bluuebunny/crossref_metadata_2025 huggingface dataset:
Nutritional Strategies for the Treatment and Prevention of Sepsis Outside the Intensive Care Unit
Authors: Gabrielli Maurizio , Zaccaria Raffaella , Impagnatiello Michele , Zileri Dal Verme Lorenzo , Gasbarrini Antonio
Published: November 2024

Background/Objectives: Sepsis is a life-threatening condition characterized by an imbalanced immune response to infection, posing a significant challenge in hospital settings due to its high morbidity and mortality rates. While much attention has been given to patients in the ICU, uncertainties remain regarding the nutritional management of septic patients in non-intensive wards. This narrative review aims to address these gaps by exploring key aspects of nutritional care in sepsis patients admitted to non-intensive wards. Methods: We examine the pathophysiological mechanisms driving metabolic alterations in sepsis, methods for effective nutritional assessment, and supplementation strategies, including the potential role of specific nutrients. Additionally, we discuss the preventive role of nutrition, with a focus on gut microbiota modulation. Conclusions: By synthesizing the available literature, this review provides evidence-based insights to guide nutritional strategies for managing sepsis in patients hospitalized in non-intensive wards and highlights critical areas for future research.
Prevalence and Associated Risk Factors for Hypovitaminosis D in Patients Scheduled for Primary Total Knee Arthroplasty in Germany
Authors: Heinz Tizian , Hoxha Miledi , Anderson Philip Mark , Jakuscheit Axel , Weißenberger Manuel , Lüdemann Martin , Rak Dominik , Rudert Maximilian , Horas Konstantin
Published: November 2024

Objective: Several studies have reported a high prevalence of hypovitaminosis D in orthopedic patients. The purpose of this prospective observational study was to report on the prevalence of hypovitaminosis D in patients scheduled for elective primary total knee arthroplasty (TKA) and its associated risk factors. Methods: In this monocentric cohort study, 25(OH) vitamin D serum levels were measured in 687 consecutive patients undergoing primary total knee arthroplasty (TKA) over a period of twelve months. Vitamin D levels were classified into deficiency (<20 ng/mL), insufficiency (20–29 ng/mL), and sufficiency (≥30 ng/mL). The study assessed the association of vitamin D levels with demographic and clinical factors, including age, sex, BMI, smoking status, and season of measurement. Statistical analyses included chi-square tests, correlation analyses, and multiple linear regression to identify significant predictors of vitamin D levels. Results: The cohort had a mean age of 67.70 ± 8.95 years and a mean BMI of 31.00 ± 5.71 kg/m2. Collectively, 33.9% of patients were vitamin D deficient, a further 32.9% were insufficient, and only 33.2% were sufficient. Vitamin D levels varied significantly with the season and were associated with obesity and smoking. Specifically, there was a small significant inverse correlation between BMI and vitamin D levels (r = −0.17, p < 0.01). Furthermore, regular nicotine abuse was linked to lower vitamin D levels (r = 0.14, p < 0.01). Multiple linear regression analysis reveals that age, BMI, nicotine abuse, and season were small significant predictors of preoperative vitamin D levels (R2 = 0.15, adjusted R2 = 0.12). A total of 121 (17.61%) patients reported routine vitamin D intake prior to surgery. Supplementing patients had a significantly higher mean serum vitamin D level and a significant reduction in the mean length of in-hospital stay (p < 0.01). Conclusions: The prevalence of vitamin D insufficiency and deficiency in patients undergoing elective primary TKA is alarmingly high. In ongoing efforts to optimize the efficacy and outcome of the TKA procedure, orthopedic surgeons should be advised to strongly implement the role of perioperative vitamin D levels in their routine practice.
Attitudes and Beliefs of Primary Care Physicians and Nurses in Spain Toward Vegan Diets
Authors: Trujillo-Garrido Nuria , Sánchez-Sánchez Eduardo , Santi-Cano María J.
Published: November 2024

Background: As dietary habits shift in response to environmental concerns and health awareness, understanding healthcare professionals’ perceptions of vegan diets is crucial. Objectives: This study aimed to identify the beliefs and attitudes of primary care doctors and nurses in Spain towards vegan diets. Methods: A questionnaire-based, observational, cross-sectional study was conducted among 208 healthcare professionals. Results: 87% of participants followed an omnivorous diet, while only 3.4% identified as lacto-ovo-vegetarian (LOV) or vegan. Statistically significant differences were observed by sex, with women more likely to agree that livestock farming contributes to global warming (27.3% and 28.0% vs. 17.0% and 12.8%, respectively; p = 0.02). Additionally, women were more inclined to consider vegan diets suitable for vulnerable groups, such as pregnant women and children, when adequately supplemented (24.8% and 17.4% vs. 10.6% and 10.6%, respectively; p = 0.030). Healthcare professionals who followed a LOV or vegan diet were more likely to disagree with the notion that vegan diets do not provide the necessary macronutrients and micronutrients compared to omnivores (strongly disagree 19.9%, 56.3%, 85.7%; p = 0.001 for omnivores, flexitarians, and LOVs/vegans, respectively). Conclusions: Current nutrition training may not meet the needs of doctors and nurses. Furthermore, it is implied that some professionals’ attitudes towards vegan diets may be more influenced by personal beliefs than by scientific literature. These findings can inform future clinical guidelines and support a more evidence-based approach to dietary counselling for vegan populations.
Increasing Access to Palliative Care in Cameroon: Progress, Gaps, and Recommendations
Authors: Bassah Nahyeni , Santos Salas Anna , Ambe Niba Clinton , Ngah Ndzi Eric
Published: November 2024

