bluuebunny/crossref_metadata_2025 huggingface dataset:
Lifetime Prevalence and Correlates of Schizophrenia and Other Psychotic Disorders in Singapore
Authors: Subramaniam Mythily , Abdin Edimansyah , Vaingankar Janhavi A. , Sambasivam Rajeswari , Zhang Yun Jue , Shafie Saleha , Basu Sutapa , Chan Chun Ting , Tan Chuen Seng , Verma Swapna K. , Tang Charmaine , Chua Hong Choon , Heng Derrick , Chong Siow Ann
Published: March 2021

Introduction: The current study aimed to establish the lifetime prevalence of schizophrenia and other psychotic disorders, its sociodemographic correlates and association with physical disorders using data from the Singapore Mental Health Study (SMHS 2016).

Methods: A two-phase design comprising population-level screening of psychotic symptoms using the World Health Organization Composite International Diagnostic Interview version 3.0 psychosis screen followed by clinical reappraisal based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria were used to establish the prevalence.

Results: A total of 6,126 respondents completed the first phase of the study, giving a response rate of 69.5%. 5.2% (n = 326) of respondents endorsed at least one symptom in the psychosis screen. After the phase two clinical reappraisal interviews and adjusting for false-negative rate, the corrected prevalence of schizophrenia and other psychotic disorders was 2.3% (95% CI: 2.3–2.3%). The odds of having DSM-IV schizophrenia and other psychotic disorders was significantly higher among those of Malay ethnicity (OR = 3.9, 95% CI 1.4–11.0), and those who were unemployed (OR = 4.3, 95% CI 1.2–15.9). 80.4% of those with a psychotic disorder had consulted a doctor or a mental health professional for their symptoms.

Conclusions: Our results indicate that approximately 2.3% of Singapore's community-dwelling adult population had a lifetime diagnosis of schizophrenia and other psychotic disorders. While the treatment gap of the disorder was relatively small, the severe nature of the disorder emphasizes the need for continued outreach and early diagnosis and treatment.
Design of Beam Shaping Assemblies for Accelerator-Based BNCT With Multi-Terminals
Authors: Li Guangru , Jiang Wei , Zhang Lu , Chen Weiqiang , Li Qiang
Published: March 2021

To moderate fast neutrons produced by accelerator to appropriate therapeutic energies for boron neutron capture therapy (BNCT), beam shaping assembly (BSA) is required definitely. In this work, based on a model of 2.5 MeV/30 mA proton accelerator, the Monte Carlo simulation software MCNPX was employed to design multi-terminal BSAs. All parameters for both the thermal and epithermal neutron beams at the exit ports of the designed BSAs meet the treatment recommendation values proposed by the International Atomic Energy Agency (IAEA). The clinical parameters of the thermal and epithermal neutron beams were also calculated for clinical indication consideration.
Antimicrobial Use Surveillance Indicators for Finfish Aquaculture Production: A Review
Authors: Narbonne Jacob A. , Radke Brian R. , Price Derek , Hanington Patrick C. , Babujee Amreen , Otto Simon J. G.
Published: March 2021

Quantification and tracking of antimicrobial use (AMU) are key factors for the development of responsible antimicrobial stewardship programs and comparison between countries. Global finfish aquaculture growth and increased AMU creates the potential for exchange of antimicrobial resistance between aquatic and terrestrial environments, making AMU surveillance imperative for this industry. The objective of this review is to collate current literature on AMU surveillance indicators and their application to commercial finfish aquaculture production. A systematic search strategy was applied to five databases: Medline, Embase, Agricola, CAB abstracts, and Biosis. To be included, studies must report on at least one AMU surveillance indicator for use in animals. There is no single, standardized indicator suitable to report finfish aquaculture AMU. The type and availability of finfish aquaculture data presents unique considerations for AMU reporting. Ultimately, the indicator used should be fit-for-purpose to satisfy the objective of the surveillance program, motivation for comparison and provide useful information to the industry stakeholders. Finfish aquaculture total annual slaughter weight allows estimation of biomass for the population correction unit (PCU) to report annual total mg of active antimicrobial ingredient per PCU. These data are commonly reported by finfish aquaculture-producing countries, allowing for international comparisons. However, this precludes the ability to compare to terrestrial livestock where the PCU is based on animal numbers and an average treatment weight, which are not available for finfish aquaculture. The mg per adjusted PCU indicator provides an interesting alternative that incorporates the length of the marine grow-out phase for finfish, but is subject to the same limitations. The number of defined daily doses animal per animal-days-at-risk is useful but also limited by a lack of a defined average treatment weight. The concept of average treatment weight remains challenging for the industry as it does not accurately reflect the timing of actual AMU to fish in the system. The term “average biomass” is more reflective of the intent of AMU surveillance indicators. Defining an average treatment weight, or average biomass, will require industry engagement, which is crucial if AMU reporting is to be deemed credible and provide value back to the finfish aquaculture industry.
Measuring Hydrogen in Indoor Air with a Selective Metal Oxide Semiconductor Sensor
Authors: Schultealbert Caroline , Amann Johannes , Baur Tobias , Schütze Andreas
Published: March 2021

