bluuebunny/crossref_metadata_2025 huggingface dataset:
Presenting Psychiatric and Neurological Symptoms and Signs of Brain Tumors before Diagnosis: A Systematic Review
Authors: Ghandour Fatima , Squassina Alessio , Karaky Racha , Diab-Assaf Mona , Fadda Paola , Pisanu Claudia
Published: February 2021

Brain tumors can present with various psychiatric symptoms, with or without neurological symptoms, an aspect that complicates the clinical picture. However, no systematic description of symptoms that should prompt a neurological investigation has been provided. This review aims to summarize available case reports describing patients with brain tumors showing psychiatric symptoms before brain tumor diagnosis, in order to provide a comprehensive description of these symptoms as well as their potential relationship with delay in the diagnosis. A systematic literature review on case reports of brain tumors and psychiatric symptoms from 1970 to 2020 was conducted on PubMed, Ovid, Psych Info, and MEDLINE. Exclusion criteria comprised tumors not included in the World Health Organization (WHO) Classification 4th edition and cases in which psychiatric symptoms were absent or followed the diagnosis. A total of 165 case reports were analyzed. In a subset of patients with brain tumors, psychiatric symptoms can be the only manifestation or precede focal neurological signs by months or even years. The appearance of focal or generalized neurological symptoms after, rather than along with, psychiatric symptoms was associated with a significant delay in the diagnosis in adults. A timely assessment of psychiatric symptoms might help to improve early diagnosis of brain tumors.
COVID-19 and Alzheimer’s Disease
Authors: Ciaccio Marcello , Lo Sasso Bruna , Scazzone Concetta , Gambino Caterina Maria , Ciaccio Anna Maria , Bivona Giulia , Piccoli Tommaso , Giglio Rosaria Vincenza , Agnello Luisa
Published: February 2021

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a neurotropic virus with a high neuroinvasive potential. Indeed, more than one-third of patients develop neurological symptoms, including confusion, headache, and hypogeusia/ageusia. However, long-term neurological consequences have received little interest compared to respiratory, cardiovascular, and renal manifestations. Several mechanisms have been proposed to explain the potential SARS-CoV-2 neurological injury that could lead to the development of neurodegenerative diseases, including Alzheimer’s Disease (AD). A mutualistic relationship between AD and COVID-19 seems to exist. On the one hand, COVID-19 patients seem to be more prone to developing AD. On the other hand, AD patients could be more susceptible to severe COVID-19. In this review, we sought to provide an overview on the relationship between AD and COVID-19, focusing on the potential role of biomarkers, which could represent precious tool for early identification of COVID-19 patients at high risk of developing AD.
Associations between News Media Coverage of the 11 September Attacks and Depression in Employees of New York City Area Businesses
Authors: Pfefferbaum Betty , Palka Jayme M. , North Carol S.
Published: February 2021

Research has examined the association between contact with media coverage of mass trauma events and various psychological outcomes, including depression. Disaster-related depression research is complicated by the relatively high prevalence of the major depressive disorder in general populations even without trauma exposure. The extant research is inconclusive regarding associations between disaster media contact and depression outcomes, in part, because most studies have not distinguished diagnostic and symptomatic outcomes, differentiated postdisaster incidence from prevalence, or considered disaster trauma exposures. This study examined these associations in a volunteer sample of 254 employees of New York City businesses after the 11 September 2001, terrorist attacks. Structured interviews and questionnaires were administered 35 months after the attacks. Poisson and logistic regression analyses revealed that post-9/11 news contact significantly predicted the number of postdisaster persistent/recurrent and incident depressive symptoms in the full sample and in the indirect and unexposed groups. The findings suggest that clinical and public health approaches should be particularly alert to potential adverse postdisaster depression outcomes related to media consumption in disaster trauma-unexposed or indirectly-exposed groups.
Circulating Tumor DNA Detection by Digital-Droplet PCR in Pancreatic Ductal Adenocarcinoma: A Systematic Review
Authors: Huerta Marisol , Roselló Susana , Sabater Luis , Ferrer Ana , Tarazona Noelia , Roda Desamparados , Gambardella Valentina , Alfaro-Cervelló Clara , Garcés-Albir Marina , Cervantes Andrés , Ibarrola-Villava Maider
Published: February 2021

Pancreatic cancer (PC) is one of the most devastating malignant tumors, being the seventh leading cause of cancer-related death worldwide. Researchers and clinicians are endeavoring to develop strategies for the early detection of the disease and the improvement of treatment results. Adequate biopsy is still challenging because of the pancreas’s poor anatomic location. Recently, circulating tumor DNA (ctDNA) could be identified as a liquid biopsy tool with huge potential as a non-invasive biomarker in early diagnosis, prognosis and management of PC. ctDNA is released from apoptotic and necrotic cancer cells, as well as from living tumor cells and even circulating tumor cells, and it can reveal genetic and epigenetic alterations with tumor-specific and individual mutation and methylation profiles. However, ctDNA sensibility remains a limitation and the accuracy of ctDNA as a biomarker for PC is relatively low and cannot be currently used as a screening or diagnostic tool. Increasing evidence suggests that ctDNA is an interesting biomarker for predictive or prognosis studies, evaluating minimal residual disease, longitudinal follow-up and treatment management. Promising results have been published and therefore the objective of our review is to understand the current role and the future perspectives of ctDNA in PC.
Radio-Iodide Treatment: From Molecular Aspects to the Clinical View
Authors: De la Vieja Antonio , Riesco-Eizaguirre Garcilaso
Published: February 2021

