Lessons learnt from an aggressive tumour masquerading as a neuropathic heel ulcer: a case report.

Cutaneous malignant melanoma (cMM) can develop at any site, but one-third of cases primarily affect the lower extremities, with ankle and foot lesions representing 3-15% of all cases. However, cMM may become a clinical conundrum when it presents as chronic ulceration that is clinically indiscernible from other lower extremity ulcers in patients with diabetes. We present the case of a 71-year-old female patient with a longstanding history of diabetes, hypertension, obesity, chronic kidney disease and heart failure who presented to our hospital with a fungating heel ulcer. The lesion was initially managed in another hospital as a neuropathic diabetic foot ulcer (DFU), treated by multiple local wound debridement. However, the ulcer progressed into a fungating heel lesion that interfered with the patient's mobility and quality of life. Consequently, the patient was referred to our specialist diabetic foot service for further management. Excisional biopsy of the lesion disclosed a cMM. Positron emission tomography/computed-tomography scanning revealed hypermetabolic ipsilateral inguinal lymphadenopathy, and a right cerebral metastasis for which palliative chemotherapy was initiated. Immunotherapy was considered, but the patient died before it was started. Atypical foot ulcers in patients with diabetes warrant a careful diagnostic approach, especially for recalcitrant cutaneous lesions not responding to standard therapies. Conscientious management, without undue delay in obtaining a histopathological diagnosis, might lead to early diagnosis of melanoma and potentially more favourable outcomes. This case highlights the importance of consideration of atypical foot lesions, in general practice in addition to referral centres, to try to identify alarming features and act accordingly.

Standardised definitions and diagnostic criteria for extranodal extension detected on histopathological examination in head and neck cancer: Head and Neck Cancer International Group consensus recommendations.

Detection of extranodal extension on histopathology in surgically treated head and neck squamous cell carcinoma indicates poor prognosis. However, there is no consensus on the diagnostic criteria, interpretation, and reporting of histology detected extranodal extension, which has contributed to conflicting evidence in the literature, and likely clinical inconsistency. The Head and Neck Cancer International Group conducted a three-round modified Delphi process with a group of 19 international pathology experts representing 15 national clinical research groups to generate consensus recommendations for histology detected extranodal extension diagnostic criteria. The expert panel strongly agreed on terminology and diagnostic features for histology detected extranodal extension and soft tissue metastasis. Moreover, the panel reached consensus on reporting of histology detected extranodal extension and on nodal sampling. These consensus recommendations, endorsed by 19 organisations representing 34 countries, are a crucial development towards standardised diagnosis and reporting of histology detected extranodal extension, and more accurate data collection and analysis.

Criteria for the diagnosis of extranodal extension detected on radiological imaging in head and neck cancer: Head and Neck Cancer International Group consensus recommendations.

Extranodal extension of tumour on histopathology is known to be a negative prognostic factor in head and neck cancer. Compelling evidence suggests that extranodal extension detected on radiological imaging is also a negative prognostic factor. Furthermore, if imaging detected extranodal extension could be identified reliably before the start of treatment, it could be used to guide treatment selection, as patients might be better managed with non-surgical approaches to avoid the toxicity and cost of trimodality therapy (surgery, chemotherapy, and radiotherapy together). There are many aspects of imaging detected extranodal extension that remain unresolved or are without consensus, such as the criteria to best diagnose them and the associated terminology. The Head and Neck Cancer International Group conducted a five-round modified Delphi process with a group of 18 international radiology experts, representing 14 national clinical research groups. We generated consensus recommendations on the terminology and diagnostic criteria for imaging detected extranodal extension to harmonise clinical practice and research. These recommendations have been endorsed by 19 national and international organisations, representing 34 countries. We propose a new classification system to aid diagnosis, which was supported by most of the participating experts over existing systems, and which will require validation in the future. Additionally, we have created an online educational resource for grading imaging detected extranodal extensions.

Age-Specific Differences in Laryngotracheal Trauma Characteristics: A Retrospective Study of Clinical Profiles, Outcomes, and Mortality Risk.

