bluuebunny/crossref_metadata_2025 huggingface dataset:
Epidemiology of Undifferentiated Carcinomas
Authors: Benesch Matthew G. K. , O’Brien Shalana B. L.
Published: November 2022

Undifferentiated carcinomas are rare cancers that lack differentiation, such that they cannot be classified into any conventional histological subtype. These cancers are uniquely codified and are contrasted to carcinomas with an ascertained histology that are grade classified as poorly differentiated, undifferentiated, or anaplastic. Given their rarity, there are no standardized overviews of undifferentiated carcinomas in the literature, and it is unknown if their classification indicates a unique prognosis profile. In this study, we summarize the clinicodemographic and mortality outcomes of undifferentiated carcinomas in twelve primary sites and for unknown primaries, comprising 92.8% of all undifferentiated carcinomas diagnosed from 1975–2017 in the Surveillance, Epidemiology, and End Results Program (SEER). Incidence has decreased to 4 per 1 million cancer diagnoses since 1980. Relative to the most common undifferentiated cancers with a defined histology, undifferentiated carcinomas have overall worse prognosis, except in nasopharyngeal and salivary gland cancers (hazard ratio (HR) 0.7–1.3). After correction for age, sex, race, detection stage, and treatment (surgery, chemotherapy, and radiotherapy), the mortality HR averages 1.3–1.4 for these cancers relative to histologically ascertainable undifferentiated cancers. However, there is a wide variance depending on site, signifying that survival outcomes for undifferentiated carcinomas depend on factors related to site tumor biology.
Complications and Mortality Rate of Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy: Italian Peritoneal Surface Malignancies Oncoteam Results Analysis
Authors: Carboni Fabio , Valle Mario , Vaira Marco , Sammartino Paolo , Federici Orietta , Robella Manuela , Deraco Marcello , Framarini Massimo , Macrì Antonio , Sassaroli Cinzia , Lippolis Piero Vincenzo , Di Giorgio Andrea , Biacchi Daniele , Martin-Roman Lorena , Sperduti Isabella , Baratti Dario
Published: November 2022

Background: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy may significantly improve survival for selected patients with peritoneal surface malignancies, but it has always been criticized due to the high incidence of postoperative morbidity and mortality. Methods: Data were collected from nine Italian centers with peritoneal surface malignancies expertise within a collaborative group of the Italian Society of Surgical Oncology. Complications and mortality rates were recorded, and multivariate Cox analysis was used to identify risk factors. Results: The study included 2576 patients. The procedure was mostly performed for ovarian (27.4%) and colon cancer (22.4%). The median peritoneal cancer index was 13. Overall postoperative morbidity and mortality rates were 34% and 1.6%. A total of 232 (9%) patients required surgical reoperation. Multivariate regression logistic analysis identified the type of perfusion (p ≤ 0.0001), body mass index (p ≤ 0.0001), number of resections (p ≤ 0.0001) and colorectal resections (p ≤ 0.0001) as the strongest predictors of complications, whereas the number of resections (p ≤ 0.0001) and age (p = 0.01) were the strongest predictors of mortality. Conclusions: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy is a valuable option of treatment for selected patients with peritoneal carcinomatosis providing low postoperative morbidity and mortality rates, if performed in high-volume specialized centers.
A Novel High-Throughput Screening Method for a Human Multicentric Osteosarcoma-Specific Antibody and Biomarker Using a Phage Display-Derived Monoclonal Antibody
Authors: Hayashi Takuma , Yamamoto Naoki , Kurosawa Gene , Tajima Kaori , Kondo Mariko , Hiramatsu Noriko , Kato Yu , Tanaka Miho , Yamaguchi Hisateru , Kurosawa Yoshikazu , Yamada Harumoto , Fujita Nobuyuki
Published: November 2022

Osteosarcoma is a malignant tumor that produces neoplastic bone or osteoid osteoma. In human multicentric osteosarcoma (HMOS), a unique variant of human osteosarcoma (HOS), multiple bone lesions occur simultaneously or asynchronously before lung metastasis. HMOS is associated with an extremely poor prognosis, and effective treatment options are lacking. Using the proteins in our previously generated HMOS cell lines as antigens, we generated antibodies using a human antibody phage library. We obtained antibody clones recognizing 95 independent antigens and developed a fluorescence probe-based enzyme-linked immunosorbent assay (ELISA) technique capable of evaluating the reactivity of these antibodies by fluorescence intensity, allowing simple, rapid, and high-throughput selection of antibody clones. These results were highly correlated with those using flow cytometry. Subsequently, the HMOS cell lysate was incubated with the antibody, the antigen–antibody complex was recovered with magnetic beads, and the protein bands from electrophoresis were analyzed using liquid chromatography-mass spectrometry (LC/MS). CAVIN1/polymerase I transcript release factor was specifically detected in the HMOS cells. In conclusion, we found via a novel high-throughput screening method that CAVIN1/PTRF is an HMOS-specific cell membrane biomarker and an antigen capable of producing human antibodies. In the future, antibody–drug conjugate targeting of these specific proteins may be promising for clinical applications.
Copy Number Alteration and Mutational Profile of High-Grade B-Cell Lymphoma with MYC and BCL2 and/or BCL6 Rearrangements, Diffuse Large B-Cell Lymphoma with MYC-Rearrangement, and Diffuse Large B-Cell Lymphoma with MYC-Cluster Amplification
Authors: Miyaoka Masashi , Kikuti Yara Yukie , Carreras Joaquim , Ito Atsushi , Ikoma Haruka , Tomita Sakura , Kawada Hiroshi , Roncador Giovanna , Bea Silvia , Campo Elias , Nakamura Naoya
Published: November 2022

