bluuebunny/crossref_metadata_2025 huggingface dataset:
Super Typhoon Saola (2023) over the Northern Part of the South China Sea—Aircraft Data Analysis
Authors: He Junyi , Chan Pak Wai , Chan Ying Wa , Cheung Ping
Published: October 2023

In situ aircraft observations in typhoons have been scarce. This paper documents and analyses the aircraft and dropsonde data collected in Super Typhoon Saola (2023) over the northern part of the South China Sea. The wind and turbulence structures of the typhoon are investigated. The turbulence intensities are quantified in terms of turbulent kinetic energy (TKE) and eddy dissipate rate (EDR), and these data are compared with other available estimates of turbulence intensities, such as those based on weather radars, meteorological satellites, and numerical weather prediction (NWP) models. It is found that the TKE and EDR are closely correlated, and they are consistent with the weather radar/satellite observations as well as NWP-based outputs. Furthermore, the boundary layer inflow, vertical wind profiles, and atmospheric stability are analysed based on the dropsonde observations. The analysed results would advance the understanding of typhoon structures and offer references for the validation of remote-sensing observations and NWP models.
Meteorological and Hydrological Drought Risks under Future Climate and Land-Use-Change Scenarios in the Yellow River Basin
Authors: Li Yunyun , Huang Yi , Fan Jingjing , Zhang Hongxue , Li Yanchun , Wang Xuemei , Deng Qian
Published: October 2023

The primary innovation of this study lies in the development of an integrated modeling framework that combines downscaled climate projections, land-use-change simulations, and copula-based risk analysis. This framework allows for the assessment of localized sub-seasonal and seasonal drought hazards under future scenarios. The BCC-CSM1-1 climate model projections from the NASA Earth Exchange Global Daily Downscaled Projections (NEX-GDDP) dataset are utilized to represent the future climate for 2025–2060 under RCP 4.5 and 8.5 scenarios. The CA-Markov model is employed to predict future land-use-change distributions. The climate–land use–drought modeling nexus enables the generation of refined spatio-temporal projections of meteorological and hydrological drought risks in the Yellow River Basin (YRB) in the future period of 2025–2060. The results highlight the increased vulnerability of the upper YRB to sub-seasonal meteorological droughts, as well as the heightened sub-seasonal hydrological drought risks in the Loess Plateau. Furthermore, downstream areas experience escalated seasonal hydrological drought exposure due to urbanization. By providing actionable insights into localized future drought patterns, this integrated assessment approach advances preparedness and climate adaptation strategies. The findings of the study enhance our understanding of potential changes in this integral system under the combined pressures of global climate change and land use shifts.
Overlapping Stent Treatment for Ruptured Dissecting Aneurysms in Posterior Circulation
Authors: Zhou Minghui , Wu Zengbao , Maalim Ali Abdi , Zeng Ying , Guo Xiao , Zhang Zhenhua , Yuan Xiaohong , Enos Zacharia Majaliwa , Shu Kai , Lei Ting , Zhu Mingxin
Published: October 2023

Ruptured dissecting aneurysms in posterior intracranial circulation present significant clinical challenges and often cause poor prognoses. Our cohort used overlapping stents as the primary treatment. We analyzed the medical records of 27 patients (18 men/nine women) with ruptured posterior circulation dissecting aneurysms (PCDAs). Their average age was 52 years. We selected 11 patients who used Enterprise (EP) and LVIS stents overlappingly and matched them 1:1 with counterparts who received either EP or LVIS stents individually. Overlapping stents was a feasible treatment in all 27 cases. We successfully followed up 26 patients for ≥6 months. Regrettably, one patient died from intracranial hypertension on Day 7 post-procedure. Immediate post-procedure angiographies indicated Raymond grade I, II, and III occlusions of PCDAs in 16 (59.3%), 7 (25.9%), and 4 (14.8%) cases, respectively. At an average follow-up duration of 16.2 months, 25 patients (96.2%) had modified Rankin Scale scores of 0–2, signifying positive outcomes. One patient (3.8%) had a score of 3–4. Recurrence rates for the EP and LVIS stent groups were higher than those of the overlapping stent group (45.45% vs. 9.09%, p = 0.15 and 27.27% vs. 9.09%, p = 0.59, respectively). No significant difference in recurrence rates existed between the overlapping and single-stent groups. Similarly, follow-up outcomes were consistent between the two groups. Overlapping stents could be an efficient method for treating ruptured PCDAs.
Neoadjuvant Chemotherapy with Laser Interstitial Thermal Therapy in Central Nervous System Neuroblastoma: Illustrative Case and Literature Review
Authors: Chung Jason E. , Iqbal Omar , Krishnan Chandra , Harrod Virginia , Tyler-Kabara Elizabeth , Lu Rongze O. , Ho Winson S.
Published: October 2023

Primitive neuroectodermal tumors of the central nervous system, or CNS neuroblastoma, are rare neoplasms in children. Recently, methylation profiling enabled the discovery of four distinct entities of these tumors. The current treatment paradigm involves surgical resection followed by chemotherapy and radiation. However, upfront surgical resection carries high surgical morbidity in this patient population due to their young age, tumor vascularity, and often deep location in the brain. We report a case of CNS neuroblastoma that can be successfully treated with neoadjuvant chemotherapy followed by minimally invasive laser interstitial thermal therapy and radiation. The patient has complete treatment with no evidence of recurrence at one year follow-up. This case illustrates a potential paradigm shift in the treatment of these rare tumors can be treated using minimally invasive surgical approach to achieve a favorable outcome.
Impact of Waiting Response Evaluation to First-Line Systemic Therapy before Considering Local Ablative Therapy in Metastatic Non-Small-Cell Lung Cancer
Authors: Belaidi Lahcene , Wang Pascal , Quintin Kevin , Durdux Catherine , Giroux-Leprieur Etienne , Giraud Philippe
Published: October 2023

