bluuebunny/crossref_metadata_2025 huggingface dataset:
3-D Rock Mass Strength Criteria—A Review of the Current Status
Authors: Kulatilake Pinnaduwa H. S. W.
Published: August 2021

The presence of complex discontinuity patterns, the inherent statistical nature of their geometrical parameters, the uncertainties involved in the estimation of the discontinuity geometrical and geo-mechanical properties and complex three dimensional (3-D) in-situ stress make the accurate prediction of rock mass strength a difficult task. It has been a great challenge for the rock mechanics and rock engineering professions to develop a rock mass strength criterion in three dimensions that incorporates the effect of the minor and intermediate principal stresses and captures the scale dependent and anisotropic properties resulting from the discontinuity geometry parameters, such as the number of discontinuity sets, 3-D discontinuity intensity, and the distributions of the discontinuity orientation and size. Rock mechanics and rock engineering researchers have dealt with this topic for more than 55 years. The paper provides a critical review of the current state of the art regarding 3-D jointed rock mass strength criteria. The shortcomings of several rock mass strength criteria are discussed. The historic development of rock mass strength criteria that incorporate the effect of the minor and intermediate principal stresses and capture the scale dependent and anisotropic properties is presented. The most advanced 3-D rock mass strength criteria currently available in the literature are presented, including suggested future improvements.
Postural Control and Functional Ankle Stability in Professional and Amateur Skateboarders
Authors: Ou Yang-Kun , Chen Zhi-Wei , Yeh Chien-Nan
Published: August 2021

Basic maneuvers in skateboarding, such as the ollie, put the player at high risk for ankle injuries because of the position of the feet required to perform the maneuvers. This study investigated ankle stability and reaction time for the tibialis anterior, fibularis longus, and fibularis brevis in professional and amateur skateboarders. In total, 16 professional and 16 amateur skateboarders were recruited as participants and underwent range of motion assessments, balance testing, and muscle reaction time measurements. The results revealed that professional skateboarders had a significantly smaller inversion angle compared to amateur players, which suggested better joint control and hence greater safety in the former. Balance testing results indicated better balance in professional skateboarders, and healthy skateboarders had better balance than did injured professional and amateur skateboarders. No significant difference in muscle reaction time was observed between amateur and professional skateboarders.
Assessing the Impact of Social Media Use on Everyday Emotion in Health Crises: A Study of International Students in China during COVID-19
Authors: Larnyo Ebenezer , Dai Baozhen , Nutakor Jonathan Aseye , Ampon-Wireko Sabina , Appiah Ruth , Larnyo Abigail , Akey-Torku Benedicta , Nkrumah Edmund Nana Kwame
Published: August 2021

Social media has become a valuable tool in providing an opportunity to stay in touch with one’s social networks, providing reassurance and practical advice to individuals to pre-empt panic and rumors in COVID-19. However, the implications of social media use on the everyday emotion (anxiety and depression) of users especially, international students, are not well understood. Thus, this study sought to examine the impact of social media use on the everyday emotion of international students in China during COVID-19. Using a structured online questionnaire based on modified questions from the generalized anxiety disorder 7 (GAD-7) and the Patient Health Questionnaire 9 (PHQ-9) and social media use instruments, data were collected from 480 participants. Of the total responses received, 474 were further analyzed employing the Partial Least Squares Path Modelling (PLS-PM). This study showed a significant positive relationship between social media use and everyday emotion (B = 0.34, 95% CI (0.26, 0.44)). Additionally, self-rated anxiety and depression associated with social media use among international students were generally mild (n = 249, 52.50% and n = 350, 73.80%, respectively). Moderating effects revealed that age and sex do not significantly moderate the relationship between social media use and everyday emotion in COVID-19. Given the nature of social media among international students, who are also prone to suffering from anxiety and depression associated with social media use, the positive effect of social media use and everyday emotion, especially in COVID-19, has important implications for international students’ education stakeholders. Thus, gaining a deeper understanding of this relationship could enable them to harness social media and use it as a valuable tool to overcome the social distancing constraints in COVID-19.
The Effect of Mid-to-Long-Term Hospitalization on the Catastrophic Health Expenditure: Focusing on the Mediating Effect of Earned Income Loss
Authors: Jung Hyunwoo , Yang Jungyeon , Kim Eunyoung , Lee Junhyup
Published: August 2021

Background: Mid-to-long-term hospitalization (MLTH) can threaten the household economy with high medical costs and loss of income. Therefore, it could increase the catastrophic health expenditure (CHE), measured as the ratio of medical expenses to the ability to pay. This study aimed to determine the effect of MLTH on the incidence of CHE and the mediating effect of earned income reduction rate (EIRR). Methods: We used 2015 to 2017 data from the Korean Welfare Panel Study and selected households with earned income through work. The final samples were 1671 households in the database. This study applied three-step regression analyses for estimating mediation effects. Results: First, MLTH affected CHE increases; second, MLTH increased EIRR; third, both EIRR and MLTH increased CHE at the same time. Additionally, the bootstrapping results were 0.364 to 0.644 in the 95% confidence interval, which suggested that EIRR mediated the effects of MLTH on CHE. Conclusions: Previous studies have only focused on medical costs when interpreting CHE; however, it is also essential to recognize that the MLTH can have a negative effect on the EIRR. This study contributed to the literature by giving another insight into interpreting the cause of CHE, focusing on income loss factors.
Development of a System for Storing and Executing Bio-Signal Analysis Algorithms Developed in Different Languages
Authors: Joo Moon-Il , Aich Satyabrata , Kim Hee-Cheol
Published: August 2021

