bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk of Fungal Growth in Nearly Zero-Energy Buildings (nZEB)
Authors: Carpino Cristina , Loukou Evangelia , Chen Austin Miguel , Andersen Birgitte , Mora Dafni , Arcuri Natale
Published: June 2023

Research on nearly zero-energy buildings has addressed mainly the aspects of energy saving or technical and economic optimization, while some studies have been conducted on comfort and indoor air quality. However, the potential problems that may arise in low-energy buildings during the operational phase, and especially the risk of fungal growth, which can deteriorate the indoor environment and pose a health risk to the occupants, are yet to be extensively investigated. The present work intends to analyze previous research on microbial contamination in zero-energy buildings in order to identify the possible risks that may lead to fungal formation and the possible strategies to prevent the proliferation of molds. The methodology is based on a systematic literature review and subsequent critical analysis to outline perspectives on this topic. The main results indicate that high envelope insulation and inadequate ventilation are the leading causes of fungal growth in energy-efficient buildings. The need for more detailed regulation in this area is also highlighted. The study’s outcomes underline the need for more attention to be paid to the design and management of zero-energy buildings, aiming to achieve the reduction in energy demands while ensuring the occupants’ well-being.
Rutting and Fatigue Resistance of High-Modulus Asphalt Mixture Considering the Combined Effects of Moisture Content and Temperature
Authors: Zhuang Shenghan , Wang Jian , Li Min , Yang Changqing , Chen Jingchun , Zhang Xiangquan , Zhao Zedong , Li Di , Ren Jiaolong
Published: June 2023

High-modulus asphalt mixtures (HMAM) have been widely used in asphalt pavement in high-temperature areas of China, owing to their advantages in rutting and fatigue resistance. However, moisture and temperature interdependently determine the degradation of pavement performance of the HMAM, owing to the unique climatic conditions in summer in some high-temperature areas of China. There were few studies on the rutting and fatigue properties of the HMAM under the combined action of moisture contents and temperatures. Hence, the moisture absorption characteristics of the HMAM at different temperatures were analyzed. The rutting performance of the HMAM was investigated under different moisture contents and temperatures. The fatigue performance of the HMAM was investigated under different moisture contents, temperatures, and stress levels. Results show that: the rutting and fatigue resistance of the HMAM decrease with the increase in temperature and moisture content. The dynamic stability decreases by 8.9% at 40 °C and by 7.0% at 60 °C on average per 10% increase in moisture content and decreases by 22.7% on average per 10 °C increase in temperature. The fatigue life decreases by 4.1% at 15 °C and by 3.1% at 40 °C on average per 10% increase in moisture content and decreases by 31.3% on average per 10 °C increase in temperature. Finally, a prediction equation was established to predict the fatigue life under different moisture contents and temperatures.
RF Sensor with Graphene Film for HRP Concentration Detection
Authors: Peinetti Fabio , Yasir Muhammad , Savi Patrizia
Published: June 2023

This paper presents a radio-frequency (RF) antenna as a sensor to detect Horseradish peroxidase (HRP). At the core of the proposed approach is a graphene film deposited on a stub connected to an RF antenna. The graphene film is doctor bladed on the stub. The film is then properly chemically functionalized in order to detect the presence of Horseradish peroxidase (HRP). We validate the proof-of-concept operation of HRP concentration detection by measuring the frequency shift of the reflection coefficient of the antenna using very small concentration of HRP (0.03 mM to 0.6 mM).
Small Molecule RBI2 Disrupts Ribosome Biogenesis through Pre-rRNA Depletion
Authors: Scull Catherine E. , Twa Guy , Zhang Yinfeng , Yang Naiheng J. , Hunter Robert N. , Augelli-Szafran Corinne E. , Schneider David A.
Published: June 2023

Cancer cells are especially sensitive to perturbations in ribosome biogenesis as they rely on finely tuned protein homeostasis to facilitate their rapid growth and proliferation. While ribosome synthesis and cancer have a well-established relationship, ribosome biogenesis has only recently drawn interest as a cancer therapeutic target. In this study, we exploited the relationship between ribosome biogenesis and cancer cell proliferation by using a potent ribosome biogenesis inhibitor, RBI2 (Ribosome Biogenesis Inhibitor 2), to perturb cancer cell growth and viability. We demonstrate herein that RBI2 significantly decreases cell viability in malignant melanoma cells and breast cancer cell lines. Treatment with RBI2 dramatically and rapidly decreased ribosomal RNA (rRNA) synthesis, without affecting the occupancy of RNA polymerase I (Pol I) on the ribosomal DNA template. Next-generation RNA sequencing (RNA-seq) revealed that RBI2 and previously described ribosome biogenesis inhibitor CX-5461 induce distinct changes in the transcriptome. An investigation of the content of the pre-rRNAs through RT-qPCR revealed an increase in the polyadenylation of cellular rRNA after treatment with RBI2, constituting a known pathway by which rRNA degradation occurs. Northern blotting revealed that RBI2 does not appear to impair or alter rRNA processing. Collectively, these data suggest that RBI2 inhibits rRNA synthesis differently from other previously described ribosome biogenesis inhibitors, potentially acting through a novel pathway that upregulates the turnover of premature rRNAs.
Prognostic Factors in Epithelioid Hemangioendothelioma: Analysis of a Nationwide Molecularly/Immunohistochemically Confirmed Cohort of 57 Cases
Authors: Tomassen Tess , Versleijen-Jonkers Yvonne M. H. , Hillebrandt-Roeffen Melissa H. S. , Van Cleef Patricia H. J. , van Dalen Thijs , Weidema Marije E. , Desar Ingrid M. E. , Flucke Uta , van Gorp Joost M.
Published: June 2023

