bluuebunny/crossref_metadata_2025 huggingface dataset:
Dietary inflammatory index and the risks of non-alcoholic fatty liver disease: a systematic review and meta-analysis
Authors: Zhang Xingfen , Ruan Jiale , He Yujing , Xu Anyi , Fang Yingying , Zhang Qiufeng , Gu Lihu , Liu Xingchen
Published: July 2024

Background

Previous studies have suggested a correlation between dietary inflammatory potential and non-alcoholic fatty liver disease (NAFLD). Therefore, the study aimed to investigate the association between dietary inflammatory potential, measured by the dietary inflammation index (DII), and NAFLD.

Methods

From establishing the database to June 2023, a systematic search of PubMed, Web of Science, Embase and Cochrane Library were performed to identify relevant observational studies. These studies reported a correlation between DII and NAFLD. The meta-analysis used odds ratio (OR) with 95% confidence intervals (CI) to evaluate the relationship between DII and NAFLD.

Results

Eight studies were included in this meta-analysis after excluding irrelevant records. A summary of the results from the included studies showed that the risk of NAFLD was higher in those exposed to higher DII (OR = 1.26, 95%CI 1.12 to 1.40, p < 0.001), with a high degree of heterogeneity (I2 = 85.7%, p < 0.001). When DII was divided into 3 tertiles from low to high for comparison, the results showed that the risk of NAFLD was higher in Tertile 2 (T2) population compared to the Tertile 1 (T1) population (OR = 1.75, 95%CI 1.20 to 2.54, p < 0.005). The risk of NAFLD was significantly higher in Tertile 3 (T3) compared to the T1 population (OR = 3.07, 95%CI 1.63 to 5.77, p = 0.001).

Conclusion

The results suggest that high DII is associated with an increased risk of NAFLD, and conversely, low DII is associated with a decreased risk of NAFLD.

Systematic Review Registration

The study complies with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and is registered on PROSPERO (CRD42023455013).
Denosumab combined with chemotherapy followed by anlotinib in the treatment of multiple metastases of malignant peripheral nerve sheath tumor: a case report and literature review
Authors: Chen Qian , Cui Haocheng , Zheng Kai , Xu Ming , Yu Xiuchun
Published: July 2024

Primary intraosseous malignant peripheral nerve sheath tumors (MPNSTs) are rare yet highly aggressive neoplasms originating from peripheral nerves. Typically manifesting as soft tissue masses accompanied by pain or functional impairment, these tumors pose significant challenges in management. Surgical intervention remains the cornerstone of treatment for patients with MPNST lacking distant metastasis, with generally modest success rates. In cases of recurrence and metastasis, the pursuit of effective systemic therapies has been a focus of clinical investigation. Herein, we present a case study involving an elderly female patient with refractory MPNST. In light of surgical limitations, a multimodal therapeutic approach combining chemotherapy, denosumab, and subsequent administration of anlotinib was pursued following collaborative consultation. This regimen yielded noteworthy clinical benefits, exemplifying a promising avenue in the management of challenging MPNST cases.
Trabectedin may be a valuable treatment option for elderly patients with metastatic soft tissue sarcomas
Authors: Miolo Gianmaria , Buonadonna Angela , Lombardi Davide , Scalone Simona , Lauretta Andrea , Della Puppa Lara , Corona Giuseppe
Published: July 2024

Background

In the landscape of metastatic soft tissue sarcoma (mSTS) treatment, anthracyclines have shown efficacy; however, their associated toxicity imposes significant limitations, especially in frail elderly patients with mSTS who are highly susceptible to severe adverse effects. In this context, trabectedin, due to its distinct pharmacological profile and safety profile, may represent an interesting alternative being demonstrated to be active in treating mSTS. These features hold particular significance for elderly and unfit patients with mSTS, where balancing treatment benefits with potential adverse effects represents the pivotal objective.

Methods

The investigation was focused on a specific group of 11 elderly patients with mSTS aged ≥70, all undergoing first-line treatment with trabectedin, and it was supported by comprehensive pharmacokinetic and pharmacodynamic studies. Among these patients, 9 out of 11 started the treatment at a dose of 1.5 mg/m2.

Results

The primary objective of this investigation is to highlight trabectedin as a valuable first-line treatment option for elderly and unfit patients with mSTS. Additionally, this investigation seeks to explore whether higher administered doses of trabectedin can enhance clinical outcomes while maintaining the same toxicity profiles. The median progression-free survival (PFS) was 77 days (95% CI, 53–89), the median overall survival (OS) was 397 days (95% CI, 66–2,102), while the overall toxicity of grade 3–4 severity amounted to 43%.

Conclusion

These findings provide new insights into the clinical outcomes and toxicity associated with trabectedin in an elderly patient population, enhancing our understanding of better treatment approaches for a specific population of patients with mSTS.
The development of prosodic focus marking in French
Authors: Destruel Emilie , Lalande Louise , Chen Aoju
Published: July 2024

Introduction

French is traditionally described as a language favoring syntactic means to mark focus, yet recent research shows that prosody is also used. We examine how French-speaking children use prosody to realize narrow focus and contrastive focus in the absence of syntactic means, compared to adults.

Method

We elicited SVO sentences using a virtual robot-mediated picture-matching task from monolingual French-speaking adults (N = 11), 4- to 5-year-olds (N = 12), and 7- to 8-year-olds (N = 15). These sentences were produced with narrow focus on either the subject or the object and contrastive focus on the object.