With the development of mobile and wearable devices with biosensors, various healthcare services in our life have been recently introduced. A significant issue that arises supports the smart interface among bio-signals developed by different vendors and different languages. Despite its importance for convenient and effective development, however, it has been nearly unexplored. This paper focuses on the smart interface format among bio-signal data processing and mining algorithms implemented by different languages. We designed and implemented an advanced software structure where analysis algorithms implemented by different languages and tools would seem to work in one common environment, overcoming different developing language barriers. By presenting our design in this paper, we hope there will be much more chances for higher service-oriented developments utilizing bio-signals in the future.
Workforce and Task Sharing of Nurses in the Japanese Intensive Care Unit-Cross-Sectional Postal Survey
Authors: Unoki Takeshi , Kawai Yusuke , Hamamoto Miya , Tamoto Mitsuhiro , Miyamoto Takeharu , Sakuramoto Hideaki , Ito Yumi , Moro Etsuko , Tatsuno Junko , Nishida Osamu
Published: August 2021

This study aimed to estimate the number of nurses who independently care for patients with severe respiratory failure receiving mechanical ventilation (MV) or veno-venous extracorporeal membrane oxygenation (VV-ECMO). Additionally, the study analyzed the actual role of nurses in the treatment of patients with MV and VV-ECMO. We performed a cross-sectional study using postal questionnaire surveys. The study included 725 Japanese intensive care units (ICUs). Data were analyzed using descriptive statistics. Among the 725 ICUs, we obtained 302 responses (41.7%) and analyzed 282 responses. The median number of nurses per bed was 3.25. The median proportion of nurses who independently cared for patients with MV was 60% (IQR: 42.3–77.3). The median proportion of nurses who independently cared for patients with VV-ECMO was 46.9 (35.7–63.3%) in the ICUs that had experience with VV-ECMO use. With regard to task-sharing, 33.8% of ICUs and nurses did not facilitate weaning from MV. Nurses always titrated sedative dosage in 44.5% of ICUs. Nurse staffing might be inadequate in all ICUs, especially for the management of patients with severe respiratory failure. The proportion of competent nurses to care for severe respiratory failure in ICUs should be considered when determining the workforce of nurses.
Effects of Storage Time and Pre-Etching Treatment of CR-39 Detectors on Their Response to Alpha Radiation Exposure
Authors: Janik Miroslaw , Hasan Md. Mahamudul , Bossew Peter , Kavasi Norbert
Published: August 2021

Radon passive monitors based on solid state nuclear track detectors (SSNTD), especially CR-39, are widely used in radon and thoron studies. They may be subjected to the influence of external factors, like changing of temperature, humidity, and pressure, both before and during the measurement. Evaluation of the exposed detectors involves chemical processing, whose conditions also influence the measurement results. The aim of this study was to check several factors, as to whether they may modify the response of CR-39 detector: concerning the phase before evaluation, storage time, and temperature during storage; and concerning the evaluation procedure, etching time, and pre-etching treatment using hot water and carbon dioxide atmosphere. Two experiments were conducted by irradiation of CR-39 detectors using alpha particles emitted from a mono-energetic 241Am source and exposed in radon atmosphere. Track density dependence of the age of production was found to be statistically not significant. On the other hand, pre-etching treatment using hot water and carbon dioxide with different etching times showed statistically significant effects on track area, track sensitivity, and roundness. It was concluded that there are simple methods to increase performance of nuclear track detectors, and that storage time is not a factor of concern.
Analysis of Incident Reports of a Dental University Hospital
Authors: Kimura Yasuyuki , Tonami Ken-ichi , Toyofuku Akira , Nitta Hiroshi
Published: August 2021

Incident reports are important for improving the quality and safety of medical care. Healthcare workers with less than one year of work experience have been reported to cause the most incidents, and the most common incident is “drug-related”. However, few studies have comprehensively analyzed incidents in dentistry, and the characteristics of dental incidents have not been understood. In this study, to understand the characteristics of dental incidents, we comprehensively analyzed 1291 incident reports submitted to the Tokyo Medical and Dental University Dental Hospital from April 2014 to March 2019. As a result, dental outpatient and dental wards had different types of incidents. In outpatient wards, incidents included many dentistry-specific incidents related to “procedures”. Among them, “poor physical condition of the patient during dental treatment” was the most common incident. In contrast, the most common incident from subjects with less than one year of work experience was “damage to soft tissues around the teeth”. Thus, to improve the quality and safety in dentistry, it is was considered necessary to analyze and understand the characteristics of dentistry-specific incidents and to take appropriate measures and educate dental professionals.
Developing Initial Middle Range Theories in Realist Evaluation: A Case of an Organisational Intervention
Authors: Roodbari Hamid , Nielsen Karina , Axtell Carolyn , Peters Susan E. , Sorensen Glorian
Published: August 2021

