bluuebunny/crossref_metadata_2025 huggingface dataset:
Are attention-deficit/hyperactivity disorder symptoms associated with negative health outcomes in individuals with psychotic experiences? Findings from a cross-sectional study in Japan
Authors: Stickley Andrew , Shirama Aya , Sumiyoshi Tomiki
Published: May 2023

Objective

Although research has indicated that the prevalence of attention-deficit/hyperactivity disorder (ADHD) may be elevated in individuals with psychotic disorders, as yet, there has been comparatively little research on this association and its effects among adults at the subclinical level. To address this deficit, the current study examined the association between psychotic experiences (PE) and ADHD symptoms in Japanese individuals and whether the presence of ADHD symptoms increases the risk for negative health outcomes in people with PE.

Method

Data were analyzed from an online sample of 1,452 individuals (age 18–89; 51.5% female) collected in 2021. Information on PE was obtained with the PRIME Screen-Revised (PS-R), while the Adult ADHD Self-Report Scale (ASRS) Screener was used to measure ADHD symptoms. Information was also obtained on a number of health outcomes including anxiety and depressive symptoms and suicidal ideation. Logistic regression was used to assess associations.

Results

In a fully adjusted analysis PE were associated with almost three times higher odds for ADHD symptoms (OR: 2.92, 95%CI: 1.19–7.17). In an analysis that was restricted to individuals with PE, ADHD symptoms were associated with significantly increased odds for depressive symptoms, lifetime suicidal ideation, perceived stress and severe sleep problems.

Conclusion

ADHD symptoms are present in some individuals with PE and increase the odds for several detrimental health outcomes in this population. Identifying co-occurring PE and ADHD/ADHD symptoms may facilitate treatment options and help prevent negative health outcomes in individuals with these conditions.
Use of big data from health insurance for assessment of cardiovascular outcomes
Authors: Krefting Johannes , Sen Partho , David-Rus Diana , Güldener Ulrich , Hawe Johann S. , Cassese Salvatore , von Scheidt Moritz , Schunkert Heribert
Published: May 2023

Outcome research that supports guideline recommendations for primary and secondary preventions largely depends on the data obtained from clinical trials or selected hospital populations. The exponentially growing amount of real-world medical data could enable fundamental improvements in cardiovascular disease (CVD) prediction, prevention, and care. In this review we summarize how data from health insurance claims (HIC) may improve our understanding of current health provision and identify challenges of patient care by implementing the perspective of patients (providing data and contributing to society), physicians (identifying at-risk patients, optimizing diagnosis and therapy), health insurers (preventive education and economic aspects), and policy makers (data-driven legislation). HIC data has the potential to inform relevant aspects of the healthcare systems. Although HIC data inherit limitations, large sample sizes and long-term follow-up provides enormous predictive power. Herein, we highlight the benefits and limitations of HIC data and provide examples from the cardiovascular field, i.e. how HIC data is supporting healthcare, focusing on the demographical and epidemiological differences, pharmacotherapy, healthcare utilization, cost-effectiveness and outcomes of different treatments. As an outlook we discuss the potential of using HIC-based big data and modern artificial intelligence (AI) algorithms to guide patient education and care, which could lead to the development of a learning healthcare system and support a medically relevant legislation in the future.
The burst observer and optical transient exploring system in the multi-messenger astronomy era
Authors: Hu Y.-D. , Fernández-García E. , Caballero-García M. D. , Pérez-García I. , Carrasco-García I. M. , Castellón A. , Pérez del Pulgar C. , Reina Terol A. J. , Castro-Tirado A. J.
Published: May 2023

The Burst Observer and Optical Transient Exploring System (BOOTES) was first designed as an asset of autonomous telescopes that started to be deployed in 1998, taking 24 years to be fully developed around the earth. Nowadays BOOTES has became a global network of robotic telescopes, being the first one present in all continents, as of 2022. Here we present the details of the network and review its achievements over the last 2 decades regarding follow-up observations of high-energy transient events. Moreover, considering the recent operations of neutrino and gravitational wave detectors, some hot-topic expectations related to robotic astronomy are discussed within the framework of multi-wavelength astrophysics.
Numerical Simulations in Ultrasonic Guided Wave Analysis for the Design of SHM Systems—Benchmark Study Based on the Open Guided Waves Online Platform Dataset
Authors: Savli Enes , Lefèvre Jean , Willberg Christian , Tschöke Kilian
Published: May 2023

Structural health monitoring (SHM) strategies based on ultrasonic guided waves are very promising regarding thin-walled lightweight structures. To study the performance of such systems, validated numerical analysis tools have to be used. For that procedure, a benchmark between two numerical methods will be presented. The first promising approach is the elastodynamic finite integration technique (EFIT). Miscellaneous research shows that its capability of capturing wave characteristics and interactions is advanced in various media and structures, including thin-walled composites. The second approach employs conventional shell-type finite elements following the Reissner–Mindlin theory for modelling layered composite structures. The advantage of using such finite element methods (FEM) is their high availability in general purpose simulation tools. As a reference model, the measurement data coming from the Open Guided Waves Project (OGW) was taken into account. The OGW dataset provides the experimental data of ultrasonic guided wave propagation in carbon fiber composite plates with an additional omega stringer. By using this contribution, this experiment was reproduced by simulation. The paper presents the results of a validation and motivates further research, such as in research related to the probability of detection analysis and numerical performance.
Animal Species Recognition with Deep Convolutional Neural Networks from Ecological Camera Trap Images
Authors: Binta Islam Sazida , Valles Damian , Hibbitts Toby J. , Ryberg Wade A. , Walkup Danielle K. , Forstner Michael R. J.
Published: May 2023

