bluuebunny/crossref_metadata_2025 huggingface dataset:
Progress in understanding and treating idiopathic pulmonary fibrosis: recent insights and emerging therapies
Authors: Guo Hehua , Sun Jiazheng , Zhang Siyu , Nie Yalan , Zhou Sirui , Zeng Yulan
Published: August 2023

Idiopathic pulmonary fibrosis (IPF) is a long-lasting, continuously advancing, and irrevocable interstitial lung disorder with an obscure origin and inadequately comprehended pathological mechanisms. Despite the intricate and uncharted causes and pathways of IPF, the scholarly consensus upholds that the transformation of fibroblasts into myofibroblasts—instigated by injury to the alveolar epithelial cells—and the disproportionate accumulation of extracellular matrix (ECM) components, such as collagen, are integral to IPF’s progression. The introduction of two novel anti-fibrotic medications, pirfenidone and nintedanib, have exhibited efficacy in decelerating the ongoing degradation of lung function, lessening hospitalization risk, and postponing exacerbations among IPF patients. Nonetheless, these pharmacological interventions do not present a definitive solution to IPF, positioning lung transplantation as the solitary potential curative measure in contemporary medical practice. A host of innovative therapeutic strategies are presently under rigorous scrutiny. This comprehensive review encapsulates the recent advancements in IPF research, spanning from diagnosis and etiology to pathological mechanisms, and introduces a discussion on nascent therapeutic methodologies currently in the pipeline.
A framework for heart-lung interaction and its application to prone position in the acute respiratory distress syndrome
Authors: Kenny Jon-Emile S.
Published: August 2023

While both cardiac output (Qcirculatory) and right atrial pressure (PRA) are important measures in the intensive care unit (ICU), they are outputs of the system and not determinants. That is to say, in a model of the circulation wherein venous return and cardiac function find equilibrium at an ‘operating point’ (OP, defined by the PRA on the x-axis and Qcirculatory on the y-axis) both the PRA and Qcirculatory are, necessarily, dependent variables. A simplified geometrical approximation of Guyton’s model is put forth to illustrate that the independent variables of the system are: 1) the mean systemic filling pressure (PMSF), 2) the pressure within the pericardium (PPC), 3) cardiac function and 4) the resistance to venous return. Classifying independent and dependent variables is clinically-important for therapeutic control of the circulation. Recent investigations in patients with acute respiratory distress syndrome (ARDS) have illuminated how PMSF, cardiac function and the resistance to venous return change when placing a patient in prone. Moreover, the location of the OP at baseline and the intimate physiological link between the heart and the lungs also mediate how the PRA and Qcirculatory respond to prone position. Whereas turning a patient from supine to prone is the focus of this discussion, the principles described within the framework apply equally-well to other more common ICU interventions including, but not limited to, ventilator management, initiating vasoactive medications and providing intravenous fluids.
“Beyond laughter”: a systematic review to understand how interventions utilise comedy for individuals experiencing mental health problems
Authors: Kafle Eshika , Papastavrou Brooks Cat , Chawner Dave , Foye Una , Declercq Dieter , Brooks Helen
Published: August 2023

Introduction

There is evidence for the impact of comedy and humour for mental health and wellbeing. Existing systematic reviews have concluded laughter has a positive impact on wellbeing, however other potential benefits of comedy interventions have remained under explored. The aim of the current study was to synthesise current evidence for comedy/humour interventions and evaluate mechanisms through which comedy interventions may impact upon the recovery of those experiencing psychological distress, using the Connectedness, Hope, Identity, Meaning and Purpose and Empowerment (CHIME) framework.

Methods

Five electronic databases were searched for studies exploring the impact of interventions using comedy on wellbeing and mental health recovery, from earliest record until January 2023. Grey literature was obtained via contacting experts in comedy interventions for mental health and supplemented by an internet search for comedy interventions. To be eligible for inclusion, studies had to include primary data, published in English or German, and explore a population of adults, with self-reported distress or a self-reported/diagnosed mental health condition. Studies included only explored interventions which utilised comedy as the main intervention and aimed to induce ‘simulated’ laughter, in response to a stimulus. 17 studies were included in the review.

Results

Studies were found to have positive impact on mental health symptoms and several mechanisms of the CHIME framework for recovery, including connectedness, hope, identity and empowerment. Potential theorised mechanisms for change included confidence in new skills, promotion of social skills, opportunities for social interaction, laughter, vulnerability, and cognitive flexibility. The current review found that comedy/humour interventions are beneficial for mental health recovery and wellbeing and found preliminary evidence for a range of mechanisms through which comedy may have positive impact.

Discussion

Further research should focus on qualitative exploration of the mechanisms by which comedy interventions may have impact on wellbeing and mental health recovery for specific populations and within different settings. It is concluded that there is a need for transdisciplinary collaboration in research on comedy interventions, which brings together the expertise of comedians delivering/developing interventions, those with lived experience of mental health issues and researchers from both health sciences and humanities disciplines.
Do bystanders always see more than the players? Exploring Solomon’s paradox through meta-analysis
Authors: Lin Hongyi , Zheng Hong , Wang Fengyan
Published: August 2023

