bluuebunny/crossref_metadata_2025 huggingface dataset:
Spatio-Temporal Gait Parameters of Hospitalized Older Patients: Comparison of Fallers and Non-Fallers
Authors: Bourgarel Emilie , Risser Clémence , Blanc Frederic , Vogel Thomas , Kaltenbach Georges , Meyer Maxence , Schmitt Elise
Published: March 2023

Gait disorders are predisposing factors for falls. They are accessible to rehabilitation and can be analyzed using tools that collect spatio-temporal parameters of walking, such as the GAITRite® mat. The objective of this retrospective study was to find differences between the spatio-temporal parameters in patients who had fallen compared to patients who did not fall in a population of older patients hospitalized in acute geriatrics department. Patients over 75 years were included. For each patient, spatio-temporal parameters were collected using the GAITRite® mat. The patients were divided into two groups according to whether they had a history of fall. The spatio-temporal parameters were compared between the two groups and in relation to the general population. Sixty-seven patients, with an average age of 85.9 ± 6 years, were included. The patients had comorbidities, cognitive impairment and were polymedicated. The mean walking speed was 51.4 cm/s in non-fallers group and 47.3 cm/s in fallers group (p = 0.539), indicating pathological walking in comparison with the general population of the same age (average 100 cm/s). No association was found between the spatio-temporal parameters and fall, probably linked to many confounding factors such as the pathogenicity of walking of our patients and their comorbidities.
Characteristics of Stress Sensitivity in Heroin Use Disorder Patients during Their Opioid Agonist Treatment
Authors: Della Rocca Filippo , Maremmani Angelo G. I. , Bacciardi Silvia , Pacini Matteo , Lamanna Francesco , Tripodi Beniamino , Miccoli Mario , Maremmani Icro
Published: March 2023

In the present study, performed on a sample of Heroin Use Disorder (HUD) patients undergoing Opioid Agonist Treatment (OAT), we attempted to explore the relationships between stress sensitivity and heroin addiction-related clinical aspects. HUD patients’ stress sensitivity was evaluated with the Heroin/PTSD-Spectrum questionnaire (H/PSTD-S). The Drug Addiction History Questionnaire (DAH-Q), the Symptomatological Check List-90 (SCL-90), and The Behavioural Covariate of Heroin Craving inventory (CRAV-HERO) were all used, as were the Deltito Subjective Wellness Scale (D-SWS), a self-report scale evaluating subjective well-being; the Cocaine Problem Severity Index (CPSI), a questionnaire determining the extent of a cocaine problem; and the Marijuana Craving Questionnaire (MC-Q), an instrument assessing craving for cannabinoids. We checked correlations between stress sensitivity and the extent of HUD clinical features and compared patients with and without problematic stress sensitivity. H/PTSD-S was positively correlated with patients’ income, altered mental status, legal problems, the lifetime different treatments index, the current treatment load index, and all SCL-90 indexes and factors. Regarding subjective well-being, stress sensitivity negatively correlated with the contrast best week (last five years) index. Patients with high-stress sensitivity were females with a low income. They exhibited a more severe mental status at treatment entry, greater difficulty in working adaptation, and legal problems during treatment. Additionally, these patients showed a higher level of psychopathology, more impairment in well-being, and more risky behaviours during treatment. Stress sensitivity, as H/PTSD-S, must be considered an outcome of HUD. HUD’s addiction history and clinical features are significant risk factors for H/PTSD-S. Therefore, social and behavioural impairment in HUD patients could be considered the clinical expression of the H/PTSD spectrum. In summary, the long-term outcome of HUD is not represented by drug-taking behaviours. Rather, the inability to cope with the contingent environmental conditions is the key feature of such a disorder. H/PTSD-S, therefore, should be seen as a syndrome caused by an acquired inability (increased salience) concerning regular (daily) life events.
COVID-19 Worries and Insomnia: A Follow-Up Study
Authors: Brown Lily A. , Zhu Yiqin , Hamlett Gabriella E. , Moore Tyler M. , DiDomenico Grace E. , Visoki Elina , Greenberg David M. , Gur Ruben C. , Gur Raquel E. , Barzilay Ran
Published: March 2023

The COVID-19 pandemic was associated with significant increases in sleep disorder symptoms and chronic worry. We previously demonstrated that worry about the pandemic was more strongly associated with subsequent insomnia than the converse during the acute (first 6 months) phase of the pandemic. In this report, we evaluated whether that association held over one year of the pandemic. Participants (n = 3560) completed self-reported surveys of worries about the pandemic, exposure to virus risk factors, and the Insomnia Severity Index on five occasions throughout the course of one year. In cross-sectional analyses, insomnia was more consistently associated with worries about the pandemic than exposure to COVID-19 risk factors. In mixed-effects models, changes in worries predicted changes in insomnia and vice versa. This bidirectional relationship was further confirmed in cross-lagged panel models. Clinically, these findings suggest that during a global disaster, patients who report elevations in either worry or insomnia should be considered for evidence-based treatments for these symptoms to prevent secondary symptoms in the future. Future research should evaluate the extent to which dissemination of evidence-based practices for chronic worry (a core feature of generalized anxiety disorder or illness anxiety disorder) or insomnia reduces the development of co-occurring symptoms during a global disaster.
Improving Safety Performance of Construction Workers through Learning from Incidents
Authors: Chan Albert P. C. , Guan Junfeng , Choi Tracy N. Y. , Yang Yang , Wu Guangdong , Lam Edmond
Published: March 2023

