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The ruins of Persepolis, the ceremonial capital of the Achaemenid Empire (559–330 BCE), are celebrated as a cultural heritage site and national monument in Iran. In 1971, these ruins became the setting for the Celebration of the 2,500th Anniversary of the Founding of the Persian Empire, orchestrated by Mohammad Reza Pahlavi. The Pahlavi regime aimed to fabricate a monarchical lineage that positioned the Pahlavi dynasty as the pinnacle of an uninterrupted historical continuum beginning with the Achaemenids and Cyrus the Great. The ceremonies featured a grandiose military parade with soldiers in historical costumes symbolically reenacting theprocessions of foreign emissaries depicted on Persepolis' walls, emphasizing the glory and grandeur of Iran's imperial past and its uninterrupted history. Conversely, a decade earlier, Iranian filmmaker and poet Fereydoun Rahnema's short documentary captured Persepolis in a starkly different light, presenting it as enigmatic ruins devoid of grandeur, prompting reflections on their lost original meaning. Utilizing Walter Benjamin's concepts of natural history, melancholia, and allegory, this article explores the allegorical implications of Rahnema's film. It argues that the documentary signifies the disintegration of the sublime image of Iran’s imperial origin, marking a shift where the imperial past becomes too eclipsed a signifier to serve as a cornerstone of national identity.

BACKGROUND: The Scale for Assessment and Rating of Ataxia (SARA) is a widely used clinical scale to assess cerebellar ataxia but faces some criticisms about the relevancy of all its items. OBJECTIVES: To prepare for future clinical trials, we analyzed the progression of SARA and its items in several polyQ spinocerebellar ataxias (SCA) from various cohorts. METHODS: We included data from patients with SCA1, SCA2, SCA3, and SCA6 from four cohorts (EUROSCA, RISCA, CRC-SCA, and SPATAX) for a total of 850 carriers and 3431 observations. Longitudinal progression of the SARA and its items was measured. Cohort, stage and genetic effects were tested. We looked at the respective contribution of each item to the total scale. Sensitivity to change of the scale and the impact of item removal was evaluated by calculating sample sizes needed in various scenarios. RESULTS: Longitudinal progression was significantly different between cohorts in SCA1, SCA2 and SCA3, the EUROSCA cohort having the fastest progression. Advanced-stage patients were progressing slower in SCA2 and SCA6. Items were not contributing equally to the full scale through ataxia severity: gait, stance, hand movement, and heel-shin contributed the most in the early stage, and finger-chase, nose-finger, and sitting in later stages. Few items drove the sensitivity to the change of SARA, but changes in the scale structure could not improve its sensitivity in all populations. CONCLUSION: SARA and its items progression pace showed high heterogeneity across cohorts and SCAs. However, no combinations of items improved the responsiveness in all SCAs or populations taken separately.

BACKGROUND: Becker muscular dystrophy is an X-linked, genetic disorder causing progressive degeneration of skeletal and cardiac muscle, with a widely variable phenotype. OBJECTIVE: A 3-year, longitudinal, prospective dataset contributed by patients with confirmed Becker muscular dystrophy was analyzed to characterize the natural history of this disorder. A better understanding of the natural history is crucial to rigorous therapeutic trials. METHODS: A cohort of 83 patients with Becker muscular dystrophy (5-75 years at baseline) were followed for up to 3 years with annual assessments. Muscle and pulmonary function outcomes were analyzed herein. Age-stratified statistical analysis and modeling were conducted to analyze cross-sectional data, time-to-event data, and longitudinal data to characterize these clinical outcomes. RESULTS: Deletion mutations of dystrophin exons 45-47 or 45-48 were most common. Subgroup analysis showed greater pairwise association between motor outcomes at baseline than association between these outcomes and age. Stronger correlations between outcomes for adults than for those under 18 years were also observed. Using cross-sectional binning analysis, a ceiling effect was seen for North Star Ambulatory Assessment but not for other functional outcomes. Longitudinal analysis showed a decline in percentage predicted forced vital capacity over the life span. There was relative stability or improved median function for motor functional outcomes through childhood and adolescence and decreasing function with age thereafter. CONCLUSIONS: There is variable progression of outcomes resulting in significant heterogeneity of the clinical phenotype of Becker muscular dystrophy. Disease progression is largely manifest in adulthood. There are implications for clinical trial design revealed by this longitudinal analysis of a Becker natural history dataset.

