bluuebunny/crossref_metadata_2025 huggingface dataset:
Associations between Heart Rate Variability and Brain Activity during a Working Memory Task: A Preliminary Electroencephalogram Study on Depression and Anxiety Disorder
Authors: Lee Deokjong , Kwon Woohyun , Heo Jaeseok , Park Jin Young
Published: January 2022

Heart rate variability (HRV) has been suggested to reflect executive function and related neural activity. Executive dysfunction has been suggested to play an important role in the pathophysiology of emotional disorders. The purpose of this study was to investigate whether HRV showed a significant correlation with electroencephalogram (EEG) during a working memory performance in patients with depressive or anxiety disorder. A retrospective analysis was conducted with data from 61 patients with depressive disorder (43 women and 18 men) and 59 patients with anxiety disorder (35 women and 24 men). HRV was measured in the resting state, and EEG was recorded in the resting state and during the execution of a working memory task. It was performed in patients with depressive and anxiety disorder, and the paired sample t-test between resting state and task performance, as well as the partial correlation analysis between HRV and EEG, was conducted. Both depressed and anxious patients showed weaker beta relative power during the working memory task compared to the rest period. The resting-state EEG did not correlate with HRV parameters in both groups. In depressed patients, HRV showed a positive correlation with delta power during the task and a negative correlation with beta relative power during the task. In patients with anxiety disorder, HRV showed a significant positive correlation with theta power of the right frontal region during the task. Our results suggest that HRV would be related to executive-function-related neural activity in patients with depressive or anxiety disorder. Future studies with more subjects, including healthy controls, are needed to verify the correlation between HRV and EEG and to come up with a more comprehensive picture of neurobiological changes in emotional disorders.
A Novel SETX Mutation in a Taiwanese Patient with Autosomal Recessive Cerebellar Ataxia Detected by Targeted Next-Generation Sequencing, and a Literature Review
Authors: Chiang Ping-I , Liao Ting-Wei , Chen Chiung-Mei
Published: January 2022

Ataxia with oculomotor apraxia type 2 (AOA2), also known as autosomal recessive spinocerebellar ataxia with axonal neuropathy-2 (SCAN2) (OMIM #606002), is a neurodegenerative disorder characterized by early-onset progressive cerebellar ataxia, polyneuropathy, and elevated levels of alpha-fetoprotein. It is caused by mutations in the SETX (OMIM #608465) gene. The prevalence of this disease is widely varied, from non-existent up to 1/150,000, depending on the region. Until now, no cases of AOA2/SCAN2 have been reported in Taiwan. Methods: Next-generation sequencing was used to detect disease-causing mutations of SETX in a Taiwanese patient presenting with autosomal recessive cerebellar ataxia, polyneuropathy, and elevated alpha-fetoprotein. The candidate mutations were further confirmed by polymerase chain reaction (PCR) and Sanger sequencing. Results: A compound heterozygous mutation of SETX c.6859C > T (p.R2287X) and c.7034-7036del was identified. The c.6859C > T (p.R2287X) has been previously found in a Saudi Arabia family, whereas c.7034-7036del is a novel mutation. Both mutations were predicted by bioinformatics programs to be likely pathogenic (having a damaging effect). We also reviewed the literature to address the reported clinical features of AOA2 from different populations. Conclusions: To our knowledge, we are the first to report a Taiwanese patient with AOA2/SCAN2, a result obtained by utilizing next-generation sequencing. The literature review shows that ataxia, polyneuropathy, and elevated AFP are common features and ocular motor apraxia (OMA) is a variable sign of AOA2 from different populations. OMA is rare and saccadic ocular pursuit and nystagmus are common in East Asian AOA2.
Attachment and the Development of Psychopathology: Introduction to the Special Issue
Authors: Bosmans Guy , Borelli Jessica L.
Published: January 2022

When Bowlby [...]
Environmental Impact on the Epigenetic Mechanisms Underlying Parkinson’s Disease Pathogenesis: A Narrative Review
Authors: Angelopoulou Efthalia , Paudel Yam Nath , Papageorgiou Sokratis G. , Piperi Christina
Published: January 2022

Parkinson’s disease (PD) is the second most common neurodegenerative disorder with an unclear etiology and no disease-modifying treatment to date. PD is considered a multifactorial disease, since both genetic and environmental factors contribute to its pathogenesis, although the molecular mechanisms linking these two key disease modifiers remain obscure. In this context, epigenetic mechanisms that alter gene expression without affecting the DNA sequence through DNA methylation, histone post-transcriptional modifications, and non-coding RNAs may represent the key mediators of the genetic–environmental interactions underlying PD pathogenesis. Environmental exposures may cause chemical alterations in several cellular functions, including gene expression. Emerging evidence has highlighted that smoking, coffee consumption, pesticide exposure, and heavy metals (manganese, arsenic, lead, etc.) may potentially affect the risk of PD development at least partially via epigenetic modifications. Herein, we discuss recent accumulating pre-clinical and clinical evidence of the impact of lifestyle and environmental factors on the epigenetic mechanisms underlying PD development, aiming to shed more light on the pathogenesis and stimulate future research.
Psychopharmacological Treatments for Mental Disorders in Patients with Neuromuscular Diseases: A Scoping Review
Authors: Brusa Chiara , Gadaleta Giulio , D’Alessandro Rossella , Urbano Guido , Vacchetti Martina , Davico Chiara , Vitiello Benedetto , Ricci Federica S. , Mongini Tiziana E.
Published: January 2022