Diffuse large B-cell lymphoma (DLBCL) with MYC alteration is classified as high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements (double/triple-hit lymphoma; DHL/THL), DLBCL with MYC rearrangement (single-hit lymphoma; SHL) and DLBCL with MYC-cluster amplification (MCAD). To elucidate the genetic features of DHL/THL, SHL, and MCAD, 23 lymphoma cases from Tokai University Hospital were analyzed. The series included 10 cases of DHL/THL, 10 cases of SHL and 3 cases of MCAD. The analysis used whole-genome copy number microarray analysis (OncoScan) and a custom-made next-generation sequencing (NGS) panel of 115 genes associated with aggressive B-cell lymphomas. The copy number alteration (CNA) profiles were similar between DHL/THL and SHL. MCAD had fewer CNAs than those of DHL/THL and SHL, except for +8q24. The NGS profile characterized DHL/THL with a higher “mutation burden” than SHL (17 vs. 10, p = 0.010), and the most relevant genes for DHL/THL were BCL2 and SOCS1, and for SHL was DTX1. MCAD was characterized by mutations of DDX3X, TCF3, HLA-A, and TP53, whereas MYC was unmutated. In conclusion, DHL/THL, SHL, and MCAD have different profiles.
How Should We Treat Meningeal Melanocytoma? A Retrospective Analysis of Potential Treatment Strategies
Authors: Ricchizzi Sarah , Gallus Marco , Stummer Walter , Holling Markus
Published: November 2022

Background: Meningeal melanocytomas (MM) are rare primary melanocytic tumors of the leptomeninges with an incidence of 1:10,000,000. Until now, there has been only sparse information about this tumor entity. Here, we provide a meta-analysis of all cases published in the English language since 1972. Methods: A literature review was performed using PubMed and Web of Science. All published cases were evaluated for location, sex, age, therapeutic approach, and outcome. In total, we included 201 patient cases in our meta–analysis. Results: The majority of MM was diagnosed more frequently in men between the third and fifth decade of life. Surgery is the preferred therapeutic approach, and total resection is associated with the best outcome. Patients with partial resection or tumor recurrence benefit from adjuvant radiotherapy, whereas chemo- or immunotherapies do not improve the disease course. Malignant transformation was described in 18 patients. Of these, 11 patients developed metastasis. Conclusions: We present the first retrospective meta-analysis of all MM cases published in the English language, including an evaluation of different treatment strategies allowing us to suggest a novel treatment guideline highlighting the importance of total resection for recurrence–free survival and characterizing those cases which benefit from adjuvant radiotherapy.
Locoregional Approaches in Cholangiocarcinoma Treatment
Authors: Hare Alexander E. , Makary Mina S.
Published: November 2022

Cholangiocarcinoma (CCA) is a rare hepatic malignant tumor with poor prognosis due to late detection and anatomic factors limiting the applicability of surgical resection. Without surgical resection, palliation is the most common approach. In non-surgical cases contained within the liver, locoregional therapies provide the best chance for increased survival and disease control. The most common methods, transarterial chemoembolization and transarterial radioembolization, target tumors by embolizing their blood supply and limiting the tumor’s ability to metabolize. Other treatments induce direct damage via thermal ablation to tumor tissue to mediate their anti-tumor efficacy. Recent studies have begun to explore roles for these therapies outside their previous role of palliation. This review will outline the mechanisms of each of these treatments, along with their effects on overall survival, while comparing these to non-locoregional therapies.
circRNF10 Regulates Tumorigenic Properties and Natural Killer Cell-Mediated Cytotoxicity against Breast Cancer through the miR-934/PTEN/PI3k-Akt Axis
Authors: Liu Fei , Sang Yang , Zheng Yang , Gu Lina , Meng Lingjiao , Li Ziyi , Dong Yuyang , Wei Zishuan , Geng Cuizhi , Sang Meixiang
Published: November 2022

Circular RNA (circRNA), a type of non-coding RNA, has received a great deal of attention with regard to the initiation and progression of tumors. However, the molecular mechanism and function of circRNAs in breast cancer (BC) remain unclear. In the current study, we discovered that hsa_circ_0028899 (also called circRNF10) was significantly reduced in BC tissues, and a higher level of circRNF10 was markedly related to a favorable prognosis. The results of CCK8, colony formation, Transwell, ELISA, and NK cell-mediated cytotoxicity assays indicated that increased circRNF10 expression could significantly repress the proliferation, invasion, and migration of BC cells and enhance the killing efficiency of NK cells against BC cells. According to these biological functions, the possible role and molecular mechanism of circRNF10 in BC cells were further investigated. We used bioinformatics prediction tools to predict circRNF10-bound miRNAs, which were verified by many experimental studies, including FISH, luciferase reporter assays, RIP, and Western blots. These data suggest that circRNF10 serves as a molecular sponge for miR-934 to further regulate PTEN expression and PI3k/Akt/MICA signaling in vitro and tumor growth in vivo. Altogether, these findings reveal that circRNF10 functions as a novel anti-oncogene in BC via sponging miR-934 and suppressing the PI3K/Akt/MICA pathway.
UBA52 Is Crucial in HSP90 Ubiquitylation and Neurodegenerative Signaling during Early Phase of Parkinson’s Disease
Authors: Tiwari Shubhangini , Singh Abhishek , Gupta Parul , Singh Sarika
Published: November 2022

