bluuebunny/crossref_metadata_2025 huggingface dataset:
Potential Pathophysiological Pathways in the Complex Relationships between OSA and Cancer
Authors: Sánchez-de-la-Torre Manuel , Cubillos Carolina , Veatch Olivia J. , Garcia-Rio Francisco , Gozal David , Martinez-Garcia Miguel Angel
Published: February 2023

Several epidemiological and clinical studies have suggested a relationship between obstructive sleep apnea (OSA) and a higher incidence or severity of cancer. This relationship appears to be dependent on a myriad of factors. These include non-modifiable factors, such as age and gender; and modifiable or preventable factors, such as specific comorbidities (especially obesity), the use of particular treatments, and, above all, the histological type or location of the cancer. Heterogeneity in the relationship between OSA and cancer is also related to the influences of intermittent hypoxemia (a hallmark feature of OSA), among others, on metabolism and the microenvironment of different types of tumoral cells. The hypoxia inducible transcription factor (HIF-1α), a molecule activated and expressed in situations of hypoxemia, seems to be key to enabling a variety of pathophysiological mechanisms that are becoming increasingly better recognized. These mechanisms appear to be operationally involved via alterations in different cellular functions (mainly involving the immune system) and molecular functions, and by inducing modifications in the microbiome. This, in turn, may individually or collectively increase the risk of cancer, which is then, further modulated by the genetic susceptibility of the individual. Here, we provide an updated and brief review of the different pathophysiological pathways that have been identified and could explain the relationship between OSA and cancer. We also identify future challenges that need to be overcome in this intriguing field of research.
Prognostic Value of the Lung Immune Prognosis Index Score for Patients Treated with Immune Checkpoint Inhibitors for Advanced or Metastatic Urinary Tract Carcinoma
Authors: Parent Pauline , Auclin Edouard , Patrikidou Anna , Mezquita Laura , Martínez Chanzá Nieves , Dumont Clément , Rodriguez-Vida Alejo , Llacer Casilda , Lozano Rebeca , Ratta Raffaele , Merseburger Axel S. , Sternberg Cora N. , Baciarello Giulia , Colomba Emeline , Fuerea Alina , Besse Benjamin , Loriot Yohann , Lavaud Pernelle
Published: February 2023

Few prognostic factors have been identified in patients with metastatic urothelial carcinoma (mUC) treated with immune checkpoint inhibitors (ICIs). The Lung Immune Prognostic Index (LIPI) was associated with clinical outcomes for ICIs in several tumor types. We aim to assess the value of the LIPI in patients with mUC treated with ICIs. A retrospective ICI cohort and a validation cohort (SAUL cohort) included, respectively, patients with mUC treated with ICI in 8 European centers (any line) and patients treated with atezolizumab in a second or further line. A chemotherapy-only cohort was also analyzed. The LIPI score was based on 2 factors, derived neutrophils/(leukocytes minus neutrophils) ratio (dNLR) > 3 and lactate dehydrogenase > upper limit of normal, and defined 3 prognostic groups. The association of LIPI with progression-free survival (PFS) and overall survival (OS) was assessed. In the ICI and SAUL cohorts, 137 and 541 patients were respectively analyzed. In the ICI cohort, mPFS and mOS were 3.6 mo (95% CI; 2.6–6.0) and 13.8 mo (95% CI; 11.5–23.2) whereas in the SAUL cohort the mPFS and mOS were 2.2 mo (95% CI; 2.1–2.3) and 8.7 mo (95% CI; 7.8–9.9) respectively. The LIPI classified the population of these cohorts in good (56%; 52%), intermediate (35%; 36%) and poor (9%; 12%) prognostic groups (values for the ICI and SAUL cohorts respectively). Poor LIPI was associated with a poorer OS in both cohorts: hazard ratio (HR) for the ICI cohort = 2.69 (95% CI; 1.24–5.84, p = 0.035); HR = 2. 89 for the SAUL cohort (CI 95%: 1.93–4.32, p < 0.0001). Similar results were found in the chemo cohort. The LIPI score allows to identify different subgroups in patients with good prognostis according to the Bellmunt score criteria, with a subset of patients with poorer outcomes having an mOS of 3.7 mo compared to the good and intermediate LIPI subgroups with mOS of 17.9 and 7.4 mo, respectively. The LIPI score was associated with survival in mUC patients treated by ICIs. Future prospective studies will be required to test the combination of Bellmunt score and the LIPI score as a more accurate prognosis tool.
Transbronchial Techniques for Lung Cancer Treatment: Where Are We Now?
Authors: Chan Joyce W. Y. , Siu Ivan C. H. , Chang Aliss T. C. , Li Molly S. C. , Lau Rainbow W. H. , Mok Tony S. K. , Ng Calvin S. H.
Published: February 2023

The demand for parenchyma-sparing local therapies for lung cancer is rising owing to an increasing incidence of multifocal lung cancers and patients who are unfit for surgery. With the latest evidence of the efficacy of lung cancer screening, more premalignant or early-stage lung cancers are being discovered and the paradigm has shifted from treatment to prevention. Transbronchial therapy is an important armamentarium in the local treatment of lung cancers, with microwave ablation being the most promising based on early to midterm results. Adjuncts to improve transbronchial ablation efficiency and accuracy include mobile C-arm platforms, software to correct for the CT-to-body divergence, metal-containing nanoparticles, and robotic bronchoscopy. Other forms of energy including steam vapor therapy and pulse electric field are under intensive investigation.
Immunotherapies against HER2-Positive Breast Cancer
Authors: Duro-Sánchez Santiago , Alonso Macarena Román , Arribas Joaquín
Published: February 2023

