A Systematic Review of Laser Treatment for Angiofibromas in Tuberous Sclerosis.

BACKGROUND: While mammalian target of rapamycin inhibitors have revolutionized the management of angiofibroma in tuberous sclerosis complex (TS), physical modalities such as laser are still indicated for recalcitrant lesions. OBJECTIVE: The authors performed a systematic review of the efficacy and safety of laser treatment for TS-related facial angiofibroma. METHODS: The electronic databases such as MEDLINE, Embase, PubMed, Cochrane Central Register of Controlled Trials, and Web of Science were searched from inception to October 10, 2023, for eligible records. RESULTS: Forty-seven articles met the inclusion criteria, representing a total of 217 patients with TS-related facial angiofibroma who received laser treatment. Several lasers have been trialed in patients including carbon dioxide (n = 95, 43.7%), pulsed dye (n = 21, 9.7%), argon (n = 16, 7.4%), neodymium-doped: yttrium aluminum garnet (n = 12, 5.5%), copper vapor (n = 9, 4.1%), potassium titanyl phosphate (n = 7, 3.2%), erbium: yttrium aluminum garnet (n = 2, 0.9%), lasers and various combination therapies (n = 55, 25.3%). CONCLUSION: Potassium titanyl phosphate, pulsed dye, and neodymium-dopsed:yttrium aluminum garnet lasers are better suited to manage the vascular components of angiofibroma while ablative lasers such as erbium: yttrium aluminum garnet and carbon dioxide lasers may present better options for lesions with a prominent fibrous component. While several lasers have been trialed with broadly favorable results, the low level of evidence precludes definitive conclusions, and no single laser appears superior.

Application of Integrated Computational Approaches in Prediction of Plant Virus Encoded miRNAs and Their Targeted Plant Genes.

This chapter presents a comprehensive approach to predict novel miRNAs encoded by plant viruses and identify their target plant genes, through integration of various ab initio computational approaches. The predictive process begins with the analysis of plant viral sequences using the VMir Analyzer software. VMir Viewer software is then used to extract primary hairpins from these sequences. To distinguish real miRNA precursors from pseudo miRNA precursors, MiPred web-based software is employed. Verified real pre-miRNA sequences with a minimum free energy of < -20 Kcal/mol, are further analyzed using the RNAshapes software. Validation of predictions involves comparing them with available Expressed Sequence Tags (ESTs) from the relevant plant using BlastN. Short sequences with lengths ranging from 19 to 25 nucleotides and exhibiting <5 mismatches are prioritized for miRNA prediction. The precise locations of these short sequences within pre-miRNA structures generated using RNAshapes are meticulously identified, with a focus on those situated on the 5' and 3' arms of the structures, indicating potential miRNAs. Sequences within the arms of pre-miRNA structures are used to predict target sites within the ESTs of the specific plant, facilitated by psRNA Target software, revealing genes with potential regulatory roles in the plant. To confirm the outcome of target prediction, results are individually submitted to the RNAhybrid web-based software. For practical demonstration, this approach is applied to analyze African cassava mosaic virus (ACMV) and East African cassava mosaic virus-Uganda (EACMV-UG) viruses, as well as the ESTs of Jatropha and cassava.

Phenotypic and Genotypic Methods for the Identification and Quantification of Cyanobacteria in Lake Water.

Early monitoring of Microcystis, a cyanobacterium that produces microcystin, is paramount in order to confirm the presence of Microcystis spp. Both phenotypic and genotypic methods have been used. The phenotypic methods provide the presence of the microcystis but do not confirm its species type and toxin produced. Additionally, phenotypic methods cannot differentiate toxigenic from non-toxigenic Microcystis. Therefore, the current protocol also describes genetic methods based on PCR to detect toxigenic Microcystis spp. based on microcystin synthetase E (mcy E) gene and 16-23S RNA genes for species-specific identification, which can effectively comprehend distinct lineages and discrimination of potential complexity of microcystin populations. The presence of these microcystin toxins in blood, in most cases, indicates contamination of drinking water by cyanobacteria. The methods presented herein are used to identify microcystin toxins in drinking water and blood.

Guselkumab for Pityriasis Rubra Pilaris and Dysregulation of IL-23/IL-17 and NFkB Signaling: A Nonrandomized Trial.