Background: The GM1 and GM2 gangliosidoses and type 2 Gaucher disease (GD2) are inherited lysosomal storage disorders with most cases having symptom onset in infancy and reduced life expectancy. The conditions are rare, and there is therefore a need for accurate and up to date information concerning the disease course and survival to assist in the design of clinical trials. RETRIEVE is a natural history study aiming to: (1) collect data on the survival of patients with early-onset (onset of first neurological manifestation before 24 months of age) GM1, GM2, or GD2; (2) collect data that could constitute a historical control group for future clinical trials; and (3) evaluate whether the conditions can be assessed together in a single interventional clinical trial. Group A included patients who were deceased or with unknown survival status at enrollment and was thus limited to retrospective data. Group B included patients who were alive at enrollment, who were followed prospectively with additional retrospective data collection. Results: Group A included 185 patients (60 with GM1, 78 with GM2, and 47 with GD2), and Group B included 40 patients (18 with GM1, 16 with GM2, and 6 with GD2). Mean and median age at diagnosis and age at onset of first neurological manifestation were youngest in patients with GD2 and oldest in patients with GM2 in both groups. In Group A, median (95% CI) survival was 19.0 (18.0, 22.0), 44.0 (37.0, 51.9) and 14.0 (10.0, 16.0) months in patients with GM1, GM2 and GD2, respectively. In Group B, hypotonia was experienced by most patients with GM1 (17/18, 94.4%), and was less common in patients with GM2 (12/16, 75.0%) and GD2 (4/6, 66.7%). Strabismus and splenomegaly were reported in all six patients with GD2. Conclusions: RETRIEVE is one of the largest natural history studies of GM1, GM2, and GD2. Results were generally consistent with the published literature, with differences potentially due to variation in inclusion criteria. The difference in median survival between patients with early-onset GM1, GM2, and GD2 reported in this study suggests that the three diseases should not be pooled for study in clinical trials. [ABSTRACT FROM AUTHOR]

Objectives: This study describes aortic growth, survival and events in patients with aortic arch pathology. Methods: Patients with an index diameter ≥4.5 cm or other pathology of the native aortic arch, were followed with longitudinal computed tomography and clinical data collected retrospectively. Aortic growth was estimated using a linear mixed model. Survival and event rates were estimated using Kaplan-Meier methods. Cox analysis assessed clinical and radiological predictors with outcomes (death, local or remote aortic events (acute aortic syndromes or intervention)). Results. 186 patients underwent 683 CT scans during 638 of patient years. The estimated annual growth was 0.28 (mm/year). 47 (25%) patients had an event and a 66% five-year event-free survival. 29 patients died, of whom 11 suffered an aortic death. 19 events were local and 25 events were remote, mostly primary events were interventions. In Cox analysis, increasing descending aortic diameter was an independent predictor of all cause of death (hazard ratio [HR], 2.16), aortic death (HR 4.81), and local event (HR 1.71). Conclusions. In patients with aortic arch pathology, growth, and aortic events should be expected. Increasing descending aortic diameter could presage an added risk, but other variables appear needed to identify patients at risk, select them for intervention or surveillance. [ABSTRACT FROM AUTHOR]

