Complementary Approaches Research Articles

Exploring the views and experiences of professionals using PBS and emotional development assessment for individuals with an intellectual disability: a case study

Purpose The purpose of this paper was to investigate the utility of including emotional development (ED) assessment into a Positive Behaviour Support (PBS) approach in clinical practice with a patient with an intellectual disability (ID) and challenging behaviour. Design/methodology/approach Interviews were conducted with four staff involved in the care of the patient. The interviews were transcribed and analysed using thematic analysis and three reflective sessions were completed with the lead psychologist of the service. Findings Using thematic analysis, four themes were identified: getting everyone around the table: a collaborative approach, complementary approaches: a feedback loop, helping to make sense of the individual and ensuring a voice for service users. Research limitations/implications This was a case study selected from routine clinical practice and as such generalisability may be limited. This case study was designed as an exploration of the potential benefits of incorporating ED alongside PBS for ID and provides a basis for future research. Practical implications This study highlights the value of integration of ED assessment for people with ID and challenging behaviour within a healthcare team. Originality/value There is a lack of literature relating to ED and challenging behaviour within an ID population, particularly exploring ED within a PBS framework. This study provides a starting point for exploring how practice can be improved through incorporating ED assessment for individuals with ID and challenging behaviour.

Deciphering the Monomeric and Dimeric Conformational Landscapes of the Full-Length TDP-43 and the Impact of the C-Terminal Domain.

The aberrant aggregation of TAR DNA-binding protein 43 kDa (TDP-43) in cells leads to the pathogenesis of multiple fatal neurodegenerative diseases. Decoding the proposed initial transition between its functional dimeric and aggregation-prone monomeric states can potentially design a viable therapeutic strategy, which is presently limited by the lack of structural detail of the full-length TDP-43. To achieve a complete understanding of such a delicate phase space, we employed a multiscale simulation approach that unearths numerous crucial features, broadly summarized in two categories: (1) state-independent features that involve inherent chain collapsibility, rugged polymorphic landscape dictated by the terminal domains, high β-sheet propensity, structural integrity preserved by backbone-based intrachain hydrogen bonds and electrostatic forces, the prominence of the C-terminal domain in the intrachain cross-domain interfaces, and equal participation of hydrophobic and hydrophilic (charged and polar) residues in cross-domain interfaces; and (2) dimerization-modulated characteristics that encompass slower collapsing dynamics, restricted polymorphic landscape, the dominance of side chains in interchain hydrogen bonds, the appearance of the N-terminal domain in the dimer interface, and the prominence of hydrophilic (specifically polar) residues in interchain homo- and cross-domain interfaces. In our work, the ill-known C-terminal domain appears as the most crucial structure-dictating domain, which preferably populates a compact conformation with a high β-sheet propensity in its isolated state stabilized by intrabackbone hydrogen bonds, and these signatures are comparatively faded in its integrated form. Validation of our simulated observables by a complementary spectroscopic approach on multiple counts ensures the robustness of the computationally predicted features of the TDP-43 aggregation landscape.

Field surveysin rural Tanzania reveal key opportunities for targeted larval source management and species sanitation to control malaria in areas dominated by Anopheles funestus.