Breast cancer is the leading cause of cancer-related deaths among women worldwide. HER2-positive breast cancer, which represents 15–20% of all cases, is characterized by the overexpression of the HER2 receptor. Despite the variety of treatments available for HER2-positive breast cancer, both targeted and untargeted, many patients do not respond to therapy and relapse and eventually metastasize, with a poor prognosis. Immunotherapeutic approaches aim to enhance the antitumor immune response to prevent tumor relapse and metastasis. Several immunotherapies have been approved for solid tumors, but their utility for HER2-positive breast cancer has yet to be confirmed. In this review, we examine the different immunotherapeutic strategies being tested in HER2-positive breast cancer, from long-studied cancer vaccines to immune checkpoint blockade, which targets immune checkpoints in both T cells and tumor cells, as well as the promising adoptive cell therapy in various forms. We discuss how some of these new approaches may contribute to the prevention of tumor progression and be used after standard-of-care therapies for resistant HER2-positive breast tumors, highlighting the benefits and drawbacks of each. We conclude that immunotherapy holds great promise for the treatment of HER2-positive tumors, with the potential to completely eradicate tumor cells and prevent the progression of the disease.
Modulation of the Tumor-Associated Immuno-Environment by Non-Invasive Physical Plasma
Authors: Förster Sarah , Niu Yuequn , Eggers Benedikt , Nokhbehsaim Marjan , Kramer Franz-Josef , Bekeschus Sander , Mustea Alexander , Stope Matthias B.
Published: February 2023

Over the past 15 years, investigating the efficacy of non-invasive physical plasma (NIPP) in cancer treatment as a safe oxidative stress inducer has become an active area of research. So far, most studies focused on the NIPP-induced apoptotic death of tumor cells. However, whether NIPP plays a role in the anti-tumor immune responses need to be deciphered in detail. In this review, we summarized the current knowledge of the potential effects of NIPP on immune cells, tumor–immune interactions, and the immunosuppressive tumor microenvironment. In general, relying on their inherent anti-oxidative defense systems, immune cells show a more resistant character than cancer cells in the NIPP-induced apoptosis, which is an important reason why NIPP is considered promising in cancer management. Moreover, NIPP treatment induces immunogenic cell death of cancer cells, leading to maturation of dendritic cells and activation of cytotoxic CD8+ T cells to further eliminate the cancer cells. Some studies also suggest that NIPP treatment may promote anti-tumor immune responses via other mechanisms such as inhibiting tumor angiogenesis and the desmoplasia of tumor stroma. Though more evidence is required, we expect a bright future for applying NIPP in clinical cancer management.
Systemic Inflammatory Indices in Second-Line Soft Tissue Sarcoma Patients: Focus on Lymphocyte/Monocyte Ratio and Trabectedin
Authors: Fausti Valentina , De Vita Alessandro , Vanni Silvia , Ghini Virginia , Gurrieri Lorena , Riva Nada , Casadei Roberto , Maraldi Marco , Ercolani Giorgio , Cavaliere Davide , Pacilio Carlo Alberto , Pieri Federica , Foca Flavia , Bongiovanni Alberto , Ranallo Nicoletta , Calpona Sebastiano , Frassineti Giovanni Luca , Ibrahim Toni , Mercatali Laura
Published: February 2023

A second-line standard of treatment has not yet been identified in patients with soft tissue sarcomas (STS), so identifying predictive markers could be a valuable tool. Recent studies have shown that the intratumoral and inflammatory systems significantly influence tumor aggressiveness. We aimed to investigate prognostic values of pre-therapy neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic inflammatory index (SII), progression-free survival (PFS), and overall survival (OS) of STS patients receiving second-line treatment. In this single-center retrospective analysis, ninety-nine patients with STS were enrolled. All patients received second-line treatment after progressing to anthracycline. PFS and OS curves were calculated using the Kaplan–Meier method of RNA sequencing, and CIBERSORT analysis was performed on six surgical specimens of liposarcoma patients. A high NLR, PLR, and SII were significantly associated with worse PFS (p = 0.019; p = 0.004; p = 0.006). Low LMR was significantly associated with worse OS (p = 0.006). Patients treated with Trabectedin showed a better PFS when the LMR was low, while patients treated with other regimens showed a worse PFS when the LMR was low (p = 0.0154). The intratumoral immune infiltrates analysis seems to show a correlation between intratumoral macrophages and LMR. PS ECOG. The metastatic onset and tumor burden showed prognostic significance for PFS (p = 0.004; p = 0.041; p = 0.0086). According to the histologies, PFS was: 5.7 mo in liposarcoma patients vs. 3.8 mo in leiomyosarcoma patients vs. 3.1 months in patients with other histologies (p = 0.053). Our results confirm the prognostic role of systemic inflammatory markers in patients with STS. Moreover, we demonstrated that LMR is a specific predictor of Trabectedin efficacy and could be useful in daily clinical practice. We also highlighted a possible correlation between LMR levels and the percentage of intratumoral macrophages.
Management of Inflammatory Bowel Disease in Patients with Current or Past Malignancy
Authors: Poullenot Florian , Laharie David
Published: February 2023