Hydrogen is a ubiquitous but often neglected gas. In analytical measurements hydrogen—as a harmless gas—often is not considered so no studies on hydrogen in indoor air can be found. For metal oxide semiconductor (MOS) gas sensors that are increasingly pushed into the application as TVOC (total volatile organic compounds) sensors, hydrogen is a severe disturbance. On the other hand, hydrogen can be an intentional choice as indicator for human presence similar to carbon dioxide. We present a field-study on hydrogen in indoor air using selective MOS sensors accompanied by an analytical reference device for hydrogen with an accuracy of 10 ppb. Selectivity is achieved by siloxane treatment combined with temperature cycled operation and training with a complex lab calibration using randomized gas mixtures, yielding an uncertainty of 40–60 ppb. The feasibility is demonstrated by release tests with several gases inside a room and by comparison to the reference device. The results show that selective MOS sensors can function as cheap and available hydrogen detectors. Fluctuations in hydrogen concentration without human presence are measured over several days to gain insight in this highly relevant parameter for indoor air quality. The results indicate that the topic needs further attention and that the usage of hydrogen as indicator for human presence might be precluded by other sources and fluctuations.
Disrupted Pallido-Thalamo-Cortical Functional Connectivity in Chronic Disorders of Consciousness
Authors: Sontheimer Anna , Pontier Bénédicte , Claise Béatrice , Chassain Carine , Coste Jérôme , Lemaire Jean-Jacques
Published: March 2021

Chronic disorders of consciousness (DOC) encompass unresponsive wakefulness syndrome and minimally conscious state. Their anatomo-functional correlates are not clearly defined yet, although impairments of functional cortical networks have been reported, as well as the implication of the thalamus and deep brain structures. However, the pallidal functional connectivity with the thalamus and the cortical networks has not been studied so far. Using resting-state functional MRI, we conducted a functional connectivity study between the pallidum, the thalamus and the cortical networks in 13 patients with chronic DOC and 19 healthy subjects. We observed in chronic DOC patients that the thalami were no longer connected to the cortical networks, nor to the pallidums. Concerning the functional connectivity of pallidums, we reported an abolition of the negative correlation with the default mode network, and of the positive correlation with the salience network. The disrupted functional connectivity observed in chronic DOC patients between subcortical structures and cortical networks could be related to the mesocircuit model. A better understanding of the DOC underlying physiopathology could provide food for thought for future therapeutic proposals.
Immunogenic Cell Death by the Novel Topoisomerase I Inhibitor TLC388 Enhances the Therapeutic Efficacy of Radiotherapy
Authors: Huang Kevin Chih-Yang , Chiang Shu-Fen , Yang Pei-Chen , Ke Tao-Wei , Chen Tsung-Wei , Hu Ching-Han , Huang Yi-Wen , Chang Hsin-Yu , Chen William Tzu-Liang , Chao K. S. Clifford
Published: March 2021

Rectal cancer accounts for 30–40% of colorectal cancer (CRC) and is the most common cancer-related death worldwide. The preoperative neoadjuvant chemoradiotherapy (neoCRT) regimen is the main therapeutic strategy for patients with locally advanced rectal cancer (LARC) to control tumor growth and reduce distant metastasis. However, 30–40% of patients achieve a partial response to neoCRT and suffer from unnecessary drug toxicity side effects and a risk of distant metastasis. In our study, we found that the novel topoisomerase I inhibitor lipotecan (TLC388) can elicit immunogenic cell death (ICD) to release damage-associated molecular patterns (DAMPs), including HMGB1, ANXA1, and CRT exposure. Lipotecan thereby increases cancer immunogenicity and triggers an antitumor immune response to attract immune cell infiltration within the tumor microenvironment (TME) in vitro and in vivo. Taken together, these results show that lipotecan can remodel the tumor microenvironment to provoke anticancer immune responses, which can provide potential clinical benefits to the therapeutic efficacy of neoCRT in LARC patients.
Potential Utility of Pre-Emptive Germline Pharmacogenetics in Breast Cancer
Authors: Bernard Philip S. , Wooderchak-Donahue Whitney , Wei Mei , Bray Steven M. , Wood Kevin C. , Parikh Baiju , McMillin Gwendolyn A.
Published: March 2021

Patients with breast cancer often receive many drugs to manage the cancer, side effects associated with cancer treatment, and co-morbidities (i.e., polypharmacy). Drug–drug and drug–gene interactions contribute to the risk of adverse events (AEs), which could lead to non-adherence and reduced efficacy. Here we investigated several well-characterized inherited (germline) pharmacogenetic (PGx) targets in 225 patients with breast cancer. All relevant clinical, pharmaceutical, and PGx diplotype data were aggregated into a single unifying informatics platform to enable an exploratory analysis of the cohort and to evaluate pharmacy ordering patterns. Of the drugs recorded, there were 38 for which high levels of evidence for clinical actionability with PGx was available from the US FDA and/or the Clinical Pharmacogenetics Implementation Consortium (CPIC). These data were associated with 10 pharmacogenes: DPYD, CYP2C9, CYP2C19, CYP2D6, CYP3A5, CYP4F2, G6PD, MT-RNR1, SLCO1B1, and VKORC1. All patients were taking at least one of the 38 drugs and had inherited at least one actionable PGx variant that would have informed prescribing decisions if this information had been available pre-emptively. The non-cancer drugs with PGx implications that were common (prescribed to at least one-third of patients) included anti-depressants, anti-infectives, non-steroidal anti-inflammatory drugs, opioids, and proton pump inhibitors. Based on these results, we conclude that pre-emptive PGx testing may benefit patients with breast cancer by informing drug and dose selection to maximize efficacy and minimize AEs.
Boosting Immunity against Multiple Myeloma
Authors: Lopes Raquel , Ferreira Bruna Velosa , Caetano Joana , Barahona Filipa , Carneiro Emilie Arnault , João Cristina
Published: March 2021

