bluuebunny/crossref_metadata_2025 huggingface dataset:
Compression Behavior of Rubber–Bentonite Mixture under Different Salinities
Authors: Wan Tong , Lu Yi , Zeng Zhenming , Xie Zeli , Lin Shan , Nong Xingzhong
Published: July 2023

This study investigated the engineering properties of a rubber–bentonite mixture under different salt solution concentrations, mass ratios, and consolidation pressures. In addition, the effects of different solute ion concentrations on the compression index of the samples were compared. The results showed that the compression coefficient could be reduced effectively by increasing the weight percentage of rubber without being affected by the salt solution. However, with the increase in the salt solution concentration, the compression coefficient of mixed materials with different mass ratios increased, and when the salt solution concentration exceeded 0.5 mol/L, the compression coefficient increased more obviously. In a 0.1 mol/L NaCl solution, the addition of different levels of rubber could increase the compression modulus of the mixed material and reduce the compression ratio of the mixed material. This showed that in an environment with a low salt solution concentration, adding rubber into the mixed material could enhance its compressive deformation resistance. However, when the rubber content exceeded 50%, significant pores appeared in the sample, and the effect of high salt solution concentration intensified. The rubber content also had an effect on the swelling properties of soil, and the degradation of rubber in the salt solution showed reduced mechanical properties. This emphasizes the need to consider the stability and resistance of saline–alkali areas to salt erosion.
Fungal Pigments: Their Diversity, Chemistry, Food and Non-Food Applications
Authors: Elkhateeb Waill , Daba Ghoson
Published: July 2023

Colorants have many applications in food, cosmetics, pharmaceutics, textile, paints, plastics, paper, ink and photographic industries. Colorants are classified according to their solubility into dyes and pigments. Those of natural origin have many advantages over synthetic ones, as natural colorants usually do not induce allergies or other health problems. In addition, their consumption in the food and drug industries is fortified with nutritional and health benefits as the majority of them possess antioxidant activity or can be used to produce some vitamins. Plants, animals, insects and microorganisms are rich sources of colorants. However, microbial pigments are favored over other natural pigments due to their higher yield, stability, economical production. Therefore, we focus in this review on fungal pigments, the history of their use, their chemistry and their applications in food and non-food fields. Additionally, the ability of the fungal genus, Epicoccum, to produce pigments is discussed. Moreover, the challenges and future prospects concerning fungal pigment production are highlighted in detail.
Modelling Water Erosion and Mass Movements (Wet) by Using GIS-Based Multi-Hazard Susceptibility Assessment Approaches: A Case Study—Kratovska Reka Catchment (North Macedonia)
Authors: Aleksova Bojana , Lukić Tin , Milevski Ivica , Spalević Velibor , Marković Slobodan B.
Published: July 2023

Kratovska Reka is a short (17.3 km) left tributary of Kriva Reka, whose watershed (68.5 km2) is located on the northwestern slopes of the Osogovo Mountains (North Macedonia). Due to the favorable natural conditions and anthropogenic factors, the Kratovska Reka catchment is under a high risk of natural hazards, especially water erosion and landslide occurrences. For this reason, the paper presents an approach of modelling of potential erosion and areas susceptible to the above-mentioned hydro-meteorological hazards in the Kratovska River catchment. Firstly, this study analyzed the main geographical features that contribute to intensive erosion processes in the area. Then, using the Gavrilović EPM erosion potential method, an average value of 0.56 was obtained for the erosion coefficient Z, indicating areas prone to high erosion risk. Furthermore, by using landslide susceptibility analysis (LSA), terrains susceptible to landslides were identified. The results shows that 1/3 of the catchment is very susceptible to mass movements in wet conditions (landslides). According to the combined multi-hazard model, 3.13% of the total area of the Kratovska River catchment is both at high risk of landslides and under severe erosion. The Kratovska River catchment is significantly endangered by the excessive water erosion processes (39.86%), especially on the steep valley sides, i.e., terrains that are completely exposed, under sparse vegetation, and open to the effects of distribution/concentration of the rainfall amounts throughout the year. Identifying locations with the highest erosion risk serves as the initial step in defining and implementing appropriate mitigation measures across local and regional scales, thus enhancing overall resilience to environmental challenges.
The Role of Sex Differences in Bone Health and Healing
Authors: Ortona Elena , Pagano Maria Teresa , Capossela Lavinia , Malorni Walter
Published: July 2023

Fracture healing is a long-term and complex process influenced by a huge variety of factors. Among these, there is a sex/gender disparity. Based on significant differences observed in the outcome of bone healing in males and females, in the present review, we report the main findings, hypotheses and pitfalls that could lead to these differences. In particular, the role of sex hormones and inflammation has been reported to have a role in the observed less efficient bone healing in females in comparison with that observed in males. In addition, estrogen-induced cellular processes such as autophagic cell cycle impairment and molecular signals suppressing cell cycle progression seem also to play a role in female fracture healing delay. In conclusion, it seems conceivable that a complex framework of events could contribute to the female bias in bone healing, and we suggest that a reappraisal of the compelling factors could contribute to the mitigation of sex/gender disparity and improve bone healing outcomes.
Sunflower Hybrids and Inbred Lines Adopt Different Physiological Strategies and Proteome Responses to Cope with Water Deficit
Authors: Duruflé Harold , Balliau Thierry , Blanchet Nicolas , Chaubet Adeline , Duhnen Alexandra , Pouilly Nicolas , Blein-Nicolas Mélisande , Mangin Brigitte , Maury Pierre , Langlade Nicolas Bernard , Zivy Michel
Published: July 2023