Epithelioid hemangioendothelioma (EHE) is an extremely rare vascular sarcoma with variable aggressive clinical behavior. In this retrospective study, we aimed to investigate prognostic factors based on clinicopathologic findings in a molecularly/immunohistochemically confirmed nationwide multicenter cohort of 57 EHE cases. Patients had unifocal disease (n = 29), multifocal disease (n = 5), lymph node metastasis (n = 8) and/or distant metastasis (n = 15) at the time of diagnosis. The overall survival rate was 71.4% at 1 year and 50.7% at 5 years. Survival did not correlate with sex, age or histopathological parameters. No survival differences were observed between multifocal and metastatic disease, suggesting that multifocality represents early metastases and treatment options are limited in comparison to unifocal disease. In unifocal tumors, survival could be predicted using the risk stratification model of Shibayama et al., dividing the cases into low- (n = 4), intermediate- (n = 15) and high- (n = 3) risk groups. No clinical or histopathological parameters were associated with progressive unifocal disease course. Lymph node metastases at the time of diagnosis occurred in 14.0% of the cases and were mainly associated with tumor localization in the head and neck area, proposing lymph node dissection. In conclusion, our results demonstrate the aggressive behavior of EHE, emphasize the prognostic value of a previously described risk stratification model and may provide new insights regarding tumor focality, therapeutic strategies and prognosis.
Exploring the Characteristics of Circulating Tumor DNA in Pt1a Clear Cell Renal Cell Carcinoma: A Pilot Study
Authors: Kim Hongkyung , Park Jee Soo , Choi Zisun , Min Seungki , Park Jihyang , Shin Saeam , Choi Jong Rak , Lee Seung-Tae , Ham Won Sik
Published: June 2023

Circulating tumor DNA (ctDNA) is a promising biomarker for clear cell renal cell carcinoma (ccRCC); however, its characteristics in small renal masses of ccRCC remain unclear. In this pilot study, we explored the characteristics of ctDNA in pT1a ccRCC. Plasma samples were collected preoperatively from 53 patients with pT1a ccRCC. The ctDNA of pT1a ccRCC was profiled using next-generation sequencing and compared with that of higher-stage ccRCC. The association of ctDNA in pT1a ccRCC with clinicopathological features was investigated. The positive relationship of mutations between ctDNA and matched tissues was evaluated. In pT1a ccRCC, the ctDNA detection rate, cell-free DNA concentration, and median variant allele frequency were 20.8%, 5.8 ng/mL, and 0.38%, respectively, which were significantly lower than those in metastatic ccRCC. The ctDNA gene proportions in pT1a samples differed from those in metastatic ccRCC samples. The relationships between ctDNA and tumor size, tumor grade, and patient age were not elucidated. The positive concordance between ctDNA and matched tissues was poor for pT1a ccRCC. Strategies are needed to increase sensitivity while eliminating noise caused by clonal hematopoiesis to increase the clinical utility of ctDNA analysis in small renal masses of ccRCC.
Treatment of Nodular Lymphocyte-Predominant Hodgkin Lymphoma: Where Do We Stand? Where Do We Go?
Authors: Eichenauer Dennis A. , Fuchs Michael
Published: June 2023

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare B cell-derived lymphoma entity accounting for ≈5% of all Hodgkin lymphoma (HL) cases. In recent decades, patients with newly diagnosed NLPHL have usually been treated very similarly to classical HL (cHL). The 10-year overall survival rates with HL-directed approaches are in excess of 90%. However, pathological and clinical characteristics of NLPHL resemble indolent B-cell non-Hodgkin lymphoma (B-NHL) in some aspects. Thus, nodular lymphocyte-predominant B-cell lymphoma has been proposed as an alternative name, and the use of B-NHL-directed treatment strategies has become more common in NLPHL despite limited data. Given the often indolent clinical course of NLPHL, even in the case of relapse, the majority of patients with disease recurrence do not require high-dose chemotherapy and autologous stem cell transplantation but are treated sufficiently with low-intensity approaches such as single-agent anti-CD20 antibody treatment. The establishment of novel prognostic scores for NLPHL patients may optimize risk group and treatment allocation in newly diagnosed and relapsed disease.
Spectrum and Frequency of Germline FANCM Protein-Truncating Variants in 44,803 European Female Breast Cancer Cases
Authors: Figlioli Gisella , Billaud Amandine , Wang Qin , Bolla Manjeet K. , Dennis Joe , Lush Michael , Kvist Anders , Adank Muriel A. , Ahearn Thomas U. , Antonenkova Natalia N. , Auvinen Päivi , Behrens Sabine , Bermisheva Marina , Bogdanova Natalia V. , Bojesen Stig E. , Bonanni Bernardo , Brüning Thomas , Camp Nicola J. , Campbell Archie , Castelao Jose E. , Cessna Melissa H. ,   NBCS Collaborators, Czene Kamila , Devilee Peter , Dörk Thilo , Eriksson Mikael , Fasching Peter A. , Flyger Henrik , Gabrielson Marike , Gago-Dominguez Manuela , García-Closas Montserrat , Glendon Gord , Gómez Garcia Encarna B. , González-Neira Anna , Grassmann Felix , Guénel Pascal , Hahnen Eric , Hamann Ute , Hillemanns Peter , Hooning Maartje J. , Hoppe Reiner , Howell Anthony , Humphreys Keith ,   kConFab Investigators, Jakubowska Anna , Khusnutdinova Elza K. , Kristensen Vessela N. , Lindblom Annika , Loizidou Maria A. , Lubiński Jan , Mannermaa Arto , Maurer Tabea , Mavroudis Dimitrios , Newman William G. , Obi Nadia , Panayiotidis Mihalis I. , Radice Paolo , Rashid Muhammad U. , Rhenius Valerie , Ruebner Matthias , Saloustros Emmanouil , Sawyer Elinor J. , Schmidt Marjanka K. , Schmutzler Rita K. , Shah Mitul , Southey Melissa C. , Tomlinson Ian , Truong Thérèse , van Veen Elke M. , Wendt Camilla , Yang Xiaohong R. , Michailidou Kyriaki , Dunning Alison M. , Pharoah Paul D. P. , Easton Douglas F. , Andrulis Irene L. , Evans D. Gareth , Hollestelle Antoinette , Chang-Claude Jenny , Milne Roger L. , Peterlongo Paolo
Published: June 2023