Larval source management (LSM) is re-emerging as a critical malaria intervention to address challenges associated with core vector control tools, such as insecticide-treated nets (ITNs), and to accelerate progress towards elimination. Presently, LSM is not widely used in rural settings and is instead more commonly applied in urban and arid settings. A systematic entomological assessment was conducted in rural communities of southeastern Tanzania, where insecticide-treated nets (ITNs) are widely used, to explore opportunities for deploying LSM to improve malaria control. Aquatic habitat surveys were conducted in 2022 and 2023 to understand habitat usage by different mosquito vectors, covering five villages during the rainy season and seven villages during the dry season. Additionally, samples of adult mosquitoes were collected to assess the role of various Anopheles species in malaria transmission in the area, and to explore opportunities for species sanitation using targeted LSM. Adult mosquito surveys showed that in this area, the total entomological inoculation rates (EIR) for indoor collections were 20.1 and 6.5 infectious bites per person per year for outdoors. Anopheles funestus and Anopheles arabiensis were the only Anopheles vectors identified. Anopheles funestus was responsible for over 97.6% of the malaria transmission indoors and 95.4% outdoors. The concurrent larval surveys found that habitats with late instar An. arabiensis and An. funestus comprised only a small subset of 11.2%-16.5% of all water bodies in the rainy season, and 9.7%-15.2% in the dry season. In terms of size, these habitats covered 66.4%-68.2% of the total habitat areas in the wet season, reducing to 33.9%-40.6% in the dry season. From the rainy season to the dry season, the surface area of habitats occupied by An. arabiensis and An. funestus decreased by 92.0% to 97.5%, while the number of habitats occupied by An. arabiensis and An. funestus decreased by 38.0% to 57.3%. Anopheles funestus preferred large, permanent habitats with clear water and vegetation year-round, while An. arabiensis showed contrasting seasonal preferences, favouring sunlit still waters in the rainy season and larger, opaque habitats in the dry season. These findings suggest that An. funestus, which is the dominant malaria vector in the area, mediating over 95% of malaria transmission, preferentially occupies only a small subset of uniquely identifiable aquatic habitats in both wet and dry seasons. This presents an opportunity to expand LSM in rural settings by carefully targeting An. funestus habitats, which might be effective and logistically feasible as a complementary approach alongside existing interventions. Further research should assess the impact of targeted LSM for species sanitation compared to blanket LSM.

Potential impacts of AluYa5 (ACE & PROGINS) and AluYb8 (MUTYH) insertions in panic disorder

Objective: The human genome contains numerous active transposable elements (TEs), including the inserts of young Alus such as AluYa5 and AluYb8. The rapid, human lineage-specific evolution of brain size may be influenced by natural selection and the genomic variation of TEs, which can act as catalysts of evolution. Given their potential effects on human brain development, Alu elements may also be relevant in exploring complementary approaches for psychiatric disorders. This study analyzed the potential impacts of three specific Alu insertions (AluYa5-ACE, AluYa5-PROGINS, and AluYb8-MUTYH) on the susceptibility to panic disorder (PD). Materials and Methods: Alu insertions were determined with Polymerase Chain Reaction (PCR) method in 120 PD patients and 120 healthy control individuals and analyzed with logistic regression. The associations of the investigated Alus with both categorical and quantitative demographic-clinical variables including the Panic Disorder Severity Scale (PDSS) were analyzed using Fisher's exact and Kruskal-Wallis tests. Results: AluYa5-PROGINS and AluYb8-MUTYH did not show an association with panic disorder risk. For AluYa5-ACE, a statistically significant association was determined; logistic regression analysis proved the highly protective effect (47.9%) of I/D genotype against PD compared with D/D genotype (p=0.030, OR=0.521, 95% CI=0.290-0.937). Alu insertions were not associated with panic disorder severity (p>0.05). Conclusion: This is the first combined study in which the potential effects of three Alu insertions in terms of both PD susceptibility and possible association with several disease parameters were evaluated. Further studies about the roles of the Alu elements in the etiology PD are highly recommended.

Abstract B013: Investigation of a novel lncRNA, TROLL-9, in breast cancer formation and progression

