Evolution Of Disease Research Articles

Dynamic analysis and data-driven inference of a fractional-order SEIHDR epidemic model with variable parameters

To analyze and predict the evolution of contagion dynamics, fractional derivative modeling has emerged as an important technique. However, inferring the dynamical structure of fractional-order models with high degrees of freedom poses a challenge. In this paper, to elucidate the spreading mechanism and non-local properties of disease evolution, we propose a novel fractional-order SEIHDR epidemiological model with variable parameters, incorporating fractional derivatives in the Caputo sense. We compute the basic reproduction number by the next-generation matrix and establish local and global stability conditions based on this reproduction number. By using the fractional Adams–Bashforth method, we validate dynamical behaviors at different equilibrium points in both autonomous and non-autonomous scenarios, while qualitatively analyze the effects of fractional order on the dynamics. To effectively address the inverse problem of the proposed fractional SEIHDR model, we construct a fractional Physics-Informed Neural Network framework to simultaneously infer time-dependent parameters, fractional orders, and state components. Graphical results based on the COVID-19 pandemic data from Canada demonstrate the effectiveness of the proposed framework.

Perceptions of Cancer Through the Ages—From Hippocratic Oncology to Precision Cancer Medicine

The unravelling of the human genome created new perceptions of the origin and evolution of diseases, and for cancer in particular, it established the notion that neoplasia has been a companion of life since its appearance on Earth. It is not surprising that neoplasms, in various forms, develop in numerous species of animals and even in plants. Unmistakable accounts of cancer with clinical features as are understood today begin in the 5th c. B.C. The principles and practice of the Hippocratic and Galenic tradition dominated cancer care virtually into the 20th century. Advanced sequencing technologies at the dawn of the 21st century generated new therapeutic opportunities with immunotherapy, oncolytic virotherapy, and gene transfer, with the latter especially being used in cases of hereditary cancer.

Ulcerative Jejunitis in Celiac Disease: A Thirty-Year U.S. Experience.

Ulcerative jejunitis (UJ) or ulcerative enteritis (UE) is a rare complication of celiac disease (CeD). Guidelines regarding diagnosis and management are missing and these cases have seldom been reported in the United States. Single center case-series of CeD in which UE developed at a large academic center in the USA. Clinical presentation, diagnosis, treatment, and evolution of disease were collected. Eight cases were identified (6M/2F, mean age 59.5 (38-77) years). Presentations included intestinal obstruction (n=3), GI hemorrhage (n=3), and malabsorption (n=2). Ulcers were present in the duodenum in 4 patients, and exclusively past the angle of Treitz in only 4 cases, which makes the term ulcerative enteritis (UE) more appropriate than UJ. Six out of eight had T-cell receptor (TCR) clonal gene rearrangements and two had definite aberrant T cells. Corticosteroids were tried in all patients without improvement and 5 underwent surgical resection. Three patients received cladribine. One patient received an autologous stem cell transplant, followed by ruxolitinib. Two were subsequently diagnosed with enteropathy-associated T-cell lymphoma (EATL), including one with cerebral EATL, and 1 died from hemophagocytic syndrome. Two are still alive, including one only on GFD and two were lost to follow-up after surviving at least 30 months post treatment. UE seems a more appropriate term to describe an ulcerative complication of CeD at high risk of obstruction or bleeding. Steroids were not effective. Treatment outcomes were variable, but with a 50% death rate.

Cardiac biomarkers can detect and track subclinical HIV-associated myocardial disease in newly diagnosed people living with HIV