Protein aggregation is one of the major pathological events in age-related Parkinson’s disease (PD) pathology, predominantly regulated by the ubiquitin–proteasome system (UPS). UPS essentially requires core component ubiquitin; however, its role in PD pathology is obscure. This study aimed to investigate the role of ubiquitin-encoding genes in sporadic PD pathology. Both cellular and rat models of PD as well as SNCA C57BL/6J-Tg (Th-SNCA*A30P*A53T)39 Eric/J transgenic mice showed a decreased abundance of UBA52 in conjunction with significant downregulation of tyrosine hydroxylase (TH) and neuronal death. In silico predictions, mass spectrometric analysis, and co-immunoprecipitation findings suggested the protein–protein interaction of UBA52 with α-synuclein, HSP90 and E3-ubiquitin ligase CHIP, and its co-localization with α-synuclein in the mitochondrion. Next, in vitro ubiquitylation assay indicated an imperative requirement of the lysine-63 residue of UBA52 in CHIP-mediated HSP90 ubiquitylation. Myc-UBA52 expressed neurons inhibited alteration in PD-specific markers such as α-synuclein and TH protein along with increased proteasome activity in diseased conditions. Furthermore, Myc-UBA52 expression inhibited the altered protein abundance of HSP90 and its various client proteins, HSP75 (homolog of HSP90 in mitochondrion) and ER stress-related markers during early PD. Taken together, the data highlights the critical role of UBA52 in HSP90 ubiquitylation in parallel to its potential contribution to the modulation of various disease-related neurodegenerative signaling targets during the early phase of PD pathology.
Prolyl Isomerase, Pin1, Controls Meiotic Progression in Mouse Oocytes
Authors: Hoshino Yumi , Uchida Takafumi
Published: November 2022

During meiotic maturation, accurate progression of meiosis is ensured by multiple protein kinases and by signal transduction pathways they are involved in. However, the mechanisms regulating the functions of phosphorylated proteins are unclear. Herein, we investigated the role of Pin1, a peptidyl-prolyl cis-trans isomerase family member that regulates protein functions by altering the structure of the peptide bond of proline in phosphorylated proteins in meiosis. First, we analyzed changes in the expression of Pin1 during meiotic maturation and found that although its levels were constant, its localization was dynamic in different stages of meiosis. Furthermore, we confirmed that the spindle rotates near the cortex when Pin1 is inhibited by juglone during meiotic maturation, resulting in an error in the extrusion of the first polar body. In Pin1−/− mice, frequent polar body extrusion errors were observed in ovulation, providing insights into the mechanism underlying the errors in the extrusion of the polar body. Although multiple factors and mechanisms might be involved, Pin1 functions in meiosis progression via actin- and microtubule-associated phosphorylated protein targets. Our results show that functional regulation of Pin1 is indispensable in oocyte production and should be considered while developing oocyte culture technologies for reproductive medicine and animal breeding.
ZO-1 Guides Tight Junction Assembly and Epithelial Morphogenesis via Cytoskeletal Tension-Dependent and -Independent Functions
Authors: Haas Alexis J. , Zihni Ceniz , Krug Susanne M. , Maraspini Riccardo , Otani Tetsuhisa , Furuse Mikio , Honigmann Alf , Balda Maria S. , Matter Karl
Published: November 2022

Formation and maintenance of tissue barriers require the coordination of cell mechanics and cell–cell junction assembly. Here, we combined methods to modulate ECM stiffness and to measure mechanical forces on adhesion complexes to investigate how tight junctions regulate cell mechanics and epithelial morphogenesis. We found that depletion of the tight junction adaptor ZO-1 disrupted junction assembly and morphogenesis in an ECM stiffness-dependent manner and led to a stiffness-dependant reorganisation of active myosin. Both junction formation and morphogenesis were rescued by inhibition of actomyosin contractility. ZO-1 depletion also impacted mechanical tension at cell-matrix and E-cadherin-based cell–cell adhesions. The effect on E-cadherin also depended on ECM stiffness and correlated with effects of ECM stiffness on actin cytoskeleton organisation. However, ZO-1 knockout also revealed tension-independent functions of ZO-1. ZO-1-deficient cells could assemble functional barriers at low tension, but their tight junctions remained corrupted with strongly reduced and discontinuous recruitment of junctional components. Our results thus reveal that reciprocal regulation between ZO-1 and cell mechanics controls tight junction assembly and epithelial morphogenesis, and that, in a second, tension-independent step, ZO-1 is required to assemble morphologically and structurally fully assembled and functionally normal tight junctions.
LncRNA/miRNA/mRNA Network Introduces Novel Biomarkers in Prostate Cancer
Authors: Taheri Mohammad , Safarzadeh Arash , Hussen Bashdar Mahmud , Ghafouri-Fard Soudeh , Baniahmad Aria
Published: November 2022

The construction of a competing endogenous RNA (ceRNA) network is an important step in the identification of the role of differentially expressed genes in cancers. In the current research, we used a number of bioinformatics tools to construct the ceRNA network in prostate cancer and identify the importance of these modules in predicting the survival of patients with this type of cancer. An assessment of microarray data of prostate cancer and normal samples using the Limma package led to the identification of differential expressed (DE) RNAs that we stratified into mRNA, lncRNA, and miRNAs, resulting in 684 DEmRNAs, including 437 downregulated DEmRNAs (such as TGM4 and SCGB1A1) and 241 upregulated DEmRNAs (such as TDRD1 and CRISP3); 6 DElncRNAs, including 1 downregulated DElncRNA (H19) and 5 upregulated DElncRNAs (such as PCA3 and PCGEM1); and 59 DEmiRNAs, including 30 downregulated DEmiRNAs (such as hsa-miR-1274a and hsa-miR-1274b) and 29 upregulated DEmiRNAs (such as hsa-miR-1268 and hsa-miR-1207-5p). The ceRNA network contained a total of 5 miRNAs, 5 lncRNAs, and 17 mRNAs. We identified hsa-miR-17, hsa-miR-93, hsa-miR-150, hsa-miR-25, PART1, hsa-miR-125b, PCA3, H19, RND3, and ITGB8 as the 10 hub genes in the ceRNA network. According to the ROC analysis, the expression levels of 19 hub genes showed a high diagnostic value. Taken together, we introduce a number of novel promising diagnostic biomarkers for prostate cancer.
Molecular Cluster Mining of Adrenocortical Carcinoma via Multi-Omics Data Analysis Aids Precise Clinical Therapy
Authors: Guan Yu , Yue Shaoyu , Chen Yiding , Pan Yuetian , An Lingxuan , Du Hexi , Liang Chaozhao
Published: November 2022