Abstract Breast cancer (BC) is the most diagnosed cancer and the second leading cancer-related cause of mortality among women in the US. Despite advances in treatment, BC remains a challenge due to its metastatic potential. The most aggressive BC subtype, triple negative (TN), often harbors mutations in the tumor suppressor gene, p53. One of the effects of mutant p53 involves the inhibition of the tumor and metastatic suppressive functions of TAp63, a p53 family member. Loss of TAp63 leads to the formation of metastatic mammary adenocarcinomas in mice, in part through the regulation of a group of nine long non-coding RNAs (lncRNAs), that we identified and named TAp63 regulated oncogenic lncRNAs (TROLLs). We previously characterized two TROLLs, TROLL-2 and TROLL-3, as markers of tumor progression in multiple cancer types via the activation of the AKT pathway. Currently we are investigating the role of another member, TROLL-9. To investigate the biological role of TROLL-9, we performed in vivo experiments using preclinical mouse models. Specifically, MCF-DCIS, MCF-CA1D, and MDA-MB-231 triple negative breast cancer (TNBC) cells constitutively expressing TROLL-9 were generated and utilized for two mouse models: orthotopic xenografts for primary tumor growth and spontaneous metastasis. The former was designed to identify the potential role of TROLL-9 in tumor formation, whereas the latter involved the resection of a primary tumor and monitoring for metastases via bioluminescence imaging. Notably, TROLL-9 overexpression led to increased formation of lung and livers metastases in all these models, suggesting a role for TROLL-9 in the metastatic cascade. In order to elucidate the mechanism of function of TROLL-9, two complementary approaches were used. Firstly, pulldown using MS2-TRAP followed by mass spectrometry (MS) was performed and led to the identification of putative protein interactors. In parallel, Laser Capture Microscopy (LCM) of the lung metastases followed by RNA-sequencing was used to assess for any gene expression changes due to TROLL-9 overexpression. Integration of the two datasets is currently being performed to unveil the network of genes and proteins perturbed by TROLL-9. Furthermore, to understand the relevance in BC patients, TROLL-9 expression levels were analyzed in the TCGA BC dataset. Interestingly, differences in TROLL-9 levels across BC subtypes were observed, thus supporting its putative role in TNBC. Overall, our data suggest a role for TROLL-9 in BC progression. Our findings provide evidence for further characterizing its mechanism of function as a potential therapeutic target for the treatment of invasive BC, particularly TNBC harboring TP53 mutations. Citation Format: Avani A Deshpande, Marco Napoli, John H Lockhart, Christina L Carr, Jaden R Baldwin, Elsa R Flores. Investigation of a novel lncRNA, TROLL-9, in breast cancer formation and progression [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: RNAs as Drivers, Targets, and Therapeutics in Cancer; 2024 Nov 14-17; Bellevue, Washington. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(11_Suppl):Abstract nr B013.

Abstract B049: Validation of the PGDx elio™ plasma complete for comprehensive genomic profiling of solid tumors through liquid biopsy with Epic Sciences

Abstract Introduction: To help guide treatment decisions and enable clinical trial matching for cancer patients, tissue-based comprehensive genomic profiling (CGP) is an essential precision oncology tool. Liquid biopsy may be used as a complementary approach to assess tumor-specific DNA alterations circulating in the blood when tissue is limited or unavailable. PGDx’s elio™ plasma complete is a next-generation-sequencing (NGS), cell-free DNA (cfDNA) CGP assay that identifies clinically significant variants from the plasma of patients with advanced and metastatic solid cancers. Methods: The PGDx elio plasma complete is a hybrid-capture, DNA-based kitted solution, optimized for 25 ng of cfDNA input with a targeted panel covering coding exons for 521 genes, and is designed to detect single nucleotide variants (SNVs), small insertions and deletions (indels), copy number amplifications (CNAs), and translocations. It also evaluates blood MSI and tumor mutational burden (bTMB) to guide immunotherapy selection. This study presents the validation of the PGDx elio plasma complete assay to enable the processing of patient blood samples in Epic Sciences' CAP/CLIA-certified laboratory. In the validated configuration, patient plasma will be received and isolated at Epic Sciences and subsequently shipped to PGDx/Labcorp Oncology for cfDNA extraction, library preparation, sequencing, and bioinformatics analysis. Finally, clinical report generation will be carried out by Velsera’s CGW software. Analytical validation was assessed using 105 replicates of SeraCare® (n=21) and Horizon (n=3) reference materials to establish analytical sensitivity, accuracy, and reproducibility and repeatability. Specificity was assessed using 20 non-cancerous plasma samples that were also tested orthogonally. For clinical validation a cohort of >150 cancer patient plasma samples were evaluated, including lung, breast, colorectal, head and neck, pancreatic, and prostate cancers, and compared to Illumina’s TSO500 ctDNA or Labcorp Plasma Focus results. Results: Analytical sensitivity and specificity were evaluated for SNVs, indels, CNAs, fusions, MSI and bTMB. Across all variant types, sensitivity was ≥90%, and specificity was ≥95% at LoDs. The reproducibility and repeatability study resulted in ≥95% agreement for all variant types. Analytical sensitivity was calculated using vendor-verified variants in each control. SeraCare® controls and Horizon reference materials were used to assess variant concordance with an aggregate analytical performance across all control samples with ≥95% PPA and NPA for all variant types. Conclusions: The validation of the PGDx elio plasma complete liquid biopsy assay as part of the Epic Sciences' CAP/CLIA diagnostic workflow for cfDNA-based NGS demonstrates that the liquid biopsy approach is highly sensitive, specific, accurate, reproducible, and robust for comprehensive genomic profiling to complement tissue- based testing and inform clinical decision making. Citation Format: Cynthia Maddox, Kenneth C Valkenburg, Cesar Nalvarte, Amanda Harvey, Amy Greer, Ellen L Verner, Renee L Sears, Martin Blankford, Eric A Severson, Taylor J Jensen, Marcia Eisenberg, Shakti Ramkissoon. Validation of the PGDx elio™ plasma complete for comprehensive genomic profiling of solid tumors through liquid biopsy with Epic Sciences [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B049.