Results

Linear mixed-effects logistic regression modeling on duration, mean intensity, mean pitch, and pitch range of the subject and object nouns showed that the 4- to 5-year-olds did not use any of these prosodic cues for focus marking but the 7- to 8-year-olds distinguished narrow focus from non-focus through an increase in duration, mean intensity and to a lesser degree, mean pitch in the object nouns, largely similar to the adults, and tended to use mean pitch for this purpose in the subject nouns, different from the adults, who used duration.

Discussion

Our study corroborates previous findings that French-speaking 4- to 5-year-olds do not use prosody for focus. Further, it provides new evidence that 7- to 8-year-olds use prosody to mark narrow focus on the object in a more adult-like manner than narrow focus on the subject, arguably caused by a more dominant role of syntactic means in the subject position in French. Together, these findings show that syntax-dominance can influence both the route and the rate of acquisition of prosodic focus marking.
A brief research report of suicide rates in the Brazilian elderly over a 12-year period: the lack of association of the "Setembro Amarelo" campaign for suicide prevention
Authors: Corrêa Matias Pereira Camila , Najafi Moghaddam Gilani Vahid , Nazif-Munoz José Ignacio
Published: July 2024

Objectives

Aiming to disseminate information related to suicide prevention in Brazil, the “Setembro Amarelo” campaign has been conducted since 2015. The objective of this study is to assess the association between this campaign and elderly suicide rates over a 12-year period.

Methods

Data were gathered from the Mortality Information System and the Notifiable Diseases Information System, established by public institutions in Brazil. An interrupted time-series framework was applied to assess the association between the “Setembro Amarelo” campaign and suicide mortality rates in the elderly population (60 et plus) in the southeastern region of Brazil. We consider three monthly outcomes: all suicides, suicides in males and suicide in females. We operationalize the campaign assuming three effects: short-term, declining and sustained. The period of analysis was from 2011-2022.

Results

The suicide-mortality rate over time has remained stable; the average rate in the pre-campaign period was 0.028 and increased slightly to 0.035. Regardless of the campaign’s operationalization and the outcome used, results show no significant associations between the campaign and elderly suicide rates. The campaign was associated with non-significant decreased effects of 15% (P=0.532) in the short term, and 16% (P=0.446) assuming the campaign was sustained.

Conclusions

There is a lack of association between the campaign and suicide rates, among the elderly in Brazil’s southeastern region. As suicide is complex and multifactorial, more research is needed. The campaign, while raising awareness and reducing stigma, may not reduce suicides. To reduce the suicide rate in the elderly requires addressing social, economic and cultural factors, multisectoral interventions, and upholding basic human rights.
Doctor AI? A pilot study examining responses of artificial intelligence to common questions asked by geriatric patients
Authors: Moore Ian , Magnante Christopher , Embry Ellie , Mathis Jennifer , Mooney Scott , Haj-Hassan Shereen , Cottingham Maria , Padala Prasad R.
Published: July 2024

Introduction

AI technologies have the potential to transform patient care. AI has been used to aid in differential diagnosis and treatment planning for psychiatric disorders, administer therapeutic protocols, assist with interpretation of cognitive testing, and patient treatment planning. Despite advancements, AI has notable limitations and remains understudied and further research on its strengths and limitations in patient care is required. This study explored the responses of AI (Chat-GPT 3.5) and trained clinicians to commonly asked patient questions.

Methods

Three clinicians and AI provided responses to five dementia/geriatric healthcare-related questions. Responses were analyzed by a fourth, blinded clinician for clarity, accuracy, relevance, depth, and ease of understanding and to determine which response was AI generated.

Results

AI responses were rated highest in ease of understanding and depth across all responses and tied for first for clarity, accuracy, and relevance. The rating for AI generated responses was 4.6/5 (SD = 0.26); the clinician s' responses were 4.3 (SD = 0.67), 4.2 (SD = 0.52), and 3.9 (SD = 0.59), respectively. The AI generated answers were identified in 4/5 instances.

Conclusions

AI responses were rated more highly and consistently on each question individually and overall than clinician answers demonstrating that AI could produce good responses to potential patient questions. However, AI responses were easily distinguishable from those of clinicians. Although AI has the potential to positively impact healthcare, concerns are raised regarding difficulties discerning AI from human generated material, the increased potential for proliferation of misinformation, data security concerns, and more.
Re-naturalizing the built environment. Plants, architecture, and pedagogy in contemporary green schools
Authors: Chiesi Leonardo , Costa Paolo , Ciaravella Fabio , Galmarini Bianca
Published: July 2024

This study discusses the essential need of re-naturalizing the built environment, focusing on schools. Leveraging research on the impact of nature on health, children’s development, and learning, we analyze case studies from America, Asia, and Europe with distinct trajectories of interplay between architecture and pedagogy. Using a theoretical framework on plant-architecture relationship, we identify effective re-naturalization solutions in some applications of biophilic design in rural and urban contexts, cautioning against superficial nature incorporations in schools. Our study asserts that technological sustainability is needed but insufficient, emphasizing the necessity of concurrent efforts in architecture and education to create meaningful student-nature connections.
Twin transformation as a strategic approach in sport management: the synergy of digitalization and sustainability in sports
Authors: Glebova Ekaterina , Madsen Dag Øivind
Published: July 2024