Despite the improvement of patient’s outcome obtained by the current use of immunomodulatory drugs, proteasome inhibitors or anti-CD38 monoclonal antibodies, multiple myeloma (MM) remains an incurable disease. More recently, the testing in clinical trials of novel drugs such as anti-BCMA CAR-T cells, antibody–drug conjugates or bispecific antibodies broadened the possibility of improving patients’ survival. However, thus far, these treatment strategies have not been able to steadily eliminate all malignant cells, and the aim has been to induce a long-term complete response with minimal residual disease (MRD)-negative status. In this sense, approaches that target not only myeloma cells but also the surrounding microenvironment are promising strategies to achieve a sustained MRD negativity with prolonged survival. This review provides an overview of current and future strategies used for immunomodulation of MM focusing on the impact on bone marrow (BM) immunome.
Molecular and Clinical Premises for the Combination Therapy Consisting of Radiochemotherapy and Immunotherapy in Non-Small Cell Lung Cancer Patients
Authors: Frąk Małgorzata , Krawczyk Paweł , Kalinka Ewa , Milanowski Janusz
Published: March 2021

Non-small cell lung cancer (NSCLC) is one of the most common malignancies around the world. Due to the advanced stage of the disease at the time of diagnosis, most patients require systemic treatment. Immunotherapy with immune checkpoints inhibitors is becoming the main treatment method for many cancers, including NSCLC. Numerous studies have shown greater efficacy of immunotherapy used monoclonal antibodies anti-PD-1 (pembrolizumab and nivolumab) or anti-PD-L1 (atezolizumab and durvalumab) compared to chemotherapy. Unfortunately, cancer cells can develop a number of mechanisms to escape from immune surveillance, including avoidance of cancer cells by the immune system (immune desert), production of immunosuppressive compounds (prostaglandins, IDO, TGF-beta), or direct immune checkpoints interactions. Therapy based on the use of radiochemotherapy with subsequent immunotherapy is becoming the main focus of research in the field of new NSCLC therapies. Radiation therapy stimulates the immune response multidirectionally, affects production of neoantigens and proinflammatory compounds, which transform non-immunogenic (“cold”) tumors into highly immunogenic (“hot”) tumors. As a result, the mechanisms of escape of cancer cells from immune surveillance break down and the effectiveness of immunotherapy increases significantly. The results of clinical trials in this area bring new hope and indicate greater effectiveness of such treatment in terms of prolongation of progression-free survival and overall survival.
Differential Involvement of ACKR3 C-Tail in β-Arrestin Recruitment, Trafficking and Internalization
Authors: Zarca Aurélien , Perez Claudia , van den Bor Jelle , Bebelman Jan Paul , Heuninck Joyce , de Jonker Rianna J. F. , Durroux Thierry , Vischer Henry F. , Siderius Marco , Smit Martine J.
Published: March 2021

Background: The atypical chemokine receptor 3 (ACKR3) belongs to the superfamily of G protein-coupled receptors (GPCRs). Unlike classical GPCRs, this receptor does not activate G proteins in most cell types but recruits β-arrestins upon activation. ACKR3 plays an important role in cancer and vascular diseases. As recruitment of β-arrestins is triggered by phosphorylation of the C-terminal tail of GPCRs, we studied the role of different potential phosphorylation sites within the ACKR3 C-tail to further delineate the molecular mechanism of internalization and trafficking of this GPCR. Methods: We used various bioluminescence and fluorescence resonance energy transfer-based sensors and techniques in Human Embryonic Kidney (HEK) 293T cells expressing WT or phosphorylation site mutants of ACKR3 to measure CXCL12-induced recruitment of β-arrestins and G-protein-coupled receptor kinases (GRKs), receptor internalization and trafficking. Results: Upon CXCL12 stimulation, ACKR3 recruits both β-arrestin 1 and 2 with equivalent kinetic profiles. We identified interactions with GRK2, 3 and 5, with GRK2 and 3 being important for β-arrestin recruitment. Upon activation, ACKR3 internalizes and recycles back to the cell membrane. We demonstrate that β-arrestin recruitment to the receptor is mainly determined by a single cluster of phosphorylated residues on the C-tail of ACKR3, and that residue T352 and in part S355 are important residues for β-arrestin1 recruitment. Phosphorylation of the C-tail appears essential for ligand-induced internalization and important for differential β-arrestin recruitment. GRK2 and 3 play a key role in receptor internalization. Moreover, ACKR3 can still internalize when β-arrestin recruitment is impaired or in the absence of β-arrestins, using alternative internalization pathways. Our data indicate that distinct residues within the C-tail of ACKR3 differentially regulate CXCL12-induced β-arrestin recruitment, ACKR3 trafficking and internalization.
Conventional and Alternative Sources of Thermal Energy in the Production of Cement—An Impact on CO2 Emission
Authors: Wojtacha-Rychter Karolina , Kucharski Piotr , Smolinski Adam
Published: March 2021