Design and Evaluation of Azaspirocycles as RNA binders.

This study presents efficient synthetic pathways for preparing novel azaspirocycles. These methodologies involve functionalizing key bicyclic hydrazines with a substituent on one of their bridgehead carbon atoms. The desired spirocyclic cores were successfully obtained through double reductive amination reactions, intramolecular cyclizations, and cleavages of the N-N bond. The isolated molecules possess unique three-dimensional structures, suggesting potential applications in medicinal chemistry and drug discovery. With the growing interest in targeting nucleic acids as a complementary approach to protein-targeting strategies for developing novel active compounds, we investigated the potential of the synthesized azaspirocycles as RNA binders. As a proof of concept, we highlight the promising activity of some compounds as strong binders of HIV-1 TAR RNA and inhibitors of Tat/TAR interactions.

Reactive Stroma and Acinar Morphology in Prostate Cancer: Implications for Progression and Prognostic Assessment.

Prostate cancer (PC) remains a significant global health concern, with prognostic assessments largely reliant on the Gleason Classification System. While it has proven effective, subjectivity in interpretation persists, prompting the need for complementary approaches. Reactive stroma (RS) has emerged as a potential candidate for enhancing PC characterization, as it reflects intricate interactions among stromal, epithelial, and extracellular matrix components. To shed light on this, we conducted a comprehensive study. Two expert pathologists independently analyzed consecutive prostate biopsies (n = 120 patients), categorized into four groups based on Gleason scores. Four acinar patterns were described, denoted as A, B, C, and D. Our study uncovered a noteworthy presence of RS, predominantly within poorly differentiated tumors. Stromogenic tumors, characterized by high RS content, were particularly associated with Gleason scores of 4 + 3 and ≥ 8. Intriguingly, acinar patterns, including the distinctive B and D patterns, exhibited strong correlations with stromogenic tumors. Incorporating quantitative imaging techniques (Second Harmonic Generation and Two-Photon Excitation Fluorescence Microscopy), we examined collagen fiber density within the stroma. Our analysis revealed a direct relationship between RS intensity and collagen fiber counts, particularly prominent in patterns B and D. These findings suggest that the stromal reaction in PC is closely linked to acinar morphology and collagen deposition. Moreover, rudimentary microacini at the tumor periphery, associated with intense RS and patterns B and D, may signify an unfavorable prognosis. Our study highlights the potential of RS as an additional prognostic factor in PC. It underscores the intricate interplay between acinar patterns, RS intensity, and collagen fiber density, providing valuable insights for future prognostic assessments and therapeutic strategies. Further exploration of these relationships is essential for a comprehensive understanding of PC progression and management.

EXPRESS: Spontaneous Transfer of Relational Category Structures Between Category Learning Tasks: A Novel Approach to Measure Analogical Transfer.

