bluuebunny/crossref_metadata_2025 huggingface dataset:
Improved Inpatient Care through Greater Patient–Doctor Contact under the Hospitalist Management Approach: A Real-Time Assessment
Authors: Chae Wonjeong , Choi Dong-Woo , Park Eun-Cheol , Jang Sung-In
Published: May 2021

Objective: To examine the difference between hospitalist and non-hospitalist frequency of patient–doctor contact, duration of contact, cumulative contact time, and the amount of time taken by the doctor to resolve an issue in response to a medical call. Research Design and Measures: Data from 18 facilities and 36 wards (18 hospitalist wards and 18 non-hospitalist wards) were collected. The patient–doctor contact slip and medical call response slips were given to each inpatient ward to record. A total of 28,926 contacts occurred with 2990 patients, and a total of 8435 medical call responses occurred with 3329 patients. Multivariate logistic regression analyses and regression analyses were used for statistical analyses. Results: The average frequency of patient–doctor contact during a hospital stay was 10.0 times per patient for hospitalist patients. Using regression analyses, hospitalist patients had more contact with the attending physician (β = 5.6, standard error (SE) = 0.28, p < 0.0001). Based on cumulative contact time, hospitalists spent significantly more time with the patient (β = 32.29, SE = 1.54, p < 0.0001). After a medical call to resolve the issue, doctors who took longer than 10 min were 4.14 times (95% CI 3.15–5.44) and those who took longer than 30 min were 4.96 times (95% CI 2.75–8.95) more likely to be non-hospitalists than hospitalists. Conclusion: This study found that hospitalists devoted more time to having frequent encounters with patients. Therefore, inpatient care by a hospitalist who manages inpatient care from admission to discharge could improve the care quality.
Smoking and Vaping in Amateur Rugby Players, Coaches and Referees: Findings from a Regional Survey Might Help to Define Prevention Targets
Authors: Chagué Frédéric , Reboursière Emmanuel , Israël Jean , Hager Jean-Philippe , Ngassa Patrice , Geneste Marc , Guinoiseau Jean-Pierre , Garet Gilles , Girardin Jacques , Sarda Jacques , Cottin Yves , Zeller Marianne
Published: May 2021

A high prevalence of cigarette smoking has been documented in France, and new patterns of tobacco and nicotine consumption are emerging, especially in some sports. In the amateur rugby population, data are scarce on harmful consumption and on the awareness of the risk of smoking. We analyzed the consumption of tobacco and other nicotine products in French amateur players, coaches and referees. Amateur players (>12 years old), coaches and referees participating in the Burgundy amateur championship were invited to answer an electronic, anonymous questionnaire during the 2017–2018 sport season. Among the 683 subjects (gender ratio M/F = 0.9), 176 (25.8%) were current smokers, including 32.4% of the referees and 28.2% of the coaches. The prevalence of smokers was higher in females (37.5%) than in males (24.6%). Most (86.4%) smoked within 2 h before/after a rugby session. Only 28 subjects (4.1%) usually vaped; 21 of them (75%) vaped within 2 h before/after a rugby session. Other tobacco or nicotine products were infrequent. The awareness about the risks of smoking before/after sport was incomplete, including in coaches and referees. The prevalence of cigarette smoking is alarming across the whole spectrum of rugby amateur actors. Education programs are urgently needed to reduce tobacco consumption in this at-risk population.
Reasons for Sports-Based Physical Activity Dropouts in University Students
Authors: Sáez Iker , Solabarrieta Josu , Rubio Isabel
Published: May 2021

Despite extensive evidence reporting the numerous health benefits of physical activity, recent studies show that many people (60%) do not follow the recommendations to meet the accepted minimums of physical activity. Some of the main problems in today’s society are the high dropout rates (35%) and low adherence to the conditions for achieving the physical activity recommendations. The aim of the study is to analyze the reasons for dropout from sports that the participants particularly liked, to design a new scale of reasons as to why they dropped out based on several previously existing scales, and to study the dropout differences based on different variables. The sample consisted of 813 Vizcaya university students (61.6% women and 38.4% men), aged between 18 and 29 (M = 20.5; SD = 1.8). Frequency distributions, univariate descriptive analyses, and bivariate statistical analyses, such as t-test, analysis of variance, and correlations, were analyzed. The construct validity of the dropout reasons questionnaire was analyzed by combining an Exploratory Factor Analysis (n = 406) and a Confirmatory Factor Analysis (n = 407). The five-factor measurement model was appropriate and allowed to identify the factor rankings and its relation to some key variables. Lack of time (or dedication to other activities unrelated to physical activity) and fatigue seem to be the main factors for dropping out. The life changes produced at the time of entry and during university life seem to guide students to value other activities.
Antibiotic-Resistant Bacteria in Aquaculture and Climate Change: A Challenge for Health in the Mediterranean Area
Authors: Pepi Milva , Focardi Silvano
Published: May 2021

