bluuebunny/crossref_metadata_2025 huggingface dataset:
Application Development of Smoke Leakage Test Apparatus for Door Sets in the Field
Authors: Hung Hsuan-Yu , Lin Ching-Yuan , Chuang Ying-Ji , Luan Chung-Pi
Published: January 2022

Heavy smoke from building fires is the main cause of casualties. As smoke typically diffuses through building openings, smoke control performance of building openings is critical to survival and requires considerable attention. In the past, the detection method could only be used in the laboratory, and the detection equipment could not be moved. Therefore, the main purpose of this research was to develop a methodology for field testing of smoke control properties of doors in order to ensure that the smoke control performance of doors tested in the laboratory and doors installed in the field can be realized without any discrepancy. Furthermore, this test method underwent a comparison test with the CNS 15038 “Method of Test for Evaluating Smoke Control Performance of Doors” for the same subject. The test results showed no significant difference based on independent sample testing, demonstrating the feasibility of this test method and test apparatus. The instrument developed by this research is light and easy to carry, and the operation method is simple. Such a test method can be applied to different doors and is non-destructive, non-hazardous, and reusable. In the future, by extending the design principle of the system, this test method can be applied to other fire protection equipment for the inspection of smoke control capabilities and can be used as a reference for relevant organizations to establish test specifications and standards.
Conflicts with Momentum
Authors: Boudreau James W. , Mathews Timothy , Sanders Shane D. , Bagchi Aniruddha
Published: January 2022

Take the fort, then take the city. In a two-stage, two-party contest, victory in the initial stage can provide an advantage in the final stage. We examine such momentum in conflict scenarios and investigate how valuable it must be to avoid a Pyrrhic victory. Our main finding is that although the elasticity of effort—which we allow to vary between the two stages—does impact the contestants’ effort levels, it has no bearing on the endogenously determined value of momentum itself. Further, rent dissipation in the two-stage conflict is equal across party whether or not an individual obtains first-stage momentum. Thus, momentum helps a player solely by enhancing marginal ability for victory in the second-stage contest. It does not, however, change the player’s net calculus of second-stage contest spending. Such contestable advantage is also found to be more rent-dissipative than innate/uncontestable advantage. Therefore, Pyrrhic victories should be more common for contests with an intermediate stage or stages in which advantages can be earned, ceteris paribus. While intermediate targets appear as useful conflict benchmarks, they dissipate additional expected contest rents. This additional rent-dissipative toll exists even for backward-inductive equilibrium behavior in a complete information setting. Whereas the quagmire theory suggests parties can become involved in problematic conflicts due to incomplete information, the present paper finds that the setting of conflict—namely, contestable intermediate advantage—can alternatively generate rent-dissipative tolls. Similarly, contestable advantage can lead parties to optimally forego contest participation (i.e., if conflict parameters do not meet the participation constraint). This is in contrast to a one-stage simultaneous contest with second-stage parametric values of the present contest.
Identification of HIV Rapid Mutations Using Differences in Nucleotide Distribution over Time
Authors: Sun Nan , Yang Jie , Yau Stephen S.-T.
Published: January 2022

Mutation is the driving force of species evolution, which may change the genetic information of organisms and obtain selective competitive advantages to adapt to environmental changes. It may change the structure or function of translated proteins, and cause abnormal cell operation, a variety of diseases and even cancer. Therefore, it is particularly important to identify gene regions with high mutations. Mutations will cause changes in nucleotide distribution, which can be characterized by natural vectors globally. Based on natural vectors, we propose a mathematical formula for measuring the difference in nucleotide distribution over time to investigate the mutations of human immunodeficiency virus. The studied dataset is from public databases and includes gene sequences from twenty HIV-infected patients. The results show that the mutation rate of the nine major genes or gene segment regions in the genome exhibits discrepancy during the infected period, and the Env gene has the fastest mutation rate. We deduce that the peak of virus mutation has a close temporal relationship with viral divergence and diversity. The mutation study of HIV is of great significance to clinical diagnosis and drug design.
Expression Profiles of miR-22-5p and miR-142-3p Indicate Hashimoto’s Disease and Are related to Thyroid Antibodies
Authors: Trummer Olivia , Foessl Ines , Schweighofer Natascha , Arifi Edi , Haudum Christoph W. , Reintar Sharmaine , Pilz Stefan , Theiler-Schwetz Verena , Trummer Christian , Zirlik Andreas , Schmidt Albrecht , Colantonio Caterina , Kolesnik Ewald , Verheyen Nicolas , Pieber Thomas R. , Obermayer-Pietsch Barbara
Published: January 2022

