation.
Oncology in Mozambique: Overview of the Diagnostic, Treatment, and Research Capacity
Authors: Tulsidás Satish , Fontes Filipa , Brandão Mariana , Lunet Nuno , Carrilho Carla
Published: February 2023

Mozambique is one of the poorest countries worldwide, with nearly two thirds of the population living below the poverty line. Similarly to other less developed countries, there is a weak provision of health care for non-communicable diseases due to competing priorities with infectious diseases. Although the leading causes of death in Mozambique in 2019 were Acquired Immune Deficiency Syndrome/Human Immunodeficiency Virus and other sexually transmitted diseases and respiratory infections and tuberculosis, with increasing urbanization and westernization of lifestyles, deaths attributed to cancer are also on the rise. This review summarizes cancer burden, cancer prevention and screening, cancer care resources, and trends in cancer training and research in Mozambique, providing a background for the development of cancer care policies in the country.
Early Detection of Therapeutic Benefit from PD-1/PD-L1 Blockade in Advanced Lung Cancer by Monitoring Cachexia-Related Circulating Cytokines
Authors: Xu Shiting , Miura Keita , Shukuya Takehito , Harada Sonoko , Fujioka Masahiro , Winardi Wira , Shimamura Shoko , Kurokawa Kana , Sumiyoshi Issei , Miyawaki Taichi , Asao Tetsuhiko , Mitsuishi Yoichiro , Tajima Ken , Takahashi Fumiyuki , Hayashi Takuo , Harada Norihiro , Takahashi Kazuhisa
Published: February 2023

Cancer cachexia is associated with poor immunotherapeutic outcomes. This prospective observational study longitudinally evaluated the role of cachexia-related circulating cytokines in predicting the risk and benefit of PD-1/PD-L1 blockade in advanced lung cancer. Forty-one circulating cytokines at baseline and after one cycle of PD-1/PD-L1 blockade treatment were measured in patients with advanced lung cancer between 2019 and 2020. The cachexia-related cytokines were identified by comparing the levels of circulating cytokines between cachectic and non-cachectic patients. Among 55 patients, 49.1% were diagnosed with cachexia at the beginning of PD-1/PD-L1 blockade therapy. Baseline levels of the circulating cytokines IL-6, IL-8, IL-10, IL-15, and IP-10 were significantly higher in cachectic patients. In contrast, the level of eotaxin-1 was lower in cachectic patients than in those without cachexia. Higher IL-6 at baseline and during treatment was associated with a greater risk of immune-related adverse events, while higher IL-10 at baseline was linked to worse overall survival. More importantly, increased eotaxin-1 after one cycle of PD-1/PD-L1 blockade treatment was associated with higher objective response and better overall survival. A blood-based, cachexia-related cytokine assay may yield potential biomarkers for the early prediction of clinical response to PD-1/PD-L1 blockade and provide clues for improving the outcomes of cachectic patients.
The Value of Tucatinib in Metastatic HER2-Positive Breast Cancer Patients: An Italian Cost-Effectiveness Analysis
Authors: Antonazzo Ippazio Cosimo , Cortesi Paolo Angelo , Miceli Sopo Gerardo , Mazzaglia Giampiero , Conte Pierfranco , Mantovani Lorenzo Giovanni
Published: February 2023

Background: This study was aimed at estimating the appropriate price of tucatinib plus trastuzumab and capecitabine (TXC), as third-line treatment, in HER2+ breast cancer (BC) patients from the Italian National Health System (NHS) perspective. Methods: A partitioned survival model with three mutually exclusive health states (i.e., progression-free survival (PFS), progressive disease (PD), and death) was used to estimate the price of tucatinib vs trastuzumab emtansine (TDM-1), considering a willingness to pay (WTP) of 60,000 EUR. Data from the HER2CLIMB trial, the Italian population, and the literature were used as input. The model also estimated the total costs and the life-years (LY) of TXC and TDM1. Deterministic and probabilistic (PSA) sensitivity analyses were conducted to evaluate the robustness of the model. Results: In the base case scenario, the appropriate price of tucatinib was 4828.44 EUR per cycle. The TXC resulted in +0.28 LYs and +16,628 EUR compared with TDM-1. Results were mainly sensitive to therapy intensity variation. In PSA analysis, TXC resulted cost-effective in 53% of the simulations. Assuming a WTP ranging 20,000–80,000 EUR, the tucatinib price ranged from 4090.60 to 5197.41 EUR. Conclusions: This study estimated the appropriate price for tucatinib according to different WTP in order to help healthcare decision makers to better understand the treatment value.
Outcomes and Patient Selection in Laparoscopic vs. Open Liver Resection for HCC and Colorectal Cancer Liver Metastasis
Authors: Alvikas Jurgis , Lo Winifred , Tohme Samer , Geller David A.
Published: February 2023