Background: Laryngotracheal trauma is associated with a substantial risk of mortality. Age can be a critical factor in trauma management, as older adults often have diminished airway protective reflexes and preexisting respiratory conditions. Objective: This study aimed to characterize the clinical profiles and outcomes in different age groups of adult patients with laryngotracheal trauma using data from the National Trauma Data Bank (NTDB). Methods: We retrospectively analyzed the NTDB and included adult patients (aged ≥ 18 years) who had laryngotracheal fractures (closed or open) and were admitted directly after the injury. The patients were categorized into different age groups for analysis. A multivariate logistic regression analysis was performed to assess whether the elderly population (age ≥ 65 years) was predisposed to post-trauma death under care. Results: The study included 1171 patients, with the following age distributions: 13.7% aged 18-24 years, 21.6% aged 25-34 years, 55.2% aged 35-64 years, and 9.6% aged ≥ 65 years. Notable differences were observed in comorbidities, mechanisms, types of injuries, and associated injuries among age groups. There was no significant trend in airway surgical outcomes according to age. In-hospital mortality was highest among patients aged ≥ 65 years (22.3%), compared to 14.4% for those aged 18-24 years. Regression analysis indicated that age ≥ 65 was an independent mortality predictor. Conclusions: These findings underscore significant age-related differences in the presentation and outcomes of laryngotracheal trauma, emphasizing the need for age-specific treatment protocols, primarily to address the elevated risk among elderly patients.

The dark side of drug repurposing. From clinical trial challenges to antimicrobial resistance: analysis based on three major fields.

Drug repurposing is a strategic endeavor that entails the identification of novel therapeutic applications for pharmaceuticals that are already available in the market. Despite the advantageous nature of implementing this particular strategy owing to its cost-effectiveness and efficiency in reducing the time required for the drug discovery process, it is essential to bear in mind that there are various factors that must be meticulously considered and taken into account. Up to this point, there has been a noticeable absence of comprehensive analyses that shed light on the limitations of repurposing drugs. The primary aim of this review is to conduct a thorough illustration of the various challenges that arise when contemplating drug repurposing from a clinical perspective in three major fields-cardiovascular, cancer, and diabetes-and to further underscore the potential risks associated with the emergence of antimicrobial resistance (AMR) when employing repurposed antibiotics for the treatment of noninfectious and infectious diseases. The process of developing repurposed medications necessitates the application of creativity and innovation in designing the development program, as the body of evidence may differ for each specific case. In order to effectively repurpose drugs, it is crucial to consider the clinical implications and potential drawbacks that may arise during this process. By comprehensively analyzing these challenges, we can attain a deeper comprehension of the intricacies involved in drug repurposing, which will ultimately lead to the development of more efficacious and safe therapeutic approaches.

The Effect of Obesity on Severity of Asthma: An Observational Prospective Study from Pakistan.

Objective: The current research study aimed to access the relationship between obesity and asthma exacerbations and severity among adult patients at the outpatient section of a federal hospital (PIMS) in Islamabad, Pakistan. Methods: A cross-sectional research study was carried out on 207 asthma adult patients belonging to different areas and ethnic groups from the country. The study setting was the PIMS hospital, which attracts patients from all over the country due to its facilities and cost-effective treatments. The body mass index (BMI) of asthma patients was calculated using the heights and weights of the study subjects. However, the pulmonary functions were calculated using a computerized spirometer i-e Spirolab III S/N 303681 in line with Winspiro PRO 7.1.version software. It presents the patient's forced vital capacity that expires in the first second of expiration to full (FEV1) in comparison to forced vital capacity (FVC) ratio, that is, Tiffeneau-Pinelli index was also recorded to determine the asthma severity. Results: According to recent surveys, the overall prevalence of patients with overweight and obesity was 29.0% and 23.7%, respectively. A Chi-square test was used, and a statistically significant relationship was observed between BMI and asthma severity (P < 0.001). The adult obese female patients presented poor pulmonary functions. The average FEV1/FVC ratio presented significant variance among four different categories of BMI with P < 0.05. This difference was due to the normal BMI category as the Tiffeneau-Pinelli index, that is, FEV1/FVC in the normal BMI group was significantly lower as compared to that in underweight and obese patients. Conclusion: The study subjects presented raised asthma severity in accordance with the raised BMI. Obese patients presented comparatively raised asthma exacerbations. Moreover, a statistically significant association of gender difference was observed between obesity and asthma severity. It was concluded that adult asthmatic women with obesity presented raised asthma severity as compared to adult asthmatic males.