Thyroid radio-iodide therapy (RAI) is one of the oldest known and used targeted therapies. In thyroid cancer, it has been used for more than eight decades and is still being used to improve thyroid tumor treatment to eliminate remnants after thyroid surgery, and tumor metastases. Knowledge at the molecular level of the genes/proteins involved in the process has led to improvements in therapy, both from the point of view of when, how much, and how to use the therapy according to tumor type. The effectiveness of this therapy has spread into other types of targeted therapies, and this has made sodium/iodide symporter (NIS) one of the favorite theragnostic tools. Here we focus on describing the molecular mechanisms involved in radio-iodide therapy and how the alteration of these mechanisms in thyroid tumor progression affects the diagnosis and results of therapy in the clinic. We analyze basic questions when facing treatment, such as: (1) how the incorporation of radioiodine in normal, tumor, and metastatic thyroid cells occurs and how it is regulated; (2) the pros and cons of thyroid hormonal deprivation vs. recombinant human Thyroid Stimulating Hormone (rhTSH) in radioiodine residence time, treatment efficacy, thyroglobulin levels and organification, and its influence on diagnostic imaging tests and metastasis treatment; and (3) the effect of stunning and the possible causes. We discuss the possible incorporation of massive sequencing data into clinical practice, and we conclude with a socioeconomical and clinical vision of the above aspects.
Stem Cell Impairment at the Host-Microbiota Interface in Colorectal Cancer
Authors: Marzano Marinella , Fosso Bruno , Piancone Elisabetta , Defazio Giuseppe , Pesole Graziano , De Robertis Mariangela
Published: February 2021

Colorectal cancer (CRC) initiation is believed to result from the conversion of normal intestinal stem cells (ISCs) into cancer stem cells (CSCs), also known as tumor-initiating cells (TICs). Hence, CRC evolves through the multiple acquisition of well-established genetic and epigenetic alterations with an adenoma-carcinoma sequence progression. Unlike other stem cells elsewhere in the body, ISCs cohabit with the intestinal microbiota, which consists of a diverse community of microorganisms, including bacteria, fungi, and viruses. The gut microbiota communicates closely with ISCs and mounting evidence suggests that there is significant crosstalk between host and microbiota at the ISC niche level. Metagenomic analyses have demonstrated that the host-microbiota mutually beneficial symbiosis existing under physiologic conditions is lost during a state of pathological microbial imbalance due to the alteration of microbiota composition (dysbiosis) and/or the genetic susceptibility of the host. The complex interaction between CRC and microbiota is at the forefront of the current CRC research, and there is growing attention on a possible role of the gut microbiome in the pathogenesis of CRC through ISC niche impairment. Here we primarily review the most recent findings on the molecular mechanism underlying the complex interplay between gut microbiota and ISCs, revealing a possible key role of microbiota in the aberrant reprogramming of CSCs in the initiation of CRC. We also discuss recent advances in OMICS approaches and single-cell analyses to explore the relationship between gut microbiota and ISC/CSC niche biology leading to a desirable implementation of the current precision medicine approaches.
Clinical and Molecular Characteristics and Outcome of Cystic Partially Differentiated Nephroblastoma and Cystic Nephroma: A Narrative Review of the Literature
Authors: van Peer Sophie E. , Pleijte Corine J. H. , de Krijger Ronald R. , Jongmans Marjolijn C. J. , Kuiper Roland P. , Lilien Marc R. , van Grotel Martine , Graf Norbert , van den Heuvel-Eibrink Marry M. , Hol Janna A.
Published: February 2021

In children presenting with a predominantly cystic renal tumor, the most likely diagnoses include cystic partially differentiated nephroblastoma (CPDN) and cystic nephroma (CN). Both entities are rare and limited information on the clinical and molecular characteristics, treatment, and outcome is available since large cohort studies are lacking. We performed an extensive literature review, in which we identified 113 CPDN and 167 CN. The median age at presentation for CPDN and CN was 12 months (range: 3 weeks–4 years) and 16 months (prenatal diagnosis–16 years), respectively. No patients presented with metastatic disease. Bilateral disease occurred in both entities. Surgery was the main treatment for both. Two/113 CPDN patients and 26/167 CN patients had previous, concomitant, or subsequent other tumors. Unlike CPDN, CN was strongly associated with somatic (n = 27/29) and germline (n = 12/12) DICER1-mutations. Four CPDN patients and one CN patient relapsed. Death was reported in six/103 patients with CPDN and six/118 CN patients, none directly due to disease. In conclusion, children with CPDN and CN are young, do not present with metastases, and have an excellent outcome. Awareness of concomitant or subsequent tumors and genetic testing is important. International registration of cystic renal tumor cohorts is required to enable a better understanding of clinical and genetic characteristics.
History of Extensive Disease Small Cell Lung Cancer Treatment: Time to Raise the Bar? A Review of the Literature
Authors: Lazzari Chiara , Mirabile Aurora , Bulotta Alessandra , Viganó Maria Grazia , Ogliari Francesca Rita , Ippati Stefania , DellOca Italo , Santarpia Mariacarmela , Lorusso Vincenza , Reck Martin , Gregorc Vanesa
Published: February 2021