Learning from incidents (LFI) is a process to seek, analyse, and disseminate the severity and causes of incidents, and take corrective measures to prevent the recurrence of similar events. However, the effects of LFI on the learner’s safety performance remain unexplored. This study aimed to identify the effects of the major LFI factors on the safety performance of workers. A questionnaire survey was administered among 210 construction workers in China. A factor analysis was conducted to reveal the underlying LFI factors. A stepwise multiple linear regression was performed to analyse the relationship between the underlying LFI factors and safety performance. A Bayesian Network (BN) was further modelled to identify the probabilistic relational network between the underlying LFI factors and safety performance. The results of BN modelling showed that all the underlying factors were important to improve the safety performance of construction workers. Additionally, sensitivity analysis revealed that the two underlying factors—information sharing and utilization and management commitment—had the largest effects on improving workers’ safety performance. The proposed BN also helped find out the most efficient strategy to improve workers’ safety performance. This research may serve as a useful guide for better implementation of LFI practices in the construction sector.
The Right to Ask, the Need to Answer—When Patients Meet Research: How to Cope with Time
Authors: Priolo Manuela , Tartaglia Marco
Published: March 2023

Reaching a diagnosis and its communication are two of the most meaningful events in the physician–patient relationship. When facing a disease, most of the patients’ expectations rely on the hope that their clinicians would be able to understand the cause of their illness and eventually end it. Rare diseases are a peculiar subset of conditions in which the search for a diagnosis might reveal a long and painful journey scattered by doubts and requiring, in most cases, a long waiting time. For many individuals affected by a rare disease, turning to research might represent their last chance to obtain an answer to their questions. Time is the worst enemy, threatening to disrupt the fragile balance among affected individuals, their referring physicians, and researchers. It is consuming at all levels, draining economic, emotional, and social resources, and triggering unpredictable reactions in each stakeholder group. Managing waiting time is one of the most burdensome tasks for all the parties playing a role in the search for a diagnosis: the patients and their referring physicians urge to obtain a diagnosis in order to know the condition they are dealing with and establish proper management, respectively. On the other hand, researchers need to be objective and scientifically act to give a rigorous answer to their demands. While moving towards the same goal, patients, clinicians, and researchers might have different expectations and perceive the same waiting time as differently hard or tolerable. The lack of information on mutual needs and the absence of effective communication among the parties are the most common mechanisms of the failure of the therapeutic alliance that risk compromising the common goal of a proper diagnosis. In the landscape of modern medicine that goes faster and claims high standards of cure, rare diseases represent an exception where physicians and researchers should learn to cope with time in order to care for patients.
Doping in Sport—Attitudes of Physical Trainers Students Regarding the Use of Prohibited Substances Increasing Performance
Authors: Zmuda Palka Magdalena , Bigosińska Monika , Siwek Matylda , Angelova-Igova Boryana , Mucha Dawid Konrad
Published: March 2023

Background: The popularity of using the advice of a personal trainer is increasing in Poland and currently most gyms offer the possibility of training under the supervision of a professional. Personal trainers present a multifaceted nature into physical activity and become their clients’ guides in achieving sporting goals. Physical trainers also work in sports clubs and supervise the training of people professionally involved in sport. Aim: Given the professional role that they play, this article aimed to analyze the knowledge and attitudes of personal trainers towards using prohibited measures to improve performance in sport, as well as counteraction measures. Methods: The study used a questionnaire created by the authors containing closed, semi-open, and open questions. Results: The results of the presented research indicate that most physical trainers and students educated in this field have a negative attitude towards the use of prohibited measures that increase performance but they noticed that doping was common in sport by 88.51% respondents. In the group of personal trainers, the majority (87.14%) admitted that good results in sport could be achieved without the use of doping. They stated that it was unfair (25%), contrary to the fair play principle—16%, while over 11% indicated this as cheating. Only 6% of people pointed out that it was legally prohibited and 3% that it was harmful. These results show that 10.13% of all respondents believe that the use of doping is a necessity to achieve very good results in sport. Conclusions: The availability of doping substances is statistically correlated with the question of persuading to use doping in both groups of trainers and students and some people justify the use of doping. The research proved that the personal trainers’ level of knowledge on doping is still insufficient.
A Causal View of the Role and Potential Limitations of Capitation in Promoting Whole Health System Performance
Authors: Matchar David Bruce , Lai Wei Xuan , Kumar Ashish , Ansah John Pastor , Ng Yeuk Fan
Published: March 2023

For several decades, health systems in developed countries have faced rapidly rising healthcare costs without concomitant improvements in health outcomes. Fee for service (FFS) reimbursement mechanisms (RMs), where health systems are paid based on volume, contribute to this trend. In Singapore, the public health service is trying to curb rising healthcare costs by transitioning from a volume-based RM to a capitated payment for a population within a geographical catchment area. To provide insight into the implications of this transition, we developed a causal loop diagram (CLD) to represent a causal hypothesis of the complex relationship between RM and health system performance. The CLD was developed with input from government policymakers, healthcare institution administrators, and healthcare providers. This work highlights that the causal relationships between government, provider organizations, and physicians involve numerous feedback loops that drive the mix of health services. The CLD clarifies that a FFS RM incentivizes high margin services irrespective of their health benefits. While capitation has the potential to mitigate this reinforcing phenomenon, it is not sufficient to promote service value. This suggests the need to establish robust mechanisms to govern common pool resources while minimizing adverse secondary effects.
mHealth Technology as a Help Tool during Breast Cancer Treatment: A Content Focus Group
Authors: Fuentes Angeles , Amat Clara , Lozano-Rubí Raimundo , Frid Santiago , Muñoz Montserrat , Escarrabill Joan , Grau-Corral Imma
Published: March 2023