Mental disorders are observed in neuromuscular diseases, especially now that patients are living longer. Psychiatric symptoms may be severe and psychopharmacological treatments may be required. However, very little is known about pharmacotherapy in these conditions. We aimed to summarize the current knowledge on the use of psychopharmacological treatments for mental disorders in patients living with a neuromuscular disease. A scoping review was performed using the methodology of the Joanna Briggs Institute. Four databases were searched from January 2000 to July 2021. Articles were screened based on titles and abstracts. Full-text papers published in peer-reviewed journals in English were selected. Twenty-six articles met eligibility criteria, all being case reports/series focusing on the psychopharmacological control of psychiatric symptoms for the following conditions: myasthenia gravis (n = 11), Duchenne (n = 5) and Becker (n = 3) muscular dystrophy, mitochondrial disorders (n = 3), glycogen storage disease (n = 1), myotonic dystrophy (n = 1), hyperkalemic periodic paralysis (n = 1), and congenital myasthenic syndrome (n = 1). None of the articles provided details on the decision-making process to choose a specific drug/regimen or on follow-up strategies to monitor safety and efficacy. Larger studies showing real-world data would be required to guide consensus-based recommendations, thus improving current standards of care and, ultimately, the quality of life of patients and their families.
The Impact of Health and Social Services on the Quality of Life in Families of Adults with Autism Spectrum Disorder (ASD): A Focus Group Study
Authors: Correale Cinzia , Borgi Marta , Cirulli Francesca , Laghi Fiorenzo , Trimarco Barbara , Ferraro Maurizio , Venerosi Aldina
Published: January 2022

Background: Autism spectrum disorder (ASD) is a complex developmental condition that affects the whole family. The gap between childrens’ needs and their satisfaction, especially regarding what concerns the presence of social and healthcare services, is still a source of burden, particularly after the transition to adulthood. Our study aimed to gather a comprehensive view on how parents of adults with ASD perceive (and interact with) health and social services, and how the provision of care impacts family quality of life with the aim to advise ASD intervention programs. The goal is to identify specific areas of change useful to influence autism intervention strategies so that they more effectively meet the needs of young people with autism and their families. Methods: We conducted two focus groups with parents of young adults with ASD. A semi-structured focus group methodology was adopted. The QoL conceptual framework guided data collection and analysis as part of a directed theory-driven content analysis approach. Results: The lack of structured care pathways and the low level of integration of different services were the main limits reported by parents during the focus group, while a shared positive perception of the experience conducted together as caring families emerged. Conclusions: The experience here reported claims for a greater role of the institutions in order to facilitate the building of networks that are really inclusive for persons with autism in society and to support the implementation of innovative solutions for the welfare system. Furthermore, parents stressed the need for the provision of support to the family.
What These Findings Tell Us. Reply to Kelly et al. What Do These Findings Tell Us? Comment on “Tinella et al. Cognitive Efficiency and Fitness-to-Drive along the Lifespan: The Mediation Effect of Visuospatial Transformations. Brain Sci. 2021, 11, 1028”
Authors: Tinella Luigi , Lopez Antonella , Caffò Alessandro Oronzo , Nardulli Francesco , Grattagliano Ignazio , Bosco Andrea
Published: January 2022

The study of the contribution of spatial transformation skills to driving behavior is a research topic substantiated by scarce evidence. In previous studies, we found that mental rotation and perspective-taking skills have an influence on performance in driving tasks by conveying the distal effects of the general cognitive efficiency on the execution of driving maneuvers. Studies have provided evidence on the relevance of the cognitive processes of encoding, imagined rotation, and spatial orientation in the accuracy of both the vehicle management during stressful driving situations and the acquisition of visual information on the traffic scenario. Results can find applications in both the training and the assessment of fitness to drive, as well as in the study of interaction between the drivers and in-vehicle devices. The lack of cross-validations in path analysis models cannot be assumed, a priori, to be capitalizing on chance and as an example of bad science. The non-replicability of a study should be demonstrated before it is proclaimed. The purpose of this reply was to address the questions raised by Kelly et al. (2022)—that is, “Do these results seem replicable?” and “How do these results advance our understanding of brain function and/or human behavior?”—by providing additional information on the study in question.
Migraine and Neuroticism: A Scoping Review
Authors: Galvez-Sánchez Carmen M. , Montoro Aguilar Casandra I.
Published: January 2022

Headache is the first cause of consultation in neurology, and one of the most frequent reasons for consultation in general medicine. Migraine is one of the most common, prevalent, and socioeconomically impactful disabling primary headache disorders. Neuroticism can be conceptualized as a disposition to suffer anxiety and emotional disorders in general. Neuroticism has been associated with various mental and physical disorders (e.g., chronic pain, depression), including migraine. With the aim to explore in depth the relationship between migraine and neuroticism, and contribute to the understanding of this relation in order to provide a better treatment for migraine patients based on a personalized and more comprehensive approach, a scoping review was performed using PubMed, Scopus, and Web of Science. Databases were searched independently by the two researchers, reaching a final set of 18 articles to be included. The search terms were: migraine and neuroticism. Neuroticism seems to be highly prevalent in migraine patients. Findings reveal that migraine patients with comorbid depression and anxiety showed higher levels of neuroticism. Depression has been associated with an increased risk of transformation from episodic to chronic migraine whereas neuroticism might be a mediator factor. Neuroticism also might be a mediator factor between childhood maltreatment and migraine. The revision conducted confirms that: (1) Migraine patients usually have a higher level of neuroticism and vulnerability to negative affect, compared to non-migraineurs and tension-type headache patients. (2) Neuroticism is associated with migraine. Nonetheless, more research is needed to clarify potential moderators of this relationship and the role of neuroticism itself in this disease. This knowledge might be useful in order to promote a better management of negative emotions as part of intervention programs in migraine.
The Identification, Development, and Evaluation of BIM-ARDM: A BIM-Based AR Defect Management System for Construction Inspections
Authors: May Kieran W. , KC Chandani , Ochoa Jose Jorge , Gu Ning , Walsh James , Smith Ross T. , Thomas Bruce H.
Published: January 2022