Several trials have tried for decades to improve the outcome of extensive disease small cell lung cancer (ED-SCLC) through attempts to modify the standard treatments. Nevertheless, platinum/etoposide combination and topotecan have remained respectively the first and the second line standard treatments for the last 40 years. With the advent of immunotherapy, this scenario has finally changed. Our review aims to provide an overview of the primary studies on the actual therapeutic strategies available for ED-SCLC patients, and to highlight emerging evidence supporting the use of immunotherapy in SCLC patients.
Hybrid Minigene Assay: An Efficient Tool to Characterize mRNA Splicing Profiles of NF1 Variants
Authors: Morbidoni Valeria , Baschiera Elisa , Forzan Monica , Fumini Valentina , Ali Dario Seif , Giorgi Gianpietro , Buson Lisa , Desbats Maria Andrea , Cassina Matteo , Clementi Maurizio , Salviati Leonardo , Trevisson Eva
Published: February 2021

Neurofibromatosis type 1 (NF1) is caused by heterozygous loss of function mutations in the NF1 gene. Although patients are diagnosed according to clinical criteria and few genotype-phenotype correlations are known, molecular analysis remains important. NF1 displays allelic heterogeneity, with a high proportion of variants affecting splicing, including deep intronic alleles and changes outside the canonical splice sites, making validation problematic. Next Generation Sequencing (NGS) technologies integrated with multiplex ligation-dependent probe amplification (MLPA) have largely overcome RNA-based techniques but do not detect splicing defects. A rapid minigene-based system was set up to test the effects of NF1 variants on splicing. We investigated 29 intronic and exonic NF1 variants identified in patients during the diagnostic process. The minigene assay showed the coexistence of multiple mechanisms of splicing alterations for seven variants. A leaky effect on splicing was documented in one de novo substitution detected in a sporadic patient with a specific phenotype without neurofibromas. Our splicing assay proved to be a reliable and fast method to validate novel NF1 variants potentially affecting splicing and to detect hypomorphic effects that might have phenotypic consequences, avoiding the requirement of patient’s RNA.
Subversion of Niche-Signalling Pathways in Colorectal Cancer: What Makes and Breaks the Intestinal Stem Cell
Authors: Sphyris Nathalie , Hodder Michael C. , Sansom Owen J.
Published: February 2021

The intestinal epithelium fulfils pleiotropic functions in nutrient uptake, waste elimination, and immune surveillance while also forming a barrier against luminal toxins and gut-resident microbiota. Incessantly barraged by extraneous stresses, the intestine must continuously replenish its epithelial lining and regenerate the full gamut of specialized cell types that underpin its functions. Homeostatic remodelling is orchestrated by the intestinal stem cell (ISC) niche: a convergence of epithelial- and stromal-derived cues, which maintains ISCs in a multipotent state. Following demise of homeostatic ISCs post injury, plasticity is pervasive among multiple populations of reserve stem-like cells, lineage-committed progenitors, and/or fully differentiated cell types, all of which can contribute to regeneration and repair. Failure to restore the epithelial barrier risks seepage of toxic luminal contents, resulting in inflammation and likely predisposing to tumour formation. Here, we explore how homeostatic niche-signalling pathways are subverted in tumorigenesis, enabling ISCs to gain autonomy from niche restraints (“ISC emancipation”) and transform into cancer stem cells capable of driving tumour initiation, progression, and therapy resistance. We further consider the implications of the pervasive plasticity of the intestinal epithelium for the trajectory of colorectal cancer, the emergence of distinct molecular subtypes, the propensity to metastasize, and the development of effective therapeutic strategies.
On Broken Ne(c)ks and Broken DNA: The Role of Human NEKs in the DNA Damage Response
Authors: Pavan Isadora , Peres de Oliveira Andressa , Dias Pedro , Basei Fernanda , Issayama Luidy , Ferezin Camila , Silva Fernando , Rodrigues de Oliveira Ana , Alves dos Reis Moura Lívia , Martins Mariana , Simabuco Fernando , Kobarg Jörg
Published: February 2021

NIMA-related kinases, or NEKs, are a family of Ser/Thr protein kinases involved in cell cycle and mitosis, centrosome disjunction, primary cilia functions, and DNA damage responses among other biological functional contexts in vertebrate cells. In human cells, there are 11 members, termed NEK1 to 11, and the research has mainly focused on exploring the more predominant roles of NEKs in mitosis regulation and cell cycle. A possible important role of NEKs in DNA damage response (DDR) first emerged for NEK1, but recent studies for most NEKs showed participation in DDR. A detailed analysis of the protein interactions, phosphorylation events, and studies of functional aspects of NEKs from the literature led us to propose a more general role of NEKs in DDR. In this review, we express that NEK1 is an activator of ataxia telangiectasia and Rad3-related (ATR), and its activation results in cell cycle arrest, guaranteeing DNA repair while activating specific repair pathways such as homology repair (HR) and DNA double-strand break (DSB) repair. For NEK2, 6, 8, 9, and 11, we found a role downstream of ATR and ataxia telangiectasia mutated (ATM) that results in cell cycle arrest, but details of possible activated repair pathways are still being investigated. NEK4 shows a connection to the regulation of the nonhomologous end-joining (NHEJ) repair of DNA DSBs, through recruitment of DNA-PK to DNA damage foci. NEK5 interacts with topoisomerase IIβ, and its knockdown results in the accumulation of damaged DNA. NEK7 has a regulatory role in the detection of oxidative damage to telomeric DNA. Finally, NEK10 has recently been shown to phosphorylate p53 at Y327, promoting cell cycle arrest after exposure to DNA damaging agents. In summary, this review highlights important discoveries of the ever-growing involvement of NEK kinases in the DDR pathways. A better understanding of these roles may open new diagnostic possibilities or pharmaceutical interventions regarding the chemo-sensitizing inhibition of NEKs in various forms of cancer and other diseases.
Eosinophil Responses at the Airway Epithelial Barrier during the Early Phase of Influenza a Virus Infection in C57BL/6 Mice
Authors: Tiwary Meenakshi , Rooney Robert J. , Liedmann Swantje , LeMessurier Kim S. , Samarasinghe Amali E.
Published: February 2021