Sunflower is a hybrid crop that is considered moderately drought-tolerant and adapted to new cropping systems required for the agro-ecological transition. Here, we studied the impact of hybridity status (hybrids vs. inbred lines) on the responses to drought at the molecular and eco-physiological level exploiting publicly available datasets. Eco-physiological traits and leaf proteomes were measured in eight inbred lines and their sixteen hybrids grown in the high-throughput phenotyping platform Phenotoul-Heliaphen. Hybrids and parental lines showed different growth strategies: hybrids grew faster in the absence of water constraint and arrested their growth more abruptly than inbred lines when subjected to water deficit. We identified 471 differentially accumulated proteins, of which 256 were regulated by drought. The amplitude of up- and downregulations was greater in hybrids than in inbred lines. Our results show that hybrids respond more strongly to water deficit at the molecular and eco-physiological levels. Because of presence/absence polymorphism, hybrids potentially contain more genes than their parental inbred lines. We propose that detrimental homozygous mutations and the lower number of genes in inbred lines lead to a constitutive defense mechanism that may explain the lower growth of inbred lines under well-watered conditions and their lower reactivity to water deficit.
Revolutionizing Precision Medicine: Exploring Wearable Sensors for Therapeutic Drug Monitoring and Personalized Therapy
Authors: Liu Yuqiao , Li Junmin , Xiao Shenghao , Liu Yanhui , Bai Mingxia , Gong Lixiu , Zhao Jiaqian , Chen Dajing
Published: July 2023

Precision medicine, particularly therapeutic drug monitoring (TDM), is essential for optimizing drug dosage and minimizing toxicity. However, current TDM methods have limitations, including the need for skilled operators, patient discomfort, and the inability to monitor dynamic drug level changes. In recent years, wearable sensors have emerged as a promising solution for drug monitoring. These sensors offer real-time and continuous measurement of drug concentrations in biofluids, enabling personalized medicine and reducing the risk of toxicity. This review provides an overview of drugs detectable by wearable sensors and explores biosensing technologies that can enable drug monitoring in the future. It presents a comparative analysis of multiple biosensing technologies and evaluates their strengths and limitations for integration into wearable detection systems. The promising capabilities of wearable sensors for real-time and continuous drug monitoring offer revolutionary advancements in diagnostic tools, supporting personalized medicine and optimal therapeutic effects. Wearable sensors are poised to become essential components of healthcare systems, catering to the diverse needs of patients and reducing healthcare costs.
Suicidal Ideations in Major Depressed Subjects: Role of the Temporal Dynamics of Anhedonia
Authors: Darquennes Gil , Wacquier Benjamin , Loas Gwenolé , Hein Matthieu
Published: July 2023

Given the limited data available in the literature, the aim of this study was to investigate the potential role played by the temporal dynamics of anhedonia (lifelong anhedonia and recent changes in anhedonia) in the occurrence of suicidal ideations in major depressed subjects. The clinical data of 285 major depressed subjects recruited from the database of the Erasme Hospital Sleep Laboratory were analyzed. A score on item nine of the Beck Depression Inventory (BDI-II) ≥1 and/or an identification during the systematic psychiatric assessment were used to determine the presence of suicidal ideations. The association between anhedonia complaints (lifelong anhedonia and recent change in anhedonia) and suicidal ideations in major depressed subjects was assessed by logistic regression analyzes. The prevalence of suicidal ideations was 39.3% in our sample of major depressed subjects. After adjusting for the main confounding factors, multivariate logistic regression analysis demonstrated that unlike lifelong anhedonia, only recent changes in anhedonia were a risk factor for suicidal ideations in major depressed subjects. Given this potential involvement of the recent change in anhedonia in the occurrence of suicidal ideations in major depressed subjects, it seems essential to better identify and adequately manage this specific form of anhedonia in order to open new perspectives for the prevention of suicide in this particular sub-population.
Goals and Success in Sport: The Perspectives of Parents and Adolescent Girls in Kayaking
Authors: Levental Orr , Yaffe Yosi , Lev Arey Dalit
Published: July 2023

Setting objectives and evaluating success are intrinsically linked to motivation in sports and behavior during training and competition. According to social cognitive theory, the perception of success is divided into “task” and ”ego”, which indicate an inner orientation versus an external perspective when analyzing an athlete’s achievements. These impressions can be influenced by various factors such as maturity level, gender, and the type of activity in which they participate. The current study compares perceptions of success among parents and adolescent girls competing in kayaking in Israel. To this end, a qualitative study was conducted with 20 in-depth interviews emphasizing goal setting and individual perceptions of success. The research findings reveal that contrary to previous studies, there is a perceptual gap between the two groups, with parents measuring success primarily in terms of enjoyment and self-fulfillment, and girls referring to perceived success in the context of achievements. It was also found that there is a discrepancy between setting goals and defining success, following experience and interactions within the training. The article discusses the reasons behind these gaps and the potential ramifications for sports activity and participation.
Optimization Analysis of Natural Ventilation in University Laboratories Based on CFD Simulation
Authors: Chen Xiao , Chen Xingyin , Su Rong , Cao Benyi
Published: July 2023