Adrenocortical carcinoma (ACC) is a malignancy of the endocrine system. We collected clinical and pathological features, genomic mutations, DNA methylation profiles, and mRNA, lncRNA, microRNA, and somatic mutations in ACC patients from the TCGA, GSE19750, GSE33371, and GSE49278 cohorts. Based on the MOVICS algorithm, the patients were divided into ACC1-3 subtypes by comprehensive multi-omics data analysis. We found that immune-related pathways were more activated, and drug metabolism pathways were enriched in ACC1 subtype patients. Furthermore, ACC1 patients were sensitive to PD-1 immunotherapy and had the lowest sensitivity to chemotherapeutic drugs. Patients with the ACC2 subtype had the worst survival prognosis and the highest tumor-mutation rate. Meanwhile, cell-cycle-related pathways, amino-acid-synthesis pathways, and immunosuppressive cells were enriched in ACC2 patients. Steroid and cholesterol biosynthetic pathways were enriched in patients with the ACC3 subtype. DNA-repair-related pathways were enriched in subtypes ACC2 and ACC3. The sensitivity of the ACC2 subtype to cisplatin, doxorubicin, gemcitabine, and etoposide was better than that of the other two subtypes. For 5-fluorouracil, there was no significant difference in sensitivity to paclitaxel between the three groups. A comprehensive analysis of multi-omics data will provide new clues for the prognosis and treatment of patients with ACC.
SARS-CoV-2-Associated ssRNAs Activate Human Neutrophils in a TLR8-Dependent Fashion
Authors: Gardiman Elisa , Bianchetto-Aguilera Francisco , Gasperini Sara , Tiberio Laura , Scandola Matteo , Lotti Virginia , Gibellini Davide , Salvi Valentina , Bosisio Daniela , Cassatella Marco A. , Tamassia Nicola
Published: November 2022

COVID-19 disease is characterized by a dysregulation of the innate arm of the immune system. However, the mechanisms whereby innate immune cells, including neutrophils, become activated in patients are not completely understood. Recently, we showed that GU-rich RNA sequences from the SARS-CoV-2 genome (i.e., SCV2-RNA1 and SCV2-RNA2) activate dendritic cells. To clarify whether human neutrophils may also represent targets of SCV2-RNAs, neutrophils were treated with either SCV2-RNAs or, as a control, R848 (a TLR7/8 ligand), and were then analyzed for several functional assays and also subjected to RNA-seq experiments. Results highlight a remarkable response of neutrophils to SCV2-RNAs in terms of TNFα, IL-1ra, CXCL8 production, apoptosis delay, modulation of CD11b and CD62L expression, and release of neutrophil extracellular traps. By RNA-seq experiments, we observed that SCV2-RNA2 promotes a transcriptional reprogramming of neutrophils, characterized by the induction of thousands of proinflammatory genes, similar to that promoted by R848. Furthermore, by using CU-CPT9a, a TLR8-specific inhibitor, we found that SCV2-RNA2 stimulates neutrophils exclusively via TLR8-dependent pathways. In sum, our study proves that single-strand RNAs from the SARS-CoV-2 genome potently activate human neutrophils via TLR8, thus uncovering a potential mechanism whereby neutrophils may contribute to the pathogenesis of severe COVID-19 disease.
CircZXDC Promotes Vascular Smooth Muscle Cell Transdifferentiation via Regulating miRNA-125a-3p/ABCC6 in Moyamoya Disease
Authors: Liu Yuan , Huang Yimin , Zhang Xincheng , Ma Xiaopeng , He Xuejun , Gan Chao , Zou Xin , Wang Sheng , Shu Kai , Lei Ting , Zhang Huaqiu
Published: November 2022

Moyamoya disease (MMD) is an occlusive, chronic cerebrovascular disease affected by genetic mutation and the immune response. Furthermore, vascular smooth muscle cells (VSMCs) and endothelial cells (ECs) participate in the neointima of MMD, but the etiology and pathophysiological changes in MMD vessels remain largely unknown. Therefore, we established the circZXDC (ZXD family zinc finger C)–miR-125a-3p–ABCC6 (ATP-binding cassette subfamily C member 6) axis from public datasets and online tools based on “sponge-like” interaction mechanisms to investigate its possible role in VSMCs. The results from a series of in vitro experiments, such as dual luciferase reporter assays, cell transfection, CCK-8 assays, Transwell assays, and Western blotting, indicate a higher level of circZXDC in the MMD plasma, especially in those MMD patients with the RNF213 mutation. Moreover, circZXDC overexpression results in a VSMC phenotype switching toward a synthetic status, with increased proliferation and migration activity. CircZXDC sponges miR-125a-3p to increase ABCC6 expression, which induces ERS (endoplasmic reticulum stress), and subsequently regulates VSMC transdifferentiation from the contractive phenotype to the synthetic phenotype, contributing to the intima thickness of MMD vessels. Our findings provide insight into the pathophysiological mechanisms of MMD and indicate that the circZXDC–miR-125a-3p–ABCC6 axis plays a pivotal role in the progression of MMD. Furthermore, circZXDC might be a diagnostic biomarker and an ABCC6-specific inhibitor and has the potential to become a promising therapeutic option for MMD.
Exploring the Tryptophan Metabolic Pathways in Migraine-Related Mechanisms
Authors: Körtési Tamás , Spekker Eleonóra , Vécsei László
Published: November 2022