Aquaculture is the productive activity that will play a crucial role in the challenges of the millennium, such as the need for proteins that support humans and the respect for the environment. Aquaculture is an important economic activity in the Mediterranean basin. A great impact is presented, however, by aquaculture practices as they involve the use of antibiotics for treatment and prophylaxis. As a consequence of the use of antibiotics in aquaculture, antibiotic resistance is induced in the surrounding bacteria in the column water, sediment, and fish-associated bacterial strains. Through horizontal gene transfer, bacteria can diffuse antibiotic-resistance genes and mobile resistance genes further spreading genetic determinants. Once triggered, antibiotic resistance easily spreads among aquatic microbial communities and, from there, can reach human pathogenic bacteria, making vain the use of antibiotics for human health. Climate change claims a significant role in this context, as rising temperatures can affect cell physiology in bacteria in the same way as antibiotics, causing antibiotic resistance to begin with. The Mediterranean Sea represents a ‘hot spot’ in terms of climate change and aspects of antibiotic resistance in aquaculture in this area can be significantly amplified, thus increasing threats to human health. Practices must be adopted to counteract negative impacts on human health, with a reduction in the use of antibiotics as a pivotal point. In the meantime, it is necessary to act against climate change by reducing anthropogenic impacts, for example by reducing CO2 emissions into the atmosphere. The One Health type approach, which involves the intervention of different skills, such as veterinary, ecology, and medicine in compliance with the principles of sustainability, is necessary and strongly recommended to face these important challenges for human and animal health, and for environmental safety in the Mediterranean area.
Forest Manners Exchange: Forest as a Place to Remedy Risky Behaviour of Adolescents: Mixed Methods Approach
Authors: Macháčková Karolina , Dudík Roman , Zelený Jiří , Kolářová Dana , Vinš Zbyněk , Riedl Marcel
Published: May 2021

This paper evaluates the impact of the forest environment on aggressive manifestations in adolescents. A remedial educative programme was performed with 68 teenagers from institutions with substitute social care with diagnoses F 30.0 (affective disorders) and F 91.0 (family-related behavioural disorders), aged 12–16 years. Adolescents observed patterns of prosocial behaviour in forest animals (wolves, wild boars, deer, bees, ants, squirrels and birds), based on the fact that processes and interactions in nature are analogous to proceedings and bonds in human society. The methodology is based on qualitative and quantitative research. Projective tests (Rorschach Test, Hand Test, Thematic Apperception Test) were used as a diagnostic tool for aggressive manifestations before and after forest therapies based on Shinrin-yoku, wilderness therapy, observational learning and forest pedagogy. Probands underwent 16 therapies lasting for two hours each. The experimental intervention has a statistically significant effect on the decreased final values relating to psychopathology, irritability, restlessness, emotional instability, egocentrism, relativity, and negativism. Forest animals demonstrated to these adolescents ways of communication, cooperation, adaptability, and care for others, i.e., characteristics without which no community can work.
Phthalate Exposure Pattern in Breast Milk within a Six-Month Postpartum Time in Southern Taiwan
Authors: Hung Shen-Che , Lin Ting-I , Suen Jau-Ling , Liu Hsien-Kuan , Wu Pei-Ling , Wu Chien-Yi , Yang Yu-Chen S. H. , Yang San-Nan , Yang Yung-Ning
Published: May 2021

Di-(2-ethylhexyl) phthalate (DEHP), a common plasticizer, has been detected in breast milk in many countries; however, whether phthalate metabolite concentration and the detection rate in breast milk change postpartum is still unknown. We measured phthalate metabolite concentrations in breast milk in the first 6 months postpartum in women enrolled in the E-Da hospital from January to July 2017. A total of 56 breastfeeding mothers and 66 samples were included in this study. We analyzed the samples’ concentration of eight phthalate metabolites using liquid chromatography mass spectrometry. The concentration of mono-2-ethylhexyl phthalate (MEHP) was significantly higher in the first month, and then decreased over time. The detection rate of ono-isobutyl phthalate (MiBP) and mono-n-butyl phthalate (MBP) was low in the first month and then increased over time. Compared with a previous study published in 2011, the levels of MEHP and MiBP in breast milk were much lower in the present study, suggesting an increased awareness of the health risks of phthalate exposure after a food scandal occurred in Taiwan. This study provides information for evaluating newborns’ exposure to different kinds of phthalate through human milk in the postpartum period.
Comparison of Generalized Anxiety and Sleep Disturbance among Frontline and Second-Line Healthcare Workers during the COVID-19 Pandemic
Authors: Meo Sultan Ayoub , Alkhalifah Joud Mohammed , Alshammari Nouf Faisal , Alnufaie Wejdan Saud
Published: May 2021

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection, also known as COVID-19, has developed into an alarming situation around the world. Healthcare workers are playing the role of frontline defense to safeguard the lives of everyone during the COVID-19 pandemic. The present study aimed to investigate the anxiety levels and sleep quality among frontline and second-line healthcare workers during the COVID-19 pandemic. In this cross-sectional study, a validated, self-administered, electronic questionnaire was distributed through email to healthcare workers. The selection of 1678 healthcare workers was based on a convenience sampling technique. The General Anxiety Disorder-7 (GAD-7) and Pittsburgh Sleep Quality Index (PSQI) instrument scales were used to assess healthcare workers’ anxiety levels and sleep quality during the COVID-19 pandemic. Out of 1678 respondents, 1200 (71.5%) were frontline healthcare workers, while 478 (28.5%) were second-line healthcare workers. Among all the healthcare workers, 435 (25.92%) were experiencing moderate to severe anxiety. Among them, 713 (59.4%) frontline healthcare workers were experiencing anxiety in comparison with 277 (57.9%) second-line healthcare workers. Severe anxiety symptoms were seen in 137 (11.41%) frontline healthcare workers compared to 44 (9.20%) second-line healthcare workers. In total, 1376 (82.0%) healthcare workers were found to have poor sleep quality; 975 (58.10%) were frontline, and 407 (23.89%) were second-line healthcare workers. The highest poor sleep quality levels were found among 642 (84.6%) of the healthcare workers who work in frontline areas (emergency departments, intensive care units, and wards) compared to 734 (79.9%) of the healthcare workers who work in second-line areas. These findings provide a substantial contribution to the consolidation of evidence concerning the negative impact of the pandemic on the mental health of healthcare workers (HCWs). These results have established an association that the COVID-19 pandemic causes larger negative psychological symptoms in frontline healthcare workers, such as severe anxiety and poor sleep quality. Preventive measures to minimize anxiety levels and maintain sleep quality, addressing this issue nationally and globally, are essential to support the healthcare workers who are sacrificing their mental health for the future of our nations.
A Matrix Metalloproteinase Mediates Tracheal Development in Bombyx mori
Authors: Wei Yi , Zhou Xiao-Lin , Liu Tai-Hang , Chen Peng , Jiang Xia , Dong Zhan-Qi , Pan Min-Hui , Lu Cheng
Published: May 2021