Accurate identification of animal species is necessary to understand biodiversity richness, monitor endangered species, and study the impact of climate change on species distribution within a specific region. Camera traps represent a passive monitoring technique that generates millions of ecological images. The vast numbers of images drive automated ecological analysis as essential, given that manual assessment of large datasets is laborious, time-consuming, and expensive. Deep learning networks have been advanced in the last few years to solve object and species identification tasks in the computer vision domain, providing state-of-the-art results. In our work, we trained and tested machine learning models to classify three animal groups (snakes, lizards, and toads) from camera trap images. We experimented with two pretrained models, VGG16 and ResNet50, and a self-trained convolutional neural network (CNN-1) with varying CNN layers and augmentation parameters. For multiclassification, CNN-1 achieved 72% accuracy, whereas VGG16 reached 87%, and ResNet50 attained 86% accuracy. These results demonstrate that the transfer learning approach outperforms the self-trained model performance. The models showed promising results in identifying species, especially those with challenging body sizes and vegetation.
Multimodal Communication in the Human–Cat Relationship: A Pilot Study
Authors: de Mouzon Charlotte , Leboucher Gérard
Published: May 2023

Across all species, communication implies that an emitter sends signals to a receiver, through one or more channels. Cats can integrate visual and auditory signals sent by humans and modulate their behaviour according to the valence of the emotion perceived. However, the specific patterns and channels governing cat-to-human communication are poorly understood. This study addresses whether, in an extraspecific interaction, cats are sensitive to the communication channel used by their human interlocutor. We examined three types of interactions—vocal, visual, and bimodal—by coding video clips of 12 cats living in cat cafés. In a fourth (control) condition, the human interlocutor refrained from emitting any communication signal. We found that the modality of communication had a significant effect on the latency in the time taken for cats to approach the human experimenter. Cats interacted significantly faster to visual and bimodal communication compared to the “no communication” pattern, as well as to vocal communication. In addition, communication modality had a significant effect on tail-wagging behaviour. Cats displayed significantly more tail wagging when the experimenter engaged in no communication (control condition) compared to visual and bimodal communication modes, indicating that they were less comfortable in this control condition. Cats also displayed more tail wagging in response to vocal communication compared to the bimodal communication. Overall, our data suggest that cats display a marked preference for both visual and bimodal cues addressed by non-familiar humans compared to vocal cues only. Results arising from the present study may serve as a basis for practical recommendations to navigate the codes of human–cat interactions.
Species and Strain Variability among Sarcina Isolates from Diverse Mammalian Hosts
Authors: Makovska Marie , Killer Jiri , Modrackova Nikol , Ingribelli Eugenio , Amin Ahmad , Vlkova Eva , Bolechova Petra , Neuzil-Bunesova Vera
Published: May 2023

Sarcina spp. has been isolated from the gastrointestinal tracts of diverse mammalian hosts. Their presence is often associated with host health complications, as is evident from many previously published medical case reports. However, only a handful of studies have made proper identification. Most other identifications were solely based on typical Sarcina-like morphology without genotyping. Therefore, the aim of this work was culture detection and the taxonomic classification of Sarcina isolates originating from different mammalian hosts. Sarcina-like colonies were isolated and collected during cultivation analyses of animal fecal samples (n = 197) from primates, dogs, calves of domestic cattle, elephants, and rhinoceroses. The study was carried out on apparently healthy animals kept in zoos or by breeders in the Czech Republic and Slovakia. Selected isolates were identified and compared using 16S rRNA gene sequencing and multi-locus sequence analysis (MLSA; Iles, pheT, pyrG, rplB, rplC, and rpsC). The results indicate the taxonomic variability of Sarcina isolates. S. ventriculi appears to be a common gut microorganism in various captive primates. In contrast, a random occurrence was also recorded in dogs. However, dog isolate N13/4e could represent the next potential novel Sarcina taxonomic unit. Also, a potentially novel Sarcina species was found in elephants, with occurrences in all tested hosts. S. maxima isolates were detected rarely, only in rhinoceroses. Although Sarcina bacteria are often linked to lethal diseases, our results indicate that Sarcina spp. appear to be a common member of the gut microbiota and seem to be an opportunistic pathogen. Further characterization and pathogenic analyses are required.
Spatial and Temporal Variation of Aerosol Optical Depth in Huaihai Economic Zone from 1982 to 2021
Authors: Wu Shuhui , Xue Yong , Sun Yuxin , Jin Chunlin , Zhang Minghao , Jiang Xingxing , Lu Xi
Published: May 2023