Eosinophils, previously considered terminally differentiated effector cells, have multifaceted functions in tissues. We previously found that allergic mice with eosinophil-rich inflammation were protected from severe influenza and discovered specialized antiviral effector functions for eosinophils including promoting cellular immunity during influenza. In this study, we hypothesized that eosinophil responses during the early phase of influenza contribute to host protection. Using in vitro and in vivo models, we found that eosinophils were rapidly and dynamically regulated upon influenza A virus (IAV) exposure to gain migratory capabilities to traffic to lymphoid organs after pulmonary infection. Eosinophils were capable of neutralizing virus upon contact and combinations of eosinophil granule proteins reduced virus infectivity through hemagglutinin inactivation. Bi-directional crosstalk between IAV-exposed epithelial cells and eosinophils occurred after IAV infection and cross-regulation promoted barrier responses to improve antiviral defenses in airway epithelial cells. Direct interactions between eosinophils and airway epithelial cells after IAV infection prevented virus-induced cytopathology in airway epithelial cells in vitro, and eosinophil recipient IAV-infected mice also maintained normal airway epithelial cell morphology. Our data suggest that eosinophils are important in the early phase of IAV infection providing immediate protection to the epithelial barrier until adaptive immune responses are deployed during influenza.
A Sensor-Based Methodology to Differentiate Pure and Mixed White Tequilas Based on Fused Infrared Spectra and Multivariate Data Treatment
Authors: Pérez-Beltrán Christian Hazael , Zúñiga-Arroyo Víctor M. , Andrade José M. , Cuadros-Rodríguez Luis , Pérez-Caballero Guadalupe , Jiménez-Carvelo Ana M.
Published: February 2021

Mexican Tequila is one of the most demanded import spirits in Europe. Its fast-raising worldwide request makes counterfeiting a profitable activity affecting both consumers and legal distillers. In this paper, a sensor-based methodology based on a combination of infrared measurements (IR) and multivariate data analysis (MVA) is presented. The case study is about differentiating two categories of white Tequila: pure Tequila (or ‘100% agave’) and mixed Tequila (or simply, Tequila). The IR spectra were treated and fused with a low-level approach. Exploratory data analysis was performed using PCA and partial least squares (PLS), whilst the authentication analyses were carried out with PLS-discriminant analysis (DA) and soft independent modeling for class analogy (SIMCA) models. Results demonstrated that data fusion of IR spectra enhanced the outcomes of the authentication models capable of differentiating pure from mixed Tequilas. In fact, PLS-DA presented the best results which correctly classified all fifteen commercial validation samples. The methodology thus presented is fast, cheap, and of simple application in the Tequila industry.
Cesium-Containing Triple Cation Perovskite Solar Cells
Authors: Ašmontas Steponas , Čerškus Aurimas , Gradauskas Jonas , Grigucevičienė Asta , Leinartas Konstantinas , Lučun Andžej , Petrauskas Kazimieras , Selskis Algirdas , Sužiedėlis Algirdas , Širmulis Edmundas , Juškėnas Remigijus
Published: February 2021

Cesium-containing triple cation perovskites are attracting significant attention as suitable tandem partners for silicon solar cells. The perovskite layer of a solar cell must strongly absorb the visible light and be transparent to the infrared light. Optical transmittance measurements of perovskite layers containing different cesium concentrations (0–15%) were carried out on purpose to evaluate the utility of the layers for the fabrication of monolithic perovskite/silicon tandem solar cells. The transmittance of the layers weakly depended on cesium concentration in the infrared spectral range, and it was more than 0.55 at 997 nm wavelength. It was found that perovskite solar cells containing 10% of cesium concentration show maximum power conversion efficiency.
Eco-Friendly Fire-Resistant Coatings Containing Dihydrogen Ammonium Phosphate Microcapsules and Tannins
Authors: Jaramillo Andrés Felipe , Díaz-Gómez Andrés , Ramirez Jesús , Berrio María Elizabeth , Cornejo Vanessa , Rojas David , Montoya Luis Felipe , Mera Adriana , Melendrez Manuel Francisco
Published: February 2021

