bluuebunny/crossref_metadata_2025 huggingface dataset:
Changing Threshold-Based Segmentation Has No Relevant Impact on Semi-Quantification in the Context of Structured Reporting for PSMA-PET/CT
Authors: Mihatsch Patrick W. , Beissert Matthias , Pomper Martin G. , Bley Thorsten A. , Seitz Anna K. , Kübler Hubert , Buck Andreas K. , Rowe Steven P. , Serfling Sebastian E. , Hartrampf Philipp E. , Werner Rudolf A.
Published: January 2022

Prostate-specific membrane antigen (PSMA)-directed positron emission tomography/computed tomography (PET/CT) is increasingly utilized for staging of men with prostate cancer (PC). To increase interpretive certainty, the standardized PSMA reporting and data system (RADS) has been proposed. Using PSMA-RADS, we characterized lesions in 18 patients imaged with 18F-PSMA-1007 PET/CT for primary staging and determined the stability of semi-quantitative parameters. Six hundred twenty-three lesions were categorized according to PSMA-RADS and manually segmented. In this context, PSMA-RADS-3A (soft-tissue) or -3B (bone) lesions are defined as being indeterminate for the presence of PC. For PMSA-RADS-4 and -5 lesions; however, PC is highly likely or almost certainly present [with further distinction based on absence (PSMA-RADS-4) or presence (PSMA-RADS-5) of correlative findings on CT]. Standardized uptake values (SUVmax, SUVpeak, SUVmean) were recorded, and volumetric parameters [PSMA-derived tumor volume (PSMA-TV); total lesion PSMA (TL-PSMA)] were determined using different maximum intensity thresholds (MIT) (40 vs. 45 vs. 50%). SUVmax was significantly higher in PSMA-RADS-5 lesions compared to all other PSMA-RADS categories (p ≤ 0.0322). In particular, the clinically challenging PSMA-RADS-3A lesions showed significantly lower SUVmax and SUVpeak compared to the entire PSMA-RADS-4 or -5 cohort (p < 0.0001), while for PSMA-RADS-3B this only applies when compared to the entire PSMA-RADS-5 cohort (p < 0.0001), but not to the PSMA-RADS-4 cohort (SUVmax, p = 0.07; SUVpeak, p = 0.08). SUVmean (p = 0.30) and TL-PSMA (p = 0.16) in PSMA-RADS-5 lesions were not influenced by changing the MIT, while PSMA-TV showed significant differences when comparing 40 vs. 50% MIT (p = 0.0066), which was driven by lymph nodes (p = 0.0239), but not bone lesions (p = 0.15). SUVmax was significantly higher in PSMA-RADS-5 lesions compared to all other PSMA-RADS categories in 18F-PSMA-1007 PET/CT. As such, the latter parameter may assist the interpreting molecular imaging specialist in assigning the correct PSMA-RADS score to sites of disease, thereby increasing diagnostic certainty. In addition, changes of the MIT in PSMA-RADS-5 lesions had no significant impact on SUVmean and TL-PSMA in contrast to PSMA-TV.
Quantitative Analysis of SPECT-CT Data in Metastatic Breast Cancer Patients—The Clinical Significance
Authors: Gherghe Mirela , Mutuleanu Mario-Demian , Stanciu Adina Elena , Irimescu Ionela , Lazar Alexandra , Bacinschi Xenia , Anghel Rodica Maricela
Published: January 2022

Purpose: To assess the potential added value of the SPECT-CT quantitative analysis in metastatic breast cancer lesions detection and differentiation from degenerative lesions. Methods: This prospective monocentric study was conducted on 70 female patients who underwent SPECT-CT bone scans using 99mTc–HDP that identified the presence of metastatic bone lesions and degenerative lesions in each patient. Once the lesions were identified, a quantitative analysis of radiotracer uptake was conducted. The highest one to five SUVmax values for both metastatic and degenerative bone lesions were identified in each patient and the data were then statistically analyzed. Results: The SUVmax value was significantly higher in metastatic bone lesions than in degenerative lesions (p < 0.001). The diagnostic accuracy of SPECT-CT quantitative data analysis revealed a sensitivity of 91.5% and a specificity of 93.3% at a cut-off value of the SUVmax of 16.6 g/mL. Conclusion: Quantitative analysis performed using SPECT-CT data can improve the diagnostic accuracy in differentiating between metastatic bone lesions and degenerative lesions, thus leading to appropriate treatment and better follow-up in metastatic breast cancer patients.
The Antitumor Effect of Caffeic Acid Phenethyl Ester by Downregulating Mucosa-Associated Lymphoid Tissue 1 via AR/p53/NF-κB Signaling in Prostate Carcinoma Cells
Authors: Chang Kang-Shuo , Tsui Ke-Hung , Hsu Shu-Yuan , Sung Hsin-Ching , Lin Yu-Hsiang , Hou Chen-Pang , Yang Pei-Shan , Chen Chien-Lun , Feng Tsui-Hsia , Juang Horng-Heng
Published: January 2022