Stereotactic radiotherapy (SRT) is gaining increasing importance in metastatic non-small-cell lung cancer (mNSCLC) management. The optimal sequence of tumor irradiation relative to systemic treatment remains unclear. If waiting response evaluation to first-line systemic therapy (FLST) before considering local treatment may allow for the exclusion of poorer prognosis progressive tumors that may not benefit from SRT, performing irradiation near immune check point inhibitor (ICI) first administration seems to improve their synergic effect. Herein, we aimed to determine whether delaying SRT after response evaluation to FLST would result in better prognosis. We compared overall survival (OS), progression-free survival (PFS), and time to first subsequent therapy (TFST) for 50 patients locally treated before or within 90 days of initiating FLST (early SRT), with 49 patients treated at least 90 days after initiating FLST (late SRT). Patients treated with conventional chemotherapy alone exhibited significantly poorer median OS, PFS, and TFST in the early SRT arm: (in months) 16.5 [8.33-NR] vs. 58.3 [35.05-NR] (p = 0.0015); 4.69 [3.57–8.98] vs. 8.20 [6.66–12.00] (p = 0.017); and 6.26 [4.82–11.8] vs. 10.0 [7.44–21.8] (p = 0.0074), respectively. Patient receiving ICI showed no difference in OS (NR [25.2-NR] vs. 36.6 [35.1-NR], p = 0.79), PFS (7.54 [6.23-NR] vs. 4.07 [2.52-NR], p = 0.19), and TFST (13.7 [9.48-NR] vs. 10.3 [3.54-NR], p = 0.49). These results suggest that delaying SRT treatment in order to filter a rapidly growing tumor may be less necessary when ICI is administered in mNSCLC.
Diagnostic Workup, Treatment Patterns, and Clinical Outcomes in Early-Stage IB–IIIA Non-Small-Cell Lung Cancer Patients in Denmark
Authors: Uldbjerg Ebbe Meldgaard , Ringgaard Lars , Andersen Klaus Kaae , Frederiksen Line Elmerdahl , Jovanovic Aleksandar , Meldgaard Peter
Published: October 2023

Despite recent improvements in early-stage non-small-cell lung cancer (NSCLC), disease relapse remains challenging. Moreover, real-world evidence on long-term follow-up of disease-free survival (DFS) and recurrence patterns in a large, unselected cohort of early-stage NSCLC patients is lacking. This cohort study aimed to assess clinical characteristics, diagnostic workup, treatment, survival, and risk of disease relapse among early-stage NSCLC patients. Adult patients with stage IB, II, or IIIA NSCLC diagnosed and/or treated at Aarhus University Hospital in Denmark from January 2010 to December 2020 were included and followed-up until May 2021. Comprehensive clinical data were collected from electronic medical records of eligible patients and linked to Danish register data. The study population comprised 1341 early-stage NSCLC patients: 22%, 40%, and 38% were diagnosed with stage IB, II, and IIIA disease, respectively. In total, 42% of patients were tested for epidermal growth factor receptor (EGFR), of whom 10% were EGFR-mutation-positive (EGFRm+). Half of all patients received surgery, and nine percent of patients received stereotactic body radiation therapy (SBRT). Disease-free survival 5 years post-diagnosis was 49%, 42%, and 22% for stage IB, II, and stage IIIA patients, respectively. DFS improved over time both for patients treated with surgery and SBRT. However, disease relapse remained a challenge, with approximately 40% of stage IIIA having relapsed 3 years post-diagnosis. This study contributes important knowledge that puts clinical trials on new perioperative treatment modalities for early-stage NSCLC patients into perspective. Our findings cover an essential evidence gap on real-world DFS and recurrence dynamics, confirming that despite an improvement in DFS over time and across different treatment modalities, disease relapse remains a monumental challenge. Therefore, better treatment strategies are needed.
Development and Assessment of Nomogram Based on AFP Response for Patients with Unresectable Hepatocellular Carcinoma Treated with Immune Checkpoint Inhibitors
Authors: Zhang Yi , Shen Hui , Zheng Ruiying , Sun Yueting , Xie Xiaoyan , Lu Ming-De , Liu Baoxian , Huang Guangliang
Published: October 2023

Background: Immune checkpoint inhibitors (ICIs) have been increasingly used to treat hepatocellular carcinoma (HCC). Prognostic biomarkers are an unmet need. We aimed to develop a prognostic nomogram for patients with unresectable HCC receiving ICIs therapy. Methods: A total of 120 patients with unresectable HCC receiving ICIs treatment were enrolled in this study. Patients were randomly divided into a training set (n = 84) and a validation set (n = 36) in a 7:3 ratio. Clinical characteristics were retrospectively analyzed. Serum α-fetoprotein protein (AFP) response was defined as a decline of ≥20% in AFP levels within the initial eight weeks of treatment. Univariable and multivariable Cox analyses were used to select relevant variables and construct the nomogram. The areas under the receiver operating characteristic curves (AUCs) were used to determine the performance of the model. Kaplan–Meier analysis with the log-rank test was used to compare different risk groups. Results: The median progression-free survival (PFS) was 7.7 months. In the multivariate Cox analysis, the presence of extrahepatic metastasis (hazard ratio [HR] = 2.08, 95% confidence interval [CI]: 1.02–4.27, p < 0.05), white blood cell count (HR = 3.48, 95% CI: 1.02–11.88, p < 0.05) and AFP response (HR = 0.41, 95% CI: 0.18–0.95, p < 0.05) independently predicted PFS. A nomogram for PFS was established with AUCs of 0.79 and 0.70 in the training and validation sets, respectively. The median PFS of the high- and low-risk subgroups was 3.5 and 11.7 months, respectively (p < 0.05). Conclusion: The nomogram could predict PFS in patients with unresectable HCC receiving ICIs treatment and further help decision making in daily clinical practice.
Modeling Myxofibrosarcoma: Where Do We Stand and What Is Missing?
Authors: Lucarelli Enrico , De Vita Alessandro , Bellotti Chiara , Frisoni Tommaso , Vanni Silvia , Guerrieri Ania Naila , Pannella Micaela , Mercatali Laura , Gambarotti Marco , Duchi Serena , Miserocchi Giacomo , Maioli Margherita , Liverani Chiara , Ibrahim Toni
Published: October 2023