Purpose: To assess the usability and preferences of the contents of mHealth software developed for breast cancer patients as a tool to obtain patient-reported outcomes (PROMs), improve the patient’s knowledge about the disease and its side effects, increase adherence to treatment, and facilitate communication with the doctor. Intervention: an mHealth tool called the Xemio app provides side effect tracking, social calendars, and a personalized and trusted disease information platform to deliver evidence-based advice and education for breast cancer patients. Method: A qualitative research study using semi-structured focus groups was conducted and evaluated. This involved a group interview and a cognitive walking test using Android devices, with the participation of breast cancer survivors. Results: The ability to track side effects and the availability of reliable content were the main benefits of using the application. The ease of use and the method of interaction were the primary concerns; however, all participants agreed that the application would be beneficial to users. Finally, participants expressed their expectations of being informed by their healthcare providers about the launch of the Xemio app. Conclusion: Participants perceived the need for reliable health information and its benefits through an mHealth app. Therefore, applications for breast cancer patients must be designed with accessibility as a key consideration.
Texting on a Smartphone While Walking Affects Gait Parameters
Authors: Sajewicz Julia , Dziuba-Słonina Alicja
Published: March 2023

Cell phone use while walking is an ever-increasing traffic hazard, and leads to an augmented risk of accidents. There is a rising number of injuries to pedestrians using a cell phone. Texting on a cell phone while walking is an emerging problem among people of different ages. The aim of this experiment was to investigate whether using a cell phone while walking affects walking velocity, as well as cadence, stride width, and length in young people. Forty-two subjects (20 males, 22 females; mean age: 20.74 ± 1.34 years; mean height: 173.21 ± 8.07 cm; mean weight: 69.05 ± 14.07 kg) participated in the study. The subjects were asked to walk on an FDM−1.5 dynamometer platform four times at a constant comfortable velocity and a fast velocity of their choice. They were asked to continuously type one sentence on a cell phone while walking at the same velocity. The results showed that texting while walking led to a significant reduction in velocity compared to walking without the phone. Width, cadence, and length of right and left single steps were statistically significantly influenced by this task. In conclusion, such changes in gait parameters may result in an increased risk of pedestrian crossing accidents and tripping while walking. Phone use is an activity that should be avoided while walking.
Estimating Mode of Transport in Daily Mobility during the COVID-19 Pandemic Using a Multinomial Logistic Regression Model
Authors: Mazanec Jaroslav , Harantová Veronika , Štefancová Vladimíra , Brůhová Foltýnová Hana
Published: March 2023

At the beginning of 2020 there was a spinning point in the travel behavior of people around the world because of the pandemic and its consequences. This paper analyzes the specific behavior of travelers commuting to work or school during the COVID-19 pandemic based on a sample of 2000 respondents from two countries. We obtained data from an online survey, applying multinomial regression analysis. The results demonstrate the multinomial model with an accuracy of almost 70% that estimates the most used modes of transport (walking, public transport, car) based on independent variables. The respondents preferred the car as the most frequently used means of transport. However, commuters without car prefer public transport to walking. This prediction model could be a tool for planning and creating transport policy, especially in exceptional cases such as the limitation of public transport activities. Therefore, predicting travel behavior is essential for policymaking based on people’s travel needs.
Validation and Analysis of the Psychometric Properties of Two Irritability-Measuring Tools: The Affective Reactivity Index (ARI) and the Born-Steiner Irritability Scale (BSIS) in the Italian Adult and Adolescent Populations
Authors: Grassi Maria Letizia , Valente Donatella , Berardi Anna , Tofani Marco , Galeoto Giovanni
Published: March 2023

Irritability is a transdiagnostic symptom that affects quality of life during the lifespan of individuals. The objective of the present research was to validate two assessment tools, namely the Affective Reactivity Index (ARI) and the Born-Steiner Irritability Scale (BSIS). We investigated internal consistency as measured with Cronbach’s alpha, test–retest with intraclass correlation coefficient (ICC) and convergent validity confronting ARI and BSIS scores with the strength and difficulties questionnaire (SDQ). Our results revealed ARI good internal consistency with a Cronbach’s α of 0.79 for adolescent and 0.78 for adults. The BSIS also demonstrated good internal consistency for both samples with Cronbach’s α = 0.87. Test–retest analysis showed excellent values for both tools. Convergent validity showed positive and significant correlation with SDW, albeit weak for some sub-scales. In conclusion, we found ARI and BSIS to be good tools for measuring irritability in adolescents and adults, and now, Italian healthcare professionals can use it with more confidence.
Cost-Benefit Analysis versus Cost-Effectiveness Analysis from a Societal Perspective in Healthcare
Authors: Brent Robert J.
Published: March 2023