The integration of digitalization and sustainability principles, encapsulated within the Twin Transformation (TT) approach, has emerged as a transformative paradigm within sport management. However, there is a critical gap in understanding how these two transformative forces can be synergistically harnessed within the field of sport management. This paper explores the conceptual underpinnings of TT and its implications for enhancing organizational performance and addressing contemporary challenges in the sports industry. Drawing upon interdisciplinary perspectives, the paper examines how TT fosters innovation, enhances fan engagement, and promotes environmental responsibility within sport management. Through a synthesis of theoretical insights and practical examples, the paper highlights the potential of TT to drive positive change across various facets of sport management, from operational practices to stakeholder engagement. Furthermore, the paper underscores the importance of ongoing research and scholarly inquiry in advancing our understanding of TT and its implications for theory and practice in sport management. Overall, this paper provides a comprehensive overview of TT in sport management, offering valuable insights for researchers, practitioners, and stakeholders seeking to navigate the dynamic landscape of the sports industry.
Aftercare Provision for Bereaved Relatives Following Euthanasia or Physician-Assisted Suicide: A Cross-Sectional Questionnaire Study Among Physicians
Authors: Renckens Sophie C. , Pasman H. Roeline , van der Heide Agnes , Onwuteaka-Philipsen Bregje D.
Published: July 2024

Objectives: Relatives of patients who died after euthanasia or physician-assisted suicide (EAS) might need (specific) aftercare. We examined if and how physicians provide aftercare to bereaved relatives of patients who died after EAS, and which patient-, physician- and process characteristics are associated with providing aftercare.

Methods: A cross-sectional questionnaire study was conducted among 127 physicians (general practitioners, clinical specialists, and elderly care physicians) in the Netherlands. Associations were examined using multivariable logistic regression analyses.

Results: Most physicians had had at least one follow-up conversation with bereaved relatives (77.2%). Clinical specialists less often provided aftercare compared to GPs. Also, aftercare was more often provided when the deceased had a cohabiting partner. Topics addressed during aftercare conversations included looking back on practical aspects of the EAS trajectory, the emotional experience of relatives during the EAS trajectory and relatives’ current mental wellbeing. A minority of aftercare conversations led to referral to additional care (6.3%).

Conclusion: Aftercare conversations with a physician covering a wide-range of topics are likely to be valuable for all bereaved relatives, and not just for “at risk” populations typically targeted by policies and guidelines.
Enhancing Indoor Positioning Accuracy with WLAN and WSN: A QPSO Hybrid Algorithm with Surface Tessellation
Authors: Scavino Edgar , Abd Rahman Mohd Amiruddin , Farid Zahid , Ahmad Sadique , Asim Muhammad
Published: July 2024

In large indoor environments, accurate positioning and tracking of people and autonomous equipment have become essential requirements. The application of increasingly automated moving transportation units in large indoor spaces demands a precise knowledge of their positions, for both efficiency and safety reasons. Moreover, satellite-based Global Positioning System (GPS) signals are likely to be unusable in deep indoor spaces, and technologies like WiFi and Bluetooth are susceptible to signal noise and fading effects. For these reasons, a hybrid approach that employs at least two different signal typologies proved to be more effective, resilient, robust, and accurate in determining localization in indoor environments. This paper proposes an improved hybrid technique that implements fingerprinting-based indoor positioning using Received Signal Strength (RSS) information from available Wireless Local Area Network (WLAN) access points and Wireless Sensor Network (WSN) technology. Six signals were recorded on a regular grid of anchor points covering the research surface. For optimization purposes, appropriate raw signal weighing was applied in accordance with previous research on the same data. The novel approach in this work consisted of performing a virtual tessellation of the considered indoor surface with a regular set of tiles encompassing the whole area. The optimization process was focused on varying the size of the tiles as well as their relative position concerning the signal acquisition grid, with the goal of minimizing the average distance error based on tile identification accuracy. The optimization process was conducted using a standard Quantum Particle Swarm Optimization (QPSO), while the position error estimate for each tile configuration was performed using a 3-layer Multilayer Perceptron (MLP) neural network. These experimental results showed a 16% reduction in the positioning error when a suitable tile configuration was calculated in the optimization process. Our final achieved value of 0.611 m of location incertitude shows a sensible improvement compared to our previous results.
An Overview of Long-Acting GnRH Agonists in Premenopausal Breast Cancer Patients: Survivorship Challenges and Management
Authors: LeVasseur Nathalie , Manna Mita , Jerzak Katarzyna J.
Published: July 2024

Managing breast cancer in premenopausal women poses unique challenges due to its considerable effect on both morbidity and mortality. Goserelin, a gonadotropin-releasing hormone agonist, has emerged among the various modalities as a preferred option for ovarian function suppression, owing to its efficacy in reducing ovarian estrogen production in premenopausal women with hormone receptor-positive breast cancer. Recent studies have affirmed the efficacy and safety of long-acting (LA) goserelin 10.8 mg every 12 weeks, offering comparable outcomes to monthly injections. This flexibility enables personalized treatment approaches, potentially enhancing patient satisfaction. Off-label utilization of goserelin LA surged during the coronavirus disease pandemic, prompting initiatives to broaden its use for breast cancer treatment. Switching to goserelin LA can streamline treatment, boost adherence, and optimize resource utilization. With the recent approval of goserelin 10.8 mg LA by Health Canada on 6 May 2024, for use in breast cancer, Canada is the latest to join over 60 countries worldwide to expand the accepted indications for goserelin LA and ensure its availability to potentially enhance healthcare delivery, patient care, and breast cancer outcomes. Goserelin LA offers premenopausal patients a means to more effectively manage the constraints imposed by breast cancer treatment and its impact on survivorship.
Northern Hemisphere Glaciation: Its Tectonic Origin in the Neogene Uplift
Authors: Ou Hsien-Wang
Published: July 2024