Hashimoto’s thyroiditis (HT) is the most prevalent autoimmune disorder of the thyroid (AITD) and characterized by the presence of circulating autoantibodies evoked by a, to date, not fully understood dysregulation of the immune system. Autoreactive lymphocytes and inflammatory processes in the thyroid gland can impair or enhance thyroid hormone secretion. MicroRNAs (miRNAs) are small noncoding RNAs, which can play a pivotal role in immune functions and the development of autoimmunity. The aim of the present study was to evaluate whether the expression of 9 selected miRNAs related to immunological functions differ in patients with HT compared to healthy controls. MiRNA profiles were analysed using quantitative reverse transcription polymerase chain reaction (qRT-PCR) in 24 patients with HT and 17 healthy controls. Systemic expressions of miR-21-5p, miR-22-3p, miR-22-5p, miR-142-3p, miR-146a-5p, miR-301-3p and miR-451 were significantly upregulated in patients with HT (p ≤ 0.01) and were suitable to discriminate between HT and healthy controls in AUC analysis. Altered expressions of miR-22-5p and miR-142-3p were associated with higher levels of thyroid antibodies, suggesting their contribution to the pathogenesis of HT.
Predicting Essential Proteins Based on Integration of Local Fuzzy Fractal Dimension and Subcellular Location Information
Authors: Shen Li , Zhang Jian , Wang Fang , Liu Kai
Published: January 2022

Essential proteins are indispensable to cells’ survival and development. Prediction and analysis of essential proteins are crucial for uncovering the mechanisms of cells. With the help of computer science and high-throughput technologies, forecasting essential proteins by protein–protein interaction (PPI) networks has become more efficient than traditional approaches (expensive experimental methods are generally used). Many computational algorithms were employed to predict the essential proteins; however, they have various restrictions. To improve the prediction accuracy, by introducing the Local Fuzzy Fractal Dimension (LFFD) of complex networks into the analysis of the PPI network, we propose a novel algorithm named LDS, which combines the LFFD of the PPI network with the protein subcellular location information. By testing the proposed LDS algorithm on three different yeast PPI networks, the experimental results show that LDS outperforms some state-of-the-art essential protein-prediction techniques.
Utilization of Palliative Care Screening Tool to Early Identify Patients with COVID-19 Needing Palliative Care: A Cohort Study
Authors: Yen Yung-Feng , Hu Hsiao-Yun , Chou Yi-Chang , Chen Chu-Chieh , Ho Chin-Yu
Published: January 2022

There are very few programs that identify patients with coronavirus disease 2019 (COVID-19) who need palliative care. This cohort study presents a model to use a validated palliative care screening tool (PCST) to systematically identify hospitalized patients with COVID-19 in need of palliative care. In this prospective study, we consecutively recruited patients with COVID-19 admitted to Taipei City Hospital between 1 January and 30 July 2021. Patients’ palliative care needs were determined by using the PCST. Advance care planning (ACP) and advance directives (AD) were systemically provided for all patients with a PCST score ≥ 4. Of 897 patients, 6.1% had a PCST score ≥ 4. During the follow-up period, 106 patients died: 75 (8.9%) with a PCST score < 4 and 31 (56.4%) with a PCST score ≥ 4. The incidence of mortality was 2.08 and 0.58/100 person-days in patients with PCST scores ≥ 4 and <4, respectively. After controlling for other covariates, a PCST score ≥ 4 was associated with a higher risk of mortality in patients with COVID-19 (adjusted HR = 2.08; 95% CI: 1.22–3.54; p < 0.001). During hospitalization, 55 patients completed an ACP discussion with their physicians, which led to 15 of them completing the AD. Since hospitalized patients with COVID-19 had a high mortality rate, it is imperative to implement a comprehensive palliative care program to early identify patients needing palliative care and promotion of AD and ACP.
An Online-Based Transition Care Program for Adolescents with Spina Bifida Using Intervention Mapping: A Protocol for Program Development
Authors: Choi Eun Kyoung , Yun Hyeseon , Bae Eunjeong
Published: January 2022

Adolescents with spina bifida (SB) face challenges in their transition to adulthood due to intensive medical regimens and delayed development of independence. Despite an increasing interest in the transition of adolescents with SB to adulthood, the clinical evidence of transition care remains limited, and existing studies have focused on the effects of intervention programs. This study aims to describe the process of systematically developing an online-based transition care program for adolescents with SB using the intervention mapping (IM) protocol. IM consists of six steps: (1) logic model of the problem; (2) program objectives; (3) program design; (4) program production; (5) plan to implement the program; (6) plan for evaluation. At first, five problems faced during the transition were identified, based on which four program objectives and six program strategies were established. The online transition care program for adolescents with SB was developed as a six-week program. The main strength of this program is that it reflects the diverse perspectives of adults with SB and health care professionals and is easy to apply because it is online. We aim to further validate the feasibility of this transitional care program to evaluate its effect based on our evaluation plan.
Five Different Lives after Suffering from Spinal Cord Injury: The Experiences of Nurses Who Take Care of Spinal Cord Injury Patients
Authors: Wang Shou-Yu , Hong Shih-Ru , Tan Jung-Ying
Published: January 2022

