bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Chemically and Green Synthesized Zinc Oxide Nanoparticles on Shelf Life and Sensory Quality of Minced Fish (Pangasius hypophthalmus)
Authors: Mahato Achinta , Chatterjee Paresh Nath , Sarkar Sougata , Sen Arup Ratan , Pal Aruna , Roy Sovan , Patra Amlan Kumar
Published: September 2024

The purpose of this study was to investigate the effect of chemically and green synthesized zinc oxide nanoparticles (ZnO-NPs) on the shelf life and sensory quality of fish meat. In this study, ZnO-NPs were synthesized by employing the colloidal chemistry (CZnO-NPs) and green synthesis (GZnO-NPs) methods, and they were also characterized to assess their morphology. The synthesized ZnO-NPs, ZnO, and zinc acetate (ZnA) were used for the preservation and fortification of fish (Pangasius hypophthalmus) meat at 20 mg/kg of Zn. In a six-day storage study at 4 °C, the fish samples were evaluated for their sensory attributes (color and odor), physicochemical quality (pH and total volatile base nitrogen), oxidative changes (thiobarbituric acid-reactive substances and peroxide value), and microbial loads at 0, 3, and 6 days of storage. The fortification of raw fish with the synthesized CZnO-NPs produced better sensory attributes (color and odor) and maintained a pH non-conducive to microbial growth throughout the entire storage period compared with the control, ZnO, and ZnA-fortified samples. The GZnO-NPs largely did not provide any added advantage over CZnO-NPs but sometimes responded better than the control, ZnO, and ZnA samples. Oxidative status and total volatile base nitrogen were lower for CZnO-NPs in refrigerated fish compared with the other treatments. The ZnO-NP-fortified fish had the lowest counts of total viable bacteria, coliforms, Staphylococcus spp., and Vibrio spp. Hence, the fortification of fish with synthesized CZnO-NPs is promising as a food additive to reduce microbial spoilage and lipid peroxidation of fish in storage.
Green Synthesis of ZnO Nanoparticles via Ganoderma Lucidum Extract: Structural and Functional Analysis in Polymer Composites
Authors: Can Ayça , Kızılbey Kadriye
Published: September 2024

Metallic nanoparticles are of growing interest due to their broad applications. This study presents the green synthesis of zinc oxide (ZnO) nanoparticles (ZnNPs) using Ganoderma Lucidum mushroom extract, characterized by DLS, SEM, XRD, and FTIR spectroscopy analyses. The synthesis parameters, including extract/salt ratio and mixing time, significantly influenced nanoparticle yield, size, and polydispersity, with longer mixing times leading to larger, more varied particles. Specifically, the sizes of ZnNPs synthesized at a 1:1 extract/ZnCl2 ratio after 3 h and 24 h were 90.0 nm and 243.3 nm, with PDI values of 48.69% and 51.91%, respectively. At a 1:2 ratio, the sizes were 242.3 nm at 3 h (PDI: 43.19%) and a mixture of 1.5 nm, 117.4 nm, and 647.9 nm at 24 h (PDI: 2.72%, 10.97%, and 12.43%). Polymer films incorporating PVA, chitosan, and ZnNPs were analyzed for their morphological, spectroscopic, and mechanical properties. Chitosan reduced tensile strength and elongation due to its brittleness, while ZnNPs further increased film brittleness and structural degradation. A comparison of the tensile strength of films A and C revealed that the addition of chitosan to the PVA film resulted in an approximately 10.71% decrease in tensile strength. Similarly, the analysis of films B1 and B2 showed that the tensile strength of the B2 film decreased by 10.53%. Swelling tests showed that ZnNPs initially enhanced swelling, but excessive amounts led to reduced capacity due to aggregation. This pioneering study demonstrates the potential of Ganoderma Lucidum extract in nanoparticle synthesis and provides foundational insights for future research, especially in wound dressing applications.
Molecular Targets in Streptococcus pyogenes for the Development of Anti-Virulence Agents
Authors: Cho Kyu Hong
Published: September 2024

Streptococcus pyogenes, commonly known as Group A Streptococcus (GAS), is a significant human pathogen responsible for a wide range of diseases, from mild pharyngitis to severe conditions such as necrotizing fasciitis and toxic shock syndrome. The increasing antibiotic resistance, especially against macrolide antibiotics, poses a challenge to the effective treatment of these infections. This paper reviews the current state and mechanisms of antibiotic resistance in S. pyogenes. Furthermore, molecular targets for developing anti-virulence agents, which aim to attenuate virulence rather than killing it outright, are explored. This review specifically focuses on virulence regulators, proteins that coordinate the expression of multiple virulence factors in response to environmental signals, playing a crucial role in the pathogen’s ability to cause disease. Key regulatory systems, such as RopB, Mga, CovRS, and the c-di-AMP signaling system, are discussed for their roles in modulating virulence gene expression. Additionally, potential molecular target sites for the development of anti-virulence agents are suggested. By concentrating on these regulatory pathways, it is proposed that anti-virulence strategies could enhance the effectiveness of existing antibiotics and reduce the selective pressure that drives the development of resistance.
“Physical Activity Is Not the Answer to Everything, but It Is to a Lot”: Stakeholders’ Perceived Determinants of Implementing Physical Activity Interventions for Older Adults
Authors: Boekhout Janet M. , Hut Rieteke , van Uffelen Jannique G. Z. , Czwikla Gesa , Peels Denise A.
Published: September 2024