The trachea of insects is a tubular epithelia tissue that transports oxygen and other gases. It serves as a useful model for the studying of the cellular and molecular events involved in epithelial tube formation. Almost all of the extracellular matrix can be degraded by Matrix metalloproteinases (MMPs), which is closely related to the processes of development and regeneration. The regulation of trachea by MMPs is roughly known in previous studies, but the detailed regulation mechanism and involved gene function are not fully explored. In this article, we found MMP1 expressed highly during tracheal remodeling, and knocked out it makes the tracheal branch number reduced in Bombyx mori. In trachea of transgenic BmMMP1-KO silkworm, the space expanding of taenidium and epidermal cells and the structure of apical membrane were abnormal. To explore the underlying mechanism, we detected that DE-cadherin and Integrin β1 were accumulated in trachea of transgenic BmMMP1-KO silkworm by immunohistochemistry. Moreover, 5-Bromo-2′-Deoxyuridine (BrdU) labeling showed that knockout of BmMMP1 in silkworm inhibited tracheal cell proliferation, and BmMMP1 also regulated the proliferation and migration of BmNS cells. All of the results demonstrated that BmMMP1 regulates the development of the tracheal tissue by expanding the space of tracheal cuticles and increases the number of tracheal branches by degrading DE-cadherin and Integrin β1.
Nanomechanical Hallmarks of Helicobacter pylori Infection in Pediatric Patients
Authors: Deptuła Piotr , Suprewicz Łukasz , Daniluk Tamara , Namiot Andrzej , Chmielewska Sylwia Joanna , Daniluk Urszula , Lebensztejn Dariusz , Bucki Robert
Published: May 2021

Background: the molecular mechanism of gastric cancer development related to Helicobacter pylori (H. pylori) infection has not been fully understood, and further studies are still needed. Information regarding nanomechanical aspects of pathophysiological events that occur during H. pylori infection can be crucial in the development of new prevention, treatment, and diagnostic measures against clinical consequences associated with H. pylori infection, including gastric ulcer, duodenal ulcer, and gastric cancer. Methods: in this study, we assessed mechanical properties of children’s healthy and H. pylori positive stomach tissues and the mechanical response of human gastric cells exposed to heat-treated H. pylori cells using atomic force microscopy (AFM NanoWizard 4 BioScience JPK Instruments Bruker). Elastic modulus (i.e., the Young’s modulus) was derived from the Hertz–Sneddon model applied to force-indentation curves. Human tissue samples were evaluated using rapid urease tests to identify H. pylori positive samples, and the presence of H. pylori cells in those samples was confirmed using immunohistopathological staining. Results and conclusion: collected data suggest that nanomechanical properties of infected tissue might be considered as markers indicated H. pylori presence since infected tissues are softer than uninfected ones. At the cellular level, this mechanical response is at least partially mediated by cell cytoskeleton remodeling indicating that gastric cells are able to tune their mechanical properties when subjected to the presence of H. pylori products. Persistent fluctuations of tissue mechanical properties in response to H. pylori infection might, in the long-term, promote induction of cancer development.
TP53 Targeted Deep Sequencing of Cell-Free DNA in Esophageal Squamous Cell Carcinoma Using Low-Quality Serum: Concordance with Tumor Mutation
Authors: Nasrollahzadeh Dariush , Roshandel Gholamreza , Delhomme Tiffany Myriam , Avogbe Patrice Hodonou , Foll Matthieu , Saidi Farrokh , Poustchi Hossein , Sotoudeh Masoud , Malekzadeh Reza , Brennan Paul , Mckay James , Hainaut Pierre , Abedi-Ardekani Behnoush
Published: May 2021