Solomon’s paradox is a widespread phenomenon regarding how we think, which asserts that people reason more wisely about other people’s social problems than they do about their own. This means that we are more likely to make rational decisions when decision-making on the behalf of others than for ourselves, which has practical implications in the field of interpersonal conflicts and social dilemmas. However, it remains unclear whether Solomon’s paradox exists across cultures, and the magnitude of its effect size. A meta-analysis was conducted, examining six studies and 20 effect sizes, to gain more insight into this phenomenon, considering the influencing effects of culture, measurement instrument, conflict type, and some other moderating factors. The results showed that Solomon’s paradox does exist in interpersonal conflict (d = 0.317; 95% CI = 0.828–0.852). Moderator analysis revealed that measurement instrument and subjects had an impact on the effect of Solomon’s paradox and there was a non-significant effect size of culture and conflict type. Future research should explore the diverse forms of Solomon’s paradox across more diverse cultural contexts (e.g., various countries) to better understand the phenomenon and help people cope with life’s problems more wisely.
Therapeutic comparison in psychological capital
Authors: Chan Gloria Hongyee
Published: August 2023

Aim

This study aimed to investigate and compare the therapeutic outcomes of psychological capital between narrative therapy, cognitive-behavioral therapy, and play therapy in the context of hikikomori.

Methods

This study included 502 hikikomori. Correlation analysis was performed to investigate the relationship between the three forms of therapy and psychological capital, while one-way ANOVA and independent samples t-tests were performed to determine the differences in the outcomes of psychological capital between the three forms of therapies.

Results

Results indicated that all three forms of therapy were significantly positively related to psychological capital. Moreover, while cognitive-behavioral therapy performed better in psychological capital (overall score) than the other two, cognitive-behavioral therapy performed better in the subscales “self-efficacy” and “resilience,” while narrative therapy performed better in the “hope” and “optimism” subscales. Also, combining features of play therapy helped enhance the outcomes of narrative therapy and cognitive-behavioral therapy on psychological capital.

Conclusion

Owing to the varied outcomes of psychological capital among different therapies, the differential use of therapies to deal with the unique needs resultant of hikikomori helps achieve optimal results.
Depression and social isolation during the COVID-19 pandemic in a student population: the effects of establishing and relaxing social restrictions
Authors: Holm-Hadulla Rainer Matthias , Wendler Hannes , Baracsi Gabriella , Storck Timo , Möltner Andreas , Herpertz Sabine C.
Published: August 2023

Introduction

In a quasi-naturalistic study design, we evaluate the change in psychopathological syndromes and general well-being after the alleviation of social restrictions. The aim of this study was to investigate the specific relationship between social isolation and depressive syndromes.

Methods

At two timepoints, the first during maximal social restrictions, the second after social restrictions had widely ended for 9 months, depressive and other syndromes were measured in an online survey addressing the total cohort of students registered at Heidelberg University, Germany via e-mail (n = 27,162). The complete Patient Health Questionnaire (PHQ) was used with nine items for depressive syndromes. In addition, well-being was measured by the Well-Being Index WHO-5. In the quantitative and qualitative part of the study psychopathological syndromes and well-being were related to social isolation and feelings of loneliness.

Results

After 1.5 years of pandemic-related social restrictions, “major” depressive syndromes were reported by 40.16% of the respondents to the PHQ in a sample of 2,318 university students. 72.52% showed a severely reduced Well-Being-Index. Nine months after the end of social restrictions, “major” depressive syndromes were reported by 28.50% of the participants. Well-being improved after the alleviation of social restrictions, as well: 53.96% showed a Well-Being Index of below 50 vs. 72.52% in the first study. The quantitative and qualitative analysis of the free texts of the respondents suggest that a significant amount of depressive syndromes and reduced well-being are related to social isolation and loneliness. While in the times of the pandemic restrictions the participants mostly reported “loneliness and social isolation” (24.2%) as their main problem, only 7.7% described these as their main problem after social restrictions had been loosened for 9 months. The qualitative analysis hints that at t2 participants were more likely to mention possible ways to actively deal with loneliness than at t1, which might be interpreted along the lines of the decrease in depressive syndromes.

Discussion

Keeping the self-selection bias in mind our study results suggest that one third of “major” depressive syndromes and one quarter of severely reduced well-being accompany social restrictions or are even caused by them, with loneliness being an important factor. These results should be taken into account by health policies when coping with future pandemics.
Case report: Atomoxetine improves chronic pain with comorbid post-traumatic stress disorder and attention deficit hyperactivity disorder
Authors: Kasahara Satoshi , Takahashi Miwako , Morita Taito , Matsudaira Ko , Sato Naoko , Momose Toshimitsu , Niwa Shin-Ichi , Uchida Kanji
Published: August 2023

Background

It is known that patients reporting chronic pain often experience trauma or post-traumatic stress disorder (PTSD) and tend to be more difficult to treat. Attention deficit hyperactivity disorder (ADHD), a neurodevelopmental disorder, is frequently associated with chronic pain. Furthermore, patients diagnosed with ADHD are more likely to encounter trauma and develop PTSD because of their inattentive and impulsive tendencies. There are reports stating that atomoxetine (ATX), a selective noradrenaline reuptake inhibitor for ADHD, is effective in patients diagnosed with PTSD and ADHD. However, there have been no reports on cases of comorbid PTSD and ADHD with chronic pain, and ATX’s potential in improving chronic pain coexisting PTSD. Furthermore, no reports have evaluated patient cerebral blood flow in conjunction with the course of treatment with ATX for chronic pain.

Case report

In this study, we reported a case where ATX improved chronic pain with PTSD and improved cerebral blood flow. The patient was a 56-year-old woman exhibiting chronic pain with PTSD, resulting from 6 years of severe domestic violence from her common-law husband. She had no history of ADHD diagnosis, but through aggressive screening, comorbid ADHD was diagnosed. When treated with ATX, there were significant improvements in her pain, quality of life, anxiety, depression, catastrophic thoughts, and cerebral blood flow. As a result, she could resume work after 11 years.