The effect of microencapsulation of dihydrogen ammonium phosphate (MAP) in the generation of fire-resistant coatings was studied in the presence of tannins extracted from Pinus radiata. MAP was encapsulated to avoid interaction with sodium carbonate (Na2CO3), which, upon contact with fire, generates unwanted gases. Thus, a fireproof (or intumescent) protective film was produced in the presence of the tannins. Microcapsules were polymerized with melamine and characterized by Fourier Transform Infrared Spectroscopy (FTIR), Thermogravimetric Analysis (TGA), and scanning electron microscopy (SEM)-Energy-Dispersive X-ray Spectroscopy (EDS). The microcapsules were spherical with diameters between 0.7 and 1 µm. The as-produced microcapsules were mixed with tannin extract and the properties of their films were evaluated on wood and structural steel substrates; their fire resistance on medium density fiberboard was also evaluated. Flame resistance tests showed a carbonization index of 26.86% using microcapsules (3% w/w); this is better than commercial coatings. The film properties were similar to commercial coatings, but the adherence was slightly decreased due to agglomeration and also film flexibility.
Metal Deposition Induced by the Step Region of Si (111)-(7 × 7) Surface
Authors: Li Wenxin , Ding Wanyu , Gong Youping , Ju Dongying
Published: February 2021

Scanning tunneling microscope results showed that Au and Fe atoms were steamed on the Si (111)-(7 × 7) substrate surface, with or without the step region. The experimental comparison proved that the induced effect of the step region is a controllable process, which CH3OH can adjust. In this paper, the latest progress on the dynamic phenomenon on the step region is discussed, including three deposition types: strong deposition, weak deposition, and the new quasi deposition. With a relatively weak interaction between Au and Si atoms, the linearity of the weak deposition is present in the step region. In contrast, Fe atoms tend to form a strong deposition along the boundary line between the flat and step regions. Different depositions correspond to different surface potential energy: a newly formed surface is stabilized by a quasi-potential made by breaking, and a metal atomic structure can be stabilized by forming several quasi depositions. After discussing the good adsorption properties, CH3OH can be used as an intermediate layer on the step region. As an important result of quasi deposition, a regular linear Fe cluster structure is created, which is perpendicular to the boundary line.
X-Ray Photoelectron Spectroscopy Depth Profiling of As-Grown and Annealed Titanium Nitride Thin Films
Authors: Maarouf Monzer , Haider Muhammad Baseer , Drmosh Qasem Ahmed , Mekki Mogtaba B.
Published: February 2021

Titanium nitride thin films were grown on Si(001) and fused silica substrates by radio frequency reactive magnetron sputtering. Post-growth annealing of the films was performed at different temperatures from 300 °C to 700 °C in nitrogen ambient. Films annealed at temperatures above 300 °C exhibit higher surface roughness, smaller grain size and better crystallinity compared to the as-grown film. Bandgap of the films decreased with the increase in the annealing temperature. Hall effect measurements revealed that all the films exhibit n-type conductivity and had high carrier concentration, which also increased slightly with the increase in the annealing temperature. A detailed depth profile study of the chemical composition of the film was performed by x-ray photoelectron spectroscopy confirming the formation of Ti-N bond and revealing the presence of chemisorbed oxygen in the films. Annealing in nitrogen ambient results in increased nitrogen vacancies and non-stoichiometric TiN films.
Twisting Structures in Liquid Crystal Polarization Gratings and Lenses
Authors: Zhang Shiyuan , Chen Wan , Yu Yang , Wang Qidong , Mu Quanquan , Li Shixiao , Chen Jin
Published: February 2021

Recently, diverse twisting structures have been discovered to be a potential approach to design liquid crystal polarization gratings and lenses (LCPGs and LCPLs) with a high diffraction efficiency, broad bandwidth, wide view, and large diffraction angle. In this review, we divide these twisting structures into two main types, namely, multi-layer twisting structures with phase compensation and twisting structures forming Bragg diffraction. We found that multi-layer twisting structure LCPGs and LCPLs presented a broader bandwidth and a wider view angle by phase compensation. While for transmissive or reflective Bragg LCPGs, a large diffraction angle with high diffraction efficiency could be achieved. Based on the theoretical analysis in the review, potential research directions on novel twisting structures were prospected.
Microbiota Biomarkers for Lung Cancer
Authors: Leng Qixin , Holden Van K. , Deepak Janaki , Todd Nevins W. , Jiang Feng
Published: February 2021

Non-small cell lung cancer (NSCLC) is the number one cancer killer and its early detection can reduce mortality. Accumulating evidences suggest an etiopathogenic role of microorganisms in lung tumorigenesis. Certain bacteria are found to be associated with NSCLC. Herein we evaluated the potential use of microbiome as biomarkers for the early detection of NSCLC. We used droplet digital PCR to analyze 25 NSCLC-associated bacterial genera in 31 lung tumor and the paired noncancerous lung tissues and sputum of 17 NSCLC patients and ten cancer-free smokers. Of the bacterial genera, four had altered abundances in lung tumor tissues, while five were aberrantly abundant in sputum of NSCLC patients compared with their normal counterparts (all p < 0.05). Acidovorax and Veillonella were further developed as a panel of sputum biomarkers that could diagnose lung squamous cell carcinoma (SCC) with 80% sensitivity and 89% specificity. The use of Capnocytophaga as a sputum biomarker identified lung adenocarcinoma (AC) with 72% sensitivity and 85% specificity. The use of Acidovorax as a sputum biomarker had 63% sensitivity and 96% specificity for distinguishing between SCC and AC, the two major types of NSCLC. The sputum biomarkers were further validated for the diagnostic values in a different cohort of 69 NSCLC cases and 79 cancer-free controls. Sputum microbiome might provide noninvasive biomarkers for the early detection and classification of NSCLC.
Diverse Adiposity and Atrio-Ventricular Dysfunction across Obesity Phenotypes: Implication of Epicardial Fat Analysis
Authors: Lai Yau-Huei , Liu Lawrence Yu-min , Sung Kuo-Tzu , Tsai Jui-Peng , Huang Wen-Hung , Yun Chun-Ho , Lin Jiun-Lu , Chen Ying-Ju , Su Cheng-Huang , Hung Ta-Chuan , Hung Chung-Lieh , Kuo Jen-Yuan
Published: February 2021