Although many physical activity (PA) interventions for older adults have proven effective in controlled research settings, optimal implementation in real life remains challenging. This study identifies determinants perceived by stakeholders when implementing community-based PA interventions for older adults. We interviewed 31 stakeholders guided by the Consolidated Framework for Implementation Research (CFIR). Results showed that stakeholders are very specific about the role they can play in implementation, making collaboration between stakeholders crucial. Barriers and motivators were identified in the CFIR intervention characteristics domain (relative advantage, complexity and costs, evidence quality and strength, and adaptability and trialability), in the outer setting domain (cosmopolitism, patient needs, and external policy and incentives), in the inner setting domain (implementation climate, relative priority, compatibility and organizational incentives and rewards) and in the individual characteristics domain (knowledge and beliefs, and other personal attributes). An overarching theme was the stakeholders’ emphasis on aiming for broad health goals in interventions, as they perceive PA as a means to reach these goals rather than an end in itself. Another overarching theme requiring attention in future implementation efforts is the need to tailor implementation efforts to the specific needs of older adults as the end users of the intervention.
How Students Learn during the Pre-Briefing and Observation of Facilitation in a High-Fidelity Patient Simulation: A Narrative Analysis
Authors: Wong Florence
Published: September 2024

The rapid development of technology has led to the emergence of innovative teaching approaches, such as high-fidelity patient simulation (HFPS). HFPSs have been shown to significantly enhance students’ decision-making and intellectual skills. This study aimed to investigate how students learn from the pre-briefing to observation period of the facilitation of the HFPS based on the original quasi-experimental studies. This study analyzed the narratives from 92 students in the intervention group about their learning during the pre-briefing and observation of facilitation. The results indicated that the students learned more independently, received better support and resources for learning, were provided with more appropriate and safe care for the simulated case, and developed higher-level intellectual skills, such as self-directed learning, critical thinking, and clinical reasoning. Importantly, the structured guidelines provided roles and responsibilities and guiding questions or aspects for observation that directed the students to learn more actively and effectively while performing their roles in the HFPS. The structured guidelines serve as a roadmap to instruct students on learning during pre-briefing and applying what they have learned during the facilitation of the HFPS. This roadmap includes the learning journey from novice to competence in knowledge and skills and also from knowing to application. Therefore, this study’s results have contributed important knowledge about well-structured HFPS guidelines for all stages of the HFPS, addressing the need for adequate guidance and learning support during the pre-briefing and observation of facilitation. The elements identified during the pre-briefing and observation of facilitation are crucial for directing students to learn and significantly enhance their understanding and application of knowledge and skills, ultimately promoting the development of higher-level intellectual skills, professionalism, and engagement. Nurse educators can incorporate these elements into HFPS training in curricula to enhance students’ involvement and optimize the HFPS as an effective teaching tool with structured guidelines providing guidance and support throughout various stages of HFPS training.
Family Experiences of Loss and Bereavement in Palliative Care Units during the COVID-19 Pandemic: An Interpretative Phenomenological Study
Authors: Mateus Maria João , Simões Luís , Ali Amira Mohammed , Laranjeira Carlos
Published: September 2024

The COVID-19 pandemic significantly interrupted the grieving experiences of bereaved families and drastically changed their ways of dealing with loss. Our study aims to gain an in-depth understanding of the experience of bereaved relatives of patients who died in palliative care units during the COVID-19 pandemic. The phenomenological research design included sixteen family members of hospitalized palliative patients who died from November 2021 to June 2022. The study involved conducting qualitative in-depth semi-structured interviews with family members 12–24 months after the death of their loved ones. The interviews aimed to gather information about the experiences of the families both before and after the death. The COREQ guidelines were applied in the study. Participants were mainly female (n = 13) with a mean age of 47.25 (SD = 12.58). Data were analysed using the Interpretative Phenomenology Analysis (IPA). The following three categories were identified: (1) navigating loved ones’ final weeks and days (troubled deaths); (2) the last farewell was robbed; (3) looking for adjustment after loss. One overall main theme emerged, which was as follows: “Struggling between stolen moments and painful losses to get back into the flow of life”. This study provides novel insights into end-of-life care and bereavement from the perspectives of family. Our findings suggest that developing and promoting family-centred culture can lead to compassionate palliative care focused on a myriad ways of affirming that their loved one matters.
Overcoming Barriers: A Comprehensive Review of Chronic Pain Management and Accessibility Challenges in Rural America
Authors: Baker Maxwell B. , Liu Eileen C. , Bully Micaiah A. , Hsieh Adam , Nozari Ala , Tuler Marissa , Binda Dhanesh D.
Published: September 2024

In the United States (U.S.), chronic pain poses substantial challenges in rural areas where access to effective pain management can be limited. Our literature review examines chronic pain management in rural U.S. settings, identifying key issues and disparities. A comprehensive search of PubMed, Web of Science, and Google Scholar identified high-quality studies published between 2000 and 2024 on chronic pain management in the rural U.S. Data were categorized into thematic areas, including epidemiology, management challenges, current strategies, research gaps, and future directions. Key findings reveal that rural populations have a significantly higher prevalence of chronic pain and are more likely to experience severe pain. Economic and systemic barriers include a shortage of pain specialists, limited access to nonpharmacologic treatments, and inadequate insurance coverage. Rural patients are also less likely to engage in beneficial modalities like physical therapy and psychological support due to geographic isolation. Additionally, rural healthcare providers more often fulfill multiple medical roles, leading to burnout and decreased quality of care. Innovative approaches such as telehealth and integrated care models show the potential to improve access and outcomes. Our review highlights the need for increased telehealth utilization, enhanced provider education, and targeted interventions to address the specific pain needs of rural populations.
Evaluation of a Video-Based Concept for Hand Hygiene Education of Parents in a Neonatal Intensive Care Unit
Authors: Rittenschober-Böhm Judith , Strassl Johanna , Kletecka-Pulker Maria , Szerémy Péter , Haidegger Tamás , Ferenci Tamás , Berger Angelika , Wagner Michael
Published: September 2024