FANCM germline protein truncating variants (PTVs) are moderate-risk factors for ER-negative breast cancer. We previously described the spectrum of FANCM PTVs in 114 European breast cancer cases. In the present, larger cohort, we report the spectrum and frequency of four common and 62 rare FANCM PTVs found in 274 carriers detected among 44,803 breast cancer cases. We confirmed that p.Gln1701* was the most common PTV in Northern Europe with lower frequencies in Southern Europe. In contrast, p.Gly1906Alafs*12 was the most common PTV in Southern Europe with decreasing frequencies in Central and Northern Europe. We verified that p.Arg658* was prevalent in Central Europe and had highest frequencies in Eastern Europe. We also confirmed that the fourth most common PTV, p.Gln498Thrfs*7, might be a founder variant from Lithuania. Based on the frequency distribution of the carriers of rare PTVs, we showed that the FANCM PTVs spectra in Southwestern and Central Europe were much more heterogeneous than those from Northeastern Europe. These findings will inform the development of more efficient FANCM genetic testing strategies for breast cancer cases from specific European populations.
Preclinical Models of Neuroblastoma—Current Status and Perspectives
Authors: Krawczyk Ewa , Kitlińska Joanna
Published: June 2023

Preclinical in vitro and in vivo models remain indispensable tools in cancer research. These classic models, including two- and three-dimensional cell culture techniques and animal models, are crucial for basic and translational studies. However, each model has its own limitations and typically does not fully recapitulate the course of the human disease. Therefore, there is an urgent need for the development of novel, advanced systems that can allow for efficient evaluation of the mechanisms underlying cancer development and progression, more accurately reflect the disease pathophysiology and complexity, and effectively inform therapeutic decisions for patients. Preclinical models are especially important for rare cancers, such as neuroblastoma, where the availability of patient-derived specimens that could be used for potential therapy evaluation and screening is limited. Neuroblastoma modeling is further complicated by the disease heterogeneity. In this review, we present the current status of preclinical models for neuroblastoma research, discuss their development and characteristics emphasizing strengths and limitations, and describe the necessity of the development of novel, more advanced and clinically relevant approaches.
The Role of Post-Operative Radiotherapy for Non-Spine Bone Metastases (NSBMs)
Authors: Ramadan Sherif , Arifin Andrew J. , Nguyen Timothy K.
Published: June 2023

Non-spine bone metastases (NSBMs) can cause significant morbidity and deterioration in the quality of life of cancer patients. This paper reviews the role of post-operative radiotherapy (PORT) in the management of NSBMs and provides suggestions for clinical practice based on the best available evidence. We identified six retrospective studies and several reviews that examined PORT for NSBMs. These studies suggest that PORT reduces local recurrence rates and provides effective pain relief. Based on the literature, PORT was typically delivered as 20 Gy in 5 fractions or 30 Gy in 10 fractions within 5 weeks of surgery. Complete coverage of the surgical hardware is an important consideration when designing an appropriate radiation plan and leads to improved local control. Furthermore, the integration of PORT in a multidisciplinary team with input from radiation oncologists and orthopedic surgeons is beneficial. A multimodal approach including PORT should be considered for an NSBM that requires surgery. However, phase III studies are needed to answer many remaining questions and optimize the management of NSBMs.
Combined Blockade of TIGIT and PD-L1 Enhances Anti-Neuroblastoma Efficacy of GD2-Directed Immunotherapy with Dinutuximab Beta
Authors: Siebert Nikolai , Zumpe Maxi , Schwencke Christian Heinrich , Biskupski Simon , Troschke-Meurer Sascha , Leopold Justus , Zikoridse Alexander , Lode Holger N.
Published: June 2023

Immunotherapies against high-risk neuroblastoma (NB), using the anti-GD2 antibody (Ab) dinutuximab beta (DB), significantly improved patient survival. Ab-dependent cellular cytotoxicity (ADCC) is one of the main mechanisms of action and it is primarily mediated by NK cells. To further improve antitumor efficacy, we investigated here a combinatorial immunotherapy with DB and the double immune checkpoint blockade of T-cell immunoreceptor with immunoglobulin and ITIM domain (TIGIT) and programmed cell death ligand-1 (PD-L1). The effects of ADCC, mediated by DB against NB cells on NK-cell activity, and the expression of TIGIT and CD226 and their ligands CD112 and CD155, as well as of PD-1 and PD-L1 on NB and effector cells, were investigated using flow cytometry. ADCC was assessed with a calcein-AM-based cytotoxicity assay. The efficacy of a combinatorial immunotherapy with DB, given as a long-term treatment, and the double immune checkpoint blockade of TIGIT and PD-L1 was shown using a resistant murine model of NB, followed by an analysis of the tumor tissue. We detected both TIGIT ligands, CD112 and CD155, on all NB cell lines analyzed. Although ADCC by DB resulted in a strong activation of NK cells leading to an effective tumor cell lysis, a remarkable induction of PD-L1 expression on NB cells, and of TIGIT and PD-1 on effector cells, especially on NK cells, was observed. Additional anti-TIGIT or anti-PD-L1 treatments effectively inhibited tumor growth and improved survival of the mice treated with DB. The superior antitumor effects were observed in the “DB + double immune checkpoint blockade” group, showing an almost complete eradication of the tumors and the highest OS, even under resistant conditions. An analysis of tumor tissue revealed both TIGIT and TIGIT ligand expression on myeloid-derived suppressor cells (MDSCs), suggesting additional mechanisms of protumoral effects in NB. Our data show that the targeting of TIGIT and PD-L1 significantly improves the antitumor efficacy of anti-GD2 immunotherapy, with DB presenting a new effective combinatorial treatment strategy against high-risk tumors.
Oncological and Peri-Operative Outcomes of Percutaneous Cryoablation of Renal Cell Carcinoma for Patients with Hereditary RCC Diseases—An Analysis of European Multi-Centre Prospective EuRECA Registry
Authors: Osman Filzah Hanis , Chan Vinson Wai-Shun , Breen David J. , King Alexander , Nielsen Tommy Kjærgaard , Garnon Julien , Alcorn Des , Lagerveld Brunolf , Graumann Ole , Keeley Francis Xavier , Walkden Miles , de Kerviler Éric , Wah Tze Min
Published: June 2023