The Earth has cooled since the early Pliocene, which was punctuated by accelerated cooling indicative of thresholds. I posit that the cooling was initiated when the Neogene uplift of the Tibetan highland caused it to ice over, augmenting the albedo. I formulate a minimal warm/cold/Arctic box model to test this hypothesis and prognose the Pliocene climate. In particular, based on model physics, I discern three thermal thresholds as Pliocene cools: (1) when the Arctic temperature falls below the marking temperature of the ice front, the East Greenland ice sheet would descend to the sea level and calve into the Nordic Seas; (2) when the Arctic temperature cools to the freezing point, the ice sheet would form and expand over circum-Arctic lowlands to cause a massive deposition of ice-rafted debris marking Northern Hemisphere glaciation (NHG); (3) when glacial state persists through low eccentricity, it would cause a transition from obliquity- to eccentricity-dominated glacial cycles. Aligning these thresholds with the observed ones around 3.5, 2.7, and 1 million years ago, the model produces a temporal evolution of the Pliocene temperature as well as its driving albedo change. Since the latter can be accommodated by the observed one, it supports the Neogene uplift as the tectonic origin of NHG.
Impacts of a Prescribed Physical Activity Program for People with Chronic Diseases Living in Community Settings in France
Authors: Martinez Christophe , Goncalves Aurélie , Coste Olivier , Pabion Sarah , Charbonnier Elodie
Published: July 2024

Background: Sedentary behavior and physical inactivity are modifiable risk factors at the forefront of prevention and health promotion strategies. The health benefits of physical activity (PA) have been widely demonstrated in chronic diseases and have led to the prescription of adapted PA. To date, French scientific data are insufficient to evaluate the effectiveness of prescribing adapted PA. This study aimed (1) to evaluate the effectiveness of a community-based program and (2) to identify patient characteristics at inclusion that could be associated with improved post-program anthropometric data. Methods: Our sample was composed of 113 participants with a chronic disease (83.18% women) with a mean age of 55.4 ± 13.9 years. Participants benefited from an 8-week adapted PA program. All participants were evaluated at the beginning and end of the program by anthropometric measurements, a subjective measure of the level of PA and a measure of physical condition. Results: Almost 86% of the participants were overweight and two-thirds were obese. Statistical analyses showed a significant improvement in physical condition, expressed by a better cardiorespiratory endurance (up to +14% for a 2 min walk test; MT0 = 78.1 m vs. MT1 = 89 m; p < 0.001 with a 2 min walk test), improved flexibility (+12.5%; MT0 = 2.4 vs. MT1 = 2.7; p < 0.001), and increased muscle strength in the lower limbs (+22.7%; MT0 = 11.9 vs. MT1 = 14.6; p < 0.001). The level of physical activity increased significantly for all participants (57.52% of inactive individuals at T0 vs. 5.31% at T1; p = 0.004). Correlational analyses revealed that the decrease in BMI and weight throughout the program correlated positively with age (r = 0.252 and p = 0.007, and r = 0.247 and p = 0.008, respectively) and negatively with BMI from baseline (r = −0.271; p = 0.004). Conclusions: The key points of this community-based PA program are the following: (1) It improves participants’ physical condition. (2) It improves anthropometric parameters. (3) It modifies physical activity behavior. Furthermore, in the context of the program set up specifically for this purpose, it would appear that elderly and overweight people are more likely to exhibit beneficial effects on anthropometric parameters than younger participants or those with a high level of obesity. However, these results need to be confirmed by a long-term evaluation of the effectiveness of such devices.
Creating and Reliving the Moment: Using Musical Improvisation and Care Aesthetics as a Lens of Connection and Self-Expression for Younger People Living with Dementia
Authors: Dowlen Robyn , McPherson Dougal Henry James , Swarbrick Caroline , Hoskin Lizzie , Thompson James , Keady John
Published: July 2024

Musical improvisation is a generative process of spontaneously creating music ‘in the moment’. For people with young onset dementia, musical improvisation provides an extended opportunity for creative self-expression and connection to one’s own body and life story. Using visual research methods, including video elicitation interviews, this paper explores the ‘in the moment’ musical experiences of five people living with young onset dementia who took part in a 15-week improvised music-making programme (Music in Mind). We frame the exploration of the group’s musical experiences through the emerging lens of ‘care aesthetics’—a concept that identifies the sensory relations and embodied practices between two (or more) people in a caring relationship. In the context of this analysis, we look to the caring practices by, with, and between people living with dementia, their family members, and the musicians who lead the programme and the relationship of these practices to feelings of self-expression and meaningful connection. Musical improvisation has the potential to support the psychological, social, and spiritual wellbeing of people living with young onset dementia. In applying a lens of care aesthetics, it is possible to observe the micro-level experiences of people living with dementia and their family carers.
New Target(s) for RNF43 Regulation: Implications for Therapeutic Strategies
Authors: Nag Jeetendra Kumar , Appasamy Priyanga , Malka Hodaya , Sedley Shoshana , Bar-Shavit Rachel
Published: July 2024