Conclusion

The study showed that chronic pain with PTSD may be comorbid with ADHD. Moreover, we found that ATX can improve chronic pain with PTSD and cerebral blood flow. Aggressive screening of ADHD is important because once the diagnosis of comorbidity is confirmed, an ideal ADHD treatment can be selected. Therefore, based on the results of this study, ATX may be a candidate for treatment for cases of chronic pain with PTSD and ADHD.
The promise and limitations of artificial intelligence in musculoskeletal imaging
Authors: Debs Patrick , Fayad Laura M.
Published: August 2023

With the recent developments in deep learning and the rapid growth of convolutional neural networks, artificial intelligence has shown promise as a tool that can transform several aspects of the musculoskeletal imaging cycle. Its applications can involve both interpretive and non-interpretive tasks such as the ordering of imaging, scheduling, protocoling, image acquisition, report generation and communication of findings. However, artificial intelligence tools still face a number of challenges that can hinder effective implementation into clinical practice. The purpose of this review is to explore both the successes and limitations of artificial intelligence applications throughout the muscuskeletal imaging cycle and to highlight how these applications can help enhance the service radiologists deliver to their patients, resulting in increased efficiency as well as improved patient and provider satisfaction.
Infectious agents present in monk parakeet (Myiopsitta monachus) and rose-ringed parakeet (Psittacula krameri) invasive species in the parks of Madrid and Seville, Spain
Authors: López Juan , Mogedas María , Ballesteros Carlos , Martín-Maldonado Bárbara , Sacristán Irene , García Raúl , Ortiz Juan Carlos , Esperón Fernando
Published: August 2023

Introduction

The introduction of invasive species into an ecosystem could result in biodiversity loss and the spread of infectious agents that could cause re-emergent or emergent zoonotic diseases. Monk parakeets (Myiopsitta monachus) and rose-ringed parakeets (Psittacula krameri) are considered widespread invasive exotic species in urban habitats from the Iberian Peninsula. The aim of this study was to assess the presence of relevant infectious agents in wild parakeets captured in urban parks in Madrid and Seville (Spain).

Methods

A total of 81 cloacal samples were collected and analysed using molecular techniques.

Results

The prevalence of infectious agents varied between parakeet species: 9.5% of monk parakeets and 15% of rose-ringed parakeets were positive for enteropathogenic E. coli (EPEC), 13.3% of rose-ringed parakeets for avian influenza virus (AIV), 3.3% of rose-ringed parakeets for Newcastle disease virus (NDV), and a 23.8% of monk parakeets for Chlamydia psittaci.

Discussion

All C. psittaci-identified isolates were classified as B, E, or E/B genotypes, indicating transmission from wild urban pigeons to parakeets. These results highlight the need for monitoring parakeet populations due to the implications for human and animal health.
Mito-Tempo improves acrosome integrity of frozen-thawed epididymal spermatozoa in tomcats
Authors: Ali Hassan Hiba , Banchi Penelope , Domain Guillaume , Vanderheyden Leen , Prochowska Sylwia , Nizański Wojciech , Van Soom Ann
Published: August 2023

Introduction

In tomcats, epididymal spermatozoa provide an additional source of male gametes available for cryopreservation. While this procedure is feasible, the survival rate and motility of epididymal cat spermatozoa are both low after thawing. Cryopreservation is known to induce oxidative stress in spermatozoa, with mitochondria and the plasma membrane being the two major generation sites, and an imbalanced presence of free radicals is a possible cause for this low survival rate. Different antioxidants have been tested before for their effect on cryopreserved cat spermatozoa quality, with varying results. Here, we used Mito-Tempo, which is a synthetic mitochondria-targeted antioxidant and a specific scavenger of the mitochondrial superoxide system. By supplementing Mito-Tempo with the freezing extender, we aimed to improve the sperm quality of frozen-thawed cat epididymal spermatozoa.

Methods

Epididymal spermatozoa obtained from twelve tomcats were assessed for motility and concentration. Prior to freezing, samples were diluted in TRIS buffered extender with egg yolk and glycerol and divided into five aliquots supplemented with 0 (control), 0.5, 5, 50, and 1005M of Mito-Tempo. After thawing, sperm motility, concentration, morphology, plasma membrane integrity, acrosome integrity, and mitochondrial membrane potential were evaluated. A Friedman rank sum test with a Bonferroni post-hoc test was used to determine statistical in-between group differences in post-thaw semen parameters.

Results and discussion

The results indicated a slight improvement in acrosome integrity across all groups that were supplemented with Mito-Tempo, with the group that received 55M of Mito-Tempo showing the greatest improvement [(median of 67.99%, IQR of 5.55) compared to the control group (median of 65.33%, IQR of 7.75; P = 0.05)]. For all other sperm parameters, no significant differences (P > 0.05) were detected between different Mito-Tempo concentrations. These findings highlight the protective effect of Mito-Tempo on acrosome integrity and suggest that 55M is the most effective concentration for maintaining acrosome integrity. Since Mito-Tempo has shown a positive effect on multiple sperm parameters in other species, such as men, boars, roosters, rams, and bulls, we need to conclude that species-specificity may play a role here.
Effects of adding Sophora alopecuroides to high concentrate diet on rumen fermentation parameters and microbial diversity of sheep
Authors: An Yawen , Wang Hairong , Zong Zichao , Gao Zhixiong , Shi Caixia , Li Shufang , Khas-Erdene
Published: August 2023

Objective

The purpose of this study was to investigate the effects of different doses of Sophora alopecuroides (SA) on the rumen fermentation and microbial diversity of sheep.