Hepatocellular carcinoma (HCC) and colorectal liver metastasis (CRLM) are the two most common malignant tumors that require liver resection. While liver transplantation is the best treatment for HCC, organ shortages and high costs limit the availability of this option for many patients and make resection the mainstay of treatment. For patients with CRLM, surgical resection with negative margins is the only potentially curative option. Over the last two decades, laparoscopic liver resection (LLR) has been increasingly adopted for the resection of a variety of tumors and was found to have similar long-term outcomes compared to open liver resection (OLR) while offering the benefits of improved short-term outcomes. In this review, we discuss the current literature on the outcomes of LLR vs. OLR for patients with HCC and CRLM. Although the use of LLR for HCC and CRLM is increasing, it is not appropriate for all patients. We describe an approach to selecting patients best-suited for LLR. The four common difficulty-scoring systems for LLR are summarized. Additionally, we review the current evidence behind the emerging robotically assisted liver resection technology.
Correction: Davidi et al. Tumor Treating Fields (TTFields) Concomitant with Sorafenib Inhibit Hepatocellular Carcinoma In Vitro and In Vivo. Cancers 2022, 14, 2959
Authors: Davidi Shiri , Jacobovitch Sara , Shteingauz Anna , Martinez-Conde Antonia , Braten Ori , Tempel-Brami Catherine , Zeevi Einav , Frechtel-Gerzi Roni , Ene Hila , Dor-On Eyal , Voloshin Tali , Tzchori Itai , Haber Adi , Giladi Moshe , Kinzel Adrian , Weinberg Uri , Palti Yoram
Published: February 2023

The authors wish to make minor corrections to Figure 1 and Figure 2 of the following paper [...]
Comparison of Invasive Pancreatic Ductal Adenocarcinoma versus Intraductal Papillary Mucinous Neoplasm: A National Cancer Database Analysis
Authors: Ziogas Ioannis A. , Rodriguez Franco Salvador , Schmoke Nicholas , Meguid Cheryl , Murphy Cassandra , Al-Musawi Mohammed , Alexopoulos Sophoclis P. , Schulick Richard D. , Del Chiaro Marco
Published: February 2023

Background: Current evidence on overall survival (OS) between invasive pancreatic ductal adenocarcinoma (PDAC) and intraductal papillary mucinous neoplasm (IPMN) is limited to single-center reports. We aimed to compare the characteristics, management, and OS of invasive PDAC vs. IPMN using a national United States (US) database. Methods: Invasive PDAC or IPMN adult (≥18 years) patients were identified in the National Cancer Database (2004–2016). OS was assessed with the Kaplan–Meier method and the stratified log-rank test. Results: We included 101,190 patients (100,834 PDAC, 356 IPMN). A higher proportion of PDAC vs. IPMN patients had clinical N1 (36.8% vs. 15.7%, p < 0.001) and M1 disease (41.2% vs. 5.9%, p < 0.001). A lower proportion of PDAC patients underwent surgery (25.5% vs. 80.3%, p < 0.001), but a higher proportion received chemotherapy (65.4% vs. 46.1%, p < 0.001) or radiation (25.3% vs. 20.5%, p = 0.04). A higher proportion of surgical patients with PDAC vs. IPMN underwent margin-positive resection (23.0% vs. 14.0%, p = 0.001). The median OS for PDAC vs. IPMN was 8.3 vs. 33.4 months. In the stratified analysis for N0M0 disease, the median OS for PDAC vs. IPMN was 12.8 vs. 43.3 months, for N1M0, it was 11.5 vs. 17.0 months, while for M1, it was 4.0 vs. 7.0 months. In both diagnoses, surgery yielded improved OS, while stratified analysis in the surgical cohort demonstrated similar findings. Conclusions: Invasive PDAC is more aggressive than invasive IPMN, yet in the case of metastasis, OS is equally poor. Excellent long-term OS is achievable with surgical resection in highly selected cases, and efforts should focus on facilitating surgical treatment.
LC-MS/MS Based Volatile Organic Compound Biomarkers Analysis for Early Detection of Lung Cancer
Authors: Sani Shuaibu Nazifi , Zhou Wei , Ismail Balarabe B. , Zhang Yongkui , Chen Zhijun , Zhang Binjie , Bao Changqian , Zhang Houde , Wang Xiaozhi
Published: February 2023