Cancer cells depend on specific oncogenic pathways or present a genetic alteration that leads to a particular disturbance. Still, personalized and targeted biological therapy remains challenging, with current efforts generally yielding disappointing results. Carefully assessing onco-target molecular pathways can, however, potently assist with such efforts for the selection of patient populations that would best respond to a given drug treatment. RNF43, an E3 ubiquitin ligase that negatively regulates Wnt/frizzled (FZD) receptors by their ubiquitination, internalization, and degradation, controls a key pathway in cancer. Recently, additional target proteins of RNF43 were described, including p85 of the PI3K/AKT/mTOR signaling pathway and protease-activated receptor 2 (PAR2), a G-protein-coupled receptor that potently induces β-catenin stabilization, independent of Wnts. RNF43 mutations with impaired E3 ligase activity were found in several types of cancers (e.g., gastrointestinal system tumors and endometrial and ovarian cancer), pointing to a high dependency on FZD receptors and possibly PAR2 and the PI3K/AKT/mTOR signaling pathway. The development of drugs toward these targets is essential for improved treatment of cancer patients.
Severe Hypothermia Induces Ferroptosis in Cerebral Cortical Nerve Cells
Authors: Lu Chao-Long , Sha Jing-Jing , Ma Ru-Fei , Dong Xue-Tong , Su Xiao-Rui , Cong Bin , Wang Song-Jun
Published: July 2024

Abnormal shifts in global climate, leading to extreme weather, significantly threaten the safety of individuals involved in outdoor activities. Hypothermia-induced coma or death frequently occurs in clinical and forensic settings. Despite this, the precise mechanism of central nervous system injury due to hypothermia remains unclear, hindering the development of targeted clinical treatments and specific forensic diagnostic indicators. The GEO database was searched to identify datasets related to hypothermia. Post-bioinformatics analyses, DEGs, and ferroptosis-related DEGs (FerrDEGs) were intersected. GSEA was then conducted to elucidate the functions of the Ferr-related genes. Animal experiments conducted in this study demonstrated that hypothermia, compared to the control treatment, can induce significant alterations in iron death-related genes such as PPARG, SCD, ADIPOQ, SAT1, EGR1, and HMOX1 in cerebral cortex nerve cells. These changes lead to iron ion accumulation, lipid peroxidation, and marked expression of iron death-related proteins. The application of the iron death inhibitor Ferrostatin-1 (Fer-1) effectively modulates the expression of these genes, reduces lipid peroxidation, and improves the expression of iron death-related proteins. Severe hypothermia disrupts the metabolism of cerebral cortex nerve cells, causing significant alterations in ferroptosis-related genes. These genetic changes promote ferroptosis through multiple pathways.
Experimental Inoculation of Aggregatibacter actinomycetemcomitans and Streptococcus gordonii and Its Impact on Alveolar Bone Loss and Oral and Gut Microbiomes
Authors: Rocha Catarina Medeiros , Kawamoto Dione , Martins Fernando Henrique , Bueno Manuela Rocha , Ishikawa Karin H. , Ando-Suguimoto Ellen Sayuri , Carlucci Aline Ramos , Arroteia Leticia Sandoli , Casarin Renato V. , Saraiva Luciana , Simionato Maria Regina Lorenzetti , Mayer Marcia Pinto Alves
Published: July 2024

Oral bacteria are implicated not only in oral diseases but also in gut dysbiosis and inflammatory conditions throughout the body. The periodontal pathogen Aggregatibacter actinomycetemcomitans (Aa) often occurs in complex oral biofilms with Streptococcus gordonii (Sg), and this interaction might influence the pathogenic potential of this pathogen. This study aims to assess the impact of oral inoculation with Aa, Sg, and their association (Aa+Sg) on alveolar bone loss, oral microbiome, and their potential effects on intestinal health in a murine model. Sg and/or Aa were orally administered to C57Bl/6 mice, three times per week, for 4 weeks. Aa was also injected into the gingiva three times during the initial experimental week. After 30 days, alveolar bone loss, expression of genes related to inflammation and mucosal permeability in the intestine, serum LPS levels, and the composition of oral and intestinal microbiomes were determined. Alveolar bone resorption was detected in Aa, Sg, and Aa+Sg groups, although Aa bone levels did not differ from that of the SHAM-inoculated group. Il-1β expression was upregulated in the Aa group relative to the other infected groups, while Il-6 expression was downregulated in infected groups. Aa or Sg downregulated the expression of tight junction genes Cldn 1, Cldn 2, Ocdn, and Zo-1 whereas infection with Aa+Sg led to their upregulation, except for Cldn 1. Aa was detected in the oral biofilm of the Aa+Sg group but not in the gut. Infections altered oral and gut microbiomes. The oral biofilm of the Aa group showed increased abundance of Gammaproteobacteria, Enterobacterales, and Alloprevotella, while Sg administration enhanced the abundance of Alloprevotella and Rothia. The gut microbiome of infected groups showed reduced abundance of Erysipelotrichaceae. Infection with Aa or Sg disrupts both oral and gut microbiomes, impacting oral and gut homeostasis. While the combination of Aa with Sg promotes Aa survival in the oral cavity, it mitigates the adverse effects of Aa in the gut, suggesting a beneficial role of Sg associations in gut health.
Biologically Active Sheep Colostrum for Topical Treatment and Skin Care
Authors: Kazimierska Kinga , Szabłowska-Gadomska Ilona , Rudziński Stefan , Kośla Katarzyna , Płuciennik Elżbieta , Bobak Łukasz , Zambrowicz Aleksandra , Kalinowska-Lis Urszula
Published: July 2024