Circulating cell-free DNA (cfDNA) is emerging as a potential tumor biomarker. CfDNA-based biomarkers may be applicable in tumors without an available non-invasive screening method among at-risk populations. Esophageal squamous cell carcinoma (ESCC) and residents of the Asian cancer belt are examples of those malignancies and populations. Previous epidemiological studies using cfDNA have pointed to the need for high volumes of good quality plasma (i.e., >1 mL plasma with 0 or 1 cycles of freeze-thaw) rather than archival serum, which is often the main available source of cfDNA in retrospective studies. Here, we have investigated the concordance of TP53 mutations in tumor tissue and cfDNA extracted from archival serum left-over from 42 cases and 39 matched controls (age, gender, residence) in a high-risk area of Northern Iran (Golestan). Deep sequencing of TP53 coding regions was complemented with a specialized variant caller (Needlestack). Overall, 23% to 31% of mutations were concordantly detected in tumor and serum cfDNA (based on two false discovery rate thresholds). Concordance was positively correlated with high cfDNA concentration, smoking history (p-value = 0.02) and mutations with a high potential of neoantigen formation (OR; 95%CI = 1.9 (1.11–3.29)), suggesting that tumor DNA release in the bloodstream might reflect the effects of immune and inflammatory context on tumor cell turnover. We identified TP53 mutations in five controls, one of whom was subsequently diagnosed with ESCC. Overall, the results showed that cfDNA mutations can be reliably identified by deep sequencing of archival serum, with a rate of success comparable to plasma. Nonetheless, 70% non-identifiable mutations among cancer patients and 12% mutation detection in controls are the main challenges in applying cfDNA to detect tumor-related variants when blindly targeting whole coding regions of the TP53 gene in ESCC.
Incorporation of Sulfonamide Moiety into Biguanide Scaffold Results in Apoptosis Induction and Cell Cycle Arrest in MCF-7 Breast Cancer Cells
Authors: Markowicz-Piasecka Magdalena , Sadowski Karol , Huttunen Johanna , Sikora Joanna , Huttunen Kristiina M.
Published: May 2021

Metformin, apart from its glucose-lowering properties, has also been found to demonstrate anti-cancer properties. Anti-cancer efficacy of metformin depends on its uptake in cancer cells, which is mediated by plasma membrane monoamine transporters (PMAT) and organic cation transporters (OCTs). This study presents an analysis of transporter mediated cellular uptake of ten sulfonamide-based derivatives of metformin in two breast cancer cell lines (MCF-7 and MDA-MB-231). Effects of these compounds on cancer cell growth inhibition were also determined. All examined sulfonamide-based analogues of metformin were characterized by greater cellular uptake in both MCF-7 and MDA-MB-231 cells, and stronger cytotoxic properties than those of metformin. Effective intracellular transport of the examined compounds in MCF-7 cells was accompanied by high cytotoxic activity. For instance, compound 2 with meta-methyl group in the benzene ring inhibited MCF-7 growth at micromolar range (IC50 = 87.7 ± 1.18 µmol/L). Further studies showed that cytotoxicity of sulfonamide-based derivatives of metformin partially results from their ability to induce apoptosis in MCF-7 and MDA-MB-231 cells and arrest cell cycle in the G0/G1 phase. In addition, these compounds were found to inhibit cellular migration in wound healing assay. Importantly, the tested biguanides are more effective in MCF-7 cells at relatively lower concentrations than in MDA-MB-231 cells, which proves that the effectiveness of transporter-mediated accumulation in MCF-7 cells is related to biological effects, including MCF-7 cell growth inhibition, apoptosis induction and cell cycle arrest. In summary, this study supports the hypothesis that effective transporter-mediated cellular uptake of a chemical molecule determines its cytotoxic properties. These results warrant a further investigation of biguanides as putative anti-cancer agents.
Rhizomal Reclassification of Living Organisms
Authors: Ibrahim Ahmad , Colson Philippe , Merhej Vicky , Zgheib Rita , Maatouk Mohamad , Naud Sabrina , Bittar Fadi , Raoult Didier
Published: May 2021

Living organisms interact with each other during their lifetime, leading to genomes rearrangement and sequences transfer. These well-known phenomena give these organisms mosaic genomes, which challenge their classification. Moreover, many findings occurred between the IXXth and XXIst century, especially the discovery of giant viruses and candidate phyla radiation (CPR). Here, we tried to provide an updated classification, which integrates 216 representative genomes of the current described organisms. The reclassification was expressed through a genetic network based on the total genomic content, not on a single gene to represent the tree of life. This rhizomal exploration represents, more accurately, the evolutionary relationships among the studied species. Our analyses show a separated branch named fifth TRUC (Things Resisting Uncompleted Classifications). This taxon groups CPRs together, independently from Bacteria, Archaea (which regrouped also Nanoarchaeota and Asgard members), Eukarya, and the giant viruses (recognized recently as fourth TRUC). Finally, the broadening of analysis methods will lead to the discovery of new organisms, which justify the importance of updating the classification at every opportunity. In this perspective, our pragmatic representation could be adjusted along with the progress of evolutionary studies.
Intracellular Na+ Modulates Pacemaking Activity in Murine Sinoatrial Node Myocytes: An In Silico Analysis
Authors: Morotti Stefano , Ni Haibo , Peters Colin H. , Rickert Christian , Asgari-Targhi Ameneh , Sato Daisuke , Glukhov Alexey V. , Proenza Catherine , Grandi Eleonora
Published: May 2021