Immunomodulators, conventional immunosuppressants, and/or biologics are used more often, earlier, and longer than before in patients with inflammatory bowel disease (IBD). Along with this, the lifetime risk for cancer is estimated to be 33% in the general population in Europe. Thus, physicians face therapeutic choices in an increasing number of IBD patients with current or past malignancy. Few data are available so far for managing this IBD subpopulation and this clinical concern still remains a critical situation for four reasons: (i) risk of reactivation of dormant micrometastasis with immunomodulators is of major concern, (ii) there is a knowledge gap about the safety of the most recent molecules, (iii) current guidelines do not recommend the use of immunomodulators within 2–5 years after a diagnosis of cancer, (iv) patients with previous cancers are excluded from clinical trials. There is a lack of scientific evidence supporting the non-use of immunomodulators in IBD patients with previous cancer. Indeed, accumulative data suggest that the risk for recurrent and new cancer in patients with a history of cancer is not increased by thiopurines and anti-TNF agents. Most recently, cohort studies have found no differences in incident cancer rates in IBD patients with prior malignancy treated with vedolizumab or ustekinumab compared to those treated with anti-TNF agents. Therefore, decisions should be shared by the oncologist and the patient, considering the natural history of cancer, the time elapsed since cancer diagnosis, and IBD prognosis.
Lower Circulating Cell-Free Mitochondrial DNA Is Associated with Heart Failure in Type 2 Diabetes Mellitus Patients
Authors: Berezina Tetiana , Kopytsya Mykola , Petyunina Olga , Berezin Alexander , Obradovic Zeljko , Schmidbauer Lukas , Lichtenauer Michael , Berezin Alexander
Published: February 2023

Cell-free nuclear (cf-nDNA) and mitochondrial (cf-mDNA) DNA are released from damaged cells in type 2 diabetes mellitus (T2DM) patients, contributing to adverse cardiac remodeling, vascular dysfunction, and inflammation. The purpose of this study was to correlate the presence and type of cf-DNAs with HF in T2DM patients. A total of 612 T2DM patients were prescreened by using a local database, and 240 patients (120 non-HF and 120 HF individuals) were ultimately selected. The collection of medical information, including both echocardiography and Doppler imagery, as well as the assessment of biochemistry parameters and the circulating biomarkers, were performed at baseline. The N-terminal brain natriuretic pro-peptide (NT-proBNP) and cf-nDNA/cf-mtDNA levels were measured via an ELISA kit and real-time quantitative PCR tests, respectively. We found that HF patients possessed significantly higher levels of cf-nDNA (9.9 ± 2.5 μmol/L vs. 5.4 ± 2.7 μmol/L; p = 0.04) and lower cf-mtDNA (15.7 ± 3.3 μmol/L vs. 30.4 ± 4.8 μmol/L; p = 0.001) than those without HF. The multivariate log regression showed that the discriminative potency of cf-nDNA >7.6 μmol/L (OR = 1.07; 95% CI = 1.03–1.12; p = 0.01) was higher that the NT-proBNP (odds ratio [OR] = 1.10; 95% confidence interval [CI] = 1.04–1.19; p = 0.001) for HF. In conclusion, we independently established that elevated levels of cf-nDNA, originating from NT-proBNP, were associated with HF in T2DM patients.
Chimeric Antigen Receptor T-Cell Therapy and Hematopoiesis
Authors: Reinhardt Bryanna , Lee Patrick , Sasine Joshua P.
Published: February 2023

Chimeric Antigen Receptor (CAR) T-cell therapy is a promising treatment option for patients suffering from B-cell- and plasma cell-derived hematologic malignancies and is being adapted for the treatment of solid cancers. However, CAR T is associated with frequently severe toxicities such as cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), macrophage activation syndrome (MAS), and prolonged cytopenias—a reduction in the number of mature blood cells of one or more lineage. Although we understand some drivers of these toxicities, their mechanisms remain under investigation. Since the CAR T regimen is a complex, multi-step process with frequent adverse events, ways to improve the benefit-to-risk ratio are needed. In this review, we discuss a variety of potential solutions being investigated to address the limitations of CAR T. First, we discuss the incidence and characteristics of CAR T-related cytopenias and their association with reduced CAR T-cell efficacy. We review approaches to managing or mitigating cytopenias during the CAR T regimen—including the use of growth factors, allogeneic rescue, autologous hematopoietic stem cell infusion, and alternative conditioning regimens. Finally, we introduce novel methods to improve CAR T-cell-infusion products and the implications of CAR T and clonal hematopoiesis.
Intermittent Fasting Resolves Dyslipidemia and Atherogenesis in Apolipoprotein E-Deficient Mice in a Diet-Dependent Manner, Irrespective of Sex
Authors: Mérian Jules , Ghezali Lamia , Trenteseaux Charlotte , Duparc Thibaut , Beuzelin Diane , Bouguetoch Vanessa , Combes Guillaume , Sioufi Nabil , Martinez Laurent O. , Najib Souad
Published: February 2023