Obesity has been conceptualized as a highly heterogeneous condition. We aim to investigate chamber-specific effects of obesity on the heart and relevant outcomes. A total of 2944 symptom-free individuals (age: 47.5 ± 10.0 years), free of known cardiovascular diseases were classified into four categories based on body mass index (BMI) (as normal-weight (NW) vs. overweight/obese (O)) and metabolic status (metabolically-healthy (MH) vs. unhealthy (MU)). Epicardial adipose thickness (EAT) using echocardiography method. Speckle-tracking based atrio-ventricular (LA/LV) deformations including global longitudinal strain (GLS) and peak atrial longitudinal strain (PALS) were also analyzed. MUNW had higher cardiometabolic risks and more impaired diastolic and GLS/PALS than MHNW phenotype. Both MHO and MUO phenotypes exhibited worst atrial functions. Greater EAT was independently associated with worse GLS and PALS after correcting for various anthropometrics, LV mass and LA volume, respectively, with unfavorable LA effects from EAT being more pronounced in the NW phenotypes (both p interactions < 0.05). During a median follow-up period of 5.3 years, BMI/EAT improved the reclassification for atrial fibrillation (AF) incidence (p for net reclassification improvement < 0.05) mainly in the NW phenotypes (p interaction < 0.001). Categorization of clinical obesity phenotypes based on excessive visceral adiposity likely provides increment prognostic impacts on atrial dysfunction, particularly in non-obese phenotypes.
Sleep Bruxism and SDB in Albanian Growing Subjects: A Cross-Sectional Study
Authors: Laganà Giuseppina , Osmanagiq Vesna , Malara Arianna , Venza Nicolò , Cozza Paola
Published: February 2021

The aim of this study was to evaluate a possible correlation between sleep bruxism and risk factors of developing obstructive sleep apnea syndrome (OSAS) in a sample of growing subjects and to assess parental awareness about sleep bruxism in their children. Methods: The sample was composed of 310 subjects (173 females and 137 males), with a mean age of 8.9 years, attending “Ndre Mjeda” school of Tirana (Albania). All parents of the children participating in the study were asked to fill in a questionnaire manually or via a digital version. The questionnaire was composed of three sections: personal data, sleep quality data, and OSAS risk factors, and it was filled out by both parents. Results: Of our samples, 41.3% presented with bruxism, and 16.5% of the parents ground their teeth. Oral breathing was reported in 11.9% of the subjects, and among these, 40% of the subjects were affected by bruxism (p > 0.05). Of the subjects, 18.7% snore overnight. Comparing it with sleep bruxism, the two phenomena are often related (p = 0.00). Conclusions: Heredity, night-sweating, nycturia, oral breathing, and snoring seem to have a significant correlation with bruxism.
A Technical Critique of Some Parts of the Free Energy Principle
Authors: Biehl Martin , Pollock Felix A. , Kanai Ryota
Published: February 2021

We summarize the original formulation of the free energy principle and highlight some technical issues. We discuss how these issues affect related results involving generalised coordinates and, where appropriate, mention consequences for and reveal, up to now unacknowledged, differences from newer formulations of the free energy principle. In particular, we reveal that various definitions of the “Markov blanket” proposed in different works are not equivalent. We show that crucial steps in the free energy argument, which involve rewriting the equations of motion of systems with Markov blankets, are not generally correct without additional (previously unstated) assumptions. We prove by counterexamples that the original free energy lemma, when taken at face value, is wrong. We show further that this free energy lemma, when it does hold, implies the equality of variational density and ergodic conditional density. The interpretation in terms of Bayesian inference hinges on this point, and we hence conclude that it is not sufficiently justified. Additionally, we highlight that the variational densities presented in newer formulations of the free energy principle and lemma are parametrised by different variables than in older works, leading to a substantially different interpretation of the theory. Note that we only highlight some specific problems in the discussed publications. These problems do not rule out conclusively that the general ideas behind the free energy principle are worth pursuing.
An Expandable Modular Internet of Things (IoT)-Based Temperature Control Power Extender
Authors: Chu Huan-Mei , Lee Chun-Te , Chen Liang-Bi , Lee Yen-Yi
Published: February 2021

Today, the world’s electricity consumption is growing rapidly, and therefore energy demands are also increasing. In the past few decades, various measures have been taken to improve equipment and system design to increase production and transmission efficiency and reduce power consumption. This article proposes a novel Internet of Things (IoT)-based temperature control power extender with two working modes of cooling and heating to solve power shortages. The power is turned on or off accurately and in a timely manner through a temperature-sensing element, thereby avoiding unnecessary power consumption to achieve the goal of energy-saving. This can directly power on or off the power extender through the Internet. It can also use a 2.4G Wi-Fi wireless transmission to transmit, for example, real-time temperature information, the switch status and the master–slave mode. Related data can be controlled, collected and uploaded to the cloud. Each proposed power extender’s temperature setting in a large-scale field can be set uniformly, and no staff is wasted to set the temperature separately. Taking a general industrial electric fan as an example, if it is changed to drive with this temperature control extension cable, and assuming that the industrial electric fan is activated for 900 s per hour, its power-saving rate is 74.75%.
Historical Buildings Dampness Analysis Using Electrical Tomography and Machine Learning Algorithms
Authors: Rymarczyk Tomasz , Kłosowski Grzegorz , Hoła Anna , Hoła Jerzy , Sikora Jan , Tchórzewski Paweł , Skowron Łukasz
Published: February 2021