According to statistics of Ministry of Health and Welfare, accidents were the sixth common causes of death in Taiwan in 2016. A total of 1200 new cases of spinal cord injury each year are caused by accidents and adverse effects. This study explored nurses’ experience of caring for patients with spinal cord injury. Hermeneutic phenomenology was used in the data analysis. The five themes emerged: dramatic changes in life, life lost control, life after catastrophic injury, life takes turns for the worse for family, and the power of rebirth. This study revealed that accidents were the primary cause of spinal cord injury, and that nurses may neglect patients’ mental and social care. Career guidance should be offered to spinal cord injury patients to ensure that they retain sociality. This study provides recommendations regarding a patient’s and their family’s post-injury adaption process. The sexual desire of patients should be further explored in future research.
Parental Attachment and Peer Relationships in Adolescence: A Systematic Review
Authors: Delgado Elena , Serna Cristina , Martínez Isabel , Cruise Edie
Published: January 2022

According to attachment theory, children’s early experiences with their primary caregivers, in terms of protection and security, are the basis for socioemotional development and for the establishment of close relationships throughout their lives. During adolescence, friends and peers become a primary developmental environment, and thereby establishing quality bonds with peers will foster good psychological adjustment. The aim of the present study was to review the evidence on the relation of parental attachment to the quality of peer relationships during adolescence. A systematic review was conducted according to the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The search was performed in the PsycInfo, Scopus, and Web of Science (WOS) databases. Inclusion criteria were studies published since 2001, in English, that are academic publications in scientific journals, that explore adolescence, and that analyze the relationship between attachment styles and adolescent peer interactions. The search resulted in 1438 studies, of which 19 studies met the criteria and were included in the review. The results highlighted that secure attachment predicts and promotes the creation of affective relationships with peers and friends based on communication, support, intimacy, trust, and quality. In addition, some variables, such as gender differences or family characteristics, were found to be involved in attachment and provide a better understanding.
The Family Is My Priority: How Motherhood Frames Participation in Physical Activity in a Group of Mothers Living in a Low Socioeconomic Status Area
Authors: Wittels Paula , Kay Tess , Mansfield Louise
Published: January 2022

Socioeconomic status (SES) is known to influence strongly both life expectancy and healthy life expectancy. Whilst there are multiple factors with complex interactions that provide the explanation for this observation, differences in the uptake of physical activity between high and low SES groups play a role. This in-depth qualitative study set out to understand the response of a group of mothers with young children living in a low SES area of a London (UK) borough to the current physical activity guidance and to investigate whether existing and established interventions based on behavior change are appropriate for this group. A series of three in depth interviews was carried out with the mothers (n = 20) over a period of 16 months, and the data collected were analyzed thematically. Four main themes were identified: (1) mothering comes before exercise; (2) mothers are a special case; (3) alone or together; and (4) facilities fail mothers. The mothers were unsure about the benefits of exercise, whether it was relevant for them and how to accommodate exercise alongside their mothering responsibilities. Family and peer group could be both a barrier and a facilitator to participation in physical activity. Without an in depth understanding of the role of physical activity in the lives of mothers of young children, behavior change-based public interventions are likely to fail to meet the needs of this group. A reduction in the current health inequities will only be possible when the needs of the mothers are acknowledged and used as the basis of appropriate public health guidance.
Serum Sestrin-1 Concentration Is Higher in Frail than Non-Frail Older People Living in Nursing Homes
Authors: Sanz Begoña , Rezola-Pardo Chloe , Arrieta Haritz , Fraile-Bermúdez Ana Belén , Alonso-Puyo Janire , Molano Irene , Rodriguez-Larrad Ana , Irazusta Jon
Published: January 2022

Given the increasing prevalence of frailty and its implications for public health, the identification of biomarkers to detect frailty is essential. Sestrin-1 is a protein with a protective role in muscle function. This study aimed to determine whether the serum sestrin-1 concentration differed between frail and non-frail populations and to investigate its association with frailty-related variables in 225 older women and men living in nursing homes (Gipuzkoa, Spain). Serum sestrin-1 concentration was measured by ELISA. Frailty, dependence, anthropometry, physical function, and physical activity were determined by validated tests and tools. The associations between sestrin-1 concentration and the other variables were determined using generalized linear models. The differences between frail and non-frail individuals were analyzed by the Mann–Whitney U-test, and receiver operating characteristic (ROC) curves were constructed to calculate the capability of sestrin-1 to detect frailty. Unexpectedly, frail individuals—according to the Fried Frailty Phenotype or the Clinical Frailty Scale—had higher serum sestrin-1 concentrations than non-frail individuals. Furthermore, the higher serum sestrin-1 concentration was associated with the increased frailty scores and dependence as well as the poorer physical function and the less physical activity. Given the contradictory results regarding serum sestrin-1 and frailty, further investigation is required to propose it as a molecular biomarker of frailty.
Comparison of Recruitment Patterns of Sessile Marine Invertebrates According to Substrate Characteristics
Authors: Bae Seongjun , Ubagan Michael Dadole , Shin Sook , Kim Dong Gun
Published: January 2022