Methods

A total of 32 healthy Dumont crossbred male lambs weighing 25.73 ± 2.17 kg were randomly assigned to 4 treatment groups with 8 replicates each: a control group (CG) fed a basal diet with a concentrate-to-forage ratio of 7:3 and three experimental groups - the 0.1% group(TG1), 0.3% group (TG2), and 0.5% group (TG3), which were fed the same basal diet but supplemented with increasing doses of SA.

Results

(1) Increasing the SA dose led to a significant linear increase (p-< 0.05) in acetate, propionate, butyrate, and total volatile fatty acid (TVFA) concentrations in the rumen, as well as a significant quadratic effect (p-< 0.05) on the propionate concentration. In contrast, there was a significant linear decrease (p-< 0.05) in the NH3-N concentration in the rumen. (2) At the level of rumen bacterial phyla, the abundance of Bacteroidetes in the rumen increased, and that of Firmicutes decreased (p = 0.08). At the genus level, the rumen abundances of Ruminococcus and Phocaeicola of sheep in the three experimental groups were significantly higher than in the control group (p-< 0.05), and the abundances of Clostridiales and Candidatus-Hepatincola were significantly increased in the 0.1% and 0.3% groups (p < 0.05). (3) Regarding rumen anaerobic fungi, the differences between the control group and experimental groups at the phylum level and genus level were not significant (p > 0.05), but the relative abundances of Neocallimastigomycota and Piromyces in the 0.1% group were significantly higher than that in the control group.

Conclusion

SA addition to a high grain diet could increase the VFA concentration and pH in the sheep rumen, reduce the NH3-N concentration in the rumen and improve rumen fermentation function. Although there was no significant change in rumen bacterial or fungal diversity, SA addition increased the rumen abundances of Bacteroidetes, Ruminococcus, Phocaeicola, Clostridiales, Neocallimastigomycota and Piromyces, decreased the rumen abundance of Firmicutes, and had a positive effect on the rumen microbiota to improve sheep health.
Therapeutic efficacy of tylvalosin combined with Poria cocos polysaccharides against porcine reproductive and respiratory syndrome
Authors: Shi Hong , Luo Wentao , Wang Shuaiyang , Dai Jun , Chen Cuilan , Li Shuo , Liu Jie , Zhang Weiyuan , Huang Qi , Zhou Rui
Published: August 2023

Porcine reproductive and respiratory syndrome (PRRS) is one of the most economically important infectious diseases of pigs worldwide. Vaccination and various management measures have been implemented to control PRRS. However, due to high genetic diversity and insufficient understanding of the pathogenesis and immunological mechanisms, PRRS is still a challenge to the pig industry. Therefore, it is important to develop novel strategies to combat PRRS virus (PRRSV) infection. In this study, our data show that tylvalosin, a third-generation animal-specific macrolide, could inhibit PRRSV replication in MARC-145 cells, and suppress the PRRSV-induced NF-κB activation and cytokines expression. The pig infection experiment further demonstrated that tylvalosin could significantly reduce the virus loads in serum and tissues, and alleviate lung lesions of pigs infected with highly pathogenic PRRSV strains. The fever and loss of daily gain (LoDG) of the pigs were decreased as well. Considering the feature of immune suppression of PRRSV, a combination of tylvalosin with the immunopotentiator Poria cocos polysaccharides (PCP) was developed. Pig experiment showed this combination had a better therapeutic efficacy against PRRSV infection than tylvalosin and PCP alone in attenuating lung lesions, alleviating fever, and suppressing cytokines production. This study suggests that tylvalosin has significant antiviral and anti-inflammatory effects against PRRSV infection, and the combination of tylvalosin and PCP provides a promising strategy for PRRS treatment.
A Multi-Objective Tri-Level Algorithm for Hub-and-Spoke Network in Short Sea Shipping Transportation
Authors: Farmakis Panagiotis , Chassiakos Athanasios , Karatzas Stylianos
Published: August 2023

Hub-and-Spoke (H&S) network modeling is a form of transport topology optimization in which network joins are connected through intermediate hub nodes. The Short Sea Shipping (SSS) problem aims to efficiently disperse passenger flows involving multiple vessel routes and intermediary hubs through which passengers are transferred to their final destination. The problem contains elements of the Hub-and-Spoke and Travelling Salesman, with different levels of passenger flows among islands, making it more demanding than the typical H&S one, as the hub selection within nodes and the shortest routes among islands are internal optimization goals. This work introduces a multi-objective tri-level optimization algorithm for the General Network of Short Sea Shipping (GNSSS) problem to reduce travel distances and transportation costs while improving travel quality and user satisfaction, mainly by minimizing passenger hours spent on board. The analysis is performed at three levels of decisions: (a) the hub node assignment, (b) the island-to-line assignment, and (c) the island service sequence within each line. Due to the magnitude and complexity of the problem, a genetic algorithm is employed for the implementation. The algorithm performance has been tested and evaluated through several real and simulated case studies of different sizes and operational scenarios. The results indicate that the algorithm provides rational solutions in accordance with the desired sub-objectives. The multi-objective consideration leads to solutions that are quite scattered in the solution space, indicating the necessity of employing formal optimization methods. Typical Pareto diagrams present non-dominated solutions varying at a range of 30 percent in terms of the total distance traveled and more than 50 percent in relation to the cumulative passenger hours. Evaluation results further indicate satisfactory algorithm performance in terms of result stability (repeatability) and computational time requirements. In conclusion, the work provides a tool for assisting network operation and transport planning decisions by shipping companies in the directions of cost reduction and traveler service upgrade. In addition, the model can be adapted to other applications in transportation and in the supply chain.
Harnessing the Eco-Friendly Potential of Asparagus racemosus Leaf Extract Fabricated Ni/Ni(OH)2 Nanoparticles for Sustainable Seed Germination and Seedling Growth of Vigna radiata
Authors: Parveen Ashna , Sonkar Sashi , Sarangi Prakash Kumar , Singh Akhilesh Kumar , Sahoo Uttam Kumar , Gupta Rahul , Prus Piotr , Imbrea Florin , Șmuleac Laura , Pașcalău Raul
Published: August 2023