In recent years, there has been a significant surge in the adoption of natural ventilation for building indoor spaces, garnering widespread attention. However, the research on human comfort optimization strategies closely related to the effect of natural ventilation is still relatively blank. Therefore, we have taken university laboratories as the research object and studied the use of CFD technology to construct numerical models. Based on previous research on the relevant theories of building ventilation and the impact of various air indicators on human comfort, we simulate the indoor airflow organization of buildings, and propose reasonable optimization design strategies based on simulation results and analysis conclusions. Compared to other studies on NV, we propose a completely new indicator, the Average rate of change in air age (ARCA), to assess the rate of improvement in air age. The results show that compared with the wind environment under basic conditions, the optimization strategy proposed by us increases the wind speed area suitable for human beings by about 14.3%, and reduces ARCA by about 53.3% at most.
Structural Behaviors of Large-Section Mine Tunnels Undercrossing Existing Metro Lines
Authors: Zhai Lihua , Cai Gensen , Liang Yuehua , Guan Shaoxiang , Wang Shuying , Liaquat Luqman
Published: July 2023

To meet the operational requirements of a new metro line in Guangzhou, China, a complex tunneling project was undertaken in a business area surrounded by high-rise buildings and underground utility pipelines. Two large-section mine tunnels, with a maximum excavation span of 15.6 m, were constructed, crossing beneath the existing metro line 7 in close proximity. To ensure construction safety, extensive field monitoring was conducted, investigating the deformation and stress characteristics of the newly built tunnel lining structures and settlement of existing tunnels during various construction stages. The findings indicate that the structural integrity of the newly built tunnels may be compromised by the ground pressure resulting from deep-hole grouting, which is aimed at protecting the existing metro line above. The primary lining of the new tunnels is particularly susceptible to stress at the arch waist, where it experiences significantly higher stress compared to the arch crown and arch foot. While constructing the secondary lining before removing temporary diaphragm supports can be advantageous in controlling ground settlement, the stress levels within the secondary lining can fluctuate significantly once the temporary supports are removed. Once the tunnels are completed as closed loops, the stress conditions in both the primary and secondary lining tend to stabilize. The secondary lining primarily undergoes flexural stress, with internal force diagrams roughly symmetrical to the cross-section center line, and the most vulnerable position being at the left arch waist or invert. This investigation provides valuable insights for the design and construction of similar engineering projects in the future.
Behaviour of a Sacrificial Cladding with Foam Concrete-Filled Square Tubes under Impact Loads
Authors: Gu Liquan , Wang Yonghui , Zhai Ximei
Published: July 2023

In this paper, a new sacrificial cladding with foam concrete-filled square tubes (FCFST sacrificial cladding) was developed for dissipating impact energy. The impact experiment was conducted on the FCFST sacrificial claddings using a drop hammer impact experiment system, and the finite element simulation analysis was performed using the explicit nonlinear program LS-DYNA. The deformation modes, force–displacement responses and energy absorption performances of the FCFST sacrificial claddings were discussed. The results indicated that the impact responses of the FCFST sacrificial cladding could be classified into four stages, and the energy absorption performance could be enhanced by increasing the contact area between the sacrificial cladding and impactor. Foam concrete-filled tubes that underwent obvious plastic deformation dissipated more impact energy than other parts of the sacrificial cladding, and three deformation modes could be identified in theses tubes. Furthermore, the effects of the thickness ratio of the top plate to tube, width-to-thickness ratio of the tube and impact location on the impact behaviour of the FCFST sacrificial cladding were numerically studied. It was found that decreasing the thickness ratio of the top plate to tube could enhance the energy absorption performance of the FCFST sacrificial cladding. However, the impact location was found to have little effect on the energy absorption unless it was close to the edge of the sacrificial cladding.
The Complex Case of Carbon-Measuring Tools in Landscape Architecture
Authors: Nikologianni Anastasia , Albans Alex
Published: July 2023

As the world takes a more strategic approach to the climate crisis, carbon in its various forms has become a key factor in ascertaining the sustainability of the landscape. Landscape has been recognised as a resource and mechanism for addressing the role of carbon in the environment, with literature focused on the landscape’s carbon capacity as interconnected systems of land, soil, water and organic life. It has, however, largely neglected the crucial role of the cultural, social and historical aspects of the landscape, particularly at the level of design. This paper acknowledges and explores the complexity of landscape as a natural-cultural system with the consequent difficulties this poses in legislating, calculating and measuring carbon for global, national and local targets for low/zero carbon and carbon offsetting. The discussion takes place in the arena of landscape architecture at regional/city/local scales and the life-cycle of a project including its integration into its wider social, cultural and environmental setting. This paper develops the discourse in three major areas: first, by examining how the complexity of landscape is obscured in the context of carbon-measuring tools used in landscape architecture; secondly exploring one such tool in practice to demonstrate how site-specific design decisions can impact carbon levels; and third by proposing how an integrated understanding of landscape can be built into projects to embrace complexity and operationalise low carbon visions.
Hybrid PET/MRI in Cerebral Glioma: Current Status and Perspectives
Authors: Langen Karl-Josef , Galldiks Norbert , Mauler Jörg , Kocher Martin , Filß Christian Peter , Stoffels Gabriele , Régio Brambilla Cláudia , Stegmayr Carina , Willuweit Antje , Worthoff Wieland Alexander , Shah Nadim Jon , Lerche Christoph , Mottaghy Felix Manuel , Lohmann Philipp
Published: July 2023

