bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Forest Thinning on Soil Litter Input Nutrients in Relation to Soil CO2, CH4, and N2O Fluxes in Greece
Authors: Doukalianou Foteini , Spyroglou Gavriil , Orfanoudakis Michail , Radoglou Kalliopi , Stefanou Stefanos , Kitikidou Kyriaki , Milios Elias , Lagomarsino Alessandra
Published: February 2022

The contribution of litterfall (dead leaves, twigs, etc., fallen to the ground) and forest floor (organic residues such as leaves, twigs, etc., in various stages of decomposition, on the top of the mineral soil) is fundamental in both forest ecosystem sustainability and soil greenhouse gases (GHG) exchange system with the atmosphere. The effect of different thinning treatments (control-no thinning, traditional-low thinning, selective-intense thinning) on litterfall and forest floor nutrients, in relation to soil GHG fluxes, is analyzed. After one year of operations, thinning had a significant seasonal effect on both litterfall and forest floor, and on their nutrient concentrations. The intense (selective) thinning significantly affected the total litterfall production and conifer fractions, reducing them by 46% and 48%, respectively, compared with the control (no thinning) sites. In the forest floor, thinning was able to significantly increase the Fe concentration intraditional thinning by 59%, and Zn concentration in the intense thinning by 55% (compared with control). Overall, litterfall acted as a bio-filter of the gasses emitting from the forest floor, acting as a GHG regulator.
Publisher’s Note: We Changed Page Numbers to Article Numbers for Articles Published in Audiology Research Volume 1–Volume 10, Issue 1
Authors:   Audiology Research Editorial Office
Published: February 2022

Audiology Research [...]
Spatial Release from Masking for Tones and Noises in a Soundfield under Conditions Where Targets and Maskers Are Stationary or Moving
Authors: Pastore M. Torben , Yost William A.
Published: February 2022

Stationary visual targets often become far more salient when they move against an otherwise static background–the so-called “pop out” effect. In two experiments conducted over loudspeakers, we tested for a similar pop-out effect in the auditory domain. Tone-in-noise and noise-in-noise detection thresholds were measured using a 2-up, 1-down adaptive procedure under conditions where target and masker(s) were presented from the same or different locations and when the target was stationary or moved via amplitude-panning. In the first experiment, target tones of 0.5 kHz and 4 kHz were tested, maskers (2–4, depending on the condition) were independent Gaussian noises, and all stimuli were 500-ms duration. In the second experiment, a single pink noise masker (0.3–12 kHz) was presented with a single target at one of four bandwidths (0.3–0.6 kHz, 3–6 kHz, 6–12 kHz, 0.3–12 kHz) under conditions where target and masker were presented from the same or different locations and where the target moved or not. The results of both experiments failed to show a decrease in detection thresholds resulting from movement of the target.
Fourier Series for the Tangent Polynomials, Tangent–Bernoulli and Tangent–Genocchi Polynomials of Higher Order
Authors: Corcino Cristina Bordaje , Corcino Roberto Bagsarsa
Published: February 2022

In this paper, the Fourier series expansion of Tangent polynomials of higher order is derived using the Cauchy residue theorem. Moreover, some variations of higher-order Tangent polynomials are defined by mixing the concept of Tangent polynomials with that of Bernoulli and Genocchi polynomials, Tangent–Bernoulli and Tangent–Genocchi polynomials. Furthermore, Fourier series expansions of these variations are also derived using the Cauchy residue theorem.
Update on Stachybotrys chartarum—Black Mold Perceived as Toxigenic and Potentially Pathogenic to Humans
Authors: Dyląg Mariusz , Spychała Klaudyna , Zielinski Jessica , Łagowski Dominik , Gnat Sebastian
Published: February 2022

In nature, there are many species of fungi known to produce various mycotoxins, allergens and volatile organic compounds (VOCs), as well as the commonly known etiological agents of various types of mycoses. So far, none of them have provoked so much emotion among homeowners, builders, conservators, mycologists and clinicians as Stachybotrys chartarum. This species compared to fungi of the genera Fusarium and Aspergillus is not as frequently described to be a micromycete that is toxigenic and hazardous to human and animal health, but interest in it has been growing consistently for three decades. Depending on the authors of any given review article, attention is focused either on the clinical aspects alongside the role of this fungus in deterioration of biomaterials, or aspects related to its biology, ecology and taxonomic position. On the one hand, it is well established that inhalation of conidia, containing the highest concentrations of toxic metabolites, may cause serious damage to the mammalian lung, particularly with repeated exposure. On the other hand, we can find articles in which authors demonstrate that S. chartarum conidia can germinate and form hyphae in lungs but are not able to establish an effective infection. Finally, we can find case reports that suggest that S. chartarum infection is linked with acute pulmonary hemorrhage, based on fungal structures recovered from patient lung tissue. New scientific reports have verified the current state of knowledge and note that clinical significance of this fungus is exceedingly controversial. For these reasons, understanding S. chartarum requires reviewing the well-known toxigenic features and harmful factors associated with this fungus, by gathering the newest ones into a coherent whole. The research problem related to this fungus seems to be not overly publicized, and there is still a demand to truthfully define the real threats of S. chartarum and phylogenetically related species. The most important problem, which should be fully elucidated as soon as possible, remains the clarification of the pathogenicity of S. chartarum and related species. Maybe it is urgent time to ask a critical question, namely what exactly do we know 28 years after the outbreak of pulmonary hemorrhage in infants in Cleveland, Ohio, USA most likely caused by S. chartarum?
Insights into Human-Induced Pluripotent Stem Cell-Derived Astrocytes in Neurodegenerative Disorders
Authors: Kumar Mandeep , Nguyen Nhung Thi Phuong , Milanese Marco , Bonanno Giambattista
Published: February 2022