Myxofibrosarcoma (MFS) is a malignant soft tissue sarcoma (STS) that originates in the body’s connective tissues. It is characterized by the presence of myxoid (gel-like) and fibrous components and typically affects patients after the fifth decade of life. Considering the ongoing trend of increasing lifespans across many nations, MFS is likely to become the most common musculoskeletal sarcoma in the future. Although MFS patients have a lower risk of developing distant metastases compared with other STS cases, MFS is characterized by a high frequency of local recurrence. Notably, in 40–60% of the patients where the tumor recurs, it does so multiple times. Consequently, patients may undergo multiple local surgeries, removing the risk of potential amputation. Furthermore, because the tumor relapses generally have a higher grade, they exhibit a decreased response to radio and chemotherapy and an increased tendency to form metastases. Thus, a better understanding of MFS is required, and improved therapeutic options must be developed. Historically, preclinical models for other types of tumors have been instrumental in obtaining a better understanding of tumor development and in testing new therapeutic approaches. However, few MFS models are currently available. In this review, we will describe the MFS models available and will provide insights into the advantages and constraints of each model.
The Association between Proton Pump Inhibitors and the Effectiveness of CDK Inhibitors in HR+/HER- Advanced Breast Cancer Patients: A Systematic Review and Meta-Analysis
Authors: Chang Yu-Cheng , Song Junmin , Chang Yu , Huang Chin-Hsuan , Sudan Aarushi , Chen Pei-Chin , Chi Kuan-Yu
Published: October 2023

There have been many clinical questions regarding whether the use of proton pump inhibitors (PPIs) could deteriorate the effects of cyclin-dependent kinase inhibitors (CDKIs) in HR+/HER2- advanced breast cancer patients. We performed a systematic review and meta-analysis of this clinical question, including studies enrolling HR+/HER2- metastatic breast cancer patients treated with CDKIs (Palbociclib or Ribociclib) and reporting at least one comparative survival outcome, either overall survival (OS) or progression-free survival (PFS), between concomitant PPI users and non-users. Eight studies met the eligibility criteria, with a total of 2584 patients included (PPI users: 830, PPI non-users: 1754), demonstrating that concomitant PPI use was associated with significantly higher risks of all-cause mortality (HR = 2.03; 95% CI, 1.49 to 2.77; I2 = 0%) and disease progression (HR = 1.75; 95% CI, 1.26 to 2.43; I2 = 59%) in breast cancer patients taking Palbociclib. In contrast, there were no significant survival impacts of PPIs on Ribociclib (HR = 1.46; 95% CI, 0.91 to 2.34; I2 = 36%). Additionally, there was no significant difference in the risk associated with CDKI dose reduction due to drug toxicity (RR = 1.12; 95% CI, 0.97 to 1.29). Therefore, when HR+/HER2- advanced breast cancer patients require the use of PPIs, it may be reasonable to consider using Ribociclib.
Auranofin Induces Lethality Driven by Reactive Oxygen Species in High-Grade Serous Ovarian Cancer Cells
Authors: Abdalbari Farah H. , Martinez-Jaramillo Elvis , Forgie Benjamin N. , Tran Estelle , Zorychta Edith , Goyeneche Alicia A. , Sabri Siham , Telleria Carlos M.
Published: October 2023

High-grade serous ovarian cancer (HGSOC) accounts for 70% of ovarian cancer cases, and the survival rate remains remarkably low due to the lack of effective long-term consolidation therapies. Clinical remission can be temporarily induced by platinum-based chemotherapy, but death subsequently results from the extensive growth of a platinum-resistant component of the tumor. This work explores a novel treatment against HGSOC using the gold complex auranofin (AF). AF primarily functions as a pro-oxidant by inhibiting thioredoxin reductase (TrxR), an antioxidant enzyme overexpressed in ovarian cancer. We investigated the effect of AF on TrxR activity and the various mechanisms of cytotoxicity using HGSOC cells that are clinically sensitive or resistant to platinum. In addition, we studied the interaction between AF and another pro-oxidant, L-buthionine sulfoximine (L-BSO), an anti-glutathione (GSH) compound. We demonstrated that AF potently inhibited TrxR activity and reduced the vitality and viability of HGSOC cells regardless of their sensitivities to platinum. We showed that AF induces the accumulation of reactive oxygen species (ROS), triggers the depolarization of the mitochondrial membrane, and kills HGSOC cells by inducing apoptosis. Notably, AF-induced cell death was abrogated by the ROS-scavenger N-acetyl cysteine (NAC). In addition, the lethality of AF was associated with the activation of caspases-3/7 and the generation of DNA damage, effects that were also prevented by the presence of NAC. Finally, when AF and L-BSO were combined, we observed synergistic lethality against HGSOC cells, which was mediated by a further increase in ROS and a decrease in the levels of the antioxidant GSH. In summary, our results support the concept that AF can be used alone or in combination with L-BSO to kill HGSOC cells regardless of their sensitivity to platinum, suggesting that the depletion of antioxidants is an efficient strategy to mitigate the course of this disease.
Correction: Brosch et al. Glucose and Inositol Transporters, SLC5A1 and SLC5A3, in Glioblastoma Cell Migration. Cancers 2022, 14, 5794
Authors: Brosch Philippa K. , Korsa Tessa , Taban Danush , Eiring Patrick , Kreisz Philipp , Hildebrand Sascha , Neubauer Julia , Zimmermann Heiko , Sauer Markus , Shirakashi Ryo , Djuzenova Cholpon S. , Sisario Dmitri , Sukhorukov Vladimir L.
Published: October 2023