(1) Background: Realist evaluation is a promising approach for evaluating organisational interventions. Crucial to realist evaluation is the development and testing of middle range theories (MRTs). MRTs are programme theories that outline how the intervention mechanisms work in a specific context to bring about certain outcomes. To the best of our knowledge, no organisational intervention study has yet developed initial MRTs. This study aimed to develop initial MRTs based on qualitative evidence from the development phase of an organisational intervention in a large multi-national organisation, the US food service industry. (2) Methods: Data were collected through 20 semi-structured interviews with the organisation′s managers, five focus groups with a total of 30 employees, and five worksite observations. Template analysis was used to analyse data. (3) Results: Four initial MRTs were developed based on four mechanisms of participation, leadership commitment, communication, and tailoring the intervention to fit the organisational context to formulate ‘what may work for whom in which circumstances?’ in organisational interventions; (4) Conclusions: Our findings provide insights into ‘how’ and ‘which’ initial MRTs can be developed in organisational interventions.
Comparison of Missing Data Infilling Mechanisms for Recovering a Real-World Single Station Streamflow Observation
Authors: Baddoo Thelma Dede , Li Zhijia , Odai Samuel Nii , Boni Kenneth Rodolphe Chabi , Nooni Isaac Kwesi , Andam-Akorful Samuel Ato
Published: August 2021

Reconstructing missing streamflow data can be challenging when additional data are not available, and missing data imputation of real-world datasets to investigate how to ascertain the accuracy of imputation algorithms for these datasets are lacking. This study investigated the necessary complexity of missing data reconstruction schemes to obtain the relevant results for a real-world single station streamflow observation to facilitate its further use. This investigation was implemented by applying different missing data mechanisms spanning from univariate algorithms to multiple imputation methods accustomed to multivariate data taking time as an explicit variable. The performance accuracy of these schemes was assessed using the total error measurement (TEM) and a recommended localized error measurement (LEM) in this study. The results show that univariate missing value algorithms, which are specially developed to handle univariate time series, provide satisfactory results, but the ones which provide the best results are usually time and computationally intensive. Also, multiple imputation algorithms which consider the surrounding observed values and/or which can understand the characteristics of the data provide similar results to the univariate missing data algorithms and, in some cases, perform better without the added time and computational downsides when time is taken as an explicit variable. Furthermore, the LEM would be especially useful when the missing data are in specific portions of the dataset or where very large gaps of ‘missingness’ occur. Finally, proper handling of missing values of real-world hydroclimatic datasets depends on imputing and extensive study of the particular dataset to be imputed.
Anthropometric Characteristics and Vertical Jump Abilities by Player Position and Performance Level of Junior Female Volleyball Players
Authors: Pocek Suncica , Milosevic Zoran , Lakicevic Nemanja , Pantelic-Babic Kristina , Imbronjev Milka , Thomas Ewan , Bianco Antonino , Drid Patrik
Published: August 2021

Although absolute jump heights should be considered an important factor in judging the performance requirements of volleyball players, limited data is available on age-appropriate categories. The purpose of this study is to determine the differences in specific anthropometric characteristics and jumping performance variables in under−19 female volleyball players in relation to playing position and performance level. The sample of subjects consisted of 354 players who prepared for the U19 Women’s Volleyball European Championship 2020 (17.4 ± 0.8 years, 1.81 ± 0.07 m, 67.5 ± 7.1 kg). Playing positions analyzed were setters (n = 55), opposites (n = 37), middle blockers (n = 82), outside hitters (n = 137), and liberos (n = 43). The results showed player position differences in every performance level group in variables of body height, spike, and block jump. Observed differences are a consequence of highly specific tasks of different positions in the composition of the team. Players of different performance levels are significantly different, with athletes of higher-ranked teams achieving better results. The acquired data could be useful for the selection and profiling of young volleyball players.
Effects of Shift Work in a Sample of Italian Nurses: Analysis of Rest-Activity Circadian Rhythm
Authors: Galasso Letizia , Mulè Antonino , Castelli Lucia , Cè Emiliano , Condemi Vincenzo , Banfi Giuseppe , Roveda Eliana , Montaruli Angela , Esposito Fabio
Published: August 2021

Shift work can lead to circadian desynchronization due to temporary misalignment between working hours and physiological and behavioral functioning, resulting in compromised health, insomnia, worsening of sleep quality, reduced ability to work during waking hours, and increased cardiovascular risk. We evaluated the effects of shift work on the rest-activity circadian rhythm (RAR) and health status of Italian orthopaedic nurses. The study population was 59 nurses: 44 worked the night shift and 15 worked the day shift. All carried out continuous 5-day actigraphic monitoring to assess RAR, including both the working and the rest period. The rhythmometric analysis showed that, during the working period, the night shift nurses had a significantly lower amplitude than the day shift nurses (p < 0.001), and the acrophase was significantly different between the two groups (p < 0.01). When we stratified the two groups by median body mass index (<25 kg/m2 normal weight and ≥25 kg/m2 overweight), during the working period, we noted a significantly lower amplitude for both the normal weight and the overweight nurses who worked the night shift (p < 0.01 and p < 0.001, normal weight and overweight respectively). The current findings suggest the need for further study of the relationship between activity levels and shift work.
Stress among Emergency Health Care Workers on Nuclear or Radiation Disaster: A Preliminary State Survey
Authors: Bouillon-Minois Jean-Baptiste , Roux Vincent , Pereira Bruno , Flannery Mara , Pelissier Carole , Occelli Céline , Schmidt Jeannot , Navel Valentin , Dutheil Frédéric
Published: August 2021