Abstract Background Cardiovascular disease (CVD) in people living with HIV (PLWH) remains poorly understood, and the profile of disease differs between high-income and low- and middle-income settings[1]. Subclinical cardiovascular abnormalities may be present at the time of HIV diagnosis and serve as potential substrate for future CVD[2]. Biochemical markers are fundamental in cardiac evaluation, and various novel assays have recently been discovered. Purpose To assess the presence and evolution of subclinical myocardial disease, we prospectively assessed the hearts of newly diagnosed PLWH and matched, HIV-uninfected controls using cardiac biomarkers and correlated our findings with cardiovascular magnetic resonance imaging (CMR). Methods Newly diagnosed, antiretroviral treatment (ART) naïve PLWH were recruited along with HIV uninfected, age- and sex-matched controls in the Western Cape Province of South Africa. All participants underwent measurement of high-sensitivity cardiac troponin T (hs-cTnT), N-terminal pro-B-type natriuretic peptide (NT-proBNP), soluble ST2 (sST2), Galectin-3, and a CMR study with multiparametric mapping. The HIV group started ART and was re-evaluated 9 months later. The cardiac biomarkers and their correlation with CMR parameters were evaluated in, and between groups. Results Compared with controls (n=22), hs-cTnT (4.0 ng/l vs 5.1 ng/l; p=0.004) , NT-proBNP (23.2 ng/l vs 40.8 ng/l; p=0.02), and Galectin-3 (6.8 ng/ml vs 9.0 ng/ml; p=0.002) were all significantly higher in the ART naïve group (n=73). After 9 months of ART, hs-cTnT (5.1 ng/l vs 4.3 ng/l; p=0.02) and NT-proBNP (40.8 ng/l vs 28.5 ng/l; p=0.03) both decreased significantly, and a trend of decrease was seen in sST2 (16.5 ng/ml vs 14.8 ng/l; p=0.08). Galectin-3 did not demonstrate decrease over time (9.0 ng/ml vs 8.8 ng/ml; p=0.6). The cardiac biomarkers that showed the best correlation with CMR measurements native T1, T2, and ECV, were NT-proBNP (rs≥0.4, p<0.001) and Galectin-3 (rs≥0.3, p<0.01). Conclusion Our cardiac biomarker data supports the presence of subclinical myocardial injury, remodelling, and fibrosis at HIV diagnosis and ART had a positive influence on these blood markers. It remains unclear if the underlying pathological processes were fully addressed by ART. The elevation of Galectin-3 despite ART may be indicative of ongoing cardiac remodelling that may incur future risk of CVD, and necessitates further study. The ability of cardiac biomarkers to detect and track tissue abnormalities diagnosed with CMR, showed promise. With additional research, this could lead to improvements in screening and monitoring myocardial abnormalities, even in CMR-limited settings.

Analysis of control measures inducing the evolution of infectious viral diseases

With the continuation of the infectious disease, pathogens mutate and interact with the resident pathogen. In this paper, we develop an SIR model that considers the evolution of viral virulence under the regulation of different defense strengths. By using infectious disease dynamics and evolutionary adaptive dynamics, we obtain the evolutionary criteria allowing for evolutionary branching and continuously stable strategy across varying intensities of prevention and control measures. Our study finds that robust prevention and control measures can contribute to a rapid evolutionary trend toward higher virulence. We perform a critical function analysis to reveal the evolutionary consequences of trade-offs of arbitrary shape and analyze a diverse range of evolutionary dynamics. Furthermore, we investigate the coexistence of two different strains and construct an evolutionary model to obtain their invasion fitness functions and the evolutionarily singular coalition of the dimorphism. We contemplate the presence of secondary branching on a significantly extended evolutionary time scale. Last, we conduct the numerical simulations to prove our theoretical findings. This reveals the law that the evolutionary state of pathogens is affected by the intensity of prevention and control strategies. The results and methods can be used as references for studying the effects of other factors on virus evolution.

An Analysis of the Influence of a Patient’s Sex on Quality of Life in Liver and Kidney Transplantation

Background: Renal and liver transplantation influences the quality of life of the patients who undergo these procedures. Therefore, the aim of the present study was to analyze possible differences in liver and kidney transplantation in relation to the patient’s sex and to determine their impact on quality of life. Methodology: An observational study was carried out with 147 patients with liver (n = 70) and kidney (n = 77) failure on the transplantation waiting list. The possible influence of sex on clinical, sociodemographic, and psychological aspects of the patients’ quality of life before and 6 months after transplantation was analyzed. Questionnaires on health-related quality of life (SF-36), the perception of social and family support (EASP), and coping strategies (CEA), the depression and anxiety scale (HAD), and the Eysenck personality inventory (EPI) were used. A univariate analysis was performed according to sex using statistical tools including the Chi-square test, the t-test, and a univariate linear analysis of variance. Results: In patients on the waiting list for liver transplantation, we found sex differences in terms of age (p = 0.040), time of evolution of end-stage liver disease (p = 0.013), etiology (p = 0.07), and associated complications, as well as in the consumption of tobacco and other psychotropic substances (p = 0.022), while patients on the waiting list for renal transplantation showed sex-related differences in terms of etiology (p = 0.012) and alcohol consumption (p = 0.005). The results showed significant sex-related differences in sociodemographic and psychological aspects, but no significant sex-related differences were observed in global quality of life in either of the two assessments in both groups. Discussion: The findings suggest that improvement in quality of life after liver or kidney transplantation is not influenced by the patient’s sex.