The article evaluates the reduction of carbon dioxide emission due to the partial substitution of coal with alternative fuels in clinker manufacture. For this purpose, the calculations were performed for seventy waste-derived samples of alternative fuels with variable calorific value and variable share in the fuel mixture. Based on annual clinker production data of the Polish Cement Association and the laboratory analysis of fuels, it was estimated that the direct net CO2 emissions from fossil fuel combustion alone were 543 Mg of CO2 per hour. By contrast with the full substitution of coal with alternative fuels (including 30% of biomass), the emission ranged from 302 up to 438 Mg of CO2 per hour, depending on fuel properties. A reduction of 70% in the share of fossil fuels resulted in about a 23% decrease in net emissions. It was proved that the increased use of alternative fuels as an additive to the fuel mix is also of economic importance. It was determined that thanks to the combustion of 70% of alternative fuels of calorific value from 15 to 26 MJ/kg, the hourly financial profit gain due to avoided CO2 emission and saved 136 megatons of coal totaled an average of 9718 euros. The results confirmed that the co-incineration of waste in cement kilns can be an effective, long-term way to mitigate carbon emissions and to lower clinker production costs. This paper may constitute a starting point for future research activities and specific case studies in terms of reducing CO2 emissions.
Special Issue: “Improving Energy Efficiency through Data-Driven Modeling, Simulation and Optimization”
Authors: Deschrijver Dirk
Published: March 2021

In October 2014, EU leaders agreed upon three key targets for the year 2030: a reduction of at least 40% in greenhouse gas emissions, a saving of at least a 27% share for renewable energy, and at least a 27% improvement in energy efficiency [...]
Field Application of Microbial Self-Healing Cement Slurry in Chunguang 17-14 Well
Authors: Li Lixia , Liu Tianle , Jiang Guosheng , Fang Changliang , Sun Jiaxin , Zheng Shaojun , Liu Haodong , Leusheva Ekaterina , Morenov Valentin , Nikolaev Nikolai
Published: March 2021

Due to the inappropriate treatment of dairy wastewater, which can easily cause underground water pollution, there is an increasing need for a novel approach to reuse dairy wastewater. The technology of microbially induced calcium carbonate precipitation with environmentally friendly characteristics and high efficiency has been widely used for underground infrastructure remediation. However, there is a lack of in-depth research on the application of this technology under extreme underground environments, such as the borehole of oil wells with high temperature, high pressure, alkaline, and aerobic conditions. In addition, to reduce the cost of this technology when applied on a large scale, we adopted dairy wastewater to cultivate bacteria. Then, we put the bacterial solution into cement slurry in the borehole to improve the cementing quality. In this paper, the rheology properties, mechanical strength, permeability, porosity, and pore distribution of microbial cementing slurry were studied. Moreover, we applied this microbial cement slurry in the Chunguang 17-14 well of China, and the sealing channeling ability of cement sheath on site was evaluated. The results showed that dairy wastewater could serve as an alternative medium to provide nutrients and energy for the growth of bacteria with low cost. Additionally, the microbial cement slurry exhibited a good right-angle thickening performance and high mechanical strength. The field application displayed an anti-gas channeling ability after microbial remediation. The application of dairy wastewater incubated bacteria to cement slurry not only provides an alternative method for the reuse of dairy wastewater but is also conducive to prolonging the lifespan of oil wells.
SMITER—A Python Library for the Simulation of LC-MS/MS Experiments
Authors: Kösters Manuel , Leufken Johannes , Leidel Sebastian A.
Published: March 2021

SMITER (Synthetic mzML writer) is a Python-based command-line tool designed to simulate liquid-chromatography-coupled tandem mass spectrometry LC-MS/MS runs. It enables the simulation of any biomolecule amenable to mass spectrometry (MS) since all calculations are based on chemical formulas. SMITER features a modular design, allowing for an easy implementation of different noise and fragmentation models. By default, SMITER uses an established noise model and offers several methods for peptide fragmentation, and two models for nucleoside fragmentation and one for lipid fragmentation. Due to the rich Python ecosystem, other modules, e.g., for retention time (RT) prediction, can easily be implemented for the tailored simulation of any molecule of choice. This facilitates the generation of defined gold-standard LC-MS/MS datasets for any type of experiment. Such gold standards, where the ground truth is known, are required in computational mass spectrometry to test new algorithms and to improve parameters of existing ones. Similarly, gold-standard datasets can be used to evaluate analytical challenges, e.g., by predicting co-elution and co-fragmentation of molecules. As these challenges hinder the detection or quantification of co-eluents, a comprehensive simulation can identify and thus, prevent such difficulties before performing actual MS experiments. SMITER allows the creation of such datasets easily, fast, and efficiently.
Wheeled Mobility Use on Accessible Fixed-Route Transit: A Field Study in Environmental Docility
Authors: Lim Sol , D’Souza Clive
Published: March 2021

Multiple field studies provide qualitative accounts of usability barriers experienced by users of wheeled mobility devices on public transit. This study aimed to examine these usability barriers from the theoretical perspective of Environmental Docility by quantifying the relationship between functional capabilities of wheeled mobility device users and ingress–egress performance on accessible fixed-route transit vehicles in an urban setting. Twenty-eight wheeled mobility users each completed three trips on a predetermined route through the local public transit system. Ingress and egress times, user-reported usability ratings and open-ended comments were analyzed. Regression analyses indicated significant interactions between age and minimum parallel-park length on ingress and egress times. Specifically, lower functional capability reflected in older age and less maneuvering ability predicted decreased performance (longer ingress–egress times), indicating less adaptability to environmental demands and agreement with the Environmental Docility Hypothesis. Usability ratings and comments revealed difficulty with negotiating access ramps and turning maneuvers in the vehicle interior and in proximity to other passengers. Despite compliance with accessibility standards, current design of transit vehicles present substantial usability barriers for wheeled mobility users. Environmental Docility provides a theoretical basis to identifying modifiable factors related to person and environment for improving usability of public transit for people aging and/or with mobility impairments.
The Future Health Workforce: Integrated Solutions and Models of Care
Authors: Balasubramanian Madhan , Short Stephanie
Published: March 2021