The article deals with the problem of detecting moisture in the walls of historical buildings. As part of the presented research, the following four methods based on mathematical modeling and machine learning were compared: total variation, least-angle regression, elastic net, and artificial neural networks. Based on the simulation data, the systems for the reconstruction of “pixel by pixel” tomographic images were trained. In order to test the reconstructive algorithms obtained during the research, images were generated based on real measurements and simulation cases. The method comparison was performed on the basis of three indicators: mean square error, relative image error, and image correlation coefficient. The above indicators were applied to four selected variants that corresponded to various parts of the walls. The variants differed in the dimensions of the tested wall sections, the number of electrodes used, and the resolution of the 3D image meshes. In all analyzed variants, the best results were obtained using the elastic net algorithm. In addition, all machine learning methods generated better tomographic reconstructions than the classic Total Variation method.
Characterizing Seasonal Variation in Landfill Leachate Using Leachate Pollution Index (LPI) at Nam Son Solid Waste Landfill in Hanoi, Vietnam
Authors: Hoai Son Tran , Nguyen Lan Huong , Thi Viet Nga Tran , Nguyen Hoang Giang , Kawamoto Ken
Published: February 2021

The improper treatment of landfill leachates is one of the major problems associated with waste landfilling and causes serious environmental pollution at waste landfill sites and their surroundings. To develop a suitable landfill leachate treatment system and to minimize the risk of environmental pollution, it is important to characterize seasonal and temporal variations of landfill leachates. This study investigated the leachate quality of the Nam Son waste landfill in Hanoi, Vietnam in 2017–2019 and characterized the potential risks of landfill leachate using a leachate pollution index (LPI). The results of this study showed that the seasonal and temporal variation of the overall LPI during the monitoring period was small and in the range of 20–25 (values 2.5 times higher than the maximum permissible limits of Vietnam National Technical Regulation on Industrial Wastewater). The LPI sub-indices attributed to organic and inorganic pollutants were major components of the LPI. Especially, the annually averaged values of LPI of inorganic pollutants were 7.7 times higher than the maximum permissible limits, suggesting that the treatment of inorganic pollutants, such as ammonium-nitrogen (NH4+–N) and total nitrogen (TN), is highly required at Nam Son landfill to prevent environmental pollution surrounding the landfill site.
Temporal Dynamic Methods for Bulk RNA-Seq Time Series Data
Authors: Oh Vera-Khlara S. , Li Robert W.
Published: February 2021

Dynamic studies in time course experimental designs and clinical approaches have been widely used by the biomedical community. These applications are particularly relevant in stimuli-response models under environmental conditions, characterization of gradient biological processes in developmental biology, identification of therapeutic effects in clinical trials, disease progressive models, cell-cycle, and circadian periodicity. Despite their feasibility and popularity, sophisticated dynamic methods that are well validated in large-scale comparative studies, in terms of statistical and computational rigor, are less benchmarked, comparing to their static counterparts. To date, a number of novel methods in bulk RNA-Seq data have been developed for the various time-dependent stimuli, circadian rhythms, cell-lineage in differentiation, and disease progression. Here, we comprehensively review a key set of representative dynamic strategies and discuss current issues associated with the detection of dynamically changing genes. We also provide recommendations for future directions for studying non-periodical, periodical time course data, and meta-dynamic datasets.
APC Splicing Mutations Leading to In-Frame Exon 12 or Exon 13 Skipping Are Rare Events in FAP Pathogenesis and Define the Clinical Outcome
Authors: Disciglio Vittoria , Forte Giovanna , Fasano Candida , Sanese Paola , Lepore Signorile Martina , De Marco Katia , Grossi Valentina , Cariola Filomena , Simone Cristiano
Published: February 2021

Familial adenomatous polyposis (FAP) is caused by germline mutations in the tumor suppressor gene APC. To date, nearly 2000 APC mutations have been described in FAP, most of which are predicted to result in truncated protein products. Mutations leading to aberrant APC splicing have rarely been reported. Here, we characterized a novel germline heterozygous splice donor site mutation in APC exon 12 (NM_000038.5: c.1621_1626+7del) leading to exon 12 skipping in an Italian family with the attenuated FAP (AFAP) phenotype. Moreover, we performed a literature meta-analysis of APC splicing mutations. We found that 119 unique APC splicing mutations, including the one described here, have been reported in FAP patients, 69 of which have been characterized at the mRNA level. Among these, only a small proportion (9/69) results in an in-frame protein, with four mutations causing skipping of exon 12 or 13 with loss of armadillo repeat 2 (ARM2) and 3 (ARM3), and five mutations leading to skipping of exon 5, 7, 8, or (partially) 9 with loss of regions not encompassing known functional domains. The APC splicing mutations causing skipping of exon 12 or 13 considered in this study cluster with the AFAP phenotype and reveal a potential molecular mechanism of pathogenesis in FAP disease.
Engineering-Geological Features Supporting a Seismic-Driven Multi-Hazard Scenario in the Lake Campotosto Area (L’Aquila, Italy)
Authors: Antonielli Benedetta , Bozzano Francesca , Fiorucci Matteo , Hailemikael Salomon , Iannucci Roberto , Martino Salvatore , Rivellino Stefano , Scarascia Mugnozza Gabriele
Published: February 2021