Management of severe tetanus in Afghanistan: lessons from the field.

INTRODUCTION: Tetanus is a rather rare disease in the Western countries thanks to widespread vaccination programs and the availability of prophylactics for patients with tetanus-prone injuries. The few cases that do occur are promptly managed in intensive care units (ICUs). However, tetanus is not so rare in developing countries, where access to a suitable level of care is limited. An unstable political situation can be a significant factor influencing patient outcomes. CASE REPORT: A ten-year-old boy presented at the EMERGENCY hospital in Lashkar-Gah (southern Afghanistan) with generalized tetanus after falling off his bicycle. In response to his rapidly deteriorating general conditions - respiratory failure and hemodynamic instability - the patient was urgently transferred by ambulance to the ICU at the EMERGENCY hospital in Kabul (northern Afghanistan). The patient was placed on mechanical ventilation while receiving intravenous sedation and pharmacologic paralysis for almost four weeks. A prolonged infusion of a high dose of magnesium sulphate and labetalol was also given to counteract autonomic dysfunction. Multiple complications related to the long stay in the ICU were observed and promptly addressed. During this period, several mass casualties took place in Kabul, which stretched the hospital's surge capacity. The patient was discharged and accompanied back to Lashkar-Gah three months after his admission to the hospital. CONCLUSION: This case report shows some of the many difficulties that arise when managing a patient with severe tetanus in a war zone where resources are limited.

Yeast Platforms for Production and Screening of Bioactive Derivatives of Rauwolscine.

Monoterpene indole alkaloids (MIAs) make up a highly bioactive class of metabolites produced by a range of tropical and subtropical plants. The corynanthe-type MIAs are a stereochemically complex subclass with therapeutic potential against a large number of indications including cancer, psychotic disorders, and erectile dysfunction. Here, we report yeast-based cell factories capable of de novo production of corynanthe-type MIAs rauwolscine, yohimbine, tetrahydroalstonine, and corynanthine. From this, we demonstrate regioselective biosynthesis of 4 fluorinated derivatives of these compounds and de novo biosynthesis of 7-chlororauwolscine by coexpression of a halogenase with the biosynthetic pathway. Finally, we capitalize on the ability of these cell factories to produce derivatives of these bioactive scaffolds to establish a proof-of-principle drug discovery pipeline in which the corynanthe-type MIAs are screened for bioactivity on human drug targets, expressed in yeast. In doing so, we identify antagonistic and agonistic behavior against the human adrenergic G protein-coupled receptors ADRA2A and ADRA2B, and the serotonergic receptor 5HT4b, respectively. This study thus demonstrates a proto-drug discovery pipeline for bioactive plant-inspired small molecules based on one-pot biocatalysis of natural and new-to-nature corynanthe-type MIAs in yeast.

Using a Disposable Flexible Fiberoptic Scope as a Bougie for Difficult Intubation.

In this case report, we describe two difficult intubations in which an endotracheal tube was threaded over a fiberoptic bronchoscope that was acting as a bougie. Our patients initially presented with limited neck extension, narrow mouth opening, and restricted view of the glottic region. A fiberoptic bronchoscope was guided through while the patient was oxygenated through a laryngeal mask. After the scope provided an unrestricted view of the vocal cords, the digital module was removed by cutting the fiberoptic thread, and an endotracheal tube was passed through. After proper confirmation of the endotracheal tube position, the intubation was deemed successful and thereby, we share our experience with the novel technique. This technique may potentially improve critical patient outcomes whether in trauma or an unexpectedly difficult intubation.

Synthesis and characterization of magnesium ferrite-activated carbon composites derived from orange peels for enhanced supercapacitor performance.