Importance: There is no US Food and Drug Administration-approved treatment for pityriasis rubra pilaris (PRP), and it is common for patients to fail to experience improvement with several systemic options. Involvement of interleukin (IL) 23 suggests a potential therapeutic target. Objective: To determine whether guselkumab, an IL-23p19 inhibitor, provides clinical improvement for participants with PRP and better understand gene and protein dysregulation in PRP. Design, Setting, and Participants: This single-arm, investigator-initiated nonrandomized trial was conducted from October 2019 to August 2022 at a single-center academic university with participants from 8 states in the US. In total, 14 adults with moderate to severe PRP were enrolled; 12 completed the trial. Age-matched and sex-matched healthy controls provided skin and blood for proteomic and transcriptomic studies. The primary outcome was observed at 24 weeks, and additional follow-up occurred at 36 weeks. Intervention: Guselkumab is a fully human immunoglobulin G1 λ monoclonal antibody that selectively binds and inhibits the p19 subunit of IL-23. Subcutaneous injections were given at the US Food and Drug Administration-approved dosing schedule for psoriasis over a 24-week period. Main Outcomes and Measures: The primary outcome was the mean change in the Psoriasis Area Severity Index (PASI) score at week 24. Secondary outcomes included pruritus, Dermatology Life Quality Index score, clinical response at week 36, and association with transcriptomics and proteomics expression. Results: A per-protocol analysis was performed for the cohort of 4 female and 8 male patients who had a mean (SD) age of 56.5 (18.7) years. The mean improvement in PASI score, pruritus, and Dermatology Life Quality Index score was 61.8% (P < .001), 62.3% (P = .001), and 60.2% (P < .001), respectively. Nine participants (75%) achieved a 50% improvement in PASI. Among these clinical responders, at week 36, 8 of 9 achieved PASI75, and 6 of 9 achieved PASI90. No participants had pathogenic CARD14 gene variations. There was 1 serious adverse event that was not associated with the study drug. Proteomics and gene expression profiles identified dysregulation of a predominance of inflammatory pathways (such as T helper 17 and nuclear factor κ B) in participants with PRP who later responded well to treatment with guselkumab and stronger dysregulation of keratinocyte development pathways in individuals who did not respond to guselkumab. Conclusion and Relevance: The results of this nonrandomized trial suggest that guselkumab has efficacy in treating refractory moderate to severe adult PRP. Trial Registration: ClinicalTrials.gov Identifier: NCT03975153.

Autonomic cardiac function in children and adolescents with long COVID: a case-controlled study.

Although the mechanisms underlying the pathophysiology of long COVID condition are still debated, there is growing evidence that autonomic dysfunction may play a role in the long-term complications or persisting symptoms observed in a significant proportion of patients after SARS-CoV-2 infection. However, studies focused on autonomic dysfunction have primarily been conducted in adults, while autonomic function has not yet been investigated in pediatric subjects. In this study, for the first time, we assessed whether pediatric patients with long COVID present abnormalities in autonomic cardiac function. Fifty-six long COVID pediatric patients (mean age 10.3 ± 3.8 y) and 27 age-, sex-, and body surface area-matched healthy controls (mean age 10.4 ± 4.5y) underwent a standard 12-lead electrocardiography (ECG) and 24-h ECG Holter monitoring. Autonomic cardiac function was assessed by time-domain and frequency-domain heart rate variability parameters. A comprehensive echocardiographic study was also obtained by two-dimensional echocardiography and tissue Doppler imaging. Data analysis showed that pediatric patients with long COVID had significant changes in HRV variables compared to healthy controls: significantly lower r-MSSD (root mean square of successive RR interval differences, 47.4 ± 16.9 versus 60.4 ± 29.1, p = 0.02), significant higher values VLF (very low frequency, 2077.8 ± 1023.3 versus 494.3 ± 1015.5 ms, p = 0.000), LF (low frequency, 1340.3 ± 635.6 versus 354.6 ± 816.8 ms, p = 0.000), and HF (high frequency, 895.7 ± 575.8 versus 278.9 ± 616.7 ms, p = 0.000). No significant differences were observed between the two groups both in systolic and diastolic parameters by echocardiography.  Conclusion: These findings suggest that pediatric patients with long COVID have an imbalance of cardiac autonomic function toward a relative predominance of parasympathetic tone, as already reported in adult patients with long COVID. Further studies are needed to clarify the clinical significance of this autonomic dysfunction and demonstrate its role as a pathophysiological mechanism of long COVID, paving the way for effective therapeutic and preventive strategies. What is Known: • Long Covid in children has been described globally, but studies have mostly focused on collecting the temporal evolution of persisting symptoms. What is New: • Cardiac autonomic imbalance toward a relative predominance of parasympathetic tone is a mechanism underlying Long Covid in children, as also described in adults.