Background/Objectives: Access to palliative care is an urgent global need. Countries with the greatest palliative care needs have limited access. In Cameroon, demand for palliative care is growing due to the rising incidence of life-limiting conditions. Identifying available palliative care services and programs could provide an understanding of access gaps and inform future roadmaps for palliative care development in the country. We aim to map available palliative care services, identify gaps and inform recommendations to promote early access to palliative care in Cameroon. Methods: We undertook a literature review of articles reporting any aspects of palliative care in Cameroon. We searched Embase, MEDLINE, Scopus, PsycINFO, CINAHL, PubMed and gray literature. Data were analyzed thematically using the World Health Organization model for the assessment of palliative care development. Results: We identified 41 articles reporting 21 organizations with some form of palliative care services such as clinical services, education, advocacy and research. These were led mostly by individual health care providers or private and faith-based organizations. Major palliative care initiatives included training in the form of workshops, and adult and pediatric outpatient, in-patient and community-based palliative care. There were few reports of oral morphine production, community engagement, advocacy and palliative care research. Conclusions: Progress in palliative care development was reported in five regions of Cameroon over the last two decades. Findings suggest the need for an intersectoral approach including government, community, and health care stakeholders to achieve sustainable palliative care. This could potentially ensure equitable access to palliative care in Cameroon.
In Situ Localization of Staphylococcus shinii and Staphylococcus succinus in Infected Rhipicephalus microplus Ticks: Implications for Biocontrol Strategies
Authors: Arreguin-Perez Cesar A. , Cossio-Bayugar Raquel , Aguilar-Diaz Hugo , Miranda-Miranda Estefan
Published: November 2024

Rhipicephalus microplus is a blood-sucking parasite that causes heavy infestations on cattle and is a vector for severe tick-borne diseases, such as anaplasmosis and babesiosis, and poses a significant threat to the cattle industry. Cattle ticks show increasing acaricide resistance, which creates an additional problem concerning the inefficient chemical control of tick populations in cattle-grazing areas, necessitating the exploration of alternative tick biocontrol methods. Our study aimed to demonstrate the acaropathogenic efficacy of two bacterial species during experimental infections on R. microplus. Our experimental data confirmed that S. shinii and S. succinus exhibited significant acaropathogenic properties against R. microplus, as demonstrated by the tracking of fluorescent-labeled bacteria within the engorged-tick body. Our experiments revealed that both bacterial species could infect the hemolymph, salivary glands, and vestibular vagina of the tick, inducing histological changes in the affected organs that may impair feeding as well as reproductive capabilities. Gené’s organ infection was detected only in S. succinus. Our findings offer valuable insights for developing biocontrol strategies to manage Rhipicephalus microplus populations effectively.
mTOR Pathway Inhibition, Anticancer Activity and In Silico Calculations of Novel Hydrazone Derivatives in Two- and Three-Dimensional Cultured Type 1 Endometrial Cancer Cells
Authors: Bulbul Muhammet Volkan , Mermer Arif , Kolbasi Bircan , Kocabas Fatih , Kalender Semiha Mervenur , Kirectepe Aydin Kiymet Asli , Demircan Turan , Keskin İlknur
Published: November 2024

Background: Endometrial cancer remains a significant health concern, with type 1 endometrial cancer characterized by aberrant expression of estrogen-dependent and mTOR pathway proteins. In this study, we evaluated the effects of two novel hydrazone derivatives against the Ishikawa cell line, a model for endometrial cancer. Methods: Two novel hydrazone derivatives, MVB1 and MVB2, were synthesized and characterized. The anticancer activity of the compounds in both two- and three-dimensional cultured Ishikawa cells was evaluated by MTT assay. The interaction of the compounds with proteins in the PI3K/AKT/mTOR pathway was evaluated by molecular docking studies and in vitro western blot analyses were performed. Additionally, ADME/T calculations were performed to evaluate the drug-like properties of the compounds. Results: MVB1 and MVB2 showed promising anticancer activity with IC50 values of 8.3 ± 0.5 µM and 9.0 ± 1.2 µM in 2D cultures, respectively, and 49.9 ± 2 µM and 20.6 ± 1.9 µM in 3D cultures, respectively. Molecular docking studies revealed significant interactions between these compounds and key proteins in the PI3K/AKT/mTOR pathway, with MVB1 exhibiting the highest mean binding score (−10.5 kcal/mol) among PI3K, AKT1, and mTOR proteins. In vitro studies confirmed that MVB1 effectively suppressed PI3K protein expression in both 2D and 3D cultures (p ≤ 0.0001). Conclusions: The findings suggest that MVB1 and MVB2, especially MVB1, are promising candidates for further development as potential therapeutics for endometrial cancer by targeting the PI3K/AKT/mTOR pathway.
Sparstolonin B Reduces Estrogen-Dependent Proliferation in Cancer Cells: Possible Role of Ceramide and PI3K/AKT/mTOR Inhibition
Authors: Dilber Yağmur , Çeker Hanife Tuğçe , Öztüzün Aleyna , Çırçırlı Bürke , Kırımlıoğlu Esma , Barut Zerrin , Aslan Mutay
Published: November 2024