Background: Current clinical guidelines support family-centered care in Neonatal Intensive Care Units (NICUs). This implies parents should also be involved in the most critical patient safety measures. Hand hygiene is the single most important tool to prevent healthcare-associated infections and related long-term effects. Although often studied in healthcare workers, the hand hygiene compliance of parents is rarely assessed. The aim of this study was to evaluate the effectiveness of an educational video, available in ten different languages, in teaching parents hand hygiene techniques in a NICU, lowering the burden on the staff. Methods: Parents in the intervention group were educated through a video; the control group received personal instruction from healthcare workers. The primary outcome parameter was the predicted probability of passing a subsequent hand scan. Results: The quality of hand hygiene among parents educated through the video was at least as good as that of those who received instruction from a healthcare worker, demonstrated by a higher predicted probability of passing the hand scan (43.8% vs. 57.1% in male and 67.9% vs. 75.9% in female participants). The feedback from the intervention group was predominantly positive, with most parents (62%) expressing a preference for video-based education. Conclusion: Implementing a video-based approach seems to be effective for educating parents about hand hygiene in a NICU and was well accepted by the parents. This method offers a consistent standard of hand hygiene education, helps to overcome language barriers, and can also be used as regular reminder of the importance and proper technique of hand hygiene.
Autoimmune Diseases Following Environmental Disasters: A Narrative Review of the Literature
Authors: Mpakosi Alexandra , Cholevas Vasileios , Tzouvelekis Ioannis , Passos Ioannis , Kaliouli-Antonopoulou Christiana , Mironidou-Tzouveleki Maria
Published: September 2024

Environmental disasters are extreme environmental processes such as earthquakes, volcanic eruptions, landslides, tsunamis, floods, cyclones, storms, wildfires and droughts that are the consequences of the climate crisis due to human intervention in the environment. Their effects on human health have alarmed the global scientific community. Among them, autoimmune diseases, a heterogeneous group of disorders, have increased dramatically in many parts of the world, likely as a result of changes in our exposure to environmental factors. However, only a limited number of studies have attempted to discover and analyze the complex association between environmental disasters and autoimmune diseases. This narrative review has therefore tried to fill this gap. First of all, the activation pathways of autoimmunity after environmental disasters have been analyzed. It has also been shown that wildfires, earthquakes, desert dust storms and volcanic eruptions may damage human health and induce autoimmune responses to inhaled PM2.5, mainly through oxidative stress pathways, increased pro-inflammatory cytokines and epithelial barrier damage. In addition, it has been shown that heat stress, in addition to increasing pro-inflammatory cytokines, may also disrupt the intestinal barrier, thereby increasing its permeability to toxins and pathogens or inducing epigenetic changes. In addition, toxic volcanic elements may accelerate the progressive destruction of myelin, which may potentially trigger multiple sclerosis. The complex and diverse mechanisms by which vector-borne, water-, food-, and rodent-borne diseases that often follow environmental diseases may also trigger autoimmune responses have also been described. In addition, the association between post-disaster stress and the onset or worsening of autoimmune disease has been demonstrated. Given all of the above, the rapid restoration of post-disaster health services to mitigate the flare-up of autoimmune conditions is critical.
eHealth Platforms Facilitate Prostate Cancer Shared Care: A Systematic Review
Authors: Homewood David C. , Mcdonald Jodie , Valaydon Zina , Ogluszko Cindy , Sukocheva Olga A. , Tse Edmund , Corcoran Niall M. , Iyngkaran Guru
Published: September 2024

Background: Prostate cancer survivorship care is essential for the early identification of cancer recurrence and progression and the monitoring of adverse effects. Prostate cancer survivorship programs have enabled care to be shared between specialists using digital healthcare platforms. We systematically reviewed the literature to examine if prostate cancer survivorship care had been successfully digitalised. Methods: English language articles were searched on PubMed, Embase, and Cochrane Libraries. The search terms included combinations of “eHealth”, “digital health”, “prostate cancer”, “shared care”, and related keywords (studies published between [1 January 1946 and 20 March 2023]). Results: Our search strategy yielded 1722 publications, of which 17 studies were included in our final review. Diverse eHealth interventions (web platforms, apps, patient portals) for digital prostate cancer shared care enabled communication, symptom management, and holistic assessment, with potential for reducing anxiety, enhancing outcomes, and increasing engagement. The studies (9 months to 5 years duration) involved participants across different care phases (16 to 3521 participants). We identified ten eHealth platforms, which provided successful symptom tracking, needs assessment, and communications. The platform-based interventions improved some aspects of communication, symptom management, and care delivery. The ongoing clinical need for a robust digital platform that caters to all domains of shared care was identified. Conclusions: eHealth will certainly play a central role in digital prostate cancer shared care, providing better health outcomes and care delivery. Future larger studies in this field should address the implementation barriers, including cost-effectiveness and primary care remuneration. It is also crucial to refine application useability and workflow, focusing on standardization and patient-centred approaches.
Satisfaction-Behavior Paradox in Lifestyle Choices: A Cross-Sectional Study of Health Behaviors and Satisfaction Levels in Jazan, Saudi Arabia
Authors: Makeen Anwar M. , Gosadi Ibrahim M. , Jareebi Mohammad A. , Muaddi Mohammed A. , Alharbi Abdullah A. , Bahri Ahmed A. , Ryani Majed A. , Mahfouz Mohamed Salih , Al Bahhawi Tariq , Alaswad Ammar K. , Hamdi Talal A. , Qussadi Rahaf I. , Munhish Aljazi A. , Alqassim Ahmad Y.
Published: September 2024