Background: The mechanisms underlying dysfunction in the sinoatrial node (SAN), the heart’s primary pacemaker, are incompletely understood. Electrical and Ca2+-handling remodeling have been implicated in SAN dysfunction associated with heart failure, aging, and diabetes. Cardiomyocyte [Na+]i is also elevated in these diseases, where it contributes to arrhythmogenesis. Here, we sought to investigate the largely unexplored role of Na+ homeostasis in SAN pacemaking and test whether [Na+]i dysregulation may contribute to SAN dysfunction. Methods: We developed a dataset-specific computational model of the murine SAN myocyte and simulated alterations in the major processes of Na+ entry (Na+/Ca2+ exchanger, NCX) and removal (Na+/K+ ATPase, NKA). Results: We found that changes in intracellular Na+ homeostatic processes dynamically regulate SAN electrophysiology. Mild reductions in NKA and NCX function increase myocyte firing rate, whereas a stronger reduction causes bursting activity and loss of automaticity. These pathologic phenotypes mimic those observed experimentally in NCX- and ankyrin-B-deficient mice due to altered feedback between the Ca2+ and membrane potential clocks underlying SAN firing. Conclusions: Our study generates new testable predictions and insight linking Na+ homeostasis to Ca2+ handling and membrane potential dynamics in SAN myocytes that may advance our understanding of SAN (dys)function.
Molecular Mechanisms of Sensorineural Hearing Loss and Development of Inner Ear Therapeutics
Authors: Vlajkovic Srdjan M. , Thorne Peter R.
Published: May 2021

The sense of hearing enables us to enjoy sounds and music and engage with other people [...]
Biodegradable Stent with mTOR Inhibitor-Eluting Reduces Progression of Ureteral Stricture
Authors: Ho Dong-Ru , Su Shih-Horng , Chang Pey-Jium , Lin Wei-Yu , Huang Yun-Ching , Lin Jian-Hui , Huang Kuo-Tsai , Chan Wai-Nga , Chen Chih-Shou
Published: May 2021

In this study, we investigated the effect of mTOR inhibitor (mTORi) drug-eluting biodegradable stent (DE stent), a putative restenosis-inhibiting device for coronary artery, on thermal-injury-related ureteral stricture in rabbits. In vitro evaluation confirmed the dose-dependent effect of mTORi, i.e., rapamycin, on fibrotic markers in ureteral component cell lines. Upper ureteral fibrosis was induced by ureteral thermal injury in open surgery, which was followed by insertion of biodegradable stents, with or without rapamycin drug-eluting. Immunohistochemistry and Western blotting were performed 4 weeks after the operation to determine gross anatomy changes, collagen deposition, expression of epithelial–mesenchymal transition markers, including Smad, α-SMA, and SNAI 1. Ureteral thermal injury resulted in severe ipsilateral hydronephrosis. The levels of type III collagen, Smad, α-SMA, and SNAI 1 were increased 28 days after ureteral thermal injury. Treatment with mTORi-eluting biodegradable stents significantly attenuated thermal injury-induced urinary tract obstruction and reduced the level of fibrosis proteins, i.e., type III collagen. TGF-β and EMT signaling pathway markers, Smad and SNAI 1, were significantly modified in DE stent-treated thermal-injury-related ureteral stricture rabbits. These results suggested that intra-ureteral administration of rapamycin by DE stent provides modification of fibrosis signaling pathway, and inhibiting mTOR may result in fibrotic process change.
Starch Granules in Arabidopsis thaliana Mesophyll and Guard Cells Show Similar Morphology but Differences in Size and Number
Authors: Liu Qingting , Li Xiaoping , Fettke Joerg
Published: May 2021

Transitory starch granules result from complex carbon turnover and display specific situations during starch synthesis and degradation. The fundamental mechanisms that specify starch granule characteristics, such as granule size, morphology, and the number per chloroplast, are largely unknown. However, transitory starch is found in the various cells of the leaves of Arabidopsis thaliana, but comparative analyses are lacking. Here, we adopted a fast method of laser confocal scanning microscopy to analyze the starch granules in a series of Arabidopsis mutants with altered starch metabolism. This allowed us to separately analyze the starch particles in the mesophyll and in guard cells. In all mutants, the guard cells were always found to contain more but smaller plastidial starch granules than mesophyll cells. The morphological properties of the starch granules, however, were indiscernible or identical in both types of leaf cells.
A Computer-Based Methodology to Design Non-Standard Peptides Potentially Able to Prevent HOX-PBX1-Associated Cancer Diseases
Authors: Gulotta Maria Rita , De Simone Giada , John Justin , Perricone Ugo , Brancale Andrea
Published: May 2021

In the last decades, HOX proteins have been extensively studied due to their pivotal role in transcriptional events. HOX proteins execute their activity by exploiting a cooperative binding to PBX proteins and DNA. Therefore, an increase or decrease in HOX activity has been associated with both solid and haematological cancer diseases. Thus, inhibiting HOX-PBX interaction represents a potential strategy to prevent these malignancies, as demonstrated by the patented peptide HTL001 that is being studied in clinical trials. In this work, a computational study is described to identify novel potential peptides designed by employing a database of non-natural amino acids. For this purpose, residue scanning of the HOX minimal active sequence was performed to select the mutations to be further processed. According to these results, the peptides were point-mutated and used for Molecular Dynamics (MD) simulations in complex with PBX1 protein and DNA to evaluate complex binding stability. MM-GBSA calculations of the resulting MD trajectories were exploited to guide the selection of the most promising mutations that were exploited to generate twelve combinatorial peptides. Finally, the latter peptides in complex with PBX1 protein and DNA were exploited to run MD simulations and the ΔGbinding average values of the complexes were calculated. Thus, the analysis of the results highlighted eleven combinatorial peptides that will be considered for further assays.
Design, Synthesis, and Biological Evaluation of Novel 6H-Benzo[c]chromen-6-one Derivatives as Potential Phosphodiesterase II Inhibitors
Authors: Tang Long , Jiang Jianchun , Song Guoqiang , Wang Yajing , Zhuang Ziheng , Tan Ying , Xia Yan , Huang Xianfeng , Feng Xiaoqing
Published: May 2021