Most neurodegenerative disorders have complex and still unresolved pathology characterized by progressive neuronal damage and death. Astrocytes, the most-abundant non-neuronal cell population in the central nervous system, play a vital role in these processes. They are involved in various functions in the brain, such as the regulation of synapse formation, neuroinflammation, and lactate and glutamate levels. The development of human-induced pluripotent stem cells (iPSCs) reformed the research in neurodegenerative disorders allowing for the generation of disease-relevant neuronal and non-neuronal cell types that can help in disease modeling, drug screening, and, possibly, cell transplantation strategies. In the last 14 years, the differentiation of human iPSCs into astrocytes allowed for the opportunity to explore the contribution of astrocytes to neurodegenerative diseases. This review discusses the development protocols and applications of human iPSC-derived astrocytes in the most common neurodegenerative conditions.
Leukotriene Signaling as a Target in α-Synucleinopathies
Authors: Strempfl Katharina , Unger Michael S. , Flunkert Stefanie , Trost Andrea , Reitsamer Herbert A. , Hutter-Paier Birgit , Aigner Ludwig
Published: February 2022

Parkinson’s disease (PD) and dementia with Lewy bodies (DLB) are two common types of α-synucleinopathies and represent a high unmet medical need. Despite diverging clinical manifestations, both neurodegenerative diseases share several facets of their complex pathophysiology. Apart from α-synuclein aggregation, an impairment of mitochondrial functions, defective protein clearance systems and excessive inflammatory responses are consistently observed in the brains of PD as well as DLB patients. Leukotrienes are lipid mediators of inflammatory signaling traditionally known for their role in asthma. However, recent research advances highlight a possible contribution of leukotrienes, along with their rate-limiting synthesis enzyme 5-lipoxygenase, in the pathogenesis of central nervous system disorders. This review provides an overview of in vitro as well as in vivo studies, in summary suggesting that dysregulated leukotriene signaling is involved in the pathological processes underlying PD and DLB. In addition, we discuss how the leukotriene signaling pathway could serve as a future drug target for the therapy of PD and DLB.
Characterization of a Programmable Argonaute Nuclease from the Mesophilic Bacterium Rummeliibacillus suwonensis
Authors: Jiang Xiaoman , Liu Yang , Liu Qi , Ma Lixin
Published: February 2022

Prokaryotic Argonautes (pAgos) from mesophilic bacteria are attracting increasing attention for their genome editing potential. So far, it has been reported that KmAgo from Kurthia massiliensis can utilize DNA and RNA guide of any sequence to effectively cleave DNA and RNA targets. Here we find that three active pAgos, which have about 50% sequence identity with KmAgo, possess typical DNA-guided DNA target cleavage ability. Among them, RsuAgo from Rummeliibacillus suwonensis is mainly explored for which can cleave both DNA and RNA targets. Interestingly, RsuAgo-mediated RNA target cleavage occurs only with short guide DNAs in a narrow length range (16–20 nt), and mismatches between the guide and target sequence greatly affect the efficiency of RNA target cleavage. RsuAgo-mediated target cleavage shows a preference for a guide strand with a 5′-terminal A residue. Furthermore, we have found that RsuAgo can cleave double-stranded DNA in a low-salt buffer at 37 °C. These properties of RsuAgo provide a new tool for DNA and RNA manipulation at moderate temperatures.
Recent Advances of Point-of-Care Devices Integrated with Molecularly Imprinted Polymers-Based Biosensors: From Biomolecule Sensing Design to Intraoral Fluid Testing
Authors: Park Rowoon , Jeon Sangheon , Jeong Jeonghwa , Park Shin-Young , Han Dong-Wook , Hong Suck Won
Published: February 2022

Recent developments of point-of-care testing (POCT) and in vitro diagnostic medical devices have provided analytical capabilities and reliable diagnostic results for rapid access at or near the patient’s location. Nevertheless, the challenges of reliable diagnosis still remain an important factor in actual clinical trials before on-site medical treatment and making clinical decisions. New classes of POCT devices depict precise diagnostic technologies that can detect biomarkers in biofluids such as sweat, tears, saliva or urine. The introduction of a novel molecularly imprinted polymer (MIP) system as an artificial bioreceptor for the POCT devices could be one of the emerging candidates to improve the analytical performance along with physicochemical stability when used in harsh environments. Here, we review the potential availability of MIP-based biorecognition systems as custom artificial receptors with high selectivity and chemical affinity for specific molecules. Further developments to the progress of advanced MIP technology for biomolecule recognition are introduced. Finally, to improve the POCT-based diagnostic system, we summarized the perspectives for high expandability to MIP-based periodontal diagnosis and the future directions of MIP-based biosensors as a wearable format.
Progress of Polyaniline Glucose Sensors for Diabetes Mellitus Management Utilizing Enzymatic and Non-Enzymatic Detection
Authors: Osuna Velia , Vega-Rios Alejandro , Zaragoza-Contreras Erasto Armando , Estrada-Moreno Iván Alziri , Dominguez Rocio B.
Published: February 2022