A community of benthic invertebrates, including sessile adult-stage invertebrates, can negatively effect corrosion, deformation, and increased fuel consumption by attaching to artificial structures, a phenomenon known as marine biofouling. Investigating the relationship between benthic communities and artificial structures or substrates (to which the organisms attach) can help clarify the factors influencing marine biofouling. Therefore, in our study, natural (stone) and artificial (rubber, tarpaulin, and iron) substrates were installed in three harbors (Mokpo, Tongyeong, and Busan), and the structures of the communities attached to each substrate were compared. The total study period was 15 months (September 2016 to December 2017), and field surveys were performed at 3-month intervals. The three survey sites had significant differences in the structure of the sessile community present. In particular, Tongyeong was significantly different from Mokpo and Busan due to the continuous dominance of Cirripedia. When comparing natural and artificial substrate by sites, significant differences were observed in the community structure in all three surveyed sites. In Mokpo and Busan, colonial ascidians were dominant on natural substrate rather than artificial substrates; post-summer, Cirripedia coverage was higher on artificial substrates than natural substrate due to corrosion. Tongyeong showed a different pattern from that of Mokpo and Busan. After the summer, Bivalvia dominated on natural substrate over artificial substrates, affecting the differences between natural and artificial substrates. Our results demonstrate the recruitment patterns of sessile marine invertebrates according to substrate characteristics and can be used as basic information for biofouling management in marine environment.
Psychometric Properties of the Treatment Satisfaction with Medicines Questionnaire (SATMED-Q) in Patients with Diabetes, Arterial Hypertension and Heart Failure
Authors: Świątoniowska-Lonc Natalia , Kołtuniuk Aleksandra , Jankowska-Polańska Beata
Published: January 2022

Background: Satisfaction with medicines is crucial in indicating patient experiences with the treatment which impact medicine adherence and compliance. Aim: The aim of this research was to adopt a general measure of patients’ satisfaction with medicines, the Treatment Satisfaction with Medicines Questionnaire (SATMED-Q), to the Polish language (BMQ-PL). Materials and Methods: A total of 197 patients qualified for the research, with the following diagnoses: type 2 diabetes (n = 42), hypertension (n = 55) and heart failure (n = 100), aged 64.73 (SD = 13.27). The criterion-related validity was determined with the use of a Polish version of the Adherence to Refills and Medications Scale. Confirmatory and exploratory factor analyses were used. Results: The respondents’ mean score was 73.63 (SD = 18.42). Cronbach’s alpha for the entire instrument was 0.847. All items of the questionnaire were found to have a positive item–total correlation. A multifactorial linear regression model showed that a significant (p ˂ 0.05) independent variable increasing the SATMED-Q score for the whole group was educational level (vocational education R = 14.576; secondary education R = 14.055; higher education R = 19.372) and low adherence (R = −1.384) was a decreasing variable. Conclusions: The present findings indicate a high level of reliability and validity of the translated SATMED-Q questionnaire, fully comparable to that of the original. The questionnaire can be used for the assessment of satisfaction with medicines among Polish patients.
Impact of Income and Industry on New-Onset Diabetes among Employees: A Retrospective Cohort Study
Authors: Ishihara Reiko , Babazono Akira , Liu Ning , Yamao Reiko
Published: January 2022

The purpose of this study was to investigate the impact of income and industry type on the risk of developing diabetes among Japanese workers, including how this impact is affected by sex. A total of 24,516 employees at small- and medium-sized enterprises in Japan aged 40–74 years who underwent health examinations in fiscal years 2010–2015 were included in this retrospective cohort study. Generalized linear regression models were used to assess the association between new-onset diabetes and income and industry. In men, the cumulative incidence rate was significantly higher in the low-income group; it was highest in the transportation and postal service industries. Although income and industry were independent risk factors for developing diabetes in men, an interaction was found between income and industry, which was affected by participants’ sex: in specific industries (i.e., lifestyle-related, personal services, and entertainment services), men had a significantly higher risk of developing diabetes in the high-income group, and women had a significantly higher risk of developing diabetes in the low-income group. These findings highlight important factors to consider in assessing diabetes risk and suggest that efficient primary and secondary prevention should be encouraged in industries where workers have a high risk of diabetes.
Predictors of the Development of Mental Disorders in Hospitalized COVID-19 Patients without Previous Psychiatric History: A Single-Center Retrospective Study in South Korea
Authors: Kim Jangrae , Seo Yae Eun , Sung Ho Kyung , Park Hye Yoon , Han Myung Hwa , Lee So Hee
Published: January 2022

The objective of this study was to investigate the predictors for new-onset mental disorders among patients with mild to moderate COVID-19 illness during hospitalization. A retrospective cohort study was performed in patients with confirmed COVID-19 admitted to a nationally designated hospital between 1 February and 30 June 2020. Demographic, clinical, psychological assessments, and psychiatric outcomes were obtained from electronic medical record review. Multivariate logistic regression analysis was used to identify predictors of new-onset mental disorders. Among 185 patients, 130 had no history of mental disorders or cognitive impairment at the time of admission. Of 130 patients, 29 (22.3%) were newly diagnosed with mental disorders during hospitalization. The following factors were significantly associated with an increased risk of a psychiatric diagnosis: Charlson comorbidity index core ≥1 (adjusted odds ratio (aOR) = 5.115, 95% confidence interval (CI): 1.737–15.058), length of stay (aOR per 1-day increase = 1.067, 95% CI: 1.035–1.100), and self-reported depressive symptoms at the time of admission (aOR = 5.357, 95% CI: 1.745–16.444). The predictive accuracy of combining these risk factors was relatively high (area under curve = 0.851, 95% CI: 0.778–0.923). These potential risk factors could help to predict the new-onset mental disorder among hospitalized patients with COVID-19.
Can Product Information Steer towards Sustainable and Healthy Food Choices? A Pilot Study in an Online Supermarket
Authors: van der Waal Nadine E. , Folkvord Frans , Azrout Rachid , Meppelink Corine S.
Published: January 2022