Colostrum is gaining popularity in cosmetic products. The present study compared the composition and selected biological properties of colostrum from Polish sheep (colostrum 1) and Swiss sheep (colostrum 2), particularly those that can affect healthy or diseased skin. The antioxidant activity of the colostrums was measured using ABTS and DPPH assays. The effect on the proliferation of human skin fibroblasts, neonatal epidermal keratinocytes, and human diabetic fibroblast (dHF) cells isolated from diabetic foot ulcers was also assayed in vitro by MTT and Presto Blue tests, respectively. The colostrum simulated dHF cell proliferation by up to 115.4%. The highest used concentration of colostrum 1 stimulated normal fibroblast proliferation by 191.2% (24 h) and 222.2% (48 h). Both colostrums inhibited epidermal keratinocyte viability. The influence of the colostrums on the expression of genes related to proliferation (Ki67) and immune response (IL-6, PTGS-2, TSG-6) in dHF cells were compared. Colostrum 1 increased the rate of wound closure (scar test). Analysis of total fat, protein and fatty acid content found the Polish colostrum to be a richer source of fat than the Swiss colostrum, which contained a larger amount of protein. Both colostrums exhibit properties that suggest they could be effective components in cosmetic or medicinal formulations for skin care, especially supporting its regeneration, rejuvenation, and wound healing.
Association of KRAS Mutation and Gene Pathways in Colorectal Carcinoma: A Transcriptome- and Methylome-Wide Study and Potential Implications for Therapy
Authors: Jasmine Farzana , Almazan Armando , Khamkevych Yuliia , Bissonnette Marc , Ahsan Habibul , Kibriya Muhammad G.
Published: July 2024

Kirsten Rat Sarcoma (KRAS) is the most commonly mutated oncogene in colorectal carcinoma (CRC). We have previously reported the interactions between microsatellite instability (MSI), DNA promoter methylation, and gene expression. In this study, we looked for associations between KRAS mutation, gene expression, and methylation that may help with precision medicine. Genome-wide gene expression and DNA methylation were done in paired CRC tumor and surrounding healthy tissues. The results suggested that (a) the magnitude of dysregulation of many major gene pathways in CRC was significantly greater in patients with the KRAS mutation, (b) the up- and down-regulation of these dysregulated gene pathways could be correlated with the corresponding hypo- and hyper-methylation, and (c) the up-regulation of CDKN2A was more pronounced in tumors with the KRAS mutation. A recent cell line study showed that there were higher CDKN2A levels in 5-FU-resistant CRC cells and that these could be down-regulated by Villosol. Our findings suggest the possibility of a better response to anti-CDKN2A therapy with Villosol in KRAS-mutant CRC. Also, the more marked up-regulation of genes in the proteasome pathway in CRC tissue, especially with the KRAS mutation and MSI, may suggest a potential role of a proteasome inhibitor (bortezomib, carfilzomib, or ixazomib) in selected CRC patients if necessary.
Elevated LAMTOR4 Expression Is Associated with Lethal Prostate Cancer and Its Knockdown Decreases Cell Proliferation, Invasion, and Migration In Vitro
Authors: Gamallat Yaser , Alwazan Huseen , Turko Rasoul , Dang Vincent , Seyedi Sima , Ghosh Sunita , Bismar Tarek A.
Published: July 2024

Late endosomal/lysosomal adaptor, MAPK and mTOR, or LAMTOR, is a scaffold protein complex that senses nutrients and integrates growth factor signaling. The role of LAMTOR4 in tumorigenesis is still unknown. However, there is a considerable possibility that LAMTOR4 is directly involved in tumor cell proliferation and metastasis. In the current study, we investigated the protein expression of LAMTOR4 in a cohort of 314 men who were undergoing transurethral resection of prostate (TURP) consisting of incidental, advanced and castration-resistant cases. We also correlated the data with ERG and PTEN genomic status and clinicopathological features including Gleason score and patients’ outcome. Additionally, we performed in vitro experiments utilizing knockdown of LAMTOR4 in prostate cell lines, and we performed mRNA expression assessment using TCGA prostate adenocarcinoma (TCGA-PRAD) to explore the potential differentially expressed genes and pathways associated with LAMTOR4 overexpression in PCa patients. Our data indicate that high LAMTOR4 protein expression was significantly associated with poor overall survival (OS) (HR: 1.44, CI: 1.01–2.05, p = 0.047) and unfavorable cause-specific survival (CSS) (HR: 1.71, CI: 1.06–2.77, p = 0.028). Additionally, when high LAMTOR4 expression was combined with PTEN-negative cases (score 0), we found significantly poorer OS (HR: 2.22, CI: 1.37–3.59, p = 0.001) and CSS (HR: 3.46, CI: 1.86–6.46, p < 0.0001). Furthermore, ERG-positive cases with high LAMTOR4 exhibited lower OS (HR: 1.98, CI: 1.18–3.31, p = 0.01) and CSS (HR: 2.54, CI: 1.32–4.87, p = 0.005). In vitro assessment showed that knockdown of LAMTOR4 decreases PCa cell proliferation, migration, and invasion. Our data further showed that knockdown of LAMTOR4 in the LNCaP cell line significantly dysregulated the β catenin/mTOR pathway and tumorigenesis associated pathways. Inhibiting components of the mTOR pathway, including LAMTOR4, might offer a strategy to inhibit tumor progression and metastasis in prostate cancer.
Expression of Iron Metabolism Genes Is Potentially Regulated by DOF Transcription Factors in Dendrocalamus latiflorus Leaves
Authors: Zhu Peng-Kai , Lin Mei-Xia , Zeng Mei-Yin , Tang Yu , Li Xin-Rui , He Tian-You , Zheng Yu-Shan , Chen Ling-Yan
Published: July 2024