Suppression of dystroglycan function accompanies pancreatic acinar-to-ductal metaplasia and favours dysplasia development.

The basement membrane (BM) is among the predominant microenvironmental factors of normal epithelia and of precancerous epithelial lesions. Evidence suggests that the BM functions not only as a barrier to tumour invasion but also as an active tumour-suppressing signalling substrate during premalignancy. However, the molecular foundations of such mechanisms have not been elucidated. Here we explore potential tumour-suppressing functions of the BM during precancer evolution, focusing on the expression and function of the extracellular matrix receptor dystroglycan in the pancreas and pancreatic disease. We show that the dystroglycan protein is highly expressed in the acinar compartment of the normal pancreas but lower in the ductal compartment. Moreover, there is a strong suppression of dystroglycan protein expression with acinar-to-ductal metaplasia in chronic pancreatitis and in all stages of pancreatic precancer and cancer evolution, from acinar-to-ductal metaplasia to dysplasia to adenocarcinoma. The conditional knockout of dystroglycan in the murine pancreas produced little evidence of developmental or functional deficiency. However, conditional deletion of dystroglycan expression in the context of oncogenic Kras expression led to a clear acceleration of pancreatic disease evolution, including accelerated dysplasia development and decreased survival. These data establish dystroglycan as a suppressor of pancreatic dysplasia development and one that is muted in chronic pancreatitis and at the earliest stages of oncogene-induced transformation. We conclude that dystroglycan is an important mediator of the tumour-suppressing functions of the BM during precancer evolution and that reduced dystroglycan function increases cancer risk, highlighting the dynamics of cell-BM interactions as important determinants of early cancer progression. © 2024 The Pathological Society of Great Britain and Ireland.

A single-center case study series assessing the effect of selumetinib use in patients with neurofibromatosis-related plexiform neurofibromas

Abstract Background Neurofibromatosis type 1 (NF1) is a common genetic disorder of phenotypic variability with age-dependent penetrance. This study describes the diagnosis, clinical characterization, management, and outcomes of a large patient cohort with plexiform neurofibroma (PN) treated with selumetinib in a real-world clinical setting. Methods This single-center observational study consecutively enrolled patients with NF1-PN treated with selumetinib from April 2018 to April 2023. Data on clinical features, tumor types and locations, and results from genetic tests were recorded at baseline; details of disease management with selumetinib and surgical intervention and disease evolution including imaging data and evaluations of pain and function were documented. Results Overall, 54 patients with a median age (range) of 16.4 (4.5–58.0) years were enrolled. Most had cutaneous manifestations (88.9%), including cutaneous neurofibromas and PN. Patients underwent [18F]fluorodeoxyglucose (FDG)-PET/CT imaging before treatment to rule out malignant lesions. Initial evaluations included directed MRI, which facilitated future comparisons and allowed for the assessment of PN resectability. Pharmacological treatment with selumetinib (with surgery, without surgery) resulted in the following proportion of patients achieving stable disease (58.8%, 54.3%), partial response (29.4%, 28.6%), and improved pain (58.8%, 37.1%), deformity (17.6%, 20.0%), and functional (17.6%, 20.0%) outcomes, respectively. Conclusions Results from this study demonstrate that NF1-PN can be managed effectively with selumetinib with surgical intervention in some patients. Most patients achieved tumor stability and improved symptom control, and the majority of patients continue under treatment. Effective diagnosis and management were achieved through individualized utility of FDG-PET/CT and MRI imaging and targeted resource allocation.

Comprehensive quantitative magnetic resonance imaging assessment of skeletal muscle pathophysiology in golden retriever muscular dystrophy: Insights from multicomponent water T2 and extracellular volume fraction.