Caffeic acid phenethyl ester (CAPE), a honeybee propolis-derived bioactive ingredient, has not been extensively elucidated regarding its effect on prostate cancer and associated mechanisms. The mucosa-associated lymphoid tissue 1 gene (MALT1) modulates NF-κB signal transduction in lymphoma and non-lymphoma cells. We investigated the functions and regulatory mechanisms of CAPE in relation to MALT1 in prostate carcinoma cells. In p53- and androgen receptor (AR)-positive prostate carcinoma cells, CAPE downregulated AR and MALT1 expression but enhanced that of p53, thus decreasing androgen-induced activation of MALT1 and prostate-specific antigen expressions. p53 downregulated the expression of MALT in prostate carcinoma cells through the putative consensus and nonconsensus p53 response elements. CAPE downregulated MALT1 expression and thus inhibited NF-κB activity in p53- and AR-negative prostate carcinoma PC-3 cells, eventually reducing cell proliferation, invasion, and tumor growth in vitro and in vivo. CAPE induced the ERK/JNK/p38/AMPKα1/2 signaling pathways; however, pretreatment with the corresponding inhibitors of MAPK or AMPK1/2 did not inhibit the CAPE effect on MALT1 blocking in PC-3 cells. Our findings verify that CAPE is an effective antitumor agent for human androgen-dependent and -independent prostate carcinoma cells in vitro and in vivo through the inhibition of MALT1 expression via the AR/p53/NF-κB signaling pathways.
Canine Oral Melanoma Genomic and Transcriptomic Study Defines Two Molecular Subgroups with Different Therapeutical Targets
Authors: Prouteau Anais , Mottier Stephanie , Primot Aline , Cadieu Edouard , Bachelot Laura , Botherel Nadine , Cabillic Florian , Houel Armel , Cornevin Laurence , Kergal Camille , Corre Sébastien , Abadie Jérôme , Hitte Christophe , Gilot David , Lindblad-Toh Kerstin , André Catherine , Derrien Thomas , Hedan Benoit
Published: January 2022

Mucosal melanoma (MM) is a rare, aggressive clinical cancer. Despite recent advances in genetics and treatment, the prognosis of MM remains poor. Canine MM offers a relevant spontaneous and immunocompetent model to decipher the genetic bases and explore treatments for MM. We performed an integrative genomic and transcriptomic analysis of 32 canine MM samples, which identified two molecular subgroups with a different microenvironment and structural variant (SV) content. The overexpression of genes related to the microenvironment and T-cell response was associated with tumors harboring a lower content of SVs, whereas the overexpression of pigmentation-related pathways and oncogenes, such as TERT, was associated with a high SV burden. Using whole-genome sequencing, we showed that focal amplifications characterized complex chromosomal rearrangements targeting oncogenes, such as MDM2 or CDK4, and a recurrently amplified region on canine chromosome 30. We also demonstrated that the genes TRPM7, GABPB1, and SPPL2A, located in this CFA30 region, play a role in cell proliferation, and thus, may be considered as new candidate oncogenes for human MM. Our findings suggest the existence of two MM molecular subgroups that may benefit from dedicated therapies, such as immune checkpoint inhibitors or targeted therapies, for both human and veterinary medicine.
Influence of the Computer-Aided Decision Support System Design on Ultrasound-Based Breast Cancer Classification
Authors: Magnuska Zuzanna Anna , Theek Benjamin , Darguzyte Milita , Palmowski Moritz , Stickeler Elmar , Schulz Volkmar , Kießling Fabian
Published: January 2022

Automation of medical data analysis is an important topic in modern cancer diagnostics, aiming at robust and reproducible workflows. Therefore, we used a dataset of breast US images (252 malignant and 253 benign cases) to realize and compare different strategies for CAD support in lesion detection and classification. Eight different datasets (including pre-processed and spatially augmented images) were prepared, and machine learning algorithms (i.e., Viola–Jones; YOLOv3) were trained for lesion detection. The radiomics signature (RS) was derived from detection boxes and compared with RS derived from manually obtained segments. Finally, the classification model was established and evaluated concerning accuracy, sensitivity, specificity, and area under the Receiver Operating Characteristic curve. After training on a dataset including logarithmic derivatives of US images, we found that YOLOv3 obtains better results in breast lesion detection (IoU: 0.544 ± 0.081; LE: 0.171 ± 0.009) than the Viola–Jones framework (IoU: 0.399 ± 0.054; LE: 0.096 ± 0.016). Interestingly, our findings show that the classification model trained with RS derived from detection boxes and the model based on the RS derived from a gold standard manual segmentation are comparable (p-value = 0.071). Thus, deriving radiomics signatures from the detection box is a promising technique for building a breast lesion classification model, and may reduce the need for the lesion segmentation step in the future design of CAD systems.
Regulation of Bcl-2 Family Proteins in Estrogen Receptor-Positive Breast Cancer and Their Implications in Endocrine Therapy
Authors: Kawiak Anna , Kostecka Anna
Published: January 2022

Estrogen receptor (ER)-positive breast cancer accounts for around two-thirds of breast cancer occurrences, with endocrine therapy serving as first-line therapy in most cases. Targeting estrogen signaling pathways, which play a central role in regulating ER+ breast cell proliferation and survival, has proven to improve patient outcomes. However, despite the undeniable advantages of endocrine therapy, a subset of breast cancer patients develop acquired or intrinsic resistance to ER-targeting agents, limiting their efficacy. The activation of downstream ER signaling pathways upregulates pro-survival mechanisms that have been shown to influence the response of cells to endocrine therapy. The Bcl-2 family proteins play a central role in cell death regulation and have been shown to contribute to endocrine therapy resistance, supporting the survival of breast cancer cells and enhancing cell death evasion. Due to the overexpression of anti-apoptotic Bcl-2 proteins in ER-positive breast cancer, the role of these proteins as potential targets in hormone-responsive breast cancer is growing in interest. In particular, recent advances in the development of BH3 mimetics have enabled their evaluation in preclinical studies with ER+ breast cancer models, and BH3 mimetics have entered early ER+ breast cancer clinical trials. This review summarizes the molecular mechanisms underlying the regulation of Bcl-2 family proteins in ER+ breast cancer. Furthermore, an overview of recent advances in research regarding the efficacy of BH3 mimetics in ER+ breast cancer has been provided.
Recurrent Spliceosome Mutations in Cancer: Mechanisms and Consequences of Aberrant Splice Site Selection
Authors: Niño Carlos , Scotto di Perrotolo Rossella , Polo Simona
Published: January 2022