Migraine is a complex neurovascular disorder, which causes intense socioeconomic problems worldwide. The pathophysiology of disease is enigmatic; accordingly, therapy is not sufficient. In recent years, migraine research focused on tryptophan, which is metabolized via two main pathways, the serotonin and kynurenine pathways, both of which produce neuroactive molecules that influence pain processing and stress response by disturbing neural and brain hypersensitivity and by interacting with molecules that control vascular and inflammatory actions. Serotonin has a role in trigeminal pain processing, and melatonin, which is another product of this pathway, also has a role in these processes. One of the end products of the kynurenine pathway is kynurenic acid (KYNA), which can decrease the overexpression of migraine-related neuropeptides in experimental conditions. However, the ability of KYNA to cross the blood–brain barrier is minimal, necessitating the development of synthetic analogs with potentially better pharmacokinetic properties to exploit its therapeutic potential. This review summarizes the main translational and clinical findings on tryptophan metabolism and certain neuropeptides, as well as therapeutic options that may be useful in the prevention and treatment of migraine.
Molecular Immunology in Bacterial Vaccine Discovery
Authors: Berisio Rita
Published: November 2022

The global threat of antimicrobial resistance (AMR) poses a difficult challenge, as underscored by the World Health Organization (WHO), which identifies AMR as one of the three greatest threats to human health [...]
A Dual Fluorometric and Colorimetric Sulfide Sensor Based on Coordinating Self-Assembled Nanorods: Applicable for Monitoring Meat Spoilage
Authors: Dalapati Rana , Hunter Matthew , Zang Ling
Published: November 2022

Psychrotrophic bacteria, commonly called spoilage bacteria, can produce highly toxic hydrogen sulfide (H2S) in meat products. Thus, monitoring the presence of hydrogen sulfide in meat samples is crucial for food safety and storage. Here, we report a unique chemical sensor based on supramolecular nanorods synthesized via copper ion induced self-assembly of N,N-bis[aspartic potassium salt]-3,4,9,10-perylenetetracarboxylic diimide (APBI-K). The self-assembled nanorods can specifically detect sulfide with a detection limit of 0.181 μM in solution. The nanorods suspended in pure water show a turn-on fluorescence sensing behavior along with color change, acting as a dual fluorometric and colorimetric sensor. Spectroscopic investigation confirms the sensing mechanism due to copper ion displacement induced by the association with sulfide. Based on the high selectivity and sensitivity, supramolecular nanorod sensors were successfully employed to detect H2S in spoiled meat sample as well as dissolved H2S in water.
Catalyzed Hairpin Assembly-Assisted DNA Dendrimer Enhanced Fluorescence Anisotropy for MicroRNA Detection
Authors: Xie Tianjin , Liu Yuxin , Xie Jiali , Luo Yujie , Mao Kai , Huang Chengzhi , Li Yuanfang , Zhen Shujun
Published: November 2022

Biomacromolecules have been employed successfully as fluorescence anisotropy (FA) amplifiers for biosensing in reported studies. However, the sensitivities of the traditional biomacromolecule amplified FA strategies need to be improved because of the relatively low molecular weight or volume of a single biomacromolecule and the 1:1 binding ratio between the fluorophore-linked probe and target. In this work, a DNA dendrimer with a high molecular weight and volume was employed as a new FA amplifier, which was coupled with target-catalyzed hairpin assembly (CHA) for the sensitive detection of miRNA-21. The fluorophore-modified probe DNA (pDNA) was fixed on the DNA dendrimer, resulting in a high FA value. The addition of miRNA-21 triggered the CHA process and produced plenty of H1-H2 hybrids. The complex of H1-H2 bound to the DNA dendrimer and released the pDNA through a toehold-mediated strand exchange reaction. Thus, a low FA value was obtained because of the low mass and volume of free pDNA. Based on the dramatically reduced FA, miRNA-21 was detected in the range of 1.0–19.0 nM and the limit of detection was 52.0 pM. In addition, our method has been successfully utilized for miRNA-21 detection in human serum. This strategy is sensitive and selective and is expected to be used to detect other biomolecules simply by changing the corresponding nucleic acid probe.
Enhanced Visible Light Absorption and Photophysical Features of Novel Isomeric Magnesium Phthalocyaninates with Cyanophenoxy Substitution
Authors: Erzunov Dmitry , Tonkova Svetlana , Belikova Anastasia , Vashurin Arthur
Published: November 2022

Novel metal-free and Mg(II) [3/4-(3,4-dicyanophenoxy)phenoxy]-substituted phthalocyanines were obtained and characterized using NMR, IR, UV-vis spectroscopy, and mass spectrometry. This substitution provided compounds with good solubility in organic media, and thus their spectroscopic and fluorescent properties were studied. The formation of the investigated phthalocyanine complexes with central magnesium ions led to the stabilization of macrocyclic molecules in solution, preventing aggregation through specific and universal solvation. From meta-substitution to para-substitution, insignificant spectroscopic changes were observed. The complexes exhibited higher values of molar light absorption coefficients and fluorescence quantum yields (up to 55%) compared to ligands. The efficiency of both the fluorescence-quenching and singlet oxygen generation processes in the case of magnesium [3/4-(3,4-dicyanophenoxy)phenoxy]phthalocyaninates was found to exceed that of the unsubstituted zinc phthalocyaninate, which suggests the potential applicability of these compounds as PDT sensitizers.
Clinical Presentation and Surgical Management of Five Pediatric Cases with Bronchogenic Cysts: Retrospective Case Series
Authors: Asseri Ali Alsuheel , Shati Ayed A. , Moshebah Amal Y. , Alshahrani Omair M. , Saad Rayan M. , Alzuhari Abdulmohsin M. , Qout Maraam M. Al , Al-Helal Abdullah S.
Published: November 2022