In humans and animal models, intermittent fasting (IF) interventions promote body weight loss, improve metabolic health, and are thought to lower cardiovascular disease risk. However, there is a paucity of reports on the relevance of such nutritional interventions in the context of dyslipidemia and atherosclerotic cardiovascular diseases. The present study assessed the metabolic and atheroprotective effects of intermittent fasting intervention (IF) in atherosclerosis-prone apolipoprotein E-deficient (Apoe-/-) mice. Groups of male and female Apoe-/- mice were fed a regular (chow) or atherogenic (high-fat, high-cholesterol, HFCD) diet for 4 months, either ad libitum or in an alternate-day fasting manner. The results show that IF intervention improved glucose and lipid metabolism independently of sex. However, IF only decreased body weight gain in males fed chow diet and differentially modulated adipose tissue parameters and liver steatosis in a diet composition-dependent manner. Finally, IF prevented spontaneous aortic atherosclerotic lesion formation in mice fed chow diet, irrespective of sex, but failed to reduce HFCD-diet-induced atherosclerosis. Overall, the current work indicates that IF interventions can efficiently improve glucose homeostasis and treat atherogenic dyslipidemia, but a degree of caution is warranted with regard to the individual sex and the composition of the dietary regimen.
Is Autophagy Inhibition in Combination with Temozolomide a Therapeutically Viable Strategy?
Authors: Elshazly Ahmed M. , Gewirtz David A.
Published: February 2023

Temozolomide is an oral alkylating agent that is used as the first line treatment for glioblastoma multiform, and in recurrent anaplastic astrocytoma, as well as having demonstrable activity in patients with metastatic melanoma. However, as the case with other chemotherapeutic agents, the development of resistance often limits the therapeutic benefit of temozolomide, particularly in the case of glioblastoma. A number of resistance mechanisms have been proposed including the development of cytoprotective autophagy. Cytoprotective autophagy is a survival mechanism that confers upon tumor cells the ability to survive in a nutrient deficient environment as well as under external stresses, such as cancer chemotherapeutic drugs and radiation, in part through the suppression of apoptotic cell death. In this review/commentary, we explore the available literature and provide an overview of the evidence for the promotion of protective autophagy in response to temozolomide, highlighting the possibility of targeting autophagy as an adjuvant therapy to potentially increase the effectiveness of temozolomide and to overcome the development of resistance.
Transition from Animal-Based to Human Induced Pluripotent Stem Cells (iPSCs)-Based Models of Neurodevelopmental Disorders: Opportunities and Challenges
Authors: Guerreiro Sara , Maciel Patrícia
Published: February 2023

Neurodevelopmental disorders (NDDs) arise from the disruption of highly coordinated mechanisms underlying brain development, which results in impaired sensory, motor and/or cognitive functions. Although rodent models have offered very relevant insights to the field, the translation of findings to clinics, particularly regarding therapeutic approaches for these diseases, remains challenging. Part of the explanation for this failure may be the genetic differences—some targets not being conserved between species—and, most importantly, the differences in regulation of gene expression. This prompts the use of human-derived models to study NDDS. The generation of human induced pluripotent stem cells (hIPSCs) added a new suitable alternative to overcome species limitations, allowing for the study of human neuronal development while maintaining the genetic background of the donor patient. Several hIPSC models of NDDs already proved their worth by mimicking several pathological phenotypes found in humans. In this review, we highlight the utility of hIPSCs to pave new paths for NDD research and development of new therapeutic tools, summarize the challenges and advances of hIPSC-culture and neuronal differentiation protocols and discuss the best way to take advantage of these models, illustrating this with examples of success for some NDDs.
The RUNX Family Defines Trk Phenotype and Aggressiveness of Human Neuroblastoma through Regulation of p53 and MYCN
Authors: Ando Kiyohiro , Nakagawara Akira
Published: February 2023

The Runt-related transcription factor (RUNX) family, which is essential for the differentiation of cells of neural crest origin, also plays a potential role in neuroblastoma tumorigenesis. Consecutive studies in various tumor types have demonstrated that the RUNX family can play either pro-tumorigenic or anti-tumorigenic roles in a context-dependent manner, including in response to chemotherapeutic agents. However, in primary neuroblastomas, RUNX3 acts as a tumor-suppressor, whereas RUNX1 bifunctionally regulates cell proliferation according to the characterized genetic and epigenetic backgrounds, including MYCN oncogenesis. In this review, we first highlight the current knowledge regarding the mechanism through which the RUNX family regulates the neurotrophin receptors known as the tropomyosin-related kinase (Trk) family, which are significantly associated with neuroblastoma aggressiveness. We then focus on the possible involvement of the RUNX family in functional alterations of the p53 family members that execute either tumor-suppressive or dominant-negative functions in neuroblastoma tumorigenesis. By examining the tripartite relationship between the RUNX, Trk, and p53 families, in addition to the oncogene MYCN, we endeavor to elucidate the possible contribution of the RUNX family to neuroblastoma tumorigenesis for a better understanding of potential future molecular-based therapies.
An Optimized Workflow to Generate and Characterize iPSC-Derived Motor Neuron (MN) Spheroids
Authors: Castellanos-Montiel María José , Chaineau Mathilde , Franco-Flores Anna Kristyna , Haghi Ghazal , Carrillo-Valenzuela Dulce , Reintsch Wolfgang E. , Chen Carol X.-Q. , Durcan Thomas M.
Published: February 2023