Splicing alterations have been widely documented in tumors where the proliferation and dissemination of cancer cells is supported by the expression of aberrant isoform variants. Splicing is catalyzed by the spliceosome, a ribonucleoprotein complex that orchestrates the complex process of intron removal and exon ligation. In recent years, recurrent hotspot mutations in the spliceosome components U1 snRNA, SF3B1, and U2AF1 have been identified across different tumor types. Such mutations in principle are highly detrimental for cells as all three spliceosome components are crucial for accurate splice site selection: the U1 snRNA is essential for 5′ splice site recognition, and SF3B1 and U2AF1 are important for 3′ splice site selection. Nonetheless, they appear to be selected to promote specific types of cancers. Here, we review the current molecular understanding of these mutations in cancer, focusing on how they influence splice site selection and impact on cancer development.
Breast Cancer Tumor Microenvironment and Molecular Aberrations Hijack Tumoricidal Immunity
Authors: Lin Huey-Jen , Liu Yingguang , Lofland Denene , Lin Jiayuh
Published: January 2022

Breast cancer is the most common malignancy among females in western countries, where women have an overall lifetime risk of >10% for developing invasive breast carcinomas. It is not a single disease but is composed of distinct subtypes associated with different clinical outcomes and is highly heterogeneous in both the molecular and clinical aspects. Although tumor initiation is largely driven by acquired genetic alterations, recent data suggest microenvironment-mediated immune evasion may play an important role in neoplastic progression. Beyond surgical resection, radiation, and chemotherapy, additional therapeutic options include hormonal deactivation, targeted-signaling pathway treatment, DNA repair inhibition, and aberrant epigenetic reversion. Yet, the fatality rate of metastatic breast cancer remains unacceptably high, largely due to treatment resistance and metastases to brain, lung, or bone marrow where tumor bed penetration of therapeutic agents is limited. Recent studies indicate the development of immune-oncological therapy could potentially eradicate this devastating malignancy. Evidence suggests tumors express immunogenic neoantigens but the immunity towards these antigens is frequently muted. Established tumors exhibit immunological tolerance. This tolerance reflects a process of immune suppression elicited by the tumor, and it represents a critical obstacle towards successful antitumor immunotherapy. In general, immune evasive mechanisms adapted by breast cancer encompasses down-regulation of antigen presentations or recognition, lack of immune effector cells, obstruction of anti-tumor immune cell maturation, accumulation of immunosuppressive cells, production of inhibitory cytokines, chemokines or ligands/receptors, and up-regulation of immune checkpoint modulators. Together with altered metabolism and hypoxic conditions, they constitute a permissive tumor microenvironment. This article intends to discern representative incidents and to provide potential innovative therapeutic regimens to reinstate tumoricidal immunity.
Radiomics-Based Detection of Radionecrosis Using Harmonized Multiparametric MRI
Authors: Acquitter Clément , Piram Lucie , Sabatini Umberto , Gilhodes Julia , Moyal Cohen-Jonathan Elizabeth , Ken Soleakhena , Lemasson Benjamin
Published: January 2022

In this study, a radiomics analysis was conducted to provide insights into the differentiation of radionecrosis and tumor progression in multiparametric MRI in the context of a multicentric clinical trial. First, the sensitivity of radiomic features to the unwanted variability caused by different protocol settings was assessed for each modality. Then, the ability of image normalization and ComBat-based harmonization to reduce the scanner-related variability was evaluated. Finally, the performances of several radiomic models dedicated to the classification of MRI examinations were measured. Our results showed that using radiomic models trained on harmonized data achieved better predictive performance for the investigated clinical outcome (balanced accuracy of 0.61 with the model based on raw data and 0.72 with ComBat harmonization). A comparison of several models based on information extracted from different MR modalities showed that the best classification accuracy was achieved with a model based on MR perfusion features in conjunction with clinical observation (balanced accuracy of 0.76 using LASSO feature selection and a Random Forest classifier). Although multimodality did not provide additional benefit in predictive power, the model based on T1-weighted MRI before injection provided an accuracy close to the performance achieved with perfusion.
Toward Tumor Fight and Tumor Microenvironment Remodeling: PBA Induces Cell Cycle Arrest and Reduces Tumor Hybrid Cells’ Pluripotency in Bladder Cancer
Authors: Rubio Carolina , Avendaño-Ortiz José , Ruiz-Palomares Raquel , Karaivanova Viktoriya , Alberquilla Omaira , Sánchez-Domínguez Rebeca , Casalvilla-Dueñas José Carlos , Montalbán-Hernández Karla , Lodewijk Iris , Rodríguez-Izquierdo Marta , Munera-Maravilla Ester , Nunes Sandra P. , Suárez-Cabrera Cristian , Pérez-Crespo Miriam , Martínez Víctor G. , Morales Lucía , Pérez-Escavy Mercedes , Alonso-Sánchez Miguel , Lozano-Rodríguez Roberto , Cueto Francisco J. , Aguirre Luis A. , Guerrero-Ramos Félix , Paramio Jesús M. , López-Collazo Eduardo , Dueñas Marta
Published: January 2022