The increasing utilization of nanoparticles (NPs) in agricultural practices has led to a surge in demand for nano-based products. Herein, we investigate the dose-dependent impacts of nickel hydroxide (Ni(OH)2)/nickel (Ni) NPs, synthesized using Asparagus racemosus Linn. leaf extract, on the seed germination and growth of Vigna radiata (Linn.) Wilczek. In all seed samples, 100% germination was observed in Treatment 1 (2.74 mg mL−1) and Treatment 2 (5.48 mg mL−1) of Ni/Ni(OH)2 NPs. However, in Treatment 3 (8.22 mg mL−1) and Treatment 4 (10.96 mg mL−1), the germination percentage was lower, reaching 80%. Further, Treatment 5 (13.70 mg mL−1) of Ni/Ni(OH)2 NPs showed a reduced germination rate of 60%, indicating a prolonged germination process at higher concentrations. Remarkably, the length of seedlings showed a significant increase in all experimental treatments compared to the control group, which received 5 mL of distilled water. Among the investigated parameters, Treatment 2 demonstrated the most promising outcomes, exhibiting the highest chlorophyll stability index (23.73%) and membrane stability index (67.89%) values, as well as the lowest root ion leakage (24.75%). These findings indicate that Ni/Ni(OH)2 has the capacity to enhance seed germination and foster seedling growth.
Peripheral Vascular Disease and Carotid Artery Disease Are Associated with Decreased Bile Acid Excretion
Authors: Charach Lior , Charach Gideon , Karniel Eli , Galin Leonid , Bar Ziv Dorin , Grossman Lior , Kaye Irit , Grosskopf Itamar
Published: August 2023

Low bile acid excretion (BAE) is associated with a higher risk of coronary artery disease (CAD) and cerebrovascular disease (stroke). This study investigated BAE in patients with peripheral vascular disease (PVD) and carotid artery disease (CA) and those without these diseases, compared to patients with CAD, stroke, or no evidence of atherosclerosis. Patients with complaints of chest pain-suspected CAD, syncope, stroke/TIA, severe headache, intermittent claudication, or falls were enrolled. All received a 4-day standard diet with 490 mg of cholesterol and internal standard copper thiocyanate. Fecal BAE was measured using gas–liquid chromatography. One hundred and three patients, sixty-eight (66%) men and thirty-five women (34%), mean age range 60.9 ± 8.9 years, were enrolled in this prospective, 22-year follow-up study. Regression analysis showed that advanced age, total BAE, and excretion of the main fractions were the only significant independent factors that predicted prolonged survival (p < 0.001). Twenty-two years’ follow-up revealed only 15% of those with BAE <262.4 mg/24 h survived, compared to >60% of participants without atherosclerosis and a mean BAE of 676 mg/24 h. BAE was lower in patients with polyvascular atherosclerosis than in those with involvement of 1–3 vascular beds. Pearson correlations were found between total BAE and various fractions of BA, as well as HDL cholesterol. BAE and short-term survival were decreased among patients with PVD compared to those with CAD or stroke. Low BAE should be considered a valuable and independent risk factor for PVD.
Social Robots and Brain–Computer Interface Video Games for Dealing with Attention Deficit Hyperactivity Disorder: A Systematic Review
Authors: Cervantes José-Antonio , López Sonia , Cervantes Salvador , Hernández Aribei , Duarte Heiler
Published: August 2023

Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by inattention, hyperactivity, and impulsivity that affects a large number of young people in the world. The current treatments for children living with ADHD combine different approaches, such as pharmacological, behavioral, cognitive, and psychological treatment. However, the computer science research community has been working on developing non-pharmacological treatments based on novel technologies for dealing with ADHD. For instance, social robots are physically embodied agents with some autonomy and social interaction capabilities. Nowadays, these social robots are used in therapy sessions as a mediator between therapists and children living with ADHD. Another novel technology for dealing with ADHD is serious video games based on a brain–computer interface (BCI). These BCI video games can offer cognitive and neurofeedback training to children living with ADHD. This paper presents a systematic review of the current state of the art of these two technologies. As a result of this review, we identified the maturation level of systems based on these technologies and how they have been evaluated. Additionally, we have highlighted ethical and technological challenges that must be faced to improve these recently introduced technologies in healthcare.
Numerical Analysis and Experimental Investigation of High Cycle Fatigue Behavior in Additively Manufactured Ti–6Al–4V Alloy
Authors: Remache Djamel , Dadouaille Florimont , Lhabitant Solene , Falandry Didier , Toufine Alain , Al Ali Musaddiq , Cohen Guillaume
Published: August 2023