Background: Lifestyle choices significantly affect health outcomes in Saudi Arabia, but the relationship between health behaviors and satisfaction is unclear. This study aimed to assess lifestyle choices and associated satisfaction levels among residents in the Jazan region of Saudi Arabia. Methods: A cross-sectional study was conducted in Jazan, Saudi Arabia, with 3411 participants. Sociodemographic, lifestyle, and satisfaction data were collected using a questionnaire that was completed during interviews. Logistic regression analyses were implemented to examine the relationships between the study variables and factors related to weight, physical activity, and eating satisfaction. Results: The study found that 38.3% of participants were inactive and 77% rarely ate fruits and vegetables. A total of 47.6% were overweight or obese. Weight (71.12%) and eating (71.59%) satisfaction were high despite these health concerns. The satisfaction-behavior paradox was especially evident in diet. Higher income, physical activity, and healthy eating habits were significantly associated with higher satisfaction (OR = 1.49, 95% CI: 1.15–1.93, p = 0.003 for weight satisfaction, OR = 34.74, 95% CI: 25.42–48.35, p < 0.001 for physical activity satisfaction, and OR = 2.08, 95% CI: 1.67–2.61, p < 0.001 for fruit and vegetable consumption). Conclusions: Lifestyle behaviors and satisfaction in Jazan, Saudi Arabia, are complex. The satisfaction-behavior paradox, especially in diet, reveals a major gap between perceived and actual health. These findings highlight the need for targeted, culturally sensitive interventions that address behavioral change and perception alignment to improve regional public health.
The Hospital as a Beacon of Science? Parisian Academic Medicine around 1800
Authors: Stahnisch Frank W.
Published: September 2024

Owing to medical historian Erwin H. Ackerknecht’s (1906–1988) pioneering study “Medicine at the Paris Hospital, 1794–1848” (1967), the year 1794 is seen as the decisive separation date on which the development and reorganization of the Parisian clinical school—as a broad movement and a system of medical education and clinical practice—distanced it from the traditions of the 18th century. This precise dating is based on the “Rapport et projet de décret sur l’établissement d’une École centrale de Santé à Paris” (1794) by the French clinician and naturalist Antoine-François Fourcroy (1755–1809), which appeared five years after the French Revolution. Fourcroy was asked by the Conseil d’État to submit a detailed report in which he was obliged to comment on the existing health situation and the state of medical care and research. His report thereby ventured so far as to request the continued dissolution of all medical faculties in France, as these institutions were seen as counter-revolutionary hotbeds in the wider educational landscape of the Grande Nation. Fourcroy’s recommendations were implemented a short time later; he had recommended that medical training should be established again in the traditional locations of Paris, Montpellier, and Strasbourg in France yet in the different settings of so-called health schools, Écoles de Santé. In this article, I look at the corresponding training and care structures after the French Revolution, as well as some of the specific reasons which led to the complete suspension of teaching in academic medicine at the time. In the more recent research literature, Ackerknecht’s view has undergone some modifications, whereby the fixation on the date 1794 has been challenged since the French traditions of the royalistic period have hardly been considered. Furthermore, it has been argued that the reorganization of medicine during the time of the Empire remained largely based on knowledge structures derived from the previous 18th century. In order to keep the complex scientific, institutional, and socio-economic conditions of the context of Parisian Academic Medicine aligned, I first explore some developments up to the time of the French Revolution (1789), before assessing the implications of the reform of knowledge structures and curricular programs instigated since the 1790s, as these remain relevant to medical history in the 19th century.
The Relationship between Bicultural Acceptance Attitude and Self-Esteem among Multicultural Adolescents: The Mediating Effects of Parental Support
Authors: Um Youn-Joo
Published: September 2024

As the rate of international marriage increases, the adaptation of multicultural families and their children—multicultural adolescents—remains an issue requiring continuous monitoring, support, and improvement. This study investigates the mediating effects of parental support on the relationship between bicultural acceptance attitude and self-esteem among multicultural adolescents. Data are derived from 1197 high school sophomores, all of whom were multicultural adolescents, surveyed by the National Youth Policy Institute in 2018. Descriptive statistics, correlation, and hierarchical regression were used during data analysis. Bicultural acceptance attitude, parental support, and self-esteem all showed mutual positive correlations. Parental support had a partial mediating effect on the relationship between bicultural acceptance attitude and self-esteem. Multicultural adolescents exposed to both parent’s cultures are more likely to develop positive self-esteem and a healthy personality if they receive the support of their parents. The self-esteem of multicultural adolescents can be improved by implementing measures to nurture a bicultural acceptance attitude and parental support.
The Effect of Periodontitis on Body Size Phenotypes in Adults without Diagnosed Chronic Diseases: The Korean National Health and Nutrition Examination Survey 2013–2015
Authors: Lyu Young Sang , Yoon Youngmin , Kim Jin Hwa , Kim Sang Yong
Published: September 2024