This article presents our findings from a three-stage research project, which consists of the identification, development, and evaluation of a defect management Augmented Reality (AR) prototype that incorporates Building Information Modelling (BIM) technologies. Within the first stage, we conducted a workshop with four construction-industry representatives to capture their opinions and perceptions of the potentials and barriers associated with the integration of BIM and AR in the construction industry. The workshop findings led us to the second stage, which consisted of the development of an on-site BIM-based AR defect management (BIM-ARDM) system for construction inspections. Finally, a study was conducted to evaluate BIM-ARDM in comparison to the current paper-based defect management inspection approach employed on construction sites. The findings from the study revealed BIM-ARDM significantly outperformed current approaches in terms of usability, workload, performance, completion time, identifying defects, locating building elements, and assisting the user with the inspection task.
Acknowledgment to Reviewers of C in 2021
Authors:   C Editorial Office
Published: January 2022

Rigorous peer-reviews are the basis of high-quality academic publishing [...]
Single-Cell Sequencing: Current Applications in Precision Onco-Genomics and Cancer Therapeutics
Authors: Mustachio Lisa Maria , Roszik Jason
Published: January 2022

Single-cell sequencing encompasses a variety of technologies that evaluate cells at the genomic, transcriptomic, epigenomic, and proteomic levels. Each of these levels can be split into additional techniques that enable specific and optimized sequencing for a specialized purpose. At the transcriptomic level, single-cell sequencing has been used to understand immune-malignant cell networks, as well as differences between primary versus metastatic tumors. At the genomic and epigenomic levels, single-cell sequencing technology has been used to study genetic mutations involved in tumor evolution or the reprogramming of regulatory elements present in metastasized disease, respectively. Lastly, at the proteomic level, single-cell sequencing has been used to identify biomarkers important for predicting patient prognosis, as well as biomarkers essential for evaluating optimal treatment strategies. Integrated databases and atlases, as a result of large sequencing experiments, provide a vast array of information that can be applied to various studies and accessed by researchers to further answer scientific questions. This review summarizes recent, high-impact literature covering these aspects, as well as single-cell sequencing in the translational setting. Specifically, we review the potential that single-cell sequencing has in the clinic and its implementation in current clinical studies.
Longitudinal Analysis of 1α,25-dihidroxyvitamin D3 and Homocysteine Changes in Colorectal Cancer
Authors: Mühl Dorottya , Herold Magdolna , Herold Zoltan , Hornyák Lilla , Szasz Attila Marcell , Dank Magdolna
Published: January 2022

Background: 1α,25-dihydroxycholecalciferol (1,25(OH)2D3) and homocysteine are known to play a role in the pathophysiology of colorectal cancer (CRC). In health, the two changes are inversely proportional to each other, but little is known about their combined effect in CRC. Methods: The serum 1,25(OH)2D3 and the homocysteine levels of eighty-six CRC patients were measured, who were enrolled into four cohorts based on the presence of metastases (Adj vs. Met) and vitamin D3 supplementation (ND vs. D). Results: 1,25(OH)2D3 was constant (Adj-ND), increased significantly (Adj-D, p = 0.0261), decreased (Met-ND), or returned close to the baseline after an initial increase (Met-D). The longitudinal increase in 1,25(OH)2D3 (HR: 0.9130, p = 0.0111) positively affected the overall survival in non-metastatic CRC, however, this effect was cancelled out in those with metastasis (p = 0.0107). The increase in homocysteine negatively affected both the overall (HR: 1.0940, p = 0.0067) and the progression-free survival (HR: 1.0845, p = 0.0073). Lower 1,25(OH)2D3 and/or higher homocysteine level was characteristic for patients with higher serum lipids, albumin, total protein, white blood cell and platelet count, male sex, and right-sided tumors. No statistically justifiable connection was found between the target variables. Conclusions: A measurement-based titration of vitamin D3 supplementation and better management of comorbidities are recommended for CRC.
Specialized Intercellular Communications via Tunnelling Nanotubes in Acute and Chronic Leukemia
Authors: Allegra Alessandro , Di Gioacchino Mario , Cancemi Gabriella , Casciaro Marco , Petrarca Claudia , Musolino Caterina , Gangemi Sebastiano
Published: January 2022