Canine Schistosomiasis in the West Coast: Heterobilharzia americana in Two Natural Intermediate Hosts Found in the Colorado River, California.

The emergence of infectious diseases presents a significant global health, economic, and security risk. Climate change can unexpectedly lead to the spread of pathogens, vectors, or hosts into new areas, contributing to the rise of infectious diseases. Surveillance plays a crucial role in monitoring disease trends and implementing control strategies. In this study, we document the first discovery of Heterobilharzia americana, a parasitic schistosome of mammals and its intermediate hosts Galba cubensis and Galba humilis along the banks of the Colorado River in California. We conducted multiple samplings of snails from various locations in the region with a previous history of canine schistosomiasis. Nucleotide sequencing of the multiple regions of the snails' and parasites' DNA revealed the coexistence of G. cubensis and G. humilis, both infected with H. americana. Phylogenetic analyses further validate the presence of H. americana in California, suggesting a wider distribution than previously reported. Our findings have implications for public health, veterinary medicine, and biodiversity conservation, contributing to developing effective control strategies to prevent the spread of this emerging infectious disease.

The Time Burden of Office Visits in Contemporary Pituitary Care, 2016 to 2019.

BACKGROUND: The concept of "time toxicity" has emerged to address the impact of time spent in the healthcare system; however, little work has examined the phenomenon in the field of otolaryngology. OBJECTIVE: To validate the use of Evaluation and Management (E/M) current procedural terminology codes as a method to assess time burden and to pilot this tool to characterize the time toxicity of office visits associated with a diagnosis of pituitary adenoma between 2016 and 2019. METHODS: A retrospective cohort study of outpatient office visits quantified differences between timestamps documenting visit length and their associated E/M code visit length. The IBM MarketScan database was queried to identify patients with a diagnosis of pituitary adenoma in 2016 and to analyze their new and return claims between 2016 and 2019. One-way ANOVA and two-sample t-tests were used to examine claim quantity, time in office, and yearly visit time. RESULTS: In the validation study, estimated visit time via E/M codes and actual visit time were statistically different (P < 0.01), with E/M codes underestimating actual time spent in 79.0% of visits. In the MarketScan analysis, in 2016, 2099 patients received a primary diagnosis of pituitary adenoma. There were 8490 additional-related claims for this cohort from 2016 to 2019. The plurality of new office visits were with endocrinologists (n = 857; 29.3%). Total time spent in office decreased yearly, from a mean of 113 min (2016) to 69 min (2019) (P < 0.001). CONCLUSIONS: E/M codes underestimate the length of outpatient visits; therefore, time toxicity experienced by pituitary patients may be greater than reported. Further studies are needed to develop additional assessment tools for time toxicity and promote increased efficiency of care for patients with pituitary adenomas.

Predictability and conceptual repeatability of the predator-associated burst speed ecophenotype in western mosquitofish (Gambusia affinis).

Predation exerts strong selection pressure on morphological traits and is often studied in freshwater fishes. A common morphological ecophenotype driven by predation from pursuit predators is the predator-associated burst speed (PABS) ecophenotype. This ecophenotype, characterized by a smaller head, smaller body, and larger caudal region, is commonly found in western mosquitofish (Gambusia affinis) residing in environments with sunfish (family Centrarchidae) predators. However, the repeatability and transferability of the PABS ecophenotype across populations have not been tested. The four objectives of this study were to (1) assess the repeatability of methods to confirm the presence of the PABS ecophenotype in independent populations, (2) test whether morphology is correlated with predator abundance, (3) assess the repeatability of utilizing a discriminant function analysis (DFA) to accurately classify fish to predator status, and (4) use a DFA to conduct a cross-validation test of the PABS model using previously studied populations of G. affinis to predict predator status of newly studied populations. There was consistency in the occurrence of the PABS ecophenotype among populations with predators. Permuted MANOVA (PMANOVA) models fit to each dataset revealed a significant effect of collection site nested within predator status (i.e., presence or absence of predator), suggesting location-specific variations of the PABS ecophenotype. In addition, a PMANOVA model fit to body shape as a function of predator abundance (i.e., 0, 0.1-1.0, or >1.0 predators per minute of electrofishing) revealed a significant effect of predation level in the newly studied populations, suggesting morphology differs among populations with varying predator abundances. Cross-study validation of the DFA revealed low between-study accuracy compared to within-study accuracy, but elongation of the caudal region in the presence of predators was consistent across studies. Our findings ultimately suggest that although the PABS ecophenotype at studied locations provides partial predictive capacity at unstudied locations, the nature and magnitude of the PABS ecophenotype depend on environmental settings, encounter histories with predators, level of abundance of predators, or other spatially structured mechanisms.