Background: Bronchogenic cysts (BCs) refer to congenital lesions that result from primitive or abnormal foregut budding, and can be pulmonary or mediastinal. Their occurrence can take place at any point on the tracheobronchial tree, but they are usually localized in the lung parenchyma and mediastinum, and may be symptomatic or asymptomatic. Bronchogenic cyst symptoms can vary, depending on the size and location of the cyst. Methods: A retrospective review of the charts of five patients with a histopathological diagnosis of bronchogenic cysts was performed between 2014 and 2020. The patients reported in this study were diagnosed and managed at Abha Maternity and Children Hospital, Abha, southwest Saudi Arabia. In addition, demographic information, as well as diagnostic and therapeutic information, was provided for each patient, both at discharge and after discharge. All patients had confirmed congenital bronchogenic cysts with different clinical phenotypes and radiological findings. Results: All patients had histopathologically confirmed bronchogenic cysts with different clinical and radiological presentations. Two patients had mediastinal-located cysts; one had a laryngeal cyst; and the last two patients had infected intrapulmonary bronchogenic cysts. All patients underwent complete excision and did not experience recurrence or other postoperative complications during the follow-up period. The latter two patients required lobectomies of the right middle and upper lobes. Conclusions: Although bronchogenic cysts are considered a rare congenital pulmonary malformation, they should be considered in the differential diagnosis of pediatric patients with unusual airway and parenchymal lung manifestations, particularly, persistent stridor, feeding difficulty, and complicated pneumonia. Surgical excision of the cyst is the gold-standard therapy for symptomatic bronchogenic cysts and is highly recommended for asymptomatic ones. Long-term follow-up studies will be required to explore any long-term complications of BCs, particularly regarding the malignancy transformation.
Utility of Cerebral Microvascular Imaging in Infants Undergoing ECMO
Authors: Tierradentro-Garcia Luis Octavio , Stern Joseph A. , Dennis Rebecca , Hwang Misun
Published: November 2022

Purpose: Infants who require extracorporeal membrane oxygenation (ECMO) therapy have an increased risk of neurological complications and mortality. Microvascular imaging (MVI) is an advanced Doppler technique that allows high-resolution visualization of microvasculature in the brain. We describe the feasibility and utility of MVI for the evaluation of cerebral microvascular perfusion in patients undergoing ECMO. Methods: We retrospectively analyzed brain MVI scans of neonates undergoing ECMO. Two pediatric radiologists qualitatively assessed MVI scans to determine the presence or absence of tortuosity, symmetry, heterogeneity, engorgement, and hypoperfusion of the basal ganglia–thalamus (BGT) region, as well as the presence or absence of white matter vascular engorgement and increased peri-gyral flow in the cortex. We tested the association between the presence of the aforementioned brain MVI features and clinical outcomes. Results: We included 30 patients, 14 of which were male (46.7%). The time of ECMO duration was 11.8 ± 6.9 days. The most prevalent microvascular finding in BGT was lenticulostriate vessel tortuosity (26/30, 86.7%), and the most common microvascular finding in the cortex was increased peri-gyral flow (10/24, 41.7%). Cortical white matter vascular engorgement was significantly associated with the presence of any poor outcome as defined by death, seizure, and/or cerebrovascular events on magnetic resonance imaging (p = 0.03). Conclusion: MVI is a feasible modality to evaluate cerebral perfusion in infants undergoing ECMO. Additionally, evidence of white matter vascular engorgement after ECMO cannulation could serve as a predictor of poor outcomes in this population.
Effectiveness of a Visual Interactive Game on Oral Hygiene Knowledge, Practices, and Clinical Parameters among Adolescents: A Randomized Controlled Trial
Authors: K Ram , Deshpande Apurva , Ankola Anil , Sankeshwari Roopali , Jalihal Sagar , Hampiholi Vinuta , Khot Atrey , Hebbal Mamata , Kotha Sree , S Lokesh
Published: November 2022

This study aimed to evaluate the effect of a novel interactive game-based visual performance technique (IGVP) and conventional oral health educational (OHE) talk on plaque control, gingival health, and oral hygiene knowledge and practices in 12–15-year-old schoolchildren. A single-blinded randomized controlled trial was undertaken in a private primary school in Belagavi, Karnataka, India. A total of 100 children aged 12–15 years were randomly assigned to either a conventional OHE talk (control group, n = 50) or the IGVP technique (test group, n = 50), using a computer-generated table of random numbers. A self-designed, pre-validated closed-ended questionnaire was collected from both groups, followed by clinical examination carried out using gingival and plaque index, pre- and post-intervention, at three months follow-up. There was a significant reduction in the mean gingival score and plaque score in the test group after intervention, indicating a 58.7% and 63.4% reduction, when compared to the control group, which had a 2.8% and 0.7% reduction, respectively (p < 0.001). The test group showed a significant increase in the percentage of knowledge gained (22.4%), compared to control group (7.8%). The IGVP technique proved to be more effective than a conventional OHE talk in the reduction of the plaque score, gingival score, and in the improvement of the knowledge of oral hygiene maintenance and its application.
Parental Burden and Quality of Life in 5q-SMA Diagnosed by Newborn Screening
Authors: Kölbel Heike , Modler Laura , Blaschek Astrid , Schara-Schmidt Ulrike , Vill Katharina , Schwartz Oliver , Müller-Felber Wolfgang
Published: November 2022