This study aims to evaluate the safety, efficacy, and renal function preservation of percutaneous cryoablation (PCA) for small renal masses (SRMs) in inherited RCC syndromes. Patients with inherited T1N0M0 RCCs (<7 cm) undergoing PCA from 2015 to 2021 were identified from the European Registry for Renal Cryoablation (EuRECA). The primary outcome was local recurrence-free survival (LRFS). The secondary outcomes included technical success, peri-operative outcomes, and other oncological outcomes estimated using the Kaplan–Meier method. Simple proportions, chi-squared tests, and t-tests were used to analyse the peri-operative outcomes. A total of 68 sessions of PCA were performed in 53 patients with RCC and 85 tumours were followed-up for a mean duration of 30.4 months (SD ± 22.0). The overall technical success rate was 99%. The major post-operative complication rate was 1.7%. In total, 7.4% (2/27) of patients had >25% reduction in renal function. All oncological events were observed in VHL patients. Estimated 5-year LRFS, metastasis-free survival, cancer-specific survival, and overall survival were 96.0% (95% CI 75–99%), 96.4% (95% CI 77–99%), 90.9% (95% CI 51–99%), and 90.9% (95% CI 51–99%), respectively. PCA of RCCs for patients with hereditary RCC SRMs appears to be safe, offers low complication rates, preserves renal function, and achieves good oncological outcomes.
Circulating and Tumor-Associated Neutrophils in the Era of Immune Checkpoint Inhibitors: Dynamics, Phenotypes, Metabolism, and Functions
Authors: Gibellini Lara , Borella Rebecca , Santacroce Elena , Serattini Eugenia , Boraldi Federica , Quaglino Daniela , Aramini Beatrice , De Biasi Sara , Cossarizza Andrea
Published: June 2023

Neutrophils are the most abundant myeloid cells in the blood and are a considerable immunological component of the tumor microenvironment. However, their functional importance has often been ignored, as they have always been considered a mono-dimensional population of terminally differentiated, short-living cells. During the last decade, the use of cutting-edge, single-cell technologies has revolutionized the classical view of these cells, unmasking their phenotypic and functional heterogeneity. In this review, we summarize the emerging concepts in the field of neutrophils in cancer, by reviewing the recent literature on the heterogeneity of both circulating neutrophils and tumor-associated neutrophils, as well as their possible significance in tumor prognosis and resistance to immune checkpoint inhibitors.
Anti-Tumor Efficacy of In Situ Vaccination Using Bacterial Outer Membrane Vesicles
Authors: Caproni Elena , Corbellari Riccardo , Tomasi Michele , Isaac Samine J. , Tamburini Silvia , Zanella Ilaria , Grigolato Martina , Gagliardi Assunta , Benedet Mattia , Baraldi Chiara , Croia Lorenzo , Di Lascio Gabriele , Berti Alvise , Valensin Silvia , Bellini Erika , Parri Matteo , Grandi Alberto , Grandi Guido
Published: June 2023

In situ vaccination (ISV) is a promising cancer immunotherapy strategy that consists of the intratumoral administration of immunostimulatory molecules (adjuvants). The rationale is that tumor antigens are abundant at the tumor site, and therefore, to elicit an effective anti-tumor immune response, all that is needed is an adjuvant, which can turn the immunosuppressive environment into an immunologically active one. Bacterial outer membrane vesicles (OMVs) are potent adjuvants since they contain several microbe-associated molecular patterns (MAMPs) naturally present in the outer membrane and in the periplasmic space of Gram-negative bacteria. Therefore, they appear particularly indicted for ISV. In this work, we first show that the OMVs from E. coli BL21(DE3)Δ60 strain promote a strong anti-tumor activity when intratumorally injected into the tumors of three different mouse models. Tumor inhibition correlates with a rapid infiltration of DCs and NK cells. We also show that the addition of neo-epitopes to OMVs synergizes with the vesicle adjuvanticity, as judged by a two-tumor mouse model. Overall, our data support the use of the OMVs in ISV and indicate that ISV efficacy can benefit from the addition of properly selected tumor-specific neo-antigens.
Functionally and Metabolically Divergent Melanoma-Associated Macrophages Originate from Common Bone-Marrow Precursors
Authors: Pizzurro Gabriela A. , Bridges Kate , Jiang Xiaodong , Vidyarthi Aurobind , Miller-Jensen Kathryn , Colegio Oscar R.
Published: June 2023