Cost-effectiveness analysis (CEA) is the main way that economic evaluations are carried out in the health care field. However, CEA has limited validity in deciding whether any health care evaluation is socially worthwhile and hence justifies funding. Cost-Benefit Analysis (CBA) is the economic evaluation method that should be used to help decide what to invest in when the objective is to record the impact on everyone in society. Cost-utility analysis (CUA), which has its roots in CEA, can be converted into CBA under certain circumstances that are not general. In this article, the strengths and weaknesses of CEA relative to CBA are analyzed in stages, starting in its most classical form and then proceeding via CUA to end up as CBA. The analysis takes place mainly in the context of five actual dementia interventions that have already been found to pass a CBA test. The CBA data is recast into CEA and CUA terms in tabular form in order that the contrast been CEA and CBA is most transparent. We find that how much of the fixed budget that is used up to fund other alternatives determines how much is left over to fund the particular intervention one is evaluating.
Prediction of Relevant Training Control Parameters at Individual Anaerobic Threshold without Blood Lactate Measurement
Authors: Römer Claudia , Wolfarth Bernd
Published: March 2023

Background: Active exercise therapy plays an essential role in tackling the global burden of obesity. Optimizing recommendations in individual training therapy requires that the essential parameters heart rate HR(IAT) and work load (W/kg(IAT) at individual anaerobic threshold (IAT) are known. Performance diagnostics with blood lactate is one of the most established methods for these kinds of diagnostics, yet it is also time consuming and expensive. Methods: To establish a regression model which allows HR(IAT) and (W/kg(IAT) to be predicted without measuring blood lactate, a total of 1234 performance protocols with blood lactate in cycle ergometry were analyzed. Multiple linear regression analyses were performed to predict the essential parameters (HR(IAT)) (W/kg(IAT)) by using routine parameters for ergometry without blood lactate. Results: HR(IAT) can be predicted with an RMSE of 8.77 bpm (p < 0.001), R2 = 0.799 (|R| = 0.798) without performing blood lactate diagnostics during cycle ergometry. In addition, it is possible to predict W/kg(IAT) with an RMSE (root mean square error) of 0.241 W/kg (p < 0.001), R2 = 0.897 (|R| = 0.897). Conclusions: It is possible to predict essential parameters for training management without measuring blood lactate. This model can easily be used in preventive medicine and results in an inexpensive yet better training management of the general population, which is essential for public health.
Toward Understanding Microbial Ecology to Restore a Degraded Ecosystem
Authors: Song Liyan
Published: March 2023

The microbial community plays an important role in maintaining human health, addressing climate change, maintaining environmental quality, etc. High-throughput sequencing leads to the discovery and identification of more microbial community composition and function in diverse ecosystems. Microbiome therapeutics such as fecal microbiota transplantation for human health and bioaugmentation for activated sludge restoration have drawn great attention. However, microbiome therapeutics cannot secure the success of microbiome transplantation. This paper begins with a view on fecal microbiota transplantation and bioaugmentation and is followed by a parallel analysis of these two microbial therapeutic strategies. Accordingly, the microbial ecology mechanisms behind them were discussed. Finally, future research on microbiota transplantation was proposed. Successful application of both microbial therapeutics for human disease and bioremediation for contaminated environments relies on a better understanding of the microbial “entangled bank” and microbial ecology of these environments.
Associations between Coronavirus and Immune Response, Cardiorespiratory Fitness Rehabilitation and Physical Activity: A Brief Report
Authors: Silva-Santos Sandra , Monteiro António , Barbosa Tiago , Teixeira José , Branquinho Luís , Ferraz Ricardo , Forte Pedro
Published: March 2023

COVID-19 has serious effects on cardiorespiratory capacity. In this sense, physical activity has been identified as beneficial in the treatment of cardiorespiratory diseases due to its anti-inflammatory and immunosuppressive benefits. To date, no study has been found on cardiorespiratory capacity and rehabilitation in patients cured after COVID-19. Thus, this brief report aims to relate the benefits of physical activity to cardiorespiratory function after COVID-19. It is important to know how different levels of physical activity can be related to the different symptoms of COVID-19. In view of this, the objectives of this brief report were to: (1) explore the theoretical associations between COVID-19 symptoms and physical activity; (2) compare the cardiorespiratory function of non-COVID-19 participants and post-COVID-19 patients; and (3) propose a physical activity program to improve the cardiorespiratory fitness of post-COVID-19 patients. Thus, we note that moderate-intensity physical activity (i.e., walking) has a greater beneficial effect on immune function, whereas vigorous activity (i.e., marathon running) tends to temporarily reduce immune function through an imbalance of cytokine types I and II in the hours and days after exercise. However, there is no consensus in the literature in this regard, since other investigations suggest that high-intensity training can also be beneficial, not causing clinically relevant immunosuppression. Physical activity has been shown to be beneficial in improving the clinical conditions most frequently associated with severe COVID-19. Thus, it is possible to infer that physically active individuals seem to be less exposed to the dangers of severe COVID-19 compared to non-active individuals through the benefits of physical activity in strengthening the immune system and fighting infections. The current study demonstrates that physical activity appears to be beneficial in improving the clinical conditions most often associated with severe COVID-19.
Endoplasmic Reticulum Stress in Renal Cell Carcinoma
Authors: Correia de Sousa Marta , Delangre Etienne , Türkal Miranda , Foti Michelangelo , Gjorgjieva Monika
Published: March 2023