Lack of antiviral activity of probenecid in vitro and in Syrian golden hamsters.

OBJECTIVES: Antiviral interventions are required to complement vaccination programmes and reduce the global burden of COVID-19. Prior to initiation of large-scale clinical trials, robust preclinical data to support candidate plausibility are required. This work sought to further investigate the putative antiviral activity of probenecid against SARS-CoV-2. METHODS: Vero E6 cells were preincubated with probenecid, or control media for 2 h before infection (SARS-CoV-2/Human/Liverpool/REMRQ0001/2020). Probenecid or control media was reapplied, plates reincubated and cytopathic activity quantified by spectrophotometry after 48 h. In vitro human airway epithelial cell (HAEC) assays were performed for probenecid against SARS-CoV-2-VoC-B.1.1.7 (hCoV-19/Belgium/rega-12211513/2020; EPI_ISL_791333, 2020-12-21) using an optimized cell model for antiviral testing. Syrian golden hamsters were intranasally inoculated (SARS-CoV-2 Delta B.1.617.2) 24 h prior to treatment with probenecid or vehicle for four twice-daily doses. RESULTS: No observable antiviral activity for probenecid was evident in Vero E6 or HAEC assays. No reduction in total or subgenomic RNA was observed in terminal lung samples (P > 0.05) from hamsters. Body weight of uninfected hamsters remained stable whereas both probenecid- and vehicle-treated infected hamsters lost body weight (P > 0.5). CONCLUSIONS: These data do not support probenecid as a SARS-CoV-2 antiviral drug.

Evaluation of Real and Perceived Risk to Health Care Workers Caring for Patients With the Omicron Variant of the SARS-CoV-2 Virus in Surgery and Obstetrics.

OBJECTIVES: The Omicron variant of the SARS-CoV-2 virus is described as more contagious than previous variants. We sought to assess risk to health care workers (HCWs) caring for patients with COVID-19 in surgical/obstetrical settings, and the perception of risk among this group. METHODS: From January to April 2022, reverse transcription polymerase chain reaction was used to detect the presence of SARS-CoV-2 viral ribonucleic acid in patient, environmental (floor, equipment, passive air) samples, and HCWs' masks (inside surface) during urgent surgery or obstetrical delivery for patients with SARS-CoV-2 infection. The primary outcome was the proportion of HCWs' masks testing positive. Results were compared with our previous cross-sectional study involving obstetrical/surgical patients with earlier variants (2020-2021). HCWs completed a risk perception electronic questionnaire. RESULTS: Eleven patients were included: 3 vaginal births and 8 surgeries. In total, 5/108 samples (5%) tested positive (SARS-CoV-2 Omicron) viral ribonucleic acid: 2/5 endotracheal tubes, 1/22 floor samples, 1/4 patient masks, and 1 nasal probe. No samples from the HCWs' masks (0/35), surgical equipment (0/10), and air (0/11) tested positive. No significant differences were found between the Omicron and 2020/21 patient groups' positivity rates (Mann-Whitney U test, P = 0.838) or the level of viral load from the nasopharyngeal swabs (P = 0.405). Nurses had a higher risk perception than physicians (P = 0.038). CONCLUSION: No significant difference in contamination rates was found between SARS-CoV-2 Omicron BA.1 and previous variants in surgical/obstetrical settings. This is reassuring as no HCW mask was positive and no HCW tested positive for COVID-19 post-exposure.