The health workforce is a vital aspect of health systems, both essential in improving patient and population health outcomes and in addressing contemporary challenges such as universal health coverage (UHC) and sustainable development goals (SDGs) [...]
Correction: Tayech, A., et al. Second Wave of COVID-19 Global Pandemic and Athletes’ Confinement: Recommendations to Better Manage and Optimize the Modified Lifestyle. Int. J. Environ. Res. Public Health 2020, 17, 8385
Authors: Tayech Amel , Mejri Mohamed Arbi , Makhlouf Issam , Mathlouthi Ameni , Behm David G. , Chaouachi Anis
Published: March 2021

In our recently published article [...]
Benefits of Regular Table Tennis Practice in Body Composition and Physical Fitness Compared to Physically Active Children Aged 10–11 Years
Authors: Pradas Francisco , Ara Ignacio , Toro Víctor , Courel-Ibáñez Javier
Published: March 2021

The aim of this study was to identify the differences in body composition and physical fitness between children who played table tennis regularly during a two-year period compared to physically active children who were not engaged in a regular activity. Three hundred seventy-four children aged 10 to 11 years were divided into two groups: table tennis players (n = 109 boys and 73 girls) and physically active group (n = 88 boys and 104 girls). Anthropometric analysis included body mass index, skinfolds, perimeters and bone diameters. Somatotype and body composition were determined according to age-specific equations. Physical fitness assessment included hand grip dynamometry (strength), sit-and-reach test (range of movement) and maximal multistage 20 m shuttle run test (cardiovascular fitness). The result show that children who regularly played table tennis had greater bone development and superior physical fitness compared to those who were physically active but not engaged in a regular physical activity. This is the largest study to date presenting data about the potential of table tennis to benefit health in children. These results constitute an important first step in clarifying the effectiveness of table tennis as a health-promotion strategy to encourage children to undertake regular physical activity and limit sedentary behavior.
Garcinol—A Natural Histone Acetyltransferase Inhibitor and New Anti-Cancer Epigenetic Drug
Authors: Kopytko Patrycja , Piotrowska Katarzyna , Janisiak Joanna , Tarnowski Maciej
Published: March 2021

Garcinol extracted from Garcinia indica fruit peel and leaves is a polyisoprenylated benzophenone. In traditional medicine it was used for its antioxidant and anti-inflammatory properties. Several studies have shown anti-cancer properties of garcinol in cancer cell lines and experimental animal models. Garcinol action in cancer cells is based on its antioxidant and anti-inflammatory properties, but also on its potency to inhibit histone acetyltransferases (HATs). Recent studies indicate that garcinol may also deregulate expression of miRNAs involved in tumour development and progression. This paper focuses on the latest research concerning garcinol as a HAT inhibitor and miRNA deregulator in the development and progression of various cancers. Garcinol may be considered as a candidate for next generation epigenetic drugs, but further studies are needed to establish the precise toxicity, dosages, routes of administration, and safety for patients.
Growth Hormone and the Auditory Pathway: Neuromodulation and Neuroregeneration
Authors: Gómez Joaquín Guerra , Devesa Jesús
Published: March 2021

Growth hormone (GH) plays an important role in auditory development during the embryonic stage. Exogenous agents such as sound, noise, drugs or trauma, can induce the release of this hormone to perform a protective function and stimulate other mediators that protect the auditory pathway. In addition, GH deficiency conditions hearing loss or central auditory processing disorders. There are promising animal studies that reflect a possible regenerative role when exogenous GH is used in hearing impairments, demonstrated in in vivo and in vitro studies, and also, even a few studies show beneficial effects in humans presented and substantiated in the main text, although they should not exaggerate the main conclusions.
New Therapeutic Opportunities for the Treatment of Squamous Cell Carcinomas: A Focus on Novel Driver Kinases
Authors: Bensen Ryan , Brognard John
Published: March 2021

Squamous cell carcinomas of the lung, head and neck, esophagus, and cervix account for more than two million cases of cancer per year worldwide with very few targetable therapies available and minimal clinical improvement in the past three decades. Although these carcinomas are differentiated anatomically, their genetic landscape shares numerous common genetic alterations. Amplification of the third chromosome’s distal portion (3q) is a distinguishing genetic alteration in most of these carcinomas and leads to copy-number gain and amplification of numerous oncogenic proteins. This area of the chromosome harbors known oncogenes involved in squamous cell fate decisions and differentiation, including TP63, SOX2, ECT2, and PIK3CA. Furthermore, novel targetable oncogenic kinases within this amplicon include PRKCI, PAK2, MAP3K13, and TNIK. TCGA analysis of these genes identified amplification in more than 20% of clinical squamous cell carcinoma samples, correlating with a significant decrease in overall patient survival. Alteration of these genes frequently co-occurs and is dependent on 3q-chromosome amplification. The dependency of cancer cells on these amplified kinases provides a route toward personalized medicine in squamous cell carcinoma patients through development of small-molecules targeting these kinases.
β3-Adrenoreceptors as ROS Balancer in Hematopoietic Stem Cell Transplantation
Authors: Pasha Amada , Calvani Maura , Favre Claudio
Published: March 2021