Transcription factors (TFs) are crucial pre-transcriptional regulatory mechanisms that can modulate the expression of downstream genes by binding to their promoter regions. DOF (DNA binding with One Finger) proteins are a unique class of TFs with extensive roles in plant growth and development. Our previous research indicated that iron content varies among bamboo leaves of different colors. However, to our knowledge, genes related to iron metabolism pathways in bamboo species have not yet been studied. Therefore, in the current study, we identified iron metabolism related (IMR) genes in bamboo and determined the TFs that significantly influence them. Among these, DOFs were found to have widespread effects and potentially significant impacts on their expression. We identified specific DOF members in Dendrocalamus latiflorus with binding abilities through homology with Arabidopsis DOF proteins, and established connections between some of these members and IMR genes using RNA-seq data. Additionally, molecular docking confirmed the binding interactions between these DlDOFs and the DOF binding sites in the promoter regions of IMR genes. The co-expression relationship between the two gene sets was further validated using q-PCR experiments. This study paves the way for research into iron metabolism pathways in bamboo and lays the foundation for understanding the role of DOF TFs in D. latiflorus.
Utilizing Plasma-Based Next-Generation Sequencing to Expedite the Diagnostic Process in Suspected Lung Cancer: A Case Report
Authors: Hung Chia-Min , Wu Chen-Te , Jain Suyog , Wu Chiao-En
Published: July 2024

Lung cancer is the leading cause of cancer mortality worldwide. Fortunately, the advent of precision medicine, which includes targeted therapy and immunotherapy, offers hope. However, identifying specific mutations is imperative before initiating precise medications. Traditional methods, such as real-time PCR examination of individual mutations, are time-consuming. Contemporary techniques, such as tissue- and plasma-based next-generation sequencing (NGS), allow comprehensive genome analysis concurrently. Notably, plasma-based NGS has a shorter turnaround time (TAT) and thus a shorter time-to-treatment (TTT). In this case report, we demonstrate the benefits of plasma-based NGS before pathological diagnosis in a patient with image-suspected non-small cell lung cancer (NSCLC). An 82-year-old Taiwanese woman presented with lower back pain persisting for one month and left-sided weakness for two weeks. Whole-body computed tomography (CT) revealed lesions suspicious for brain and bone metastases, along with a mass consistent with a primary tumor in the left upper lobe, indicative of advanced NSCLC with T4N3M1c staging. The patient underwent a bronchoscopic biopsy on Day 0, and the preliminary report that came out on Day 1 was suggestive of metastatic NSCLC. Blood was also collected for plasma-based NGS on Day 0. The patient was Coronavirus disease 2019-positive and was treated with molnupiravir on Day 6. On Day 7, pathology confirmed pulmonary adenocarcinoma, and the results of plasma-based NGS included EGFR L858R mutation. The patient was started on targeted therapy (afatinib) on Day 9. Unfortunately, the patient died of hypoxic respiratory failure on Day 26, a complication of underlying viral infection. Plasma-based NGS offers a rapid and efficient means of mutation detection in NSCLC, streamlining treatment initiation and potentially improving the negative emotions of patients. Its utility, particularly in regions with a high prevalence of specific mutations, such as EGFR alterations in East Asian populations, highlights its relevance in guiding personalized therapy decisions.
Clinical Application of Blood Biomarkers in Neurodegenerative Diseases—Present and Future Perspectives
Authors: Krawczuk Daria , Kulczyńska-Przybik Agnieszka , Mroczko Barbara
Published: July 2024

Neurodegenerative diseases are a group of complex diseases characterized by a progressive loss of neurons and degeneration in different areas of the nervous system. They share similar mechanisms, such as neuroinflammation, oxidative stress, and mitochondrial injury, resulting in neuronal loss. One of the biggest challenges in diagnosing neurodegenerative diseases is their heterogeneity. Clinical symptoms are usually present in the advanced stages of the disease, thus it is essential to find optimal biomarkers that would allow early diagnosis. Due to the development of ultrasensitive methods analyzing proteins in other fluids, such as blood, huge progress has been made in the field of biomarkers for neurodegenerative diseases. The application of protein biomarker measurement has significantly influenced not only diagnosis but also prognosis, differentiation, and the development of new therapies, as it enables the recognition of early stages of disease in individuals with preclinical stages or with mild symptoms. Additionally, the introduction of biochemical markers into routine clinical practice may improve diagnosis and allow for a stratification group of people with higher risk, as well as an extension of well-being since a treatment could be started early. In this review, we focus on blood biomarkers, which could be potentially useful in the daily medical practice of selected neurodegenerative diseases.
Chitosan Extracted from the Biomass of Tenebrio molitor Larvae as a Sustainable Packaging Film
Authors: Mwita Chacha Saidi , Muhammad Riaz , Nettey-Oppong Ezekiel Edward , Enkhbayar Doljinsuren , Ali Ahmed , Ahn Jiwon , Kim Seong-Wan , Seok Young-Seek , Choi Seung Ho
Published: July 2024