Bladder cancer (BC) is the second most frequent cancer of the genitourinary system. The most successful therapy since the 1970s has consisted of intravesical instillations of Bacillus Calmette–Guérin (BCG) in which the tumor microenvironment (TME), including macrophages, plays an important role. However, some patients cannot be treated with this therapy due to comorbidities and severe inflammatory side effects. The overexpression of histone deacetylases (HDACs) in BC has been correlated with macrophage polarization together with higher tumor grades and poor prognosis. Herein we demonstrated that phenylbutyrate acid (PBA), a HDAC inhibitor, acts as an antitumoral compound and immunomodulator. In BC cell lines, PBA induced significant cell cycle arrest in G1, reduced stemness markers and increased PD-L1 expression with a corresponding reduction in histone 3 and 4 acetylation patterns. Concerning its role as an immunomodulator, we found that PBA reduced macrophage IL-6 and IL-10 production as well as CD14 downregulation and the upregulation of both PD-L1 and IL-1β. Along this line, PBA showed a reduction in IL-4-induced M2 polarization in human macrophages. In co-cultures of BC cell lines with human macrophages, a double-positive myeloid–tumoral hybrid population (CD11b+EPCAM+) was detected after 48 h, which indicates BC cell–macrophage fusions known as tumor hybrid cells (THC). These THC were characterized by high PD-L1 and stemness markers (SOX2, NANOG, miR-302) as compared with non-fused (CD11b−EPCAM+) cancer cells. Eventually, PBA reduced stemness markers along with BMP4 and IL-10. Our data indicate that PBA could have beneficial properties for BC management, affecting not only tumor cells but also the TME.
Cardiovascular Characteristics of Patients with Genetic Variation in Desmoplakin (DSP)
Authors: Reza Nosheen , de Feria Alejandro , Chowns Jessica L. , Hoffman-Andrews Lily , Vann Laura , Kim Jessica , Marzolf Amy , Owens Anjali Tiku
Published: January 2022

Background: Variants in the desmoplakin (DSP) gene have been recognized in association with the pathogenesis of arrhythmogenic right ventricular cardiomyopathy (ARVC) for nearly 20 years. More recently, genetic variation in DSP has also been associated with left-dominant arrhythmogenic cardiomyopathy. Data regarding the cardiac phenotypes associated with genetic variation in DSP have been largely accumulated from phenotype-first studies of ARVC. Methods: We aimed to evaluate the clinical manifestations of cardiac disease associated with variants in DSP through a genotype-first approach employed in the University of Pennsylvania Center for Inherited Cardiovascular Disease registry. We performed a retrospective study of 19 individuals with “pathogenic” or “likely pathogenic” variants in DSP identified by clinical genetic testing. Demographics and clinical characteristics were collected. Results: Among individuals with disease-causing variants in DSP, nearly 40% had left ventricular enlargement at initial assessment. Malignant arrhythmias were prevalent in this cohort (42%) with a high proportion of individuals undergoing primary and secondary prevention implantable cardioverter defibrillator implantation (68%) and ablation of ventricular arrhythmias (16%). Probands also experienced end-stage heart failure requiring heart transplantation (11%). Conclusions: Our data suggest DSP cardiomyopathy may manifest with a high burden of heart failure and arrhythmic events, highlighting its importance in the pathogenesis of dilated and arrhythmogenic cardiomyopathies. Targeted strategies for diagnosis and risk stratification for DSP cardiomyopathy should be investigated.
Methodologies to Isolate and Purify Clinical Grade Extracellular Vesicles for Medical Applications
Authors: Akbar Asma , Malekian Farzaneh , Baghban Neda , Kodam Sai Priyanka , Ullah Mujib
Published: January 2022

The use of extracellular vesicles (EV) in nano drug delivery has been demonstrated in many previous studies. In this study, we discuss the sources of extracellular vesicles, including plant, salivary and urinary sources which are easily available but less sought after compared with blood and tissue. Extensive research in the past decade has established that the breadth of EV applications is wide. However, the efforts on standardizing the isolation and purification methods have not brought us to a point that can match the potential of extracellular vesicles for clinical use. The standardization can open doors for many researchers and clinicians alike to experiment with the proposed clinical uses with lesser concerns regarding untraceable side effects. It can make it easier to identify the mechanism of therapeutic benefits and to track the mechanism of any unforeseen effects observed.
Role of MicroRNAs and Long Non-Coding RNAs in Sarcopenia
Authors: Lee Jihui , Kang Hara
Published: January 2022

Sarcopenia is an age-related pathological process characterized by loss of muscle mass and function, which consequently affects the quality of life of the elderly. There is growing evidence that non-coding RNAs, including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), play a key role in skeletal muscle physiology. Alterations in the expression levels of miRNAs and lncRNAs contribute to muscle atrophy and sarcopenia by regulating various signaling pathways. This review summarizes the recent findings regarding non-coding RNAs associated with sarcopenia and provides an overview of sarcopenia pathogenesis promoted by multiple non-coding RNA-mediated signaling pathways. In addition, we discuss the impact of exercise on the expression patterns of non-coding RNAs involved in sarcopenia. Identifying non-coding RNAs associated with sarcopenia and understanding the molecular mechanisms that regulate skeletal muscle dysfunction during aging will provide new insights to develop potential treatment strategies.
Nephropathic Cystinosis: Pathogenic Roles of Inflammation and Potential for New Therapies
Authors: Elmonem Mohamed A. , Veys Koenraad R. P. , Prencipe Giusi
Published: January 2022