Advanced MRI methods and PET using radiolabelled amino acids provide valuable information, in addition to conventional MR imaging, for brain tumour diagnostics. These methods are particularly helpful in challenging situations such as the differentiation of malignant processes from benign lesions, the identification of non-enhancing glioma subregions, the differentiation of tumour progression from treatment-related changes, and the early assessment of responses to anticancer therapy. The debate over which of the methods is preferable in which situation is ongoing, and has been addressed in numerous studies. Currently, most radiology and nuclear medicine departments perform these examinations independently of each other, leading to multiple examinations for the patient. The advent of hybrid PET/MRI allowed a convergence of the methods, but to date simultaneous imaging has reached little relevance in clinical neuro-oncology. This is partly due to the limited availability of hybrid PET/MRI scanners, but is also due to the fact that PET is a second-line examination in brain tumours. PET is only required in equivocal situations, and the spatial co-registration of PET examinations of the brain to previous MRI is possible without disadvantage. A key factor for the benefit of PET/MRI in neuro-oncology is a multimodal approach that provides decisive improvements in the diagnostics of brain tumours compared with a single modality. This review focuses on studies investigating the diagnostic value of combined amino acid PET and ‘advanced’ MRI in patients with cerebral gliomas. Available studies suggest that the combination of amino acid PET and advanced MRI improves grading and the histomolecular characterisation of newly diagnosed tumours. Few data are available concerning the delineation of tumour extent. A clear additive diagnostic value of amino acid PET and advanced MRI can be achieved regarding the differentiation of tumour recurrence from treatment-related changes. Here, the PET-guided evaluation of advanced MR methods seems to be helpful. In summary, there is growing evidence that a multimodal approach can achieve decisive improvements in the diagnostics of cerebral gliomas, for which hybrid PET/MRI offers optimal conditions.
Clinicopathological Profiles Associated with Discordant RAS Mutational Status between Liquid and Tissue Biopsies in a Real-World Cohort of Metastatic Colorectal Cancer
Authors: Brozos-Vázquez Elena , Lago-Lestón Ramón Manuel , Covela Marta , de la Cámara Gómez Juan , Fernández-Montes Ana , Candamio Sonia , Vidal Yolanda , Vázquez Francisca , Abalo Alicia , López Rosa , Blanco Cristina , Muinelo-Romay Laura , Ferreirós-Vidal Isabel , López-López Rafael
Published: July 2023

We aimed to identify common mCRC profiles associated with a discordant mutational status of RAS between the standard of care (SoC) tumour tissue tests and ctDNA tests to understand ctDNA detection and improve treatment responses. This was a multicentre, retrospective and prospective study. A total of 366 Spanish mCRC patients were independently recruited. BEAMing ddPCR technology was employed to detect ctDNA RAS mutations, and logistic regression analyses were performed to investigate clinicopathological factors associated with discordance. The highest concordance ratios were observed in profiles with multiple metastatic sites when the liver was present (89.7%; 95% CI 84.8–93.2), profiles with synchronous disease without primary tumour resection (90.2%; 95% CI 83.6–94.3) and profiles with mCRC originating in the left colon (91.3%; 95% CI 85.0–95.0). Metachronous disease originating in the right colon (OR = 6.1; 95% CI 1.7–26.5; p-value = 0.006) or rectum (OR = 5.0; 95% CI 1.5–17.8; p-value = 0.009) showed the highest probability of discrepancies. Primary tumour resection and a higher frequency of single metastases in the peritoneum or lungs in these patients were associated with reduced plasmatic mutation allele fractions (MAFs) and an increased probability of showing false-negative genotypes. Additional testing of patients with mCRC originating in the right colon or rectum with a single non-mutated ctDNA test is advised before the choice of therapy.
KRAS p.G12C Mutation in Metastatic Colorectal Cancer: Prognostic Implications and Advancements in Targeted Therapies
Authors: Ottaiano Alessandro , Sabbatino Francesco , Perri Francesco , Cascella Marco , Sirica Roberto , Patrone Renato , Capuozzo Maurizio , Savarese Giovanni , Ianniello Monica , Petrillo Nadia , Circelli Luisa , Granata Vincenza , Berretta Massimiliano , Santorsola Mariachiara , Nasti Guglielmo
Published: July 2023

KRAS is frequently mutated in tumors. It is mutated in approximately 30% of all cancer cases and in nearly 50% of cases of metastatic colorectal cancer (CRC), which is the third leading cause of cancer-related deaths worldwide. Recent advancements in understanding CRC biology and genetics have highlighted the significance of KRAS mutations in the progression of CRC. The KRAS gene encodes a small GTPase (Guanosine TriPhosphatases) that plays a key role in signaling pathways associated with important proteins involved in amplifying growth factor and receptor signals. Mutations in KRAS are frequently observed in codons 12 and 13, and these mutations have oncogenic properties. Abnormal activation of KRAS proteins strongly stimulates signals associated with various cancer-related processes in CRC, including cell proliferation, migration and neoangiogenesis. In this review, we explore the distinct prognostic implications of KRAS mutations. Specifically, the KRAS p.G12C mutation is associated with a worse prognosis in metastatic CRC. The correlation between structure, conformation and mutations is visually presented to emphasize how alterations in individual amino acids at the same position in a single protein can unexpectedly exhibit complex involvement in cancer. Last, KRAS p.G12C is discussed as an emerging and promising therapeutic target in metastatic CRC, providing a concise overview of available clinical data regarding the use of new inhibitors.
MRI Apparent Diffusion Coefficient (ADC) as a Biomarker of Tumour Response: Imaging-Pathology Correlation in Patients with Hepatic Metastases from Colorectal Cancer (EORTC 1423)
Authors: Jackson Alan , Pathak Ryan , deSouza Nandita M. , Liu Yan , Jacobs Bart K. M. , Litiere Saskia , Urbanowicz-Nijaki Maria , Julie Catherine , Chiti Arturo , Theysohn Jens , Ayuso Juan R. , Stroobants Sigrid , Waterton John C.
Published: July 2023