Aerosol Optical Depth (AOD), quantifying the amount of aerosol in the atmosphere, is widely regarded as a crucial indicator for research on atmospheric physics and regional air quality. At present, the inversion of AOD from observation of satellite remote sensing sensors has become the main technology for large-scale monitoring of aerosol load. The Huaihai Economic Zone is the connecting belt of two key areas of atmospheric governance (the Yangtze River Delta and the Beijing-Tianjin-Hebei region, China), and it has been suffering from air pollution for many years and few studies of AOD focus on this region. Therefore, the spatial and temporal characteristics of the AOD are explored using MODIS AOD data and AVHRR AOD data in this region during the period from 1982 to 2021 in this study. The correlation coefficients between the AOD of satellite observation and actual air pollution were analyzed by combining PM2.5 pollutant concentration and air quality index (AQI) data. The results showed that the AOD is higher in the northwest than in the southeast, and it is different from season to season. The annual variation of AOD in the Huaihai Economic Zone is a W-shaped trend from 1982 to 2011, while the trend of annual AOD is decreasing after 2011. In terms of seasons, the whole differences in AOD are evident, exhibiting AOD values in summer > those in spring > those in autumn > and those in winter. Furthermore, it indicated that the quarterly and monthly variation of the AOD tends to be flat in recent years. Since 2015, the concentration of PM2.5 has continued to decline, the same as that of AQI. Meanwhile, the quarterly and monthly differences in PM2.5 are still obvious, with higher PM2.5 in winter and lower PM2.5 in summer. However, it also represented that PM2.5 is significantly higher in spring than in autumn from 2015 to 2018, which is the opposite for 2019 to 2021. Lastly, the correlation between AOD and PM2.5/AQI is also given; i.e., the correlation coefficients of AOD with PM2.5/AQI are 0.84/0.82, with the highest correlation coefficient in autumn (R = 0.86/0.91) and the lowest in winter (R = 0.46/0.48).
Recent Developments in the Field of Endoscopic Ultrasound for Diagnosis, Staging, and Treatment of Pancreatic Lesions
Authors: Poiraud Marie , Gkolfakis Paraskevas , Arvanitakis Marianna
Published: May 2023

Endoscopic ultrasound (EUS) plays a crucial role in the diagnosis of both solid and cystic pancreatic lesions and in the staging of patients with pancreatic cancer through its use for tissue and fluid sampling. Additionally, in cases of precancerous lesions, EUS-guided therapy can also be provided. This review aims to describe the most recent developments regarding the role of EUS in the diagnosis and staging of pancreatic lesions. Moreover, complementary EUS imaging modalities, the role of artificial intelligence, new devices, and modalities for tissue acquisition, and techniques for EUS-guided treatment are discussed.
Oral Microbiome Community Composition in Head and Neck Squamous Cell Carcinoma
Authors: Benjamin William J. , Wang Kai , Zarins Katherine , Bellile Emily , Blostein Freida , Argirion Ilona , Taylor Jeremy M. G. , D’Silva Nisha J. , Chinn Steven B. , Rifkin Samara , Sartor Maureen A. , Rozek Laura S.
Published: May 2023

The impact of the oral microbiome on head and neck cancer pathogenesis and outcomes requires further study. 16s rRNA was isolated and amplified from pre-treatment oral wash samples for 52 cases and 102 controls. The sequences were binned into operational taxonomic units (OTUs) at the genus level. Diversity metrics and significant associations between OTUs and case status were assessed. The samples were binned into community types using Dirichlet multinomial models, and survival outcomes were assessed by community type. Twelve OTUs from the phyla Firmicutes, Proteobacteria, and Acinetobacter were found to differ significantly between the cases and the controls. Beta-diversity was significantly higher between the cases than between the controls (p < 0.01). Two community types were identified based on the predominant sets of OTUs within our study population. The community type with a higher abundance of periodontitis-associated bacteria was more likely to be present in the cases (p < 0.01), in older patients (p < 0.01), and in smokers (p < 0.01). Significant differences between the cases and the controls in community type, beta-diversity, and OTUs indicate that the oral microbiome may play a role in HNSCC.
Expression of Hemangioblast Proteins in von Hippel-Lindau Disease Related Tumors
Authors: Vergauwen Evelynn , Forsyth Ramses , Vortmeyer Alexander , Gläsker Sven
Published: May 2023

Von Hippel-Lindau (VHL) disease is a hereditary tumor syndrome that targets a highly selective subset of organs causing specific types of tumors. The biological basis for this principle of organ selectivity and tumor specificity is not well understood. VHL-associated hemangioblastomas share similar molecular and morphological features with embryonic blood and vascular precursor cells. Therefore, we suggest that VHL hemangioblastomas are derived from developmentally arrested hemangioblastic lineage keeping their potential of further differentiation. Due to these common features, it is of major interest to investigate whether VHL-associated tumors other than hemangioblastoma also share these pathways and molecular features. The expression of hemangioblast proteins has not yet been assessed in other VHL-related tumors. To gain a better understanding of VHL tumorigenesis, the expression of hemangioblastic proteins in different VHL-associated tumors was investigated. The expression of embryonic hemangioblast proteins Brachyury and TAL1 (T-cell acute lymphocytic leukemia protein 1) was assessed by immunohistochemistry staining on 75 VHL-related tumors of 51 patients: 47 hemangioblastomas, 13 clear cell renal cell carcinomas, 8 pheochromocytomas, 5 pancreatic neuroendocrine tumors, and 2 extra-adrenal paragangliomas. Brachyury and TAL1 expression was, respectively, observed in 26% and 93% of cerebellar hemangioblastomas, 55% and 95% of spinal hemangioblastomas, 23% and 92% of clear cell renal cell carcinomas, 38% and 88% of pheochromocytomas, 60% and 100% of pancreatic neuroendocrine tumors, and 50% and 100% of paragangliomas. We concluded that the expression of hemangioblast proteins in different VHL-associated tumors indicates a common embryological origin of these lesions. This may also explain the specific topographic distribution of VHL-associated tumors.
Bone Remodeling Markers in Children with Acute Lymphoblastic Leukemia after Intensive Chemotherapy: The Screenshot of a Biochemical Signature
Authors: Muggeo Paola , Grassi Massimo , D’Ascanio Vito , Brescia Vincenzo , Fontana Antonietta , Piacente Laura , Di Serio Francesca , Giordano Paola , Faienza Maria Felicia , Santoro Nicola
Published: May 2023