Additive Manufacturing (AM) of the Ti–6Al–4V alloy has gained significant importance across various industries, including biomedical, aerospace, cellular, and land vehicle applications, due to its numerous benefits. The certification of performance and reliability of AM materials, particularly for critical applications, heavily relies on evaluating fatigue strength. In this study, a numerical analysis based on the finite element method is presented to predict the High Cycle Fatigue (HCF) behavior of AM Ti–6Al–4V alloy. The investigation focuses on exploring the sensitivity of material fatigue life to surface roughness and Ultimate Tensile Strength (UTS). Uniaxial tensile and High Cycle Fatigue (HCF) tests were conducted on Ti–6Al–4V alloy samples extracted from rectangular walls manufactured using the Laser Metal Deposition (LMD) process. The walls were surface machined prior to sample extraction. Porosity and surface roughness measurements were performed on the samples. Numerical simulations of the HCF tests were carried out, considering various surface roughness ranges and UTS values. The numerical results were then compared to experimental data. The findings consistently demonstrated that higher surface roughness led to a shorter fatigue life, while higher UTS values resulted in a longer fatigue life. The numerical solutions aligned with the experimental results, indicating the efficacy of the finite element method in predicting the fatigue behavior of AM Ti–6Al–4V alloy. These insights contribute to a better understanding of the relationship between surface roughness, UTS, and fatigue life of Ti–6Al–4V alloys manufactured by AM.
Methylene Blue for the Treatment of Radiation-Induced Oral Mucositis during Head and Neck Cancer Treatment: An Uncontrolled Cohort
Authors: Roldan Carlos J. , Rosenthal David I. , Koyyalagunta Dhanalakshmi , Feng Lei , Warner Keith
Published: August 2023

Pain from radiation-therapy-induced oral mucositis during head-neck cancer treatment is aggravated by concurrent chemotherapy and commonly fails traditional treatments. To explore safe and sustainable alternatives, we investigated methylene blue oral rinse to reduce radiation-therapy-related oral mucositis pain. For this, we conducted a retrospective observational cohort study in a tertiary-care academic care cancer center including 85 patients with refractory oral mucositis pain during radiation therapy for head-neck cancer. Changes in pain (scale 0–10), oral function burden (scale 0–6) and requirement for percutaneous endoscopic gastrostomy tube placement were measured. Among 58 patients, 60% received radiation therapy alone and 40% received concurrent chemotherapy-radiation therapy. Methylene blue oral rinse (MBOR) significantly decreased oral mucositis pain for at least 6.2 h (median + SD 8 ± 1.68 before vs. 2 ± 2.20 after; p < 0.0001) and oral function burden (3.5 ± 1.33 before vs. 0 ± 0.86 after; p < 0.0001). Eleven patients (19%) had percutaneous endoscopic gastrostomy tubes placed before using methylene blue oral rinse; subsequently, four (36%) resumed oral alimentation after methylene blue oral rinse. Two patients (3%) required percutaneous endoscopic gastrostomy tubes despite methylene blue oral rinse. Minimal adverse events were reported (n = 9, 15%). Our study showed that methylene blue oral rinse was an effective and safe topical treatment for opioid-refractory oral pain from oral mucositis associated with radiation therapy for head-neck cancer.
Circulating Tumor DNA Analysis on Metastatic Prostate Cancer with Disease Progression
Authors: Bang Sungun , Won Dongju , Shin Saeam , Cho Kang Su , Park Jae Won , Lee Jongsoo , Choi Young Deuk , Kang Suwan , Lee Seung-Tae , Choi Jong Rak , Han Hyunho
Published: August 2023

The positivity rate of circulating tumor DNA (ctDNA) next-generation sequencing (NGS) varies among patients with metastatic prostate cancer (mPC), complicating its incorporation into regular practice. This retrospective study analyzed the ctDNA sequencing results of 100 mPC patients from May 2021 to March 2023 to identify the factors associated with positive ctDNA. Three custom gene panels were used for sequencing. Overall, 63% of the patients exhibited tier I/II somatic alterations, while 12% had pathogenic/likely pathogenic germline alterations. The key genes that were altered included AR, TP53, RB1, PTEN, and APC. Mutations in BRCA1/2, either germline or somatic, were observed in 21% of the patients. Among the metastatic castration-resistant prostate cancer (mCRPC) patients, the ctDNA-positive samples generally showed higher median prostate-specific antigen (PSA) levels and were more likely to be at the radiographic and clinical progressive disease stages, although they were not significantly associated with PSA progression. Our results suggest that ctDNA analysis could detect meaningful genetic changes in mPC patients, especially during disease progression.
Irisin Induces Apoptosis in Metastatic Prostate Cancer Cells and Inhibits Tumor Growth In Vivo
Authors: Alshanqiti Khalil H. , Alomar Sumayyah F. , Alzoman Nourah , Almomen Aliyah
Published: August 2023