Background: Tumour apparent diffusion coefficient (ADC) from diffusion-weighted magnetic resonance imaging (MRI) is a putative pharmacodynamic/response biomarker but the relationship between drug-induced effects on the ADC and on the underlying pathology has not been adequately defined. Hypothesis: Changes in ADC during early chemotherapy reflect underlying histological markers of tumour response as measured by tumour regression grade (TRG). Methods: Twenty-six patients were enrolled in the study. Baseline, 14 days, and pre-surgery MRI were performed per study protocol. Surgical resection was performed in 23 of the enrolled patients; imaging-pathological correlation was obtained from 39 lesions from 21 patients. Results: There was no evidence of correlation between TRG and ADC changes at day 14 (study primary endpoint), and no significant correlation with other ADC metrics. In scans acquired one week prior to surgery, there was no significant correlation between ADC metrics and percentage of viable tumour, percentage necrosis, percentage fibrosis, or Ki67 index. Conclusions: Our hypothesis was not supported by the data. The lack of meaningful correlation between change in ADC and TRG is a robust finding which is not explained by variability or small sample size. Change in ADC is not a proxy for TRG in metastatic colorectal cancer.
Prognostic Implications of PET-Derived Tumor Volume and Uptake in Patients with Neuroendocrine Tumors
Authors: Weber Manuel , Telli Tugce , Kersting David , Seifert Robert
Published: July 2023

Historically, molecular imaging of somatostatin receptor (SSTR) expression in patients with neuroendocrine tumors (NET) was performed using SSTR scintigraphy (SRS). Sustained advances in medical imaging have led to its gradual replacement with SSTR positron-emission tomography (SSTR-PET). The higher sensitivity in comparison to SRS on the one hand and conventional cross-sectional imaging, on the other hand, enables more accurate staging and allows for image quantification. In addition, in recent years, a growing body of evidence has assessed the prognostic implications of SSTR-PET-derived prognostic biomarkers for NET patients, with the aim of risk stratification, outcome prognostication, and prediction of response to peptide receptor radionuclide therapy. In this narrative review, we give an overview of studies examining the prognostic value of advanced SSTR-PET-derived (semi-)quantitative metrics like tumor volume, uptake, and composite metrics. Complementing this analysis, a discussion of the current trends, clinical implications, and future directions is provided.
Study of Alternative Imaging Methods for In Vivo Boron Neutron Capture Therapy
Authors: Ramos López Dayron Ramos , Pugliese Gabriella Maria Incoronata , Iaselli Giuseppe , Amoroso Nicola , Gong Chunhui , Pascali Valeria , Altieri Saverio , Protti Nicoletta
Published: July 2023

Boron Neutron Capture Therapy (BNCT) is an innovative and highly selective treatment against cancer. Nowadays, in vivo boron dosimetry is an important method to carry out such therapy in clinical environments. In this work, different imaging methods were tested for dosimetry and tumor monitoring in BNCT based on a Compton camera detector. A dedicated dataset was generated through Monte Carlo tools to study the imaging capabilities. We first applied the Maximum Likelihood Expectation Maximization (MLEM) iterative method to study dosimetry tomography. As well, two methods based on morphological filtering and deep learning techniques with Convolutional Neural Networks (CNN), respectively, were studied for tumor monitoring. Furthermore, clinical aspects such as the dependence on the boron concentration ratio in image reconstruction and the stretching effect along the detector position axis were analyzed. A simulated spherical gamma source was studied in several conditions (different detector distances and boron concentration ratios) using MLEM. This approach proved the possibility of monitoring the boron dose. Tumor monitoring using the CNN method shows promising results that could be enhanced by increasing the training dataset.
Current Landscape of Genome-Wide Association Studies in Acute Myeloid Leukemia: A Review
Authors: Marrero Richard J. , Lamba Jatinder K.
Published: July 2023

Acute myeloid leukemia (AML) is a clonal hematopoietic disease that arises from chromosomal and genetic aberrations in myeloid precursor cells. AML is one of the most common types of acute leukemia in adults; however, it is relatively rare overall, comprising about 1% of all cancers. In the last decade or so, numerous genome-wide association studies (GWAS) have been conducted to screen between hundreds of thousands and millions of variants across many human genomes to discover genetic polymorphisms associated with a particular disease or phenotype. In oncology, GWAS has been performed in almost every commonly occurring cancer. Despite the increasing number of studies published regarding other malignancies, there is a paucity of GWAS studies for AML. In this review article, we will summarize the current status of GWAS in AML.
How Asian Breast Cancer Patients Experience Unequal Incidence of Chemotherapy Side Effects: A Look at Ethnic Disparities in Febrile Neutropenia Rates
Authors: Lim Zi Lin , Ho Peh Joo , Hartman Mikael , Tan Ern Yu , Riza Nur Khaliesah Binte Mohamed , Lim Elaine Hsuen , Nitar Phyu ,   Joint Breast Cancer Registry (JBCR), Wong Fuh Yong , Li Jingmei
Published: July 2023