Purpose: to investigate the effects of intensive chemotherapy and glucocorticoid (GC) treatment on bone remodeling markers in children with acute lymphoblastic leukemia (ALL). Methods: A cross-sectional study was carried out in 39 ALL children (aged 7.64 ± 4.47) and 49 controls (aged 8.7 ± 4.7 years). Osteoprotegerin (OPG), receptor activator of NF-κB ligand (RANKL), osteocalcin (OC), C-terminal telopeptide of type I collagen (CTX), bone alkaline phosphatase (bALP), tartrate-resistant acid phosphatase 5b (TRACP5b), procollagen type I N-terminal propeptide (P1NP), Dickkopf-1 (DKK-1), and sclerostin were assessed. Statistical analysis was conducted using the principal component analysis (PCA) to study patterns of associations in bone markers. Results: ALL patients showed significantly higher OPG, RANKL, OC, CTX, and TRACP5b than the controls (p ≤ 0.02). Considering ALL group, we found a strong positive correlation among OC, TRACP5b, P1NP, CTX, and PTH (r = 0.43–0.69; p < 0.001); between CTX and P1NP (r = 0.5; p = 0.001); and between P1NP and TRAcP (r = 0.63; p < 0.001). The PCA revealed OC, CTX, and P1NP as the main markers explaining the variability of the ALL cohort. Conclusions: Children with ALL showed a signature of bone resorption. The assessment of bone biomarkers could help identify ALL individuals who are most at risk of developing bone damage and who need preventive interventions.
Radioiodine-131 Therapy Used for Differentiated Thyroid Cancer Can Impair Titanium Dental Implants: An In Vitro Analysis
Authors: Piciu Doina , Bran Simion , Moldovan Marioara , Varvara Simona , Piciu Andra , Cuc Stanca , Moisescu-Goia Cristina , Barbus Elena , Mester Alexandru , Onisor Florin
Published: May 2023

Background: The aim was to assess, in vitro, the effects of radioiodine-131 (I-131) on the structure of titanium implants. Material and Methods: A total of 28 titanium implants were divided into 7 groups (n = 4) and irradiated at 0, 6, 12, 24, 48, 192 and 384 hours. At the end of the experiment, each sample was investigated via scanning electron microscopy (SEM) and electrochemical measures. Results: The control sample revealed a smooth and compact surface. The small micro-sized porosity is slightly visible at the macroscopic level, but the precise details cannot be observed. A mild exposure to the radioactive solution for 6 to 24 h showed a good preservation of the macro-structural aspects such as thread details and surface quality. Significant changes occurred after 48 h of exposure. It was noticed that the open-circuit potential (OCP) value of the non-irradiated implants move toward more noble potentials during the first 40 min of exposure to the artificial saliva and then stabilizes at a constant value of −143 mV. A displacement of the OCP values toward more negative values was observed for all irradiated implants; these potential shifts are decreasing, as the irradiation period of the tested implants increased. Conclusion: After exposure to I-131, the structure of titanium implants is well preserved up to 12 h. The eroded particles start to appear in the microstructural details after 24 h of exposure and their numbers progressively increase up to 384 h after exposure.
Pediatric Extra-Renal Nephroblastoma (Wilms’ Tumor): A Systematic Case-Based Review
Authors: Karim Akzhol , Shaikhyzada Kundyz , Abulkhanova Nazgul , Altyn Akzhunis , Ibraimov Bakytkali , Nurgaliyev Dair , Poddighe Dimitri
Published: May 2023

Wilms Tumor (WT) is one of the most common renal tumors in the pediatric population. Occasionally, WT can primarily develop outside the kidneys (Extra-Renal Wilms Tumor, ERWT). Most pediatric ERWTs develop in the abdominal cavity and pelvis, whereas the occurrence of this tumor in other extra-renal sites represents a minor part of ERWT cases. In addition to describing a case of spinal ERWT (associated with spinal dysraphism) in a 4-year boy (to add a further clinical experience on this very rare pediatric tumor), we performed a case-based systematic literature review on pediatric ERWT. We retrieved 72 papers providing enough information on the diagnosis, treatment, and outcomes of 98 ERWT pediatric patients. Our research highlighted that a multimodal approach involving both chemotherapy and radiotherapy, after partial or complete tumor resection in most cases, was typically used, but there is no standardized therapeutic approach for this pediatric malignancy. However, this tumor may be potentially treated with a better success rate if the diagnostic confirmation is not delayed, the mass can be totally resected, and an appropriate and, possibly, tailored multimodal treatment can be promptly established. In this regard, an international agreement on a unique staging system for (pediatric) ERWT is definitely needed, as well as the development of international research, which may be able to gather several children diagnosed with ERWT and, possibly, lead to clinical trials which should also include developing countries.
Diagnostic and Prognostic Roles of Urine Nectin-2 and Nectin-4 in Human Bladder Cancer
Authors: Miyake Makito , Nishimura Nobutaka , Ohnishi Sayuri , Oda Yuki , Owari Takuya , Ohnishi Kenta , Morizawa Yosuke , Hori Shunta , Gotoh Daisuke , Nakai Yasushi , Torimoto Kazumasa , Fujii Tomomi , Tanaka Nobumichi , Fujimoto Kiyohide
Published: May 2023