(1) Background: lung cancer is the world’s deadliest cancer, but early diagnosis helps to improve the cure rate and thus reduce the mortality rate. Annual low-dose computed tomography (LD-CT) screening is an efficient lung cancer-screening program for a high-risk population. However, LD-CT has often been characterized by a higher degree of false-positive results. To meet these challenges, a volatolomic approach, in particular, the breath volatile organic compounds (VOCs) fingerprint analysis, has recently received increased attention for its application in early lung cancer screening thanks to its convenience, non-invasiveness, and being well tolerated by patients. (2) Methods: a LC-MS/MS-based volatolomics analysis was carried out according to P/N 5046800 standard based breath analysis of VOC as novel cancer biomarkers for distinguishing early-stage lung cancer from the healthy control group. The discriminatory accuracy of identified VOCs was assessed using subject work characterization and a random forest risk prediction model. (3) Results: the proposed technique has good performance compared with existing approaches, the differences between the exhaled VOCs of the early lung cancer patients before operation, three to seven days after the operation, as well as four to six weeks after operation under fasting and 1 h after the meal were compared with the healthy controls. The results showed that only 1 h after a meal, the concentration of seven VOCs, including 3-hydroxy-2-butanone (TG-4), glycolaldehyde (TG-7), 2-pentanone (TG-8), acrolein (TG-11), nonaldehyde (TG-19), decanal (TG-20), and crotonaldehyde (TG-22), differ significantly between lung cancer patients and control, with the invasive adenocarcinoma of the lung (IAC) having the most significant difference. (4) Conclusions: this novel, non-invasive approach can improve the detection rate of early lung cancer, and LC-MS/MS-based breath analysis could be a promising method for clinical application.
Facile Synthesis of Metal-Impregnated Sugarcane-Derived Catalytic Biochar for Ozone Removal at Ambient Temperature
Authors: Verdida Reginald A. , Caparanga Alvin R. , Chang Chang-Tang
Published: February 2023

This study presents the first attempt at employing catalytic biochar to remove ground-level ozone at ambient temperature. With the increase in human activity, ozone has become a critical inorganic pollutant that needs to be addressed, using more sustainable methods. Fe- and Mn-impregnated catalytic biochars were prepared from a sugarcane feedstock via the wet impregnation method and pyrolysis at various temperatures, where the optimum value was determined to be 550 °C. The metal-impregnated biochar samples demonstrated enhanced surface areas and pore volumes compared with the pristine biochar (SCB550), resulting in improved ozone-adsorption capacity. SCB550-Fe exhibited an ozone-adsorption capacity of 52.1 mg/g at 20 ppm, which was approximately four times higher than that of SCB550. SCB550-Fe demonstrated superior ozone-removal performance compared to SCB550-Mn; 122 mg/g capacity as opposed to 116.2 mg/g at 80 ppm, respectively. Isothermal and kinetic modeling are also presented to suggest a plausible mechanism of ozone removal by catalytic biochar. This includes physical adsorption, complexation, electrostatic interaction, and electron transfer during the redox reaction between ozone and metals. Overall, this study should provide preliminary insights into ozone removal using biochar and promote further research regarding material optimization and kinetic studies.
Mechanochemical Synthesized CaO/ZnCo2O4 Nanocomposites for Biodiesel Production
Authors: Narasimharao Katabathini , Mostafa Mohamed Mokhtar M. , Al-Amshany Zahra M. , Bajafar Wejdan
Published: February 2023