The activation of several inflammatory pathways has recently been documented in patients and different cellular and animal models of nephropathic cystinosis. Upregulated inflammatory signals interact with many pathogenic aspects of the disease, such as enhanced oxidative stress, abnormal autophagy, inflammatory cell recruitment, enhanced cell death, and tissue fibrosis. Cysteamine, the only approved specific therapy for cystinosis, ameliorates many but not all pathogenic aspects of the disease. In the current review, we summarize the inflammatory mechanisms involved in cystinosis and their potential impact on the disease pathogenesis and progression. We further elaborate on the crosstalk between inflammation, autophagy, and apoptosis, and discuss the potential of experimental drugs for suppressing the inflammatory signals in cystinosis.
Ionic Liquids as Components of Systems for Metal Extraction
Authors: Yudaev Pavel A. , Chistyakov Evgeniy M.
Published: January 2022

This review addresses research and development on the use of ionic liquids as extractants and diluents in the solvent extraction of metals. Primary attention is given to the efficiency and selectivity of metal extraction from industrial wastewater with ionic liquids composed of various cations and anions. The review covers literature sources published in the period of 2010–2021. The bibliography includes 98 references dedicated to research on the extraction and separation of lanthanides (17 sources), actinides (5 sources), heavy metals (35 sources), noble metals, including the platinum group (16 sources), and some other metals.
Sensors to the Diagnostic Assessment of Anticancer and Antimicrobial Therapies Effectiveness by Drugs a with Pyrazine Scaffold
Authors: Domżalska Marta , Dąbrowska Aleksandra M. , Chojnowski Dawid , Makowski Mariusz , Chylewska Agnieszka
Published: January 2022

Treatment with pyrazine derivatives—antituberculosis pyrazinamide (PZA), anticancer bortezomib (BZM), and antifungal pyrazine-2-amidoxime (PAOX) and pyrazine-2-thiocarboxamide (PTCA)—is associated with side effects, as observed in the case of other therapeutic drugs. To prevent the side effects of pyrazine derivatives, researchers are working to develop a universal method that will detect these compounds in body fluids. There is a lack of literature data about voltammetric measurements with poly-L-amino acid-modified GCEs surfaces. The available reports describe the application of various modifications of these electrodes for the detection of different active substances of drugs; however, they do not indicate one particular method for the detection of drugs with a pyrazine skeleton. This research aimed to prepare three types of glassy carbon electrodes (GCEs) with modified surfaces by electropolymerization using 1, 10, and 100 mM solutions of L-glycine (Gly), L-alanine (Ala), L-lysine (Lys), respectively. The poly-amino acid coatings applied on GCE surfaces were analyzed in detail under a three-dimensional (3D) microscope and were used as chemosensors of four pyrazine drugs in stoichiometric tests. The results were compared with the measurements made on an unmodified GCE. To obtain reliable results, the linearity of measurements was also verified in the concentration gradient and appropriate scanning speed was chosen to achieve the most accurate measurements.
Participatory Design of a Medication Module in an Electronic Medical Record for Paediatric Palliative Care: A Think-Aloud Approach with Nurses and Physicians
Authors: Kernebeck Sven , Jux Chantal , Busse Theresa Sophie , Meyer Dorothee , Dreier Larissa Alice , Zenz Daniel , Zernikow Boris , Ehlers Jan Peter
Published: January 2022

Background: Electronic medical records (EMRs) play a key role in improving documentation and quality of care in paediatric palliative care (PPC). Inadequate EMR design can cause incorrect prescription and administration of medications. Due to the fact of complex diseases and the resulting high level of medical complexity, patients in PPC are vulnerable to medication errors. Consequently, involving users in the development process is important. Therefore, the aim of this study was to evaluate the acceptance of a medication module from the perspective of potential users in PPC and to involve them in the development process. Methods: A qualitative observational study was conducted with 10 nurses and four physicians using a concurrent think-aloud protocol and semi-structured qualitative interviews. A qualitative content analysis was applied based on a unified theory of acceptance and use of technology. Results: Requirements from the user’s perspective could be identified as possible influences on acceptance and actual use. Requirements were grouped into the categories “performance expectancies” and “effort expectancies”. Conclusions: The results serve as a basis for further development. Attention should be given to the reduction of display fragmentation, as it decreases cognitive load. Further approaches to evaluation should be taken.
Santulli Procedure Revisited in Congenital Intestinal Malformations and Postnatal Intestinal Injuries: Preliminary Report of Experience
Authors: Vinit Nicolas , Rousseau Véronique , Broch Aline , Khen-Dunlop Naziha , Hachem Taymme , Goulet Olivier , Sarnacki Sabine , Beaudoin Sylvie
Published: January 2022

In our experience, the Santulli procedure (SP) can improve bowel recovery in congenital intestinal malformations, necrotizing enterocolitis (NEC), and bowel perforation. All cases managed at our institution using SP between 2012 and 2017 were included in this study. Forty-one patients underwent SP (median age: 39 (0–335) days, median weight: 2987 (1400–8100) g) for intestinal atresia (51%, two gastroschisis), NEC (29%), midgut volvulus (10%), Hirschsprung’s disease (5%), or bowel perforation (5%), with at least one intestinal suture below the Santulli in 10% of cases. The SP was performed as a primary procedure (57%) or as a double-ileostomy reversal. Anal-stool passing occurred within a median of 9 (2–36) days for 95% of patients, regardless of the diversion level or the underlying disease. All three patients requiring repeated surgery for Santulli dysfunction had presented with stoma prolapse (p < 0.01). Stoma closure was performed after a median of 45 (14–270) days allowing efficient transit after a median of 2 (1–6) days. After a median follow-up of 2.9 (0.7–7.2) years, two patients died (cardiopathy and brain hemorrhage), full oral intake had been achieved in 90% of patients, and all survivors had normal bowel movement. Whether used as primary or secondary surgery, the SP allows rapid recovery of intestinal motility and function.
Fanconi Anemia: Examining Guidelines for Testing All Patients with Hand Anomalies Using a Machine Learning Approach
Authors: Wallner Christoph , Hurst Jane , Behr Björn , Rony Mohammad Abu Tareq , Barabás Anthony , Smith Gill
Published: January 2022