Objectives. This study describes growth, local and remote aortic events, and survival in patients with proximal (root, ascending) aortic diameters just below threshold for operation. Methods. Patients with proximal aortic diameter of 4.5 to 5.4 cm at baseline, were followed with serial computed tomography studies and data collected retrospectively. Aortic growth rate was estimated using mixed effects modelling. Clinical and radiological features associated with outcomes (all-cause death, aortic death, local or remote aortic events (dissection, rupture, intramural hematoma, or intervention)) were assessed with Cox analysis. Survival and freedom from events were estimated using Kaplan-Meier methods. Results. 80 patients underwent 274 CT scans during 265 patient-years. Median proximal aortic growth was 0.2 cm in 3 years. 32 events occurred in 28 patients (35%). Eleven events were local, all elective proximal aortic surgery. Nine events were remote: 5 type B aortic dissections, 3 descending aneurysms undergoing elective repair, and one infrarenal aortic rupture. Twelve patients died, half of type B aortic dissection. Relative survival compared to a matched normal population was 82% (95% confidence limits 55–98%) at 10 years. In Cox analysis, increased descending aortic diameter was an independent predictor of all-cause death (hazard ratio [HR], 1.39) and aortic death (HR 1.96). Conclusions. Descending, but not proximal, aortic growth was predictive of lethal events. The decreased relative survival, the substantial number of remote aortic events and aortic deaths strongly suggest continuous serial CT surveillance of the entire aorta. Other indicators than proximal aortic diameter appear needed to improve management of this patient group. [ABSTRACT FROM AUTHOR]

During the mid-nineteenth century, the shifting boundaries of natural history and hunting practices were at the core of debates about general and practical knowledge, science and leisure, hunters and poachers. Focusing on the Swiss naturalist Johann Jakob von Tschudi and his travels to South America, this article reexamines the relationships of natural history and hunting skills in forging a kind of scientific "hegemonic" masculinity. For this purpose, it reconstructs Tschudi's social formation in bourgeois circles during the institutionalization of natural history in Switzerland. More than his natural history knowledge, Tschudi's hunting skills were crucial for the success of his Peruvian expedition (1838–1842), and thus his zoological treatise Fauna peruana could be considered a manual for hunting in the Amazonian rainforest and the Andes. Finally, this article analyzes the class and race intersections of Tschudi's scientific discourse about poachers in the German states and in the Brazilian empire. The study of Tschudi's biography, especially his roles as a global naturalist and a "true hunter," sheds light on natural history as a space for constructing class, gender, and race hierarchies during the mid-nineteenth century, in both South American and German-speaking contexts. [ABSTRACT FROM AUTHOR]

Background and purpose: Spinal muscular atrophy (SMA) is a genetic disorder caused by SMN1 gene mutations. Although studies on available disease‐modifying treatments have reported their efficacy and safety, long‐term natural history data are lacking for comparison. The aim of this prospective study was to report 4‐year changes on the Hammersmith Functional Motor Scale Expanded (HFMSE) in type II and III SMA in relation to several variables such as age, functional status and SMN2 copy number. Methods: The study involves retrospective analysis of prospectively collected data from international datasets (Belgium, Italy, Spain, USA, UK). HFMSE longitudinal changes were analyzed using linear mixed effect models, examining annualized HFMSE change and its association with variables such as age at baseline, sex, motor function, SMN2 copy number. Results: In SMA type II (n = 226), the 4‐year mean change was −2.20 points. The largest mean changes were observed in sitters aged 5–14 years and the lowest in those who lost the ability to sit unsupported. In SMA type III (n = 162), the 4‐year mean change was −2.75 points. The largest mean changes were in those aged 7–15 years, whilst the lowest were in those below 7 and in the SMA type IIIa subgroup over 15. Age and score at baseline were predictive of 4‐year changes. Conclusions: Our findings provide natural history reference data for comparison with long‐term follow‐up of clinical trials or real‐world data, highlighting the need to define patterns of changes in smaller SMA subgroups instead of reporting mean changes across an entire SMA cohort. [ABSTRACT FROM AUTHOR]

ABSTRACT Shprintzen‐Goldberg‐syndrome (SGS) is caused by pathogenic exon 1 variants of SKI. Symptoms include dysmorphic features, skeletal and cardiovascular comorbidities, and cognitive and developmental impairments. We delineated the neurodevelopmental and behavioral features of SGS, as they are not well‐documented. We collected physician‐reported data of people with molecularly confirmed SGS through an international collaboration. We identified and deep‐phenotyped the neurodevelopmental and behavioral features in four patients. Within our cohort, all exhibited developmental delays in motor skills and/or speech, with the average age of first words at 2 years and 6 months and independent walking at 3 years and 5 months. All four had learning disabilities and difficulties regulating emotions and behavior. Intellectual disability, ranging from borderline to moderate, was present in all four participants. Moreover, we reviewed the literature and identified 52 additional people with SGS, and summarized the features across both datasets. Mean age was 23 years (9–48 years). When combining our cohort and reported cases, we found that 80% (45/56) had developmental and/or cognitive impairment, with the remainder having normal intelligence. Our study elucidates the developmental, cognitive, and behavioral features in participants with SGS and contributes to a better understanding of this rare condition. [ABSTRACT FROM AUTHOR]