Background: The aim of this study was to determine the effect of Sparstolonin B (SsnB) on cell proliferation and apoptosis in human breast cancer (MCF-7) and human ovarian epithelial cancer (OVCAR-3) cell lines in the presence and absence of estradiol hemihydrate (ES). Phosphoinositol-3 kinase (PI3K), phosphorylated protein kinase B alpha (p-AKT), phosphorylated mTOR (mechanistic target of rapamycin) signaling proteins, and sphingomyelin/ceramide metabolites were also measured within the scope of the study. Methods: The anti-proliferative effects of SsnB therapy were evaluated over a range of times and concentrations. Cell proliferation was determined by measuring the Proliferating Cell Nuclear Antigen (PCNA). PCNA was quantified by ELISA and cell distribution was assessed by immunofluorescence microscopy. MTT analysis was used to test the vitality of the cells, while LC-MS/MS was used to analyze the amounts of ceramides (CERs), sphingosine-1-phosphate (S1P), and sphingomyelins (SMs). TUNEL labeling was used to assess apoptosis, while immunofluorescence staining and enzyme-linked immunosorbent assay (ELISA) were used to measure the levels of PI3K, p-AKT, and p-mTOR proteins. Results: Sparstolonin B administration significantly decreased cell viability in MCF-7 and OVCAR-3 cells both in the presence and absence of ES, while it did not cause toxicity in healthy human fibroblasts. In comparison to controls, cancer cells treated with SsnB showed a significant drop in the levels of S1P, PI3K, p-AKT, and p-mTOR. In cancer cells cultured with SsnB, a significant increase in intracellular concentrations of C16-C24 CERs and apoptosis was observed. Conclusions: SsnB downregulated the levels of S1P, PI3K, p-AKT, and p-mTOR while reducing cell proliferation and promoting ceramide buildup and apoptosis.
Microparticles Loaded with Bursera microphylla A. Gray Fruit Extract with Anti-Inflammatory and Antimicrobial Activity
Authors: Reyna-Urrutia Víctor Alonso , Robles-Zepeda Ramón Enrique , Estevez Miriam , Gonzalez-Reyna Marlen Alexis , Alonso-Martínez Grecia Vianney , Cáñez-Orozco Juan Ramón , López-Romero Julio César , Torres-Moreno Heriberto
Published: November 2024

Background: Bursera microphylla (B) A. Gray, a plant native to northwest Mexico, has long been utilized in traditional medicine for its anti-inflammatory effects. Previous studies have highlighted the bioactivity of B. microphylla fruit extract. Chitosan (Cs), a biopolymer known for its favorable physicochemical properties, has proven effective in encapsulating bioactive compounds. This study aimed to synthesize and characterize Cs-based microparticles containing B. microphylla fruit extract and evaluate their in vitro anti-inflammatory activity. Methods: Cs-based three-dimensional hydrogels were synthesized using physical cross-linking with ammonium hydroxide, incorporating B. microphylla fruit extract. The hydrogels were freeze-dried and mechanically ground into microparticles. The physicochemical properties of the microencapsulates were analyzed through scanning electron microscopy (SEM), optical microscopy (OM), Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), and moisture absorption tests. Anti-inflammatory activity was assessed by measuring nitric oxide (NO) reduction in LPS-activated RAW 264.7 cells. Antimicrobial activity was evaluated against Staphylococcus aureus. Results: SEM and OM analyses revealed irregular morphologies with rounded protuberances, with particle sizes ranging from 135 to 180 µm. FTIR spectra indicated that no new chemical bonds were formed, preserving the integrity of the original compounds. TGA confirmed that the encapsulated extract was heat-protected. The moisture absorption test indicated the microparticles’ hydrophilic nature. In vitro, the microencapsulated extract reduced NO production by 46%, compared to 32% for the non-encapsulated extract. The microencapsulated extract was effective in reducing the microbial load of S. aureus between 15–24%. Conclusions: Cs-based microencapsulates containing B. microphylla fruit extract exhibited no chemical interactions during synthesis and demonstrated significant anti-inflammatory and antimicrobial activity. These results suggest that the Cs-based system is a promising candidate for managing inflammatory conditions.
The Inappropriate Use of GLP-1 Analogs: Reflections from Pharmacoepidemiology
Authors: Echeverry-Guerrero Sofía , González-Vélez Salomé , Arévalo-Lara Ana-Sofía , Calvache-Orozco Juan-Camilo , Villarroel-Hagemann Sebastián Kurt , Rojas-Rodríguez Luis Carlos , Pérez-Acosta Andrés M. , Calderon-Ospina Carlos-Alberto
Published: November 2024

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have emerged as a potent therapeutic option for the management of obesity, demonstrating exceptional efficacy in several large-scale clinical trials. Despite their promising therapeutic outcomes, the rising popularity of these agents raises significant concerns, particularly regarding their off-label use by individuals seeking weight loss for aesthetic reasons rather than addressing underlying metabolic health conditions. This article critically evaluates the efficacy and safety of GLP-1 RAs in obesity management. Additionally, it explores the economic implications and ethical challenges associated with the increasing demand for GLP-1 RAs. By addressing these dimensions, this article aims to facilitate informed and responsible decision-making in clinical practice, highlighting the need for individualized patient assessments and careful consideration of both short- and long-term safety risks.
Recent Advances in Peptide Drug Discovery: Novel Strategies and Targeted Protein Degradation
Authors: Vrbnjak Katarina , Sewduth Raj Nayan
Published: November 2024