Glucose measurement is a fundamental tool in the daily care of Diabetes Mellitus (DM) patients and healthcare professionals. While there is an established market for glucose sensors, the rising number of DM cases has promoted intensive research to provide accurate systems for glucose monitoring. Polyaniline (PAni) is a conductive polymer with a linear conjugated backbone with sequences of single C–C and double C=C bonds. This unique structure produces attractive features for the design of sensing systems such as conductivity, biocompatibility, environmental stability, tunable electrochemical properties, and antibacterial activity. PAni-based glucose sensors (PBGS) were actively developed in past years, using either enzymatic or non-enzymatic principles. In these devices, PAni played roles as a conductive material for electron transfer, biocompatible matrix for enzymatic immobilization, or sensitive layer for detection. In this review, we covered the development of PBGS from 2015 to the present, and it is not even exhaustive; it provides an overview of advances and achievements for enzymatic and non-enzymatic PBGB PBGS for self-monitoring and continuous blood glucose monitoring. Additionally, the limitations of PBGB PBGS to advance into robust and stable technology and the challenges associated with their implementation are presented and discussed.
A Flexible, Wearable, and Wireless Biosensor Patch with Internet of Medical Things Applications
Authors: Phan Duc Tri , Nguyen Cong Hoan , Nguyen Thuy Dung Pham , Tran Le Hai , Park Sumin , Choi Jaeyeop , Lee Byeong-il , Oh Junghwan
Published: February 2022

Monitoring the vital signs and physiological responses of the human body in daily activities is particularly useful for the early diagnosis and prevention of cardiovascular diseases. Here, we proposed a wireless and flexible biosensor patch for continuous and longitudinal monitoring of different physiological signals, including body temperature, blood pressure (BP), and electrocardiography. Moreover, these modalities for tracking body movement and GPS locations for emergency rescue have been included in biosensor devices. We optimized the flexible patch design with high mechanical stretchability and compatibility that can provide reliable and long-term attachment to the curved skin surface. Regarding smart healthcare applications, this research presents an Internet of Things-connected healthcare platform consisting of a smartphone application, website service, database server, and mobile gateway. The IoT platform has the potential to reduce the demand for medical resources and enhance the quality of healthcare services. To further address the advances in non-invasive continuous BP monitoring, an optimized deep learning architecture with one-channel electrocardiogram signals is introduced. The performance of the BP estimation model was verified using an independent dataset; this experimental result satisfied the Association for the Advancement of Medical Instrumentation, and the British Hypertension Society standards for BP monitoring devices. The experimental results demonstrated the practical application of the wireless and flexible biosensor patch for continuous physiological signal monitoring with Internet of Medical Things-connected healthcare applications.
A Novel Approach to Increase Attention during Mirror Therapy among Stroke Patients: A Video-Based Behavioral Analysis
Authors: Jo Sungbae , Kim Hyunjin , Song Changho
Published: February 2022

Stroke is a major cause of disability and an evident rehabilitation strategy is crucial. Mirror therapy (MT) is one of the popular rehabilitation methods that is known to be effective as the patients benefit from the mirror illusion. However, the patient’s attention to the mirror illusion during treatment is unclear. Therefore, the present study assesses the duration and frequency of the mirror gaze, distraction, and preparation of sixteen stroke patients during two MT methods using a behavioral coding software. During the 30 min treatment, the total mirror gaze duration during conventional bilateral MT (BMT) was 564.04 s, while it was 1482.45 s in unilateral MT using a screen (UMT). The total distracted time was 945.61 s in BMT, while it was only 162.03 s in UMT. The total preparatory duration was 290.35 s in BMT and 155.53 s in UMT. The total number of distracted bouts were 136.45 in BMT, while it was 73.38 in UMT. The total number of preparatory bouts were 18.42 in BMT and 9.56 in UMT. The average times of gaze duration per bout were 5.52 s in BMT and 21.81 s in UMT. The average times of distraction per bout were 9.22 s in BMT and 3.00 s in UMT. The total number of mirror gaze bouts and average time of preparation per bout did not present a statistical significance in the comparisons of the two methods. This study assesses two methods of MT using observational coding software to evaluate the duration and frequency of the mirror gaze during treatment. The results suggest that UMT may be an alternative option to provide MT for stroke patients to increase their attention towards the mirror.
Job Satisfaction and Psychological Distress among Help-Seeking Men: Does Meaning in Life Play a Role?
Authors: Simard Aiden A. P. , Seidler Zac E. , Oliffe John L. , Rice Simon M. , Kealy David , Walther Andreas , Ogrodniczuk John S.
Published: February 2022