Supercapacitors have emerged as highly efficient energy storage devices, relying on electrochemical processes. The performance of these devices can be influenced by several factors, with key considerations including the selection of electrode materials and the type of electrolyte utilized. Transition metal oxide electrodes are commonly used in supercapacitors, as they greatly influence the electrochemical performance of these devices. Nonetheless, ferrites' low energy density poses a limitation. Hence, it is crucial to create electrode materials featuring unique and distinct structures, while also exploring the ideal electrolyte types, to enhance the electrochemical performance of supercapacitors incorporating magnesium ferrites (MF). In this study, we effectively prepared magnesium ferrites (MgFe2O4) supported on activated carbon (AC) derived from orange peels (OP) using a simple hydrothermal method. The resulting blends underwent comprehensive characterization employing various methods, including FTIR, XRD, TEM, SEM, EDX, and mapping analysis. Moreover, the electrochemical performance of MgFe2O4@AC composites was evaluated using GCD and CV techniques. Remarkably, the MF45-AC electrode material showed exceptional electrochemical behavior, demonstrating a specific capacitance of 870 F·g-1 within current density of 1.0 A g-1 and potential windows spanning from 0 to 0.5 V. Additionally, the prepared electrodes displayed exceptional cycling stability, with AC, MF, and MF45-AC retaining 89.6%, 94.2%, and 95.1% of their initial specific capacitance, respectively, even after 5000 cycles. These findings underscore the potential of MF-AC composites as superior electrode materials for supercapacitors. The development of such composites, combined with tailored electrolyte concentrations, holds significant promise for advancing the electrochemical performance and energy density of supercapacitor devices.

The Gut Connection: Exploring the Possibility of Implementing Gut Microbial Metabolites in Lymphoma Treatment.

Recent research has implicated the gut microbiota in the development of lymphoma. Dysbiosis of the gut microbial community can disrupt the production of gut microbial metabolites, thereby impacting host physiology and potentially contributing to lymphoma. Dysbiosis-driven release of gut microbial metabolites such as lipopolysaccharides can promote chronic inflammation, potentially elevating the risk of lymphoma. In contrast, gut microbial metabolites, such as short-chain fatty acids, have shown promise in preclinical studies by promoting regulatory T-cell function, suppressing inflammation, and potentially preventing lymphoma. Another metabolite, urolithin A, exhibited immunomodulatory and antiproliferative properties against lymphoma cell lines in vitro. While research on the role of gut microbial metabolites in lymphoma is limited, this article emphasizes the need to comprehend their significance, including therapeutic applications, molecular mechanisms of action, and interactions with standard chemotherapies. The article also suggests promising directions for future research in this emerging field of connection between lymphoma and gut microbiome.

Essential data variables for a minimum dataset for head and neck cancer trials and clinical research: HNCIG consensus recommendations and database.

The Head and Neck Cancer International Group (HNCIG) has undertaken an international modified Delphi process to reach consensus on the essential data variables to be included in a minimum database for HNC research. Endorsed by 19 research organisations representing 34 countries, these recommendations provide the framework to facilitate and harmonise data collection and sharing for HNC research. These variables have also been incorporated into a ready to use downloadable HNCIG minimum database, available from the HNCIG website.

Oversaturating Liquid Interfaces with Nanoparticle-Surfactants.

Assemblies of nanoparticles at liquid interfaces hold promise as dynamic "active" systems when there are convenient methods to drive the system out of equilibrium via crowding. To this end, we show that oversaturated assemblies of charged nanoparticles can be realized and held in that state with an external electric field. Upon removal of the field, strong interparticle repulsive forces cause a high in-plane electrostatic pressure that is released in an explosive emulsification. We quantify the packing of the assembly as it is driven into the oversaturated state under an applied electric field. Physiochemical conditions substantially affect the intensity of the induced explosive emulsification, underscoring the crucial role of interparticle electrostatic repulsion.

Early Versus Late Antipseudomonal ß-Lactam Antibiotic Dose Adjustment in Critically Ill Sepsis Patients With Acute Kidney Injury: A Prospective Observational Cohort Study.

Background: Acute kidney injury (AKI) is a common complication of sepsis, contributing to an increased mortality rate. However, some studies have demonstrated that renal function improves in sepsis patients with AKI within 48 hours, raising questions about the necessity for early antibiotic adjustment. This study evaluates the association between the timing of antipseudomonal ß-lactam dose adjustment and the outcomes of critically ill sepsis patients with AKI. Methods: A prospective, multicenter observational study of critically ill patients aged ≥18 years admitted to the intensive care unit with sepsis and AKI and started on antipseudomonal ß-lactam therapy. After the initial dose, eligible patients were grouped as early ß-lactam antibiotic (E-BLA) or late ß-lactam antibiotic (L-BLA) dose adjustments based on the administration of subsequent renally adjusted doses within 24 hours and after 24 hours of sepsis recognition, respectively. The main outcome of interest was in-hospital mortality. Results: Among 1185 patients screened, 224 (mean age, 62.7 ± 16.8 years; 62% were male) met inclusion criteria. Eighty-four and 140 patients were included in the E-BLA and L-BLA groups, respectively. Approximately half of the cohort presented with AKI stage II, and piperacillin-tazobactam was prescribed as initial empirical therapy in more than 50% of the cohort. In the multivariable Cox proportional hazards model, L-BLA was associated with a significant reduction in in-hospital mortality compared to E-BLA (hazard ratio, 0.588 [95% confidence interval, .355-.974]). Conclusions: In sepsis patients with AKI, L-BLA was associated with in-hospital mortality benefits.