Philipp Kreisz was not included as an author in the original publication [...]
Inflammatory Bone Marrow Mesenchymal Stem Cells in Multiple Myeloma: Transcriptional Signature and In Vitro Modeling
Authors: Wang Lei , Yi Weijun , Ma Li , Lecea Emily , Hazlehurst Lori A. , Adjeroh Donald A. , Hu Gangqing
Published: October 2023

Bone marrow mesenchymal stem cells (BM MSCs) play a tumor-supportive role in promoting drug resistance and disease relapse in multiple myeloma (MM). Recent studies have discovered a sub-population of MSCs, known as inflammatory MSCs (iMSCs), exclusive to the MM BM microenvironment and implicated in drug resistance. Through a sophisticated analysis of public expression data from unexpanded BM MSCs, we uncovered a positive association between iMSC signature expression and minimal residual disease. While in vitro expansion generally results in the loss of the iMSC signature, our meta-analysis of additional public expression data demonstrated that cytokine stimulation, including IL1-β and TNF-α, as well as immune cells such as neutrophils, macrophages, and MM cells, can reactivate the signature expression of iMSCs to varying extents. These findings underscore the importance and potential utility of cytokine stimulation in mimicking the gene expression signature of early passage of iMSCs for functional characterizations of their tumor-supportive roles in MM.
Immune Effector Cell-Associated HLH-like Syndrome: A Review of the Literature of an Increasingly Recognized Entity
Authors: Fugere Tyler , Baltz Alan , Mukherjee Akash , Gaddam Mamatha , Varma Ankur , Veeraputhiran Muthu , Gentille Sanchez Cesar Giancarlo
Published: October 2023

Since CAR-T cell therapy was initially approved in 2017, its use has become more prevalent and so have its side effects. CAR-T-related HLH, also named immune effector cell-associated HLH-like syndrome (IEC-HS), is a rare but fatal toxicity if not recognized promptly. We conducted a review of the literature in order to understand the prevalence of IEC-HS as well as clarify the evolution of the diagnostic criteria and treatment recommendations. IEC-HS occurrence varies between CAR-T cell products and the type of malignancy treated. Diagnosis can be challenging as there are no standardized diagnostic criteria, and its clinical features can overlap with cytokine release syndrome and active hematological disease. Suggested treatment strategies have been extrapolated from prior experience in HLH and include anakinra, corticosteroids and ruxolitinib. IEC-HS is a potentially fatal toxicity associated with CAR-T cell therapy. Early recognition with reliable diagnostic criteria and prompt implementation of treatment specific to IEC-HS is imperative for improving patient outcomes.
The Heterogeneous Impact of Prediagnostic Folate Intake for Fluorouracil-Containing Induction Chemotherapy for Head and Neck Cancer
Authors: Sawabe Michi , Kawakita Daisuke , Oze Isao , Iwasaki Shinichi , Hasegawa Yasuhisa , Murakami Shingo , Ito Hidemi , Hanai Nobuhiro , Matsuo Keitaro
Published: October 2023

Fluorouracil (FU) exerts its antitumor activity by inhibiting folate-mediated one-carbon metabolism. Evidence that folate may play a role in the carcinogenic process via folate-mediated one-carbon metabolism has given rise to the hypothesis that pre-diagnostic folate intake may induce heterogeneous chemosensitivity to FU-containing induction chemotherapy (IC) in head and neck cancer. To assess this hypothesis, we conducted a cohort study to investigate whether the association between prediagnostic dietary folate intake and cancer survival differed between treatment regimens with and without FU-containing IC in 504 cases of locally advanced (stage III/IV) HNSCC, using an epidemiologic database combined with clinical data. In total, 240 patients were treated with FU-containing IC followed by definitive treatment, and 264 patients were treated with definitive treatment alone. Definitive treatment is defined as (1) the surgical excision of a tumor with clear margins, with or without neck lymph node dissection; or (2) radiotherapy with or without chemotherapy. In the overall cohort of the FU-containing IC group, a higher folate intake was significantly associated with better overall survival (adjusted hazard ratios (HRs) for the highest compared to the lowest folate tertiles (HRT3-T1) = 0.42, 95%CI, 0.25–0.76, Ptrend = 0.003). Conversely, no apparent association between prediagnostic folate intake and survival was observed with definitive treatment alone (HRT3-T1: 0.83, 95%CI, 0.49–1.42, Ptrend = 0.491)). A consideration of the cumulative dose of FU-containing IC showed that the survival impact of prediagnostic folate intake differed statistically significantly by treatment regimen (Pinteraction = 0.012). In conclusion, an association between prediagnostic folate intake and HNSCC survival significantly differed by FU-containing IC. This finding indicates that in the carcinogenic process, folate status causes HNSCC to be heterogenous in terms of one-carbon metabolism.
Peak Risk of Recurrence Occurs during the First Two Years after a Pancreatectomy in Patients Receiving Neoadjuvant FOLFIRINOX
Authors: Alfano Marie-Sophie , Garnier Jonathan , Palen Anaïs , Ewald Jacques , Piana Gilles , Poizat Flora , Mitry Emmanuel , Delpero Jean-Robert , Turrini Olivier
Published: October 2023