The ability to spontaneously access knowledge of relational concepts acquired in one domain and apply it to a novel domain has traditionally been explored in the analogy literature via the problem-solving paradigm (cf. Gick & Holyoak, 1980, 1983). In the present work, we propose a novel procedure based on categorization as a complementary approach to assess spontaneous analogical transfer-using one category learning task to enhance learning of the same underlying category structures in another domain. In Experiment 1, we demonstrate larger improvements in classification performance across blocks of training in a Target Category Learning task among participants that underwent a Base Category Learning task relative to a separate group of participants learning the Target category structures for the first time; thus providing evidence for spontaneous transfer of the category structures. In Experiment 2, we demonstrate similar evidence of spontaneous transfer for participants that underwent a comparison-based Base Category Learning task under a more rigorous context-shift between the Base and Target Category Learning tasks. Additional exploratory analyses across both experiments showcase ways in which this paradigm can be used to answer questions regarding the analogical transfer of relational category structures and generate promising paths for future work.

INTEGRATIVE ONCOLOGY AS A PROMISING VECTOR FOR THE TREATMENT OF CANCER TREATMENT

The article presents an analysis of the possibilities for early diagnosis, treatment, and rehabilitation of patients with cancer within the framework of integrative oncology. Introduction. Oncological diseases remain one of the most pressing medical challenges of our time, driven by a steady increase in incidence, late-stage diagnoses, and unsatisfactory treatment outcomes. WHO experts predict that by 2050, the number of new cancer cases will rise by 77% compared to 2022. Despite significant advancements in diagnostics and conventional treatments, including surgery, chemotherapy, and radiotherapy, there remains a need for a more holistic approach. This approach would not only target tumor control but also aim to enhance the overall quality of life for patients. Discussion. Timely and accurate diagnosis is a crucial aspect of the fight against cancer. Early detection can significantly improve the chances of successful treatment and patient survival. However, conventional cancer treatments are often aggressive, leading to complications, side effects, and patient disability. Integrative oncology combines traditional therapies with complementary approaches, focusing on maintaining overall patient health, reducing side effects, facilitating restorative rehabilitation, and enhancing quality of life. This comprehensive, integrative approach broadens and strengthens the options for cancer treatment, offering a more holistic care strategy. Conclusion. Integrative oncology represents a promising direction in cancer treatment by providing a comprehensive approach to addressing the disease. The combination of conventional treatments with complementary therapies not only enhances treatment effectiveness but also significantly improves patient quality of life, an essential aspect in the ongoing battle against cancer.

Exploring the Therapeutic Potential of Theobroma cacao L.: Insights from In Vitro, In Vivo, and Nanoparticle Studies on Anti-Inflammatory and Anticancer Effects

Theobroma cacao L., commonly known as cocoa, has been an integral part of human culture and diet for thousands of years. However, recent scientific research has highlighted its potential therapeutic properties, particularly in the treatment of cancer and inflammatory diseases. This comprehensive review analyzes the anti-inflammatory and anticancer effects of Theobroma cacao extracts combined with nanoparticles using in vitro and in vivo studies. Its diverse biological activity can be attributed to its rich phytochemical profile, including polyphenols, flavonoids, and alkaloids. In vitro studies have found that cocoa extracts, alone or in combination with nanoparticles, inhibit cancer cell proliferation, induce apoptosis and modulate key signaling pathways in various cancer cell lines. The extracts have also been found to reduce tumor growth and enhance the efficacy of conventional chemotherapeutic agents, potentially reducing their side effects, in vivo. Its anti-inflammatory properties are based on its ability to modulate inflammatory mediators, inhibit NF-κB signaling, and regulate macrophage polarization. These effects have been observed in both cellular and animal models of inflammation. This review opens up new possibilities for future research and therapeutic applications, highlighting the potential of Theobroma cacao as a valuable complementary approach in the treatment and prevention of cancer and inflammatory diseases.