In the last decades, the therapeutic potential of hematopoietic stem cell transplantation (HSCT) has acquired a primary role in the management of a broad spectrum of diseases including cancer, hematologic conditions, immune system dysregulations, and inborn errors of metabolism. The different types of HSCT, autologous and allogeneic, include risks of severe complications including acute and chronic graft-versus-host disease (GvHD) complications, hepatic veno-occlusive disease, lung injury, and infections. Despite being a dangerous procedure, it improved patient survival. Hence, its use was extended to treat autoimmune diseases, metabolic disorders, malignant infantile disorders, and hereditary skeletal dysplasia. HSCT is performed to restore or treat various congenital conditions in which immunologic functions are compromised, for instance, by chemo- and radiotherapy, and involves the administration of hematopoietic stem cells (HSCs) in patients with depleted or dysfunctional bone marrow (BM). Since HSCs biology is tightly regulated by oxidative stress (OS), the control of reactive oxygen species (ROS) levels is important to maintain their self-renewal capacity. In quiescent HSCs, low ROS levels are essential for stemness maintenance; however, physiological ROS levels promote HSC proliferation and differentiation. High ROS levels are mainly involved in short-term repopulation, whereas low ROS levels are associated with long-term repopulating ability. In this review, we aim summarize the current state of knowledge about the role of β3-adrenoreceptors (β3-ARs) in regulating HSCs redox homeostasis. β3-ARs play a major role in regulating stromal cell differentiation, and the antagonist SR59230A promotes differentiation of different progenitor cells in hematopoietic tumors, suggesting that β3-ARs agonism and antagonism could be exploited for clinical benefit.
Palindromes in DNA—A Risk for Genome Stability and Implications in Cancer
Authors: Svetec Miklenić Marina , Svetec Ivan Krešimir
Published: March 2021

A palindrome in DNA consists of two closely spaced or adjacent inverted repeats. Certain palindromes have important biological functions as parts of various cis-acting elements and protein binding sites. However, many palindromes are known as fragile sites in the genome, sites prone to chromosome breakage which can lead to various genetic rearrangements or even cell death. The ability of certain palindromes to initiate genetic recombination lies in their ability to form secondary structures in DNA which can cause replication stalling and double-strand breaks. Given their recombinogenic nature, it is not surprising that palindromes in the human genome are involved in genetic rearrangements in cancer cells as well as other known recurrent translocations and deletions associated with certain syndromes in humans. Here, we bring an overview of current understanding and knowledge on molecular mechanisms of palindrome recombinogenicity and discuss possible implications of DNA palindromes in carcinogenesis. Furthermore, we overview the data on known palindromic sequences in the human genome and efforts to estimate their number and distribution, as well as underlying mechanisms of genetic rearrangements specific palindromic sequences cause.
Microscopic Interactions of Melatonin, Serotonin and Tryptophan with Zwitterionic Phospholipid Membranes
Authors: Martí Jordi , Lu Huixia
Published: March 2021

The interactions at the atomic level between small molecules and the main components of cellular plasma membranes are crucial for elucidating the mechanisms allowing for the entrance of such small species inside the cell. We have performed molecular dynamics and metadynamics simulations of tryptophan, serotonin, and melatonin at the interface of zwitterionic phospholipid bilayers. In this work, we will review recent computer simulation developments and report microscopic properties, such as the area per lipid and thickness of the membranes, atomic radial distribution functions, angular orientations, and free energy landscapes of small molecule binding to the membrane. Cholesterol affects the behaviour of the small molecules, which are mainly buried in the interfacial regions. We have observed a competition between the binding of small molecules to phospholipids and cholesterol through lipidic hydrogen-bonds. Free energy barriers that are associated to translational and orientational changes of melatonin have been found to be between 10–20 kJ/mol for distances of 1 nm between melatonin and the center of the membrane. Corresponding barriers for tryptophan and serotonin that are obtained from reversible work methods are of the order of 10 kJ/mol and reveal strong hydrogen bonding between such species and specific phospholipid sites. The diffusion of tryptophan and melatonin is of the order of 10−7 cm2/s for the cholesterol-free and cholesterol-rich setups.
3-(tert-Butyl)-N-(4-methoxybenzyl)-1-methyl-1H-pyrazol-5-amine
Authors: Becerra Diana , Rojas Hugo , Castillo Juan-Carlos
Published: March 2021

We reported an efficient one-pot two-step synthesis of 3-(tert-butyl)-N-(4-methoxybenzyl)-1-methyl-1H-pyrazol-5-amine 3 in good yield by a solvent-free condensation/reduction reaction sequence starting from 3-(tert-butyl)-1-methyl-1H-pyrazol-5-amine 1 and p-methoxybenzaldehyde 2. The one-pot reductive amination proceeded by the formation in situ of the N-(5-pyrazolyl)imine 4 as key synthetic intermediate of other valuable pyrazole derivatives. This methodology is distinguished by its operational easiness, short reaction time, isolation and purification of the aldimine intermediate is not required. The structure of the synthesized N-heterocyclic amine 3 was fully characterized by FTIR-ATR, 1D and 2D NMR experiments, EIMS, and elemental analysis.
Evaluation of Biodegradable PVA-Based 3D Printed Carriers during Dissolution
Authors: Basa Bálint , Jakab Géza , Kállai-Szabó Nikolett , Borbás Bence , Fülöp Viktor , Balogh Emese , Antal István
Published: March 2021