The clinical utility of urine nectins in bladder cancer (BCa) is unclear. We investigated the potential diagnostic and prognostic values of urine Nectin-2 and Nectin-4. Levels of urine Nectin-2, Nectin-4, and NMP-22 were quantified using an enzyme-linked immunosorbent assay in 122 patients with BCa, consisting of 78 with non-muscle-invasive BCa (NMIBC) and 44 with muscle-invasive BCa (MIBC), and ten healthy controls. Tumor nectin expression in MIBC was evaluated with immunohistochemical staining of transurethral resection specimens. The level of urine Nectin-4 (mean: 18.3 ng/mL) was much higher than that of urine Nectin-2 (mean: 0.40 ng/mL). The sensitivities of Nectin-2, Nectin-4, NMP-22, and cytology assays were 84%, 98%, 52%, and 47%, respectively; their specificities were 40%, 80%, 100%, and 100%, respectively. Both urine Nectin-2 and Nectin-4, though not NMP-22, were found to be significantly more sensitive than cytology. A four-titer grouping based on levels of urine Nectin-2/Nectin-4 (low/high, high/high, low/low, and high/low) showed a high capability for discriminating between NMIBC and MIBC. Neither urine Nectin-2 nor Nectin-4 levels had a significant prognostic value in NMIBC or MIBC. Urine levels correlated with tumor expression and serum levels in the Nectin-4 analysis, but not in the Nectin-2 analysis. Urine nectins are potential diagnostic biomarkers for BCa.
Selecting a TNT Schedule in Locally Advanced Rectal Cancer: Can We Predict Who Actually Benefits?
Authors: Aschele Carlo , Glynne-Jones Robert
Published: May 2023

Many consider the standard of care for locally advanced rectal cancer (LARC) to be preoperative chemoradiotherapy, radical surgery involving a total mesorectal excision, and post-operative adjuvant chemotherapy based on the pathology of the specimen. The poor impact on distant control is a major limitation of this strategy, with metastasis rates remaining in the 25–35% range and recovery after radical surgery leading to reluctance with prescription and inconsistent patient compliance with adjuvant chemotherapy. A second limitation is the low rate of pathologic complete response (pCR) (around 10–15%) despite multiple efforts to potentiate preoperative chemoradiation regimens, which in turn means it is less effective at achieving non-operative management (NOM). Total neoadjuvant treatment (TNT) is a pragmatic approach to solving these problems by introducing systemic chemotherapy at an early timepoint. Enthusiasm for delivering TNT for patients with LARC is increasing in light of the results of published randomized phase III trials, which show a doubling of the pCR rate and a significant reduction in the risk of subsequent metastases. However, there has been no demonstrated improvement in quality of life or overall survival. A plethora of potential chemotherapy schedules are available around the radiotherapy component, which include preoperative induction or consolidation with a range of options (FOLFOXIRI, FOLFOX, or CAPEOX,) and a varying duration of 6–18 weeks, prior to long course chemoradiation (LCCRT) or consolidation NACT following short-course preoperative radiation therapy (SCPRT) using 5 × 5 Gy or LCCRT using 45–60 Gy, respectively. The need to maintain optimal local control is a further important factor, and preliminary data appear to indicate that the RT schedule remains a crucial issue, especially in more advanced tumors, i.e., mesorectal fascia (MRF) invasion. Thus, there is no consensus as to the optimum combination, sequence, or duration of TNT. The selection of patients most likely to benefit is challenging, as clear-cut criteria to individuate patients benefiting from TNT are lacking. In this narrative review, we examine if there are any necessary or sufficient criteria for the use of TNT. We explore potential selection for the individual and their concerns with a generalized use of this strategy.
Preclinical and Basic Research Strategies for Overcoming Resistance to Targeted Therapies in HER2-Positive Breast Cancer
Authors: Cao Yi , Li Yunjin , Liu Ruijie , Zhou Jianhua , Wang Kuansong
Published: May 2023

The amplification of epidermal growth factor receptor 2 (HER2) is associated with a poor prognosis and HER2 gene is overexpressed in approximately 15–30% of breast cancers. In HER2-positive breast cancer patients, HER2-targeted therapies improved clinical outcomes and survival rates. However, drug resistance to anti-HER2 drugs is almost unavoidable, leaving some patients with an unmet need for better prognoses. Therefore, exploring strategies to delay or revert drug resistance is urgent. In recent years, new targets and regimens have emerged continuously. This review discusses the fundamental mechanisms of drug resistance in the targeted therapies of HER2-positive breast cancer and summarizes recent research progress in this field, including preclinical and basic research studies.
Racial Disparities in Brachytherapy Treatment among Women with Cervical and Endometrial Cancer in the United States
Authors: Taparra Kekoa , Ing Brandon I. , Ewongwo Agnes , Vo Jacqueline B. , Shing Jaimie Z. , Gimmen Megan Y. , Keli‘i Kiana M. K. , Uilelea Jason , Pollom Erqi , Kidd Elizabeth
Published: May 2023

Brachytherapy improves clinical outcomes among women diagnosed with cervical and endometrial cancers. Recent evidence demonstrates that declining brachytherapy boosts for women with cervical cancer were associated with higher mortality. In this retrospective cohort study, women diagnosed with endometrial or cervical cancer in the United States between 2004 and 2017 were selected from the National Cancer Database for evaluation. Women ≥18 years of age were included for high intermediate risk (PORTEC-2 and GOG-99 definition) or FIGO Stage II-IVA endometrial cancers and FIGO Stage IA-IVA—non-surgically treated cervical cancers. The aims were to (1) evaluate brachytherapy treatment practice patterns for cervical and endometrial cancers in the United States; (2) calculate rates of brachytherapy treatment by race; and (3) determine factors associated with not receiving brachytherapy. Treatment practice patterns were evaluated over time and by race. Multivariable logistic regression assessed predictors of brachytherapy. The data show increasing rates of brachytherapy for endometrial cancers. Compared to non-Hispanic White women; Native Hawaiian and other Pacific Islander (NHPI) women with endometrial cancer and Black women with cervical cancer were significantly less likely to receive brachytherapy. For both NHPI and Black women, treatment at community cancer centers was associated with a decreased likelihood of brachytherapy. The data suggest racial disparities among Black women with cervical cancer and NHPI women with endometrial cancer and emphasize an unmet need for brachytherapy access within community hospitals.
Acidic Growth Conditions Promote Epithelial-to-Mesenchymal Transition to Select More Aggressive PDAC Cell Phenotypes In Vitro
Authors: Audero Madelaine Magalì , Carvalho Tiago Miguel Amaral , Ruffinatti Federico Alessandro , Loeck Thorsten , Yassine Maya , Chinigò Giorgia , Folcher Antoine , Farfariello Valerio , Amadori Samuele , Vaghi Chiara , Schwab Albrecht , Reshkin Stephan J. , Cardone Rosa Angela , Prevarskaya Natalia , Fiorio Pla Alessandra
Published: May 2023