Urolithins (hydroxylated 6H-benzo[c]chromen-6-ones) are the main bioavailable metabolites of ellagic acid (EA), which was shown to be a cognitive enhancer in the treatment of neurodegenerative diseases. As part of this research, a series of alkoxylated 6H-benzo[c]chromen-6-one derivatives were designed and synthesized. Furthermore, their biological activities were evaluated as potential PDE2 inhibitors, and the alkoxylated 6H-benzo[c]chromen-6-one derivative 1f was found to have the optimal inhibitory potential (IC50: 3.67 ± 0.47 μM). It also exhibited comparable activity in comparison to that of BAY 60-7550 in vitro cell level studies.
Gamma—Ray Counters to Monitor Radioactive Waste Packages in the MICADO Project
Authors: Cosentino Luigi , Giuffrida Martina , Lo Meo Sergio , Longhitano Fabio , Pappalardo Alfio , Passaro Giuseppe , Finocchiaro Paolo
Published: May 2021

One of the goals of the MICADO Euratom project is to monitor the gamma-rays emitted by radioactive waste drums in storage sites on a medium to long term basis. For this purpose, 36 low-cost gamma-ray counters were designed and built to act as a demonstrator. These counters, named SciFi, are based on a scintillating fiber readout at each end by a silicon photomultiplier, assembled in a robust arrangement in the form of 80 cm long pipes. Several counters will be placed around radwaste packages in order to monitor the gamma dose-rate by collecting a continuous data stream. The 36 sensors were thoroughly tested with a 22Na and a 137Cs gamma-ray sources, and with an AmBe neutron and gamma-ray source, the results are quite satisfactory, and the next step will be the test in a real environment.
The Effects of Technological Interventions on Social Participation of Community-Dwelling Older Adults with and without Dementia: A Systematic Review
Authors: Heins Pascale , Boots Lizzy M. M. , Koh Wei Qi , Neven An , Verhey Frans R. J. , de Vugt Marjolein E.
Published: May 2021

Social isolation in community-dwelling older adults with dementia is a growing health issue that can negatively affect health and well-being. To date, little attention has been paid to the role of technology in improving their social participation. This systematic review aims to provide a systematic overview of the effects of technological interventions that target social participation in community-dwelling older adults with and without dementia. The scientific databases Medline (PubMed), PsycINFO, CINAHL, Web of Science, and the Cochrane Library were systematically searched and independently screened by two reviewers. Results were synthesized narratively. The methodological quality of included studies was independently assessed by two reviewers. In total, 36 studies of varying methodological quality were identified. Most studies evaluated social networking technology and ICT training programs. Three studies focused on people with dementia. Quantitative findings showed limited effects on loneliness, social isolation, and social support. Nevertheless, several benefits related to social participation were reported qualitatively. Social interaction, face-to-face contact, and intergenerational engagement were suggested to be successful elements of technological interventions in improving the social participation of community-dwelling older adults. Rigorous studies with larger sample sizes are highly needed to evaluate the long-term effects of technology on the multidimensional concept of social participation.
Proteomic Analyses of Vitreous in Proliferative Diabetic Retinopathy: Prior Studies and Future Outlook
Authors: Weber Sarah R. , Zhao Yuanjun , Gates Christopher , Ma Jingqun , da Veiga Leprevost Felipe , Basrur Venkatesha , Nesvizhskii Alexey I. , Gardner Thomas W. , Sundstrom Jeffrey M.
Published: May 2021

Vitreous fluid is becoming an increasingly popular medium for the study of retinal disease. Numerous studies have demonstrated that proteomic analysis of the vitreous from patients with proliferative diabetic retinopathy yields valuable molecular information regarding known and novel proteins and pathways involved in this disease. However, there is no standardized methodology for vitreous proteomic studies. Here, we share a suggested protocol for such studies and outline the various experimental and analytic methods that are currently available. We also review prior mass spectrometry-based proteomic studies of the vitreous from patients with proliferative diabetic retinopathy, discuss common pitfalls of these studies, and propose next steps for moving the field forward.
IgA Vasculitis and IgA Nephropathy: Same Disease?
Authors: Pillebout Evangeline
Published: May 2021

Many authors suggested that IgA Vasculitis (IgAV) and IgA Nephropathy (IgAN) would be two clinical manifestations of the same disease; in particular, that IgAV would be the systemic form of the IgAN. A limited number of studies have included sufficient children or adults with IgAN or IgAV (with or without nephropathy) and followed long enough to conclude on differences or similarities in terms of clinical, biological or histological presentation, physiopathology, genetics or prognosis. All therapeutic trials available on IgAN excluded patients with vasculitis. IgAV and IgAN could represent different extremities of a continuous spectrum of the same disease. Due to skin rash, patients with IgAV are diagnosed precociously. Conversely, because of the absence of any clinical signs, a renal biopsy is practiced for patients with an IgAN to confirm nephropathy at any time of the evolution of the disease, which could explain the frequent chronic lesions at diagnosis. Nevertheless, the question that remains unsolved is why do patients with IgAN not have skin lesions and some patients with IgAV not have nephropathy? Larger clinical studies are needed, including both diseases, with a common histological classification, and stratified on age and genetic background to assess renal prognosis and therapeutic strategies.
Role of 11C Methionine Positron Emission Tomography (11CMETPET) for Surgery and Radiation Therapy Planning in Newly Diagnosed Glioblastoma Patients Enrolled into a Phase II Clinical Study
Authors: Pessina Federico , Navarria Pierina , Clerici Elena , Bellu Luisa , Franzini Andrea , Milani Davide , Simonelli Matteo , Persico Pasquale , Politi Letterio S. , Casarotti Alessandra , Fernandes Bethania , Olei Simone , Sollini Martina , Chiti Arturo , Scorsetti Marta
Published: May 2021