Quantitative MRI and MRS have become important tools for the assessment and management of patients with neuromuscular disorders (NMDs). Despite significant progress, there is a need for new objective measures with improved specificity to the underlying pathophysiological alteration. This would enhance our ability to characterize disease evolution and improve therapeutic development. In this study, qMRI methods that are commonly used in clinical studies involving NMDs, like water T2 (T2H2O) and T1 and fat-fraction (FF) mapping, were employed to evaluate disease activity and progression in the skeletal muscle of golden retriever muscular dystrophy (GRMD) dogs. Additionally, extracellular volume (ECV) fraction and single-voxel bicomponent water T2 relaxometry were included as potential markers of specific histopathological changes within the tissue. Apart from FF, which was not significantly different between GRMD and control dogs and showed no trend with age, T2H2O, T1, ECV, and the relative fraction of the long-T2 component, A2, were significantly elevated in GRMD dogs across all age ranges. Moreover, longitudinal assessment starting at 2months of age revealed significant decreases in T2H2O, T1, ECV, A2, and the T2 of the shorter-T2 component, T21, in both control and GRMD dogs during their first year of life. Notably, insights from ECV and bicomponent water T2 indicate that (I) the elevated T2H2O and T1 values observed in dystrophic muscle are primarily driven by an expansion of the extracellular space, likely driven by the edematous component of inflammatory responses to tissue injury and (II) the significant decrease of T2H2O and T1 with age in control and GRMD dogs reflects primarily the progressive increase in fiber diameter and protein content during tissue development. Our study underscores the potential of multicomponent water T2 relaxometry and ECV to provide valuable insights into muscle pathology in NMDs.

Temporal ordering of cognitive impairment in Parkinson's disease patients based on disease progression models

IntroductionIdentifying Parkinson's disease (PD) patients at risk of cognitive decline is crucial for enhancing clinical interventions. While several models predicting cognitive decline in PD exist, a new machine learning framework called disease progression models (DPMs) offers a data-driven approach to understand disease evolution. MethodsWe enrolled 423 PD patients and 196 healthy controls from the Parkinson's Progression Markers Initiative (PPMI). Our study encompassed a range of biomarkers, including motor, neurocognitive, and neuroimaging evaluations at baseline and annually. A methodology was employed to select optimal combinations of biomarkers for constructing DPMs with superior predictive capabilities for both diagnosing and estimating conversion times toward cognitive decline. ResultsAt baseline, the approach showed excellent performance in identifying individuals at high risk of cognitive decline within the first five years. Furthermore, the proposed timeline from cognitive impairment to dementia was also used to explore clinical events such as the onset of cognitive impairment, the development of dementia or amyloid pathology. The presence of amyloid pathology did not alter the progression of cognitive impairment among PD patients. ConclusionsNeuropsychological measures and certain biomarkers, including cerebrospinal fluid (CSF) amyloid beta 42 (Aβ42) and dopamine transporter deficits, can be used to predict cognitive decline and estimate a timeline from cognitive impairment to dementia, with amyloid pathology preceding the onset of dementia in many cases. Our DPMs suggested that the profiles of CSF Aβ42 and phosphorylated tau in PD patients may differ from those in aging patients and those with Alzheimer's disease.

Management of acute pain in adults with sickle cell disease: the experience of the Clinical Hematology Department of the University of Dakar.

The evolution of sickle cell disease (SCD) is marked by the occurrence of painful episodes linked to the obstruction of microvessels by sickle cells, known as vaso-occlusive crisis (VOC). The aim of this work was to report the practical aspects of the management of acute pain in adults with SCD. Recommendations based on these practices are also provided. This prospective, cross-sectional, descriptive, and analytical study was conducted over a four-month period of all sickle cell patients admitted to emergency departments for VOC. The parameters studied were sociodemographic, clinicobiological, therapeutic, and evolutionary. There were 118 cases of VOC identified, representing a prevalence of 78.14% of sickle cell emergencies. The mean age of the patients was 28.41 years. The SS sickle cell phenotype accounted for 86.61% of the cases. Osteoarticular pain was the reason for admission for 88.39% of the patients; it was located in the lower limbs in 39.08% and in the spine in 27.1%. Pain intensity was moderate in 6.25% of the patients, intense in 31.25%, and unbearable in 55.55%. Multimodal analgesia was the most commonly used treatment method, combining those of levels one and two (74.31%) and levels one and three (8.25%). The mean dose of morphine administered was 17.14 mg when morphine alone was prescribed for titration, 13.57 mg when paracetamol and morphine were combined, and 15.83 mg when nefopam and morphine were combined. Clinical outcome was favorable in 68.87% of the cases. Wide variability was observed in the modalities of analgesic treatment of sickle cell VOC. These variations reflect different views on the appropriateness of opioids. This study highlights the efficacy of multimodal analgesia in the management of acute pain in patients with SCD, particularly in regard to morphine sparing. Context-specific recommendations will be needed to harmonize practices.