Recent technological advancements, including computer-assisted drug discovery, gene-editing techniques, and high-throughput screening approaches, have greatly expanded the palette of methods for the discovery of peptides available to researchers. These emerging strategies, driven by recent advances in bioinformatics and multi-omics, have significantly improved the efficiency of peptide drug discovery when compared with traditional in vitro and in vivo methods, cutting costs and improving their reliability. An added benefit of peptide-based drugs is the ability to precisely target protein–protein interactions, which are normally a particularly challenging aspect of drug discovery. Another recent breakthrough in this field is targeted protein degradation through proteolysis-targeting chimeras. These revolutionary compounds represent a noteworthy advancement over traditional small-molecule inhibitors due to their unique mechanism of action, which allows for the degradation of specific proteins with unprecedented specificity. The inclusion of a peptide as a protein-of-interest-targeting moiety allows for improved versatility and the possibility of targeting otherwise undruggable proteins. In this review, we discuss various novel wet-lab and computational multi-omic methods for peptide drug discovery, provide an overview of therapeutic agents discovered through these cutting-edge techniques, and discuss the potential for the therapeutic delivery of peptide-based drugs.
Quality by Design (QbD)-Driven Development and Optimization of Tacrolimus-Loaded Microemulsion for the Treatment of Skin Inflammation
Authors: Srishti Sanjida Ahmed , Pinky Paromita Paul , Taylor Ryan , Guess Jacob , Karlik Natasha , Janjic Jelena M.
Published: November 2024

Background: Skin inflammation represents a hallmark of many skin conditions, from psoriasis to eczema. Here, we present a novel microemulsion formulation for delivering a low dose of potent immunosuppressant, tacrolimus, to the skin for local inflammation control. The efficacy of topically delivered tacrolimus in controlling skin inflammation can be enhanced by packaging it into microemulsions. Microemulsions are small-size, thermodynamically stable, and surfactant-rich emulsions that can enhance tissue penetration and local tissue retention of poorly soluble drugs, which can reduce dosing frequency and potentially improve patient compliance. Methods: We present a novel approach for microemulsion manufacturing that uses a combination of both low and high-energy methods. The microemulsion composition and manufacturing parameters were optimized by adopting Quality by Design methodologies. The FMECA (Failure, Mode, Effects, Criticality Analysis)-based risk assessment, D-optimal Design of Experiment (DoE), and statistical analysis of parameters impacting responses through the multiple linear regression (MLR) was implemented for identifying critical formulation and process parameters. Results: Through QbD strategy, a stable microemulsion with optimized drug loading that met all critical quality attributes (CQAs) was identified. The optimal microemulsion candidate was successfully scaled up three-fold with retained CQAs. The presented microemulsion showed a slow and extended drug release profile in vitro. Conclusions: Presented findings suggest that microemulsions are a promising novel approach for tacrolimus delivery to the skin. Further, we also demonstrated that a combination of low-energy emulsification and microfluidization processes can produce stable and robust microemulsions with small droplet size that can be implemented in drug delivery of poorly soluble anti-inflammatory drugs. To the best of our knowledge, this is the first report of QbD-driven optimization of microemulsion manufacturing by microfluidization.
Tailoring Mesalazine Nanosuspension Using Chitosan Polyelectrolyte Complexes with Alginate and Alginate/Hydroxypropyl-Methylcellulose Phthalate
Authors: Pereira Amélia Aparecida Rocca , Aparecida José Vitor Melchiades , Ramalho Maria Eduarda , Ferreira Leonardo Miziara Barboza , Gremião Maria Palmira Daflon
Published: November 2024

Background/Objectives: This study evaluated how the relative proportion of chitosan (CS) to the polyanions alginate (ALG) and hydroxypropyl-methylcellulose phthalate (HP) affects the colloidal properties of mesalazine (MSZ) nanosuspensions as a strategy to produce particles with specific characteristics. Methods: Nanosuspensions were prepared using a bottom–up approach based on acid–base reactions and were modified with CS in a binary mixture with ALG or a ternary mixture with ALG and HP. The particle size, polydispersity index (PDI), zeta potential, morphology, and drug association efficiency were analyzed. Results: Higher proportions of CS relative to the polyanions resulted in smaller, less polydisperse particles. The zeta potential inversion was influenced by the relative proportion of CS in the system. These results were consistent over 30 days and pH exerted an influence on the magnitude of the observed effect. The optimized NS modified with binary CS/ALG blends had the following properties at pH 6.0: an average particle size of 324.9 nm, PDI of 0.5, and zeta potential of +40.8 mV; at pH 4.0, it had an average particle size of 310.4 nm, PDI of 0.4, and zeta potential of +43.6 mV. The optimized NS modified with ternary CS/ALG/HP had the following properties at pH 6.0: an average particle size of 316.7 nm, PDI of 0.5, and zeta potential of +33.9 mV; at pH 4.0, it had an average particle size of 363.5 nm, PDI of 0.6, and zeta potential of +33.9 mV. Conclusions: CS-based polyelectrolyte complexes with ALG and ALG/HP offer an approach to modulating the properties of MSZ nanosuspensions, enabling the production of particles with tailored characteristics.
Nanotheranostics in Breast Cancer Bone Metastasis: Advanced Research Progress and Future Perspectives
Authors: Miao Lin , Zhu Yidan , Chang Hong , Zhang Xinfeng
Published: November 2024