(1) Background: We investigated the role of [11C]-methionine PET in a cohort of newly diagnosed glioblastoma multiforme (GBM) patients to evaluate whether it could modify the extent of surgical resection and improve radiation therapy volume delineation. (2) Methods: Newly diagnosed GBM patients, ages 18–70, with a Karnofsky performance scale (KPS) ≥ 70 with available MRI and [11C]-methionine PET were included. Patients were treated with different amounts of surgical resection followed by radio-chemotherapy. The role of [11C]-methionine PET in surgical and RT planning was analyzed. A threshold of SUVmax was searched. (3) Results: From August 2013 to April 2016, 93 patients were treated and included in this analysis. Residual tumor volume was detected in 63 cases on MRI and in 78 on [11C]-methionine PET, including 15 receiving gross total resection. The location of uptake was mainly observed in FLAIR abnormalities. [11C]-methionine uptake changed RT volume in 11% of patients. The presence of [11C]-methionine uptake in patients receiving GTR proved to influence survival (p = 0.029). The threshold of the SUVmax conditioning outcome was five. (4) Conclusions: [11C]-methionine PET allowed to detect areas at higher risk of recurrence located in FLAIR abnormalities in patients affected by GBM. A challenging issue is represented by integrating morphological and functional imaging to better define the extent of surgical resection to perform.
Population-Level Prevalence, Bother, and Treatment Behavior for Urinary Incontinence in an Eastern European Country: Findings from the LUTS POLAND Study
Authors: Przydacz Mikolaj , Chlosta Marcin , Chlosta Piotr
Published: May 2021

Objectives: Population-level data are lacking for urinary incontinence (UI) in Central and Eastern European countries. Therefore, the objective of this study was to estimate the prevalence, bother, and behavior regarding treatment for UI in a population-representative group of Polish adults aged ≥ 40 years. Methods: Data for this epidemiological study were derived from the larger LUTS POLAND project, in which a group of adults that typified the Polish population were surveyed, by telephone, about lower urinary tract symptoms. Respondents were classified by age, sex, and place of residence. UI was assessed with a standard protocol and established International Continence Society definitions. Results: The LUTS POLAND survey included 6005 completed interviews. The prevalence of UI was 14.6–25.4%; women reported a greater occurrence compared with men (p < 0.001). For both sexes, UI prevalence increased with age. Stress UI was the most common type of UI in women, and urgency UI was the most prevalent in men. We did not find a difference in prevalence between urban and rural areas. Individuals were greatly bothered by UI. For women, mixed UI was the most bothersome, whereas for men, leak for no reason was most annoying. More than half of respondents (51.4–62.3%) who reported UI expressed anxiety about the effect of UI on their quality of life. Nevertheless, only around one third (29.2–38.1%) of respondents with UI sought treatment, most of whom received treatment. Persons from urban and rural areas did not differ in the degrees of treatment seeking and treatment receiving. Conclusion: Urinary incontinence was prevalent and greatly bothersome among Polish adults aged ≥ 40 years. Consequently, UI had detrimental effects on quality of life. Nonetheless, most affected persons did not seek treatment. Therefore, we need to increase population awareness in Poland about UI and available treatment methods, and we need to ensure adequate allocation of government and healthcare system resources.
Digital Technology in Clinical Trials for Multiple Sclerosis: Systematic Review
Authors: De Angelis Marcello , Lavorgna Luigi , Carotenuto Antonio , Petruzzo Martina , Lanzillo Roberta , Brescia Morra Vincenzo , Moccia Marcello
Published: May 2021

Clinical trials in multiple sclerosis (MS) have been including digital technology tools to overcome limitations in treatment delivery and disease monitoring. In March 2020, we conducted a systematic search on pubmed.gov and clinicaltrials.gov databases (with no restrictions) to identify all relevant published and unpublished clinical trials, in English language, including MS patients, in which digital technology was applied. We used “multiple sclerosis” and “clinical trial” as the main search words, and “app”, “digital”, “electronic”, “internet” and “mobile” as additional search words, separately. Digital technology is part of clinical trial interventions to deliver psychotherapy and motor rehabilitation, with exergames, e-training, and robot-assisted exercises. Digital technology has been used to standardise previously existing outcome measures, with automatic acquisitions, reduced inconsistencies, and improved detection of symptoms (e.g., electronic recording of motor performance). Other clinical trials have been using digital technology for monitoring symptoms that would be otherwise difficult to detect (e.g., fatigue, balance), for measuring treatment adherence and side effects, and for self-assessment purposes. Collection of outcome measures is progressively shifting from paper-based on site, to internet-based on site, and, in the future, to internet-based at home, with the detection of clinical and treatment features that would have remained otherwise invisible. Similarly, remote interventions provide new possibilities of motor and cognitive rehabilitation.
Practical Rubber Pre-Treatment Approch for Concrete Use—An Experimental Study
Authors: Roychand Rajeev , Gravina Rebecca J. , Zhuge Yan , Ma Xing , Mills Julie E. , Youssf Osama
Published: May 2021