The corticospinal tract in multiple sclerosis: correlation between cortical excitability and magnetic resonance imaging measures.

Multiple sclerosis (MS) is a central nervous system disease involving gray and white matters. Transcranial magnetic stimulation (TMS) and magnetic resonance imaging (MRI) could help identify potential markers of disease evolution, disability, and treatment response. This work evaluates the relationship between intracortical inhibition and facilitation, motor cortex lesions, and corticospinal tract (CST) integrity. Consecutive adult patients with progressive MS were included. Sociodemographic and clinical data were collected. MRI was acquired to assess primary motor cortex lesions (double inversion and phase-sensitive inversion recovery) and CST integrity (diffusion tensor imaging). TMS outcomes were obtained: motor evoked potentials (MEP) latency, resting motor threshold, short-interval intracortical facilitation (ICF) and inhibition. Correlation analysis was performed. Twenty-five patients completed the study (13 females, age: 55.60 ± 11.49 years, Expanded Disability Status Score: 6.00 ± 1.25). Inverse correlations were found between ICF mean and each of CST radial diffusivity (RD) (ρ =-0.56; p < 0.01), CST apparent diffusion coefficient (ADC) (ρ=-0.44; p = 0.03), and disease duration (ρ=-0.46; p = 0.02). MEP latencies were directly correlated with disability scores (ρ = 0.55; p < 0.01). High ADC/RD and low ICF have been previously reported in patients with MS. While the former could reflect structural damage of the CST, the latter could hint towards an aberrant synaptic transmission as well as a depletion of facilitatory compensatory mechanisms that helps overcoming functional decline. The findings suggest concomitant structural and functional abnormalities at later disease stages that would be accompanied with a heightened disability. The results should be interpreted with caution mainly because of the small sample size that precludes further comparisons (e.g., treated vs. untreated patients, primary vs. secondary progressive MS). The role of these outcomes as potential MS biomarkers merit to be further explored.

Trajectories of disease evolution upon treatment initiation in systemic lupus erythematosus: results from four clinical trials of belimumab.

Upon commencement of therapy for active disease, patients with systemic lupus erythematosus (SLE) show varying evolution regarding disease activity measures and patient-reported outcomes (PROs). Our objective was to identify disease evolution trajectories to gain a deeper understanding of SLE progression, ultimately improving future trial design. Patients with ≥2 visits and available data on SLEDAI-2K, BILAG, PGA, FACIT-F, and glucocorticoid use were included in a post-hoc analysis of four randomised controlled trials of belimumab (BLISS-52, BLISS-76, BLISS-SC, EMBRACE). Growth mixture modelling identified latent classes. Among 2868 patients analysed, baseline median disease duration was 4.5 (IQR: 1.5-9.7) years and mean (± standard deviation) SDI 0.7 (±2.0), SLEDAI-2K 10.2 (±3.6), BILAG 17.0 (±7.8), PGA 1.5 (±0.5), FACIT-F 30.6 (±11.9), and prednisone dose 11.0 (±8.9) mg/day. In the initial model, glucocorticoid use and dose yielded high standard errors, indicating a weak link with the latent process. A refined model considered only clinical measures and FACIT-F, corrected for intervention and SDI; no other covariates improved the fit. Four classes best described disease evolution: highly active, responders; highly active, non-responders; moderately active, responders; moderately active, non-responders. LLDAS and DORIS remission attainment associated with latent classes. By linking disease activity measures with PROs, we identified four distinct trajectories describing SLE evolution following the initiation of therapy. This classification could be valuable for personalising treatment and guiding biological studies aimed at distinguishing patients with varying anticipated treatment responses, as no single clinical variable alone can predict disease progression.

An insight into understanding ancient perspectives of respiratory health

This article explores the historical evolution of respiratory diseases highlighting its references in early Vedic texts such as the Rigveda, Yajurveda, Atharvaveda &amp; Upanishads, offering insights into ancient understandings of respiratory diseases. It also delves into Ayurvedic treatments and practices detailed in classical texts like Veerasimhavalokana in relation to respiratory disease . Additionally, it covers traditional healing practices including Vedic mantras and their impact on human health. The narrative extends to folklore with the story of Ondine’s Curse, which inspired the term for central hypoventilation syndrome. By synthesizing these historical sources and practices, it underscores the depth of ancient knowledge in managing respiratory health and its influence on contemporary respiratory therapy.