A multitude of in vitro models based on induced pluripotent stem cell (iPSC)-derived motor neurons (MNs) have been developed to investigate the underlying causes of selective MN degeneration in motor neuron diseases (MNDs). For instance, spheroids are simple 3D models that have the potential to be generated in large numbers that can be used across different assays. In this study, we generated MN spheroids and developed a workflow to analyze them. To start, the morphological profiling of the spheroids was achieved by developing a pipeline to obtain measurements of their size and shape. Next, we confirmed the expression of different MN markers at the transcript and protein levels by qPCR and immunocytochemistry of tissue-cleared samples, respectively. Finally, we assessed the capacity of the MN spheroids to display functional activity in the form of action potentials and bursts using a microelectrode array approach. Although most of the cells displayed an MN identity, we also characterized the presence of other cell types, namely interneurons and oligodendrocytes, which share the same neural progenitor pool with MNs. In summary, we successfully developed an MN 3D model, and we optimized a workflow that can be applied to perform its morphological, gene expression, protein, and functional profiling over time.
The “3Ds” of Growing Kidney Organoids: Advances in Nephron Development, Disease Modeling, and Drug Screening
Authors: Chambers Brooke E. , Weaver Nicole E. , Wingert Rebecca A.
Published: February 2023

A kidney organoid is a three-dimensional (3D) cellular aggregate grown from stem cells in vitro that undergoes self-organization, recapitulating aspects of normal renal development to produce nephron structures that resemble the native kidney organ. These miniature kidney-like structures can also be derived from primary patient cells and thus provide simplified context to observe how mutations in kidney-disease-associated genes affect organogenesis and physiological function. In the past several years, advances in kidney organoid technologies have achieved the formation of renal organoids with enhanced numbers of specialized cell types, less heterogeneity, and more architectural complexity. Microfluidic bioreactor culture devices, single-cell transcriptomics, and bioinformatic analyses have accelerated the development of more sophisticated renal organoids and tailored them to become increasingly amenable to high-throughput experimentation. However, many significant challenges remain in realizing the use of kidney organoids for renal replacement therapies. This review presents an overview of the renal organoid field and selected highlights of recent cutting-edge kidney organoid research with a focus on embryonic development, modeling renal disease, and personalized drug screening.
Congenital Diaphragmatic Hernia: Perinatal Prognostic Factors and Short-Term Outcomes in a Single-Center Series
Authors: Pagliara Camilla , Zambaiti Elisa , Brooks Giulia , Bonadies Luca , Tognon Costanza , Salvadori Sabrina , Sgrò Alberto , Leon Francesco Fascetti
Published: February 2023

Background: Many prognostic factors for CDH patients are described and validated in the current literature: the size of diaphragmatic defects, need for patch repair, pulmonary hypertension and left ventricular dysfunction are recognized as the most influencing outcomes. The aim of this study is to analyze the influence of these parameters in the outcome of CDH patients in our department and identify any further prognostic factors. Methods: An observational retrospective single-center study was conducted including all patients treated at our centre with posterolateral CDH between 01.01.1997 and 12.31.2019. The main outcomes evaluated were mortality and length of hospital stay. A univariate and multivariate analysis was performed. Results: We identified 140 patients with posterolateral CDH; 34.8% died before discharge. The overall median length of stay was 24 days. A univariate analysis confirmed that both outcomes are associated with the size of diaphragmatic defects, need for patch repair and presence of spleen-up (p < 0.05). A multivariate analysis identified that the need for patch repair and maximum dopamine dose used for cardiac dysfunction are independent parameters associated with the length of stay only (p < 0.001). Conclusions: In our series, the duration of hospitalization is longer for newborns with CDH treated with higher doses of dopamine for left ventricular dysfunction or needing patch repair in large diaphragmatic defects.
Therapeutic Approaches to Dysautonomia in Childhood, with a Special Focus on Long COVID
Authors: Buchhorn Reiner
Published: February 2023

Background: Dysautonomia seems to be important for the pathophysiology of psychosomatic diseases and, more recently, for long COVID. This concept may explain the clinical symptoms and could help open new therapeutic approaches. Methods: We compared our data from an analysis of heart rate variability (HRV) in an active standing test in 28 adolescents who had developed an inappropriate sinus tachycardia (IST, n = 13) or postural orthostatic tachycardia syndrome (POTS, n = 15) after contracting COVID-19 disease and/or vaccination with 64 adolescents from our database who developed dysautonomia due to psychosomatic diseases prior to the COVID-19 pandemic. We prove the effects of our treatment: omega-3 fatty acid supplementation (O3-FA, n = 18) in addition to propranolol (low dose, up to 20-20-0 mg, n = 32) or ivabradine 5-5-0 mg (n = 17) on heart rate regulation and heart rate variability (HRV). Results: The HRV data were not different between the adolescents with SARS-CoV-2-related disorders and the adolescents with dysautonomia prior to the pandemic. The heart rate increases in children with POTS while standing were significantly lower after low-dose propranolol (27.2 ± 17.4 bpm***), ivabradine (23.6 ± 8.12 bpm*), and O-3-FA (25.6 ± 8.4 bpm*). The heart rate in children with IST while lying/standing was significantly lower after propranolol (81.6 ± 10.1 bpm**/101.8 ± 18.8***), ivabradine (84.2 ± 8.4 bpm***/105.4 ± 14.6**), and O-3-FA (88.6 ± 7.9 bpm*/112.1/14.9*). Conclusions: The HRV data of adolescents with dysautonomia after COVID-19 disease/vaccination are not significantly different from a historical control of adolescents with dysautonomia due to psychosomatic diseases prior to the pandemic. Low-dose propranolol > ivabradine > omega-3 fatty acids significantly decrease elevated heart rates in patients with IST and the heart rate increases in patients with POTS and may be beneficial in these children with dysautonomia.
Is an Exercise Program for Pediatric Cancer Patients in Palliative Care Feasible and Supportive?—A Case Series
Authors: Beller Ronja , Gauß Gabriele , Reinhardt Dirk , Götte Miriam
Published: February 2023