Tumor-associated macrophages (TAMs) can be widely heterogeneous, based on their ontogeny and function, and driven by the tissue-specific niche. TAMs are highly abundant in the melanoma tumor microenvironment (TME), usually correlating with worse prognoses. However, the understanding of their diversity may be harnessed for therapeutic purposes. Here, we used the clinically relevant YUMM1.7 model to study melanoma TAM origin and dynamics during tumor progression. In i.d. YUMM1.7 tumors, we identified distinct TAM subsets based on F4/80 expression, with the F4/80high fraction increasing over time and displaying a tissue-resident-like phenotype. While skin-resident macrophages showed mixed ontogeny, F4/80+ TAM subsets in the melanoma TME originated almost exclusively from bone-marrow precursors. A multiparametric analysis of the macrophage phenotype showed a temporal divergence of the F4/80+ TAM subpopulations, which also differed from the skin-resident subsets and their monocytic precursors. Overall, the F4/80+ TAMs displayed co-expressions of M1- and M2-like canonical markers, while RNA sequencing showed differential immunosuppressive and metabolic profiles. Gene-set enrichment analysis (GSEA) revealed F4/80high TAMs to rely on oxidative phosphorylation, with increased proliferation and protein secretion, while F4/80low cells had high pro-inflammatory and intracellular signaling pathways, with lipid and polyamine metabolism. Overall, we provide an in-depth characterization of and compelling evidence for the BM-dependency of melanoma TAMs. Interestingly, the transcriptomic analysis of these BM-derived TAMs matched macrophage subsets with mixed ontogeny, which have been observed in other tumor models. Our findings may serve as a guide for identifying potential ways of targeting specific immunosuppressive TAMs in melanoma.
Association of Myelofibrosis Phenotypes with Clinical Manifestations, Molecular Profiles, and Treatments
Authors: Chifotides Helen T. , Verstovsek Srdan , Bose Prithviraj
Published: June 2023

Myelofibrosis (MF) presents an array of clinical manifestations and molecular profiles. The two distinct phenotypes− myeloproliferative and myelodepletive or cytopenic− are situated at the two poles of the disease spectrum and are largely defined by different degrees of cytopenias, splenomegaly, and distinct molecular profiles. The myeloproliferative phenotype is characterized by normal/higher peripheral blood counts or mildly decreased hemoglobin, progressive splenomegaly, and constitutional symptoms. The myeloproliferative phenotype is typically associated with secondary MF, higher JAK2 V617F burden, fewer mutations, and superior overall survival (OS). The myelodepletive phenotype is usually associated with primary MF, ≥2 cytopenias, modest splenomegaly, lower JAK2 V617F burden, higher fibrosis, greater genomic complexity, and inferior OS. Cytopenias are associated with mutations in epigenetic regulators/splicing factors, clonal evolution, disease progression, and shorter OS. Clinical variables, in conjunction with the molecular profiles, inform integrated prognostication and disease management. Ruxolitinib/fedratinib and pacritinib/momelotinib may be more suitable to treat patients with the myeloproliferative and myelodepletive phenotypes, respectively. Appreciation of MF heterogeneity and two distinct phenotypes, the different clinical manifestations and molecular profiles associated with each phenotype alongside the growing treatment expertise, the development of non-myelosuppressive JAK inhibitors, and integrated prognostication are leading to a new era in patient management. Physicians can increasingly tailor personalized treatments that will address the unique unmet needs of MF patients, including those presenting with the myelodepletive phenotype, to elicit optimal outcomes and extended OS across the disease spectrum.
Ionizing Radiation Reduces Head and Neck Squamous Cell Carcinoma Cell Viability and Is Associated with Predictive Tumor-Specific T Cell Responses
Authors: Upadhaya Puja , Ryan Nathan , Roth Peyton , Pero Travis , Lamenza Felipe , Springer Anna , Jordanides Pete , Pracha Hasan , Mitchell Darrion , Oghumu Steve
Published: June 2023

Head and neck squamous cell carcinoma (HNSCC) is common and deadly, and there is a need for improved strategies to predict treatment responses. Ionizing radiation (IR) has been demonstrated to improve HNSCC outcomes, but its effects on immune responses are not well characterized. We determined the impact of IR on T cell immune responses ex vivo. Human and mouse HNSCC cells were exposed to IR ranging from 20 to 200 Gy to determine cell viability and the ability to stimulate T-cell-specific responses. Lymph node cells of LY2 and MOC2 tumor-bearing or non-tumor-bearing mice were re-stimulated with a tumor antigen derived from LY2 or MOC2 cells treated with 200 Gy IR, ultraviolet (UV) exposure, or freeze/thaw cycle treatments. T cell proliferation and cytokine production were compared to T cells restimulated with plate-bound CD3 and CD28 antibodies. Human and mouse HNSCC cells showed reduced viability in response to ionizing radiation in a dose-dependent manner, and induced expression of T cell chemotactic cytokines. Tumor antigens derived from IR-treated LY2 and MOC2 cells induced greater proliferation of lymph node cells from tumor-bearing mice and induced unique T cell cytokine expression profiles. Our results demonstrate that IR induces potent tumoral immune responses, and IR-generated tumor antigens can potentially serve as an indicator of antitumor immune responses to HNSCC in ex vivo T cell restimulation assays.
Pulsed Electric Fields in Oncology: A Snapshot of Current Clinical Practices and Research Directions from the 4th World Congress of Electroporation
Authors: Campana Luca G. , Daud Adil , Lancellotti Francesco , Arroyo Julio P. , Davalos Rafael V. , Di Prata Claudia , Gehl Julie
Published: June 2023