Men’s low job satisfaction has been shown to be associated with greater symptoms of psychological distress. Meaning in life may be an important factor in this relationship, but its role as a mediator has not been reported. The present study investigated meaning in life as a mediator in the relationship between job satisfaction and psychological distress among men. A total of 229 employed Canadian men participated in a cross-sectional survey, completing measures of depression and anxiety symptoms, anger severity, job satisfaction, and the presence of meaning in life. Zero-order correlations were calculated, and regression with mediation analyses were conducted; two models were tested: one for anxiety/depression symptoms and one for anger, as the dependent variables. Both mediation models emerged as significant, revealing a significant mediating effect for job satisfaction on the symptoms of psychological distress (anxiety/depression symptoms, anger) through meaning in life, even while controlling for salient confounding variables including COVID-related impacts. Lower job satisfaction was associated with less meaning in life, which in turn was associated with more symptoms of depression, anxiety, and anger. The findings highlight the importance of job satisfaction in the promotion of a sense of meaning in life among men, leading to improved psychological well-being both inside and outside of the workplace.
Americans’ Perspectives on Online Media Warning Labels
Authors: Straub Jeremy , Spradling Matthew
Published: February 2022

Americans are pervasively exposed to social media, news, and online content. Some of this content is designed to be deliberately deceptive and manipulative. However, it is interspersed amongst other content from friends and family, advertising, and legitimate news. Filtering content violates key societal values of freedom of expression and inquiry. Taking no action, though, leaves users at the mercy of individuals and groups who seek to use both single articles and complex patterns of content to manipulate how Americans consume, act, work, and even think. Warning labels, which do not block content but instead aid the user in making informed consumption decisions, have been proposed as a potential solution to this dilemma. Ideally, they would respect the autonomy of users to determine what media they consume while combating intentional deception and manipulation through its identification to the user. This paper considers the perception of Americans regarding the use of warning labels to alert users to potentially deceptive content. It presents the results of a population representative national study and analysis of perceptions in terms of key demographics.
Geometry in 18th Century Bell Towers in Bajo Segura, Spain
Authors: García-González Encarnación , Saura-Gómez Pascual , Pérez-Sánchez Vicente Raúl
Published: February 2022

Bell towers are essential elements of religious architecture, which have been part of villagers’ lives for centuries and have marked their identity and orientation from a far distance. This research provides widens our knowledge of geometrical aspects of bell towers through a search for common building patterns. Throughout the history of construction and architecture, there have been specific studies about particular bell towers, but few have taken a more general approach, studying 18th-century architectural treatises and building warnings for ecclesiastical buildings after the Council of Trent. In the Spanish ecclesiastical territorial organisation, the Diocese of Orihuela and its region (Bajo Segura) had great importance, with outstanding social development and territorial expansion due to the colonising action of the clergy and nobility in the 18th century. In 1829, an earthquake had destructive effects on the area’s architectural heritage. This paper studies the bell towers that endured the earthquake by recording data in situ, generating a catalogue, and analysing and comparing the data obtained. The results outline a construction model that meets the established guidelines of the architectural treatises as far as geometrical proportions and building patterns are concerned.
Dynamics and Decoupling Analysis of Carbon Emissions from Construction Industry in China
Authors: Zhang Ping , Hu Jing , Zhao Kaixu , Chen Hua , Zhao Sidong , Li Weiwei
Published: February 2022

The construction industry is the backbone of most countries, but its carbon emissions are huge and growing rapidly, constraining the achievement of global carbon-peaking and carbon-neutrality goals. China’s carbon emissions are the highest in the world, and the construction industry is the largest contributor. Due to significant differences between provinces in pressure, potential, and motivation to reduce emissions, the “one-size-fits-all” emission reduction policy has failed to achieve the desired results. This paper empirically investigates the spatial and temporal evolution of carbon emissions in China’s construction industry and their decoupling relationship with economic growth relying on GIS tools and decoupling model in an attempt to provide a basis for the formulation of differentiated construction emission reduction policies and plans in China. The study shows that, firstly, the changes in carbon emissions and carbon intensity in the provincial construction industry are becoming increasingly complex, with a variety of types emerging, such as declining, “inverted U-shaped”, growing, “U-shaped”, and smooth fluctuating patterns. Secondly, the coefficient of variation is higher than 0.65 for a long time, indicating high spatial heterogeneity. However, spatial agglomeration and correlation are low, with only a few cluster-like agglomerations formed in the Pearl River Delta, Yangtze River Delta, Bohai Bay, Northeast China, and Loess and Yunnan–Guizhou Plateau regions. Thirdly, most provinces have not reached peak carbon emissions from the construction industry, with 25% having reached peak and being in the plateau stage, respectively. Fourthly, the decoupling relationship between carbon emissions from the construction industry and economic growth, as well as their changes, is increasingly diversified, and most provinces are in a strong and weak decoupling state. Moreover, a growing number of provinces that have achieved decoupling are moving backward to re-coupling, due to the impact of economic transformation and the outbreaks of COVID-19, with the degraded regions increasingly concentrated in the northeast and northwest. Fifthly, we classify China’s 30 provinces into Leader, Intermediate, and Laggard policy zones and further propose differentiated response strategies. In conclusion, studying the trends and patterns of carbon-emission changes in the construction industry in different regions, revealing their spatial differentiation and correlation, and developing a classification management strategy for low carbonized development of the construction industry help significantly improve the reliability, efficiency, and self-adaptability of policy design and implementation.
Deformation Performance Analysis of a Truss Structure Based on the Deformation Decomposition Method
Authors: Wang Dongwei , Shang Mengfei , Sun Panxu
Published: February 2022