We aimed to examine the correlation between periodontitis and body size phenotypes in 7301 participants without diagnosed chronic diseases in the Korean National Health and Nutrition Examination Survey 2013–2015. The participants were categorized into the following body size phenotype groups based on body mass index and the presence of metabolic syndrome: metabolically healthy normal weight (MHNW), metabolically abnormal normal weight (MANW), metabolically healthy obese (MHO), and metabolically abnormal obese (MAO). The prevalence rates of mild and severe periodontitis were 18.1% and 7.5%, respectively. Patients with periodontitis were older, current smokers, had a lower family income, were less likely to engage in regular tooth brushing or exercise, and had a higher body mass index and glucose levels. Periodontitis was more prevalent in the MANW and MAO groups than in the MHNW and MHO groups. Compared with the MHNW phenotype, the MAO and MANW phenotypes were significantly associated with mild and severe periodontitis, and the MHO phenotype was significantly associated with mild periodontitis. The MANW and MAO phenotypes are independent risk factors for periodontitis in adults without diagnosed chronic diseases. To enhance public health, a greater focus and effective approaches for identifying metabolic disease phenotypes among individuals with periodontal disease may be clinically relevant.
Post-Occupancy Evaluation of the Improved Old Residential Neighborhood Satisfaction Using Principal Component Analysis: The Case of Wuxi, China
Authors: Zhao Jing , Abdul Aziz Faziawati , Cheng Ziyi , Ujang Norsidah , Zhang Hui , Xu Jiajun , Xiao Yi , Shi Lin
Published: September 2024

Recently, many Chinese cities have initiated improvement projects aimed at enhancing living conditions in older residential neighborhoods. Urban improvement should be closely linked to the needs of occupants to determine “what to improve”. Governmental initiatives and the various stakeholders involved in the project influence the impact of improvement efforts. The objectives of the study are essential to identify the factors influencing occupants’ satisfaction and to evaluate whether the occupants are satisfied with the improved old residential neighborhoods. This study conducts a post-occupancy evaluation (POE) of improved outdoor spaces in old residential neighborhoods, focusing on neighborhoods in Wuxi, China. A principal component analysis (PCA) was used to evaluate residents’ efficacy and satisfaction with the enhancements implemented in outdoor spaces. The methodology involved collecting data through surveys and on-site observations, which were then analyzed to identify the pivotal factors impacting the effectiveness of these improvements. The results indicated that enhancing outdoor spaces had a substantial positive impact on residents’ quality of life, social interactions, and physical activity levels. Additionally, the PCA identified accessibility, safety, and aesthetic quality as the main factors contributing to resident satisfaction. This study offers valuable insights for urban planners and policymakers aiming to rejuvenate aging residential districts, emphasizing the importance of data-driven approaches to improve the design and functionality of outdoor spaces.
Systematic Review and Meta-Analysis of Clinical Efficacy and Safety of Meropenem-Vaborbactam versus Best-Available Therapy in Patients with Carbapenem-Resistant Enterobacteriaceae Infections
Authors: Bucataru Alexandra , Turcu-Stiolica Adina , Calina Daniela , Balasoiu Andrei Theodor , Zlatian Ovidiu Mircea , Osman Andrei , Balasoiu Maria , Ghenea Alice Elena
Published: September 2024

Antimicrobial resistance is increasingly concerning, causing millions of deaths and a high cost burden. Given that carbapenemase-producing Enterobacterales are particularly concerning due to their ability to develop structural modifications and produce antibiotic-degrading enzymes, leading to high resistance levels, we sought to summarize the available data on the efficacy and safety regarding the combination of meropenem-vaborbactam (MV) versus the best available therapy (BAT). Articles related to our objective were searched in the PubMed and Scopus databases inception to July 2024. To assess the quality of the studies, we used the Cochrane risk-of-bias tool, RoB2. The outcomes were pooled as a risk ratio (RR) and a 95% confidence interval (95%CI). A total of four published studies were involved: one retrospective cohort study and three phase 3 trials, including 432 patients treated with MV and 426 patients treated with BAT (mono/combination therapy with polymyxins, carbapenems, aminoglycosides, colistin, and tigecycline; or ceftazidime-avibactam; or piperacillin-tazobactam). No significant difference in the clinical response rate was observed between MV and the comparators at the TOC (RR = 1.29, 95%CI [0.92, 1.80], p = 0.14) and EOT (RR = 1.66, 95%CI [0.58, 4.76], p = 0.34) visits. MV was associated with a similar microbiological response as the comparators at TOC (RR = 1.63, 95%CI [0.85, 3.11], p = 0.14) and EOT assessment (RR = 1.16, 95%CI [0.88, 1.54], p = 0.14). In the pooled analysis of the four studies, 28-day all-cause mortality was lower for MV than the control groups (RR = 0.47, 95%CI [0.24, 0.92], p = 0.03). MV was associated with a similar risk of adverse events (AEs) as comparators (RR = 0.79, 95%CI [0.53, 1.17], p = 0.23). Additionally, MV was associated with fewer renal-related AEs than the comparators (RR = 0.32, 95%CI [0.15, 0.66], p = 0.002). MV was associated with a similar risk of treatment discontinuation due to AEs (RR = 0.76, 95%CI [0.38, 1.49], p = 0.42) or drug-related AEs (RR = 0.56, 95%CI [0.28, 1.10], p = 0.09) as the comparators. In conclusion, MV presents a promising therapeutic option for treating CRE infections, demonstrating similar clinical and microbiological responses as other comparators, with potential advantages in mortality outcomes and renal-related AEs.
Photodegradation of Amoxicillin in Aqueous Systems: A Review
Authors: Ali Mohammad Ashraf , Maafa Ibrahim M.
Published: September 2024