Background: The nuclear or radiation disaster risk within the French Auvergne-Rhone-Alpes state is low (but not absent) due to its proximity to four Nuclear Power Generation Centers and two regional cancer control centers. This study aims to compare subjective stress ratings for emergency health care workers regarding nuclear and radiation disasters between two locations: at work versus at home. Materials and Methods: We distributed an anonymous online questionnaire via RedCap® to all emergency health care workers who could be involved in patient care after a nuclear or radiation disaster. It comprised 18 questions divided into three parts—theoretical knowledge and practical assessment, stress assessment, and sociodemographic criteria. Results: We analyzed 107 responses. There was a significant 11-point increase in stress levels between work and home regarding nuclear or radiation disaster risks (p = 0.01). Less than 25% of emergency health care workers surveyed benefited from annual training. Conclusion: The stress levels of emergency health care workers regarding nuclear or radiation disaster were higher at work than at home and increased without annual training. It is important to increase knowledge about these protocols and to mandate yearly training for all workers potentially involved in these disasters.
Development of the Level of Preventive Action Method by Observation of the Characteristic Value for the Assessment of Occupational Risks on Construction Sites
Authors: Carpio de los Pinos Antonio José , González García María de las Nieves , Soriano José Antonio , Yáñez Araque Benito
Published: August 2021

The special circumstances of the high accident rate in the construction industry compared to other sectors are significant and represent a major concern for many countries. Construction work involves a large number of risks that cause or may cause accidents with serious consequences for the worker’s health, even death. The Level of Preventive Action is a novel methodology of occupational risk assessment adapted to building works. It is based on the development of the mathematical formulation of William T. Fine’s method. Its implementation covers four of the techniques for combating risk: Safety at Work, Industrial Hygiene, Ergonomics and Psychosociology. It evaluates, quantitatively, the amount of preventive action required based on the characteristic complexity of the work units, their location and their interdependence. The method protocol defines a new observation parameter called Characteristic Value which is inherent to the real situation of the construction process. The aim of this study is to develop the characterisation of the Characteristic Value in the Level of Preventive Action method. It also justifies the procedure to obtain this Characteristic Value and how its implementation and result should be interpreted. Finally, the methodology is applied on a real case.
Development Work in Healthcare: What Supportive and Deterrent Factors Do Employees Working in a Hospital Department Experience in an Improved Work Environment?
Authors: Perä Susanna , Hellman Therese , Molin Fredrik , Svartengren Magnus
Published: August 2021

Work-related mental health issues, accounting for high worker absenteeism in the world’s developed economies, are increasing, with the main cause being workplace conditions. The health services sector is especially experiencing great problems with this, because of challenging psychosocial working conditions. The aim of this study was to explore employees’ experiences of development work with a focus on the work environment within a hospital department with an outspoken special development assignment. The special assignment was decided by the highest management at the hospital and concerned work environment, caring processes, and ways of organizing the work. Eleven employees completed two individually semi-structured interviews, approximately 7 and 13 months after the start of the special assignment at the department. Interviews were analyzed using thematic analysis. The results reveal that both internal and external aspects influence the development work and highlight the importance of viewing the local development work in relation to how the rest of the organization functions. Important factors and conditions for a supportive and change-friendly work culture are discussed, as well as the need to plan for integration and change to create conditions for successful implementation of the results from organizational development and change initiatives.
Erratum: Hołub et al. Predicting Breaststroke and Butterfly Stroke Results in Swimming Based on Olympics History. Int. J. Environ. Res. Public Health 2021, 18, 6621
Authors: Hołub Maciej , Stanula Arkadiusz , Baron Jakub , Głyk Wojciech , Rosemann Thomas , Knechtle Beat
Published: August 2021

In the original article [...]
Modeling SF-6D Health Utilities: Is Bayesian Approach Appropriate?
Authors: Kharroubi Samer A.
Published: August 2021

Background: Valuation studies of preference-based health measures like SF6D have been conducted in many countries. However, the cost of conducting such studies in countries with small populations or low- and middle-income countries (LMICs) can be prohibitive. There is potential to use results from readily available countries’ valuations to produce better valuation estimates. Methods: Data from Lebanon and UK SF-6D value sets were analyzed, where values for 49 and 249 health states were extracted from samples of Lebanon and UK populations, respectively, using standard gamble techniques. A nonparametric Bayesian model was used to estimate a Lebanon value set using the UK data as informative priors. The resulting estimates were then compared to a Lebanon value set obtained using Lebanon data by itself via various prediction criterions. Results: The findings permit the UK evidence to contribute potential prior information to the Lebanon analysis by producing more precise valuation estimates than analyzing Lebanon data only under all criterions used. Conclusions: The positive findings suggest that existing valuation studies can be merged with a small valuation set in another country to produce value sets, thereby making own country value sets more attainable for LMICs.
Instrumental Validity of the Motion Detection Accuracy of a Smartphone-Based Training Game
Authors: Guggenberger Bernhard , Jocham Andreas J. , Jocham Birgit , Nischelwitzer Alexander , Ritschl Helmut
Published: August 2021