Effectual cell-to-cell communication is essential to the development and differentiation of organisms, the preservation of tissue tasks, and the synchronization of their different physiological actions, but also to the proliferation and metastasis of tumor cells. Tunneling nanotubes (TNTs) are membrane-enclosed tubular connections between cells that carry a multiplicity of cellular loads, such as exosomes, non-coding RNAs, mitochondria, and proteins, and they have been identified as the main participants in healthy and tumoral cell communication. TNTs have been described in numerous tumors in in vitro, ex vivo, and in vivo models favoring the onset and progression of tumors. Tumor cells utilize TNT-like membranous channels to transfer information between themselves or with the tumoral milieu. As a result, tumor cells attain novel capabilities, such as the increased capacity of metastasis, metabolic plasticity, angiogenic aptitude, and chemoresistance, promoting tumor severity. Here, we review the morphological and operational characteristics of TNTs and their influence on hematologic malignancies’ progression and resistance to therapies, focusing on acute and chronic myeloid and acute lymphoid leukemia. Finally, we examine the prospects and challenges for TNTs as a therapeutic approach for hematologic diseases by examining the development of efficient and safe drugs targeting TNTs.
Assessment of Patient Reported Outcomes (PROs) in Outpatients Taking Oral Anticancer Drugs Included in the Real-Life Oncoral Program
Authors: Collomb Bastien , Dubromel Amélie , Caffin Anne Gaëlle , Herledan Chloé , Larbre Virginie , Baudouin Amandine , Cerutti Ariane , Couturier Laurence , Maire Magali , Karlin Lionel , Maucort-Boulch Delphine , Huot Laure , Dalle Stéphane , Bachy Emmanuel , Ghesquieres Hervé , Salles Gilles , Couraud Sébastien , You Benoit , Freyer Gilles , Trillet-Lenoir Véronique , Ranchon Florence , Rioufol Catherine
Published: January 2022

Background In previous studies, patient-reported outcomes (PROs) have been shown to improve survival in cancer patients. The aim of the present study was to assess symptoms potentially related to adverse events experienced by cancer outpatients treated by oral anticancer agents (OAAs) using PROs. Methods Between September 2018 and May 2019, outpatients starting OAAs were included in a 12-week follow-up to assess 15 symptoms listed in the National Cancer Institute PRO Common Terminology Criteria for Adverse Events, using a 5-point scale of severity or frequency. Patients were requested to alert a referral nurse or pharmacist when they self-assessed high-level (level 3 or 4) symptoms. Results 407 questionnaires were completed by 63 patients in which 2333 symptoms were reported. Almost three-quarters (74.6%) reported at least one high-level symptom. The symptoms that were most commonly experienced were fatigue (>9 in 10 patients; 13.2% of symptoms declared), various psychological disorders (>9 in 10 patients; 28.6% of symptoms declared) and general pain (>8 in 10 patients; 9.4% of symptoms declared). Conclusion PROs are appropriate to detect potential adverse events in cancer outpatients treated by OAAs. This study is the first step for integrating the patient’s perspective in a digital e-health device in routine oncology care.
Biological and Clinical Insight from Analysis of the Tumor B-Cell Receptor Structure and Function in Chronic Lymphocytic Leukemia
Authors: Forconi Francesco , Lanham Stuart A. , Chiodin Giorgia
Published: January 2022

The B-cell receptor (BCR) is essential to the behavior of the majority of normal and neoplastic mature B cells. The identification in 1999 of the two major CLL subsets expressing unmutated immunoglobulin (Ig) variable region genes (U-IGHV, U-CLL) of pre-germinal center origin and poor prognosis, and mutated IGHV (M-CLL) of post-germinal center origin and good prognosis, ignited intensive investigations on structure and function of the tumor BCR. These investigations have provided fundamental insight into CLL biology and eventually the mechanistic rationale for the development of successful therapies targeting BCR signaling. U-CLL and M-CLL are characterized by variable low surface IgM (sIgM) expression and signaling capacity. Variability of sIgM can in part be explained by chronic engagement with (auto)antigen at tissue sites. However, other environmental elements, genetic changes, and epigenetic signatures also contribute to the sIgM variability. The variable levels have consequences on the behavior of CLL, which is in a state of anergy with an indolent clinical course when sIgM expression is low, or pushed towards proliferation and a more aggressive clinical course when sIgM expression is high. Efficacy of therapies that target BTK may also be affected by the variable sIgM levels and signaling and, in part, explain the development of resistance.
An Integrated Epigenomic and Genomic View on Phyllodes and Phyllodes-like Breast Tumors
Authors: Hench Juergen , Vlajnic Tatjana , Soysal Savas Deniz , Obermann Ellen C. , Frank Stephan , Muenst Simone
Published: January 2022

Fibroepithelial lesions (FL) of the breast, in particular, phyllodes tumors (PT) and fibroadenomas, pose a significant diagnostic challenge. There are no generally accepted criteria that distinguish benign, borderline, malignant PT and fibroadenomas. Combined genome-wide DNA methylation and copy number variant (CNV) profiling is an emerging strategy to classify tumors. We compiled a series of patient-derived archival biopsy specimens reflecting the FL spectrum and histological mimickers including clinical follow-up data. DNA methylation and CNVs were determined by well-established microarrays. Comparison of the patterns with a pan-cancer dataset assembled from public resources including “The Cancer Genome Atlas” (TCGA) and “Gene Expression Omnibus” (GEO) suggests that FLs form a methylation class distinct from both control breast tissue as well as common breast cancers. Complex CNVs were enriched in clinically aggressive FLs. Subsequent fluorescence in situ hybridization (FISH) analysis detected respective aberrations in the neoplastic mesenchymal component of FLs only, confirming that the epithelial component is non-neoplastic. Of note, our approach could lead to the elimination of the diagnostically problematic category of borderline PT and allow for optimized prognostic patient stratification. Furthermore, the identified recurrent genomic aberrations such as 1q gains (including MDM4), CDKN2a/b deletions, and EGFR amplifications may inform therapeutic decision-making.
Germline Variants of CYBA and TRPM4 Predispose to Familial Colorectal Cancer
Authors: Zhu Lizhen , Miao Beiping , Dymerska Dagmara , Kuswik Magdalena , Bueno-Martínez Elena , Sanoguera-Miralles Lara , Velasco Eladio A. , Paramasivam Nagarajan , Schlesner Matthias , Kumar Abhishek , Yuan Ying , Lubinski Jan , Bandapalli Obul Reddy , Hemminki Kari , Försti Asta
Published: January 2022