Breast cancer is the leading cause of cancer-related morbidity and mortality among women worldwide, with bone being the most common site of all metastatic breast cancer. Bone metastases are often associated with pain and skeletal-related events (SREs), indicating poor prognosis and poor quality of life. Most current therapies for breast cancer bone metastasis primarily serve palliative purposes, focusing on pain management, mitigating the risk of bone-related complications, and inhibiting tumor progression. The emergence of nanodelivery systems offers novel insights and potential solutions for the diagnosis and treatment of breast cancer-related bone metastasis. This article reviews the recent advancements and innovative applications of nanodrug delivery systems in the context of breast cancer bone metastasis and explores future directions in nanotheranostics.
Molecular Targeting of Ischemic Stroke: The Promise of Naïve and Engineered Extracellular Vesicles
Authors: Lee Jihun , Geum Dongho , Park Dong-Hyuk , Kim Jong-Hoon
Published: November 2024

Ischemic stroke (IS) remains a leading cause of mortality and long-term disability worldwide, with limited therapeutic options available. Despite the success of early interventions, such as tissue-type plasminogen activator administration and mechanical thrombectomy, many patients continue to experience persistent neurological deficits. The pathophysiology of IS is multifaceted, encompassing excitotoxicity, oxidative and nitrosative stress, inflammation, and blood–brain barrier disruption, all of which contribute to neural cell death, further complicating the treatment of IS. Recently, extracellular vesicles (EVs) secreted naturally by various cell types have emerged as promising therapeutic agents because of their ability to facilitate selective cell-to-cell communication, neuroprotection, and tissue regeneration. Furthermore, engineered EVs, designed to enhance targeted delivery and therapeutic cargo, hold the potential to improve their therapeutic benefits by mitigating neuronal damage and promoting neurogenesis and angiogenesis. This review summarizes the characteristics of EVs, the molecular mechanisms underlying IS pathophysiology, and the emerging role of EVs in IS treatment at the molecular level. This review also explores the recent advancements in EV engineering, including the incorporation of specific proteins, RNAs, or pharmacological agents into EVs to enhance their therapeutic efficacy.
Biopharmaceutical Characterization and Stability of Nabumetone–Cyclodextrins Complexes Prepared by Grinding
Authors: Klarić David , Soldin Željka , Vincze Anna , Szolláth Rita , Balogh György Tibor , Jug Mario , Galić Nives
Published: November 2024

Background: Nabumetone (NAB) is a poorly soluble nonsteroidal anti-inflammatory prodrug (BCS class II drug) whose solubility is significantly improved by complexation with cyclodextrins (CDs). Methods: The solid complexes, in a 1:1 molar ratio, were prepared by mechanochemical activation by grinding, using β-cyclodextrin (β-CD) and its derivatives, hydroxypropyl- and sulfobutylether-β-cyclodextrin (HP-β-CD and SBE-β-CD). The complexation was confirmed by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and attenuated total reflectance Fourier-transformed infrared spectroscopy (ATR–FTIR). Obtained products were further characterized regarding their solubility, in vitro dissolution, permeability and chemical stability. Results: Co-grinding with HP-β-CD and SBE-β-CD yielded products that showed in vitro dissolution profiles in hydrochloric acid medium (pH 1.2) that were substantially different from that of pure NAB, yielding dissolution efficiency enhancements of 34.86 ± 1.64 and 58.30 ± 0.28 times, respectively, for the optimized products. Their in vitro dissolution and gastrointestinal permeability were also studied in a low-volume environment at pH 6.8, corresponding to the intestinal environment. Both β-CD derivatives increased NAB dissolution rate and NAB mass transport across the biomimetic membrane. The effect of β-CD derivatives on NAB chemical stability was studied under the stress conditions by the developed and validated UHPLC–DAD–HRMS method. In acidic conditions, pure and complexed NAB was prone to hydrolytic degradation, yielding one degradation product—pharmacologically inactive NAB metabolite. However, under the oxidative conditions at elevated temperatures, 10 NAB degradation products were identified from co-ground samples. All systems were stable during photo- and long-term stability studies. Conclusions: NAB complexes with HP-β-CD and SBE-β-CD are promising candidates for pharmaceutical product development.
Two in One: Size Characterization and Accelerated Short-Term Physical Stability of Dual-Drug Suspensions with Two Acidic Compounds (Indomethacin and Naproxen)
Authors: Zulbeari Nadina , Hansen Signe Malig , Holm René
Published: November 2024