Amoxicillin (AMX) is utilized in the treatment of several infectious diseases, and its concentration in wastewater has increased quite significantly over the years, posing high health hazards for humans and other living organisms. Investigations are in progress globally to eliminate AMX and other related pollutants using several methods that include adsorption, photolysis, photocatalytic degradation, photoelectrocatalytic degradation, and electrochemical conversion. AMX can be eliminated efficiently from the environment using photodegradation, either by photolysis or a photocatalytic process. Several types of semiconductor NMs have been used to eliminate AMX and other related drugs present in wastewater. This review spans the photodegradation studies conducted during the years 2018–2024 to degrade and eliminate AMX in aquatic systems. Several studies have been reported to eliminate AMX from different water streams. These studies are categorized into TiO2-containing and non-TiO2-based catalysts for better comparison. A section on photolysis is also included, showing the use of UV alone or with H2O2 or PS without using any nanomaterial. A tabulated summary of both types of catalysts showing the catalysts, reaction conditions, and degradation efficiency is presented. Researchers have used a variety of reaction conditions that include radiation types (UV, solar, and visible), pH of the solution, concentration of AMX, number of nanomaterials, presence of other additives and activators such as H2O2 as oxidant, and the influence of different salts like NaCl and CaCl2 on the photodegradation efficiency. TiO2 was the best nanomaterial found that achieved the highest degradation of AMX in ultraviolet irradiation. TiO2 doped with other nanomaterials showed very good performance under visible light. WO3 was also used by several investigators and found quite effective for AMX degradation. Other metal oxides used for AMX elimination were derived from molybdenum, zinc, manganese, copper, cerium, silver, etc. Some researchers have used UV and/or visible irradiation or sunlight, without using solid catalysts, in the presence of oxidants such as H2O2. A summarized description of earlier published reviews is also presented.
Distinct FLT3 Pathways Gene Expression Profiles in Pediatric De Novo Acute Lymphoblastic and Myeloid Leukemia with FLT3 Mutations: Implications for Targeted Therapy
Authors: Zhao Lizhen , Chen Hongbo , Lan Fengli , Hao Jinjin , Zhang Wenzhi , Li Ying , Yin Yuhong , Huang Minchun , Wu Xiaoyan
Published: September 2024

Activating FLT3 mutations plays a crucial role in leukemogenesis, but identifying the optimal candidates for FLT3 inhibitor therapy remains controversial. This study aims to explore the impacts of FLT3 mutations in pediatric acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) and to compare the mutation profiles between the two types to inspire the targeted application of FLT3 inhibitors. We retrospectively analyzed 243 ALL and 62 AML cases, grouping them into FLT3-mutant and wild-type categories, respectively. We then assessed the associations between FLT3 mutations and the clinical manifestations, genetic characteristics, and prognosis in ALL and AML. Additionally, we compared the distinct features of FLT3 mutations between ALL and AML. In ALL patients, those with FLT3 mutations predominantly exhibited hyperdiploidy (48.6% vs. 14.9%, p < 0.001) and higher FLT3 expression (108.02 [85.11, 142.06] FPKM vs. 23.11 [9.16, 59.14] FPKM, p < 0.001), but lower expression of signaling pathway-related genes such as HRAS, PIK3R3, BAD, MAP2K2, MAPK3, and STAT5A compared to FLT3 wild-type patients. There was no significant difference in prognosis between the two groups. In contrast, AML patients with FLT3 mutations were primarily associated with leucocytosis (82.90 [47.05, 189.76] G/L vs. 20.36 [8.90, 55.39] G/L, p = 0.001), NUP98 rearrangements (30% vs. 4.8%, p = 0.018), elevated FLT3 expression (74.77 [54.31, 109.46] FPKM vs. 34.56 [20.98, 48.28] FPKM, p < 0.001), and upregulated signaling pathway genes including PIK3CB, AKT1, MTOR, BRAF, and MAPK1 relative to FLT3 wild-type, correlating with poor prognosis. Notably, internal tandem duplications were the predominant type of FLT3 mutation in AML (66.7%) with higher inserted base counts, whereas they were almost absent in ALL (6.3%, p < 0.001). In summary, our study demonstrated that the forms and impacts of FLT3 mutations in ALL differed significantly from those in AML. The gene expression profiles of FLT3-related pathways may provide a rationale for using FLT3 inhibitors in AML rather than ALL when FLT3 mutations are present.
Upregulation of Insulin-like Growth Factor-I in Response to Chemotherapy in Children with Acute Lymphoblastic Leukemia
Authors: Kocadag Helin Berna , Weischendorff Sarah , De Pietri Silvia , Nielsen Claus Henrik , Rathe Mathias , Als-Nielsen Bodil , Hasle Henrik , Juul Anders , Müller Klaus , Sørum Maria Ebbesen
Published: September 2024