The presence of additive manufacturing, especially 3D printing, has the potential to revolutionize pharmaceutical manufacturing owing to the distinctive capabilities of personalized pharmaceutical manufacturing. This study’s aim was to examine the behavior of commonly used polyvinyl alcohol (PVA) under in vitro dissolution conditions. Polylactic acid (PLA) was also used as a comparator. The carriers were designed and fabricated using computer-aided design (CAD). After printing the containers, the behavior of PVA under in vitro simulated biorelevant conditions was monitored by gravimetry and dynamic light scattering (DLS) methods. The results show that in all the dissolution media PVA carriers were dissolved; the particle size was under 300 nm. However, the dissolution rate was different in various dissolution media. In addition to studying the PVA, as drug delivery carriers, the kinetics of drug release were investigated. These dissolution test results accompanied with UV spectrophotometry tracking indirectly determine the possibilities for modifying the output of quality by computer design.
Calcium Sulfate Hemihydrate (Bassanite) Crystals in the Wood of the Tamarix Tree
Authors: Weiner Steve , Pinkas Iddo , Kossoy Anna , Feldman Yishai (Isai)
Published: March 2021

The most abundant mineral produced in the wood and leaves of trees is calcium oxalate monohydrate (whewellite), and after burning the wood the ash obtained is calcite. In the case of the Tamarix sp. tree, the freshly prepared ash is calcium sulfate (anhydrite). The aim of this study is to determine the calcium sulfate mineral phase in the fresh wood of Tamarix aphylla prior to burning. SEM images of the crystals show that they express smooth faces, are about 5–15 microns in their longest dimensions and are located in the ray cells. Fourier transform infrared spectroscopy (FTIR) and Raman microspectroscopy of the crystals in the wood and after extraction, both showed that the crystals are composed of calcium sulfate hemihydrate (bassanite). As elemental analyses of the crystals showed that in addition to calcium and sulfur, around 20 atom percent of the cations are sodium and potassium, we also obtained an X-ray powder diffraction pattern. This pattern excluded the possibility that the crystals are composed of another related mineral, and confirmed that, indeed, the crystals in the T. aphylla wood are composed of calcium sulfate hemihydrate (bassanite).
Evolution of the Astonishing Naica Giant Crystals in Chihuahua, Mexico
Authors: Carreño-Márquez Iván , Castillo-Sandoval Isaí , Pérez-Cázares Bernardo , Fuentes-Cobas Luis , Esparza-Ponce Hilda , Menéndez-Méndez Esperanza , Fuentes-Montero María , Montero-Cabrera María
Published: March 2021

Calcium sulfate (CaSO4) is one of the most common evaporites found in the earth’s crust. It can be found as four main variations: gypsum (CaSO4∙2H2O), bassanite (CaSO4∙0.5H2O), soluble anhydrite, and insoluble anhydrite (CaSO4), being the key difference the hydration state of the sulfate mineral. Naica giant crystals’ growth starts from a supersaturated solution in a delicate thermodynamic balance close to equilibrium, where gypsum can form nanocrystals able to grow up to 11–12 m long. The growth rates are reported to be as slow as (1.4 ± 0.2) × 10−5 nm/s, taking thousands of years to form crystals with a unique smoothness and diaphaneity, which may or may not include solid or liquid inclusions. Conservation efforts can be traced back to other gypsum structures found prior to Naica’s. Furthermore, in the last two decades, several authors have explored the unique requirements in which these crystals grow, the characterization of their environment and microclimatic conditions, and the prediction of deterioration scenarios. We present a state-of-the-art review on the mentioned topics. Beyond the findings on the origin, in this work we present the current state and the foreseeable future of these astounding crystals.
Solution and Solid-State Photophysical Properties of Positional Isomeric Acrylonitrile Derivatives with Core Pyridine and Phenyl Moieties: Experimental and DFT Studies
Authors: Castillo Armando , Ceballos Paulina , Santos Pilar , Cerón Margarita , Venkatesan Perumal , Pérez-Gutiérrez Enrique , Sosa-Rivadeneyra Martha , Thamotharan Subbiah , Siegler Maxime A. , Percino María Judith
Published: March 2021

The compounds I (Z)-2-(phenyl)-3-(2,4,5-trimethoxyphenyl)acrylonitrile with one side (2,4,5-MeO-), one symmetrical (2Z,2′Z)-2,2′-(1,4-phenylene)bis(3-(2,4,5-trimethoxyphenyl)acrylonitrile), II (both sides with (2,4,5-MeO-), and three positional isomers with pyridine (Z)-2-(pyridin-2- 3, or 4-yl)-3-(2,4,5-trimethoxyphenyl)acrylonitrile, III–V were synthetized and characterized by UV-Vis, fluorescence, IR, H1-NMR, and EI mass spectrometry as well as single crystal X-ray diffraction (SCXRD). The optical properties were strongly influenced by the solvent (hyperchromic and hypochromic shift), which were compared with the solid state. According to the solvatochromism theory, the excited-state (μe) and ground-state (μg) dipole moments were calculated based on the variation of Stokes shift with the solvent’s relative permittivity, refractive index, and polarity parameters. SCXRD analyses revealed that the compounds I and II crystallized in the monoclinic system with the space group, P21/n and P21/c, respectively, and with Z = 4 and 2. III, IV, and V crystallized in space groups: orthorhombic, Pbca; triclinic, P-1; and monoclinic, P21 with Z = 1, 2, and 2, respectively. The intermolecular interactions for compounds I–V were investigated using the CCDC Mercury software and their energies were quantified using PIXEL. The density of states (DOS), molecular electrostatic potential surfaces (MEPS), and natural bond orbitals (NBO) of the compounds were determined to evaluate the photophysical properties.
Constructing Large 2D Lattices Out of DNA-Tiles
Authors: Parikka Johannes M. , Sokołowska Karolina , Markešević Nemanja , Toppari J. Jussi
Published: March 2021