Ernst Hajek (1934-2024) was a pioneer of ecology in Chile, with a distinguished academic career that spanned several decades. He made significant contributions to ecological research, particularly in the areas of bioclimatology and ecosystem dynamics. Hajek's work extended beyond academia, as he also played a key role in promoting environmental awareness and establishing platforms for scientific dissemination in Chile. His legacy continues to influence ecological studies in the country, earning him recognition as a visionary in the field. [Extracted from the article]

Aim Method Results Interpretation To identify, describe, and synthesize available evidence on the longitudinal relationship between hip displacement and hip function, using the International Classification of Functioning, Disability and Health (ICF) framework, in children and adolescents with cerebral palsy (CP) aged up to 18 years.Five databases were searched systematically from inception to May 2022. Study and sample characteristics, and hip displacement and hip function measures, mapped to the ICF domains, were extracted for narrative synthesis.Twenty‐nine studies were included: four longitudinal registry‐based studies; 12 prospective studies; 12 retrospective studies; and one randomized controlled trial. Sample size ranged from 11 to 267. Twenty‐seven (93%) studies entailed an intervention: surgery (n = 16); rehabilitation (n = 2); nerve block or botulinum neurotoxin A injection (n = 4); and combined surgery and injection (n = 2). Twenty‐six studies (90%) reported outcomes at the body structure and function and impairment domain of the ICF; 17 (59%) reported outcomes in the activity domain; and three (10%) included participation measures. The most common hip displacement measure was Reimers' migration percentage (79%).Because of the inclusion of interventions in most studies, and the preponderance of retrospective studies, the relationship between hip displacement and hip function in CP is unclear. More high‐quality prospective evidence on the natural history of hip displacement, and its effect on function, is needed to improve population‐wide screening of children with CP. [ABSTRACT FROM AUTHOR]

Simple Summary: Captive breeding and headstarting programs are useful conservation tools to assist imperiled species in recovery. The eastern indigo snake (EIS) benefits from managed breeding colonies, but there are concerns regarding their reproductive fitness given the incidence of complications during egg-laying in first-time mothers. Potential causes include body overconditioning or nutrient imbalances, yet little information is available regarding snake nutrition, as domestic rodents are regarded as a nutritionally complete diet irrespective of the snake's natural history. In this study, we examined the health and nutritional status of adult EIS maintained on standard mixed-whole-prey diets or a "faux-snake" sausage diet aligned with the nutritional profile of the EIS's preferred prey. While domestic rodents are significantly higher in fat and lower in vitamin E compared to snakes predated by free-ranging EIS, our study demonstrated that current mixed-prey diets appear sufficient to meet the vitamin E and selenium needs of EIS, although further investigation into the vitamin D3 status of captive snakes is warranted. There were no ill effects associated with the consumption of an atypical diet in an atypical format, and longitudinal studies with juvenile snakes are suggested to examine the influence of nutrient composition on reproductive health in this species. The federally threatened eastern indigo snake (EIS; Drymarchon couperi) is an active ophiophagous snake once found throughout the southeastern US that is now restricted to southeastern Georgia and peninsular Florida. There are concerns regarding the potential impact of overconditioning or nutrient imbalances on the reproductive fitness of breeding programs due to the occurrence of dystocia in nulliparous dams and the differing nutritional profiles of domestic and free-range prey species. We examined the blood cell counts, plasma biochemistry, and circulating plasma levels of nutrients in snakes consuming standard or experimental diets over a one-year period. Treatments included mixed whole laboratory animal prey (rodents, birds), whole prey ground into sausage, or a sausage with similar nutrient profiles measured in prey found in free-ranging EIS stomach contents. Plasma concentrations of vitamin E (maximum = 0.80 mg/mL) and selenium (maximum = 371 ng/mL) were within range of and exceeded values reported in free-ranging EIS (0.0365 mg/mL and 107.45 ng/mL), while plasma vitamin D3 concentrations (maximum = 64.1 ng/mL) were typically below minimum values observed in free-ranging EIS (46 ng/mL). Additional dietary studies initiated on juvenile subjects throughout reproductive maturity would provide an ideal experimental design for studying the linkage between reproductive health and nutrition. [ABSTRACT FROM AUTHOR]