Sustainable dietary choices have become increasingly important because of the current environmental threats the world is facing. Nonetheless, consumers find it difficult to assess a product’s sustainability and therefore make better choices. This pilot study tested whether explanatory product information about sustainability increased sustainable purchases in an online supermarket and whether additional health information increased message effectiveness. Perceived consumer effectiveness (i.e., the perception of the degree to which individual actions can contribute to environmental problems) and green skepticism were hypothesized to mediate the effect of message type, and environmental attitudes were included as the moderator. An experiment using a one-factor design was conducted among 101 participants who were assigned to one of three experimental conditions: sustainability claim only, explanatory sustainability claim, and explanatory sustainability and health claim. Analyses showed that an explanatory sustainability claim (regardless of whether this claim was accompanied by a health claim) led to fewer sustainable purchases through perceived consumer effectiveness but only for those with low environmental attitudes. No effects were found for the addition of a health claim. The results from this pilot provide insight for future studies that aim to examine how online supermarkets should communicate to increase sustainable purchases.
The Impact of Urban Public Transport on Residential Transaction Prices: A Case Study of Poznań, Poland
Authors: Chwiałkowski Cyprian , Zydroń Adam
Published: January 2022

This study aims to determine the magnitude and nature of the impact of public urban transport accessibility on the value of residential properties in Poznań. The study was based on 2561 residential transactions completed within the study area in 2020. The input data obtained from the Board of Geodesy and Municipal Cadastre “GEOPOZ” were analysed statistically and spatially. The main part of both the spatial and the statistical analysis was performed using the hedonic pricing method (HPM)-OLS (ordinary least squares) and WLS (weighted least squares). The use of statistical tools enabled the finding of evidence to prove that the convenient accessibility of trams is positively related to housing prices. This has also been confirmed by previous research works conducted in other parts of the world. However, the collected data did not enable the identification of statistically significant relationships between housing prices and the distance from bus stops. The study also attempts to use spatial choropleth maps to clearly illustrate the mechanisms within the local housing market.
Lifestyle Factors Involved in the Pathogenesis of Alopecia Areata
Authors: Minokawa Yoko , Sawada Yu , Nakamura Motonobu
Published: January 2022

Alopecia areata is a representative inflammatory skin disease that is associated with various environmental stimuli. While psychological stress is believed to be a major pathogenetic trigger in alopecia areata, infants and newborns also suffer from the disease, suggesting the possible presence of other environmental factors. Daily lifestyle is well known to be involved in various inflammatory diseases and influences the severity of inflammatory skin diseases. However, only a limited number of studies have summarized these influences on alopecia areata. In this review article, we summarize lifestyle factor-related influences on the pathogenesis of alopecia areata and focus on environmental factors, such as smoking, alcohol consumption, sleep, obesity, fatty acids, and gluten consumption.
Osteopontin on the Dental Implant Surface Promotes Direct Osteogenesis in Osseointegration
Authors: Makishi Sanako , Yamazaki Tomohiko , Ohshima Hayato
Published: January 2022

After dental implantation, osteopontin (OPN) is deposited on the hydroxyapatite (HA) blasted implant surface followed by direct osteogenesis, which is significantly disturbed in Opn-knockout (KO) mice. However, whether applying OPN on the implant surface promotes direct osteogenesis remains unclarified. This study analyzed the effects of various OPN modified protein/peptides coatings on the healing patterns of the bone-implant interface after immediately placed implantation in the maxilla of four-week-old Opn-KO and wild-type (WT) mice (n = 96). The decalcified samples were processed for immunohistochemistry for OPN and Ki67 and tartrate-resistant acid phosphatase histochemistry. In the WT mice, the proliferative activity in the HA binding peptide-OPN mimic peptide fusion coated group was significantly higher than that in the control group from day 3 to week 1, and the rates of OPN deposition and direct osteogenesis around the implant surface significantly increased in the recombinant-mouse-OPN (rOPN) group compared to the Gly-Arg-Gly-Asp-Ser peptide group in week 2. The rOPN group achieved the same rates of direct osteogenesis and osseointegration as those in the control group in a half period (week 2). None of the implant surfaces could rescue the direct osteogenesis in the healing process in the Opn-KO mice. These results suggest that the rOPN coated implant enhances direct osteogenesis during osseointegration following implantation.
Secondary Structures of the Transmembrane Domain of SARS-CoV-2 Spike Protein in Detergent Micelles
Authors: Li Qingxin , Huang Qiwei , Kang Congbao
Published: January 2022