Background: This study investigated the questionable necessity of genetic testing for Fanconi anemia in children with hand anomalies. The current UK guidelines suggest that every child with radial ray dysplasia or a thumb anomaly should undergo further cost intensive investigation for Fanconi anemia. In this study we reviewed the numbers of patients and referral patterns, as well as the financial and service provision implications UK guidelines provide. Methods: Over three years, every patient with thumb or radial ray anomaly referred to our service was tested for Fanconi Anemia. CART Analysis and machine learning techniques using Waikato Environment for Knowledge Analysis were applied to evaluate single clinical features predicting Fanconi anemia. Results: Youden Index and Predictive Summary Index (PSI) scores suggested no clinical significance of hand anomalies associated with Fanconi anemia. CART Analysis and attribute evaluation with Waikato Environment for Knowledge Analysis (WEKA) showed no single feature predictive for Fanconi anemia. Furthermore, none of the positive Fanconi anemia patients in this study had an isolated upper limb anomaly without presenting other features of Fanconi anemia. Conclusion: As a conclusion, this study does not support Fanconi anemia testing for isolated hand abnormalities in the absence of other features associated with this blood disease.
Small Particle DEBIRI TACE as Salvage Therapy in Patients with Liver Dominant Colorectal Cancer Metastasis: Retrospective Analysis of Safety and Outcomes
Authors: Voizard Nicolas , Ni Tiffany , Kiss Alex , Pugash Robyn , Raphael Michael Jonathon , Coburn Natalie , David Elizabeth
Published: January 2022

The aim of this study was to examine the safety and efficacy of 40 µm and 75 µm calibrated irinotecan-eluting beads (DEBIRI-TACE) for the treatment of colorectal cancer metastases. We conducted a retrospective review of 36 patients with unresectable liver metastases from colorectal cancer who were treated with DEBIRI-TACE between 2017 to 2020. Patients who received at least one session of DEBIRI were included in our analysis. A total of 105 DEBIRI sessions were completed. 86% of patients (n = 31) underwent one round of treatment, 14% of patients (n = 5) underwent two distinct rounds of treatment. The majority of patients were discharged the next day (92%, n = 33 patients) with no 30-day post-DEBIRI mortality. Five high-grade adverse events occurred, including longer stay for pain management (n = 2), postembolization syndrome requiring readmission (n = 2), and liver abscess (n = 1). The average survival from diagnosis of metastatic disease was 33.3 months (range 11–95, median 28). Nine of 36 patients are still alive (December 2020) and have an average follow-up time of 36.8 months from T0 (range 12–63, median 39). Small particle DEBIRI is safe and well-tolerated in the salvage setting, with outcomes comparable to that of larger bead sizes.
Multi-Temporal Surface Water Classification for Four Major Rivers from the Peruvian Amazon
Authors: Kalacska Margaret , Arroyo-Mora J. Pablo , Coomes Oliver T. , Takasaki Yoshito , Abizaid Christian
Published: January 2022

We describe a new minimum extent, persistent surface water classification for reaches of four major rivers in the Peruvian Amazon (i.e., Amazon, Napo, Pastaza, Ucayali). These data were generated by the Peruvian Amazon Rural Livelihoods and Poverty (PARLAP) Project which aims to better understand the nexus between livelihoods (e.g., fishing, agriculture, forest use, trade), poverty, and conservation in the Peruvian Amazon over a 35,000 km river network. Previous surface water datasets do not adequately capture the temporal changes in the course of the rivers, nor discriminate between primary main channel and non-main channel (e.g., oxbow lakes) water. We generated the surface water classifications in Google Earth Engine from Landsat TM 5, 7 ETM+, and 8 OLI satellite imagery for time periods from circa 1989, 2000, and 2015 using a hierarchical logical binary classification predominantly based on a modified Normalized Difference Water Index (mNDWI) and shortwave infrared surface reflectance. We included surface reflectance in the blue band and brightness temperature to minimize misclassification. High accuracies were achieved for all time periods (>90%).
Experimental Diagnostics of the Emotional State of Individuals Using External Stimuli and a Model of Neurocognitive Brain Activity
Authors: Petukhov Alexandr Y. , Polevaya Sofia A. , Polevaya Anna V.
Published: January 2022

In this paper, we study ways and methods to diagnose the emotional state of individuals using external audiovisual stimuli and heart telemetry tools. We apply a mathematical model of neurocognitive brain activity developed specifically for this study to interpret the experimental scheme and its results. This experimental technique is based on monitoring and analyzing the dynamics of heart rate variability (HRV), taking into account the particular context and events occurring around the subject of the study. In addition, we provide a brief description of the theory of information images/representations used for the paradigm and interpretation of the experiment. For this study, we viewed the human mind as a one-dimensional potential hole with finite walls of different sizes and an internal potential barrier modeling the border between consciousness and subconsciousness. We also provided the foundations of the mathematical apparatus for this particular view. This experiment allowed us to identify the characteristic markers of influencing external stimuli, which form a foundation for diagnosing the emotional state of an individual.
Incidence of Complicated Appendicitis during the COVID-19 Pandemic versus the Pre-Pandemic Period: A Systematic Review and Meta-Analysis of 2782 Pediatric Appendectomies
Authors: Pogorelić Zenon , Anand Sachit , Žuvela Tomislav , Singh Apoorv , Križanac Zvonimir , Krishnan Nellai
Published: January 2022