Biodiesel has been recognized as an environmentally friendly, renewable alternative to fossil fuels. In this work, CaO/ZnCo2O4 nanocomposites were successfully synthesized via simple mechanochemical reaction between ZnCo2O4 and CaO powders by varying the CaO loading from 5 to 20 wt.%. The synthesized materials were found to be highly efficient heterogeneous catalysts for transesterification of tributyrin with methanol to produce biodiesel. The nanocomposite, which contained 20 wt.% CaO and 80 wt.% ZnCo2O4 (CaO/ZnCo2O4-20), exhibited superior and stable transesterification activity (98% conversion) under optimized reaction conditions (1:12 TBT to methanol molar ratio, 5 wt.% catalyst and 180 min. reaction time). The experimental results revealed that the reaction mechanism on the CaO/ZnCo2O4 composite followed pseudo first-order kinetics. The physicochemical characteristics of the synthesized nanocomposites were measured using X-ray diffraction (XRD), high resolution transmission electron microscopy (HRTEM), Fourier-transformed infrared spectroscopy (FTIR), X-ray photoelectron spectrometer (XPS), N2-physisorption, and CO2- temperature-programmed desorption (CO2-TPD) techniques. The results indicated the existence of coalescence between the CaO and ZnCo2O4 particles, Additionally, the CaO/ZnCo2O4-20 catalyst was found to possess the greater number of highly basic sites and high porosity, which are the key factors affecting catalytic performance in transesterification reactions.
Synthesis and Characterization of Fe Doped Aurivillius-Phase PbBi2Nb2O9 Perovskite and Their Photocatalytic Activity on the Degradation of Methylene Blue
Authors: Gu Yunjang , Kim Minkyum , Kim Hee Soo , Lim Dong-Ha
Published: February 2023

A simple solid-state reaction was applied to synthesize Fe-doped perovskite-type PBFNO catalysts, and methylene blue decomposition studies were performed in the form of visible light according to the changes in the Fe doping content (0.4 to 1.9 mol ratio compared with Bi mol) and the amount of catalyst used (0.05 to 0.2 g used). As the Fe doping content increases, the absorbance and bang gap energy of the PBFNOs sample rapidly increase and decrease, respectively, because the Fe dopant in the PBNO lattice acts as an intermediate band between the valence and conduction bands of the PBNO and reduces the band gap energy. As a result, it showed a performance degradation of approximately 42% compared to the maximum performance. In addition, the presence of Fe dopants in the PBNO lattice greatly reduces the intensity of the photoluminescent lines. This is because the Fe dopant can play an important role in light-induced electron transfer and as a hole trap, reducing the recombination rate. Additionally, when too much photocatalyst was used (>0.1 g used), the Fe dopant played an important role as a light-induced electron transfer and hole trap, reducing the recombination rate and lowering the overall photocatalytic activity by 51%. In particular, 0.1 g of PBNO-0.2-F showed continuous catalytic activity, even when the photocatalytic reaction proceeded for 180 min. Therefore, this study demonstrates that the Fe-doped aurivillius-phase PBFNO photocatalyst is very promising for the dye manufacturing industry.
Bioinspired Green Synthesis of Bimetallic Iron and Zinc Oxide Nanoparticles Using Mushroom Extract and Use against Aspergillus niger; The Most Devastating Fungi of the Green World
Authors: Kamal Asif , Saba Malka , Kamal Asif , Batool Momal , Asif Muhammad , Al-Mohaimeed Amal M. , Al Farraj Dunia A. , Habib Darima , Ahmad Shabir
Published: February 2023