The majority of published findings on chemotherapy-induced febrile neutropenia (FN) are restricted to three ethnic groups: Asians, Caucasians, and African Americans. In this two-part study, we examined FN incidence and risk factors in Chinese, Malay, and Indian chemotherapy-treated breast cancer (BC) patients. Hospital records or ICD codes were used to identify patients with FN. In both the Singapore Breast Cancer Cohort (SGBCC) and the Joint Breast Cancer Registry (JBCR), the time of the first FN from the start of chemotherapy was estimated using Cox regression. Multinomial regression was used to evaluate differences in various characteristics across ethnicities. FN was observed in 170 of 1014 patients in SGBCC. The Cox model showed that non-Chinese were at higher risk of developing FN (HRMalay [95% CI]:2.04 [1.44–2.88], p < 0.001; HRIndian:1.88 [1.11–3.18], p = 0.018). In JBCR, FN was observed in 965 of 7449 patients. Univariable Cox models identified ethnicity, a lower baseline absolute neutrophil count, non-luminal A proxy subtypes, and anthracycline-containing regimens as risk factors. Disparities across ethnicities’ risk (HRMalay:1.29 [1.07–1.54], p = 0.006; HRIndian:1.50 [1.19–1.88], p < 0.001) remained significant even after further adjustments. Finally, an age-adjusted multinomial model showed that Malays (p = 0.006) and Indians (p = 0.009) were significantly more likely to develop multiple episodes of FN during treatment. Ethnic differences in chemotherapy-induced FN among BC patients exist. Further studies can focus on investigating pharmacogenetic differences across ethnicities.
Landscape of Genetic Mutations in Appendiceal Cancers
Authors: Constantin Marian , Mătanie Cristina , Petrescu Livia , Bolocan Alexandra , Andronic Octavian , Bleotu Coralia , Mitache Mihaela Magdalena , Tudorache Sorin , Vrancianu Corneliu Ovidiu
Published: July 2023

In appendiceal cancers, the most frequently mutated genes are (i) KRAS, which, when reactivated, restores signal transduction via the RAS–RAF–MEK–ERK signaling pathway and stimulates cell proliferation in the early stages of tumor transformation, and then angiogenesis; (ii) TP53, whose inactivation leads to the inhibition of programmed cell death; (iii) GNAS, which, when reactivated, links the cAMP pathway to the RAS–RAF–MEK–ERK signaling pathway, stimulating cell proliferation and angiogenesis; (iv) SMAD4, exhibiting typical tumor-suppressive activity, blocking the transmission of oncogenic TGFB signals via the SMAD2/SMAD3 heterodimer; and (v) BRAF, which is part of the RAS–RAF–MEK–ERK signaling pathway. Diverse mutations are reported in other genes, which are part of secondary or less critical signaling pathways for tumor progression, but which amplify the phenotypic diversity of appendiceal cancers. In this review, we will present the main genetic mutations involved in appendix tumors and their roles in cell proliferation and survival, and in tumor invasiveness, angiogenesis, and acquired resistance to anti-growth signals.
In-Vivo Somatostatin-Receptor Expression in Small Cell Lung Cancer as a Prognostic Image Biomarker and Therapeutic Target
Authors: Şen Feyza , Sheikh Gabriel T. , von Hinten Johannes , Schindele Andreas , Kircher Malte , Dierks Alexander , Pfob Christian H. , Serfling Sebastian E. , Buck Andreas K. , Pelzer Theo , Higuchi Takahiro , Weich Alexander , Bundschuh Ralph A. , Werner Rudolf A. , Lapa Constantin
Published: July 2023

Background: Given the dismal prognosis of small cell lung cancer (SCLC), novel therapeutic targets are urgently needed. We aimed to evaluate whether SSTR expression, as assessed by positron emission tomography (PET), can be applied as a prognostic image biomarker and determined subjects eligible for peptide receptor radionuclide therapy (PRRT). Methods: A total of 67 patients (26 females; age, 41–80 years) with advanced SCLC underwent SSTR-directed PET/computed tomography (somatostatin receptor imaging, SRI). SRI-avid tumor burden was quantified by maximum standardized uptake values (SUVmax) and tumor-to-liver ratios (T/L) of the most intense SCLC lesion. Scan findings were correlated with progression-free (PFS) and overall survival (OS). In addition, subjects eligible for SSTR-directed radioligand therapy were identified, and treatment outcome and toxicity profile were recorded. Results: On a patient basis, 36/67 (53.7%) subjects presented with mainly SSTR-positive SCLC lesions (>50% lesions positive); in 10/67 patients (14.9%), all lesions were positive. The median SUVmax was found to be 8.5, while the median T/L was 1.12. SRI-uptake was not associated with PFS or OS, respectively (SUVmax vs. PFS, ρ = 0.13 with p = 0.30 and vs. OS, ρ = 0.00 with p = 0.97; T/L vs. PFS, ρ = 0.07 with p = 0.58 and vs. OS, ρ = −0.05 with p = 0.70). PRRT was performed in 14 patients. One patient succumbed to treatment-independent infectious complications immediately after PRRT. In the remaining 13 subjects, disease control was achieved in 5/13 (38.5%) with a single patient achieving a partial response (stable disease in the remainder). In the sub-group of responding patients, PFS and OS were 357 days and 480 days, respectively. Conclusions: SSTR expression as detected by SRI is not predictive of outcome in patients with advanced SCLC. However, it might serve as a therapeutic target in selected patients.
CDC20 Is Regulated by the Histone Methyltransferase, KMT5A, in Castration-Resistant Prostate Cancer
Authors: Alebady Zainab A. H. , Azizyan Mahsa , Nakjang Sirintra , Lishman-Walker Emma , Al-Kharaif Dhuha , Walker Scott , Choo Hui Xian , Garnham Rebecca , Scott Emma , Johnson Katya L. , Robson Craig N. , Coffey Kelly
Published: July 2023