The endoplasmic reticulum is an organelle exerting crucial functions in protein production, metabolism homeostasis and cell signaling. Endoplasmic reticulum stress occurs when cells are damaged and the capacity of this organelle to perform its normal functions is reduced. Subsequently, specific signaling cascades, together forming the so-called unfolded protein response, are activated and deeply impact cell fate. In normal renal cells, these molecular pathways strive to either resolve cell injury or activate cell death, depending on the extent of cell damage. Therefore, the activation of the endoplasmic reticulum stress pathway was suggested as an interesting therapeutic strategy for pathologies such as cancer. However, renal cancer cells are known to hijack these stress mechanisms and exploit them to their advantage in order to promote their survival through rewiring of their metabolism, activation of oxidative stress responses, autophagy, inhibition of apoptosis and senescence. Recent data strongly suggest that a certain threshold of endoplasmic reticulum stress activation needs to be attained in cancer cells in order to shift endoplasmic reticulum stress responses from a pro-survival to a pro-apoptotic outcome. Several endoplasmic reticulum stress pharmacological modulators of interest for therapeutic purposes are already available, but only a handful were tested in the case of renal carcinoma, and their effects in an in vivo setting remain poorly known. This review discusses the relevance of endoplasmic reticulum stress activation or suppression in renal cancer cell progression and the therapeutic potential of targeting this cellular process for this cancer.
Antibacterial Activity of Two New Cassane Diterpenoids from Caesaplinia pulcherrima against Bacillus cereus by Damage to Cell Membrane
Authors: Zhang Zihan , Wang Panpan , Chen Mengsong , Xie Lu , Zhang Xiujuan , Shi Yefan , Lu Wang , Zhang Qiang , Li Chunhuan
Published: March 2023

Bacillus cereus, a Gram-positive bacterium, is a food contaminant that threatens the health of thousands of people around the world. Because of the continuous emergence of drug-resistant strains, the development of new classes of bactericides from natural products is of high priority. In this study, two novel cassane diterpenoids (pulchins A and B) and three known ones (3–5) were elucidated from the medicinal plant Caesaplinia pulcherrima (L.) Sw. Pulchin A, with a rare “6/6/6/3” carbon skeleton, showed significant antibacterial activity against B. cereus and Staphylococcus aureus, with MIC values of 3.13 and 6.25 μM, respectively. Further investigation of its mechanism of antibacterial activity against B. cereus is also discussed in detail. The results revealed that the antibacterial activity of pulchin A against B. cereus may be caused by pulchin A interfering with bacterial cell membrane proteins, affecting membrane permeability and causing cell damage or death. Thus, pulchin A may have a potential application as an antibacterial agent in the food and agricultural industries.
Imbalanced Inflammatory Responses in Preterm and Term Cord Blood Monocytes and Expansion of the CD14+CD16+ Subset upon Toll-like Receptor Stimulation
Authors: Glaser Kirsten , Kern David , Speer Christian P. , Schlegel Nicolas , Schwab Michael , Thome Ulrich H. , Härtel Christoph , Wright Clyde J.
Published: March 2023

Developmentally regulated features of innate immunity are thought to place preterm and term infants at risk of infection and inflammation-related morbidity. Underlying mechanisms are incompletely understood. Differences in monocyte function including toll-like receptor (TLR) expression and signaling have been discussed. Some studies point to generally impaired TLR signaling, others to differences in individual pathways. In the present study, we assessed mRNA and protein expression of pro- and anti-inflammatory cytokines in preterm and term cord blood (CB) monocytes compared with adult controls stimulated ex vivo with Pam3CSK4, zymosan, polyinosinic:polycytidylic acid, lipopolysaccharide, flagellin, and CpG oligonucleotide, which activate the TLR1/2, TLR2/6, TLR3, TLR4, TLR5, and TLR9 pathways, respectively. In parallel, frequencies of monocyte subsets, stimulus-driven TLR expression, and phosphorylation of TLR-associated signaling molecules were analyzed. Independent of stimulus, pro-inflammatory responses of term CB monocytes equaled adult controls. The same held true for preterm CB monocytes—except for lower IL-1β levels. In contrast, CB monocytes released lower amounts of anti-inflammatory IL-10 and IL-1ra, resulting in higher ratios of pro-inflammatory to anti-inflammatory cytokines. Phosphorylation of p65, p38, and ERK1/2 correlated with adult controls. However, stimulated CB samples stood out with higher frequencies of intermediate monocytes (CD14+CD16+). Both pro-inflammatory net effect and expansion of the intermediate subset were most pronounced upon stimulation with Pam3CSK4 (TLR1/2), zymosan (TR2/6), and lipopolysaccharide (TLR4). Our data demonstrate robust pro-inflammatory and yet attenuated anti-inflammatory responses in preterm and term CB monocytes, along with imbalanced cytokine ratios. Intermediate monocytes, a subset ascribed pro-inflammatory features, might participate in this inflammatory state.
The Cellular Response to Complex DNA Damage Induced by Ionising Radiation
Authors: Wilkinson Beth , Hill Mark A. , Parsons Jason L.
Published: March 2023