This paper aims to describe the seismic-driven multi-hazard scenario of the Lake Campotosto artificial basin (Abruzzo Region, Central Italy), and it can represent a preparatory study for a quantitative multi-hazard analysis. A comprehensive multi-hazard scenario considers all the effects that can occur following the base ground shaking, providing a holistic approach to assessing the real hazard potential and helping to improve management of disaster mitigation. The study area might be affected by a complex earthquake-induced chain of geologic hazards, such as the seismic shaking, the surface faulting of the Gorzano Mt. Fault, which is very close to one of the three dams that form the Lake Campotosto, and by the earthquake-triggered landslides of different sizes and typologies. These hazards were individually and qualitatively analyzed, using data from an engineering-geological survey and a geomechanical classification of the rock mass. With regard to the seismic shaking, a quantitative evaluation of the seismic response of the Poggio Cancelli valley, in the northern part of Lake Campotosto, was performed, highlighting different seismic amplification phenomena due to morphologic and stratigraphic features. Some insights about the possible multi-hazard approaches are also discussed.
Geospatial Analysis of COVID-19: A Scoping Review
Authors: Fatima Munazza , O’Keefe Kara J. , Wei Wenjia , Arshad Sana , Gruebner Oliver
Published: February 2021

The outbreak of SARS-CoV-2 in Wuhan, China in late December 2019 became the harbinger of the COVID-19 pandemic. During the pandemic, geospatial techniques, such as modeling and mapping, have helped in disease pattern detection. Here we provide a synthesis of the techniques and associated findings in relation to COVID-19 and its geographic, environmental, and socio-demographic characteristics, following the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) methodology for scoping reviews. We searched PubMed for relevant articles and discussed the results separately for three categories: disease mapping, exposure mapping, and spatial epidemiological modeling. The majority of studies were ecological in nature and primarily carried out in China, Brazil, and the USA. The most common spatial methods used were clustering, hotspot analysis, space-time scan statistic, and regression modeling. Researchers used a wide range of spatial and statistical software to apply spatial analysis for the purpose of disease mapping, exposure mapping, and epidemiological modeling. Factors limiting the use of these spatial techniques were the unavailability and bias of COVID-19 data—along with scarcity of fine-scaled demographic, environmental, and socio-economic data—which restrained most of the researchers from exploring causal relationships of potential influencing factors of COVID-19. Our review identified geospatial analysis in COVID-19 research and highlighted current trends and research gaps. Since most of the studies found centered on Asia and the Americas, there is a need for more comparable spatial studies using geographically fine-scaled data in other areas of the world.
“They Do Not Care about Us Anymore”: Understanding the Situation of Older People in Ghana
Authors: Braimah Joseph Asumah , Rosenberg Mark W.
Published: February 2021

While existing research acknowledges copious challenges faced by older adults (people aged 60 and over) in Ghana and most countries in sub-Saharan Africa, they fail to situate the lived experiences of this vulnerable group within the broader context of health geography and public health. This paper draws insights from ecological systems theory and the “geographies of older people” literature to examine the lived experiences of older people in Ghana. Data for the study were gathered using interviews (42) and sharing circles (10). Our findings reveal a complex mix of experiences consistent with the different levels of the environment. Dominant themes include access to social support, functional impairment and poor health status, social status, poor access to water and sanitation services, food insecurity, economic insecurity, and caregiving burden. These findings support the wide-held notion that the experiences of older people are complex and produced by the interplay of both individual and structural factors. Our findings demonstrate that sociocultural, economic, political, and climatic factors are important consideration in promoting elderly wellbeing and quality of life in Ghana.
Economic Stressors, COVID-19 Attitudes, Worry, and Behaviors among U.S. Working Adults: A Mixture Analysis
Authors: Bazzoli Andrea , Probst Tahira M. , Lee Hyun Jung
Published: February 2021

Since the unfolding of the novel coronavirus global pandemic, public health research has increasingly suggested that certain groups of individuals may be more exposed to the virus. The aim of this contribution was to investigate whether workers grouped into several latent classes, based on two perceived economic stressors, would report different levels of enactment of the Centers for Disease Control (CDC) recommended behaviors to prevent the spread of such virus. We also tested propositions regarding the potential differential predictors of compliance behavior, differentiating between cognitive (i.e., attitudes toward the CDC guidelines) and affective (i.e., COVID-specific worry) predictors. Using a longitudinal dataset of 419 U.S. workers, we did not find significant differences among the levels of CDC guidelines enactment across three latent classes, representing a range of economic vulnerability. We found that cognitive attitudes were a significantly stronger predictor of compliance with CDC guidelines for workers in the most economically secure class, whereas worry was a significantly stronger predictor of compliance for the most vulnerable counterpart. We discuss these findings in light of the Conservation of Resources theory and other health behavior theories, being mindful of the need to further understand the differential impact of this health and economic crisis on employees facing economic stressors.