The methyltransferase KMT5A has been proposed as an oncogene in prostate cancer and therefore represents a putative therapeutic target. To confirm this hypothesis, we have performed a microarray study on a prostate cancer cell line model of androgen independence following KMT5A knockdown in the presence of the transcriptionally active androgen receptor (AR) to understand which genes and cellular processes are regulated by KMT5A in the presence of an active AR. We observed that 301 genes were down-regulated whilst 408 were up-regulated when KMT5A expression was reduced. KEGG pathway and gene ontology analysis revealed that apoptosis and DNA damage signalling were up-regulated in response to KMT5A knockdown whilst protein folding and RNA splicing were down-regulated. Under these conditions, the top non-AR regulated gene was found to be CDC20, a key regulator of the spindle assembly checkpoint with an oncogenic role in several cancer types. Further investigation revealed that KMT5A regulates CDC20 in a methyltransferase-dependent manner to modulate histone H4K20 methylation within its promoter region and indirectly via the p53 signalling pathway. A positive correlation between KMT5A and CDC20 expression was also observed in clinical prostate cancer samples, further supporting this association. Therefore, we conclude that KMT5A is a valid therapeutic target for the treatment of prostate cancer and CDC20 could potentially be utilised as a biomarker for effective therapeutic targeting.
Clinical Features and Risk Stratification of Multiple Myeloma Patients with COVID-19
Authors: Zheng Ruifang , Mieth Kelsey , Bennett Christen , Miller Carol , Anderson Larry D. , Chen Mingyi , Cao Jing
Published: July 2023

SARS-CoV-2 infection often results in a more severe COVID-19 disease course in multiple myeloma (MM) patients compared to immunocompetent individuals. The aim of this report is to summarize the clinical features of the MM patients with COVID-19 and the impact of MM treatment on outcomes to guide risk stratification and ensure the appropriate management of the patients. Serological responses in MM patients post-infection or -vaccination are also reviewed to better understand the strategy of prevention. Along with reports from the literature, we presented findings from a retrospective analysis of the clinical characteristics and outcomes of COVID-19 infection in MM patients in our institution. Study population includes 34 MM patients with a median age of 61 (range: 35–82 years) who tested positive for SARS-CoV-2 between 1 March 2020–15 August 2021. We examined the effect of chemotherapy, the benefit of neutralizing monoclonal antibody (Bamlanivimab) and the impact of anti-CD38 antibody (daratumumab) on the hospitalization and mortality of the patients, as well as the efficacy of native antibody production. Our results showed that MM patients have increased hospitalization and mortality rates from COVID-19 compared with that of general population, especially those on active chemotherapy. Advanced age, high-risk myeloma, renal disease, and suboptimal disease control are independent predictors of adverse outcomes. The use of daratumumab does not increase the disease severity/hospitalization or the post-infection/vaccination seropositivity of SARS-CoV-2. The neutralizing antibody decreases overall mortality. Evidence from the current study and previous publications suggest that testing of neutralizing antibody post-SARS-CoV-2 vaccination in MM patients may be needed in reducing COVID-19 risk.
Impact of the Recipient’s Pre-Treatment Blood Lymphocyte Count on Intended and Unintended Effects of Anti-T-Lymphocyte Globulin in Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Nikoloudis Alexander , Buxhofer-Ausch Veronika , Aichinger Christoph , Binder Michaela , Hasengruber Petra , Kaynak Emine , Wipplinger Dagmar , Milanov Robert , Strassl Irene , Stiefel Olga , Machherndl-Spandl Sigrid , Petzer Andreas , Weltermann Ansgar , Clausen Johannes
Published: July 2023

Background: In allogeneic hematopoietic stem cell transplantation (HSCT), Anti-T-Lymphocyte Globulin (ATLG) may be used for the prevention of severe graft-versus-host disease (GVHD). ATLG targets both the recipient’s lymphocytes and those transferred with the graft. Assuming an inverse relation between the recipient’s absolute lymphocyte count (ALC) and exposure of remaining ATLG to the graft, we aim to evaluate the impact of the recipient’s ALC before the first ATLG administration on the benefits (prevention of GVHD and GVHD-associated mortality) and potential risks (increased relapse incidence) associated with ATLG. Methods: In recipients of HLA-matched, ATLG-based HSCT (n = 311), we assessed the incidence of acute GVHD, GVHD-related mortality and relapse, as well as other transplant-related outcomes, in relation to the respective ALC (divided into tertiles) before ATLG. Results: The top-tertile ALC group had a significantly increased risk of aGVHD (subhazard ratio (sHR) 1.81; [CI 95%; 1.14–2.88]; p = 0.01) and aGVHD-associated mortality (sHR 1.81; [CI 95%; 1.03–3.19]; p = 0.04). At the highest ATLG dose level (≥45 mg/kg), recipients with lowest-tertile ALC had a trend towards increased relapse incidence (sHR 4.19; [CI 95%; 0.99–17.7]; p = 0.05, n = 32). Conclusions: ATLG dosing based on the recipient’s ALC may be required for an optimal balance between GVHD suppression and relapse prevention.
LncRNAs as Regulators of Atherosclerotic Plaque Stability
Authors: Petkovic Aleksa , Erceg Sanja , Munjas Jelena , Ninic Ana , Vladimirov Sandra , Davidovic Aleksandar , Vukmirovic Luka , Milanov Marko , Cvijanovic Dane , Mitic Tijana , Sopic Miron
Published: July 2023