The Effect of Long-term Biofeedback Therapy on Depression of Elderly Stroke Patients

Background and Objectives: Depression is a common problem after stroke, with a high prevalence. Multiple studies have suggested that biofeedback therapy can effectively treat depression without causing side effects. This research aims to investigate the long-term impact of biofeedback therapy on depression in stroke survivors. Methods: A quasi-experimental study was conducted with 40 stroke patients who were divided into a rehabilitation control group and a rehabilitation group that underwent long biofeedback electromyography exercises. All patients were assessed for their level of depression at the start of the study and again after two years of treatment, after completing occupational therapy sessions with and without biofeedback intervention. Statistical analysis was performed using paired t-tests and correlated t-tests with a significance level (P≤0.05). Results: In both control and intervention groups, no significant differences were observed in the level of depression between the pre-test and post-test stages. However, a crucial difference was observed between the intervention and control groups after using biofeedback. The average depression in patients who used long-term biofeedback decreased after two years compared to the control group (P≤0.05). Conclusion: Long-term utilization of biofeedback therapy impacts the depression levels of stroke patients. This method is highly recommended as a complementary approach to conventional rehabilitation.

Berberine Mediates Exosomes Regulating the Lipid Metabolism Pathways to Promote Apoptosis of RA-FLS Cells

Objectives: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint damage and commonly linked to symptoms such as inflammation, swelling, and pain. Traditional Chinese Medicine offers complementary and integrative approaches in the management of rheumatoid arthritis, potentially providing additional options that may help address treatment challenges and enhance overall patient care. This paper explores the mechanism of action of berberine from the perspective of cellular exosomes by mediating exosomal contents and thus treating RA. Methods: With the help of flow cytometry and confocal laser scanning microscope, it was determined that berberine promotes apoptosis in RA-FLS cells, and then lipid metabolomics technology was applied to screen and characterize the exosomes of RA-FLS cells to identify lipid core biomarkers closely related to RA, which were then projected into various databases for comprehensive analysis. Results: The data analysis showed that berberine could call back 11 lipid core biomarkers closely associated with RA, and interactive visualization of the database revealed that these markers were mainly focused on lipid metabolism aspects such as fatty acid elongation, degradation, and biosynthesis, as well as the biosynthesis of unsaturated fatty acids or PPARA activation of gene expression, PPARα‘s role in lipid metabolism regulation, glycerophospholipid metabolism, mitochondrial fatty acid oxidation disorders, and organelle biogenesis and maintenance. Conclusions: Berberine exerts its therapeutic effect on RA by mediating exosomal contents and thus regulating multiple lipid-related biological pathways, affecting the PPARγ-NF-κB complex binding rate, CREB and EGR-1 expression, cellular phagocytosis, and other aspects needed to inhibit proliferation and inflammatory responses in RA-FLS. This study offers a research foundation for exploring the mechanism of action of berberine in the treatment of RA.

SoftBoMI: a non-invasive wearable body-machine interface for mapping movement of shoulder to commands

Objective.Customized human-machine interfaces for controlling assistive devices are vital in improving the self-help ability of upper limb amputees and tetraplegic patients. Given that most of them possess residual shoulder mobility, using it to generate commands to operate assistive devices can serve as a complementary approach to brain-computer interfaces.Approach.We propose a hybrid body-machine interface prototype that integrates soft sensors and an inertial measurement unit. This study introduces both a rule-based data decoding method and a user intent inference-based decoding method to map human shoulder movements into continuous commands. Additionally, by incorporating prior knowledge of the user's operational performance into a shared autonomy framework, we implement an adaptive switching command mapping approach. This approach enables seamless transitions between the two decoding methods, enhancing their adaptability across different tasks.Main results.The proposed method has been validated on individuals with cervical spinal cord injury, bilateral arm amputation, and healthy subjects through a series of center-out target reaching tasks and a virtual powered wheelchair driving task. The experimental results show that using both the soft sensors and the gyroscope exhibits the most well-rounded performance in intent inference. Additionally, the rule-based method demonstrates better dynamic performance for wheelchair operation, while the intent inference method is more accurate but has higher latency. Adaptive switching decoding methods offer the best adaptability by seamlessly transitioning between decoding methods for different tasks. Furthermore, we discussed the differences and characteristics among the various types of participants in the experiment.Significance.The proposed method has the potential to be integrated into clothing, enabling non-invasive interaction with assistive devices in daily life, and could serve as a tool for rehabilitation assessment in the future.