teemi: An open-source literate programming approach for iterative design-build-test-learn cycles in bioengineering.

Synthetic biology dictates the data-driven engineering of biocatalysis, cellular functions, and organism behavior. Integral to synthetic biology is the aspiration to efficiently find, access, interoperate, and reuse high-quality data on genotype-phenotype relationships of native and engineered biosystems under FAIR principles, and from this facilitate forward-engineering strategies. However, biology is complex at the regulatory level, and noisy at the operational level, thus necessitating systematic and diligent data handling at all levels of the design, build, and test phases in order to maximize learning in the iterative design-build-test-learn engineering cycle. To enable user-friendly simulation, organization, and guidance for the engineering of biosystems, we have developed an open-source python-based computer-aided design and analysis platform operating under a literate programming user-interface hosted on Github. The platform is called teemi and is fully compliant with FAIR principles. In this study we apply teemi for i) designing and simulating bioengineering, ii) integrating and analyzing multivariate datasets, and iii) machine-learning for predictive engineering of metabolic pathway designs for production of a key precursor to medicinal alkaloids in yeast. The teemi platform is publicly available at PyPi and GitHub.

Self-Propulsion by Directed Explosive Emulsification.

An active droplet system, programmed to repeatedly move autonomously at a specific velocity in a well-defined direction, is demonstrated. Coulombic energy is stored in oversaturated interfacial assemblies of charged nanoparticle-surfactants by an applied DC electric field and can be released on demand. Spontaneous emulsification is suppressed by an increase in the stiffness of the oversaturated assemblies. Rapidly removing the field releases the stored energy in an explosive event that propels the droplet, where thousands of charged microdroplets are ballistically ejected from the surface of the parent droplet. The ejection is made directional by a symmetry breaking of the interfacial assembly, and the combined interaction force of the microdroplet plume on one side of the droplet propels the droplet distances tens of times its size, making the droplet active. The propulsion is autonomous, repeatable, and agnostic to the chemical composition of the nanoparticles. The symmetry-breaking in the nanoparticle assembly controls the microdroplet velocity and direction of propulsion. This mechanism of droplet propulsion will advance soft micro-robotics, establishes a new type of active matter, and introduces new vehicles for compartmentalized delivery.

Exploring moisture adsorption on cobalt-doped ZnFe2O4 for applications in atmospheric water harvesting.

Sorption-based atmospheric water harvesting (SBAWH) is a highly promising approach for extracting water from the atmosphere thanks to its sustainability, exceptional energy efficiency, and affordability. In this work, ZnFe2O4 and Zn0.4Co0.6Fe2O4 were evaluated for moisture adsorption. The desired materials were synthesized by a surfactant-assisted sol-gel method. Synthesized samples were characterized using X-ray diffraction (XRD) analysis, scanning electron microscopy (SEM), energy dispersive X-ray (EDX) spectroscopy, Fourier transform infrared (FTIR) spectroscopy, vibrating sample magnetometry (VSM), and point of zero charge (PZC). Crystallinity and phase composition were evaluated by XRD analysis. Several parameters were determined using XRD analysis: lattice parameter, unit cell volume, crystallite size, and bulk density. The morphology of synthesized materials was assessed via SEM, and unveiled the acquisition of consistent, homogeneous, and uniform crystals. Elemental composition was determined through EDX spectroscopy. Water adsorption on the surface was evaluated by FTIR spectroscopy. The magnetic properties of synthesized ZnFe2O4 and cobalt-doped ZnFe2O4 ferrites were investigated using VSM. The negative charge on the Zn0.4Co0.6Fe2O4 surface was explored using PZC. Adsorption studies on synthesized materials were conducted with the help of an atmospheric water harvesting (AWH) plant created by our team. Moisture adsorption isotherms of synthesized materials were determined using a gravimetric method under varying temperature and relative humidity (45-95%) conditions. The moisture content (Mc) of Zn0.4Co0.6Fe2O4 and ZnFe2O4 was 597 mg g-1 and 104 mg g-1, respectively. Key thermodynamic properties, including isosteric heat of adsorption (Qst), change in Gibbs free energy (ΔG), and change in sorption entropy (ΔS), were evaluated. Qst was negative, which confirmed the sorption of water vapors on the material surface. ΔG and ΔS indicated that water-vapor adsorption was spontaneous and exothermic. A second-order kinetics study was carried out on synthesized materials, demonstrating their chemisorption behavior. The latter was due to the oxygen defects created by replacement of Co2+ and Fe3+ at tetrahedral and octahedral sites. Water vapors in the atmosphere became attached to the surface and deprotonation occurred, and the hydroxyl ions were formed. Water vapor attached to these hydroxyl ions. A second-order kinetics study was carried out to confirm the chemisorption behavior of synthesized materials.