Current clinical data show that, despite constant efforts to develop novel therapies and clinical approaches, atherosclerotic cardiovascular diseases (ASCVD) are still one of the leading causes of death worldwide. Advanced and unstable atherosclerotic plaques most often trigger acute coronary events that can lead to fatal outcomes. However, despite the fact that different plaque phenotypes may require different treatments, current approaches to prognosis, diagnosis, and classification of acute coronary syndrome do not consider the diversity of plaque phenotypes. Long non-coding RNAs (lncRNAs) represent an important class of molecules that are implicated in epigenetic control of numerous cellular processes. Here we review the latest knowledge about lncRNAs’ influence on plaque development and stability through regulation of immune response, lipid metabolism, extracellular matrix remodelling, endothelial cell function, and vascular smooth muscle function, with special emphasis on pro-atherogenic and anti-atherogenic lncRNA functions. In addition, we present current challenges in the research of lncRNAs’ role in atherosclerosis and translation of the findings from animal models to humans. Finally, we present the directions for future lncRNA-oriented research, which may ultimately result in patient-oriented therapeutic strategies for ASCVD.
Chemokine/ITGA4 Interaction Directs iPSC-Derived Myogenic Progenitor Migration to Injury Sites in Aging Muscle for Regeneration
Authors: Ashraf Muhammad , Tipparaju Srinivas M. , Kim Joung Woul , Xuan Wanling
Published: July 2023

The failure of muscle to repair after injury during aging may be a major contributor to muscle mass loss. We recently generated muscle progenitor cells (MPCs) from human-induced pluripotent stem-cell (iPSC) cell lines using small molecules, CHIR99021 and Givinostat (Givi-MPCs) sequentially. Here, we test whether the chemokines overexpressed in injured endothelial cells direct MPC migration to the site by binding to their receptor, ITGA4. ITGA4 was heavily expressed in Givi-MPCs. To study the effects on the mobilization of Givi-MPCs, ITGA4 was knocked down by an ITGA4 shRNA lentiviral vector. With and without ITGA4 knocked down, cell migration in vitro and cell mobilization in vivo using aged NOD scid gamma (NSG) mice and mdx/scid mice were analyzed. The migration of shITGA4-Givi-MPCs was significantly impaired, as shown in a wound-healing assay. The knockdown of ITGA4 impaired the migration of Givi-MPCs towards human aortic endothelial cells (HAECs), in which CX3CL1 and VCAM-1 were up-regulated by the treatment of TNF-α compared with scramble ones using a transwell system. MPCs expressing ITGA4 sensed chemokines secreted by endothelial cells at the injury site as a chemoattracting signal to migrate to the injured muscle. The mobilization of Givi-MPCs was mediated by the ligand–receptor interaction, which facilitated their engraftment for repairing the sarcopenic muscle with injury.
Design of a Portable and Reliable Fluorimeter with High Sensitivity for Molecule Trace Analysis
Authors: López-Pérez Germán , González-Arjona Domingo , Roldán González Emilio , Román-Hidalgo Cristina
Published: July 2023

There is a growing need for portable, highly sensitive measuring equipment to analyze samples in situ and in real time. For these reasons, it is becoming increasingly important to research new experimental equipment to carry out this work with advanced, robust and low-cost devices. In this framework, a flexible, portable and low-cost fluorimeter (under EUR 500), based on a C12880 MA MEMS micro-spectrometer with an Arduino compatible breakout board, has been developed for the trace analysis of biological substances. The proposed system can employ two selectable excitation sources for flexibility, one in the visible region at 405 nm (incorporated in the board) and an external LED at 365 nm in the UV region. This additional excitation source can be easily interchanged, varying the LED type for investigating any fluorophore compound of interest. The measurement process is micro-controlled, which allows the precise control of the spectrometer sensitivity by adjusting the integration time of each experiment separately. Data acquisition is easy, reliable and interfaced with a spreadsheet for fast spectra visualization and calculations. For testing the performance of the new device in fluorescence measurements, different fluorophore molecules which can be commonly found in biological samples, such as Fluorescein, Riboflavin, Quinine, Rhodamine b and Ru (II)-bipyridyl, have been employed. A high sensitivity and low quantitation limits (in the ppb range) have been found in all cases for the investigated chemicals. The portable device is also suitable for the study of other interesting phenomena, such as fluorescence quenching induced by chemical agents (such as halide anions or even auto-quenching). In this sense, an application for the quantification of chloride anions in aqueous solutions has been performed obtaining a LOD value of 18 ppm. The obtained results for all chemicals investigated with the proposed fluorimeter are always very similar in quantification figures, or even better than the data reported in literature, when using commercial laboratory equipment.