Demographic changes associated with an expanding and aging population will lead to an increasing number of orthopedic surgeries, such as joint replacements. To support patients’ home exercise programs after total hip replacement and completing subsequent inpatient rehabilitation, a low-cost, smartphone-based augmented reality training game (TG) was developed. To evaluate its motion detection accuracy, data from 30 healthy participants were recorded while using the TG. A 3D motion analysis system served as reference. The TG showed differences of 18.03 mm to 24.98 mm along the anatomical axes. Surveying the main movement direction of the implemented exercises (squats, step-ups, side-steps), differences between 10.13 mm to 24.59 mm were measured. In summary, the accuracy of the TG’s motion detection is sufficient for use in exergames and to quantify progress in patients’ performance. Considering the findings of this study, the presented exer-game approach has potential as a low-cost, easily accessible support for patients in their home exercise program.
Health Impact and Psychosocial Perceptions among French Medical Residents during the SARS-CoV-2 Outbreak: A Cross-Sectional Survey
Authors: Lucas David , Brient Sandrine , Eveillard Bisi Moriamo , Gressier Annabelle , Le Grand Tanguy , Pougnet Richard , Dewitte Jean-Dominique , Loddé Brice
Published: August 2021

This study compared the impact on mental health and the psychosocial perceptions of medical residents and healthcare workers (HCWs) in a hospital after the first peak of the SARS-CoV2 outbreak in France. A validated version of the SATIN questionnaire with a modified scoring system was used to collect data on health and psychosocial factors. This questionnaire was sent to all workers at the hospital in July 2020 and was self-administered online. Using a multivariate multinomial regression model, the study included demographic variables such as age, gender, years at workplace and the relevant of covariate as HCW status. One thousand, four hundred and six questionnaires were available for analysis including 393 non-HCWs, 891 HCWs and 122 medical residents. Medical resident status is a risk factor for stress (OR 4.77 [2.48–9.18] p < 0.001), worse global health (OR 4 [1.7–9.6] p < 0.001) and mental health (OR 2.58 [1.3–5.1] p = 0.02), negative perception of work demand (OR 8.25 [3.5–19.6] p <0.001), work activity environment (OR 3.18 [1.5–6.7] p = 0.02) and organizational context (OR 4.9 [2.38–10.4] p <0.001). Action on collective support, protection equipment, organizational context and framework are important.
Immunonano-Lipocarrier-Mediated Liver Sinusoidal Endothelial Cell-Specific RUNX1 Inhibition Impedes Immune Cell Infiltration and Hepatic Inflammation in Murine Model of NASH
Authors: Tripathi Dinesh Mani , Rohilla Sumati , Kaur Impreet , Siddiqui Hamda , Rawal Preety , Juneja Pinky , Kumar Vikash , Kumari Anupama , Naidu Vegi Ganga Modi , Ramakrishna Seeram , Banerjee Subham , Puria Rekha , Sarin Shiv K. , Kaur Savneet
Published: August 2021

Background: Runt-related transcription factor (RUNX1) regulates inflammation in non-alcoholic steatohepatitis (NASH). Methods: We performed in vivo targeted silencing of the RUNX1 gene in liver sinusoidal endothelial cells (LSECs) by using vegfr3 antibody tagged immunonano-lipocarriers encapsulated RUNX1 siRNA (RUNX1 siRNA) in murine models of methionine choline deficient (MCD) diet-induced NASH. MCD mice given nanolipocarriers-encapsulated negative siRNA were vehicle, and mice with standard diet were controls. Results: Liver RUNX1 expression was increased in the LSECs of MCD mice in comparison to controls. RUNX1 protein expression was decreased by 40% in CD31-positive LSECs of RUNX1 siRNA mice in comparison to vehicle, resulting in the downregulation of adhesion molecules, ICAM1 expression, and VCAM1 expression in LSECs. There was a marked decrease in infiltrated T cells and myeloid cells along with reduced inflammatory cytokines in the liver of RUNX1 siRNA mice as compared to that observed in the vehicle. Conclusions: In vivo LSEC-specific silencing of RUNX1 using immunonano-lipocarriers encapsulated siRNA effectively reduces its expression of adhesion molecules, infiltrate on of immune cells in liver, and inflammation in NASH.
NGS in Hereditary Ataxia: When Rare Becomes Frequent
Authors: Galatolo Daniele , De Michele Giovanna , Silvestri Gabriella , Leuzzi Vincenzo , Casali Carlo , Musumeci Olimpia , Antenora Antonella , Astrea Guja , Barghigiani Melissa , Battini Roberta , Battisti Carla , Caputi Caterina , Cioffi Ettore , De Michele Giuseppe , Dotti Maria Teresa , Fico Tommasina , Fiorillo Chiara , Galosi Serena , Lieto Maria , Malandrini Alessandro , Melone Marina A. B. , Mignarri Andrea , Natale Gemma , Pegoraro Elena , Petrucci Antonio , Ricca Ivana , Riso Vittorio , Rossi Salvatore , Rubegni Anna , Scarlatti Arianna , Tinelli Francesca , Trovato Rosanna , Tedeschi Gioacchino , Tessa Alessandra , Filla Alessandro , Santorelli Filippo Maria
Published: August 2021

