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Al hilo de la nueva edición y traducción que estoy llevando a cabo del poema agrícola del almeriense Ibn Luyūn (s. XIV), ofrezco en este artículo un estudio sobre el conjunto de capítulos que tratan las plantas que son usadas como decoración por su belleza o su buen olor. En dicho estudio, realizo en primer lugar una nueva edición y traducción tanto de los capítulos citados como de las notas marginales que los acompañan. Para la edición he utilizado tres de las cinco copias registradas de esta obra, lo que conlleva una nueva lectura más completa que la realizada anteriormente por Joaquina Eguaras. A continuación, analizo los datos que se encuentran en las notas marginales (no editadas ni traducidas en su día por la aludida arabista), las cuales son muy numerosas y de gran interés al abarcar temas muy variados y reflejar las diferentes fuentes que usa Ibn Luyūn. Este último aspecto, sin duda, permitirá profundizar en el conocimiento agronómico, tanto teórico como práctico, propio del periodo nazarí y la aportación del autor de Almería al mismo.

Ex vivo programming of T cells can be efficacious but is complex and expensive; therefore, the development of methods to transfect T cells in situ is important. We developed and optimized anti-CD3-targeted lipid nanoparticles (aCD3-LNPs) to deliver tightly packed, reporter gene mRNA specifically to T cells. In vitro, targeted LNPs efficiently delivered mCherry mRNA to Jurkat T cells, and T-cell activation and depletion were associated with aCD3 antibody coating on the surface of LNPs. aCD3-LNPs, but not non-targeted LNPs, accumulated within the spleen following systemic injection, with mCherry and Fluc signals visible within 30 min after injection. At 24 h after aCD3-LNP injection, 2-4% of all splenic T cells and 2-7% of all circulating T cells expressed mCherry, and this was dependent on aCD3 coating density. Targeting and transfection were accompanied by systemic CD25+, OX40+, and CD69+ T-cell activation with temporary CD3e ligand loss and depletion of splenic and circulating subsets. Migration of splenic CD8a+ T cells from the white-pulp to red-pulp, and differentiation from naïve to memory and effector phenotypes, followed upon aCD3-LNP delivery. Additionally, aCD3-LNP injection stimulated the secretion of myeloid-derived chemokines and T-helper cytokines into plasma. Lastly, we administered aCD3-LNPs to tumor bearing mice and found that transfected T cells localized within tumors and tumor-draining lymph nodes following immunotherapy treatment. In summary, we show that CD3-targeted transfection is feasible, yet associated with complex immunological consequences that must be further studied for potential therapeutic applications.

Background: Although combination immunotherapies incorporating local and systemic components have shown promising results in treating solid tumors, varied tumor microenvironments (TMEs) can impact immunotherapeutic efficacy. Method: We designed and evaluated treatment strategies for breast and pancreatic cancer combining magnetic resonance-guided focused ultrasound (MRgFUS) ablation and antibody therapies. With a combination of single-cell sequencing, spectral flow cytometry, and histological analyses, we profiled an immune-suppressed KPC (Kras+/LSL-G12D; Trp53+/LSL-R172H; Pdx1-Cre) pancreatic adenocarcinoma (MT4) model and a dense epithelial neu deletion (NDL) HER2+ mammary adenocarcinoma model with a greater fraction of lymphocytes, natural killer cells and activated dendritic cells. We then performed gene ontology analysis, spectral and digital cytometry to assess the immune response to combination immunotherapies and correlation with survival studies. Result: Based on gene ontology analysis, adding ablation to immunotherapy enriched immune cell migration pathways in the pancreatic cancer model and extensively enriched wound healing pathways in the breast cancer model. With CIBERSORTx digital cytometry, aCD40 + aPD-1 immunotherapy combinations enhanced dendritic cell activation in both models. In the MT4 TME, adding the combination of aCD40 antibody and checkpoint inhibitors (aPD-1 and aCTLA-4) with ablation was synergistic, increasing activated natural killer cells and T cells in distant tumors. Furthermore, ablation with immunotherapy upregulated critical Ly6c myeloid remodeling phenotypes that enhance T-cell effector function and increased granzyme and protease encoding genes by as much as 100-fold. Ablation combined with immunotherapy then extended survival in the MT4 model to a greater extent than immunotherapy alone. Conclusion: In summary, TME profiling informed a successful multicomponent treatment protocol incorporating ablation and facilitated differentiation of TMEs in which ablation is most effective.