Inducible cell lines producing replication-defective human immunodeficiency virus particles containing envelope glycoproteins stabilized in a pretriggered conformation.

During the process by which human immunodeficiency virus (HIV-1) enters cells, the envelope glycoprotein (Env) trimer on the virion surface engages host cell receptors. Binding to the receptor CD4 induces Env to undergo transitions from a pretriggered, "closed" (State-1) conformation to more "open" (State 2/3) conformations. Most broadly neutralizing antibodies (bNAbs), which are difficult to elicit, recognize the pretriggered (State-1) conformation. More open Env conformations are recognized by poorly neutralizing antibodies (pNAbs), which are readily elicited during natural infection and vaccination with current Env immunogens. Env heterogeneity likely contributes to HIV-1 persistence by skewing antibody responses away from the pretriggered conformation. The conformationally flexible gp160 Env precursor on the infected cell or virion surface potentially presents multiple pNAb epitopes to the host immune system. Although proteolytic cleavage to produce the functional, mature Env trimer [(gp120/gp41)3] stabilizes State-1, many primary HIV-1 Envs spontaneously sample more open conformations. Here, we establish inducible cell lines that produce replication-defective HIV-1 particles with Env trimers stabilized in a pretriggered conformation. The mature Env is enriched on virus-like particles (VLPs). Using complementary approaches, we estimate an average of 25-50 Env trimers on each VLP. The stabilizing changes in Env limit the natural conformational heterogeneity of the VLP Env trimers, allowing recognition by bNAbs but not pNAbs. These defective VLPs provide a more homogeneous source of pretriggered Env trimers in a native membrane environment. Thus, these VLPs may facilitate the characterization of this functionally important Env conformation and its interaction with the immune system.IMPORTANCEA major impediment to the development of an effective HIV/AIDS vaccine is the inefficiency with which human immunodeficiency virus (HIV-1) envelope glycoproteins elicit antibodies that neutralize multiple virus strains. Neutralizing antibodies recognize a particular shape of the envelope glycoproteins that resides on the viral membrane before the virus engages the host cell. Here, we report the creation of stable cell lines that inducibly produce non-infectious HIV-like particles. The normally flexible envelope glycoprotein spikes on these virus-like particles have been stabilized in a conformation that is recognized by broadly neutralizing antibodies. These virus-like particles allow the study of the envelope glycoprotein conformation, its modification by sugars, and its ability to elicit desired neutralizing antibodies.

Comparing parameterized and self-consistent approaches to abinitio cavity quantum electrodynamics for electronic strong coupling.

Molecules under strong or ultra-strong light-matter coupling present an intriguing route to modify chemical structure, properties, and reactivity. A rigorous theoretical treatment of such systems requires handling matter and photon degrees of freedom on an equal quantum mechanical footing. In the regime of molecular electronic strong or ultra-strong coupling to one or a few molecules, it is desirable to treat the molecular electronic degrees of freedom using the tools of abinitio quantum chemistry, yielding an approach referred to as abinitio cavity quantum electrodynamics (ai-QED), where the photon degrees of freedom are treated at the level of cavity QED. We analyze two complementary approaches to ai-QED: (1) a parameterized ai-QED, a two-step approach where the matter degrees of freedom are computed using existing electronic structure theories, enabling the construction of rigorous ai-QED Hamiltonians in a basis of many-electron eigenstates, and (2) self-consistent ai-QED, a one-step approach where electronic structure methods are generalized to include coupling between electronic and photon degrees of freedom. Although these approaches are equivalent in their exact limits, we identify a disparity between the projection of the two-body dipole self-energy operator that appears in the parameterized approach and its exact counterpart in the self-consistent approach. We provide a theoretical argument that this disparity resolves only under the limit of a complete orbital basis and a complete many-electron basis for the projection. We present numerical results highlighting this disparity and its resolution in a particularly simple molecular system of helium hydride cation, where it is possible to approach these two complete basis limits simultaneously. In this same helium hydride system, we examine and compare the practical issue of the computational cost required to converge each approach toward the complete orbital and many-electron bases limit. Finally, we assess the aspect of photonic convergence for polar and charged species, finding comparable behavior between parameterized and self-consistent approaches.