Radiotherapy (ionising radiation; IR) is utilised in the treatment of ~50% of all human cancers, and where the therapeutic effect is largely achieved through DNA damage induction. In particular, complex DNA damage (CDD) containing two or more lesions within one to two helical turns of the DNA is a signature of IR and contributes significantly to the cell killing effects due to the difficult nature of its repair by the cellular DNA repair machinery. The levels and complexity of CDD increase with increasing ionisation density (linear energy transfer, LET) of the IR, such that photon (X-ray) radiotherapy is deemed low-LET whereas some particle ions (such as carbon ions) are high-LET radiotherapy. Despite this knowledge, there are challenges in the detection and quantitative measurement of IR-induced CDD in cells and tissues. Furthermore, there are biological uncertainties with the specific DNA repair proteins and pathways, including components of DNA single and double strand break mechanisms, that are engaged in CDD repair, which very much depends on the radiation type and associated LET. However, there are promising signs that advancements are being made in these areas and which will enhance our understanding of the cellular response to CDD induced by IR. There is also evidence that targeting CDD repair, particularly through inhibitors against selected DNA repair enzymes, can exacerbate the impact of higher LET, which could be explored further in a translational context.
New Insights into the Identification of Metabolites and Cytokines Predictive of Outcome for Patients with Severe SARS-CoV-2 Infection Showed Similarity with Cancer
Authors: Costantini Susan , Madonna Gabriele , Di Gennaro Elena , Capone Francesca , Bagnara Palmina , Capone Mariaelena , Sale Silvia , Nicastro Carmine , Atripaldi Lidia , Fiorentino Giuseppe , Parrella Roberto , Montesarchio Vincenzo , Atripaldi Luigi , Ascierto Paolo A. , Budillon Alfredo
Published: March 2023

SARS-CoV-2 infection is characterized by several clinical manifestations, ranging from the absence of symptoms to severe forms that necessitate intensive care treatment. It is known that the patients with the highest rate of mortality develop increased levels of proinflammatory cytokines, called the “cytokine storm”, which is similar to inflammatory processes that occur in cancer. Additionally, SARS-CoV-2 infection induces modifications in host metabolism leading to metabolic reprogramming, which is closely linked to metabolic changes in cancer. A better understanding of the correlation between perturbed metabolism and inflammatory responses is necessary. We evaluated untargeted plasma metabolomics and cytokine profiling via 1H-NMR (proton nuclear magnetic resonance) and multiplex Luminex assay, respectively, in a training set of a limited number of patients with severe SARS-CoV-2 infection classified on the basis of their outcome. Univariate analysis and Kaplan–Meier curves related to hospitalization time showed that lower levels of several metabolites and cytokines/growth factors, correlated with a good outcome in these patients and these data were confirmed in a validation set of patients with similar characteristics. However, after the multivariate analysis, only the growth factor HGF, lactate and phenylalanine retained a significant prediction of survival. Finally, the combined analysis of lactate and phenylalanine levels correctly predicted the outcome of 83.3% of patients in both the training and the validation set. We highlighted that the cytokines and metabolites involved in COVID-19 patients’ poor outcomes are similar to those responsible for cancer development and progression, suggesting the possibility of targeting them by repurposing anticancer drugs as a therapeutic strategy against severe SARS-CoV-2 infection.
Silencing of Pepper CaFtsH1 or CaFtsH8 Genes Alters Normal Leaf Development
Authors: Xu Kai , Li Ning , Zhang Yiwen , Gao Shenghua , Yin Yanxu , Yao Minghua , Wang Fei
Published: March 2023

Filamentation temperature-sensitive H (FtsH) is a proteolytic enzyme that plays an important role in plant photomorphogenesis and stress resistance. However, information regarding the FtsH family genes in pepper is limited. In our research, through genome-wide identification, 18 members of the pepper FtsH family (including five FtsHi members) were identified and renamed based on phylogenetic analysis. CaFtsH1 and CaFtsH8 were found to be essential for pepper chloroplast development and photosynthesis because FtsH5 and FtsH2 were lost in Solanaceae diploids. We found that the CaFtsH1 and CaFtsH8 proteins were located in the chloroplasts and specifically expressed in pepper green tissues. Meanwhile, CaFtsH1 and CaFtsH8-silenced plants created by virus-induced gene silencing exhibited albino leaf phenotypes. In addition, CaFtsH1-silenced plants were observed to contain very few dysplastic chloroplasts and lost the capacity for photoautotrophic growth. Transcriptome analysis revealed that the expression of chloroplast-related genes such as those coding the photosynthesis-antenna protein and structural proteins was downregulated in CaFtsH1-silenced plants, resulting in the inability to form normal chloroplasts. This study improves our understanding of pepper chloroplast formation and photosynthesis through the identification and functional study of CaFtsH genes.
Special Issue: Yeast Cell Signaling Pathways (Volume 1)
Authors: Teixeira Vitor
Published: March 2023

This Special Issue was devoted to unravelling novel aspects of yeast biology and signal transduction in numerous yet intricate basic processes [...]
The Proteome of Circulating Large Extracellular Vesicles in Diabetes and Hypertension
Authors: Abolbaghaei Akram , Turner Maddison , Thibodeau Jean-François , Holterman Chet E. , Kennedy Christopher R. J. , Burger Dylan
Published: March 2023