The term hereditary ataxia (HA) refers to a heterogeneous group of neurological disorders with multiple genetic etiologies and a wide spectrum of ataxia-dominated phenotypes. Massive gene analysis in next-generation sequencing has entered the HA scenario, broadening our genetic and clinical knowledge of these conditions. In this study, we employed a targeted resequencing panel (TRP) in a large and highly heterogeneous cohort of 377 patients with a clinical diagnosis of HA, but no molecular diagnosis on routine genetic tests. We obtained a positive result (genetic diagnosis) in 33.2% of the patients, a rate significantly higher than those reported in similar studies employing TRP (average 19.4%), and in line with those performed using exome sequencing (ES, average 34.6%). Moreover, 15.6% of the patients had an uncertain molecular diagnosis. STUB1, PRKCG, and SPG7 were the most common causative genes. A comparison with published literature data showed that our panel would have identified 97% of the positive cases reported in previous TRP-based studies and 92% of those diagnosed by ES. Proper use of multigene panels, when combined with detailed phenotypic data, seems to be even more efficient than ES in clinical practice.
Biocatalyzed Synthesis of Flavor Esters and Polyesters: A Design of Experiments (DoE) Approach
Authors: Fabbri Filippo , Bertolini Federico A. , Guebitz Georg M. , Pellis Alessandro
Published: August 2021

In the present work, different hydrolases were adsorbed onto polypropylene beads to investigate their activity both in short-esters and polyesters synthesis. The software MODDE® Pro 13 (Sartorius) was used to develop a full-factorial design of experiments (DoE) to analyse the thermostability and selectivity of the immobilized enzyme towards alcohols and acids with different chain lengths in short-esters synthesis reactions. The temperature optima of Candida antarctica lipase B (CaLB), Humicola insolens cutinase (HiC), and Thermobifida cellulosilytica cutinase 1 (Thc_Cut1) were 85 °C, 70 °C, and 50 °C. CaLB and HiC preferred long-chain alcohols and acids as substrate in contrast to Thc_Cut1, which was more active on short-chain monomers. Polymerization of different esters as building blocks was carried out to confirm the applicability of the obtained model on larger macromolecules. The selectivity of both CaLB and HiC was investigated and best results were obtained for dimethyl sebacate (DMSe), leading to polyesters with a Mw of 18 kDa and 6 kDa. For the polymerization of dimethyl adipate (DMA) with BDO and ODO, higher molecular masses were obtained when using CaLB onto polypropylene beads (CaLB_PP) as compared with CaLB immobilized on macroporous acrylic resin beads (i.e., Novozym 435). Namely, for BDO the Mn were 7500 and 4300 Da and for ODO 8100 and 5000 Da for CaLB_PP and for the commercial enzymes, respectively. Thc_Cut1 led to polymers with lower molecular masses, with Mn < 1 kDa. This enzyme showed a temperature optimum of 50 °C with 63% of DMA and BDO when compared to 54% and 27%, at 70 °C and at 85 °C, respectively.
Mitochondrial Carriers and Substrates Transport Network: A Lesson from Saccharomyces cerevisiae
Authors: Ferramosca Alessandra , Zara Vincenzo
Published: August 2021

The yeast Saccharomyces cerevisiae is one of the most widely used model organisms for investigating various aspects of basic cellular functions that are conserved in human cells. This organism, as well as human cells, can modulate its metabolism in response to specific growth conditions, different environmental changes, and nutrient depletion. This adaptation results in a metabolic reprogramming of specific metabolic pathways. Mitochondrial carriers play a fundamental role in cellular metabolism, connecting mitochondrial with cytosolic reactions. By transporting substrates across the inner membrane of mitochondria, they contribute to many processes that are central to cellular function. The genome of Saccharomyces cerevisiae encodes 35 members of the mitochondrial carrier family, most of which have been functionally characterized. The aim of this review is to describe the role of the so far identified yeast mitochondrial carriers in cell metabolism, attempting to show the functional connections between substrates transport and specific metabolic pathways, such as oxidative phosphorylation, lipid metabolism, gluconeogenesis, and amino acids synthesis. Analysis of the literature reveals that these proteins transport substrates involved in the same metabolic pathway with a high degree of flexibility and coordination. The understanding of the role of mitochondrial carriers in yeast biology and metabolism could be useful for clarifying unexplored aspects related to the mitochondrial carrier network. Such knowledge will hopefully help in obtaining more insight into the molecular basis of human diseases.
Theoretical Investigation of the Mechanism by which A Gain-of-Function Mutation of the TRPM4 Channel Causes Conduction Block
Authors: Hu Yaopeng , Li Qin , Shen Yanghua , Fujita Takayuki , Zhu Xin , Inoue Ryuji
Published: August 2021

In the heart, TRPM4 is most abundantly distributed in the conduction system. Previously, a single mutation, ‘E7K’, was identified in its distal N-terminus to cause conduction disorder because of enhanced cell-surface expression. It remains, however, unclear how this expression increase leads to conduction failure rather than abnormally enhanced cardiac excitability. To address this issue theoretically, we mathematically formulated the gating kinetics of the E7K-mutant TRPM4 channel by a combined use of voltage jump analysis and ionomycin-perforated cell-attached recording technique and incorporated the resultant rate constants of opening and closing into a human Purkinje fiber single-cell action potential (AP) model (Trovato model) to perform 1D-cable simulations. The results from TRPM4 expressing HEK293 cells showed that as compared with the wild-type, the open state is much preferred in the E7K mutant with increased voltage-and Ca2+-sensitivities. These theoretical predictions were confirmed by power spectrum and single channel analyses of expressed wild-type and E7K-mutant TRPM4 channels. In our modified Trovato model, the facilitated opening of the E7K mutant channel markedly prolonged AP duration with concomitant depolarizing shifts of the resting membrane potential in a manner dependent on the channel density (or maximal activity). This was, however, little evident in the wild-type TRPM4 channel. Moreover, 1D-cable simulations with the modified Trovato model revealed that increasing the density of E7K (but not of wild-type) TRPM4 channels progressively reduced AP conduction velocity eventually culminating in complete conduction block. These results clearly suggest the brady-arrhythmogenicity of the E7K mutant channel which likely results from its pathologically enhanced activity.
Effect of Active Lengthening and Shortening on Small-Angle X-ray Reflections in Skinned Skeletal Muscle Fibres
Authors: Joumaa Venus , Smith Ian C. , Fukutani Atsuki , Leonard Timothy R. , Ma Weikang , Mijailovich Srboljub M. , Irving Thomas C. , Herzog Walter
Published: August 2021