Simple Summary: Hymenoptera venom allergy (HVA) is a potentially life-threatening systemic hypersensitivity reaction. In this study, data from 178 dogs with insect sting allergic reactions were analyzed and several risk factors for severe systemic reactions to Hymenoptera stings were identified. Furthermore, a significant number of dogs suffered subsequent systemic reactions to Hymenoptera stings, indicating that venom immunotherapy may be a valuable intervention to prevent future reactions. This study should raise the awareness of dog owners that Hymenoptera stings are associated with HVA and its possible consequences. Hymenoptera, which includes honeybees, wasps, bumblebees, and hornets, is an order of the class Insecta, whose venom can induce anaphylactic reactions in dogs. While several studies have investigated the natural histories and risk factors of Hymenoptera venom allergy (HVA) in humans, only limited information is available on canine patients. Therefore, the aim of this study was to identify risk factors leading to severe systemic reactions (SSRs) and to explore the natural history of these patients. This was achieved with an inquiry into the case histories of 178 dogs that were stung by Hymenoptera and presented to the Vetsuisse Faculty Animal Hospital of the University of Zurich between 2018 and 2022. Dogs under two years old, dogs that weighed under 10 kg, purebred dogs, and dogs that were stung in the oral cavity were at a greater risk of developing SSRs. Almost two thirds of patients with SSRs experienced the same or worse symptoms after subsequent stings and >40% of patients with local reactions developed SSRs when stung again. Next to providing valuable clinical information about HVA in dogs, these findings strongly support the recommendation of venom immunotherapy (VIT) for patients with HVA. [ABSTRACT FROM AUTHOR]

Mucocele of the appendix and pseudomyxoma peritonei are rare diseases. The clinical findings are nonspecific in the early stages of the disease. The sequelae of appendiceal mucocele, its perforation, and extensive peritoneal involvement via pseudomyxoma peritonei (jelly belly) are repeatedly described in the literature. We present the typical findings in the natural history of the disease. [ABSTRACT FROM AUTHOR]

Myeloproliferative neoplasms, polycythemia vera, essential thrombocytosis, and primary myelofibrosis are a unique group of clonal hematopoietic stem cell neoplasms that share somatic, gain-in-function driver mutations in JAK2, CALR, and MPL. As a consequence, these disorders exhibit similar phenotypic features, the most common of which are the ceaseless production of normal erythrocytes, myeloid cells, platelets alone or in combination, extramedullary hematopoiesis, myelofibrosis, and a potential for leukemic transformation. In the case of polycythemia vera and essential thrombocytosis, however, prolonged survival is possible. With an incidence value in the range of 0.5–2.0/100,000, myeloproliferative neoplasms are rare disorders, but they are not new disorders, and after a century of scrutiny, their clinical features and natural histories are well-defined, though their individual management continues to be controversial. With respect to polycythemia vera, there has been a long-standing dispute between those who believe that the suppression of red blood cell production by chemotherapy is superior to phlebotomy to prevent thrombosis, and those who do not. With respect to essential thrombocytosis, there is a similar dispute about the role of platelets in veinous thrombosis, and the role of chemotherapy in preventing thrombosis by suppressing platelet production. Linked to these disputes is another: whether therapy with hydroxyurea promotes acute leukemia in disorders with a substantial possibility of longevity. The 21st century revealed new insights into myeloproliferative neoplasms with the discovery of their three somatic, gain-of-function driver mutations. Almost immediately, this triggered changes in the diagnostic criteria for myeloproliferative neoplasms and their therapy. Most of these changes, however, conflicted with prior well-validated, phenotypically driven diagnostic criteria and the management of these disorders. The aim of this review is to examine these conflicts and demonstrate how genomic discoveries in myeloproliferative neoplasms can be used to effectively complement the known phenotypic features of these disorders for their diagnosis and management. [ABSTRACT FROM AUTHOR]