Hypertension and diabetes induce vascular injury through processes that are not fully understood. Changes in extracellular vesicle (EV) composition could provide novel insights. Here, we examined the protein composition of circulating EVs from hypertensive, diabetic and healthy mice. EVs were isolated from transgenic mice overexpressing human renin in the liver (TtRhRen, hypertensive), OVE26 type 1 diabetic mice and wild-type (WT) mice. Protein content was analyzed using liquid chromatography–mass spectrometry. We identified 544 independent proteins, of which 408 were found in all groups, 34 were exclusive to WT, 16 were exclusive to OVE26 and 5 were exclusive to TTRhRen mice. Amongst the differentially expressed proteins, haptoglobin (HPT) was upregulated and ankyrin-1 (ANK1) was downregulated in OVE26 and TtRhRen mice compared with WT controls. Conversely, TSP4 and Co3A1 were upregulated and SAA4 was downregulated exclusively in diabetic mice; and PPN was upregulated and SPTB1 and SPTA1 were downregulated in hypertensive mice, compared to WT mice. Ingenuity pathway analysis identified enrichment in proteins associated with SNARE signaling, the complement system and NAD homeostasis in EVs from diabetic mice. Conversely, in EVs from hypertensive mice, there was enrichment in semaphroin and Rho signaling. Further analysis of these changes may improve understanding of vascular injury in hypertension and diabetes.
Amino Acids in Health and Disease: The Good, the Bad, and the Ugly
Authors: Ishii Isao , Bhatia Madhav
Published: March 2023

The Special Issue “Amino Acid Metabolism and Regulation in Health and Disease 2 [...]
Phytochemical Study on Seeds of Paeonia clusii subsp. rhodia—Antioxidant and Anti-Tyrosinase Properties
Authors: Klontza Vithleem , Graikou Konstantia , Cheilari Antigoni , Kasapis Vasilios , Ganos Christos , Aligiannis Nektarios , Chinou Ioanna
Published: March 2023

In this study, the black fertile (BSs) and the red unfertile seeds (RSs) of the Greek endemic Paeonia clusii subsp. rhodia (Stearn) Tzanoud were studied for the first time. Nine phenolic derivatives, trans-resveratol, trans-resveratrol-4′-O-β-d-glucopyranoside, trans-ε-viniferin, trans-gnetin H, luteolin, luteolin 3′-O-β-d-glucoside, luteolin 3′,4′-di-O-β-d-glucopyranoside, and benzoic acid, along with the monoterpene glycoside paeoniflorin, have been isolated and structurally elucidated. Furthermore, 33 metabolites have been identified from BSs through UHPLC-HRMS, including 6 monoterpene glycosides of the paeoniflorin type with the characteristic cage-like terpenic skeleton found only in plants of the genus Paeonia, 6 gallic acid derivatives, 10 oligostilbene compounds, and 11 flavonoid derivatives. From the RSs, through HS-SPME and GC-MS, 19 metabolites were identified, among which nopinone, myrtanal, and cis-myrtanol have been reported only in peonies’ roots and flowers to date. The total phenolic content of both seed extracts (BS and RS) was extremely high (up to 289.97 mg GAE/g) and, moreover, they showed interesting antioxidative activity and anti-tyrosinase properties. The isolated compounds were also biologically evaluated. Especially in the case of trans-gnetin H, the expressed anti-tyrosinase activity was higher than that of kojic acid, which is a well-known whitening agent standard.
Full-Length Transcriptome of the Great Himalayan Leaf-Nosed Bats (Hipposideros armiger) Optimized Genome Annotation and Revealed the Expression of Novel Genes
Authors: Bao Mingyue , Wang Xue , Sun Ruyi , Wang Zhiqiang , Li Jiqian , Jiang Tinglei , Lin Aiqing , Wang Hui , Feng Jiang
Published: March 2023

The Great Himalayan Leaf-nosed bat (Hipposideros armiger) is one of the most representative species of all echolocating bats and is an ideal model for studying the echolocation system of bats. An incomplete reference genome and limited availability of full-length cDNAs have hindered the identification of alternatively spliced transcripts, which slowed down related basic studies on bats’ echolocation and evolution. In this study, we analyzed five organs from H. armiger for the first time using PacBio single-molecule real-time sequencing (SMRT). There were 120 GB of subreads generated, including 1,472,058 full-length non-chimeric (FLNC) sequences. A total of 34,611 alternative splicing (AS) events and 66,010 Alternative Polyadenylation (APA) sites were detected by transcriptome structural analysis. Moreover, a total of 110,611 isoforms were identified, consisting of 52% new isoforms of known genes and 5% of novel gene loci, as well as 2112 novel genes that have not been annotated before in the current reference genome of H. armiger. Furthermore, several key novel genes, including Pol, RAS, NFKB1, and CAMK4, were identified as being associated with nervous, signal transduction, and immune system processes, which may be involved in regulating the auditory nervous perception and immune system that helps bats to regulate in echolocation. In conclusion, the full-length transcriptome results optimized and replenished existing H. armiger genome annotation in multiple ways and offer advantages for newly discovered or previously unrecognized protein-coding genes and isoforms, which can be used as a reference resource.
Classification of Common Food Lipid Sources Regarding Healthiness Using Advanced Lipidomics: A Four-Arm Crossover Study
Authors: Monfort-Pires Milena , Lamichhane Santosh , Alonso Cristina , Egelandsdal Bjørg , Orešič Matej , Jordahl Vilde Overrein , Skjølsvold Oda , Pérez-Ruiz Irantzu , Blanco María Encarnación , Skeie Siv , Martins Catia , Haug Anna
Published: March 2023