Our purpose was to use small-angle X-ray diffraction to investigate the structural changes within sarcomeres at steady-state isometric contraction following active lengthening and shortening, compared to purely isometric contractions performed at the same final lengths. We examined force, stiffness, and the 1,0 and 1,1 equatorial and M3 and M6 meridional reflections in skinned rabbit psoas bundles, at steady-state isometric contraction following active lengthening to a sarcomere length of 3.0 µm (15.4% initial bundle length at 7.7% bundle length/s), and active shortening to a sarcomere length of 2.6 µm (15.4% bundle length at 7.7% bundle length/s), and during purely isometric reference contractions at the corresponding sarcomere lengths. Compared to the reference contraction, the isometric contraction after active lengthening was associated with an increase in force (i.e., residual force enhancement) and M3 spacing, no change in stiffness and the intensity ratio I1,1/I1,0, and decreased lattice spacing and M3 intensity. Compared to the reference contraction, the isometric contraction after active shortening resulted in decreased force, stiffness, I1,1/I1,0, M3 and M6 spacings, and M3 intensity. This suggests that residual force enhancement is achieved without an increase in the proportion of attached cross-bridges, and that force depression is accompanied by a decrease in the proportion of attached cross-bridges. Furthermore, the steady-state isometric contraction following active lengthening and shortening is accompanied by an increase in cross-bridge dispersion and/or a change in the cross-bridge conformation compared to the reference contractions.
The Contribution of Autophagy and LncRNAs to MYC-Driven Gene Regulatory Networks in Cancers
Authors: Jahangiri Leila , Pucci Perla , Ishola Tala , Trigg Ricky M. , Williams John A. , Pereira Joao , Cavanagh Megan L. , Turner Suzanne D. , Gkoutos Georgios V. , Tsaprouni Loukia
Published: August 2021

MYC is a target of the Wnt signalling pathway and governs numerous cellular and developmental programmes hijacked in cancers. The amplification of MYC is a frequently occurring genetic alteration in cancer genomes, and this transcription factor is implicated in metabolic reprogramming, cell death, and angiogenesis in cancers. In this review, we analyse MYC gene networks in solid cancers. We investigate the interaction of MYC with long non-coding RNAs (lncRNAs). Furthermore, we investigate the role of MYC regulatory networks in inducing changes to cellular processes, including autophagy and mitophagy. Finally, we review the interaction and mutual regulation between MYC and lncRNAs, and autophagic processes and analyse these networks as unexplored areas of targeting and manipulation for therapeutic gain in MYC-driven malignancies.
Selenium Deficiency Due to Diet, Pregnancy, Severe Illness, or COVID-19—A Preventable Trigger for Autoimmune Disease
Authors: Schomburg Lutz
Published: August 2021

The trace element selenium (Se) is an essential part of the human diet; moreover, increased health risks have been observed with Se deficiency. A sufficiently high Se status is a prerequisite for adequate immune response, and preventable endemic diseases are known from areas with Se deficiency. Biomarkers of Se status decline strongly in pregnancy, severe illness, or COVID-19, reaching critically low concentrations. Notably, these conditions are associated with an increased risk for autoimmune disease (AID). Positive effects on the immune system are observed with Se supplementation in pregnancy, autoimmune thyroid disease, and recovery from severe illness. However, some studies reported null results; the database is small, and randomized trials are sparse. The current need for research on the link between AID and Se deficiency is particularly obvious for rheumatoid arthritis and type 1 diabetes mellitus. Despite these gaps in knowledge, it seems timely to realize that severe Se deficiency may trigger AID in susceptible subjects. Improved dietary choices or supplemental Se are efficient ways to avoid severe Se deficiency, thereby decreasing AID risk and improving disease course. A personalized approach is needed in clinics and during therapy, while population-wide measures should be considered for areas with habitual low Se intake. Finland has been adding Se to its food chain for more than 35 years—a wise and commendable decision, according to today’s knowledge. It is unfortunate that the health risks of Se deficiency are often neglected, while possible side effects of Se supplementation are exaggerated, leading to disregard for this safe and promising preventive and adjuvant treatment options. This is especially true in the follow-up situations of pregnancy, severe illness, or COVID-19, where massive Se deficiencies have developed and are associated with AID risk, long-lasting health impairments, and slow recovery.
Modular and Molecular Optimization of a LOV (Light–Oxygen–Voltage)-Based Optogenetic Switch in Yeast
Authors: Romero Andrés , Rojas Vicente , Delgado Verónica , Salinas Francisco , Larrondo Luis F.
Published: August 2021