Background: Alport syndrome (AS) is a genetic disorder characterized by progressive renal disease, ocular abnormalities, and sensorineural hearing loss. However, the audiological profile of patients with AS remains elusive. Thus, this study aims to evaluate the natural history of auditory function in patients with AS. Methods: Exome or targeted sequencing for deafness genes was performed to confirm the pathogenic variants in patients with AS. Results: We identified fifteen individuals with AS who carried pathogenic variants of COL4A3, COL4A4, or COL4A5. Among fifteen, twelve (80%) showed hematuria, and six (40%) showed proteinuria. The patients exhibited bilateral sensorineural hearing loss, which was progressive and symmetric. The hearing thresholds increased according to age and plateaued at the level of 53 dB HL, indicating the hearing loss did not reach the severe-to-moderate level. The auditory dysfunction showed a distinct natural history depending on the inheritance pattern, but there was no remarkable difference between males and females among X-linked AS. Conclusions: Auditory dysfunction in AS is progressive up to the level of moderate hearing loss. Precise auditory rehabilitation for patients with AS is warranted depending on the inheritance pattern and genetic predisposition. [ABSTRACT FROM AUTHOR]

The article discusses Davian behavior and functional egg fertilization in the Italian Stream Frog Rana italica, focusing on a case of thanatophilia observed in Central Italy. The study highlights the reproductive ecology of the Italian Stream Frog, emphasizing the unique mating habitats and reproductive outcomes of the species. The observation of Davian behavior in R. italica sheds light on the rare occurrence of such behavior in anurans and calls for further research to understand the contextual factors influencing this behavior. [Extracted from the article]

Amblyomma maculatum sensu lato (s.l.) is an ixodid tick found in the semi-arid southwestern United States and northern Mexico where it is a parasite of medical and veterinary significance, including as a vector for Rickettsia parkeri, a cause of spotted fever rickettsiosis in the Americas. To describe the comprehensive natural history of this tick, monthly small mammal trapping and avian mist netting sessions were conducted at sites in Cochise County Arizona, within the Madrean Archipelago region where human cases of R. parkeri rickettsiosis and adult stages of A. maculatum s.l. were previously documented. A total of 1949 larvae and nymphs were removed from nine taxonomic groups of rodents and ten species of birds and were used in combination with records for adult stages collected both from vegetation and hunter-harvested animals to model seasonal activity patterns. A univoltine phenology was observed, initiated by the onset of the annual North American monsoon and ceasing during the hot, dry conditions preceding the following monsoon season. Cotton rats (Sigmodon spp.) were significantly more likely to be infested than other rodent taxa and carried the highest tick loads, reflecting a mutual affinity of host and ectoparasite for microhabitats dominated by grass. [ABSTRACT FROM AUTHOR]