Background: Prostate cancer is the second most common cancer in males worldwide, with αVβ5 in-tegrin, a coactivator receptor, being highly expressed in advanced prostate cancer. Irisin, a hormone secreted from skeletal muscles, can reduce cell viability and migration and potentially inhibit αVβ5. Objective: This study investigates the potential impact of irisin on prostate cancer cells and its underlying mechanism. Methods: In vitro evaluation of the antiproliferative action of irisin on metastatic prostate cancer (PC-3) cells was tested through MTT assay, flow cytometry, and Western blot. An in vivo evaluation of the antiproliferative effect on prostate cancer xenograft was evaluated in nude mice. Results: In vitro evaluations showed that irisin reduced PC-3 cell viability to 70% and increased the Annexin-V/7AAD positive cell population. Irisin altered the expression of apoptotic proteins, αVβ5, and proteins involved in the P13k-Akt pathway. In vivo, irisin inhibited tumor growth and progression, positively affecting animal well-being. In conclusion, irisin has an apoptotic effect on PC-3, possibly through altering αVβ5 and the Bcl2/BAX and P13k-Akt signaling pathway, inhibiting tumor growth in vivo. Conclusion: Our findings can serve as a foundation for further evaluation of irisin’s role in prostate cancer.
Chemoprevention of Colon Cancer by DFMO, Sulindac, and NO-Sulindac Administered Individually or in Combinations in F344 Rats
Authors: Madka Venkateshwar , Patlolla Jagan M. R. , Venkatachalam Karthikkumar , Zhang Yuting , Pathuri Gopal , Stratton Nicole , Lightfoot Stanley , Janakiram Naveena B. , Mohammed Altaf , Rao Chinthalapally V.
Published: August 2023

Non-steroidal anti-inflammatory drugs (NSAIDs) are promising colorectal cancer (CRC) chemopreventive drugs; however, to overcome NSAIDs’ associated side effects, there is a need to develop safer and efficacious approaches. The present study was designed to evaluate (i) the efficacy of nitric-oxide releasing (NO)-Sulindac as compared to Sulindac; (ii) whether NO-Sulindac is superior to Sulindac in enhancing low-dose difluoromethylornithine (DFMO)-induced chemopreventive efficacy, and (iii) assessing the key biomarkers associated with colon tumor inhibition by these combinations. In F344 rats, colonic tumors were induced by azoxymethane (AOM). At the adenoma stage (13 weeks post AOM), groups of rats were fed the experimental diets containing 0 ppm, 500 ppm DFMO, 150 ppm Sulindac, and 200 ppm NO-Sulindac, individually or in combinations, for 36 weeks. Colon tumors were evaluated histopathologically and assayed for expression levels of proliferative, apoptotic, and inflammatory markers. Results suggest that (except for NO-Sulindac alone), DFMO, Sulindac individually, and DFMO combined with Sulindac or NO-Sulindac significantly suppressed AOM-induced adenocarcinoma incidence and multiplicities. DFMO and Sulindac suppressed adenocarcinoma multiplicity by 63% (p < 0.0001) and 51% (p < 0.0011), respectively, whereas NO-Sulindac had a modest effect (22.8%, p = 0.09). Combinations of DFMO plus Sulindac or NO-Sulindac suppressed adenocarcinoma incidence (60%, p < 0.0001; 50% p < 0.0004), and multiplicity (81%, p < 0.0001; 62%, p < 0.0001). Rats that were fed the combination of DFMO plus Sulindac showed significant inhibition of tumor cell proliferation and induction of apoptosis. In addition, enhancement of p21, Bax, and caspases; downregulation of Ki-67, VEGF, and β-catenin; and modulation of iNOS, COX-2, and ODC activities in colonic tumors were observed. These observations show that a lower-dose of DFMO and Sulindac significantly enhanced CRC chemopreventive efficacy when compared to NO-Sulindac alone, and the combination of DFMO and NO-Sulindac was modestly efficacious as compared to DFMO alone.
Tracking Therapy Response in Glioblastoma Using 1D Convolutional Neural Networks
Authors: Ortega-Martorell Sandra , Olier Ivan , Hernandez Orlando , Restrepo-Galvis Paula D. , Bellfield Ryan A. A. , Candiota Ana Paula
Published: August 2023

Background: Glioblastoma (GB) is a malignant brain tumour that is challenging to treat, often relapsing even after aggressive therapy. Evaluating therapy response relies on magnetic resonance imaging (MRI) following the Response Assessment in Neuro-Oncology (RANO) criteria. However, early assessment is hindered by phenomena such as pseudoprogression and pseudoresponse. Magnetic resonance spectroscopy (MRS/MRSI) provides metabolomics information but is underutilised due to a lack of familiarity and standardisation. Methods: This study explores the potential of spectroscopic imaging (MRSI) in combination with several machine learning approaches, including one-dimensional convolutional neural networks (1D-CNNs), to improve therapy response assessment. Preclinical GB (GL261-bearing mice) were studied for method optimisation and validation. Results: The proposed 1D-CNN models successfully identify different regions of tumours sampled by MRSI, i.e., normal brain (N), control/unresponsive tumour (T), and tumour responding to treatment (R). Class activation maps using Grad-CAM enabled the study of the key areas relevant to the models, providing model explainability. The generated colour-coded maps showing the N, T and R regions were highly accurate (according to Dice scores) when compared against ground truth and outperformed our previous method. Conclusions: The proposed methodology may provide new and better opportunities for therapy response assessment, potentially providing earlier hints of tumour relapsing stages.
Learning Needs of Patients with Cancer and a Pre-Existing Autoimmune Disease Who Are Candidates to Receive Immune Checkpoint Inhibitors
Authors: Lopez-Olivo Maria A. , Kachira Johncy J. , Buni Maryam , Kim Sang Taek , Lu Huifang , Tayar Jean H. , Duhon Gabrielle F. , Ruiz Juan I. , Bingham Clifton O. , Calabrese Cassandra , Volk Robert J. , Suarez-Almazor Maria E.
Published: August 2023