Buds and Bugs: A Fascinating Tale of Gut Microbiota and Cannabis in the Fight against Cancer.

Emerging research has revealed a complex bidirectional interaction between the gut microbiome and cannabis. Preclinical studies have demonstrated that the gut microbiota can significantly influence the pharmacological effects of cannabinoids. One notable finding is the ability of the gut microbiota to metabolise cannabinoids, including Δ9-tetrahydrocannabinol (THC). This metabolic transformation can alter the potency and duration of cannabinoid effects, potentially impacting their efficacy in cancer treatment. Additionally, the capacity of gut microbiota to activate cannabinoid receptors through the production of secondary bile acids underscores its role in directly influencing the pharmacological activity of cannabinoids. While the literature reveals promising avenues for leveraging the gut microbiome-cannabis axis in cancer therapy, several critical considerations must be accounted for. Firstly, the variability in gut microbiota composition among individuals presents a challenge in developing universal treatment strategies. The diversity in gut microbiota may lead to variations in cannabinoid metabolism and treatment responses, emphasising the need for personalised medicine approaches. The growing interest in understanding how the gut microbiome and cannabis may impact cancer has created a demand for up-to-date, comprehensive reviews to inform researchers and healthcare practitioners. This review provides a timely and invaluable resource by synthesizing the most recent research findings and spotlighting emerging trends. A thorough examination of the literature on the interplay between the gut microbiome and cannabis, specifically focusing on their potential implications for cancer, is presented in this review to devise innovative and effective therapeutic strategies for managing cancer.

The Neurotherapeutic Arsenal in Cannabis sativa: Insights into Anti-Neuroinflammatory and Neuroprotective Activity and Potential Entourage Effects.

Cannabis, renowned for its historical medicinal use, harbours various bioactive compounds-cannabinoids, terpenes, and flavonoids. While major cannabinoids like delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) have received extensive scrutiny for their pharmacological properties, emerging evidence underscores the collaborative interactions among these constituents, suggesting a collective therapeutic potential. This comprehensive review explores the intricate relationships and synergies between cannabinoids, terpenes, and flavonoids in cannabis. Cannabinoids, pivotal in cannabis's bioactivity, exhibit well-documented analgesic, anti-inflammatory, and neuroprotective effects. Terpenes, aromatic compounds imbuing distinct flavours, not only contribute to cannabis's sensory profile but also modulate cannabinoid effects through diverse molecular mechanisms. Flavonoids, another cannabis component, demonstrate anti-inflammatory, antioxidant, and neuroprotective properties, particularly relevant to neuroinflammation. The entourage hypothesis posits that combined cannabinoid, terpene, and flavonoid action yields synergistic or additive effects, surpassing individual compound efficacy. Recognizing the nuanced interactions is crucial for unravelling cannabis's complete therapeutic potential. Tailoring treatments based on the holistic composition of cannabis strains allows optimization of therapeutic outcomes while minimizing potential side effects. This review underscores the imperative to delve into the intricate roles of cannabinoids, terpenes, and flavonoids, offering promising prospects for innovative therapeutic interventions and advocating continued research to unlock cannabis's full therapeutic potential within the realm of natural plant-based medicine.