Trusses are among the basic components of large-span bridges and large-space structures. A method is proposed to conduct a comprehensive deformation analysis of a truss in terms of the basic rigid body displacements and the tension and compression deformation based on complete mathematical orthogonality and mechanical equilibrium. The correctness of the proposed method is verified by comparison with a traditional strain analysis. Furthermore, a relative deformation decomposition of the mode shape is proposed to analyse in detail its relative displacement and deformation. The correctness and superiority of the proposed method are verified by comparison with the modal mass participation coefficient method and the animation from observation method. Additionally, the relative deformation decomposition of a plane truss structure is realized under any load conditions based on the superposition of mode shapes. The quantitative analysis of the basic deformation performance of a plane truss structure can also be conducted by countable mode shapes, which do not involve load conditions. Finally, the number of mode shapes that must be considered differs when using the maximum displacement and the tension and compression deformation analysis indicators.
Targeting Protein Kinase C for Cancer Therapy
Authors: He Sijia , Li Qi , Huang Qian , Cheng Jin
Published: February 2022

Protein kinase C (PKC) isoforms, a group of serine-threonine kinases, are important regulators in carcinogenesis. Numerous studies have demonstrated that PKC isoforms exert both positive and negative effects on cancer cell demise. In this review, we systematically summarize the current findings on the architecture, activity regulation and biological functions of PKCs, especially their relationship with anti-cancer therapy-induced cell death. Additionally, we elaborate on current knowledge of the effects of PKCs on tumor metabolism and microenvironment, which have gained increasing attention in oncology-related areas. Furthermore, we underscore the basic experimental and clinical implications of PKCs as a target for cancer therapy to evaluate their therapeutic benefits and potential applications.
RAB20 Promotes Proliferation via G2/M Phase through the Chk1/cdc25c/cdc2-cyclinB1 Pathway in Penile Squamous Cell Carcinoma
Authors: Tan Xingliang , Yuan Gangjun , Wang Yanjun , Zou Yuantao , Luo Sihao , Han Hui , Qin Zike , Liu Zhuowei , Zhou Fangjian , Liu Yanling , Yao Kai
Published: February 2022

RAB20, a member of the RAS GTPase oncogene family, is overexpressed in several cancers with poor outcomes, promoting tumorigenesis and inducing genomic instability. Here, we performed comprehensive genomic sequencing on eight penile squamous cell carcinoma (PSCC) and normal tissue pairs and found that RAB20 was upregulated in tumors, especially in metastatic lymph nodes. RAB20 overexpression in tumors was further verified by qPCR, Western blotting, and immunohistochemistry of our newly established PSCC cell lines and paired tissues. The clinical significance of RAB20 was validated in 259 PSCC patients, the largest cohort to date, and high RAB20 expression positively correlated with the T, N, M status, extranodal extension, and clinical stage (all p < 0.01). RAB20 was an unfavorable independent prognostic indicator in the survival analysis (p = 0.011, HR = 2.090; 95% Cl: 1.183–4.692), and PSCC patients with high RAB20 expression experienced shorter 5-year cancer-specific survival times (p < 0.001). Furthermore, tumorigenesis assays demonstrated that RAB20 knockdown inhibited cell proliferation, migration, and colony formation in vitro and tumor growth in vivo. RAB20 depletion also induced PSCC cell cycle arrest at G2/M by increasing Chk1 expression and promoting cdc25c phosphorylation to reduce cdc2-cyclinB1 complex formation. Our study revealed an oncogenic role for RAB20 in promoting PSCC cell proliferation at the G2/M phase via the Chk1/cdc25c/cdc2-cyclinB1 pathway. Thus, RAB20 could be a promising prognostic biomarker of advanced PSCC with poor patient survival outcomes and could be a potential therapeutic target.
The Role of Purinergic P2X7 Receptor in Inflammation and Cancer: Novel Molecular Insights and Clinical Applications
Authors: Rotondo John Charles , Mazziotta Chiara , Lanzillotti Carmen , Stefani Chiara , Badiale Giada , Campione Giulia , Martini Fernanda , Tognon Mauro
Published: February 2022

The purinergic P2X7 receptor (P2X7R) is a transmembrane protein whose expression has been related to a variety of cellular processes, while its dysregulation has been linked to inflammation and cancer. P2X7R is expressed in cancer and immune system cell surfaces. ATP plays a key role in numerous metabolic processes due to its abundance in the tumour microenvironment. P2X7R plays an important role in cancer by interacting with ATP. The unusual property of P2X7R is that stimulation with low doses of ATP causes the opening of a permeable channel for sodium, potassium, and calcium ions, whereas sustained stimulation with high doses of ATP favours the formation of a non-selective pore. The latter effect induces a change in intracellular homeostasis that leads to cell death. This evidence suggests that P2X7R has both pro- and anti-tumour proprieties. P2X7R is increasingly recognised as a regulator of inflammation. In this review, we aimed to describe the most relevant characteristics of P2X7R function, activation, and its ligands, while also summarising the role of P2X7R activation in the context of inflammation and cancer. The currently used therapeutic approaches and clinical trials of P2X7R modulators are also described.
Past, Current, and Future Strategies to Target ERG Fusion-Positive Prostate Cancer
Authors: Lorenzin Francesca , Demichelis Francesca
Published: February 2022