Course of immune thrombocytopenia according to the site of platelet destruction identified by indium-111 platelet scintigraphy.

In primary immune thrombocytopenia (ITP), predictors of disease evolution and treatment response are needed. Data based on the site of platelet destruction are scarce. We performed a retrospective single-centre study of adult patients with primary ITP undergoing at least one Indium-111 platelet scintigraphy (IPS) between 2009 and 2018. Thirty-three patients had isolated hepatic platelet destruction (H-group), and 97 isolated splenic destruction (S-group). Median age at diagnosis (p < 0.001), proportion of associated cardiovascular (p < 0.001), organ-specific autoimmune diseases (p = 0.02), dependence on steroids (p = 0.003) and failure to rituximab (p = 0.01) were higher and relapse more frequent (p = 0.03) in H-group compared to non-splenectomized patients in S-group. Splenectomy was only performed in patients from S-group (as patients with hepatic sequestration are not splenectomized in our centre): 79% were in relapse-free remission at the end of a median 3.4-year post-IPS follow-up, 16% relapsed. In multivariate analyses, only a history of organ-specific autoimmune or inflammatory disease was significantly associated with hepatic sequestration (OR = 4.3, 95% CI = 1.2-15, p = 0.02). Patients with isolated hepatic sequestration were older, had more cardiovascular events and organ-specific autoimmune diseases, greater dependence on steroids, more relapses and a decreased response rate to rituximab suggesting an increased refractoriness to immunomodulatory therapies. Patients with isolated splenic sequestration responded well to splenectomy.

Trends and Gaps in the Scientific Literature about the Effects of Nutritional Supplements on Canine Leishmaniosis.

In canine leishmaniosis (CanL), complex interactions between the parasites and the immunological background of the host influence the clinical presentation and evolution of infection and disease. Therefore, the potential use of nutraceuticals as immunomodulatory agents becomes of considerable interest. Some biological principles, mainly derived from plants and referred to as plant-derived nutraceuticals, are considered as supplementation for Leishmania spp. infection. This study provides a systematic review regarding the use of nutraceuticals as a treatment using a text mining (TM) and topic analysis (TA) approach to identify dominant topics of nutritional supplements in leishmaniosis-based research, summarize the temporal trend in topics, interpret the evolution within the last century and highlight any possible research gaps. Scopus® database was screened to select 18 records. Findings revealed an increasing trend in research records since 1994. TM identified terms with the highest weighted frequency and TA highlighted the main research areas, namely "Nutraceutical supports and their anti-inflammatory/antioxidant properties", "AHCC and nucleotides in CanL", "Vit. D3 and Leishmaniosis", "Functional food effects and Leishmaniosis" and "Extract effects and Leishmaniosis". Despite the existing academic interest, there are only a few studies on this issue so far, which reveals a gap in the literature that should be filled.

Dietary Rhythms and MASLD-Related Hepatocellular Carcinoma.

Dietary rhythms have emerged as a relevant variable in the equation relating nutrition and health. Both experimental and epidemiological studies point to potential beneficial effects of adequate fasting intervals between meals on the evolution of chronic diseases associated with aging. Metabolic dysfunction-associated steatotic liver disease (MASLD) is eminently related to diet and unsurprisingly, diet-based approaches are a mainstay in countering its long-term clinical evolution, including the emergence of hepatocellular carcinoma (HCC). We briefly discuss current evidence linking fasting intervals, MASLD, and HCC and propose a working hypothesis to reconcile some of the apparently conflicting results. This hypothesis relates the beneficial effects of time-restricted eating schedules to the quantity and quality of food, and it is easily amenable to testing.

Breast cancer diagnosis and staging in Chile: A non-randomized survey-based study to assess frequency and delays.