Pancreatic Ductal Adenocarcinoma (PDAC) is characterized by an acidic microenvironment, which contributes to therapeutic failure. So far there is a lack of knowledge with respect to the role of the acidic microenvironment in the invasive process. This work aimed to study the phenotypic and genetic response of PDAC cells to acidic stress along the different stages of selection. To this end, we subjected the cells to short- and long-term acidic pressure and recovery to pHe 7.4. This treatment aimed at mimicking PDAC edges and consequent cancer cell escape from the tumor. The impact of acidosis was assessed for cell morphology, proliferation, adhesion, migration, invasion, and epithelial–mesenchymal transition (EMT) via functional in vitro assays and RNA sequencing. Our results indicate that short acidic treatment limits growth, adhesion, invasion, and viability of PDAC cells. As the acid treatment progresses, it selects cancer cells with enhanced migration and invasion abilities induced by EMT, potentiating their metastatic potential when re-exposed to pHe 7.4. The RNA-seq analysis of PANC-1 cells exposed to short-term acidosis and pHe-selected recovered to pHe 7.4 revealed distinct transcriptome rewiring. We describe an enrichment of genes relevant to proliferation, migration, EMT, and invasion in acid-selected cells. Our work clearly demonstrates that upon acidosis stress, PDAC cells acquire more invasive cell phenotypes by promoting EMT and thus paving the way for more aggressive cell phenotypes.
Development of a Duplex Serological Multiplex Assay for the Simultaneous Detection of Epstein-Barr Virus IgA and IgG Antibodies in Nasopharyngeal Carcinoma Patients
Authors: Schieber Jennifer , Pring Miranda , Ness Andy , Liu Zhiwei , Hsu Wan-Lun , Brenner Nicole , Butt Julia , Waterboer Tim , Simon Julia
Published: May 2023

Epstein-Barr virus (EBV) IgA and IgG antibodies in serum from nasopharyngeal carcinoma (NPC) patients are well-established markers for EBV-positive NPC. Luminex-based multiplex serology can analyze antibodies to multiple antigens simultaneously; however, the detection of both IgA and IgG antibodies requires separate measurements. Here we describe the development and validation of a novel duplex multiplex serology assay, which can analyze IgA and IgG antibodies against several antigens simultaneously. Secondary antibody/dye combinations, as well as serum dilution factors, were optimized, and 98 NPC cases matched to 142 controls from the Head and Neck 5000 study (HN5000) were assessed and compared to data previously generated in separate IgA and IgG multiplex assays. EBER in situ hybridization (EBER-ISH) data available for 41 tumors was used to calibrate antigen-specific cut-offs using receiver operating characteristic (ROC) analysis with a prespecified specificity of ≥90%. A directly R-Phycoerythrin-labeled IgG antibody in combination with a biotinylated IgA antibody and streptavidin-BV421 reporter conjugate was able to quantify both IgA and IgG antibodies in a duplex reaction in a 1:1000 serum dilution. The combined assessment of IgA and IgG antibodies in NPC cases and controls from the HN5000 study yielded similar sensitivities as the separate IgA and IgG multiplex assays (all > 90%), and the duplex serological multiplex assay was able to unequivocally define the EBV-positive NPC cases (AUC = 1). In conclusion, the simultaneous detection of IgA and IgG antibodies provides an alternative for the separate IgA/IgG antibody quantification and may present a promising approach for larger NPC screening studies in NPC endemic areas.
Surgery for Sporadic Primary Hyperparathyroidism: Evolution over the Last Twenty Years in a Monocentric Setting
Authors: Giudici Francesco , Fortuna Laura , Russo Edda , Badii Benedetta , Coratti Francesco , Staderini Fabio , Morandi Alessio , Sparano Clotilde , Petrone Luisa , Cianchi Fabio , Perigli Giuliano
Published: May 2023