Familial colorectal cancer (CRC) is only partially explained by known germline predisposing genes. We performed whole-genome sequencing in 15 Polish families of many affected individuals, without mutations in known CRC predisposing genes. We focused on loss-of-function variants and functionally characterized them. We identified a frameshift variant in the CYBA gene (c.246delC) in one family and a splice site variant in the TRPM4 gene (c.25–1 G > T) in another family. While both variants were absent or extremely rare in gene variant databases, we identified four additional Polish familial CRC cases and two healthy elderly individuals with the CYBA variant (odds ratio 2.46, 95% confidence interval 0.48–12.69). Both variants led to a premature stop codon and to a truncated protein. Functional characterization of the variants showed that knockdown of CYBA or TRPM4 depressed generation of reactive oxygen species (ROS) in LS174T and HT-29 cell lines. Knockdown of TRPM4 resulted in decreased MUC2 protein production. CYBA encodes a component in the NADPH oxidase system which generates ROS and controls, e.g., bacterial colonization in the gut. Germline CYBA variants are associated with early onset inflammatory bowel disease, supported with experimental evidence on loss of intestinal mucus barrier function due to ROS deficiency. TRPM4 encodes a calcium-activated ion channel, which, in a human colonic cancer cell line, controls calcium-mediated secretion of MUC2, a major component of intestinal mucus barrier. We suggest that the gene defects in CYBA and TRPM4 mechanistically involve intestinal barrier integrity through ROS and mucus biology, which converges in chronic bowel inflammation.
Loss of Neuropilin-2 in Murine Mesenchymal-like Colon Cancer Organoids Causes Mesenchymal-to-Epithelial Transition and an Acquired Dependency on Insulin-Receptor Signaling and Autophagy
Authors: Poghosyan Susanna , Frenkel Nicola , Lentzas Aristeidis , Laoukili Jamila , Rinkes Inne Borel , Kranenburg Onno , Hagendoorn Jeroen
Published: January 2022

Neuropilin-2 (Nrp2), an important regulator of lymphangiogenesis and lymphatic metastasis, has been associated with progression in colorectal cancer (CRC). However, the tumor cell-intrinsic role of Nrp2 in cancer progression is incompletely understood. To address this question, we employed CRISPR-Cas9 technology to generate Nrp2-knockout organoids derived from murine CRC tumors with a mesenchymal phenotype. Transcriptome profiling and tumor tissue analysis showed that Nrp2 loss resulted in mesenchymal-to-epithelial transition (MET), which was accompanied with restored polarity and tight junction stabilization. Signaling pathway analysis revealed that Nrp2-knockout organoids acquire de novo dependency on insulin receptor (IR) signaling and autophagy as alternative survival mechanisms. Combined inhibition of IR signaling and autophagy prevented the stabilization of cell-cell junctions, reduced metabolic activity, and caused profound cell death in Nrp2-knockout organoids. Collectively, the data demonstrate a key role for Nrp2 in maintaining the aggressive phenotype and survival of tumor-derived CRC organoids. The identified connection between Nrp2, insulin receptor signaling and autophagy may guide the development of novel combination-treatment strategies for aggressive CRC.
Systemic Effects Reflected in Specific Biomarker Patterns Are Instrumental for the Paradigm Change in Prostate Cancer Management: A Strategic Paper
Authors: Golubnitschaja Olga , Kubatka Peter , Mazurakova Alena , Samec Marek , Alajati Abdullah , Giordano Frank A. , Costigliola Vincenzo , Ellinger Jörg , Ritter Manuel
Published: January 2022

Prostate cancer (PCa) is reported as the most common malignancy and second leading cause of death in America. In Europe, PCa is considered the leading type of tumour in 28 European countries. The costs of treating PCa are currently increasing more rapidly than those of any other cancer. Corresponding economic burden is enormous, due to an overtreatment of slowly developing disease on one hand and underestimation/therapy resistance of particularly aggressive PCa subtypes on the other hand. The incidence of metastatic PCa is rapidly increasing that is particularly characteristic for young adults. PCa is a systemic multi-factorial disease resulting from an imbalanced interplay between risks and protective factors. Sub-optimal behavioural patterns, abnormal stress reactions, imbalanced antioxidant defence, systemic ischemia and inflammation, mitochondriopathies, aberrant metabolic pathways, gene methylation and damage to DNA, amongst others, are synergistically involved in pathomechanisms of PCa development and progression. To this end, PCa-relevant systemic effects are reflected in liquid biopsies such as blood patterns which are instrumental for predictive diagnostics, targeted prevention and personalisation of medical services (PPPM/3P medicine) as a new paradigm in the overall PCa management. This strategic review article highlights systemic effects in prostate cancer development and progression, demonstrates evident challenges in PCa management and provides expert recommendations in the framework of 3P medicine.
A Propensity Score Matched Analysis of Superparamagnetic Iron Oxide versus Radioisotope Sentinel Node Biopsy in Breast Cancer Patients after Neoadjuvant Chemotherapy
Authors: Pelc Zuzanna , Skórzewska Magdalena , Kurylcio Maria , Nowikiewicz Tomasz , Mlak Radosław , Sędłak Katarzyna , Gęca Katarzyna , Rawicz-Pruszyński Karol , Zegarski Wojciech , Polkowski Wojciech P. , Kurylcio Andrzej
Published: January 2022