Spike protein of SARS-CoV-2 contains a single-span transmembrane (TM) domain and plays roles in receptor binding, viral attachment and viral entry to the host cells. The TM domain of spike protein is critical for viral infectivity. Herein, the TM domain of spike protein of SARS-CoV-2 was reconstituted in detergent micelles and subjected to structural analysis using solution NMR spectroscopy. The results demonstrate that the TM domain of the protein forms a helical structure in detergent micelles. An unstructured linker is identified between the TM helix and heptapeptide repeat 2 region. The linker is due to the proline residue at position 1213. Side chains of the three tryptophan residues preceding to and within the TM helix important for the function of S-protein might adopt multiple conformations which may be critical for their function. The side chain of W1212 was shown to be exposed to solvent and the side chains of residues W1214 and W1217 are buried in micelles. Relaxation study shows that the TM helix is rigid in solution while several residues have exchanges. The secondary structure and dynamics of the TM domain in this study provide insights into the function of the TM domain of spike protein.
Impairment of Anti-Aggregatory Responses to Nitric Oxide and Prostacyclin: Mechanisms and Clinical Implications in Cardiovascular Disease
Authors: Chirkov Yuliy Y. , Nguyen Thanh H. , Horowitz John D.
Published: January 2022

The propensity towards platelet-rich thrombus formation increases substantially during normal ageing, and this trend is mediated by decreases in platelet responsiveness to the anti-aggregatory nitric oxide (NO) and prostacyclin (PGI2) pathways. The impairment of soluble guanylate cyclase and adenylate cyclase-based signalling that is associated with oxidative stress represents the major mechanism of this loss of anti-aggregatory reactivity. Platelet desensitization to these autacoids represents an adverse prognostic marker in patients with ischemic heart disease and may contribute to increased thrombo-embolic risk in patients with heart failure. Patients with platelet resistance to PGI2 also are unresponsive to ADP receptor antagonist therapy. Apart from ischemia, diabetes and aortic valve disease are also associated with impaired anti-aggregatory homeostasis. This review examines the association of impaired platelet cyclic nucleotide (i.e., cGMP and cAMP) signalling with the emerging evidence of thromboembolic risk in cardiovascular diseases, and discusses the potential therapeutic strategies targeting this abnormality.
Active Materials for 3D Printing in Small Animals: Current Modalities and Future Directions for Orthopedic Applications
Authors: Memarian Parastoo , Pishavar Elham , Zanotti Federica , Trentini Martina , Camponogara Francesca , Soliani Elisa , Gargiulo Paolo , Isola Maurizio , Zavan Barbara
Published: January 2022

The successful clinical application of bone tissue engineering requires customized implants based on the receiver’s bone anatomy and defect characteristics. Three-dimensional (3D) printing in small animal orthopedics has recently emerged as a valuable approach in fabricating individualized implants for receiver-specific needs. In veterinary medicine, because of the wide range of dimensions and anatomical variances, receiver-specific diagnosis and therapy are even more critical. The ability to generate 3D anatomical models and customize orthopedic instruments, implants, and scaffolds are advantages of 3D printing in small animal orthopedics. Furthermore, this technology provides veterinary medicine with a powerful tool that improves performance, precision, and cost-effectiveness. Nonetheless, the individualized 3D-printed implants have benefited several complex orthopedic procedures in small animals, including joint replacement surgeries, critical size bone defects, tibial tuberosity advancement, patellar groove replacement, limb-sparing surgeries, and other complex orthopedic procedures. The main purpose of this review is to discuss the application of 3D printing in small animal orthopedics based on already published papers as well as the techniques and materials used to fabricate 3D-printed objects. Finally, the advantages, current limitations, and future directions of 3D printing in small animal orthopedics have been addressed.
Beneficial and Sexually Dimorphic Response to Combined HDAC Inhibitor Valproate and AMPK/SIRT1 Pathway Activator Resveratrol in the Treatment of ALS Mice
Authors: Bankole Oluwamolakun , Scambi Ilaria , Parrella Edoardo , Muccilli Matilde , Bonafede Roberta , Turano Ermanna , Pizzi Marina , Mariotti Raffaella
Published: January 2022

Amyotrophic lateral sclerosis (ALS) is a fatal adult-onset neurodegenerative disorder. There is no cure and current treatments fail to slow the progression of the disease. Epigenetic modulation in the acetylation state of NF-kB RelA and the histone 3 (H3) protein, involved in the development of neurodegeneration, is a drugable target for the class-I histone deacetylases (HDAC) inhibitors, entinostat or valproate, and the AMP-activated kinase (AMPK)-sirtuin 1 pathway activator, resveratrol. In this study, we demonstrated that the combination of valproate and resveratrol can restore the normal acetylation state of RelA in the SOD1(G93A) murine model of ALS, in order to obtain the neuroprotective form of NF-kB. We also investigated the sexually dimorphic development of the disease, as well as the sex-sensibility to the treatment administered. We showed that the combined drugs, which rescued AMPK activation, RelA and the histone 3 acetylation state, reduced the motor deficit and the disease pathology associated with motor neuron loss and microglial reactivity, Brain-Derived Neurotrophic Factor (BDNF) and B-cell lymphoma-extra large (Bcl-xL) level decline. Specifically, vehicle-administered males showed earlier onset and slower progression of the disease when compared to females. The treatment, administered at 50 days of life, postponed the time of onset in the male by 22 days, but not in a significant way in females. Nevertheless, in females, the drugs significantly reduced symptom severity of the later phase of the disease and prolonged the mice’s survival. Only minor beneficial effects were produced in the latter stage in males. Overall, this study shows a beneficial and sexually dimorphic response to valproate and resveratrol treatment in ALS mice.
EVI1 Promotes the Proliferation and Invasive Properties of Human Head and Neck Squamous Cell Carcinoma Cells
Authors: Grandits Alexander Michael , Bromberger Sophie , Heller Gerwin , Reinoehl Barbara Andrea , Tomasich Erwin , Schossleitner Klaudia , Berghoff Anna Sophie , Fuereder Thorsten , Wieser Rotraud
Published: January 2022