The treatment of childhood cancer is challenged by toxic side effects mainly due to chemotherapy-induced organ damage and infections, which are accompanied by severe systemic inflammation. Insulin-like growth factor I (IGF-I) is a key regulating factor in tissue repair. This study investigated associations between the circulating IGF-I levels and chemotherapy-related toxicity in pediatric acute lymphoblastic leukemia (ALL). In this prospective study, we included 114 patients (age: 1–17 years) with newly diagnosed ALL treated according to The Nordic Society of Paediatric Haematology and Oncology (NOPHO) ALL2008 protocol between 2013 and 2018. The patients’ plasma levels of IGF-I, and the primary binding protein, IGFBP-3, were measured weekly during the first six weeks of treatment, including the induction therapy. The patients’ systemic inflammation was monitored by their C-reactive protein (CRP) and interleukin (IL)-6 levels and their intestinal epithelial damage by their plasma citrulline levels. IGF-I and IGFBP-3 were converted into sex-and age-adjusted standard deviation scores (SDS) using 1621 healthy children as reference. At ALL diagnosis, IGF-I levels were decreased (median (quartiles): −1.2 SDS (−1.9 to −0.5), p = 0.001), but increased significantly following the initiation of chemotherapy, peaking on day 8 (0.0 SDS (from −0.8 to 0.7), p < 0.001). This increase correlated with the levels of CRP (rho = 0.37, p < 0.001) and IL-6 (rho = 0.39, p = 0.03) on day 15, when these markers reached maximum levels. A larger IGF-I increase from day 1 to 15 correlated with a slower recovery rate of the intestinal damage marker citrulline from day 15 to 29 (rho = −0.28, p = 0.01). Likewise, IGFBP-3 was reduced at diagnosis, followed by an increase after treatment initiation, and was highly correlated with same-day IGF-I levels. This study demonstrates a chemotherapy-induced increase in IGF-I, with a response that appears to reflect the severity of tissue damage and systemic inflammation, preceding CRP and IL-6 increases. IGF-I may have potential as an early reactive biomarker for acute toxicity in patients with ALL.
The Effect of Statins on Markers of Breast Cancer Proliferation and Apoptosis in Women with In Situ or Early-Stage Invasive Breast Cancer
Authors: Kamal Anam , Boerner Julie , Assad Hadeel , Chen Wei , Simon Michael S.
Published: September 2024

Statins, inhibitors of HMG-CoA reductase, have been shown to have potential anti-carcinogenic effects through the inhibition of the mevalonate pathway and their impact on Ras and RhoGTAases. Prior studies have demonstrated a reduction in breast tumor proliferation, as well as increased apoptosis, among women with early-stage breast cancer who received statins between the time of diagnosis and the time of surgery. The aim of this study was to evaluate the impact of short-term oral high-potency statin therapy on the expression of markers of breast tumor proliferation, apoptosis, and cell cycle arrest in a window-of-opportunity trial. This single-arm study enrolled 24 women with stage 0-II invasive breast cancer who were administered daily simvastatin (20 mg) for 2–4 weeks between diagnosis and surgical resection. Pre- and post-treatment tumor samples were analyzed for fold changes in Ki-67, cyclin D1, p27, and cleaved caspase-3 (CC3) expression. Out of 24 enrolled participants, 18 received statin treatment and 17 were evaluable for changes in marker expression. There was no significant change in Ki-67 expression (fold change = 1.4, p = 0.597). There were, however, significant increases in the expression of cyclin D1 (fold change = 2.8, p = 0.0003), p27 cytoplasmic (fold change = 3.2, p = 0.025), and CC3 (fold change = 2.1, p = 0.016). Statin treatment was well tolerated, with two reported grade-1 adverse events. These results align with previous window-of-opportunity studies suggesting a pro-apoptotic role of statins in breast cancer. The increased expression of markers of cell cycle arrest and apoptosis seen in this window-of-opportunity study supports further investigation into the anti-cancer properties of statins in larger-scale clinical trials.
Transcriptomic Alterations in Spliceosome Components in Advanced Heart Failure: Status of Cardiac-Specific Alternative Splicing Factors
Authors: Giménez-Escamilla Isaac , Pérez-Carrillo Lorena , González-Torrent Irene , Delgado-Arija Marta , Benedicto Carlota , Portolés Manuel , Tarazón Estefanía , Roselló-Lletí Esther
Published: September 2024

Heart failure (HF) is associated with global changes in gene expression. Alternative mRNA splicing (AS) is a key regulatory mechanism underlying these changes. However, the whole status of molecules involved in the splicing process in human HF is unknown. Therefore, we analysed the spliceosome transcriptome in cardiac tissue (n = 36) from control subjects and HF patients (with ischaemic (ICM) and dilated (DCM) cardiomyopathies) using RNA-seq. We found greater deregulation of spliceosome machinery in ICM. Specifically, we showed widespread upregulation of the E and C complex components, highlighting an increase in SNRPD2 (FC = 1.35, p < 0.05) and DHX35 (FC = 1.34, p < 0.001) mRNA levels. In contrast, we observed generalised downregulation of the A complex and cardiac-specific AS factors, such as the multifunctional protein PCBP2 (FC = −1.29, p < 0.001) and the RNA binding proteins QKI (FC = −1.35, p < 0.01). In addition, we found a relationship between SNPRD2 (an E complex component) and the left ventricular mass index in ICM patients (r = 0.779; p < 0.01). On the other hand, we observed the specific underexpression of DDX46 (FC = −1.29), RBM17 (FC = −1.33), SDE2 (FC = −1.35) and RBFOX1 (FC = −1.33), p < 0.05, in DCM patients. Therefore, these aetiology-related alterations may indicate the differential involvement of the splicing process in the development of ICM and DCM.
In Vitro and In Vivo Assessments of Newly Isolated N4-like Bacteriophage against ST45 K62 Capsular-Type Carbapenem-Resistant Klebsiella pneumoniae: vB_kpnP_KPYAP-1
Authors: Natarajan Shanmuga Priya , Teh Soon-Hian , Lin Ling-Chun , Lin Nien-Tsung
Published: September 2024