There is a lot of ongoing active research all over the world looking for various applications of used tyre rubber, to increase its utilisation rate. One of the common research applications is to incorporate rubber into concrete as a partial replacement for conventional aggregates. However, due to its poor bonding performance with cement paste, the utilisation of rubber in concrete has been hindered to date. A cost-effective and time-saving rubber pre-treatment method is of great interest, especially for the concrete industry. Out of all the various pre-treatment methods, soaking rubber particles in water is the most cost-effective and least complex method. In addition, sodium sulphate accelerates the hydration reaction of the cement composites. This study looks at the effect of soaking crumb rubber in tap water for short (2 h) and long (24 h) durations, and the optimised duration was then compared with soaking the crumb rubber in a 5% concentration of sodium sulphate solution. Compressive strength, bond behaviour, and rubber/cement interfacial transition zone (ITZ) were investigated using X-ray diffraction (XRD) and scanning electron microscopy (SEM) analysis. The results demonstrate that a soaking duration of 2 h provides much better performance in both the strength and bond properties compared to 24-h soaking. A further improvement in the 7-day strength was achieved with the rubber soaked in 5% sodium sulphate solution for 2 h, providing a more practical and economical rubber pre-treatment method for concrete industry use.
The Lausanne Infant Crying Stress Paradigm: Validation of an Early Postpartum Stress Paradigm with Women at Low vs. High Risk of Childbirth-Related Posttraumatic Stress Disorder
Authors: Sandoz Vania , Stuijfzand Suzannah , Lacroix Alain , Deforges Camille , Quillet Diop Magali , Ehlert Ulrike , Rubo Marius , Messerli-Bürgy Nadine , Horsch Antje
Published: May 2021

Stress reactivity is typically investigated in laboratory settings, which is inadequate for mothers in maternity settings. This study aimed at validating the Lausanne Infant Crying Stress Paradigm (LICSP) as a new psychosocial stress paradigm eliciting psychophysiological stress reactivity in early postpartum mothers (n = 52) and to compare stress reactivity in women at low (n = 28) vs. high risk (n = 24) of childbirth-related posttraumatic stress disorder (CB-PTSD). Stress reactivity was assessed at pre-, peri-, and post-stress levels through salivary cortisol, heart rate variability (high-frequency (HF) power, low-frequency (LF) power, and LF/HF ratio), and perceived stress via a visual analog scale. Significant time effects were observed for all stress reactivity outcomes in the total sample (all p < 0.01). When adjusting for perceived life threat for the infant during childbirth, high-risk mothers reported higher perceived stress (p < 0.001, d = 0.91) and had lower salivary cortisol release (p = 0.023, d = 0.53), lower LF/HF ratio (p < 0.001, d = 0.93), and marginally higher HF power (p = 0.07, d = 0.53) than low-risk women. In conclusion, the LICSP induces subjective stress and autonomic nervous system (ANS) reactivity in maternity settings. High-risk mothers showed higher perceived stress and altered ANS and hypothalamic–pituitary–adrenal reactivity when adjusting for infant life threat. Ultimately, the LICSP could stimulate (CB-)PTSD research.
KRT20, KRT5, ESR1 and ERBB2 Expression Can Predict Pathologic Outcome in Patients Undergoing Neoadjuvant Chemotherapy and Radical Cystectomy for Muscle-Invasive Bladder Cancer
Authors: Jütte Hendrik , Reike Moritz , Wirtz Ralph M. , Kriegmair Maximilian , Erben Philipp , Tully Karl , Weyerer Veronika , Eckstein Markus , Hartmann Arndt , Eidt Sebastian , Wezel Felix , Bolenz Christian , Tannapfel Andrea , Noldus Joachim , Roghmann Florian
Published: May 2021

Patients with muscle-invasive bladder cancer (MIBC) that underwent neoadjuvant chemotherapy (NAC) prior to radical cystectomy (RC) show improved overall survival, especially those with pathological complete response (pCR). The response to NAC according to molecular subtypes has been discussed. Molecular targets such as estrogen receptor (ESR1) and human epidermal growth factor receptor 2 (ERBB2) play an important role in breast cancer management and have also been associated with urothelial bladder cancer. Hence, the association of Keratin 20 (KRT20) Keratin 5 (KRT5), ESR1, and ERBB2 mRNA expression in MIBC at transurethral resection (TUR-BT) with pCR after NAC was analyzed retrospectively. Formalin-fixed paraffin-embedded tumour tissue samples from TUR-BT of 54 patients (42 males, 12 females, median age of 64) with MIBC were analyzed for KRT20, KRT5, ESR1, and ERBB2 mRNA expression. After NAC, RC was performed, and the specimens were evaluated for pCR. Statistical analyses comprised nonparametric and chi2 testing, partition models, and Spearman correlation analyses. After NAC, 22 out of 54 patients (40.7%) had pCR. Tumours with an elevated expression of markers associated with luminal differentiation (KRT20, ERBB2, ESR1) were associated with a higher chance of pCR (55% vs. 15.8%, p = 0.009). Elevated ERBB2 expression was positively correlated with luminal expression features such as KRT20, and negatively with basal characteristics such as KRT5. Patients with MIBC showing a high expression of ERBB2, ESR1, or KRT20 have a significantly higher chance of pCR following NAC. These findings might improve patient selection for NAC in MIBC.