In the current study, a macro fungus was collected and identified by using morphological and molecular tools to study the ITS region, which has been described as a universal barcode marker during molecular investigation for the identification of fungi. Based on morphology and molecular evidence, the collected fungus was identified as Daedalea Mushroom. The identified fungus was used for the synthesis of Iron and ZnO nanoparticles as an eco-friendly agent for nanoparticle synthesis. The synthesized nanoparticles were confirmed by, Fourier transfer infrared spectroscopy analysis (FTIR), X-ray diffraction analysis (XRD), energy dispersive X-ray analysis (EDX), and scanning electron microscopy analysis (SEM). All these characterizations revealed the synthesis of Iron and ZnO NPs with an irregular shape and a size of 16.8 nm. The zinc oxide nanoparticles had a size in the range of 18.53 nm. Daedalea Mushroom was used for the first time to synthesize Iron and zinc nanoparticles. The mycosynthesized Iron and ZnO NPs were assessed as control agents at various dosage rates against the pathogenic fungus Aspergillus niger, which was isolated from an apple and identified using its morphology. At higher concentrations (0.75 mg/mL), the iron nanoparticles inhibited fungal growth by 72%, whereas at lower concentrations (0.25 mg/mL), they inhibited fungal growth by 60%. ZnO NPs showed good antifungal activity at different concentrations including growth inhibition at 0.25 mg/mL (88%), 1.0 mg/mL (68%), 0.75 mg/mL (75%), and 0.5 mg/mL (70%) concentrations of ZnO NPs. However, the maximum growth inhibition of ZnO NPs was observed at 0.25 mg/mL (88%) concentration and minimum growth inhibition at 0.1 mg/mL (22%). The current study concludes that Daedalea Mushroom works as a novel and eco-friendly source for the synthesis of Iron and ZnO NPs with prominent antifungal activities that can be further applied in different fields.
Short- and Long-Term Effects of Cocaine on Enteric Neuronal Functions
Authors: Elfers Kristin , Menne Laura , Colnaghi Luca , Hoppe Susanne , Mazzuoli-Weber Gemma
Published: February 2023

Cocaine is one of the most consumed illegal drugs among (young) adults in the European Union and it exerts various acute and chronic negative effects on psychical and physical health. The central mechanism through which cocaine initially leads to improved performance, followed by addictive behavior, has already been intensively studied and includes effects on the homeostasis of the neurotransmitters dopamine, partly mediated via nicotinic acetylcholine receptors, and serotonin. However, effects on the peripheral nervous system, including the enteric nervous system, are much less understood, though a correlation between cocaine consumption and gastrointestinal symptoms has been reported. The aim of the present study was to gain more information on the effects of cocaine on enteric neuronal functions and the underlying mechanisms. For this purpose, functional experiments using an organ bath, Ussing chamber and neuroimaging techniques were conducted on gastrointestinal tissues from guinea pigs. Key results obtained are that cocaine (1) exhibits a stimulating, non-neuronal effect on gastric antrum motility, (2) acutely (but not chronically) diminishes responses of primary cultured enteric neurons to nicotinic and serotonergic stimulation and (3) reversibly attenuates neuronal-mediated intestinal mucosal secretion. It can be concluded that cocaine, among its central effects, also alters enteric neuronal functions, providing potential explanations for the coexistence of cocaine abuse and gastrointestinal complaints.
Alpha1A- and Beta3-Adrenoceptors Interplay in Adipose Multipotent Mesenchymal Stromal Cells: A Novel Mechanism of Obesity-Driven Hypertension
Authors: Chechekhin Vadim , Ivanova Anastasia , Kulebyakin Konstantin , Sysoeva Veronika , Naida Daria , Arbatsky Mikhail , Basalova Nataliya , Karagyaur Maxim , Skryabina Mariya , Efimenko Anastasia , Grigorieva Olga , Kalinina Natalia , Tkachuk Vsevolod , Tyurin-Kuzmin Pyotr
Published: February 2023

Hypertension is a major risk factor for cardiovascular diseases, such as strokes and myocardial infarctions. Nearly 70% of hypertension onsets in adults can be attributed to obesity, primarily due to sympathetic overdrive and the dysregulated renin-angiotensin system. Sympathetic overdrive increases vasoconstriction via α1-adrenoceptor activation on vascular cells. Despite the fact that a sympathetic outflow increases in individuals with obesity, as a rule, there is a cohort of patients with obesity who do not develop hypertension. In this study, we investigated how adrenoceptors’ expression and functioning in adipose tissue are affected by obesity-driven hypertension. Here, we demonstrated that α1A is a predominant isoform of α1-adrenoceptors expressed in the adipose tissue of patients with obesity, specifically by multipotent mesenchymal stromal cells (MSCs). These cells respond to prolonged exposure to noradrenaline in the model of sympathetic overdrive through the elevation of α1A-adrenoceptor expression and signaling. The extent of MSCs’ response to noradrenaline correlates with a patient’s arterial hypertension. scRNAseq analysis revealed that in the model of sympathetic overdrive, the subpopulation of MSCs with contractile phenotype expanded significantly. Elevated α1A-adrenoceptor expression is triggered specifically by beta3-adrenoceptors. These data define a novel pathophysiological mechanism of obesity-driven hypertension by which noradrenaline targets MSCs to increase microvessel constrictor responsivity.