The aim of this study was to assess the psychosocial burden in parents of children with spinal muscular atrophy (SMA), detected by newborn screening (NBS), for which first pilot projects started in January 2018 in Germany. The survey, performed 1–2 years after children’s diagnosis of SMA via NBS, included 3 parent-related questionnaires to evaluate the psychosocial burden, quality of life (QoL)/satisfaction and work productivity and activity impairment in the families. 42/44 families, detected between January 2018 and February 2020, could be investigated. Interestingly, statistical analysis revealed a significant difference between families with children that received SMN-targeted therapy vs. children with a wait-and-see strategy as to social burden (p = 0.016) and personal strain/worries about the future (p = 0.02). However, the evaluation of QoL showed no significant differences between treated vs. untreated children. Fathers of treated children felt more negative impact regarding their productivities at work (p = 0.005) and more negative effects on daily activities (p = 0.022) than fathers of untreated children. Thus, NBS in SMA has a psychosocial impact on families, not only in terms of diagnosis but especially in terms of treatment, and triggers concerns about the future, emphasizing the need for comprehensive multidisciplinary care. Understanding the parents’ perspective allows genetic counselors and NBS programs to proactively develop a care plan for parents during the challenging time of uncertainty, anxiety, frustration, and fear of the unknown.
Knowledge and Practice of Pediatricians Regarding Hypovitaminosis D—A Survey across 33 European Countries
Authors: Petrović Davor , Runjić Edita , Buljan Ivan , Jeličić Kadić Antonia , Markić Joško
Published: November 2022

Hypovitaminosis D has been recognized as a worldwide pandemic, but there are disagreements regarding its diagnosis and treatment. This study aimed to evaluate the knowledge and practice of European pediatricians concerning vitamin D (VD) and hypovitaminosis D and their adherence to relevant guidelines. A cross-sectional study was conducted through an anonymous survey via SurveyMonkey on 304 European pediatricians. Most of the participants were general pediatricians, followed by endocrinologists and neonatologists. ESPGHAN’s and the national guidelines were the most frequently used. VD testing was mostly performed in patients with skeletal, chronic kidney, and autoimmune diseases. Participants predominantly answered the questions regarding the definition of hypovitaminosis D and VD supplementation correctly, especially in children younger than 12 months. They showed the least knowledge regarding the cut off-point for the initiation of the therapy and therapeutic doses used to treat confirmed hypovitaminosis D. Participants’ conflicting answers could be related to the differences between the guidelines. We consider that experts in this field should create uniform guidelines, and that those guidelines should also be promoted by national or local pediatric associations.
Chest Compression Rates of 90/min versus 180/min during Neonatal Cardiopulmonary Resuscitation: A Randomized Controlled Animal Trial
Authors: Bruckner Marlies , Neset Mattias , Garcia-Hidalgo Catalina , Lee Tze-Fun , O’Reilly Megan , Cheung Po-Yin , Schmölzer Georg M.
Published: November 2022

Background: To compare chest compression (CC) rates of 90/min with 180/min and their effect on the time to return of spontaneous circulation (ROSC), survival, hemodynamic, and respiratory parameters. We hypothesized that asphyxiated newborn piglets that received CC at 180/min vs. 90/min during cardiopulmonary resuscitation would have a shorter time to ROSC. Methods: Newborn piglets (n = 7/group) were anesthetized, intubated, instrumented and exposed to 45 min normocapnic hypoxia followed by asphyxia and cardiac arrest. Piglets were randomly allocated to a CC rate of 180/min or 90/min. CC was performed using an automated chest compression machine using CC superimposed with sustained inflation. Hemodynamic and respiratory parameters and applied compression force were continuously measured. Results: The mean (SD) time to ROSC was 91 (34) and 256 (97) s for CC rates of 180/min and 90/min, respectively (p = 0.08). The number of piglets that achieved ROSC was 7 (100%) and 5 (71%) with 180/min and 90/min CC rates, respectively (p = 0.46). Hemodynamic parameters (i.e., diastolic and mean blood pressure, carotid blood flow, stroke volume, end-diastolic volume, left ventricular contractile function) and respiratory parameters (i.e., minute ventilation, peak inflation and peak expiration flow) were all improved with a CC rate of 180/min. Conclusion: Time to ROSC and hemodynamic and respiratory parameters were not statistical significant different between CC rates of 90/min and 180/min. Higher CC rates during neonatal resuscitation warrant further investigation.
Adverse Childhood Experiences: Mental Health Consequences and Risk Behaviors in Women and Men in Chile
Authors: Ramírez Labbé Sofía , Santelices María Pía , Hamilton James , Velasco Carolina
Published: November 2022