No codified/systematic surveillance program exists for borderline/locally advanced pancreatic ductal carcinoma treated with neoadjuvant FOLFIRINOX and a secondary resection. This study aimed to determine the trend of recurrence in patients who were managed using such a treatment strategy. From 2010, 101 patients received FOLFIRINOX and underwent a pancreatectomy, in a minimum follow-up of 5 years. Seventy-one patients (70%, R group) were diagnosed with recurrence after a median follow-up of 11 months postsurgery. In the multivariable analysis, patients in the R-group had a higher rate of weight loss (p = 0.018), higher carbohydrate antigen (CA 19-9) serum levels at diagnosis (p = 0.012), T3/T4 stage (p = 0.017), and positive lymph nodes (p < 0.01) compared to patients who did not experience recurrence. The risk of recurrence in patients with T1/T2 N0 R0 was the lowest (19%), and all recurrences occurred during the first two postoperative years. The peak risk of recurrence for the entire population was observed during the first two postoperative years. The probability of survival decreased until the second year and rebounded to 100% permanently, after the ninth postoperative year. Close monitoring is needed at reduced intervals during the first 2 years following a pancreatectomy and should be extended to later than 5 years for those with unfavorable pathological results.
Preventing Cardiotoxicity in Personalized Breast Irradiation
Authors: Ippolito Edy , Greco Carlo , Marrocco Maristella , Rinaldi Carla Germana , Fiore Michele , Trodella Luca Eolo , D’Angelillo Rolando Maria , Ramella Sara
Published: October 2023

Background: This study aims to assess the benefit of a deep inspiration breath hold (DIBH) over the standard irradiation technique, and eventually to identify anatomical and/or treatment preplanning characteristics correlated with the LAD dose. Methods: Patients with left-sided breast cancer undergoing whole breast radiotherapy with DIBH were analyzed. All patients included in the analysis had plans in DIBH and free-breathing (FB). Receiving operating characteristics (ROC analysis) were used to identify the cut-off point of parameters to predict the LAD maximum dose > 10 Gy and LAD mean dose > 4 Gy, and the areas under the curve (AUCs) were computed. Post-test probability has been performed to evaluate the effect of parameters’ combination. Results: One hundred ninety-seven patients were analyzed. The LAD dose was significantly reduced in DIBH plans with the maximum and mean dose reduced by 31.7% (mean value 3.5 Gy vs. 4.8 Gy, p ≤ 0.001) and 28.1% (mean value 8.2 Gy vs. 12.8 Gy, p ≤ 0.001) in DIBH plans compared to FB plans. The strongest predictor of the LAD dose (maximum > 10 Gy and mean > 4 Gy) was the minimum distance of LAD from tangent open fields. Other parameters were lung volume and heart volume (LAD Dmax > 10 Gy) and lung volume, heart volume, and breast separation (LAD Dmean > 4 Gy). Conclusion: The dosimetric advantage of DIBH is clear in all patients and DIBH should always be preferred.
Dedifferentiated Endometrial Carcinoma: A Rare Aggressive Neoplasm-Clinical, Morphological and Immunohistochemical Features
Authors: Giordano Giovanna , Ferioli Elena , Guareschi Debora , Tafuni Alessandro
Published: October 2023

Dedifferentiated endometrioid adenocarcinoma is characterised by the coexistence of an undifferentiated carcinoma and a low-grade endometrioid adenocarcinoma. The low-grade component in this subtype of endometrial carcinoma is Grade 1 or 2 according to the Federation of Gynaecology and Obstetrics (FIGO) grading system. The coexistence of low-grade endometrial carcinoma and solid undifferentiated carcinoma can cause diagnostic problems on histological examination. In fact, this combination can often be mistaken for a more common Grade 2 or Grade 3 endometrial carcinoma. Therefore, this subtype of uterine carcinoma can often go under-recognised. An accurate diagnosis of dedifferentiated endometrial carcinoma is mandatory because of its poorer prognosis compared to Grade 3 endometrial carcinoma, with a solid undifferentiated component that can amount to as much as 20% of the entire tumour. The aim of this review is to provide clinical, immunohistochemical, and molecular data to aid with making an accurate histological diagnosis and to establish whether there are any findings which could have an impact on the prognosis or therapeutic implications of this rare and aggressive uterine neoplasm.
Plasma-Derived Exosome Proteins as Novel Diagnostic and Prognostic Biomarkers in Neuroblastoma Patients
Authors: Morini Martina , Raggi Federica , Bartolucci Martina , Petretto Andrea , Ardito Martina , Rossi Chiara , Segalerba Daniela , Garaventa Alberto , Eva Alessandra , Cangelosi Davide , Bosco Maria Carla
Published: October 2023

Neuroblastoma (NB) is the most common extracranial solid tumor during infancy, causing up to 10% of mortality in children; thus, identifying novel early and accurate diagnostic and prognostic biomarkers is mandatory. NB-derived exosomes carry proteins (Exo-prots) reflecting the status of the tumor cell of origin. The purpose of this study was to characterize, for the first time, the Exo-prots specifically expressed in NB patients associated with tumor phenotype and disease stage. We isolated exosomes from plasma specimens of 24 HR-NB patients and 24 low-risk (LR-NB) patients at diagnosis and of 24 age-matched healthy controls (CTRL). Exo-prot expression was measured by liquid chromatography–mass spectrometry. The data are available via ProteomeXchange (PXD042422). The NB patients had a different Exo-prot expression profile compared to the CTRL. The deregulated Exo-prots in the NB specimens acted mainly in the tumor-associated pathways. The HR-NB patients showed a different Exo-prot expression profile compared to the LR-NB patients, with the modulation of proteins involved in cell migration, proliferation and metastasis. NCAM, NCL, LUM and VASP demonstrated a diagnostic value in discriminating the NB patients from the CTRL; meanwhile, MYH9, FN1, CALR, AKAP12 and LTBP1 were able to differentiate between the HR-NB and LR-NB patients with high accuracy. Therefore, Exo-prots contribute to NB tumor development and to the aggressive metastatic NB phenotype.
Exhaled Nitric Oxide as Biomarker of Type 2 Diseases
Authors: Maniscalco Mauro , Fuschillo Salvatore , Mormile Ilaria , Detoraki Aikaterini , Sarnelli Giovanni , Paulis Amato de , Spadaro Giuseppe , Cantone Elena
Published: October 2023