Head and neck squamous cell carcinoma (HNSCC) is a frequent malignancy with a poor prognosis. So far, the EGFR inhibitor cetuximab is the only approved targeted therapy. A deeper understanding of the molecular and genetic basis of HNSCC is needed to identify additional targets for rationally designed, personalized therapeutics. The transcription factor EVI1, the major product of the MECOM locus, is an oncoprotein with roles in both hematological and solid tumors. In HNSCC, high EVI1 expression was associated with an increased propensity to form lymph node metastases, but its effects in this tumor entity have not yet been determined experimentally. We therefore overexpressed or knocked down EVI1 in several HNSCC cell lines and determined the impact of these manipulations on parameters relevant to tumor growth and invasiveness, and on gene expression patterns. Our results revealed that EVI1 promoted the proliferation and migration of HNSCC cells. Furthermore, it augmented tumor spheroid formation and the ability of tumor spheroids to displace an endothelial cell layer. Finally, EVI1 altered the expression of numerous genes in HNSCC cells, which were enriched for Gene Ontology terms related to its cellular functions. In summary, EVI1 represents a novel oncogene in HNSCC that contributes to cellular proliferation and invasiveness.
Local Accumulation of Lymphocytes in the Intima of Human Aorta Is Associated with Giant Multinucleated Endothelial Cells: Possible Explanation for Mosaicism of Atherosclerosis
Authors: Nikiforov Nikita G. , Zlenko Dmitry V. , Orekhova Varvara A. , Melnichenko Alexandra A. , Orekhov Alexander N.
Published: January 2022

Distribution of different types of atherosclerotic lesions in the arterial wall is not diffuse, but is characterized by mosaicism. The causes of such distribution remain to be established. At the early stages of atherogenesis, low-density lipoprotein (LDL) particles and immune cells penetrate into the intimal layer of the arterial wall through the endothelium. In adult humans, the luminal surface of the arterial wall is a heterogeneous monolayer of cells with varying morphology including typical endothelial cells (ECs) and multinucleated variant endothelial cells (MVECs). We hypothesized that distribution of MVECs in the endothelial monolayer can be related to the distribution pattern of early atherosclerotic lesions. We obtained en face preparations of intact adult (22–59 years old) aortic wall sections that allowed us to study the endothelial monolayer and the subendothelial layer. We compared the distribution of MVECs in the endothelial monolayer with the localization of early atherosclerotic lesions in the subendothelial layer, which were characterized by lipid accumulation and immune cell recruitment. In primary culture, MVECs demonstrated increased phagocytic activity compared to mononuclear ECs. Moreover, we have shown that unaffected aortic intima contained associates formed as a result of aggregation and/or fusion of LDL particles that are non-randomly distributed. This indicated that MVECs may be involved in the accumulation of LDL in the subendothelial layer through increased transcytosis. Interaction of LDL with subendothelial cells of human aorta in primary culture increased their adhesive properties toward circulating immune cells. Study of unaffected aortic intima revealed non-random distribution of leukocytes in the subendothelial layer and increased localization of CD45+ leukocytes in the subendothelial layer adjacent to MVECs. Together, our observations indicate that MVECs may be responsible for the distribution of atherosclerotic lesions in the arterial wall by participating in LDL internalization and immune cell recruitment.
GILT Expression in Human Melanoma Cells Enhances Generation of Antigenic Peptides for HLA Class II-Mediated Immune Recognition
Authors: Hathaway-Schrader Jessica D. , Norton Duncan , Hastings Katherine , Doonan Bently P. , Fritz Shaun Tompkins , Bethard Jennifer R. , Blum Janice S. , Haque Azizul
Published: January 2022