Background: Giardia lamblia is an intestinal protozoan estimated to cause ~200 million symptomatic infections annually, mainly in children in low- and middle-income countries associated with intestinal damage, increased permeability, and malabsorption. Methods and results: We describe here the epidemiology, incidence, clinical characteristics, and risk factors of acute gastroenteritis episodes (AGE) with G. lamblia detection (GAGE) using a birth cohort of 443 Nicaraguan children followed weekly until 36 months of life. From June 2017 to July 2021, 1385 AGE samples were tested by qPCR. G. lamblia was detected in 104 (7.5%) of AGE episodes. In all, 69 (15.6%) children experienced at least one GAGE episode, and 25 of them (36.2%) experienced more than one episode. The incidence rate of the first episode of GAGE was 6.8/100 child-years (95% CI, 4.5–9.1). During GAGE, bloody stools, vomiting, and fever were uncommon, and children were less likely to be treated at a primary care clinic, suggesting that GAGE is typically mild and most cases did not receive medical attention, which could facilitate higher parasite loads with increased possibilities of establishing chronic carriage. GAGE was more common in children 12–24 months of age (13.9/100 child-years [95% CI, 10.7–17.1]) as compared to other age groups. In our birth-cohort, children living in a home with an indoor toilet (aHR, 0.52 [95%CI, 0.29–0.92]), and being breastfed in the first year of life (aHR: 0.10 [95%IC, 0.02, 0.57]) had a lower incidence of GAGE. In contrast, being breastfed for ≤ 6 months was associated with a higher incidence if the children were living in houses without indoor toilets and earthen floors (HR, 7.79 [95% CI, 2.07, 29.3]). Conclusion: Taken together, GAGE is more frequent under poor household conditions. However, breastfeeding significantly reduces the incidence of GAGE in those children. Author summary: G. lamblia is an intestinal protozoan having mixed associations with acute gastroenteritis, yet positive associations with impaired child growth. G. lamblia infects millions of people worldwide annually and is more prevalent in children residing in low- and middle-income countries, making it an important target for prevention and control efforts. Although G. lamblia carriage is widespread, its epidemiology, natural history, genetic diversity, host genetic susceptibility factors, and post-infectious sequelae in children are still under investigation. As no human vaccine is available, understanding its risk factors in an endemic country is the first step for reducing the burden and mitigating its sequelae. In a birth cohort in León, Nicaragua, we found that children living in households with poor sanitation conditions are at higher risk of AGE with G. lamblia detection (GAGE), but prolonged duration of breastfeeding despite these conditions may reduce the risk in these children. The study highlights the importance of breastfeeding and the need to better understand how G. lamblia contributes to the global burden of disease in children, and the mechanisms of host protection to guide future interventions. [ABSTRACT FROM AUTHOR]

Background: The search for neuroprotective treatments for Parkinson's disease (PD) still relies largely on motor disability scales. A limitation of these tools is the strong influence of symptomatic dopaminergic treatment effects. Drawing on a wealth of published information, we conducted a systematic review and meta-analysis of motor progression in PD and its relationships with dopaminergic therapy. Methods: We searched Medline, Embase, and Central to identify 84 publications with adequate serial motor scores to calculate progression, expressed as an increase in the percentage of maximum disability. Results: A random-effects model showed motor progression at 2.0% p.a. (95% CI 1.7–2.4%). There were no significant differences by baseline age, sample size, or observation period. However, untreated patients, in 8 publications, progressed at 4.5% p.a. compared to 1.6% p.a. in 76 studies containing individuals on dopaminergic drugs (p = 0.0004, q = 0.003). This was supported by research on phenoconversion in prodromal PD, where motor progression exceeded 5% p.a. in the 2 years before diagnosis. Starting levodopa improved pre-treatment disability by 40.3 ± 15.2%. Practically defined off state measurements increase faster than on scores by a modest degree (p = 0.05). Conclusion: This survey suggests that accurate long-term measurements of motor progression to assess disease-modifying therapies can be conducted despite the sequential commencement of dopaminergic drugs and sample attrition over time. While study designs involving prodromal or untreated PD avoid confounding effects of symptomatic treatment, different assumptions about motor progression may be needed. A defined off state with the levodopa test dose method maximizes information about the medication cycle once dopaminergic therapy has begun. [ABSTRACT FROM AUTHOR]

We designed a prospective multicenter cohort study to clarify a long-term, > 10-year prevalence and aggravation of cervical spine instabilities in rheumatoid arthritis (RA). In 2001–2002, 634 outpatients were enrolled, and 233 (36.8%) were followed for > 10 years. Cervical spine instability was defined as atlantoaxial subluxation (AAS, > 3-mm atlantodental interval), vertical subluxation (VS, < 13-mm Ranawat value), and subaxial subluxation (SAS, ≥ 2-mm irreducible vertebral translation). The aggravation was determined as ≥ 2 mm decrease of the Ranawat value in VS, ≥ 2-mm increase of slippage in SAS, and these new developments. The prevalence of VS and SAS increased during both the initial and last > 5 years (all, p ≤ 0.049). While VS aggravation was associated with pre-existing AAS (p = 0.007) and VS (p = 0.002), SAS aggravation correlated with pre-existing VS (p = 0.002). Multivariable analysis found hand mutilating changes (odds ratio [OR] = 4.048, p = 0.008), RA duration ≥ 5 years (OR = 3.711, p = 0.013), C-reactive protein (CRP) level ≥ 3.8 mg/dL (OR = 2.187, p = 0.044), and previous joint surgery (OR = 2.147, p = 0.021) as predictors for VS aggravation. Pre-existing VS (OR = 2.252, p = 0.024) and CRP ≥ 1.0 mg/dL (OR = 2.139, p = 0.013) were disclosed as predictors for SAS aggravation. Low disease activity and clinical remission before the development of VS and advanced peripheral joint destruction are essential to prevent progressive cervical spine instability in RA. [ABSTRACT FROM AUTHOR]