Prospective studies have failed to establish a causal relationship between animal fat intake and cardiovascular diseases in humans. Furthermore, the metabolic effects of different dietary sources remain unknown. In this four-arm crossover study, we investigated the impact of consuming cheese, beef, and pork meat on classic and new cardiovascular risk markers (obtained from lipidomics) in the context of a healthy diet. A total of 33 young healthy volunteers (23 women/10 men) were assigned to one out of four test diets in a Latin square design. Each test diet was consumed for 14 days, with a 2-week washout. Participants received a healthy diet plus Gouda- or Goutaler-type cheeses, pork, or beef meats. Before and after each diet, fasting blood samples were withdrawn. A reduction in total cholesterol and an increase in high density lipoprotein particle size were detected after all diets. Only the pork diet upregulated plasma unsaturated fatty acids and downregulated triglycerides species. Improvements in the lipoprotein profile and upregulation of circulating plasmalogen species were also observed after the pork diet. Our study suggests that, within the context of a healthy diet rich in micronutrients and fiber, the consumption of animal products, in particular pork meat, may not induce deleterious effects, and reducing the intake of animal products should not be regarded as a way of reducing cardiovascular risk in young individuals.
Human Neuromuscular Junction on a Chip: Impact of Amniotic Fluid Stem Cell Extracellular Vesicles on Muscle Atrophy and NMJ Integrity
Authors: Gatti Martina , Dittlau Katarina Stoklund , Beretti Francesca , Yedigaryan Laura , Zavatti Manuela , Cortelli Pietro , Palumbo Carla , Bertucci Emma , Van Den Bosch Ludo , Sampaolesi Maurilio , Maraldi Tullia
Published: March 2023

Neuromuscular junctions (NMJs) are specialized synapses, crucial for the communication between spinal motor neurons (MNs) and skeletal muscle. NMJs become vulnerable in degenerative diseases, such as muscle atrophy, where the crosstalk between the different cell populations fails, and the regenerative ability of the entire tissue is hampered. How skeletal muscle sends retrograde signals to MNs through NMJs represents an intriguing field of research, and the role of oxidative stress and its sources remain poorly understood. Recent works demonstrate the myofiber regeneration potential of stem cells, including amniotic fluid stem cells (AFSC), and secreted extracellular vesicles (EVs) as cell-free therapy. To study NMJ perturbations during muscle atrophy, we generated an MN/myotube co-culture system through XonaTM microfluidic devices, and muscle atrophy was induced in vitro by Dexamethasone (Dexa). After atrophy induction, we treated muscle and MN compartments with AFSC-derived EVs (AFSC-EVs) to investigate their regenerative and anti-oxidative potential in counteracting NMJ alterations. We found that the presence of EVs reduced morphological and functional in vitro defects induced by Dexa. Interestingly, oxidative stress, occurring in atrophic myotubes and thus involving neurites as well, was prevented by EV treatment. Here, we provided and validated a fluidically isolated system represented by microfluidic devices for studying human MN and myotube interactions in healthy and Dexa-induced atrophic conditions—allowing the isolation of subcellular compartments for region-specific analyses—and demonstrated the efficacy of AFSC-EVs in counteracting NMJ perturbations.
The Impact of Semicarbazide Sensitive Amine Oxidase Activity on Rat Aortic Vascular Smooth Muscle Cells
Authors: Manasieva Vesna , Thakur Shori , Lione Lisa A. , Baydoun Anwar R. , Skamarauskas John
Published: March 2023

Semicarbazide-sensitive amine oxidase (SSAO) is both a soluble- and membrane-bound transmembrane protein expressed in the vascular endothelial and in smooth muscle cells. In vascular endothelial cells, SSAO contributes to the development of atherosclerosis by mediating a leukocyte adhesion cascade; however, its contributory role in the development of atherosclerosis in VSMCs has not yet been fully explored. This study investigates SSAO enzymatic activity in VSMCs using methylamine and aminoacetone as model substrates. The study also addresses the mechanism by which SSAO catalytic activity causes vascular damage, and further evaluates the contribution of SSAO in oxidative stress formation in the vascular wall. SSAO demonstrated higher affinity for aminoacetone when compared to methylamine (Km = 12.08 µM vs. 65.35 µM). Aminoacetone- and methylamine-induced VSMCs death at concentrations of 50 & 1000 µM, and their cytotoxic effect, was reversed with 100 µM of the irreversible SSAO inhibitor MDL72527, which completely abolished cell death. Cytotoxic effects were also observed after 24 h of exposure to formaldehyde, methylglyoxal and H2O2. Enhanced cytotoxicity was detected after the simultaneous addition of formaldehyde and H2O2, as well as methylglyoxal and H2O2. The highest ROS production was observed in aminoacetone- and benzylamine-treated cells. MDL72527 abolished ROS in benzylamine-, methylamine- and aminoacetone-treated cells (**** p < 0.0001), while βAPN demonstrated inhibitory potential only in benzylamine-treated cells (* p < 0.05). Treatment with benzylamine, methylamine and aminoacetone reduced the total GSH levels (**** p < 0.0001); the addition of MDL72527 and βAPN failed to reverse this effect. Overall, a cytotoxic consequence of SSAO catalytic activity was observed in cultured VSMCs where SSAO was identified as a key mediator in ROS formation. These findings could potentially associate SSAO activity with the early developing stages of atherosclerosis through oxidative stress formation and vascular damage.