The ETS family member ERG is a transcription factor with physiological roles during development and in the vascular and hematopoietic systems. ERG oncogenic activity characterizes several malignancies, including Ewing’s sarcoma, leukemia and prostate cancer (PCa). In PCa, ERG rearrangements with androgen-regulated genes—mostly TMPRSS2—characterize a large subset of patients across disease progression and result in androgen receptor (AR)-mediated overexpression of ERG in the prostate cells. Importantly, PCa cells overexpressing ERG are dependent on ERG activity for survival, further highlighting its therapeutic potential. Here, we review the current understanding of the role of ERG and its partners in PCa. We discuss the strategies developed in recent years to inhibit ERG activity, the current therapeutic utility of ERG fusion detection in PCa patients, and the possible future approaches to target ERG fusion-positive tumors.
Update on Epidemiology, Diagnosis, and Biomarkers in Gastroenteropancreatic Neuroendocrine Neoplasms
Authors: Takayanagi Daisuke , Cho Hourin , Machida Erika , Kawamura Atsushi , Takashima Atsuo , Wada Satoshi , Tsunoda Takuya , Kohno Takashi , Shiraishi Kouya
Published: February 2022

Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are a heterogeneous group of malignancies that originate from the diffuse neuroendocrine cell system of the pancreas and gastrointestinal tract and have increasingly increased in number over the decades. GEP-NENs are roughly classified into well-differentiated neuroendocrine tumors and poorly differentiated neuroendocrine carcinomas; it is essential to understand the pathological classification according to the mitotic count and Ki67 proliferation index. In addition, with the advent of molecular-targeted drugs and somatostatin analogs and advances in endoscopic and surgical treatments, the multidisciplinary treatment of GEP-NENs has made great progress. In the management of GEP-NENs, accurate diagnosis is key for the proper selection among these diversified treatment methods. The evaluation of hormone-producing ability, diagnostic imaging, and histological diagnosis is central. Advances in the study of the genetic landscape have led to deeper understanding of tumor biology; it has also become possible to identify druggable mutations and predict therapeutic effects. Liquid biopsy, based on blood mRNA expression for GEP-NENs, has been developed, and is useful not only for early detection but also for assessing minimal residual disease after surgery and prediction of therapeutic effects. This review outlines the updates and future prospects of the epidemiology, diagnosis, and management of GEP-NENs.
What Defines Quality of Life for Older Patients Diagnosed with Cancer? A Qualitative Study
Authors: Seghers Petronella A. L. (Nelleke) , Kregting Jolina A. , van Huis-Tanja Lieke H. , Soubeyran Pierre , O'Hanlon Shane , Rostoft Siri , Hamaker Marije E. , Portielje Johanneke E. A.
Published: February 2022

The treatment of cancer can have a significant impact on quality of life in older patients and this needs to be taken into account in decision making. However, quality of life can consist of many different components with varying importance between individuals. We set out to assess how older patients with cancer define quality of life and the components that are most significant to them. This was a single-centre, qualitative interview study. Patients aged 70 years or older with cancer were asked to answer open-ended questions: What makes life worthwhile? What does quality of life mean to you? What could affect your quality of life? Subsequently, they were asked to choose the five most important determinants of quality of life from a predefined list: cognition, contact with family or with community, independence, staying in your own home, helping others, having enough energy, emotional well-being, life satisfaction, religion and leisure activities. Afterwards, answers to the open-ended questions were independently categorized by two authors. The proportion of patients mentioning each category in the open-ended questions were compared to the predefined questions. Overall, 63 patients (median age 76 years) were included. When asked, “What makes life worthwhile?”, patients identified social functioning (86%) most frequently. Moreover, to define quality of life, patients most frequently mentioned categories in the domains of physical functioning (70%) and physical health (48%). Maintaining cognition was mentioned in 17% of the open-ended questions and it was the most commonly chosen option from the list of determinants (72% of respondents). In conclusion, physical functioning, social functioning, physical health and cognition are important components in quality of life. When discussing treatment options, the impact of treatment on these aspects should be taken into consideration.
L-Proline-Based Natural Deep Eutectic Solvents as Efficient Solvents and Catalysts for the Ultrasound-Assisted Synthesis of Aurones via Knoevenagel Condensation
Authors: Karadendrou Maria-Anna , Kostopoulou Ioanna , Kakokefalou Vasiliki , Tzani Andromachi , Detsi Anastasia
Published: February 2022

Aurones are minor flavonoids that possess a wide variety of bioactivity, including antioxidant, anticancer, and enzyme inhibitory activity. L-proline-based natural deep eutectic solvents (NaDES) were synthesized and applied as solvents and catalysts for the Knoevenagel condensation reaction between benzofuranone and substituted benzaldehydes to produce aurones in high yields and purity. The reaction between benzofuranone and vanillin served as the model reaction. After screening three NaDESs, and testing microwave, as well as ultrasound as energy sources, we concluded that the optimum results are obtained using L-proline/glycerol 1:2 as catalyst and solvent and ultrasound irradiation. The scope of the reaction was evaluated using a variety of benzaldehydes, and the corresponding aurones were obtained in moderate to satisfactory yields (57–89%) and high purity. An important additional feature of the described methodology is the recyclability and reusability of the NaDES, which was recycled and effectively reused after 6 cycles.
Hydrogen Peroxide Activation with Sulfidated Zero-Valent Iron for Synchronous Removal of Cr(VI) and BPA
Authors: Ling Haibo , Zhu Xiaowei , Zhou Ting , Su Fan , Du Jiangkun , Bao Jianguo
Published: February 2022