The sporadic parathyroid pathology of surgical interest is primarily limited to lesions that are the cause of hormonal hyperfunction (primary hyperparathyroidism). In recent years, parathyroid surgery has evolved significantly, and numerous minimally invasive parathyroidectomy techniques have been developed. In this study, we describe a single-center and well-documented case series of sporadic primary hyperparathyroidism, surgically treated by a single operator in the Endocrine Surgery Unit of the Surgical Clinic of the University of Florence-Careggi University Hospital, recorded and updated in a dedicated database that embraces the entire evolutionary timeframe of parathyroid surgery. From January 2000 to May 2020, 504 patients with a clinical and instrumental diagnosis of hyperparathyroidism were included in the study. The patients were divided into two groups, based on the application of intraoperative parathyroid hormone (ioPTH). The analysis shows that the use of ioPTH with the rapid method could be ineffective in helping surgeons in primary operations, especially when ultrasound and scintiscan are concordant. The advantages obtained by not using intraoperative PTH are not only economic. In fact, our data shows shorter operating and general anesthesia times and hospital stays, having an important impact on patient biological commitment. Furthermore, the significant reduction in operating time makes it possible to almost triple the volume of activity in the same unit of time available, with an undeniable advantage for the reduction of waiting lists. In recent years, minimally invasive approaches have allowed surgeons to reach the best compromise between invasiveness and aesthetic results.
Current Approaches for the Curative-Intent Surgical Treatment of Pancreatic Ductal Adenocarcinoma
Authors: Słodkowski Maciej , Wroński Marek , Karkocha Dominika , Kraj Leszek , Śmigielska Kaja , Jachnis Aneta
Published: May 2023

Radical resection is the only curative treatment for pancreatic cancer. However, only up to 20% of patients are considered eligible for surgical resection at the time of diagnosis. Although upfront surgery followed by adjuvant chemotherapy has become the gold standard of treatment for resectable pancreatic cancer there are numerous ongoing trials aiming to compare the clinical outcomes of various surgical strategies (e.g., upfront surgery or neoadjuvant treatment with subsequent resection). Neoadjuvant treatment followed by surgery is considered the best approach in borderline resectable pancreatic tumors. Individuals with locally advanced disease are now candidates for palliative chemo- or chemoradiotherapy; however, some patients may become eligible for resection during the course of such treatment. When metastases are found, the cancer is qualified as unresectable. It is possible to perform radical pancreatic resection with metastasectomy in selected cases of oligometastatic disease. The role of multi-visceral resection, which involves reconstruction of major mesenteric veins, is well known. Nonetheless, there are some controversies in terms of arterial resection and reconstruction. Researchers are also trying to introduce personalized treatments. The careful, preliminary selection of patients eligible for surgery and other therapies should be based on tumor biology, among other factors. Such selection may play a key role in improving survival rates in patients with pancreatic cancer.
Surgical Anatomy and Approaches of the Anterior Cranial Fossa from a Transcranial and Endonasal Perspective
Authors: Plou Pedro , Serioli Simona , Leonel Luciano C. P. C. , Alexander A. Yohan , Agosti Edoardo , Vilany Larissa , Graepel Stephen , Choby Garret , Pinheiro-Neto Carlos D. , Peris-Celda Maria
Published: May 2023

The anterior cranial fossa (ACF) is a complex anatomical region that can be affected by a broad spectrum of pathology. For the surgical treatment of these lesions, many approaches have been described, each of them with different scope and potential surgical complications, often associated with significant morbidity. Traditionally, tumors involving the ACF have been operated by transcranial approaches; however, in the last two decades, endoscopic endonasal approaches (EEAs) have been gaining popularity. In this work, the authors review and describe the anatomical aspects of the ACF and the technical nuances of transcranial and endoscopic approaches for tumors located in this region. Four approaches were performed in embalmed cadaveric specimens and the key steps were documented. Four illustrative cases of ACF tumors were selected to demonstrate the clinical application of anatomical and technical knowledge, which are essential in the preoperative decision-making process.
Female Sex but Not Oestrogen Receptor Expression Predicts Survival in Advanced Gastroesophageal Adenocarcinoma—A Post-hoc Analysis of the GO2 Trial
Authors: Baxter Mark A. , Spender Lindsay C. , Walsh Shaun , Bray Susan , Skinner Gemma , King Sharon , Hall Peter S. , Seymour Matthew J. , Petty Russell D. ,   on behalf of the GO2 Investigators
Published: May 2023

Gastroesophageal adenocarcinoma is a disease of older adults that is associated with a very poor prognosis. It is less common and has better outcomes in females. The reason for this is unknown but may relate to signalling via the main oestrogen receptors (ER) α and β. In this study, we sought to investigate this using the GO2 clinical trial patient cohort. GO2 recruited older and/or frail patients with advanced gastroesophageal cancer. Immunohistochemistry was performed on tumour samples from 194 patients. The median age of the population was 76 years (range 52–90), and 25.3% were female. Only one (0.5%) tumour sample was positive for ERα, compared to 70.6% for ERβ expression. There was no survival impact according to ERβ expression level. Female sex and younger age were associated with lower ERβ expression. Female sex was also associated with improved overall survival. To our knowledge, this is the largest study worldwide of ER expression in a cohort of patients with advanced gastroesophageal adenocarcinoma. It is also unique, given the age of the population. We have demonstrated that female sex is associated with better survival outcomes with palliative chemotherapy but that this does not appear to be related to ER IHC expression. The differing ER expression according to age supports the concept of a different disease biology with age.
A Non-Canonical Role for the Glycosyltransferase Enzyme UGT2B17 as a Novel Constituent of the B Cell Receptor Signalosome
Authors: Wagner Antoine , Rouleau Michèle , Villeneuve Lyne , Le Trang , Peltier Cheryl , Allain Éric P. , Beaudoin Caroline , Tremblay Sophie , Courtier Fréderic , Nguyen Van Long Flora , Laverdière Isabelle , Lévesque Éric , Banerji Versha , Vanura Katrina , Guillemette Chantal
Published: May 2023