Breast cancer progression involves physiological mechanisms such as metastasis. Delays in diagnosis and treatment increase the risk of mortality and are associated with barriers to healthcare access. In Chile, breast cancer is highly prevalent, and early diagnosis has improved, although disparities in the disease evolution persist. This study characterized diagnostic and staging tests, waiting times, and sociodemographic profiles to identify delays and inequities in care. Survey study. Using a non-probabilistic sample, a questionnaire was applied in an encrypted platform with prior informed consent. The instrument collected data on requested tests, associated times, staging, and sociodemographic characteristics. These variables were analyzed using descriptive statistics, tests of association, confidence intervals, and comparison tests using bootstrapping. A sample of 263 persons was obtained. The most requested tests were biopsy (99.62%) and blood tests (80.23%). The median number of tests requested was six (Q1:4, Q3:8), with a mean of 5.87 (standard deviation: 2.24). No significant differences were observed in the percentage of persons from whom the total number of examinations were requested according to the studied variables. The day-hour-result intervals ranged from 1 to 365 days. The median day-hour-result of the biopsy was 15 days (Q1:10, Q3:30). People between 40 and 49 years old, non-residents of the capital city, belonging to income quintile I, with high school education, from the public health system, with late-stage diagnosis had higher median day-hour-result in biopsy. There was no significant difference in the number of requested tests according to staging (I and II, or III and IV). Biopsy in Chile is the test of choice for diagnostic confirmation in breast cancer. Other tests are requested regardless of the diagnosis stage, contrary to the recommendations of clinical guidelines. Cancer prognosis is crucial, especially in countries with greater inequalities.

Extensive longevity and DNA virus-driven adaptation in nearctic Myotis bats.

The rich species diversity of bats encompasses extraordinary adaptations, including extreme longevity and tolerance to infectious disease. While traditional approaches using genetic screens in model organisms have uncovered some fundamental processes underlying these traits, model organisms do not possess the variation required to understand the evolution of traits with complex genetic architectures. In contrast, the advent of genomics at tree-of-life scales enables us to study the genetic interactions underlying these processes by leveraging millions of years of evolutionary trial-and-error. Here, we use the rich species diversity of the genus Myotis - one of the longest-living clades of mammals - to study the evolution of longevity-associated traits and infectious disease using functional evolutionary genomics. We generated reference genome assemblies and cell lines for 8 closely-related (∼11 MYA) species of Myotis rich in phenotypic and life history diversity. Using genome-wide screens of positive selection, analysis of structural variation and copy number variation, and functional experiments in primary cell lines, we identify new patterns of adaptation in longevity, cancer resistance, and viral interactions both within Myotis and across bats. We find that the rapid evolution of lifespan in Myotis has some of the most significant variations in cancer risk across mammals, and demonstrate a unique DNA damage response in the long-lived M. lucifugus using primary cell culture models. Furthermore, we find evidence of abundant adaptation in response to DNA viruses, but not RNA viruses, in Myotis and other bats. This is in contrast to these patterns of adaptation in humans, which might contribute to the importance of bats as a reservoir of zoonotic viruses. Together, our results demonstrate the utility of leveraging natural variation to understand the genomics of traits with implications for human health and suggest important pleiotropic relationships between infectious disease tolerance and cancer resistance.

Developmental and epileptic encephalopathy 56 due to YWHAG variants: 12 new cases and review of the literature

Background and objectivesDevelopmental and epileptic encephalopathy 56 (DEE-56) is caused by pathogenic variants in YWHAG and is characterized by early-onset epilepsy and neurodevelopmental delay. This study reports on a cohort of DEE-56 individuals, correlating antiseizure medication usage and comorbidities, to aid in understanding disease evolution. MethodsWe analyzed data from thirty-nine individuals aged 3–40 years with YWHAG variants, including 12 previously unreported individuals (2 of these with recurrent distal 7q11.23 deletions) and 27 previously published cases (21 families, including 3 adult individuals reported in a family case). Our assessments encompassed clinical, radiological, and genetic evaluations. All procedures adhered to standardized protocols for patient approvals, registrations, and data collection. ResultsIndividuals with YWHAG variants exhibited variable psychomotor delay, with the majority experiencing mild intellectual disability. Early-onset seizures, particularly febrile seizures, were common, with various seizure types reported. Valproic acid has emerged as an effective antiseizure medication. Movement disorders were present in a subset of individuals, primarily manifesting as ataxia and tremor. Comorbidities such as autism spectrum disorders and attention deficit-hyperreactivity disorder were observed in a proportion of individuals. We identified a novel YWHAG variant (c.634_645del/p.Asn212_Ser215del) and expanded the genotypic spectrum of the disease. ConclusionsWe provide insights into the clinical, radiological, and genetic features of YWHAG-related epileptic encephalopathy. Despite mild clinical symptoms, affected individuals face challenges in daily functioning, underscoring the need for comprehensive care. Valproic acid has been used for seizure control with variable results.