Background/Objectives: Co-delivering dual-drug systems have proven to be effective in, for example, anticancer therapy or HIV prophylaxis due to a higher target selectivity and therapeutic efficacy from compound synergism. However, various challenges regarding physical stability can arise during the formulation definition when multiple drug compounds are included in the same formulation. In this work, the focus was on aqueous suspensions, which could be applied as long-acting injectable formulations to release the drug compounds over weeks to months after administration. Methods: It was possible to gain insights into dual-drug nano- and microsuspensions containing two acidic compounds (indomethacin and naproxen) prepared by milling with dual centrifugation. Information regarding the physical stability of individual suspensions was subtracted and compared to dual-drug suspensions when prepared with the same milling conditions and stored at elevated temperatures of 40 °C. Results: Distinct particle size profiles after milling were obtained dependent on the stabilizer used in both individual and dual-drug suspensions. Most notably, the combination of indomethacin and naproxen in one formulation resulted in smaller sizes of drug particles compared to individual suspensions under the presence of some stabilizers. The obtained particle size profiles further indicated that at least one of the model compounds needed to be sufficiently stabilized from a stabilizer to obtain physically stable dual-drug suspensions over 28 days when stored at 40 °C. Similarly, the particle size distribution was dependent on the individual distribution of the suspensions, which showed a monomodal distribution could be achieved for dual-drug suspensions when at least one of the individual suspensions demonstrated a monomodal distribution in the presence of the stabilizer alone. Over a 28-day period, the smallest particle size was obtained in dual-drug suspensions stabilized with a combination of polysorbate 85 and poloxamer 338 compared to dual-drug suspensions stabilized with only a single stabilizer during preparation, indicating tendencies towards stabilization synergism from a combination of stabilizers as well as the model compounds. Conclusion: Overall, the study showed insights into the preparation and physical stability of dual-drug suspensions containing indomethacin and naproxen.
Comprehensive Genome-Wide Analysis of the Receptor-like Protein Gene Family and Functional Analysis of PeRLP8 Associated with Crown Rot Resistance in Passiflora edulis
Authors: Yu Weijun , Liang Fan , Li Yue , Jiang Wenjie , Li Yongkang , Shen Zitao , Fang Ting , Zeng Lihui
Published: November 2024

Passion fruit (Passiflora edulis Sims) is a Passifloraceae plant with high economic value. Crown rot caused by Rhizoctonia solani is a major fungal disease, which can seriously reduce the yield and quality of passion fruit. Receptor-like proteins (RLPs), which act as pathogen recognition receptors, are widely involved in plant immune responses and developmental processes. However, the role of RLP family members of passion fruit in resistance to crown rot remains unclear. In this study, evolutionary dynamics analysis and comprehensive genomic characterization of the RLP genes family were performed on passion fruit. A total of 141 PeRLPs in the genome of the ‘Zixiang’ cultivar and 79 PesRLPs in the genome of the ‘Tainong’ cultivar were identified, respectively. Evolutionary analysis showed that proximal and dispersed duplication events were the primary drivers of RLP family expansion. RNA-seq data and RT-qPCR analysis showed that PeRLPs were constitutively expressed in different tissues and induced by low temperature, JA, MeJA, and SA treatments. The PeRLP8 gene was identified as the hub gene by RNA-seq analysis of passion fruit seedlings infected by Rhizoctonia solani. The expression levels of PeRLP8 of the resistant variety Passiflora maliformis (LG) were significantly higher than those of the sensitive variety Passiflora edulis f. flavicarpa (HG). Transient overexpression of PeRLP8 tobacco and passion fruit leaves enhanced the resistance to Rhizoctonia solani, resulting in reduced lesion areas by 52.06% and 54.17%, respectively. In addition, it can increase reactive oxygen species levels and upregulated expression of genes related to active oxygen biosynthesis and JA metabolism in passion fruit leaves. Our research provides new insights into the molecular mechanism and breeding strategy of passion fruit resistance to crown rot.
Volatile Distribution in Flowers of Lathyrus odoratus L. by HS-SPME-GC Technique and Enantiomeric Separation Data
Authors: Calva James , Parra Mayerly , Benítez Ángel
Published: November 2024

Lathyrus odoratus L., commonly known as sweet pea, is a plant with a distinctive aroma that can develop in various habitats. An analysis of the aromatic profile of the species was conducted using the HS-SPME (solid-phase microextraction headspace) technique. This study aimed to explore the composition of and variation in the floral scent emissions of L. odorathus. The floral scents from fresh flowers were collected over different months and analyzed using gas chromatography coupled with mass spectrometry on apolar and polar stationary phase columns. In the apolar column, the majority compounds included linalool (19.27–5.79%), α-trans-bergamotene (29.4–14.21%), and phenyl ethyl alcohol (30.01–1.56%), while on the polar column, the predominant compounds included myrcene (13.25%), (E,E)-α-farnesene (26.33–8.16%), α-trans-bergamotene (42.09–24.82%), and others. This investigation was complemented by enantioselective analysis using a chiral phase based in cyclodextrins, which revealed the presence of (1R)-(+)-α-pinene, (S)-(−)-limonene, (R)-(+)-germacrene D, and (R)-(E)-nerolidol as enantiomerically pure components and linalool as a racemic mixture. Notably, the principal component analysis (PCA) and heatmap revealed variations among the chemical compounds collected at different harvest times. This demonstrates that temporal factors indeed impact chemical compound production. Furthermore, research on the aromatic properties of flowers provides a theoretical basis for studying and improving the components of their scent.
Effects of Diverse Crop Rotation Sequences on Rice Growth, Yield, and Soil Properties: A Field Study in Gewu Station
Authors: Yang Ruiping , Shen Yu , Kong Xiangyi , Ge Baoming , Sun Xiaoping , Cao Mingchang
Published: November 2024