Background: The Coronavirus Disease 2019 (COVID-19) pandemic has impacted volume, management strategies and patient outcomes of acute appendicitis. The aim of this systematic review and meta-analysis was to evaluate whether the COVID-19 pandemic resulted in higher incidence of complicated appendicitis in children presenting with acute appendicitis compared to the pre-COVID-19 period. The secondary aim was to investigate the proportion of the patients treated by non-operative management (NOM). Methods: A systematic search of four scientific databases was performed. The search terms used were (coronavirus OR SARS-CoV-2 OR COVID-19 OR novel coronavirus) AND (appendicitis). The inclusion criteria were all patients aged <18 years and diagnosed with acute appendicitis during the COVID-19 and pre-COVID-19 periods. The proportion of children presenting with complicated appendicitis and the proportion of children managed by NOM was compared between the two groups. The Downs and Black scale was used for methodological quality assessment. Results: The present meta-analysis included thirteen studies (twelve retrospective studies and one cross-sectional study). A total of 2782 patients (1239 during the COVID-19 period) were included. A significantly higher incidence of complicated appendicitis (RR = 1.63, 95% CI 1.33–2.01, p < 0.00001) and a significantly higher proportion of children managed via the NOM (RR = 1.95, 95% CI 1.45–2.61, p < 0.00001) was observed in patients during the COVID-19 pandemic when compared to the pre-COVID-19 period. Conclusion: There is a significantly higher incidence of complicated appendicitis in children during the COVID-19 pandemic than in the pre-COVID-19 period. Additionally, a significantly higher proportion of children was managed via the NOM during the pandemic in comparison to the pre-pandemic period.
Ultrasonographic Visualization of the Ovaries to Detect Ovarian Cancer According to Age, Menopausal Status and Body Type
Authors: Pavlik Edward J. , Brekke Emily , Gorski Justin , Baldwin-Branch Lauren , Miller Rachel , DeSimone Christopher P. , Dietrich Charles S. , Gallion Holly S. , Ueland Frederick Rand , van Nagell John R.
Published: January 2022

Because the effects of age, menopausal status, weight and body mass index (BMI) on ovarian detectability by transvaginal ultrasound (TVS) have not been established, we determined their contributions to TVS visualization of the ovaries. A total of 29,877 women that had both ovaries visualized on their first exam were followed over 202,639 prospective TVS exams. All images were reviewed by a physician. While visualization of both ovaries decreased with age, one or both ovaries could be visualized in two of every three women over 80 years of age. Around 93% of pre-menopausal women and ~69% of post-menopausal women had both ovaries visualized. Both ovaries were visualized in ~72% of women weighing over 300 lbs. and in ~70% of women with a BMI over 40. Conclusions: Age had the greatest influence on the visualization of the ovaries. The ovaries can be visualized well past the menopause. Body habitus was not limiting to TVS ovarian imaging, and TVS should be considered capable of imaging one or both ovaries in two of every three women over 80 years of age. Thus, older and obese patients remain good candidates for TVS exams.
Axonemal Symmetry Break, a New Ultrastructural Diagnostic Tool for Primary Ciliary Dyskinesia?
Authors: Blanco-Máñez Rosana , Armengot-Carceller Miguel , Jaijo Teresa , Vera-Sempere Francisco
Published: January 2022

Diagnosis testing for primary ciliary dyskinesia (PCD) requires a combination of investigations that includes study of ciliary beat pattern by high-speed video-microscopy, genetic testing and assessment of the ciliary ultrastructure by transmission electron microscopy (TEM). Historically, TEM was considered to be the “gold standard” for the diagnosis of PCD. However, with the advances in molecular genetic techniques, an increasing number of PCD variants show normal ultrastructure and cannot be diagnosed by TEM. During ultrastructural assessment of ciliary biopsies of patients with suspicion of PCD, we observed an axonemal defect not previously described that affects peripheral doublets tilting. To further characterize this defect of unknown significance, we studied the ciliary axonemes by TEM from both PCD-confirmed patients and patients with other sino-pulmonary diseases. We detected peripheral doublets tilting in all the PCD patients, without any significant difference in the distribution of ciliary beat pattern or mutated gene. This defect was also present in those patients with normal ultrastructure PCD subtypes. We believe that the performance of axonemal asymmetry analysis would be helpful to enhance diagnosis of PCD.
Clinical Utility of Oncuria™, a Multiplexed Liquid Biopsy for the Non-Invasive Detection of Bladder Cancer—A Pilot Study
Authors: Murakami Kaoru , Pagano Ian , Furuya Hideki , Daskivich Timothy , Mori Dave , Rosser Charles J.
Published: January 2022