Abstract Manipulating gene expression in the host genome with high precision is crucial for controlling cellular function and behavior. Here, we present a precise, non-invasive, and tunable strategy for controlling the expression of multiple endogenous genes both in vitro and in vivo, utilizing ultrasound as the stimulus. By engineering a hyper-efficient dCas12a and effector under a heat shock promoter, we demonstrate a system that can be inducibly activated through thermal energy produced by ultrasound absorption. This system allows versatile thermal induction of gene activation or base editing across cell types, including primary T cells, and enables multiplexed gene activation using a single guide RNA array. In mouse models, localized temperature elevation guided by high-intensity focused ultrasound effectively triggers reporter gene expression in implanted cells. Our work underscores the potential of ultrasound as a clinically viable approach to enhance cell and gene-based therapies via precision genome and epigenome engineering.

Resiquimod is an immunopotent toll-like receptor 7/8 agonist with antitumor activity. Despite being potent against skin cancers, it is poorly tolerated systemically due to toxicity. Integrating resiquimod into nanoparticles presents an avenue to circumvent the toxicity problem. Herein, the preparation of degradable nanoparticles with covalently bound resiquimod and their systemic application in cancer immunotherapy is reported. Dispersion in water of amphiphilic constructs integrating resiquimod covalently bound via degradable amide or ester linkages yields immune-activating nanoparticles. The degradable agonist-nanoparticle bonds allow the release of resiquimod from the carrier nanoparticles. In vitro assays with antigen presenting cells demonstrate that the nanoparticles retain the immunostimulatory activity of resiquimod. Systemic administration of the nanoparticles and checkpoint blockade (aPD-1) to a breast cancer mouse model with multiple established tumors triggers antitumor activity evidenced by suppressed tumor growth and enhanced CD8+ T-cell infiltration. Nanoparticles with ester links, which hydrolyze more readily, yield a stronger immune response with 75% of tumors eliminated when combined with aPD-1. The reduced tumor growth and the presence of activated CD8+ T-cells across multiple tumors suggest the potential for treating metastatic cancer.

Resiquimod (R848) is a toll-like receptor 7 and 8 (TLR7/8) agonist with potent antitumor and immunostimulatory activity. However, systemic delivery of R848 is poorly tolerated because of its poor solubility in water and systemic immune activation. In order to address these limitations, we developed an intravenously-injectable formulation with R848 using thermosensitive liposomes (TSLs) as a delivery vehicle. R848 was remotely loaded into TSLs composed of DPPC: DSPC: DSPE-PEG2K (85:10:5, mol%) with 100 mM FeSO4 as the trapping agent inside. The final R848 to lipid ratio of the optimized R848-loaded TSLs (R848-TSLs) was 0.09 (w/w), 10-fold higher than the previously-reported values. R848-TSLs released 80% of R848 within 5 min at 42 °C. These TSLs were then combined with αPD-1, an immune checkpoint inhibitor, and ultrasound-mediated hyperthermia in a neu deletion (NDL) mouse mammary carcinoma model (Her2+, ER/PR negative). Combined with αPD-1, local injection of R848-TSLs showed superior efficacy with complete NDL tumor regression in both treated and abscopal sites achieved in 8 of 11 tumor bearing mice over 100 days. Immunohistochemistry confirmed enhanced CD8+ T cell infiltration and accumulation by R848-TSLs. Systemic delivery of R848-TSLs, combined with local hyperthermia and αPD-1, inhibited tumor growth and extended median survival from 28 days (non-treatment control) to 94 days. Upon re-challenge with reinjection of tumor cells, none of the previously cured mice developed tumors, as compared with 100% of age-matched control mice. The dose of R848 (10 μg for intra-tumoral injection or 6 mg/kg for intravenous injection delivered up to 4 times) was well-tolerated without weight loss or organ hypertrophy. In summary, we developed R848-TSLs that can be administered locally or systematically, resulting in tumor regression and enhanced survival when combined with αPD-1 in mouse models of breast cancer.