This long-term field study conducted in Yancheng, China, evaluated the effects of diverse crop rotation sequences on rice growth, yield, and soil properties. Six rotation treatments were implemented from 2016 to 2023 as follows: rice–wheat (control), rice–rape, rice–hairy vetch, rice–barley, rice–faba bean, and rice–winter fallow. Rice growth parameters, yield components, biomass accumulation, and soil properties were measured. Results showed that legume-based rotations, particularly rice–faba bean and rice–hairy vetch, significantly improved rice growth and yield compared to the rice–wheat control. The rice–faba bean rotation increased yield by 19.1% to 8.73 t/ha compared to 7.33 t/ha for the control, while rice–hairy vetch increased yield by 11.9% to 8.20 t/ha. These rotations also demonstrated higher biomass production efficiency, with increases of 33.33% and 25.00%, respectively, in spring crop biomass. Soil nutrients improvements were observed, particularly in available nitrogen, potassium, and electrical conductivity. Legume-based rotations increased the available nitrogen by up to 35.9% compared to the control. The study highlights the potential of diversified crop rotations, especially those incorporating legumes, to enhance rice productivity and soil health in subtropical regions. These findings have important implications for developing sustainable and resilient rice-based cropping systems to address challenges of food security and environmental sustainability in the face of climate change and resource constraints.
Propolis Extract: Weaving Antioxidant Power into Polymeric Composites Through Electrospinning
Authors: Ramos Sergiana dos Passos , Bernardo Leonardo Ribeiro , Bürck Monize , Líbero Laura Ordonho , Assis Marcelo , Braga Anna Rafaela Cavalcante
Published: November 2024

The manufacture of composites with bioactive compounds represents a promising strategy for developing advanced materials in biomedical, food, and industrial applications. However, challenges such as stability, bioactivity retention, and controlled release hinder their effectiveness. Electrospinning emerges as a viable technique for encapsulating bioactive compounds, offering advantages such as high surface area, porosity, and gradual release, which are critical for maintaining the bioactivity of embedded compounds. Regarding bioactive composition, propolis has been highlighted as a potential source and has great potential as a biopolymer ingredient due to its antioxidant and antimicrobial properties. This study analyzed the composition and antioxidant activity of three commercial propolis extracts to select the most suitable extract for fiber composite production using zein and polyethylene oxide (PEO), both recognized as safe. The characterization of the electrospun fibers, including morphology, thermal properties, and antioxidant release, was conducted through various analytical techniques. The findings highlight the effectiveness of electrospinning for developing composite materials with bioactive compounds, paving the way for innovations in antioxidant technologies across multiple sectors.
Impact of Hexyl Branch Content on the Mechanical Properties and Deformation Mechanisms of Amorphous Ethylene/1-Octene Copolymers: A Molecular Dynamics Study
Authors: Zhang Ruijun , He Qiqi , Yu Hongbo , Li Junhua , Hu Yuexin , Qian Jianhua
Published: November 2024

Ethylene/1-octene copolymers exhibit enhanced flexibility and impact resistance compared to polyethylene, which makes them well suited for applications in advanced plastics and elastomers. United-atom molecular dynamics (MD) simulations were conducted to explore the mechanical behavior and deformation mechanisms of ethylene/1-octene copolymers under uniaxial tensile loading. This study systematically examined the influence of temperature, polymer chain length, chain quantity, and strain rate, with a specific focus on how hexyl branch content impacts the mechanical properties of amorphous ethylene/1-octene copolymers. The simulation results indicate that as the branch content increases, the yield strength and elastic modulus decrease, suggesting a trade-off between flexibility and mechanical strength. Energy decomposition analysis reveals that copolymers with more branched chains undergo greater changes in van der Waals energy. Additionally, as the branch content increases, the reduction in dihedral angle energy in the strain hardening region becomes more gradual, and the rate and the extent of the transition of dihedral angles from gauche to trans conformation decrease under deformation. Ethylene/1-octene copolymers exhibit higher chain entanglement parameters compared to linear polyethylene, with these parameters increasing as the branch content rises. Moreover, increasing the branch content results in a less pronounced increase in chain orientation along the loading direction.
Percutaneous Computed Tomography-Guided Cryoablation as a Treatment Option in Patients with Small Renal Masses: A 10 Year Experience in a Single Center
Authors: Marinelli Luca , Mercogliano Sara , Selvaggio Oscar , Carrieri Giuseppe , Sorrentino Raffaele , Mangano Paola , Prencipe Gianluca , Macarini Luca , Casavecchia Grazia , Gravina Matteo
Published: November 2024

Background: To evaluate p-Cry in 10 years as a feasible and radical approach in patients with small renal masses (<5 cm), we evaluated technical success, side effects, and survival rates. Materials and Methods: We retrospectively evaluated 421 patients with small renal masses (<5 cm) with a median age of 70 years (47–92 C.I.) between June 2014 and July 2024 at our department. We also evaluated side effects, surgical radicality, and therapeutic outcomes of renal functions. Survivals were also evaluated in terms of disease-free, metastasis-free, and cancer-related survival rates. Results: Median follow-up was 90 months (1–120 months C.I.), and median size of the tumor was 3.85 cm (1–4 C.I.). Two cryoprobes were used in median, and two 10-min freeze–thaw cycles were performed. The technical efficacy rate was 100%, whereas only one of 121 lesions required retreatment. No impact on the renal function was registered after p-Cry. Cancer-free survival and metastases-free survival was reached. Conclusions: Compared to surgery, p-Cry is a feasible treatment option in patients with small renal masses, as it does not affect renal function and gives patients good survival rates.
The Divinity of the Emperor and Postwar Japanese Conservative Nationalism
Authors: Zhong Yijiang
Published: November 2024