The rise of carbapenem-resistant Klebsiella pneumoniae (CRKP) presents a significant global challenge in clinical and healthcare settings, severely limiting treatment options. This study aimed to utilize a bacteriophage as an alternative therapy against carbapenem-resistant K. pneumoniae. A novel lytic N4-like Klebsiella phage, vB_kpnP_KPYAP-1 (KPYAP-1), was isolated from sewage. It demonstrated efficacy against the K62 serotype polysaccharide capsule of blaOXA-48-producing K. pneumoniae. KPYAP-1 forms small, clear plaques, has a latent period of 20 min, and reaches a growth plateau at 35 min, with a burst size of 473 plaque-forming units (PFUs) per infected cell. Phylogenetic analysis places KPYAP-1 in the Schitoviridae family, Enquatrovirinae subfamily, and Kaypoctavirus genus. KPYAP-1 employs an N4-like direct terminal repeat mechanism for genome packaging and encodes a large virion-encapsulated RNA polymerase. It lacks integrase or repressor genes, antibiotic resistance genes, bacterial virulence factors, and toxins, ensuring its safety for therapeutic use. Comparative genome analysis revealed that the KPYAP-1 genome is most similar to the KP8 genome, yet differs in tail fiber protein, indicating variations in host recognition. In a zebrafish infection model, KPYAP-1 significantly improved the survival rate of infected fish by 92% at a multiplicity of infection (MOI) of 10, demonstrating its potential for in vivo treatment. These results highlight KPYAP-1 as a promising candidate for developing phage-based therapies targeting carbapenemase-producing K. pneumoniae.
Determining Gene Order Patterns in the Suillus and Boletales through Comparative Analysis of Their Mitogenomes
Authors: Tao Jiawei , Wang Xianyi , Long Yaohang , Gao Zexin , Zhang Gongyou , Guo Zhongyao , Wang Guoyu , Xu Guangyin , Wang Yaping , Liu Hongmei
Published: September 2024

Suillus is one of the most important genera of ectomycorrhizal fungi. As a model for studying host specificity, its molecular fragments and nuclear genome have been analyzed. However, its mitochondrial genome has not yet been reported. In this study, we assembled five mitogenomes of Suillus and analyzed and compared their basic characteristics. Owing to the large number of introns as well as intergenic regions, the mitogenomic lengths of species of Suillus were greater than those of other species of Boletales. We identified two main patterns of gene order arrangement in the members of the order Boletales. The Ka/Ks values of 15 protein-coding genes were <1 for the mitochondrial genes of 39 Boletales species, indicating their conserved evolution. Phylogenetic trees, reconstructed using the mitogenomes, indicated that the genus Suillus was monophyletic. Phylogenetic results based on the internal transcribed spacer region and mitogenome were used to confirm the distribution of Suillus placidus in China. The results showed that the mitogenome was superior in distinguishing species compared with a single molecular fragment. This is the first study to investigate the mitogenome of Suillus, enriching the mitogenome information and providing basic data for the phylogeny, resource conservation, and genetic diversity of this genus.
Fluoride Alters Gene Expression via Histone H3K27 Acetylation in Ameloblast-like LS8 Cells
Authors: Yamashita Shohei , Okamoto Motoki , Mendonca Melanie , Fujiwara Natsumi , Kitamura Eiko , Chang Chang-Sheng Sam , Brueckner Susanne , Shindo Satoru , Kuriki Nanako , Cooley Marion A. , Gill Dhillon Navi , Kawai Toshihisa , Bartlett John D. , Everett Eric T. , Suzuki Maiko
Published: September 2024

Excessive fluoride ingestion during tooth development can cause dental fluorosis. Previously, we reported that fluoride activates histone acetyltransferase (HAT) to acetylate p53, promoting fluoride toxicity in mouse ameloblast-like LS8 cells. However, the roles of HAT and histone acetylation status in fluoride-mediated gene expression remain unidentified. Here, we demonstrate that fluoride-mediated histone modification causes gene expression alterations in LS8 cells. LS8 cells were treated with or without fluoride followed by ChIP-Seq analysis of H3K27ac. Genes were identified by differential H3K27ac peaks within ±1 kb from transcription start sites. The levels of mRNA of identified genes were assessed using rea-time PCR (qPCR). Fluoride increased H3K27ac peaks associated with Bax, p21, and Mdm2 genes and upregulated their mRNA levels. Fluoride decreased H3K27ac peaks and p53, Bad, and Bcl2 had suppressed transcription. HAT inhibitors (Anacardic acid or MG149) suppressed fluoride-induced mRNA of p21 and Mdm2, while fluoride and the histone deacetylase (HDAC) inhibitor sodium butyrate increased Bad and Bcl2 expression above that of fluoride treatment alone. To our knowledge, this is the first study that demonstrates epigenetic regulation via fluoride treatment via H3 acetylation. Further investigation is required to elucidate epigenetic mechanisms of fluoride toxicity in enamel development.