Robust cytotoxic T cell infiltration has proven to be difficult to achieve in solid tumors. We set out to develop a flexible protocol to efficiently transfect tumor and stromal cells to produce immune-activating cytokines, and thus enhance T cell infiltration while debulking tumor mass. By combining ultrasound with tumor-targeted microbubbles, membrane pores are created and facilitate a controllable and local transfection. Here, we applied a substantially lower transmission frequency (250 kHz) than applied previously. The resulting microbubble oscillation was significantly enhanced, reaching an effective expansion ratio of 35 for a peak negative pressure of 500 kPa in vitro. Combining low-frequency ultrasound with tumor-targeted microbubbles and a DNA plasmid construct, 20% of tumor cells remained viable, and ∼20% of these remaining cells were transfected with a reporter gene both in vitro and in vivo. The majority of cells transfected in vivo were mucin 1+/CD45- tumor cells. Tumor and stromal cells were then transfected with plasmid DNA encoding IFN-β, producing 150 pg/106 cells in vitro, a 150-fold increase compared to no-ultrasound or no-plasmid controls and a 50-fold increase compared to treatment with targeted microbubbles and ultrasound (without IFN-β). This enhancement in secretion exceeds previously reported fourfold to fivefold increases with other in vitro treatments. Combined with intraperitoneal administration of checkpoint inhibition, a single application of IFN-β plasmid transfection reduced tumor growth in vivo and recruited efficacious immune cells at both the local and distant tumor sites.

Abstract Background Strawberry fruit is a rich source of antioxidants that are beneficial for human health. However, the rapid decline of strawberries dramatically reduces the shelf life and raises postharvest losses. To develop an efficient and ecological approach for maintaining the quality, strawberries (Fragaria x ananassa, cv. Festival) were treated with 0.5% chitosan coating (0.5% Ch), guava leaf-based chitosan nanoparticles coating (Gl-ChNps), and a combination treatment of 1.3 mW/cm2 laser light followed by Gl-ChNps coating (combined treatment), then stored for 12 days at 10 °C and 85–90% RH. The untreated fruit served as a control. Results Semi-spherical particles with an average size of 21.92 nm, a monodisperse nature, and high solution stability were formed. The findings revealed that the combined treatment completely suppressed fungal decay compared to 50% decay in control, and significantly reduced weight loss percentage to 4.68% compared to 27.35% in control. In accordance, the combined treatment had the maximum anthocyanin content and vitamin C, at 42 and 81.1 mg/100 g, respectively. The results showed that treated strawberries had less change in color, total soluble solids, titratable acidity, and pH during storage than untreated strawberries, which exhibited higher chemical changes. Conclusions The edible film of chitosan nanoparticles acted as a semi-permeable barrier that modified and restricted gas exchange, reduced water loss, and delayed fruit senescence. In addition, the combination of laser light with chitosan nanoparticles has been shown to control the pathogens and retain the freshness of strawberries. Graphical Abstract

Abstract PARP inhibitors were recently approved for treatment of molecularly-defined subsets of metastatic castrate-resistant prostate cancer (mCRPC) patients. Although the PARP inhibitor olaparib was approved for use in patients with a mutation in one of fourteen genes, the mutation frequency of the genes varies widely in mCRPC and the impact of the less commonly altered genes on PARP inhibitor sensitivity is uncertain. We used functional approaches to directly test the impact of PALB2 and BARD1 loss on homologous recombination (HR) function and PARP inhibitor sensitivity in prostate cancer cell lines. PALB2 or BARD1 loss led to decreased HR function as measured by loss of radiation-induced Rad51 foci formation as well as decreased HR capacity in a cell-based reporter assay. PALB2 or BARD1 loss also significantly increased sensitivity to the PARP inhibitors olaparib and rucaparib across a panel of prostate cancer cell lines. These data support PALB2 and BARD1 loss as markers of clinically relevant PARP inhibitor sensitivity and highlight the potential to use functional approaches to complement and extend findings from clinical trials of targeted agents.

The geography of Iran is a haven of historical farmsteads with specific physical and functional characteristics. These small bio-complexes have a fixed population and physical structures related to agriculture and settlement, and they grew and developed in the centre of Iran from before Islam to the Zand and Qajar periods and then reached a low point in the Pahlavi period. The moot point of the research is the need to know more about the nature of historical residential farmsteads. Many farmsteads, including buildings related to them, are subject to destruction. The purpose of the research is to obtain more information about the locality of farmsteads in the geographical arrangement of Iran, and to this end, the interpretive approach and historical interpretive strategy are used in the form of document research and field studies. According to the study findings, residential farmsteads, as the infinitesimal living complexes, were a subcategory of villages, acting independently or subordinately, and were considered a part of Iran's geographical system. Physical, agricultural and customary areas are their three significant influencers. The physical and agricultural zone is compared to the farmstead's core zone, while the customary area is equivalent to its buffer zone.