Oncuria™ is a validated quantitative multiplex immunoassay capable of detecting bladder cancer from a voided urine sample. Herein, we sought to determine whether Oncuria™ affects physicians’ use of non-invasive and invasive diagnostic tests for microhematuria, gross hematuria, and bladder cancer surveillance. We conducted a survey-based study to assess physician management of nine clinical scenarios involving real-world data from patients with gross hematuria, microhematuria, and bladder cancer on surveillance. We randomly sampled 15 practicing urologists and generated data including 135 patient-by-urologist interactions and 2160 decision points. Urologists recommended a selection of diagnostic tests and procedures before and after Oncuria™ results were provided. We assessed changes in provider use of non-invasive and invasive diagnostic tests after Oncuria™ results were provided. Over 90% of all urologists changed their diagnostic behavior in at least one patient case with the addition of Oncuria™ results. The total number of diagnostic procedures was reduced by 31% following the disclosure of a negative Oncuria™ test and 27% following the disclosure of a positive Oncuria™ test. This is pilot study has the potential to shed light on the analysis of our four large multicenter international studies deploying OncuriaTM. The Oncuria™ urine-based test, a molecular diagnostic capable of ruling out the presence of bladder cancer, reduces both unnecessary invasive and non-invasive diagnostics and has the potential to reduce costs and improve patient outcomes.
The Potential Roles of Cervical Plexus Abnormalities in Occipital Neuralgia: An Anatomic Variant Explored
Authors: Mirande Mitchell H. , Smith Heather F.
Published: January 2022

Occipital neuralgia (ON) is a condition defined as a headache characterized by paroxysmal burning and stabbing pain located in the distribution of the greater occipital nerve (GON), lesser occipital nerve (LON), or third occipital nerves (TON). This condition can be severely impairing in symptomatic patients and is known to have numerous etiologies deriving from various origins such as trauma, anatomical abnormalities, tumors, infections, and degenerative changes. This study reports four cases of a previously undescribed anatomical variant in which the (spinal) accessory nerve (SAN) fuses with the LON before piercing the sternocleidomastoid (SCM). The fusion of these two nerves and their route through the SCM points to a potential location for nerve compression within the SCM and, in turn, another potential source of ON. This anatomical presentation has clinical significance as it provides clinicians with another possible cause of ON to consider when diagnosing patients who present with complaints of a headache. Additionally, this study explores the prevalence of piercing anatomy of the LON and GAN and discusses their clinical implications.
Comparing Diagnosis and Treatment of Pulmonary Hypertension Patients at a Pulmonary Hypertension Center versus Community Centers
Authors: Saunders Hollie , Helgeson Scott A. , Abdelrahim Ahmed , Rottman-Pietrzak Kathleen , Reams Victoria , Zeiger Tonya K. , Moss John E. , Burger Charles D.
Published: January 2022

Once patients are diagnosed with pulmonary hypertension it is important to identify the correct diagnostic group as it will have implications on the disease state management. Pulmonary hypertension is increasingly diagnosed and treated in general medical practices; however, evidence-based guidelines recommend evaluation and treatment in pulmonary hypertension centers for accurate diagnosis and appropriate treatment recommendations. We conducted a retrospective cohort study of 509 random patients 18 years and older who were evaluated in our pulmonary hypertension clinic from January 2005 to December 2018. 68.4% (n = 348) had their diagnostic group clarified or changed. Pulmonary hypertension was deemed an incorrect diagnosis in 12.4% (n = 63). A total of 114 patients (22.4%) had been initiated on pulmonary hypertension specific treatment prior to presentation. Pulmonary hypertension specific medication was stopped in 57 (50.0%) cases. The estimated monthly saving of the stopped medication based on wholesale acquisition costs was USD 396,988.05–419,641.05, a monthly saving of USD 6964.70–7362.12 per patient. Evaluation outside of a pulmonary hypertension center may lead to misdiagnosis and inappropriate or inadequate treatment. Pulmonary arterial hypertension directed therapy improves median survival, but inappropriate therapy may cause harm; therefore, patients benefit from a specialized center with multiple resources to secure an accurate diagnosis and tailored treatment for their condition.
A Review of Unmanned System Technologies with Its Application to Aquaculture Farm Monitoring and Management
Authors: Ubina Naomi A. , Cheng Shyi-Chyi
Published: January 2022

This paper aims to provide an overview of the capabilities of unmanned systems to monitor and manage aquaculture farms that support precision aquaculture using the Internet of Things. The locations of aquaculture farms are diverse, which is a big challenge on accessibility. For offshore fish cages, there is a difficulty and risk in the continuous monitoring considering the presence of waves, water currents, and other underwater environmental factors. Aquaculture farm management and surveillance operations require collecting data on water quality, water pollutants, water temperature, fish behavior, and current/wave velocity, which requires tremendous labor cost, and effort. Unmanned vehicle technologies provide greater efficiency and accuracy to execute these functions. They are even capable of cage detection and illegal fishing surveillance when equipped with sensors and other technologies. Additionally, to provide a more large-scale scope, this document explores the capacity of unmanned vehicles as a communication gateway to facilitate offshore cages equipped with robust, low-cost sensors capable of underwater and in-air wireless connectivity. The capabilities of existing commercial systems, the Internet of Things, and artificial intelligence combined with drones are also presented to provide a precise aquaculture framework.
Conducting Causal Analysis by Means of Approximating Probabilistic Truths
Authors: Andrée Bo Pieter Johannes
Published: January 2022

The current paper develops a probabilistic theory of causation using measure-theoretical concepts and suggests practical routines for conducting causal inference. The theory is applicable to both linear and high-dimensional nonlinear models. An example is provided using random forest regressions and daily data on yield spreads. The application tests how uncertainty in short- and long-term inflation expectations interacts with spreads in the daily Bitcoin price. The results are contrasted with those obtained by standard linear Granger causality tests. It is shown that the suggested measure-theoretic approaches do not only lead to better predictive models, but also to more plausible parsimonious descriptions of possible causal flows. The paper concludes that researchers interested in causal analysis should be more aspirational in terms of developing predictive capabilities, even if the interest is in inference and not in prediction per se. The theory developed in the paper provides practitioners guidance for developing causal models using new machine learning methods that have, so far, remained relatively underutilized in this context.