Hemophagocyte morphology and hypertriglyceridemia correlate with diagnosis of hemophagocytic lymphohistiocytosis in patients with bone marrow hemophagocytes.

OBJECTIVES: To investigate laboratory and bone marrow findings that can help predict a diagnosis of hemophagocytic lymphohistiocytosis (HLH) for patients who have demonstrated hemophagocytes (HPCs) in the bone marrow. METHODS: A total of 57 cases from 48 patients with HPCs present on bone marrow examination were included. The numbers and morphologic characteristics of HPCs with ingested nucleated cells (nHPC) were counted. Pertinent medical history, relevant laboratory values, and flow cytometry data at the time of bone marrow biopsy were collected. RESULTS: A total of 24 patients fulfilled diagnostic criteria for HLH, and the remaining 24 patients did not. By using HLH-2004 cutoffs, only hypertriglyceridemia (≥265 mg/dL) was significantly associated with HLH diagnosis. The HLH cases more frequently had nHPC-ingesting granulocytic cells (gHPC) (75.9% vs 24.1%, P = .009). The percentage of gHPC to all nHPC was also significantly higher in HLH cases (median, 15.4% vs 0%; P = .0002). Both triglyceride level (area under the curve [AUC] = 0.88, P < .0001) and gHPC percentage (AUC = 0.81, P = .0005) were significant in predicting HLH diagnosis. Finally, no overt immunophenotypic abnormality was noted for 19 HLH cases with available flow cytometry data. CONCLUSIONS: The presence of hypertriglyceridemia and more frequent gHPC has predictive value for HLH diagnosis in patients with bone marrow HPC.

Disturbed sleep after lung transplantation is associated with worse patient-reported outcomes and chronic lung allograft dysfunction.

Many lung transplant recipients fail to derive the expected improvements in functioning, HRQL, or long-term survival. Sleep may represent an important, albeit rarely examined, factor influencing lung transplant outcomes. Within a larger cohort study, 141 lung transplant recipients completed the Medical Outcomes Study (MOS) Sleep Scale along with a broader survey of patient-reported outcome (PRO) measures and frailty assessment. MOS Sleep yields the Sleep Problems Index (SPI); we also derived an insomnia-specific subscale. Potential perioperative predictors of disturbed sleep and time to chronic lung allograft dysfunction (CLAD) and death were derived from medical records. We investigated associations between perioperative predictors on SPI and Insomnia and associations between SPI and Insomnia on PROs and frailty by linear regressions, adjusting for age, sex, and lung function. We evaluated the associations between SPI and Insomnia on time to CLAD and death using Cox models, adjusting for age, sex, and transplant indication. Post-transplant hospital length of stay >30 days was associated with worse sleep by SPI and insomnia (SPI: p=0.01; Insomnia p=0.02). Worse sleep by SPI and insomnia was associated with worse depression, cognitive function, HRQL, physical disability, health utilities, and Fried Frailty Phenotype frailty (all p<0.01). Those in the worst quartile of SPI and insomnia exhibited increased risk of CLAD (HR 2.18; 95%CI: 1.22-3.89 ; p=0.01 for SPI and HR 1.96; 95%CI 1.09-3.53; p=0.03 for insomnia). Worsening in SPI but not insomnia was also associated with mortality (HR: 1.29; 95%CI: 1.05-1.58; p=0.01). Poor sleep after lung transplant may be a novel predictor of patient reported outcomes, frailty, CLAD, and death with potentially important screening and treatment implications.

Tackling the escalating burden of care in Uganda: a qualitative exploration of the challenges experienced by family carers of patients with chronic non-communicable diseases.