Background: Hospitalization of a premature neonate in the Neonatal Intensive Care Unit (NICU) is stressful for mothers. They show symptoms of Post-Traumatic Stress Disorder (PTSD). It is important to use the proper strategy to manage PTSD. This study was designed to investigate the effect of non-verbal music on the PTSD in mothers of premature neonates hospitalized in NICU. Materials and Methods: In this clinical trial study, the convenience sampling method was applied and 45 mothers of premature neonates were selected and categorized randomly into the intervention (N = 23) and control (N = 22) groups in 2018. The babies were hospitalized in one of the NICUs in Yazd (Iran). The intervention group were supposed to listen to the non-verbal music for 20 minutes daily for two weeks using MP3 player and headphones. All participants completed the Perinatal PTSD Questionnaire (PPQ). The data were analyzed by SPSS 21 using paired t-test, independent t-test, and Chi-square test. Results: The PTSD mean (SD) scores before and after the intervention was 9.39 (1.67) and 4.39 (1.49), respectively, in experimental group. It was 8.54 (1.59) and 5.31 (1.71) in control group. The severity of PTSD decreased in the intervention (p = 0.003) and control (p < 0.001) groups after the intervention. The difference between the two groups was significant (F1,07 = 1058, p < 0.03), which confirmed the significant effect of the non-verbal music on decreasing the PTSD severity (0.92). Conclusions: Non-verbal music can be used as an effective and low-cost intervention for managing PTSD in mothers of premature neonates hospitalized in the NICU.

Background: Preterm birth and admission to neonatal intensive care unit as stressors can cause physiologicalinstability that may lead to prolong hospitalization and mortality. This study aimed to determine the effect of artificialnights and facilitated tucking on the physiological indices of premature infants.Methods: This randomized clinical trial was conducted on 60 preterm infants admitted to the neonatal intensive careunit at Shohadaye Kargar Hospital in Yazd, Iran, during 2017-18. The infants were selected through a convenientsampling method, and were randomly assigned into three groups of arti icial nights with facilitated tucking (group 1)(n=20), arti icial nights (group 2) (n=20) and control group (group 3) (n=20). Subsequently, the physiological indices(i.e., heart rate, respiration rate, arterial oxygen saturation) were measured twice a day at 7:00 a.m. and 19:00 p.m. for3 days. The data were analyzed in SPSS software (version 20). A p-value less than 0.05 was considered statisticallysignificant.Results: There was a significant difference among the three groups in terms of mean values of heart, respiratory, andarterial oxygen saturation rates (Prespiratory rate on the third day (at 19:00 p.m.), as well as a greater increase in arterial oxygen saturation rate on thesecond (at 19:00 p.m.) and third days (at 7:00 a.m. and 19:00 p.m.), compared to the other two groups (PAdditionally, , the mean value of heart and respiratory rates were lower and arterial oxygen saturation rates werehigher in the intervention group 1, compared to the other groups.Conclusion: According to the results of the study, the simulation of the mother’s womb environment through creatingartificial night and maintaining facilitated tucking resulted in the improvement of physiological indices of thepremature infants. Furthermore, artificial night together with facilitated tucking leads to better results, compared toartificial night alone.

Collaborative care has emerged as a critical framework in modern healthcare, emphasizing the interconnected roles of various professionals, including nursing, radiology, pharmacy, health security, and emergency medical services (EMS). This approach recognizes that effective patient management requires the integration of diverse expertise to address the multifaceted needs of individuals. By fostering communication, shared decision-making, and coordinated care, collaborative care models aim to enhance patient outcomes and improve the efficiency of healthcare delivery. In traditional healthcare settings, the compartmentalization of roles often leads to fragmented care, resulting in potential gaps in patient management. In contrast, collaborative care seeks to bridge these gaps by promoting teamwork among healthcare providers. Nurses serve as primary advocates for patients, conducting assessments and facilitating communication among team members. Radiologists contribute critical diagnostic information through imaging studies, ensuring that results are integrated into the overall care plan. Pharmacists optimize medication management and provide essential education to patients, while health security professionals and EMS ensure preparedness for emergencies and public health threats. This article explores the vital contributions of each discipline within the collaborative care framework, highlighting the importance of interdisciplinary collaboration in optimizing patient management. It also addresses the challenges and opportunities associated with implementing collaborative care models, emphasizing the need for effective communication, standardized protocols, and the integration of technology to support teamwork. As healthcare continues to evolve, the emphasis on collaborative care is increasingly relevant, particularly in the context of rising chronic diseases and an aging population. By embracing this model, healthcare systems can enhance the quality of care, reduce costs, and improve overall health outcomes. This review aims to provide a comprehensive understanding of collaborative care, illustrating its significance in contemporary healthcare and its potential to transform patient management through integrated, patient-centered approaches. [ABSTRACT FROM AUTHOR]

Purpose: This article explores the results of community-engaged PhotoVoice research with the Family Tree Clinic (FTC) in St. Paul, MN. FTC has >45 years of experience providing sexual, reproductive, and primary health care, with a central mission of overcoming issues for their patients including those of poverty, oppression, lack of access, and discrimination in meeting health care needs. Methods: This research presents the findings of social justice-inspired PhotoVoice focus groups with patients of the clinic that asked two central questions: ?Why do you choose Family Tree Clinic? and ?What stands in the way of achieving your goals for your health?? Results: When health equity is a central priority and evident in clinic culture, practices, and policies, patients articulate positive experiences despite real structural and systemic barriers outside the clinic. Conclusion: We offer suggestions for a health equity-oriented approach to clinic care.