This paper explores the scholarly discourse on the divinity of the emperor in postwar Japan to better understand Japanese conservative nationalism, which has been regaining momentum since the 1990s. Viewing the idea of the divinity of the emperor as ideologically fundamental to Japanese conservative nationalism, this paper looks at how conservative scholars from the 1970s developed a culturalist argument for the divinity of the emperor, first to negate the “humanity declaration”, i.e., the New Year’s greeting by the Showa emperor on 1 January 1946 renouncing his divinity, and then to reconfigure conservative ideology into a popular discourse on Japanese identity (i.e., the Nihonjin-ron), thereby making it more easily accepted by postwar society. Key to this culturalist argument is an essentialized dichotomy between Japanese culture and Western culture, more specifically a binary between Shinto kami and the Christian God—that the Japanese concept of kami is qualitatively different from that of the Christian God, so the emperor is not God but is kami; therefore, the emperor’s divinity is not really denied and he remains the spiritual pillar of the Japanese nation even under the postwar constitutional regime. Refashioning itself as part of the increasingly popular but depoliticized Nihonjin-ron discourse, the culturalist argument on the divinity of the emperor helped make the imperial house a popular topic of the discourse on Japanese identities, even while it completely circumvented the very issues of war responsibility and historical memory which gave rise to the “humanity declaration” in 1946 in the first place. In its depoliticized, popularly appealing form, the culturalist argument played a role in legitimating the regressive conservative nationalism that seeks to revive the pre-1945 divine emperor-centered political regime. Exploring the scholarly discourse on the divinity of the emperor, then, helps shed light on how and why conservative nationalism could persist and gain momentum in the 21st century.
Bible Use and Human Flourishing Among Members of the U.S. Military Community
Authors: Jang Sung Joon , Bradshaw Matt , Johnson Byron R.
Published: November 2024

We examined an understudied aspect of religiosity, namely engagement with a sacred text, in relation to a multidimensional construct of well-being. Specifically, we hypothesized that the relationship between Bible use (various ways of utilizing the Bible) and human flourishing would be positive and mediated by three likely outcomes of Bible use: spiritual engagement, positive beliefs about the Bible, and the behavioral influence of the Bible. These relationships were also hypothesized to be reciprocal over time. To test these hypotheses, we estimated three-wave structural equation models using panel survey data from a quasi-experiment that assessed a scripture engagement program developed for the U.S. military members and their families. The results showed that Bible use and human flourishing were positively related, and that this relationship was partially explained by the behavioral influence of the Bible and, to a lesser extent, spiritual engagement and positive beliefs about the Bible. However, these relationships were not reciprocal across all waves.
Maturity Prediction in Soybean Breeding Using Aerial Images and the Random Forest Machine Learning Algorithm
Authors: Pérez Osvaldo , Diers Brian , Martin Nicolas
Published: November 2024

Several studies have used aerial images to predict physiological maturity (R8 stage) in soybeans (Glycine max (L.) Merr.). However, information for making predictions in the current growing season using models fitted in previous years is still necessary. Using the Random Forest machine learning algorithm and time series of RGB (red, green, blue) and multispectral images taken from a drone, this work aimed to study, in three breeding experiments of plant rows, how maturity predictions are impacted by a number of factors. These include the type of camera used, the number and time between flights, and whether models fitted with data obtained in one or more environments can be used to make accurate predictions in an independent environment. Applying principal component analysis (PCA), it was found that compared to the full set of 8–10 flights (R2 = 0.91–0.94; RMSE = 1.8–1.3 days), using data from three to five fights before harvest had almost no effect on the prediction error (RMSE increase ~0.1 days). Similar prediction accuracy was achieved using either a multispectral or an affordable RGB camera, and the excess green index (ExG) was found to be the important feature in making predictions. Using a model trained with data from two previous years and using fielding notes from check cultivars planted in the test season, the R8 stage was predicted, in 2020, with an error of 2.1 days. Periodically adjusted models could help soybean breeding programs save time when characterizing the cycle length of thousands of plant rows each season.
Cotton Yield Prediction via UAV-Based Cotton Boll Image Segmentation Using YOLO Model and Segment Anything Model (SAM)
Authors: Reddy Janvita , Niu Haoyu , Scott Jose L. Landivar , Bhandari Mahendra , Landivar Juan A. , Bednarz Craig W. , Duffield Nick
Published: November 2024

Accurate cotton yield prediction is essential for optimizing agricultural practices, improving storage management, and efficiently utilizing resources like fertilizers and water, ultimately benefiting farmers economically. Traditional yield estimation methods, such as field sampling and cotton weighing, are time-consuming and labor intensive. Emerging technologies provide a solution by offering farmers advanced forecasting tools that can significantly enhance production efficiency. In this study, the authors employ segmentation techniques on cotton crops collected using unmanned aerial vehicles (UAVs) to predict yield. The authors apply Segment Anything Model (SAM) for semantic segmentation, combined with You Only Look Once (YOLO) object detection, to enhance the cotton yield prediction model performance. By correlating segmentation outputs with yield data, we implement a linear regression model to predict yield, achieving an R2 value of 0.913, indicating the model’s reliability. This approach offers a robust framework for cotton yield prediction, significantly improving accuracy and supporting more informed decision-making in agriculture.