BACKGROUND: Family carers face challenges that could significantly affect their health and the health of those they care for. However, these challenges are not well documented in low-income settings, including Uganda. We explored the challenges of caring for someone with chronic non-communicable disease (NCD) in Uganda. METHODS: We conducted a qualitative exploratory study at Hospice Africa, Uganda (an urban setting) and Hampton Health Center (a rural setting) in Uganda in February and March 2021. Family carers (n = 44) were recruited using snowball and purposive sampling techniques. Data were collected using focus group discussions and in-depth interviews, gathering family carer perspectives of (a) their caring role (b) their support needs, and (c) attitudes of the wider community. In total, four focus group discussions and 10 individual interviews were completed. RESULTS: The average age of carers was 46 years old. The majority of family care was provided by female relatives, who also experienced intersectional disadvantages relating to economic opportunities and employment. Family carers carried a huge burden of care, experiencing significant challenges that affected their physical health, and material and emotional well-being. These challenges also affected the quality of care of the patients for whom they cared. Carers struggled to provide for the basic needs of the patient including the provision of medication and transport to health facilities. Carers received no formal training and limited support to carry out the caring role. They reported that they had little understanding of the patient's illness, or how best to provide care. CONCLUSIONS: As NCDs continue to rise globally, the role of family caregivers is becoming more prominent. The need to support carers is an urgent concern. Family carer needs should be prioritised in policy and resource allocation. The need for a carer's toolkit of resources, and the enhancement of community support, have been identified.

Fatigue risk assessment of a Helicopter Emergency Medical Service crew working a 24/7 shift pattern: results of a prospective service evaluation.

BACKGROUND: The work of Helicopter Emergency Medical Services (HEMS) teams crosses the boundaries of several high-risk occupations including medicine, aviation, and transport. Working conditions can be challenging and operational demands requires a 24-h rota, resulting in disruption of the normal circadian rhythm. HEMS crews are therefore prone to both mental and physical fatigue. As fatigue in medical providers is linked to poor cognitive performance, degradation of psychomotor skills and error, this study aimed to explore the existence of predictable patterns of crew-fatigue in a HEMS service. METHODS: HEMS medical crew members working a 3-on 3-off forward rotating rota with a 5-week shift cycle were asked to do psychomotor vigilance tests (PVT) as an objective measure of fatigue. PVT testing was undertaken at the start, mid- and at the end of every shift during a full 5-week shift cycle. In addition, they were asked to score subjective tiredness with the Samn-Perelli Fatigue Scale (SPFS), and to keep a Transport Fatigue Assessment shift log, wherein they noted shift characteristics potentially related to fatigue. Primary outcome of interest was defined as the change in PVT and SPFS scores over time. RESULTS: Mean baseline resting PVT in milliseconds at the start of the study period was 427 [390-464]. There was an overall trend towards higher PVT-scores with shift progression mean [95% CI] PVT at the start of shifts 447 [433-460]; halfway through the shift 452 [440-463]; end of the shift 459 [444-475], p = 0.10), whereas SPFS scores remained constant. Within a 5 week forward-rotating cycle, an overall trend towards a gradual increase in both average PVT (from 436 [238-454] to 460 [371-527, p = 0.68] ms;) and SPFS (from 2.9 [2.6-3.2] to 3.6 [3.1-4.0], p = 0.38) was observed, although significant interindividual variation was present. Reported SPFS scores ≥ 4 (moderate fatigue) were mainly related to workload (number of jobs) and transport mode (car-based shifts). CONCLUSION: An overall trend towards a decline in psychomotor vigilance and an increase in self-reported tiredness was found for HEMS crew over a 5-week shift cycle. Using a bespoke predictive fatigue tool on a day-to-day basis could increase fatigue awareness and provide a framework to which relevant mitigating options can be applied.

A dual-core NMR system for field-cycling singlet assisted diffusion NMR.

Long-lived singlet spin order offers the possibility to extend the spin memory by more than an order of magnitude. This enhancement can be used, among other applications, to assist NMR diffusion experiments in porous media where the extended lifetime of singlet spin order can be used to gain information about structural features of the medium as well as the dynamics of the imbibed phase. Other than offering the possibility to explore longer diffusion times of the order of many minutes that, for example, gives unprecedented access to tortuosity in structures with interconnected pores, singlet order has the important advantage to be immune to the internal field gradients generated by magnetic susceptibility inhomogeneities. These inhomogeneities, however, are responsible for very short T2 decay constants in high magnetic field and this precludes access to the singlet order in the first instance. To overcome this difficulty and take advantage of singlet order in diffusion experiments in porous media, we have here developed a dual-core system with radiofrequency and 3-axis pulsed field gradients facilities in low magnetic field, for preparation and manipulation of singlet order and a probe, in high magnetic field, for polarisation and detection. The system operates in field-cycling and can be used for a variety of NMR experiments including diffusion tensor imaging (both singlet assisted and not). In this paper we present and discuss the new hardware and its calibration, and demonstrate its capabilities through a variety of examples.