Nitric oxide (NO) is a short-lived gas molecule which has been studied for its role as a signaling molecule in the vasculature and later, in a broader view, as a cellular messenger in many other biological processes such as immunity and inflammation, cell survival, apoptosis, and aging. Fractional exhaled nitric oxide (FeNO) is a convenient, easy-to-obtain, and non-invasive method for assessing active, mainly Th2-driven, airway inflammation, which is sensitive to treatment with standard anti-inflammatory therapy. Consequently, FeNO serves as a valued tool to aid the diagnosis and monitoring of several asthma phenotypes. More recently, FeNO has been evaluated in several other respiratory and/or immunological conditions, including allergic rhinitis, chronic rhinosinusitis with/without nasal polyps, atopic dermatitis, eosinophilic esophagitis, and food allergy. In this review, we aim to provide an extensive overview of the current state of knowledge about FeNO as a biomarker in type 2 inflammation, outlining past and recent data on the application of its measurement in patients affected by a broad variety of atopic/allergic disorders.
Single-Cell Analysis with Silver-Coated Pipette by Combined SERS and SICM
Authors: Dubkov Sergey , Overchenko Aleksei , Novikov Denis , Kolmogorov Vasilii , Volkova Lidiya , Gorelkin Petr , Erofeev Alexander , Parkhomenko Yuri
Published: October 2023

The study of individual cell processes that occur both on their surface and inside is highly interesting for the development of new medical drugs, cytology and cell technologies. This work presents an original technique for fabricating the silver-coated pipette and its use for the cell analysis by combination with surface-enhanced Raman spectroscopy (SERS) and scanning ion-conducting microscopy (SICM). Unlike the majority of other designs, the pipette opening in our case remains uncovered, which is important for SICM. SERS-active Ag nanoparticles on the pipette surface are formed by vacuum–thermal evaporation followed by annealing. An array of nanoparticles had a diameter on the order of 36 nm and spacing of 12 nm. A two-particle model based on Laplace equations is used to calculate a theoretical enhancement factor (EF). The surface morphology of the samples is investigated by scanning electron microscopy while SICM is used to reveal the surface topography, to evaluate Young’s modulus of living cells and to control an injection of the SERS-active pipettes into them. A Raman microscope–spectrometer was used to collect characteristic SERS spectra of cells and cell components. Local Raman spectra were obtained from the cytoplasm and nucleus of the same HEK-293 cancer cell. The EF of the SERS-active pipette was 7 × 105. As a result, we demonstrate utilizing the silver-coated pipette for both the SICM study and the molecular composition analysis of cytoplasm and the nucleus of living cells by SERS. The probe localization in cells is successfully achieved.
Influence of Pulse-Plasma Treatment Distance on Structure and Properties of Cr3C2-NiCr-Based Detonation Coatings
Authors: Kakimzhanov Dauir , Rakhadilov Bauyrzhan , Sulyubayeva Laila , Dautbekov Merkhat
Published: October 2023

In this work, the coatings obtained by a combined method, including Cr3C2-NiCr coating applied using a multichamber detonation device and subsequent pulse-plasma treatment, were investigated. This paper presents the results of an investigation of the influence of the pulse-plasma treatment (PPT) exposure distance on the structural-phase state of the surface layer of Cr3C2-NiCr-based detonation coatings. It was seen that after the PPT melting and alignment of the structural elements of coatings there were no signs of coating destruction from the impact of plasma pulses. It was established that the microstructure of the coatings was a molten metal–ceramic material based on Cr3C2-NiCr. It was also found that after pulse-plasma treatment, Cr2O3 chromium oxide phases are found on the surface, and the intensity of Cr3C2 peaks increased and new Cr3C2 reflexes appeared. It was further found that after pulse-plasma treatment the microstructure became more homogeneous, which led to the densification of the Cr3C2-NiCr-based detonation coating. It was established that the pulse-plasma treatment (PPT) contributed to increased hardness of the Cr3C2-NiCr coating material, from ~13.4 GPa (before PPT) to ~17.6 GPa (after PPT) and wear resistance twice that of the non-treated coating. The abrasive wear resistance and erosion resistance of Cr3C2-NiCr coatings were improved after pulse-plasma treatment.
Superhydrophobic Coatings on Cellulose-Based Materials with Alkyl Ketene Dimer Pickering Emulsion: Fabrication and Properties
Authors: Wang Yating , Huang Yuanfei , Zhong Jing , Yu Chenghua
Published: October 2023