The 4th World Congress of Electroporation (Copenhagen, 9–13 October 2022) provided a unique opportunity to convene leading experts in pulsed electric fields (PEF). PEF-based therapies harness electric fields to produce therapeutically useful effects on cancers and represent a valuable option for a variety of patients. As such, irreversible electroporation (IRE), gene electrotransfer (GET), electrochemotherapy (ECT), calcium electroporation (Ca-EP), and tumour-treating fields (TTF) are on the rise. Still, their full therapeutic potential remains underappreciated, and the field faces fragmentation, as shown by parallel maturation and differences in the stages of development and regulatory approval worldwide. This narrative review provides a glimpse of PEF-based techniques, including key mechanisms, clinical indications, and advances in therapy; finally, it offers insights into current research directions. By highlighting a common ground, the authors aim to break silos, strengthen cross-functional collaboration, and pave the way to novel possibilities for intervention. Intriguingly, beyond their peculiar mechanism of action, PEF-based therapies share technical interconnections and multifaceted biological effects (e.g., vascular, immunological) worth exploiting in combinatorial strategies.
3′UTR of mRNA Encoding CPEB Protein Orb2 Plays an Essential Role in Intracellular Transport in Neurons
Authors: Kozlov Eugene N. , Deev Roman V. , Tokmatcheva Elena V. , Tvorogova Anna , Kachaev Zaur M. , Gilmutdinov Rudolf A. , Zhukova Mariya , Savvateeva-Popova Elena V. , Schedl Paul , Shidlovskii Yulii V.
Published: June 2023

Intracellular trafficking plays a critical role in the functioning of highly polarized cells, such as neurons. Transport of mRNAs, proteins, and other molecules to synaptic terminals maintains contact between neurons and ensures the transmission of nerve impulses. Cytoplasmic polyadenylation element binding (CPEB) proteins play an essential role in long-term memory (LTM) formation by regulating local translation in synapses. Here, we show that the 3′UTR of the Drosophila CPEB gene orb2 is required for targeting the orb2 mRNA and protein to synapses and that this localization is important for LTM formation. When the orb2 3′UTR is deleted, the orb2 mRNAs and proteins fail to localize in synaptic fractions, and pronounced LTM deficits arise. We found that the phenotypic effects of the orb2 3′UTR deletion were rescued by introducing the 3′UTR from the orb, another Drosophila CPEB gene. In contrast, the phenotypic effects of the 3′UTR deletion were not rescued by the 3′UTR from one of the Drosophila α-tubulin genes. Our results show that the orb2 mRNAs must be targeted to the correct locations in neurons and that proper targeting depends upon sequences in the 3′UTR.
Electrochemical Sensor for Food Monitoring Using Metal-Organic Framework Materials
Authors: Hosseinzadeh Batoul , Rodriguez-Mendez Maria Luz
Published: June 2023

Feeding the world’s increasing inhabitants requires considerable quantities of food, whose quality is essential to personal and economic health. Food quality parameters are mandatory to control throughout the fresh produce supply chain to meet consumer requests. Until now, different analytical techniques have been employed in food safety control. However, most of these are laboratory needed, expensive, and time-consuming. To address these obstacles, many researchers have concentrated on developing electrochemical sensors (ECSs) as a powerful method with great sensitivity and reliability for food evaluation. Metal-organic frameworks (MOFs) with surprisingly porous morphology provide uniform yet tunable features, a high specific surface, and established practical applications in various fields. MOF-based ECSs present novel routes for the fast and effective detection of food contaminants or nutrients. In this current review, we concentrate on the MOF-based ECSs for food evaluation by first overviewing the library of available MOF sensors from pristine to MOF-bio composites and then exploiting recent application fields, with an emphasis on how this novel material unlocks new opportunities to monitor food nutrients or hazards.
Synthesis and Spectrophotometric Studies of Heterocyclic Bay-Substituted Naphthalenediimide Colorimetric pH Indicators
Authors: Magro Filippa , Camenzuli Luke , Magri David C.
Published: June 2023

Four naphthalenediimide colorimetric pH indicators were synthesized with N,N-dimethylethyleneamine at the imide positions and with 5- to 7-membered heterocyclic rings at the bay positions, namely pyrrolidine, morpholine, piperidine and azepane. The pH indicators are constructed in a modular receptor–spacer–fluorophore–spacer–receptor format based on a photoinduced electron transfer (PET) design. The compounds were studied by UV–visible absorption and steady-state fluorescence spectroscopy in 1:1 (v/v) methanol/water. Brilliant colour changes are observed between pH 2 and 4 due to an internal charge transfer (ICT) mechanism. Fluorescence turn-on enhancements range from 10–37 fold; however, the maximum fluorescence quantum yield in the presence of acid is <0.004, which is below naked eye detection. Hence, from the viewpoint of a human observer, these chemosensors function as colorimetric YES logic gates, and fluorimetric PASS 0 logic gates.
Intra-Amniotic Inflammation or Infection: Suspected and Confirmed Diagnosis of “Triple I” at Term
Authors: Consonni Sara , Salmoiraghi Elettra , Vaglio Tessitore Isadora , Pintucci Armando , Vitale Valentina , Calzi Patrizia , Moltrasio Francesca , Locatelli Anna
Published: June 2023