Optogenetic switches allow light-controlled gene expression with reversible and spatiotemporal resolution. In Saccharomyces cerevisiae, optogenetic tools hold great potential for a variety of metabolic engineering and biotechnology applications. In this work, we report on the modular optimization of the fungal light–oxygen–voltage (FUN-LOV) system, an optogenetic switch based on photoreceptors from the fungus Neurospora crassa. We also describe new switch variants obtained by replacing the Gal4 DNA-binding domain (DBD) of FUN-LOV with nine different DBDs from yeast transcription factors of the zinc cluster family. Among the tested modules, the variant carrying the Hap1p DBD, which we call “HAP-LOV”, displayed higher levels of luciferase expression upon induction compared to FUN-LOV. Further, the combination of the Hap1p DBD with either p65 or VP16 activation domains also resulted in higher levels of reporter expression compared to the original switch. Finally, we assessed the effects of the plasmid copy number and promoter strength controlling the expression of the FUN-LOV and HAP-LOV components, and observed that when low-copy plasmids and strong promoters were used, a stronger response was achieved in both systems. Altogether, we describe a new set of blue-light optogenetic switches carrying different protein modules, which expands the available suite of optogenetic tools in yeast and can additionally be applied to other systems.
Chromosomal Characterization of Tripidium arundinaceum Revealed by Oligo-FISH
Authors: Yu Fan , Chai Jin , Li Xueting , Yu Zehuai , Yang Ruiting , Ding Xueer , Wang Qiusong , Wu Jiayun , Yang Xiping , Deng Zuhu
Published: August 2021

Sugarcane is of important economic value for producing sugar and bioethanol. Tripidium arundinaceum (old name: Erianthus arundinaceum) is an intergeneric wild species of sugarcane that has desirable resistance traits for improving sugarcane varieties. However, the scarcity of chromosome markers has hindered the cytogenetic study of T. arundinaceum. Here we applied maize chromosome painting probes (MCPs) to identify chromosomes in sorghum and T. arundinaceum using a repeated fluorescence in situ hybridization (FISH) system. Sequential FISH revealed that these MCPs can be used as reliable chromosome markers for T. arundinaceum, even though T. arundinaceum has diverged from maize over 18 MYs (million years). Using these MCPs, we identified T. arundinaceum chromosomes based on their sequence similarity compared to sorghum and labeled them 1 through 10. Then, the karyotype of T. arundinaceum was established by multiple oligo-FISH. Furthermore, FISH results revealed that 5S rDNA and 35S rDNA are localized on chromosomes 5 and 6, respectively, in T. arundinaceum. Altogether, these results represent an essential step for further cytogenetic research of T. arundinaceum in sugarcane breeding.
Autophagy and Metabolism in Normal and Malignant Hematopoiesis
Authors: Stergiou Ioanna E. , Kapsogeorgou Efstathia K.
Published: August 2021

The hematopoietic system relies on regulation of both metabolism and autophagy to maintain its homeostasis, ensuring the self-renewal and multipotent differentiation potential of hematopoietic stem cells (HSCs). HSCs display a distinct metabolic profile from that of their differentiated progeny, while metabolic rewiring from glycolysis to oxidative phosphorylation (OXPHOS) has been shown to be crucial for effective hematopoietic differentiation. Autophagy-mediated regulation of metabolism modulates the distinct characteristics of quiescent and differentiating hematopoietic cells. In particular, mitophagy determines the cellular mitochondrial content, thus modifying the level of OXPHOS at the different differentiation stages of hematopoietic cells, while, at the same time, it ensures the building blocks and energy for differentiation. Aberrations in both the metabolic status and regulation of the autophagic machinery are implicated in the development of hematologic malignancies, especially in leukemogenesis. In this review, we aim to investigate the role of metabolism and autophagy, as well as their interconnections, in normal and malignant hematopoiesis.
Transcriptomic Characterization of Nitrate-Enhanced Stevioside Glycoside Synthesis in Stevia (Stevia rebaudiana) Bertoni
Authors: Sun Yuming , Zhang Ting , Xu Xiaoyang , Yang Yongheng , Tong Haiying , Mur Luis Alejandro Jose , Yuan Haiyan
Published: August 2021

Nitrogen forms (nitrate (NO3−) or ammonium (NH4+)) are vital to plant growth and metabolism. In stevia (Stevia rebaudiana), it is important to assess whether nitrogen forms can influence the synthesis of the high-value terpene metabolites-steviol glycosides (SGs), together with the underlying mechanisms. Field and pot experiments were performed where stevia plants were fertilized with either NO3− or NH4+ nutrition to the same level of nitrogen. Physiological measurements suggested that nitrogen forms had no significant impact on biomass and the total nitrogen content of stevia leaves, but NO3−-enhanced leaf SGs contents. Transcriptomic analysis identified 397 genes that were differentially expressed (DEGs) between NO3− and NH4+ treatments. Assessment of the DEGs highlighted the responses in secondary metabolism, particularly in terpenoid metabolism, to nitrogen forms. Further examinations of the expression patterns of SGs synthesis-related genes and potential transcription factors suggested that GGPPS and CPS genes, as well as the WRKY and MYB transcription factors, could be driving N form-regulated SG synthesis. We concluded that NO3−, rather than NH4+, can promote leaf SG synthesis via the NO3−-MYB/WRKY-GGPPS/CPS module. Our study suggests that insights into the molecular mechanism of how SG synthesis can be affected by nitrogen forms.