Sleep-related breathing disorders (SBDs) are characterized by abnormal respiration during sleep. Obstructive sleep apnea (OSA), a common SBD increasingly recognized by physicians, is characterized by recurrent episodes of partial or complete closure of the upper airway resulting in disturbed breathing during sleep. OSA syndrome (OSAS) is associated with decreased patients' quality of life (QoL) and the presence of significant comorbidities, such as daytime sleepiness. Similarly to what seen for OSAS, the prevalence of asthma has been steadily rising in recent years. Interestingly, severe asthma (SA) patients are also affected by poor sleep quality—often attributed to nocturnal worsening of their asthma—and increased daytime sleepiness and snoring compared to the general population. The fact that such symptoms are also found in OSAS, and that these two conditions share common risk factors, such as obesity, rhinitis, and gastroesophageal reflux, has led many to postulate an association between these two conditions. Specifically, it has been proposed a bidirectional correlation between SA and OSAS, with a mutual negative effect in term of disease severity. According to this model, OSAS not only acts as an independent risk factor of asthma exacerbations, but its co-existence can also worsen asthma symptoms, and the same is true for asthma with respect to OSAS. In this comprehensive review, we summarize past and present studies on the interrelationship between OSAS and SA, from endo-phenotype to clinical aspects, highlighting possible implications for clinical practice and future research directions.

Shrines, as part of the most magnificent works of Islamic art, not only play an essential role in the social life of cities but also reflect the architecture and arts of their time. Sometimes, these buildings are grouped and have been constructed over various periods. In the present study, the shrine of Al-Kadhimiya is examined. The Al-Kadhimiya shrine complex, located in Baghdad, includes the tombs of two Shiite Imams. The construction of this complex began in the ninth century. The oldest inscription in this collection dates back to 1519 AD. According to historical evidence, the structure was built during the Safavid period. However, the construction rules, proportions, and principles of covering the space, as well as the design of the dome and the surrounding porch, incorporate pre-Safavid (Azeri) and Timurid art styles. This raises the question: how can a comparative study of the dome of the Al-Kadhimiya shrine with similar examples from the Timurid period prove that the change in artistic styles is a gradual process and not necessarily subject to changes in government? Therefore, this study examines the following hypothesis: the historical discontinuation of governments does not directly affect the architectural structures related to the subsequent period, which instead follow a gradual developmental course. This article employs a historical research method and comparative analysis. It compares the Al-Kadhimiya shrine with two complexes: the shrine of the eighth Imam of the Shiites in Mashhad, Iran, and the tomb of Shah Nematullah Vali in Kerman, Iran, as well as other Timurid domes. The results indicate that architectural techniques and structures are not necessarily updated with changes in government but follow a gradual process. [ABSTRACT FROM AUTHOR]

Bladder cancer is a genetically heterogeneous disease, and novel therapeutic strategies are needed to expand treatment options and improve clinical outcomes. Here, we identified a unique subset of urothelial tumors with focal amplification of the RAF1 (CRAF) kinase gene. RAF1-amplified tumors had activation of the RAF/MEK/ERK signaling pathway and exhibited a luminal gene expression pattern. Genetic studies demonstrated that RAF1-amplified tumors were dependent upon RAF1 activity for survival, and RAF1-activated cell lines and patient- derived models were sensitive to available and emerging RAF inhibitors as well as combined RAF plus MEK inhibition. Furthermore, we found that bladder tumors with HRAS- or WRAS-activating mutations were dependent on RAF1-mediated signaling and were sensitive to RAF1-targeted therapy. Together, these data identified RAF1 activation as a dependency in a subset making up nearly 20% of urothelial tumors and suggested that targeting RAF1-mediated signaling represents a rational therapeutic strategy., Introduction Bladder cancer accounts for approximately 80,000 new cancer diagnoses and nearly 20,000 deaths annually in the United States (1). Approximately 25% of patients present with muscle-invasive bladder cancer (MIBC), [...]