(1) Background: Growing evidence indicates benefits through exercise programs in pediatric oncology throughout the whole cancer trajectory. This should include palliative care, too. This project analyzes the feasibility of a supervised exercise program offered during hospital and home-based care for children with advanced cancer diagnoses. (2) Methods: Four children (7–13 years old) with advanced cancer diagnoses participated in this project. It consisted of supervised exercise sessions offered once a week (30–90 min), mainly home-based, but also on an in- and outpatient basis. Regular data assessments included psychological and physical capacity-related endpoints and body composition. Details and contents of exercise sessions and adverse events were recorded. (3) Results: Exercise was feasible with 73 ± 9% adherence to the minimum number of planned sessions. The exercise offer was accepted until shortly before death. Effects on fatigue, quality of life and muscular endurance were noted. Participants showed major deviations from age-specific reference values. No exercise-related adverse events occurred. (4) Conclusions: The exercise program was safe, feasible, and might have served as a supportive tool to reduce overall burden. Evaluation of exercise as usual palliative care should be assessed by further studies.
Facile Synthesis of Polyacrylic Acid/Graphene Oxide Composite Hydrogel Electrolyte for High-Performance Flexible Supercapacitors
Authors: Xin Yue , Yu Zhaoxin , Soomro Razium Ali , Sun Ning
Published: February 2023

The development of hydrogel electrolytes plays a critical role in high-performance flexible supercapacitor devices. Herein, a composite hydrogel electrolyte of polyacrylic acid (PAA) and graphene oxide (GO) has been successfully prepared, where the oxygen-containing functional groups of GO may crosslink and form hydrogen bonds with carboxyl on the molecular chain of PAA, thereby significantly enhancing the mechanical properties of a PAA-based gel electrolyte. The tensile strength increases from 4.0 MPa for pristine PAA gel to 6.1 MPa for PAA/GO composite gel, with the elongation at break rising from 1556% to 1950%. Meanwhile, GO promotes the transportation of electrolyte ions, which are favorable for enhancing the ionic conductivity of the PAA hydrogel. As a result, the assembled supercapacitor based on PAA/GO composite hydrogel electrolyte shows enhanced capacitance retention of 64.3% at a large current density of 20 A g−1 and excellent cycling stability over 10,000 cycles at 5 A g−1. Furthermore, the fabricated flexible supercapacitor devices could maintain outstanding electrochemical performance at various bending angles of 0–90°, indicating a promising prospect for the PAA/GO hydrogel electrolyte in flexible wearable fields.
Electrochemical Deposition of Conductive Polymers on Fabrics
Authors: Serrano-Claumarchirant Jose F. , Muñoz-Espí Rafael , Cantarero Andrés , Culebras Mario , Gómez Clara M.
Published: February 2023

The development of wearable technology has promoted the research of new power supply sources to feed wearable devices without the need of batteries. Wearable thermoelectric generators (wTEGs) can generate energy using the thermal gradient between the human body and the ambient temperature. The most comfortable way to adapt wTEGs to the human body is by using textiles, which are flexible and breathable. In this work, we have developed a method to coat textiles with conductive polymers by electrodeposition on fabrics previously coated with multi-walled carbon nanotubes (MWCNT). The results show that the fabrics coated with polyaniline: sulfuric acid (PANI:H2SO4) present a very low thermal stability, and the variation of the electrical conductivity under wearable stress is not suitable for their use in smart textiles. However, the fabrics coated with poly (3,4-ethylenedioxythiophene: perchlorate) (PEDOT:ClO4) and polypyrrole: perchlorate (PPy:ClO4) show a good thermal stability, positive evolution of the electrical conductivity as a function of the twist angle, bending cycles, and bending radius, demostrating their potential use in practical wearable applications to coat fabrics by electrochemical deposition.
Investigation of Factors Affecting the Intermediate-Temperature Cracking Resistance of In-Situ Asphalt Mixtures Based on Semi-Circular Bending Test
Authors: Xu Duo , Ni Fujian , Du Hui , Zhao Zili , Wang Jingling , Chen Sheng
Published: February 2023

Cracking is one of the main distresses in asphalt pavement. At present, few studies have been conducted on the cracking performance of asphalt mixtures from the field due to the difficulty of sample collection. Therefore, this study aims to assess the cracking resistance of in-service asphalt pavement at intermediate temperature using a large number of field cores in Jiangsu province, China. A semi-circular bending (SCB) test at 25 °C was conducted on field-cored samples covering three asphalt layers from 16 in-service road sections that represent a combination of influencing factors, including air void, mixture type, service age, cumulative number of equivalent single-axle loads (ESALs), and overload rate. The flexibility index (FI) and tensile strength were calculated from the experimental data as cracking performance evaluation indices. According to the analysis of variance results, at the top layer, ESALs and service age had a strong influence on cracking resistance. The decline rate of FI became slower with increasing ESALs. The most rapid decline in crack resistance with service age occurred on medium-traffic-level sections that served for over 14 years. At the middle layer, the overload rate replaced service age as a significant factor for FI. At the bottom layer, the air void was the only significant factor affecting the cracking resistance. In general, as the depth of layer increased, the effect of traffic load and service age decreased, whereas the effect of material properties increased. In addition, the FI and tensile strength were more sensitive to traffic load and air void, respectively.
Radiomic Machine-Learning Analysis of Multiparametric Magnetic Resonance Imaging in the Diagnosis of Clinically Significant Prostate Cancer: New Combination of Textural and Clinical Features
Authors: Prata Francesco , Anceschi Umberto , Cordelli Ermanno , Faiella Eliodoro , Civitella Angelo , Tuzzolo Piergiorgio , Iannuzzi Andrea , Ragusa Alberto , Esperto Francesco , Prata Salvatore Mario , Sicilia Rosa , Muto Giovanni , Grasso Rosario Francesco , Scarpa Roberto Mario , Soda Paolo , Simone Giuseppe , Papalia Rocco
Published: February 2023