Profiling of 24-nt phasiRNAs in Rice Anther by Massively Parallel Sequencing and Stem-Loop Reverse Transcription PCR.

Small RNAs are highly abundant and play important roles in plant reproduction. Profiling of small RNAs in reproductive tissues is a critical step in understanding their biology. Here, we describe a protocol for small RNA profiling in rice anthers, with a focus on an abundantly expressed but little-understood reproductive small RNA class named 24-nucleotide phased secondary small interfering RNAs (24-nt phasiRNAs). The protocol details small RNA library preparation steps for high-throughput sequencing, with a subsequent bioinformatic analysis framework. A low-throughput stem-loop reverse transcription PCR protocol for quick semi-quantification of small RNAs is also included as a complementary approach. The collective protocol, although focused on 24-nt phasiRNAs, should be amenable to other small RNA classes in various plant reproductive tissues.

Human dignity and the pursuit of knowledge in Islamic thought: Insights from the Quran

This research examines the interplay between human dignity and the pursuit of knowledge within Islamic thought, using insights from the Quran. It explores how Islamic epistemology emphasizes the harmonious integration of divine revelation and human reason, underscoring the importance of knowledge as a key factor in both intellectual and spiritual development. By analyzing the contributions of classical Islamic scholars, such as Al-Farabi, Ibn Sina, and Al-Ghazali, alongside Western epistemological traditions, the study highlights complementary and contrasting approaches to understanding knowledge and its role in shaping ethics and governance. Furthermore, the research draws on contemporary case studies, such as the Marrakesh Declaration and Masdar City, to illustrate how Quranic principles of cooperation, justice, and environmental stewardship can inform modern societal frameworks. Ultimately, the study argues for the continued relevance of Islamic thought in addressing contemporary global challenges, emphasizing that the pursuit of knowledge not only advances scientific discovery but also promotes human dignity, justice, and societal well-being.

Efficacy of R-N cusp-overlap view as a complementary approach for optimal neocommissural alignment with Navitor valve.

Efficacy of R-N cusp-overlap view as a complementary approach for optimal neocommissural alignment with Navitor valve.

Anti-inflammatory activity of Ziziphus jujuba hydroalcoholic extract in acetic acid-induced ulcerative colitis model.

Ulcerative colitis (UC) is a common gastrointestinal (GI) disorder characterized by chronic inflammation. Current treatments primarily focus on symptom management, but they have inherent limitations. Global attention is increasingly directed towards exploring herbal remedies as complementary approaches. This study aims to investigate the effects of the hydroalcoholic extract of jujuba on an experimental model of ulcerative colitis. In this study, 15 male BALB/c mice were divided into three experimental groups. The first group served as the untreated UC model, acting as the positive control (PC). The second group received treatment with the hydroalcoholic extract of Ziziphus jujuba, while the third group was treated with mesalamine. UC was induced by injecting 100 μL of 4 % acetic acid (AA) intra-rectally several times. Treatment commenced after the onset of symptoms such as diarrhea and bloody stools. The mice were eventually euthanized ethically, and their spleen and intestinal tissues were collected for analysis. Evaluations included the Disease Activity Index (DAI), myeloperoxidase activity (MPO), nitric oxide (NO) levels, cytokine levels (IL-1β, IL-6, TNF-α), and gene expression (iNOS, COX-2, and cytokines). The hydroalcoholic extract of the jujuba plant significantly reduced MPO, NO, the DAI, and the production and expression of inflammatory cytokines, as well as the genes iNOS and COX-2, in the group receiving this extract compared to the positive control group (p<0.05). The study demonstrates that the hydroalcoholic extract of Ziziphus jujuba significantly reduces inflammation markers such as TNF-α, NO, MPO, IL-1β, and IL-6 in a mouse model of ulcerative colitis. Additionally, itdownregulates the expression of pro-inflammatory genes, including iNOS and COX-2. These findings suggest that Z.jujuba extract has potential as an effective anti-inflammatory treatment for managing ulcerative colitis symptoms.