Waste from non-degradable packaging materials poses a serious environmental risk and has led to interest in developing sustainable bio-based packaging materials. Sustainable packaging materials have been made from diverse naturally derived materials such as bamboo, sugarcane, and corn starch. In this study, we made a sustainable packaging film using chitosan extracted from the biomass of yellow mealworm (Tenebrio molitor) shell waste. The extracted chitosan was used to create films, cross-linked with citric acid (CA) and with the addition of glycerol to impart flexibility, using the solvent casting method. The successful cross-linking was evaluated using Fourier-Transform Infrared (FTIR) analysis. The CA cross-linked mealworm chitosan (CAMC) films exhibited improved water resistance with moisture content reduced from 19.9 to 14.5%. Improved barrier properties were also noted, with a 28.7% and 10.2% decrease in vapor permeability and vapor transmission rate, respectively. Bananas were selected for food preservation, and significant changes were observed over a duration of 10 days. Compared to the control sample, bananas packaged in CAMC pouches exhibited a lesser loss in weight because of excellent barrier properties against water vapor. Moreover, the quality and texture of bananas packaged in CAMC pouch remained intact over the duration of the experiment. This indicates that adding citric acid and glycerol to the chitosan structure holds promise for effective food wrapping and contributes to the enhancement of banana shelf life. Through this study, we concluded that chitosan film derived from mealworm biomass has potential as a valuable resource for sustainable packaging solutions, promoting the adoption of environmentally friendly practices in the food industry.
From Tooth Adhesion to Bioadhesion: Development of Bioabsorbable Putty-like Artificial Bone with Adhesive to Bone Based on the New Material “Phosphorylated Pullulan”
Authors: Nakanishi Ko , Akasaka Tsukasa , Hayashi Hiroshi , Yoshihara Kumiko , Nakamura Teppei , Nakamura Mariko , Meerbeek Bart Van , Yoshida Yasuhiro
Published: July 2024

Bioabsorbable materials have a wide range of applications, such as scaffolds for regenerative medicine and cell transplantation therapy and carriers for drug delivery systems. Therefore, although many researchers are conducting their research and development, few of them have been used in clinical practice. In addition, existing bioabsorbable materials cannot bind to the body’s tissues. If bioabsorbable materials with an adhesive ability to biological tissues can be made, they can ensure the mixture remains fixed to the affected area when mixed with artificial bone or other materials. In addition, if the filling material in the bone defect is soft and uncured, resorption is rapid, which is advantageous for bone regeneration. In this paper, the development and process of a new bioabsorbable material “Phosphorylated pullulan” and its capability as a bone replacement material were demonstrated. Phosphorylated pullulan, which was developed based on the tooth adhesion theory, is the only bioabsorbable material able to adhere to bone and teeth. The phosphorylated pullulan and β-TCP mixture is a non-hardening putty. It is useful as a new resorbable bone replacement material with an adhesive ability for bone defects around implants.
A Survey on Fused Filament Fabrication to Produce Functionally Gradient Materials
Authors: Dey Arup , Ramoni Monsuru , Yodo Nita
Published: July 2024

Fused filament fabrication (FFF) is a key extrusion-based additive manufacturing (AM) process for fabricating components from polymers and their composites. Functionally gradient materials (FGMs) exhibit spatially varying properties by modulating chemical compositions, microstructures, and design attributes, offering enhanced performance over homogeneous materials and conventional composites. These materials are pivotal in aerospace, automotive, and medical applications, where the optimization of weight, cost, and functional properties is critical. Conventional FGM manufacturing techniques are hindered by complexity, high costs, and limited precision. AM, particularly FFF, presents a promising alternative for FGM production, though its application is predominantly confined to research settings. This paper conducts an in-depth review of current FFF techniques for FGMs, evaluates the limitations of traditional methods, and discusses the challenges, opportunities, and future research trajectories in this emerging field.
Effects of Using Laser Technology for Cutting Polymer Films
Authors: Olender-Skóra Małgorzata , Banaś Wacław , Turek Marian , Skóra Paweł , Gwiazda Aleksander , Foit Krzysztof , Sękala Agnieszka , Stawowiak Michał
Published: July 2024

In connection with the need to obtain a properly made and cut material and the appearance of the surface layer, new manufacturing technologies were used for tests, namely the laser cutting technology. This article describes the laboratory stand built for the purpose of research, as well as the possibility of using laser cutting on several sample materials (polymer films), together with an indication of the results obtained. The idea was to elaborate on the cutting technology that will be proper for manufacturing the desired type of spacers for ion-exchange membranes separating while maintaining the required level of product quality and chemical purity. The latter criterion was the basic one, due to the scope of use of the manufactured elements. This article also describes the problem encountered during the construction of the stand or during the research. The last part of this article describes the further steps of the research that will be carried out in the future along with a discussion and summary of the research performed. It is important from the point of view of the development of production technology, but also because of the characteristics of materials for the production of surface layers and coatings resistant to mechanical or thermal wear used in industry. The introduction of innovative solutions is also aimed at studying the improvement of the economics of the production of materials that are significant, in particular, for small- and medium-sized enterprises.