The predictable nature of deoxyribonucleic acid (DNA) interactions enables assembly of DNA into almost any arbitrary shape with programmable features of nanometer precision. The recent progress of DNA nanotechnology has allowed production of an even wider gamut of possible shapes with high-yield and error-free assembly processes. Most of these structures are, however, limited in size to a nanometer scale. To overcome this limitation, a plethora of studies has been carried out to form larger structures using DNA assemblies as building blocks or tiles. Therefore, DNA tiles have become one of the most widely used building blocks for engineering large, intricate structures with nanometer precision. To create even larger assemblies with highly organized patterns, scientists have developed a variety of structural design principles and assembly methods. This review first summarizes currently available DNA tile toolboxes and the basic principles of lattice formation and hierarchical self-assembly using DNA tiles. Special emphasis is given to the forces involved in the assembly process in liquid-liquid and at solid-liquid interfaces, and how to master them to reach the optimum balance between the involved interactions for successful self-assembly. In addition, we focus on the recent approaches that have shown great potential for the controlled immobilization and positioning of DNA nanostructures on different surfaces. The ability to position DNA objects in a controllable manner on technologically relevant surfaces is one step forward towards the integration of DNA-based materials into nanoelectronic and sensor devices.
Conventional vs. Microwave- or Mechanically-Assisted Synthesis of Dihomooxacalix[4]arene Phthalimides: NMR, X-ray and Photophysical Analysis
Authors: Miranda Alexandre , Marcos Paula , Ascenso José , Robalo M. , Bonifácio Vasco , Berberan-Santos Mário , Hickey Neal , Geremia Silvano
Published: March 2021

Direct O-alkylation of p-tert-butyldihomooxacalix[4]arene (1) with N-(bromopropyl)- or N-(bromoethyl)phthalimides and K2CO3 in acetonitrile was conducted under conventional heating (reflux) and using microwave irradiation and ball milling methodologies. The reactions afforded mono- and mainly distal di-substituted derivatives in the cone conformation, in a total of eight compounds. They were isolated by column chromatography, and their conformations and the substitution patterns were established by NMR spectroscopy (1H, 13C, COSY and NOESY experiments). The X-ray structures of four dihomooxacalix[4]arene phthalimide derivatives (2a, 3a, 3b and 5a) are reported, as well as their photophysical properties. The microwave (MW)-assisted alkylations drastically reduced the reaction times (from days to less than 45 min) and produced higher yields of both 1,3-di-substituted phthalimides (3a and 6a) with higher selectivity. Ball milling did not reveal to be a good method for this kind of reaction.
Encapsulation of Vitamin E in Yogurt-Based Beverage Emulsions: Influence of Bulk Pasteurization and Chilled Storage on Physicochemical Stability and Starter Culture Viability
Authors: Raikos Vassilios , Pirie Lynn P. , Gürel Sati , Hayes Helen E.
Published: March 2021

Yogurt is a nutritious food that is regularly consumed in many countries around the world and is widely appreciated for its organoleptic properties. Despite its contribution to human dietary requirements, yogurt in its traditional recipe is a poor source of fat-soluble vitamins. To respond to consumer demands and further increase the nutritional value of this product, this work aimed to fortify yogurt with vitamin E by using emulsification as the method of encapsulation. The effects of thermal processing and chilled storage on the physicochemical stability of the yogurt-based beverage was investigated. Vitamin E was only minorly affected by bulk pasteurization at 63 °C for 30 min and remained stable during storage at 4 °C for 28 days. Fortified samples showed increased in vitro antioxidant activity compared with non-fortified samples. Lactic acid bacterial counts were above the minimum recommended levels (>106 cfu/g) after processing and storage. In conclusion, this work has demonstrated that emulsification can be an effective strategy for developing yogurt-based products fortified with fat soluble vitamins.
Novel Carbon Dots Derived from Glycyrrhizae Radix et Rhizoma and Their Anti-Gastric Ulcer Effect
Authors: Liu Yuhan , Zhang Meiling , Cheng Jinjun , Zhang Yue , Kong Hui , Zhao Yan , Qu Huihua
Published: March 2021

Glycyrrhizae Radix et Rhizoma (GRR) is one of the commonly used traditional Chinese medicines in clinical practice, which has been applied to treat digestive system diseases for hundreds of years. GRR is preferred for anti-gastric ulcer, however, the main active compounds are still unknown. In this study, GRR was used as precursor to synthesize carbon dots (CDs) by a environment-friendly one-step pyrolysis process. GRR-CDs were characterized by using transmission electron microscopy, high-resolution TEM, fourier transform infrared, ultraviolet-visible and fluorescence spectroscopy, X-ray photoelectron spectroscopy, X-ray diffraction and high-performance liquid chromatography. In addition, cellular toxicity of GRR-CDs was studied by using CCK-8 in RAW264.7 cells, and the anti-gastric ulcer activity was evaluated and confirmed using mice model of acute alcoholic gastric ulcer. The experiment confirmed that GRR-CDs were the spherical structure with a large number of active groups on the surface and their particle size ranged from 2 to 10 nm. GRR-CDs had no toxicity to RAW264.7 cells at concentration of 19.5 to 5000 μg/mL and could reduce the oxidative damage of gastric mucosa and tissues caused by alcohol, as demonstrated by restoring expression of malondialdehyde, superoxide dismutase and nitric oxide in serum and tissue of mice. The results indicated the explicit anti-ulcer activity of GRR-CDs, which provided a new insights for the research on effective material basis of GRR.