In this study, a stable alkyl ketene dimer (AKD) Pickering emulsion was obtained using chitosan and titanium dioxide (TiO2) as effective emulsifiers to disperse AKD. Superhydrophobic filter paper was prepared, using the filter paper as the substrate, by dipping it into AKD Pickering emulsion and then drying the coating papers at different temperature. The contact angle of the treated filter papers dried at 45 °C could reach more than 150°, and these filter papers effectively separated oil–water mixtures with an efficiency of over 93%. It is worth noting that the preparation process of the superhydrophobic material was simple and mild, and all the raw material was green without secondary pollution to the environment, so it has great practical application potential. This experiment could provide a new idea for the preparation of AKD superhydrophobic coatings and broaden their application.
EXtra-Xwiz: A Tool to Streamline Serial Femtosecond Crystallography Workflows at European XFEL
Authors: Turkot Oleksii , Dall’Antonia Fabio , Bean Richard J. , E Juncheng , Fangohr Hans , Ferreira de Lima Danilo E. , Kantamneni Sravya , Kirkwood Henry J. , Koua Faisal H. M. , Mancuso Adrian P. , Melo Diogo V. M. , Round Adam , Schuh Michael , Sobolev Egor , de Wijn Raphaël , Wrigley James J. , Gelisio Luca
Published: October 2023

X-ray free electron lasers deliver photon pulses that are bright enough to observe diffraction from extremely small crystals at a time scale that outruns their destruction. As crystals are continuously replaced, this technique is termed serial femtosecond crystallography (SFX). Due to its high pulse repetition rate, the European XFEL enables the collection of rich and extensive data sets, which are suited to study various scientific problems, including ultra-fast processes. The enormous data rate, data complexity, and the nature of the pixelized multimodular area detectors at the European XFEL pose severe challenges to users. To streamline the analysis of the SFX data, we developed the semiautomated pipeline EXtra-Xwiz around the established CrystFEL program suite, thereby processing diffraction patterns on detector frames into structure factors. Here we present EXtra-Xwiz, and we introduce its architecture and use by means of a tutorial. Future plans for its development and expansion are also discussed.
4-Methyl/Phenyl-1,2,5,6-tetraazafluoranthen-3(2H)-ones Synthesis: Mechanistic Pathway Study and Single-Crystal X-ray Analysis of the Intermediates
Authors: Sarhan Ahmed A. M. , Haukka Matti , Barakat Assem , Soliman Saied M. , Boraei Ahmed T. A. , Sopaih Manar , Salama Eid E.
Published: October 2023

The synthesis of 4-methyl/phenyl-1,2,5,6-tetraazafluoranthen-3(2H)-one 4 and 7 has been reported with ninhydrin via a reaction first with ethyl acetoacetate or ethyl benzoylacetate and then a reaction of the resultant esters with hydrazine hydrate. The mechanism of hydrazinolysis and cyclization to obtain tetraazafluoranthen-3(2H)-ones is ambiguous, and the previously proposed mechanism was not based on facts because the actual intermediates were not isolated. Herein, the important intermediates involved in the hydrazinolysis–cyclization mechanistic pathway were isolated and characterized using NMR and X-ray single-crystal analysis. The intermediates demonstrate that the reaction carried out via two hydrazinolysis–cyclization reactions, the first of which includes the condensation of one hydrazine molecule with two ketone groups and the second of which includes the reaction of another hydrazine molecule with the ester and then condensation with the other ketone group. The stability of hydrazide 11 enabled the hydrazine to reduce the carbonyl of the ketone group to form 12 via a Wolff–Kishner-like reduction. The structure of the three intermediates was confirmed using X-ray crystallographic analysis. It was found that the three fused ring systems deviated from planarity to different extents, with their deviation from being coplanar reaching up to 5.3°. The possible non-covalent interactions which control the molecular packing of these intermediates were elucidated with the aid of Hirshfeld analysis.
Cancer and Pregnancy in the Post-Roe v. Wade Era: A Comprehensive Review
Authors: Arup Ganguly , Shravan Narmala
Published: October 2023

Cancer during pregnancy, affecting 1 in 1000 pregnancies, is rising in incidence due to delayed childbearing and improved detection. Common types include breast cancer, melanoma and cervical cancer and Hodgkin’s Lymphoma. There are several physiological changes that occur during pregnancy that make its management a challenge to clinicians. Managing it requires multidisciplinary approaches and cautious test interpretation due to overlapping symptoms. To minimize fetal radiation exposure, non-ionizing imaging is preferred, and the interpretation of tumor markers is challenging due to inflammation and pregnancy effects. In terms of treatment, chemotherapy is avoided in the first trimester but may be considered later. Immunotherapy’s safety is under investigation, and surgery depends on gestational age and cancer type. Ethical and legal concerns are growing, especially with changes in U.S. abortion laws. Access to abortion for medical reasons is vital for pregnant cancer patients needing urgent treatment. Maternal outcomes may depend on the type of cancer as well as chemotherapy received but, in general, they are similar to the non-pregnant population. Fetal outcomes are usually the same as the general population with treatment exposure from the second trimester onwards. Fertility preservation may be an important component of the treatment discussion depending on the patient’s wishes, age and type of treatment. This article addresses the complicated nature of a diagnosis of cancer in pregnancy, touching upon the known medical literature as well as the ethical–legal implications of such a diagnosis, whose importance has increased in the light of recent judicial developments.
Bats of the Tunisian Desert: Preliminary Data Using Acoustic Identification and First Record of Taphozous nudiventris in the Country
Authors: Dalhoumi Ridha , El Mokni Ridha , Ouni Ridha , Beyrem Hamouda , Aulagnier Stéphane
Published: October 2023