Chorioamnionitis (CA) at term of pregnancy can have an infectious and/or inflammatory origin and is associated with adverse outcomes. Triple I (intrauterine inflammation, infection, or both, TI) has been proposed to reduce the overdiagnosis of infection and neonatal overtreatment. The aim of this study is to identify clinical and histological variables that could predict adverse outcomes when TI is suspected and/or confirmed. This retrospective cohort study included 404 pregnancies (gestational age ≥ 37 weeks) that were divided into 5 all-inclusive and mutually exclusive groups. TI was defined according to the NICHD definition of 2015, and it could be confirmed (TI+) or not confirmed (TI−) via histological examination. Signs of infection/inflammation that did not conform to the definition of TI were classified as “clinical suspicion” and could be supported (CS+) or not supported (CS−) by histology. Cases of histological chorioamnionitis (HCA) without clinical manifestation represented a fifth group. Whole placental involvement (WPLI) was defined as a histological inflammation involving the maternal and fetal sides. There were 113 TI+, 30 TI−, 186 CS+, 35 CS−, and 40 isolated HCA cases. WPLI was diagnosed in 133 cases (39.2%). Composite neonatal outcome (CNO) occurred in 114 cases (28.2%) while composite maternal outcome (CMO) occurred in 192 cases (47.5%). Compared with CS+, TI+ was more predictive of CNO (p = 0.001), CMO (p < 0.001), and WPLI (p = 0.005). WPLI was related both to CNO (p < 0.001) and to CMO (p = 0.046). TI+ and WPLI showed similar sensitivity but different specificity in predicting CNO. At logistic regression, CNO was independently predicted by TI+ (OR 2.21; p = 0.001) and by WPLI (OR 2.23; p = 0.001). Compared with CS, TI is a better predictor of CNO and can be useful for the identification of newborns at risk.
Temporal Variability of Particulate Matter and Black Carbon Concentrations over Greater Cairo and Its Atmospheric Drivers
Authors: Dawoud W. , El Kenawy Ahmed M. , Abdel Wahab M. M. , Oraby A. H.
Published: June 2023

This study examines the seasonal and annual variability of black carbon (BC) and particular matter (PM1, 2.5, and 10) over Greater Cairo (Egypt) from 2003 to 2020. Data on PM and BC concentrations were gathered from the European Center for Medium-Range Weather Forecasts (ECWMF) reanalysis dataset. The Observed data from Abbasiya Station were employed to verify the accuracy of the reanalysis data, and a good agreement on both seasonal and annual scales was suggested. The results demonstrate that the highest concentrations of PM and BC were generally witnessed during wintertime, while the lowest was observed in summer. Trend analysis showed that, apart from fall, a significant increase (p < 0.05) in PM levels was evident in all seasons from 2003 to 2020. Contrarily, BC concentrations exhibited a statistically significant decline from 2003 to 2020. Moreover, BC concentrations correlated negatively with PM (1, 2.5 and 10) in all seasons and annually. However, weak and statistically non-significant (p > 0.05) correlations were found between PM and BC concentrations during wintertime. Additionally, this study looked at the atmospheric configurations corresponding to the most anomalous positive and negative phases of air pollution concentrations over Greater Cairo. The results indicate that the increase in PM concentrations is related to the positive anomalies observed at 250 hPa, which suggest a prevalence of stable atmospheric conditions, particularly during winter. Overall, our findings can serve as a foundation for improved urban planning and more effective strategies to lessen the negative effects of air quality in the largest megacity in Africa and the Middle East.
The Relationship between Madden–Julian Oscillation Moist Convective Circulations and Tropical Cyclone Genesis
Authors: Haertel Patrick
Published: June 2023

The Madden–Julian Oscillation (MJO) is a planetary-scale weather system that creates a 30–60 day oscillation in zonal winds and precipitation in the tropics. Its envelope of enhanced rainfall forms over the Indian Ocean and moves slowly eastward before dissipating near the Date Line. The MJO modulates tropical cyclone (TC) genesis, intensity, and landfall in the Indian, Pacific, and Atlantic Oceans. This study examines the mechanisms by which the MJO alters TC genesis. In particular, MJO circulations are partitioned into Kelvin and Rossby waves for each of the developing, mature, and dissipating stages of the convective envelope, and locations of TC genesis are related to these circulations. Throughout the MJO’s convective life cycle, TC genesis is inhibited to the east of the convective envelope, and enhanced just west of the convective envelope. The inhibition of TC genesis to the east of the MJO is largely due to vertical motion associated with the Kelvin wave circulation, as is the enhancement of TC genesis just west of the MJO during the developing stage. During the mature and dissipating stages, the MJO’s Rossby gyres intensify, creating regions of low-level vorticity, favoring TC genesis to its west. Over the 36-year period considered here, the MJO modulation of TC genesis increases due to the intensification of the MJO’s Kelvin wave circulation.
Improvement of Human Epidermal Barrier Structure and Lipid Profile in Xerotic- and Atopic-Prone Skin via Application of a Plant-Oil and Urea Containing pH 4.5 Emulsion
Authors: Blaak Jürgen , Dähnhardt Dorothee , Bielfeldt Stephan , Theiss Christiane , Simon Isabel , Wilhelm Klaus-Peter , Dähnhardt-Pfeiffer Stephan , Staib Peter
Published: June 2023

Epidermal barrier dysfunction can lead to xerotic skin and promote skin disorders like atopic dermatitis. Atopic skin is characterized by reduced water-retaining compounds, altered lipid composition and elevated skin pH. Against this background, a study was conducted to investigate the impact of a specific skin care product on epidermal barrier function in dry and atopic-prone skin. A marketed pH 4.5 cosmetic formulation containing 10% urea and specific plant oils was evaluated on 25 subjects with dry and atopic-prone skin. Measurements of skin hydration, pH, and barrier function were performed before and after 3 weeks of product usage. Additionally, visual scoring and stratum corneum lipid analysis using electron microscopy were conducted to investigate lipid composition. An improved skin hydration compared to the untreated area and a tendency to decrease the baseline elevated skin surface pH were observed. The visual scoring showed reduced dryness, roughness, and tension through the application. Furthermore, the stratum corneum lipid matrix was improved in terms of lipid content and organization. The combination of an acidic product’s pH, a relevant urea content and effective plant oils is shown to be beneficial in terms of improving the skin barrier function, structure and appearance and is recommended for dry and atopic-prone skin.
Management of Very Early Small Cell Lung Cancer: A Canadian Survey Study
Authors: Malakouti-Nejad Bayan , Moore Sara , Wheatley-Price Paul , Tiberi David
Published: June 2023