Background: The aim of our study was to develop a radiomic tool for the prediction of clinically significant prostate cancer. Methods: From September 2020 to December 2021, 91 patients who underwent magnetic resonance imaging prostate fusion biopsy at our institution were selected. Prostate cancer aggressiveness was assessed by combining the three orthogonal planes-Llocal binary pattern the 3Dgray level co-occurrence matrix, and other first order statistical features with clinical (semantic) features. The 487 features were used to predict whether the Gleason score was clinically significant (≥7) in the final pathology. A feature selection algorithm was used to determine the most predictive features, and at the end of the process, nine features were chosen through a 10-fold cross validation. Results: The feature analysis revealed a detection accuracy of 83.5%, with a clinically significant precision of 84.4% and a clinically significant sensitivity of 91.5%. The resulting area under the curve was 80.4%. Conclusions: Radiomic analysis allowed us to develop a tool that was able to predict a Gleason score of ≥7. This new tool may improve the detection rate of clinically significant prostate cancer and overcome the limitations of the subjective interpretation of magnetic resonance imaging, reducing the number of useless biopsies.
Performance-Status Deterioration during Sequential Chemo-Radiotherapy as a Predictive Factor in Locally Advanced Non-Small Cell Lung Cancer
Authors: Olszyna-Serementa Marta , Zaborowska-Szmit Magdalena , Szmit Sebastian , Jaśkiewicz Piotr , Zajda Katarzyna , Krzakowski Maciej , Kowalski Dariusz M.
Published: February 2023

The role of sequential chemoradiotherapy in non-small cell lung cancer (NSCLC) patients who are not eligible for concurrent therapy has not been clearly defined. The aim of this study was to determine the usefulness of Karnofsky performance status (KPS) monitoring and to define the factors determining clinical deterioration during sequential chemoradiotherapy in patients treated from July 2009 to October 2014. The study included 196 patients. The clinical stage was defined as III A in 94 patients (48%) and III B in 102 patients (52%). Reduced KPS was found in 129 patients (65.8%). Baseline KPS had no significant prognostic significance. Deterioration of KPS during chemoradiotherapy was observed in 53 patients (27%) and had a negative predictive value for both worse-progression free survival (HR = 1.44; 95% CI: 1.03–1.99; p = 0.03) and overall survival (HR = 1.42; 95% CI: 1.02–1, 99; p = 0.04). The deterioration of KPS correlated with the disease control rate 6 weeks after the end of chemoradiotherapy (p = 0.0085). The risk of KPS worsening increased with each subsequent day between the end of chemotherapy and the start of radiotherapy (OR = 1.03; 95%CI: 1.01–1.05; p = 0.001), but decreased with each year of older age of patients (OR = 0.94, 95% CI: 0.9–0.98, p = 0.009). The time between the end of chemotherapy and the start of radiotherapy determined the prognosis of NSCLC after chemoradiotherapy. It should be adjusted to the age of patients.
Microstructural Changes in the Macula Following Cataract Surgery in Patients with Type 2 Diabetes Mellitus Detected Using Optical Coherence Tomography Angiography
Authors: Svjaščenkova Lelde , Laganovska Guna , Tzivian Lilian
Published: February 2023

Background. Ophthalmologists treat diabetic macular edema before cataract surgery to reduce possible complications. Despite improvements in diagnostic techniques, whether cataract surgery per se causes the progression of diabetic retinopathy with macular edema remains unclear. This study aimed to evaluate the impact of phacoemulsification on the central retina and its correlation with diabetes compensation as well as changes in the retina before surgery. Methods. Thirty-four type 2 diabetes mellitus patients who underwent phacoemulsification cataract surgery were included in this prospective longitudinal study. Of them, 29.4% had macular edema before surgery, and 70.6% had a normal macular structure. All patients underwent ophthalmic examinations, including optical coherence tomography angiography, at baseline and at one and three months after surgery. The Mann-Whitney test was performed to compare the area of the foveal avascular zone, perimeter of the foveal avascular zone, and mean vascular density in the para- and perifoveal deep and superficial capillary plexuses. All parameters were measured before and at one and three months after surgery. Multiple linear regression models with adjustments for glycated hemoglobin and duration of diabetes mellitus were constructed to assess the association between the area of the foveal avascular zone and diabetic macular edema. Results. Significant differences in the area of the foveal avascular zone, perimeter of the foveal avascular zone, and perifoveal density in the deep capillary plexus were observed at all three time points. In the fully adjusted linear regression model, those without diabetic macular edema had a reduced probability for changes in the foveal avascular zone at one and three months after surgery (effect estimate β = −0.20 [95% CI −0.31; −0.09] and β = −0.13 [−0.22; −0.03] for one and three months, respectively) compared with those with diabetic macular edema. Conclusions. Cataract surgery itself does not cause significant and permanent increase in diabetic macular edema three months post-surgery. On the contrary, in a group with diabetic macular edema before the surgery, central retinal thickness tended to stabilize three months after surgery. If the duration of diabetes is shorter and diabetes is better compensated, the possibility of changes in the foveal avascular zone is reduced.
Joint Cancer Segmentation and PI-RADS Classification on Multiparametric MRI Using MiniSegCaps Network
Authors: Jiang Wenting , Lin Yingying , Vardhanabhuti Varut , Ming Yanzhen , Cao Peng
Published: February 2023