The standard method for nodal staging in breast cancer (BC) patients after neoadjuvant chemotherapy (NAC) is sentinel lymph node biopsy (SLNB) with a radioisotope (RI) injection. However, SLNB after NAC results in high false-negative rates (FNR), and the RI method is restricted by nuclear medicine unit dependency. These limitations resulted in the development of the superparamagnetic iron oxide (SPIO) method, reducing FNR and presenting a comparable detection rate. This bi-institutional cohort comparison study aimed to assess the efficacy of SPIO and radioisotope SNLB in BC patients after NAC using Propensity Score Matching (PSM) analysis. The study group comprised 508 patients who underwent SLNB after NAC for ycT1-4N0M0 BC between 2013 and 2021 in two high volume centers. Data were retrieved from prospectively conducted databases. In the SPIO group, the median of retrieved sentinel lymph nodes (SLNs) was significantly higher than in the RI group (3 vs. 2; p < 0.0001). The SPIO method was associated with a significantly higher chance of retrieving at least three lymph nodes when compared to the RI method (71% vs. 11.3%; p < 0.0001). None of the analyzed demographic and clinical variables had a statistically significant influence on the efficacy of SLNs retrieval in the RI group, while in the SPIO group, patients with ≥three harvested SLNs had lower weight and decreased BMI. Based on this PSM analysis, SPIO-guided SLNB allowed the efficient retrieval and detection of SLNs in BC patients after NAC compared to RI.
TFF1 in Aqueous Humor—A Potential New Biomarker for Retinoblastoma
Authors: Busch Maike Anna , Haase André , Miroschnikov Natalia , Doege Annika , Biewald Eva , Bechrakis Nikolaos E. , Beier Manfred , Kanber Deniz , Lohmann Dietmar , Metz Klaus , Dünker Nicole
Published: January 2022

Retinoblastoma (RB) is the most common childhood eye cancer. The expression of trefoil factor family peptide 1 (TFF1), a small secreted peptide, has been correlated with more advanced RB stages and it might be a promising new candidate as a RB biomarker. The study presented addressed the question of if TFF1 is detectable in aqueous humor (AH) of RB patients’ eyes, providing easy accessibility as a diagnostic and/or therapy accompanying predictive biomarker. The TFF1 expression status of 15 retinoblastoma AH samples was investigated by ELISA and Western blot analyses. The results were correlated with the TFF1 expression status in the tumor of origin and compared to TFF1 expression in established corresponding primary tumor cell cultures and supernatants. Nine out of fifteen AH patient samples exhibited TFF1 expression, which correlated well with TFF1 levels of the original tumor. TFF1 expression in most of the corresponding primary cell cultures reflects the levels of the original tumor, although not all TFF1-expressing tumor cells seem to secret into the AH. Together, our findings strongly suggest TFF1 as a reliable new RB biomarker.
A Decision Support Tool to Optimize Selection of Head and Neck Cancer Patients for Proton Therapy
Authors: Tambas Makbule , van der Laan Hans Paul van der , van der Schaaf Arjen van der , Steenbakkers Roel J. H. M. , Langendijk Johannes Albertus
Published: January 2022

Selection of head and neck cancer (HNC) patients for proton therapy (PT) using plan comparison (VMAT vs. IMPT) for each patient is labor-intensive. Our aim was to develop a decision support tool to identify patients with high probability to qualify for PT, at a very early stage (immediately after delineation) to avoid delay in treatment initiation. A total of 151 HNC patients were included, of which 106 (70%) patients qualified for PT. Linear regression models for individual OARs were created to predict the Dmean to the OARs for VMAT and IMPT plans. The predictors were OAR volume percentages overlapping with target volumes. Then, actual and predicted plan comparison decisions were compared. Actual and predicted OAR Dmean (VMAT R2 = 0.953, IMPT R2 = 0.975) and NTCP values (VMAT R2 = 0.986, IMPT R2 = 0.992) were highly correlated. The sensitivity, specificity, PPV and NPV of the decision support tool were 64%, 87%, 92% and 51%, respectively. The expected toxicity reduction with IMPT can be predicted using only the delineation data. The probability of qualifying for PT is >90% when the tool indicates a positive outcome for PT. This tool will contribute significantly to a more effective selection of HNC patients for PT at a much earlier stage, reducing treatment delay.
Low-Dose Nivolumab with or without Ipilimumab as Adjuvant Therapy Following the Resection of Melanoma Metastases: A Sequential Dual Cohort Phase II Clinical Trial
Authors: Schwarze Julia Katharina , Garaud Soizic , Jansen Yanina J. L. , Awada Gil , Vandersleyen Valérie , Tijtgat Jens , de Wind Alexandre , Kristanto Paulus , Seremet Teofila , Willard-Gallo Karen , Neyns Bart
Published: January 2022