Concurrent chemoradiotherapy (CRT) is the standard of care for limited-stage small cell lung cancer (LS-SCLC). Local therapy—surgery or stereotactic body radiotherapy (SBRT)—with adjuvant chemotherapy may be appropriate for very early (T1-T2, N0) disease. There is variability in the management of these cases, which may lead to variability in patient outcomes. This study aimed to determine practice patterns for the management of very early LS-SCLC in Canada. A survey was developed and distributed to Canadian medical and radiation oncologists specialising in lung cancer. The survey consisted of three sections: (1) physician demographics, (2) general practice approach, and (3) preferred approach for three clinical scenarios (1: peripheral T1 lesion; 2: central T1 lesion; 3: peripheral T2 lesion). Responses were analysed to detect differences across cases and among physician groups. There were 77 respondents. In case 1, assuming medical operability, most respondents (73%) chose surgery and adjuvant chemotherapy, with 19% choosing CRT. CRT was selected by a higher proportion in case 2 (48%) and case 3 (61%) (p < 0.05). If medically inoperable, most chose CRT over local therapy in all cases, with more choosing CRT in case 2 (84%) and case 3 (86%) than in case 1 (55%) (p < 0.05). Subgroup analysis showed a predilection towards CRT in Western Canada and among more experienced physicians, and towards SBRT in Ontario. There is variability in the management of very early LS-SCLC in Canada. CRT remains the most popular strategy in most cases, with surgery preferred for small peripheral lesions. Larger and more central tumours are more likely to be managed with CRT. Variation in practice is correlated with region and physician experience. Our study illustrates the variability in the management of very early LS-SCLC in Canada and highlights the need for more robust investigations into the ideal approach for these patients.
Skin Cancer Prevention across the G7, Australia and New Zealand: A Review of Legislation and Guidelines
Authors: Conte Santina , Aldien Ammar Saed , Jetté Sébastien , LeBeau Jonathan , Alli Sauliha , Netchiporouk Elena , Lagacé François , Lefrançois Philippe , Iannattone Lisa , Litvinov Ivan V.
Published: June 2023

Incidence rates of melanoma and keratinocyte skin cancers have been on the rise globally in recent decades. While there has been a select focus on personal sun protection awareness, to our knowledge, there is a paucity of legislation in place to help support citizens’ efforts to protect themselves from the harmful effects of ultraviolet radiation (UVR). Given this, we conducted a comprehensive review of legislation and guidelines pertaining to a variety of sun protection-related topics in countries of the Group of Seven (G7), Australia and New Zealand. Australia was the only country to have banned tanning beds for individuals of all ages, while other select countries have instituted bans for minors. In workplace policy, there is very little recognition of the danger of occupational UVR exposure in outdoor workers, and thus very few protective measures are in place. With regard to sports and recreation, certain dermatological/professional associations have put forward recommendations, but no legislation was brought forward by government bodies outside of Australia and New Zealand. With regard to youth, while there are various guidelines and frameworks in place across several countries, adherence remains difficult in the absence of concrete legislation and standardization of procedures. Finally, only Australia and a few select jurisdictions in the United States have implemented sales tax exemptions for sunscreen products. In light of our findings, we have made several recommendations, which we anticipate will help reduce the rates of melanoma and keratinocyte cancers in years to come. However, minimizing UVR exposure is not without risk, and we, therefore, suggest the promotion of vitamin D supplementation in conjunction with sun protective practices to limit potential harm.
Capecitabine Plus Aromatase Inhibitor as First Line Therapy for Hormone Receptor Positive, HER2 Negative Metastatic Breast Cancer
Authors: Alvarado-Miranda Alberto , Lara-Medina Fernando Ulises , Muñoz-Montaño Wendy R. , Zinser-Sierra Juan W. , Galeana Paula Anel Cabrera , Garza Cynthia Villarreal , Sanchez Benitez Daniel , Limón Rodríguez Jesús Alberto , Arce Salinas Claudia Haydee , Guijosa Alberto , Arrieta Oscar
Published: June 2023

(1) Background: recent evidence suggests that long low-dose capecitabine regimens have a synergistic effect with endocrine therapy as aromatase inhibitors (AIs), and might increase overall survival for hormone-receptor-positive, HER2-negative, metastatic breast cancer compared to both treatments. We performed a retrospective study to confirm the efficacy and expand the safety data for capecitabine plus AI (a combination henceforth named XELIA) for this indication. (2) We conducted a single-center retrospective cohort study of 163 hormone receptor-positive metastatic breast cancer patients who received either the XELIA regimen, capecitabine, or an aromatase inhibitor (AI) as single agents in first-line treatment. The primary endpoint was progression-free survival, and the secondary endpoints were overall survival, best objective response, and toxicity incidence. (3) Results: the median progression-free survival for patients receiving XELIA, AI, and capecitabine was 29.37 months (20.91 to 37.84; 95% CI), 20.04 months (7.29 to 32.80; 95% CI) and 10.48 (8.69 to 12.28; 95% CI), respectively. The overall response rate was higher in the XELIA group (29.5%) than in the AI (14.3%) and capecitabine (9.1%) groups. However, the differences in overall survival were not statistically significant. Apart from hand–foot syndrome, there were no statistically significant differences in adverse events between the groups. (4) Conclusions: this retrospective study suggests that progression-free survival and overall response rates improved with the XELIA regimen compared to use of aromatase inhibitors and capecitabine alone. Combined use demonstrated an adequate safety profile and might represent an advantageous treatment in places where CDK 4/6 is not available. Larger studies and randomized clinical trials are required to confirm the effects shown in our study.