In this work, the synchronous removal of Cr(VI) and bisphenol A (BPA) in a heterogeneous Fenton process with sulfidated nanoscale zero-valent iron (S-nZVI) as the reductant and catalyst was systematically evaluated. Compared to other systems including S-nZVI or H2O2 alone, a simultaneous BPA degradation and Cr(VI) removal could be achieved in the S-nZVI/H2O2 system at an optimum pH of 3. It was, interestingly, found that 7.8% of BPA and 98.2% of Cr(VI) were removed within 60 min in presence of S-nZVI alone, whereas, correspondingly, 98.2% of BPA and 96.9% of Cr(VI) were eliminated in the S-nZVI/H2O2 system. Specifically, humic acid (HA) and H2PO4− inhibited the deterioration of BPA but posed no significant effect on Cr(VI) removal. NO3− had a slight lifting effect on the removal of BPA and Cr(VI), while HCO3− showed a relatively weak prohibition. Experiments with EPR and radical probe tests also provide direct evidence that hydroxyl radicals was monitored in the S-nZVI/H2O2 system, which not only degraded BPA but also inhibited the reduction of Cr(VI). It could not be ignored that FeS accelerated Fe0 corrosion to release Fe2+. In, addition, Fe0, Fe2+ and S2+ could react with Cr(VI) while the most of produced Cr(III) was co-precipitated in the form of CrxFe1−xOOH film. The study confirmed that it was feasible for S-nZVI/H2O2 system to remove synchronously organic pollutants and heavy metal.
The Effect of Magnetic Field Gradient and Gadolinium-Based MRI Contrast Agent Dotarem on Mouse Macrophages
Authors: Chanana Priyanka , Uosef Ahmed , Vaughn Nicole , Suarez-Villagran Martha , Ghobrial Rafik M. , Kloc Malgorzata , Wosik Jarek
Published: February 2022

Magnetic resonance imaging (MRI) is widely used in diagnostic medicine. MRI uses the static magnetic field to polarize nuclei spins, fast-switching magnetic field gradients to generate temporal and spatial resolution, and radiofrequency (RF) electromagnetic waves to control the spin orientation. All these forms of magnetic static and electromagnetic RF fields interact with human tissue and cells. However, reports on the MRI technique’s effects on the cells and human body are often inconsistent or contradictory. In both research and clinical MRI, recent progress in improving sensitivity and resolution is associated with the increased magnetic field strength of MRI magnets. Additionally, to improve the contrast of the images, the MRI technique often employs contrast agents, such as gadolinium-based Dotarem, with effects on cells and organs that are still disputable and not fully understood. Application of higher magnetic fields requires revisiting previously observed or potentially possible bio-effects. This article focuses on the influence of a static magnetic field gradient with and without a gadolinium-based MRI contrast agent (Dotarem) and the cellular and molecular effects of Dotarem on macrophages.
Atypical Centriolar Composition Correlates with Internal Fertilization in Fish
Authors: Turner Katerina , Solanki Nisha , Salouha Hassan O. , Avidor-Reiss Tomer
Published: February 2022

The sperm competition theory, as proposed by Geoff Parker, predicts that sperm evolve through a cascade of changes. As an example, internal fertilization is followed by sperm morphology diversification. However, little is known about the evolution of internal sperm structures. The centriole has an ancient and evolutionarily conserved canonical structure with signature 9-fold, radially symmetric microtubules that form the cell’s centrosomes, cilia, and flagella. Most animal spermatozoa have two centrioles, one of which forms the spermatozoan flagellum. Both are delivered to the egg and constitute the embryo’s first two centrosomes. The spermatozoa of mammals and insects only have one recognizable centriole with a canonical structure. A second sperm centriole with an atypical structure was recently reported in both animal groups and which, prior to this, eluded discovery by standard techniques and criteria. Because the ancestors of both mammals and insects reproduced by internal fertilization, we hypothesized that the transition from two centrioles with canonical composition in ancestral sperm to an atypical centriolar composition characterized by only one canonical centriole evolved preferentially after internal fertilization. We examined fish because of the diversity of species available to test this hypothesis–as some species reproduce via internal and others via external fertilization–and because their spermatozoan ultrastructure has been extensively studied. Our literature search reports on 277 fish species. Species reported with atypical centriolar composition are specifically enriched among internal fertilizers compared to external fertilizers (7/34, 20.6% versus 2/243, 0.80%; p < 0.00001, odds ratio = 32.4) and represent phylogenetically unrelated fish. Atypical centrioles are present in the internal fertilizers of the subfamily Poeciliinae. Therefore, internally fertilizing fish preferentially and independently evolved spermatozoa with atypical centriolar composition multiple times, agreeing with Parker’s cascade theory.
Cerebral Organoids Maintain the Expression of Neural Stem Cell-Associated Glycoepitopes and Extracellular Matrix
Authors: Roll Lars , Lessmann Katrin , Brüstle Oliver , Faissner Andreas
Published: February 2022