Increasing aridity usually results in decreasing bat abundance and species richness, and the Saharan desert is an example of such impoverishment. Moreover, the harsh climatic and field conditions in this area restrict the feasibility of surveys. Therefore, the bat fauna of the Tunisian Sahara was unstudied until an expedition was conducted in May 2021. A total of seven species were recorded using passive bat detectors set mainly at water bodies, which concentrate bat activity. Echolocation calls of these species did not depart from published records for the Mediterranean area. Our data failed to identify the two ecomorphotypes of Pipistrellus kuhlii but confirmed the adaptability of this species to local conditions. For the first time in Tunisia, we recorded echolocation calls of Taphozous nudiventris, a species that has been rarely reported in North Africa. The highest species richness was identified at the largest wetlands of Oued Daghsen (Oued Dkouk Nature Reserve) and at Bordj el Khadra (only six and four species, respectively). Most Mediterranean species were recorded in the northern locality, while desert species were more active in the most southern one. The importance of water bodies for bats was confirmed once more. No sign of competition among species was detected, as the Mediterranean and desert-dwelling bat species were active at the same time. Additional surveys should be planned in order to enlarge the list of seven species recorded in only one week.
The Release and Spread of Basidiospores of Red-Listed Wood-Decay Fungus Fistulina hepatica in Oak Stands
Authors: Marčiulynas Adas , Menkis Audrius
Published: October 2023

The aim of this study was to obtain a better understanding on short-distance basidiospore dispersal of the wood-decay fungus Fistulina hepatica, thereby providing valuable knowledge for the conservation management of this protected species. Specifically, the study was expected to reveal site-specific patterns of basidiospore release and spread in oak stands during one fruiting season under north European conditions. The trapping of fungal spores was carried out between August and October 2022 using passive spore traps placed in three oak stands (>200-year-old) in central Lithuania. The average daily temperature was recorded throughout the period of spore trapping. Collected samples were analyzed using high-throughput sequencing of fungal ITS2 rDNA. The results showed that the relative abundance of F. hepatica reads was influenced by the time of fruitbody maturation, but not by the average daily temperature. Although there was a certain variation among different study sites, the results showed that a great majority of F. hepatica spores were deposited within 50 m from the fruitbody, showing that the fungus to a large extent is dependent on local habitats for colonization.
Invasion of Bythotrephes longimanus and Cercopagis pengoi in Lake Champlain: Impacts on the Native Zooplankton Community
Authors: Cutter Zachary A. , Mihuc Timothy B. , Myers Luke W.
Published: October 2023

The zooplankton community of Lake Champlain has been altered over the past decade due to the introduction of two predatory zooplankton species. Bythotrephes longimanus Leydig, 1860 was first detected in Lake Champlain in August 2014, and Cercopagis pengoi (Ostroumov, 1891) was detected in August 2018. Monitoring for both invasive species at 15 lake sites using whole water tow sampling has been ongoing since 2010 with no detection of either species until 2014. Utilizing data from the Lake Champlain long-term monitoring program, we assessed pre- and post-invasion population dynamics of both invasive species on the native zooplankton community. Our results showed shifts in community structure following invasion, including a reduction in Diacyclops thomasi (Forbes, 1882) populations by both invaders and a reduction in Daphnia retrocurva Forbes, 1882 following the introduction of B. longimanus. Other cyclopoids, bosminids, and rotifers were also reduced, corresponding to both introduced species. The native large-bodied plankton predator Leptodora kindtii (Focke, 1844) appears to be unable to coexist with either invasive predatory cladoceran, displaying seasonal partitioning between L. kindtii and the Cercopagidae. These findings suggest that the invasion of both large predators in Lake Champlain have impacted pelagic zooplankton community structure.
Temporal Variation of Genetic Diversity in Rutilus rutilus Populations from Lithuania Using mtDNA Markers in the Context of Anthropogenic Activities
Authors: Butkauskas Dalius , Ignatavičienė Ieva , Ragauskas Adomas , Rakauskas Vytautas
Published: October 2023

One of the most abundant fish species, Rutilus rutilus, is widely distributed in Lithuania and its potential to adapt to environmental changes attracted our interest. Unfortunately, it is not properly understood how anthropogenic activities can affect the genetic diversity within this species. We studied three populations of roaches (samples collected in the Neris and Žeimena rivers, and Lake Drūkšiai) over a period of five years (from 2017 to 2022) to determine genetic diversity using mtDNA D-loop and ATP6 genetic markers. Genetic diversity parameters, AMOVA analysis, haplotype network, and PCoA analysis revealed a greater genetic variability in roach samples collected in 2017, and the greatest differences were noticed in the population inhabiting Lake Drūkšiai, as compared with other samples studied over a five-year period. Differences in genetic diversity detected after a five-year period led us to the assumption that roach populations may be related to the effects of natural (changing climatic conditions) and anthropogenic (operating nuclear power plant) origin.
Fractal-Based Hybrid Cryptosystem: Enhancing Image Encryption with RSA, Homomorphic Encryption, and Chaotic Maps
Authors: Mfungo Dani Elias , Fu Xianping
Published: October 2023

Protecting digital data, especially digital images, from unauthorized access and malicious activities is crucial in today’s digital era. This paper introduces a novel approach to enhance image encryption by combining the strengths of the RSA algorithm, homomorphic encryption, and chaotic maps, specifically the sine and logistic map, alongside the self-similar properties of the fractal Sierpinski triangle. The proposed fractal-based hybrid cryptosystem leverages Paillier encryption for maintaining security and privacy, while the chaotic maps introduce randomness, periodicity, and robustness. Simultaneously, the fractal Sierpinski triangle generates intricate shapes at different scales, resulting in a substantially expanded key space and heightened sensitivity through randomly selected initial points. The secret keys derived from the chaotic maps and Sierpinski triangle are employed for image encryption. The proposed scheme offers simplicity, efficiency, and robust security, effectively safeguarding against statistical, differential, and brute-force attacks. Through comprehensive experimental evaluations, we demonstrate the superior performance of the proposed scheme compared to existing methods in terms of both security and efficiency. This paper makes a significant contribution to the field of digital image encryption, paving the way for further exploration and optimization in the future.