Studies conducted worldwide indicate that adverse childhood experiences (ACEs) are among the most intense and frequent sources of stress, considerably influencing mental and physical health while also resulting in risk behaviors in adulthood. Methodology: We used data from the Pilot National Survey of Adversity and Sexual Abuse in Childhood (2020), conducted by CUIDA UC, which comprises the Adverse Childhood Experiences International Questionnaire [ACE-IQ] (Adapted). The cross-sectional methodology used made it possible to directly calculate the prevalence of adverse childhood experiences in the population sampled, at a single point in time. We performed a bivariate and univariate descriptive analysis, a correlation analysis, and a multivariate analysis, all of which will be detailed in the section entitled “General Data Analysis Procedure”. Results: We found equally high rates of adverse childhood experiences in men and women, with community violence exhibiting the highest prevalence. We found significant low- to moderate-sized associations between the multiple types of ACEs considered and mental health problems, substance use problems, criminal behaviors, and intrafamily violence (IFV), which differed between men and women. Significant correlations were detected between the ACE score and mental health, substance use, criminal behaviors, and IFV in both men and women. Importantly, ACEs were found to be predictors of all of these variables, with differences observed between men and women. Conclusions: Nearly all participants reported having had at least one ACE and more than half reported had four or more ACEs. Those who had had four or more ACEs were more likely to report problems throughout their life. Having an ACE of any type was found to be a better predictor of mental health problems and IFV in men than in women and might be a stronger risk factor for substance use and criminal behaviors in women than in men.
Modifiable Risk Factors of Non-Syndromic Orofacial Clefts: A Systematic Review
Authors: Inchingolo Angelo Michele , Fatone Maria Celeste , Malcangi Giuseppina , Avantario Pasquale , Piras Fabio , Patano Assunta , Di Pede Chiara , Netti Anna , Ciocia Anna Maria , De Ruvo Elisabetta , Viapiano Fabio , Palmieri Giulia , Campanelli Merigrazia , Mancini Antonio , Settanni Vito , Carpentiere Vincenzo , Marinelli Grazia , Latini Giulia , Rapone Biagio , Tartaglia Gianluca Martino , Bordea Ioana Roxana , Scarano Antonio , Lorusso Felice , Di Venere Daniela , Inchingolo Francesco , Inchingolo Alessio Danilo , Dipalma Gianna
Published: November 2022

OFCs (orofacial clefts) are among the most frequent congenital defects, but their etiology has yet to be clarified. OFCs affect different structures and functions with social, psychological and economic implications in children and their families. Identifying modifiable risk factors is mandatory to prevent the occurrence of non-syndromic OFCs (NSOFCs). PubMed, Cochrane Library, Scopus and Web of Science were searched from 1 January 2012 to 25 May 2022 and a total of 7668 publications were identified. Studies focusing on the risk factors of NSOFCs were selected, leading to 62 case-control and randomized clinical trials. Risk factors were categorized into non-modifiable and modifiable. The first group includes genetic polymorphisms, gender of the newborn, ethnicity, and familiarity. Within the second group, risk factors that can only be modified before conception (consanguinity, parental age at conception, socio-economical and educational level, area of residency and climate), and risk factors modifiable before and after conception (weight, nutritional state, acute and chronic diseases, psychophysical stress, licit and illicit drugs, alcohol, smoke, pollutants and contaminants) have been distinguished. This study provides a wide overview of the risk factors of NSOFCs, focusing on modifiable ones, to suggest new perspectives in education, prevention, medical interventions and clinical research.
Maternal Group B Streptococcal Rectovaginal Colonization after Intrapartum Antibiotic Prophylaxis
Authors: Liu Ping , Feng Qiaoli , Liang Yiheng , Wang Xinxin , Xiao Zhansong , Huang Liting , Li Yun , Deng Yuqing , Yu Lin , Xin Yang , Fan Shangrong
Published: November 2022

Maternal rectovaginal colonization with Group B Streptococcus (GBS) during labor is a prerequisite for neonatal early-onset GBS disease. Intrapartum antibiotic prophylaxis (IAP) has been proven to prevent GBS perinatal infection, while there are few studies on the evaluation of the effectiveness of different antibiotic prophylaxis regimens. This study aimed to assess the maternal rectovaginal GBS colonization status after IAP, antimicrobial susceptibility and maternal and neonatal outcomes among women administered different antibiotic prophylaxis regimens. A prospective study was conducted between June 2018 and June 2022. GBS carriers identified at 35–37 weeks of gestation were provided IAP (penicillin, cefazolin or clindamycin) at delivery based on the local protocol for GBS prevention. Rectovaginal samples were obtained from participants again after delivery. Antimicrobial susceptibility testing in GBS isolates was performed using the broth microdilution method. A total of 295 cases were included in this study. In the postpartum re-examination for GBS, the overall negative rectovaginal culture rate was 90.8% (268/295). Women who received cefazolin prophylaxis had the highest negative culture rate (95.2%, 197/207), which was followed by those who received penicillin (80.7%, 67/83) and clindamycin (80.0%, 4/5) (p = 0.001). All GBS isolates achieved sensitivity to penicillin and cefazolin, whereas resistance to clindamycin was shown in 21.4% of the strains. There were no significant differences in maternal and neonatal outcomes among the IAP groups. The use of IAP is highly effective in reducing the maternal rectovaginal GBS colonization. Cefazolin may offer equivalent efficacy and safety compared to standard penicillin prophylaxis.
Different Dental Manifestations in Sisters with the Same ALPL Gene Mutation: A Report of Two Cases
Authors: Kadota Tamami , Ochiai Marin , Okawa Rena , Nakano Kazuhiko
Published: November 2022

Hypophosphatasia (HPP) is an inherited disease caused by mutation of the alkaline phosphatase (ALPL) gene in an autosomal dominant or an autosomal recessive manner. The main symptoms of HPP are bone hypomineralization and early exfoliation of the primary teeth. Some of the mutations identified in autosomal dominant families are reported to have dominant negative effects. In addition, the penetrance can vary among patients with the same variant even within the same family, resulting in various phenotypes of systemic symptoms. However, differences in dental symptoms between patients with HPP and carriers with the same ALPL variant have not been reported. Herein, we report on two sisters who had the same heterozygous ALPL variant with dominant negative effects. The older sister had bone and dental symptoms and was diagnosed with childhood HPP. In contrast, the younger sister was a carrier with no bone and dental symptoms. It can be inferred that this phenomenon was caused by the difference in penetrance. This case revealed that carriers with the ALPL mutation may have no dental symptoms characteristic of HPP. Because HPP is sometimes progressive, it is very important to carefully monitor carriers to detect the possible onset of dental and systemic symptoms.