MRI is the primary imaging approach for diagnosing prostate cancer. Prostate Imaging Reporting and Data System (PI-RADS) on multiparametric MRI (mpMRI) provides fundamental MRI interpretation guidelines but suffers from inter-reader variability. Deep learning networks show great promise in automatic lesion segmentation and classification, which help to ease the burden on radiologists and reduce inter-reader variability. In this study, we proposed a novel multi-branch network, MiniSegCaps, for prostate cancer segmentation and PI-RADS classification on mpMRI. MiniSeg branch outputted the segmentation in conjunction with PI-RADS prediction, guided by the attention map from the CapsuleNet. CapsuleNet branch exploited the relative spatial information of prostate cancer to anatomical structures, such as the zonal location of the lesion, which also reduced the sample size requirement in training due to its equivariance properties. In addition, a gated recurrent unit (GRU) is adopted to exploit spatial knowledge across slices, improving through-plane consistency. Based on the clinical reports, we established a prostate mpMRI database from 462 patients paired with radiologically estimated annotations. MiniSegCaps was trained and evaluated with fivefold cross-validation. On 93 testing cases, our model achieved a 0.712 dice coefficient on lesion segmentation, 89.18% accuracy, and 92.52% sensitivity on PI-RADS classification (PI-RADS ≥ 4) in patient-level evaluation, significantly outperforming existing methods. In addition, a graphical user interface (GUI) integrated into the clinical workflow can automatically produce diagnosis reports based on the results from MiniSegCaps.
Electrophysiology as a Tool to Decipher the Network Mechanism of Visceral Pain in Functional Gastrointestinal Disorders
Authors: Alam Md Jahangir , Chen Jiande D. Z.
Published: February 2023

Abdominal pain, including visceral pain, is prevalent in functional gastrointestinal (GI) disorders (FGIDs), affecting the overall quality of a patient’s life. Neural circuits in the brain encode, store, and transfer pain information across brain regions. Ascending pain signals actively shape brain dynamics; in turn, the descending system responds to the pain through neuronal inhibition. Pain processing mechanisms in patients are currently mainly studied with neuroimaging techniques; however, these techniques have a relatively poor temporal resolution. A high temporal resolution method is warranted to decode the dynamics of the pain processing mechanisms. Here, we reviewed crucial brain regions that exhibited pain-modulatory effects in an ascending and descending manner. Moreover, we discussed a uniquely well-suited method, namely extracellular electrophysiology, that captures natural language from the brain with high spatiotemporal resolution. This approach allows parallel recording of large populations of neurons in interconnected brain areas and permits the monitoring of neuronal firing patterns and comparative characterization of the brain oscillations. In addition, we discussed the contribution of these oscillations to pain states. In summary, using innovative, state-of-the-art methods, the large-scale recordings of multiple neurons will guide us to better understanding of pain mechanisms in FGIDs.
An Italian Multicenter Perspective Harmonization Trial for the Assessment of MET Exon 14 Skipping Mutations in Standard Reference Samples
Authors: Bironzo Paolo , Pepe Francesco , Russo Gianluca , Pisapia Pasquale , Gragnano Gianluca , Aquino Gabriella , Bessi Silvia , Buglioni Simonetta , Bartoccini Federico , Ferrero Giuseppina , Bresciani Michela Anna , Francia di Celle Paola , Sibona Francesca , Giusti Andrea , Movilia Alessandra , Farioli Renata Mariella , Santoro Alessandra , Salemi Domenico , Scarpino Stefania , Galafate Dino , Tommasi Stefania , Lacalamita Rosanna , Seminati Davide , Sajjadi Elham , Novello Silvia , Pagni Fabio , Troncone Giancarlo , Malapelle Umberto
Published: February 2023

Lung cancer remains the leading cause of cancer deaths worldwide. International societies have promoted the molecular analysis of MET proto-oncogene, receptor tyrosine kinase (MET) exon 14 skipping for the clinical stratification of non-small cell lung cancer (NSCLC) patients. Different technical approaches are available to detect MET exon 14 skipping in routine practice. Here, the technical performance and reproducibility of testing strategies for MET exon 14 skipping carried out in various centers were evaluated. In this retrospective study, each institution received a set (n = 10) of a customized artificial formalin-fixed paraffin-embedded (FFPE) cell line (Custom METex14 skipping FFPE block) that harbored the MET exon 14 skipping mutation (Seracare Life Sciences, Milford, MA, USA), which was previously validated by the Predictive Molecular Pathology Laboratory at the University of Naples Federico II. Each participating institution managed the reference slides according to their internal routine workflow. MET exon 14 skipping was successfully detected by all participating institutions. Molecular analysis highlighted a median Cq cut off of 29.3 (ranging from 27.1 to 30.7) and 2514 (ranging from 160 to 7526) read counts for real-time polymerase chain reaction (RT-PCR) and NGS-based analyses, respectively. Artificial reference slides were a valid tool to harmonize technical workflows in the evaluation of MET exon 14 skipping molecular alterations in routine practice.