Patients with pre-existing autoimmune disorders and cancer considering immune checkpoint inhibitors (ICIs) need to receive balanced information about the benefits and risk of developing immune-related adverse events (irAEs) and flare-ups of their autoimmune disease. To assess the learning needs of patients with cancer and pre-existing autoimmune disease regarding ICI treatment, we interviewed 29 patients with autoimmune disease and cancer from a comprehensive cancer center, of whom 20 had received ICI and 9 were candidates to receive ICI at a US Cancer Center. In-depth semi-structured interviews were conducted from August 2021 and January 2022. Interviewee’s opinions and preferences about content and information delivery methods were collected. We recorded and transcribed interviews and analyzed them using thematic analysis. Half of the participants were female, and their median (SD) age was 62.9 (±10.9) years. The identified health information needs included the following: (1) information on irAEs and autoimmune disease flare-ups; (2) benefits of ICI; (3) ICI mechanism in the context of autoimmune disease; (4) management of flare-ups; (5) reasons for stopping or modifying cancer or autoimmune disease treatment; (6) likelihood of autoimmune disease progression or organ damage; and (7) lifestyle changes that could help avoid irAEs. Patients who had received ICI and those who had not yet received treatment reported similar needs, although patients who had received ICI had more questions about cancer treatment modifications. Patients also expressed the need to better understand when to contact their provider and how to share information with multiple providers. Most patients wanted to receive information in visual formats for review at home and at their own pace. Patients expressed interest in having educational tools to facilitate shared decision-making with their physicians, and they identified several areas of health information concerning therapy with ICI. They also highlighted the importance of communication among their various providers.
Α Humanized RANKL Transgenic Mouse Model of Progestin-Induced Mammary Carcinogenesis for Evaluation of Novel Therapeutics
Authors: Kolokotroni Anthi , Gkikopoulou Evi , Rinotas Vagelis , Ntari Lydia , Zareifi Danae , Rouchota Maritina , Sarpaki Sophia , Lymperopoulos Ilias , Alexopoulos Leonidas G. , Loudos George , Denis Maria C. , Karagianni Niki , Douni Eleni
Published: August 2023

Receptor activator of nuclear factor-κB ligand (RANKL) is critically involved in mammary gland pathophysiology, while its pharmaceutical inhibition is being currently investigated in breast cancer. Herein, we investigated whether the overexpression of human RANKL in transgenic mice affects hormone-induced mammary carcinogenesis, and evaluated the efficacy of anti-RANKL treatments, such as OPG-Fc targeting both human and mouse RANKL or Denosumab against human RANKL. We established novel MPA/DMBA-driven mammary carcinogenesis models in TgRANKL mice that express both human and mouse RANKL, as well as in humanized humTgRANKL mice expressing only human RANKL, and compared them to MPA/DMBA-treated wild-type (WT) mice. Our results show that TgRANKL and WT mice have similar levels of susceptibility to mammary carcinogenesis, while OPG-Fc treatment restored mammary ductal density, and prevented ductal branching and the formation of neoplastic foci in both genotypes. humTgRANKL mice also developed MPA/DMBA-induced tumors with similar incidence and burden to those of WT and TgRANKL mice. The prophylactic treatment of humTgRANKL mice with Denosumab significantly prevented the rate of appearance of mammary tumors from 86.7% to 15.4% and the early stages of carcinogenesis, whereas therapeutic treatment did not lead to any significant attenuation of tumor incidence or tumor burden compared to control mice, suggesting the importance of RANKL primarily in the initial stages of tumorigenesis. Overall, we provide unique genetic tools for investigating the involvement of RANKL in breast carcinogenesis, and allow the preclinical evaluation of novel therapeutics that target hormone-related breast cancers.
Assessing Osteolytic Lesion Size on Sequential CT Scans Is a Reliable Study Endpoint for Bone Remineralization in Newly Diagnosed Multiple Myeloma
Authors: Grunz Jan-Peter , Kunz Andreas Steven , Baumann Freerk T. , Hasenclever Dirk , Sieren Malte Maria , Heldmann Stefan , Bley Thorsten Alexander , Einsele Hermann , Knop Stefan , Jundt Franziska
Published: August 2023

Multiple myeloma (MM) frequently induces persisting osteolytic manifestations despite hematologic treatment response. This study aimed to establish a biometrically valid study endpoint for bone remineralization through quantitative and qualitative analyses in sequential CT scans. Twenty patients (seven women, 58 ± 8 years) with newly diagnosed MM received standardized induction therapy comprising the anti-SLAMF7 antibody elotuzumab, carfilzomib, lenalidomide, and dexamethasone (E-KRd). All patients underwent whole-body low-dose CT scans before and after six cycles of E-KRd. Two radiologists independently recorded osteolytic lesion sizes, as well as the presence of cortical destruction, pathologic fractures, rim and trabecular sclerosis. Bland–Altman analyses and Krippendorff’s α were employed to assess inter-reader reliability, which was high for lesion size measurement (standard error 1.2 mm) and all qualitative criteria assessed (α ≥ 0.74). After six cycles of E-KRd induction, osteolytic lesion size decreased by 22% (p < 0.001). While lesion size response did not correlate with the initial lesion size at baseline imaging (Pearson’s r = 0.144), logistic regression analysis revealed that the majority of responding osteolyses exhibited trabecular sclerosis (p < 0.001). The sum of osteolytic lesion sizes on sequential CT scans defines a reliable study endpoint to characterize bone remineralization. Patient level response is strongly associated with the presence of trabecular sclerosis.