Melanoma is an aggressive skin cancer that has become increasingly prevalent in western populations. Current treatments such as surgery, chemotherapy, and high-dose radiation have had limited success, often failing to treat late stage, metastatic melanoma. Alternative strategies such as immunotherapies have been successful in treating a small percentage of patients with metastatic disease, although these treatments to date have not been proven to enhance overall survival. Several melanoma antigens (Ags) proposed as targets for immunotherapeutics include tyrosinase, NY-ESO-1, gp-100, and Mart-1, all of which contain both human leukocyte antigen (HLA) class I and class II-restricted epitopes necessary for immune recognition. We have previously shown that an enzyme, gamma-IFN-inducible lysosomal thiol-reductase (GILT), is abundantly expressed in professional Ag presenting cells (APCs), but absent or expressed at greatly reduced levels in many human melanomas. In the current study, we report that increased GILT expression generates a greater pool of antigenic peptides in melanoma cells for enhanced CD4+ T cell recognition. Our results suggest that the induction of GILT in human melanoma cells could aid in the development of a novel whole-cell vaccine for the enhancement of immune recognition of metastatic melanoma.
Smart Nucleic Acid Hydrogels with High Stimuli-Responsiveness in Biomedical Fields
Authors: Li Jie , Zhang Yangzi , Zhu Longjiao , Chen Keren , Li Xiangyang , Xu Wentao
Published: January 2022

Due to their hydrophilic, biocompatible and adjustability properties, hydrogels have received a lot of attention. The introduction of nucleic acids has made hydrogels highly stimuli-responsiveness and they have become a new generation of intelligent biomaterials. In this review, the development and utilization of smart nucleic acid hydrogels (NAHs) with a high stimulation responsiveness were elaborated systematically. We discussed NAHs with a high stimuli-responsiveness, including pure NAHs and hybrid NAHs. In particular, four stimulation factors of NAHs were described in details, including pH, ions, small molecular substances, and temperature. The research progress of nucleic acid hydrogels in biomedical applications in recent years is comprehensively discussed. Finally, the opportunities and challenges facing the future development of nucleic acid hydrogels are also discussed.
Mapping PP1c and Its Inhibitor 2 Interactomes Reveals Conserved and Specific Networks in Asexual and Sexual Stages of Plasmodium
Authors: De Witte Caroline , Aliouat El Moukhtar , Chhuon Cerina , Guerrera Ida Chiara , Pierrot Christine , Khalife Jamal
Published: January 2022

Malaria parasites require multiple phosphorylation and dephosphorylation steps to drive signaling pathways for proper differentiation and transformation. Several protein phosphatases, including protein phosphatase 1 (PP1), one of the main dephosphorylation enzymes, have been shown to be indispensable for the Plasmodium life cycle. The catalytic subunit of PP1 (PP1c) participates in cellular processes via dynamic interactions with a vast number of binding partners that contribute to its diversity of action. In this study, we used Plasmodium berghei transgenic parasite strains stably expressing PP1c or its inhibitor 2 (I2) tagged with mCherry, combined with the mCherry affinity pulldown of proteins from asexual and sexual stages, followed by mass spectrometry analyses. Mapped proteins were used to identify interactomes and to cluster functionally related proteins. Our findings confirm previously known physical interactions of PP1c and reveal enrichment of common biological processes linked to cellular component assembly in both schizonts and gametocytes to biosynthetic processes/translation in schizonts and to protein transport exclusively in gametocytes. Further, our analysis of PP1c and I2 interactomes revealed that nuclear export mediator factor and peptidyl-prolyl cis-trans isomerase, suggested to be essential in P. falciparum, could be potential targets of the complex PP1c/I2 in both asexual and sexual stages. Our study emphasizes the adaptability of Plasmodium PP1 and provides a fundamental study of the protein interaction landscapes involved in a myriad of events in Plasmodium, suggesting why it is crucial to the parasite and a source for alternative therapeutic strategies.
Successful Implementation of Expanded Newborn Screening in the Philippines Using Tandem Mass Spectrometry
Authors: Padilla Carmencita D. , Therrell Bradford L. , Alcausin Maria Melanie Liberty B. , Chiong Mary Anne D. , Abacan Mary Ann R. , Reyes Ma. Elouisa L. , Jomento Charity M. , Dizon-Escoreal Maria Truda T. , Canlas Margarita Aziza E. , Abadingo Michelle E. , Posecion J. Edgar Winston C. , Abarquez Conchita G. , Andal Alma P. , Elizaga Anna Lea G. , Halili-Mendoza Bernadette C. , Otayza Maria Paz Virginia K. , Millington David S.
Published: January 2022

Newborn bloodspot screening (NBS) began as a research project in the Philippines in 1996 and was mandated by law in 2004. The program initially included screening for five conditions, with a sixth added in 2012. As screening technology and medical knowledge have advanced, NBS programs in countries with developed economies have also expanded, not only in the number of newborns screened but also in the number of conditions included in the screening. Various approaches have been taken regarding selection of conditions to be screened. With limited resources, low- and middle-income countries face significant challenges in selecting conditions for screening and in implementing sustainable screening programs. Building on expansion experiences in the U.S. and data from California on Filipinos born and screened there, the Philippine NBS program has recently completed its expansion to include 29 screening conditions. This report focuses on those conditions detectable through tandem mass spectrometry. Expanded screening was implemented in a stepwise fashion across the seven newborn screening laboratories in the Philippines. A university-based biochemical genetics laboratory provides confirmatory testing. Follow-up care for confirmed cases is monitored and provided through the NBS continuity clinics across the archipelago. Pre-COVID-19 pandemic, the coverage was 91.6% but dropped to 80.4% by the end of 2020 due to closure of borders between cities, provinces, and islands.