During development, the nervous system with its highly specialized cell types forms from a pool of relatively uniform stem cells. This orchestrated process requires tight regulation. The extracellular matrix (ECM) is a complex network rich in signaling molecules, and therefore, of interest in this context. Distinct carbohydrate structures, bound to ECM molecules like Tenascin C (TNC), are associated with neural stem/progenitor cells. We have analyzed the expression patterns of the LewisX (LeX) trisaccharide motif and of the sulfation-dependent DSD-1 chondroitin sulfate glycosaminoglycan epitope in human cerebral organoids, a 3D model for early central nervous system (CNS) development, immunohistochemically. In early organoids we observed distinct expression patterns of the glycoepitopes, associated with rosette-like structures that resemble the neural tube in vitro: Terminal LeX motifs, recognized by the monoclonal antibody (mAb) 487LeX, were enriched in the lumen and at the outer border of neural rosettes. In contrast, internal LeX motif repeats detected with mAb 5750LeX were concentrated near the lumen. The DSD-1 epitope, labeled with mAb 473HD, was detectable at rosette borders and in adjacent cells. The epitope expression was maintained in older organoids but appeared more diffuse. The differential glycoepitope expression suggests a specific function in the developing human CNS.
Constitutive Heterochromatin in Eukaryotic Genomes: A Mine of Transposable Elements
Authors: Marsano René Massimiliano , Dimitri Patrizio
Published: February 2022

Transposable elements (TEs) are abundant components of constitutive heterochromatin of the most diverse evolutionarily distant organisms. TEs enrichment in constitutive heterochromatin was originally described in the model organism Drosophila melanogaster, but it is now considered as a general feature of this peculiar portion of the genomes. The phenomenon of TE enrichment in constitutive heterochromatin has been proposed to be the consequence of a progressive accumulation of transposable elements caused by both reduced recombination and lack of functional genes in constitutive heterochromatin. However, this view does not take into account classical genetics studies and most recent evidence derived by genomic analyses of heterochromatin in Drosophila and other species. In particular, the lack of functional genes does not seem to be any more a general feature of heterochromatin. Sequencing and annotation of Drosophila melanogaster constitutive heterochromatin have shown that this peculiar genomic compartment contains hundreds of transcriptionally active genes, generally larger in size than that of euchromatic ones. Together, these genes occupy a significant fraction of the genomic territory of heterochromatin. Moreover, transposable elements have been suggested to drive the formation of heterochromatin by recruiting HP1 and repressive chromatin marks. In addition, there are several pieces of evidence that transposable elements accumulation in the heterochromatin might be important for centromere and telomere structure. Thus, there may be more complexity to the relationship between transposable elements and constitutive heterochromatin, in that different forces could drive the dynamic of this phenomenon. Among those forces, preferential transposition may be an important factor. In this article, we present an overview of experimental findings showing cases of transposon enrichment into the heterochromatin and their positive evolutionary interactions with an impact to host genomes.
Renoprotective Effect of KLF2 on Glomerular Endothelial Dysfunction in Hypertensive Nephropathy
Authors: Bae Eunjin , Yu Mi-Yeon , Moon Jong-Joo , Kim Ji-Eun , Lee Saram , Han Sang-Woong , Park Dong-Jun , Kim Yon-Su , Yang Seung-Hee
Published: February 2022

Kruppel-like factor 2 (KLF2) regulates endothelial cell metabolism; endothelial dysfunction is associated with hypertension and is a predictor of atherosclerosis development and cardiovascular events. Here, we investigated the role of KLF2 in hypertensive nephropathy by regulating KLF2 expression in human primary glomerular endothelial cells (hPGECs) and evaluating this expression in the kidney tissues of a 5/6 nephrectomy mouse model as well as patients with hypertension. Hypertension-mimicking devices and KLF2 siRNA were used to downregulate KLF2 expression, while the expression of KLF2 was upregulated by administering simvastatin. After 4 mmHg of pressure was applied on hPGECs for 48 h, KLF2 mRNA expression decreased, while alpha-smooth muscle actin (αSMA) mRNA expression increased. Apoptosis and fibrosis rates were increased under pressure, and these phenomena were aggravated following KLF2 knockdown, but were alleviated after simvastatin treatment; additionally, these changes were observed in angiotensin II, angiotensin type-1 receptor (AT1R) mRNA, and interleukin-18 (IL-18), but not in angiotensin type-2 receptor mRNA. Reduced expression of KLF2 in glomerular endothelial cells due to hypertension was found in both 5/6 nephrectomy mice and patients with hypertensive nephropathy. Thus, our study demonstrates that the pressure-induced apoptosis and fibrosis of glomerular endothelial cells result from angiotensin II, AT1R activation, and KLF2 inhibition, and are associated with IL-18.
Adult Neurogenesis under Control of the Circadian System
Authors: Ali Amira A. H. , von Gall Charlotte
Published: February 2022

The mammalian circadian system is a hierarchically organized system, which controls a 24-h periodicity in a wide variety of body and brain functions and physiological processes. There is increasing evidence that the circadian system modulates the complex multistep process of adult neurogenesis, which is crucial for brain plasticity. This modulatory effect may be exercised via rhythmic systemic factors including neurotransmitters, hormones and neurotrophic factors as well as rhythmic behavior and physiology or via intrinsic factors within the neural progenitor cells such as the redox state and clock genes/molecular clockwork. In this review, we discuss the role of the circadian system for adult neurogenesis at both the systemic and the cellular levels. Better understanding of the role of the circadian system in modulation of adult neurogenesis can help develop new treatment strategies to improve the cognitive deterioration associated with chronodisruption due to detrimental light regimes or neurodegenerative diseases.