In chronic lymphocytic leukemia (CLL), an elevated glycosyltransferase UGT2B17 expression (UGT2B17HI) identifies a subgroup of patients with shorter survival and poor drug response. We uncovered a mechanism, possibly independent of its enzymatic function, characterized by an enhanced expression and signaling of the proximal effectors of the pro-survival B cell receptor (BCR) pathway and elevated Bruton tyrosine kinase (BTK) phosphorylation in B-CLL cells from UGT2B17HI patients. A prominent feature of B-CLL cells is the strong correlation of UGT2B17 expression with the adverse marker ZAP70 encoding a tyrosine kinase that promotes B-CLL cell survival. Their combined high expression levels in the treatment of naïve patients further defined a prognostic group with the highest risk of poor survival. In leukemic cells, UGT2B17 knockout and repression of ZAP70 reduced proliferation, suggesting that the function of UGT2B17 might involve ZAP70. Mechanistically, UGT2B17 interacted with several kinases of the BCR pathway, including ZAP70, SYK, and BTK, revealing a potential therapeutic vulnerability. The dual SYK and JAK/STAT6 inhibitor cerdulatinib most effectively compromised the proliferative advantage conferred by UGT2B17 compared to the selective BTK inhibitor ibrutinib. Findings point to an oncogenic role for UGT2B17 as a novel constituent of BCR signalosome also connected with microenvironmental signaling.
Vessel-on-a-Chip: A Powerful Tool for Investigating Endothelial COVID-19 Fingerprints
Authors: Shevchuk Oksana , Palii Svitlana , Pak Anastasiia , Chantada Nuria , Seoane Nuria , Korda Mykhaylo , Campos-Toimil Manuel , Álvarez Ezequiel
Published: May 2023

Coronavirus disease (COVID-19) causes various vascular and blood-related reactions, including exacerbated responses. The role of endothelial cells in this acute response is remarkable and may remain important beyond the acute phase. As we move into a post-COVID-19 era (where most people have been or will be infected by the SARS-CoV-2 virus), it is crucial to define the vascular consequences of COVID-19, including the long-term effects on the cardiovascular system. Research is needed to determine whether chronic endothelial dysfunction following COVID-19 could lead to an increased risk of cardiovascular and thrombotic events. Endothelial dysfunction could also serve as a diagnostic and therapeutic target for post-COVID-19. This review covers these topics and examines the potential of emerging vessel-on-a-chip technology to address these needs. Vessel-on-a-chip would allow for the study of COVID-19 pathophysiology in endothelial cells, including the analysis of SARS-CoV-2 interactions with endothelial function, leukocyte recruitment, and platelet activation. “Personalization” could be implemented in the models through induced pluripotent stem cells, patient-specific characteristics, or genetic modified cells. Adaptation for massive testing under standardized protocols is now possible, so the chips could be incorporated for the personalized follow-up of the disease or its sequalae (long COVID) and for the research of new drugs against COVID-19.
The Activity of Natural Polymorphic Variants of Human DNA Polymerase β Having an Amino Acid Substitution in the Transferase Domain
Authors: Kladova Olga A. , Tyugashev Timofey E. , Mikushina Elena S. , Kuznetsov Nikita A. , Novopashina Daria S. , Kuznetsova Aleksandra A.
Published: May 2023

To maintain the integrity of the genome, there is a set of enzymatic systems, one of which is base excision repair (BER), which includes sequential action of DNA glycosylases, apurinic/apyrimidinic endonucleases, DNA polymerases, and DNA ligases. Normally, BER works efficiently, but the enzymes themselves (whose primary function is the recognition and removal of damaged bases) are subject to amino acid substitutions owing to natural single-nucleotide polymorphisms (SNPs). One of the enzymes in BER is DNA polymerase β (Polβ), whose function is to fill gaps in DNA with complementary dNMPs. It is known that many SNPs can cause an amino acid substitution in this enzyme and a significant decrease in the enzymatic activity. In this study, the activity of four natural variants of Polβ, containing substitution E154A, G189D, M236T, or R254I in the transferase domain, was analyzed using molecular dynamics simulations and pre-steady-state kinetic analyses. It was shown that all tested substitutions lead to a significant reduction in the ability to form a complex with DNA and with incoming dNTP. The G189D substitution also diminished Polβ catalytic activity. Thus, a decrease in the activity of studied mutant forms may be associated with an increased risk of damage to the genome.
Intra- and Juxta-Articular Osteoid Osteoma Mimicking Arthritis: Case Series and Literature Review
Authors: Civino Adele , Diomeda Federico , Giordano Luca , Damasio Maria Beatrice , Perrone Sandra , Gallizzi Romina , Ravelli Angelo , Piscitelli Prisco , Maggio Maria Cristina
Published: May 2023

Background: Intra- and juxta-articular osteoid osteomas are rare, representing less than 10% of all osteomas. Compared to the classic diaphyseal or metaphyseal site of long bones, they often have an atypical onset, a longest diagnostic delay, and frequent initial misdiagnoses, with pictures that can mimic inflammatory monoarthritis. We aimed to describe a case series, and to provide a literature review of this uncommon and misleading tumor location. Methods: We performed a retrospective analysis of patients referred to three pediatric rheumatology centers, with a final diagnosis of articular osteoid osteoma. A review of the literature was additionally conducted. Results: We included 10 patients with a mean age of 14 years. All patients with unusual sites (olecranon fossa, lumbar vertebra, distal phalanx of the toe, fibula) had a misdiagnosis, and cases with initial suspicion of monoarthritis had the longest diagnostic delay, up to 24 months. The literature review confirms the significant risk of misdiagnosis, and an average time from symptom onset to diagnosis ranging from 0.4 to 1.8 years. Conclusions: Articular osteoid osteoma may mimic arthritis, especially in adolescence. Knowledge of the atypical forms of presentation, and of the clinical and radiological pitfalls, reduces the risk of diagnostic error.