Background: Optimal dosing and duration of adjuvant treatment with PD-1 and CTLA-4 immune checkpoint inhibitors have not been established. Prior to their regulatory approval we investigated a low-dose regimen of nivolumab with or without ipilimumab in a sequential dual-cohort phase II clinical trial. Methods: Following the complete resection of melanoma metastases, patients were treated with a single fixed dose of ipilimumab (50 mg) plus 4 bi-weekly fixed doses of nivolumab (10 mg) (cohort-1), or nivolumab for 1 year (10 mg fixed dose, Q2w x9, followed by Q8w x4) (cohort-2). Twelve-months relapse-free survival (RFS) served as the primary endpoint. Results: After a median follow-up of 235 weeks for cohort-1 (34 patients), and 190 weeks for cohort-2 (21 patients), the 12-months RFS-rate was, respectively, 55.9% (95% CI, 39–72), and 85.7% (95% CI, 70–100). Treatment-related adverse events occurred in 27 (79%), and 18 (86%) patients, with 3 (9%), and 1 (5%) grade 3 adverse events in cohort-1 and -2, respectively. Immunohistochemical quantification of intra- and peritumoral CD3+ T cells and CD20+ B cells, but not PD-1/PD-L1 staining, correlated significantly with RFS. Conclusions: One year of adjuvant low-dose nivolumab could be an effective and economically advantageous alternative for standard dosing, at the condition of further confirmation in a larger patient cohort. A shorter low-dose nivolumab plus ipilimumab regimen seems inferior and less tolerable.
Commercial Gold Complexes Supported on Functionalised Carbon Materials as Efficient Catalysts for the Direct Oxidation of Ethane to Acetic Acid
Authors: Ribeiro Ana P. C. , Matias Inês A. S. , Carabineiro Sónia A. C. , Martins Luísa M. D. R. S.
Published: January 2022

The single-pot efficient oxidation of ethane to acetic acid catalysed by Au(I) or Au(III) compounds, chlorotriphenylphosphinegold(I) (1), chlorotrimethylphosphinegold(I) (2), 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidenegold(I) chloride (3), dichloro(2-pyridinecarboxylato)gold(III) (4), homogenous and supported on different carbon materials: activated carbon (AC), multi-walled carbon nanotubes (CNT) and carbon xerogel (CX), oxidised with nitric acid followed by treatment with NaOH (-ox-Na), is reported. The reactions were performed in water/acetonitrile. The materials were selective for the production of acetic acid, with no trace of by-products being detected. The best homogenous catalysts were complexes 2 and 3 which showed the highest ethane conversion and an acetic acid yield of ca. 21%, followed by 4 and 1. The heterogenised materials showed much better activity than the homogenous counterparts, with acetic acid yields up to 41.4% for 4@CNT-ox-Na, and remarkable selectivity (with acetic acid being the only product detected). The heterogenised catalysts with the best results were reused up to five cycles, with no significant loss of activity, and maintaining high selectivity for acetic acid. 4@CNT-ox-Na showed not only the best catalytic activity but also the best stability during the recycling runs.
Photocatalytic Degradation of Fluoroquinolone Antibiotics in Solution by Au@ZnO-rGO-gC3N4 Composites
Authors: Machín Abniel , Fontánez Kenneth , Duconge José , Cotto María C. , Petrescu Florian I. , Morant Carmen , Márquez Francisco
Published: January 2022

The photocatalytic degradation of two quinolone-type antibiotics (ciprofloxacin and levofloxacin) in aqueous solution was studied, using catalysts based on ZnO nanoparticles, which were synthesized by a thermal procedure. The efficiency of ZnO was subsequently optimized by incorporating different co-catalysts of gC3N4, reduced graphene oxide, and nanoparticles of gold. The catalysts were fully characterized by electron microscopy (TEM and SEM), XPS, XRD, Raman, and BET surface area. The most efficient catalyst was 10%Au@ZnONPs-3%rGO-3%gC3N4, obtaining degradations of both pollutants above 96%. This catalyst has the largest specific area, and its activity was related to a synergistic effect, involving factors such as the surface of the material and the ability to absorb radiation in the visible region, mainly produced by the incorporation of rGO and gC3N4 in the semiconductor. The use of different scavengers during the catalytic process, was used to establish the possible photodegradation mechanism of both antibiotics.
Acknowledgment to Reviewers of Catalysts in 2021
Authors:   Catalysts Editorial Office
Published: January 2022

Rigorous peer-reviews are the basis of high-quality academic publishing [...]
Production of Light Olefins via Fischer-Tropsch Process Using Iron-Based Catalysts: A Review
Authors: Gholami Zahra , Gholami Fatemeh , Tišler Zdeněk , Hubáček Jan , Tomas Martin , Bačiak Miroslav , Vakili Mohammadtaghi
Published: January 2022

The production of light olefins, as the critical components in chemical industries, is possible via different technologies. The Fischer–Tropsch to olefin (FTO) process aims to convert syngas to light olefins with high selectivity over a proper catalyst, reduce methane formation, and avoid the production of excess CO2. This review describes the production of light olefins through the FTO process using both unsupported and supported iron-based catalysts. The catalytic properties and performances of both the promoted and bimetallic unsupported catalysts are reviewed. The effect of support and its physico-chemical properties on the catalyst activity are also described. The proper catalyst should have high stability to provide long-term performance without reducing the activity and selectivity towards the desired product. The good dispersion of active metals on the surface, proper porosity, optimized metal-support interaction, a high degree of reducibility, and providing a sufficient active phase for the reaction are important parameters affecting the reaction. The selection of the suitable catalyst with enhanced activity and the optimum process conditions can increase the possibility of the FTO reaction for light-olefins production. The production of light olefins via the FTO process over iron-based catalysts is a promising method, as iron is cheap, shows higher resistance to sulfur, and has a higher WGS activity which can be helpful for the feed gas with a low H2/CO ratio, and also has higher selectivity towards light olefins.
Testicular Torsion: Preliminary Results of In Vitro Cell Stimulation Using Chorionic Gonadotropin
Authors: Errico Andrea , Camoglio Francesco Saverio , Zampieri Nicola , Dando Ilaria
Published: January 2022

Testicular torsion is a pathology that occurs in young males generally before the age of 25. Despite surgery representing the only effective approach, there is still a need to identify a marker that can predict whether a preserved testicle will be functional. In addition, no therapeutic approach is currently considered in the post-operative phase. Through an approach based on the in vitro culture of a tissue strictly linked to the testicle, the gubernaculum, we defined the healthy state of the organ and the possible responsiveness to a therapy used in the andrology field, chorionic gonadotropin (hCG). Firstly, we optimized a protocol to obtain viable cells starting from a small piece of gubernacular tissue harvested during surgery with the aim to amplify cells in vitro. Intriguingly, only for a patient whose testicle had been removed during surgery due to an excessive necrotic area, gubernacular cells were not able to grow in culture. These data support the possibility of exploiting the gubernaculum to evaluate the healthy state of the testicle. Then, as we demonstrate that gubernacular cells express a luteinizing hormone receptor, to which hCG is specific, we analyzed the cellular response to hCG treatment on in vitro cultured cells derived from patients affected by testicular torsion. Our study opens the way for the possibility of evaluating testicle wellbeing after derotation through in vitro culture of a small piece of gubernaculum together with predicting the response to the treatment with hCG, which can have a positive effect on cell proliferation and vascularization.
miRNAs as Biomarkers and Possible Therapeutic Strategies in Rheumatoid Arthritis
Authors: Kmiołek Tomasz , Paradowska-Gorycka Agnieszka
Published: January 2022

Within the past years, more and more attention has been devoted to the epigenetic dysregulation that provides an additional window for understanding the possible mechanisms involved in the pathogenesis of autoimmune rheumatic diseases. Rheumatoid arthritis (RA) is a heterogeneous disease where a specific immunologic and genetic/epigenetic background is responsible for disease manifestations and course. In this field, microRNAs (miRNA; miR) are being identified as key regulators of immune cell development and function. The identification of disease-associated miRNAs will introduce us to the post-genomic era, providing the real probability of manipulating the genetic impact of autoimmune diseases. Thereby, different miRNAs may be good candidates for biomarkers in disease diagnosis, prognosis, treatment and other clinical applications. Here, we outline not only the role of miRNAs in immune and inflammatory responses in RA, but also present miRNAs as diagnostic/prognostic biomarkers. Research into miRNAs is still in its infancy; however, investigation into these novel biomarkers could progress the use of personalized medicine in RA treatment. Finally, we discussed the possibility of miRNA-based therapy in RA patients, which holds promise, given major advances in the therapy of patients with inflammatory arthritis.
Cancer Immunology: From Molecular Mechanisms to Therapeutic Opportunities
Authors: Mattei Fabrizio , Alfaro Carlos , Keisari Yona
Published: January 2022

The gradual and more profound dissection of the molecular basis of cancer progression, carcinogenesis, and metastatic spread of cancer cells has led to more focused, effective, and targeted therapeutic approaches in the disparate types of solid and hematological tumors, particularly those with high ability to metastasize distant organs [...]
Harnessing the Power of Stem Cell Models to Study Shared Genetic Variants in Congenital Heart Diseases and Neurodevelopmental Disorders
Authors: Chang Xuyao , Gu Mingxia , Tchieu Jason
Published: January 2022

Advances in human pluripotent stem cell (hPSC) technology allow one to deconstruct the human body into specific disease-relevant cell types or create functional units representing various organs. hPSC-based models present a unique opportunity for the study of co-occurring disorders where “cause and effect” can be addressed. Poor neurodevelopmental outcomes have been reported in children with congenital heart diseases (CHD). Intuitively, abnormal cardiac function or surgical intervention may stunt the developing brain, leading to neurodevelopmental disorders (NDD). However, recent work has uncovered several genetic variants within genes associated with the development of both the heart and brain that could also explain this co-occurrence. Given the scalability of hPSCs, straightforward genetic modification, and established differentiation strategies, it is now possible to investigate both CHD and NDD as independent events. We will first overview the potential for shared genetics in both heart and brain development. We will then summarize methods to differentiate both cardiac & neural cells and organoids from hPSCs that represent the developmental process of the heart and forebrain. Finally, we will highlight strategies to rapidly screen several genetic variants together to uncover potential phenotypes and how therapeutic advances could be achieved by hPSC-based models.