Acute intoxication with cholinesterase inhibiting organophosphates (OP) can produce life-threatening cholinergic crisis and status epilepticus (SE). Survivors often develop long-term neurological consequences, including spontaneous recurrent seizures (SRS) and impaired cognition. Numerous studies implicate OP-induced neuroinflammation as a pathogenic mechanism contributing to these chronic sequelae; however, little is known about the inflammatory phenotype of innate immune cells in the brain following acute OP intoxication. Thus, the aim of this study was to characterize the natural history of microglial and astrocytic inflammatory phenotypes following acute intoxication with the OP, diisopropylfluorophosphate (DFP). Adult male and female Sprague–Dawley rats were administered a single dose of DFP (4 mg/kg, sc) followed by standard medical countermeasures. Within minutes, animals developed benzodiazepine-resistant SE as determined by monitoring seizures using a modified Racine scale. At 1, 3, 7, 14, and 28 d post-exposure (DPE), neuroinflammation was assessed using translocator protein (TSPO) positron emission tomography (PET) and magnetic resonance imaging (MRI). In both sexes, we observed consistently elevated radiotracer uptake across all examined brain regions and time points. A separate group of animals was euthanized at these same time points to collect tissues for immunohistochemical analyses. Colocalization of IBA-1, a marker for microglia, with iNOS or Arg1 was used to identify pro- and anti-inflammatory microglia, respectively; colocalization of GFAP, a marker for astrocytes, with C3 or S100A10, pro- and anti-inflammatory astrocytes, respectively. We observed shifts in the inflammatory profiles of microglia and astrocyte populations during the first month post-intoxication, largely in hyperintense inflammatory lesions in the piriform cortex and amygdala regions. In these areas, iNOS+ proinflammatory microglial cell density peaked at 3 and 7 DPE, while anti-inflammatory Arg1+ microglia cell density peaked at 14 DPE. Pro- and anti-inflammatory astrocytes emerged within 7 DPE, and roughly equal ratios of C3+ pro-inflammatory and S100A10+ anti-inflammatory astrocytes persisted at 28 DPE. In summary, microglia and astrocytes adopted mixed inflammatory phenotypes post-OP intoxication, which evolved over one month post exposure. These activated cell populations were most prominent in the piriform and amygdala areas and were more abundant in males compared to females. The temporal relationship between microglial and astrocytic responses suggests that initial microglial activity may influence delayed, persistent astrocytic responses. Further, our findings identify putative windows for inhibition of OP-induced neuroinflammatory responses in both sexes to evaluate the therapeutic benefit of anti-inflammation in this context. [ABSTRACT FROM AUTHOR]

Premise Methods Results Discussion One of the slowest steps in digitizing natural history collections is converting labels associated with specimens into a digital data record usable for collections management and research. Here, we address how herbarium specimen labels can be converted into digital data records via extraction into standardized Darwin Core fields.We first showcase the development of a rule‐based approach and compare outcomes with a large language model–based approach, in particular ChatGPT4. We next quantified omission and commission error rates across target fields for a set of labels transcribed using optical character recognition (OCR) for both approaches. For example, we find that ChatGPT4 often creates field names that are not Darwin Core compliant while rule‐based approaches often have high commission error rates.Our results suggest that these approaches each have different strengths and limitations. We therefore developed an ensemble approach that leverages the strengths of each individual method and documented that ensembling strongly reduced overall information extraction errors.This work shows that an ensemble approach has particular value for creating high‐quality digital data records, even for complicated label content. While human validation is still needed to ensure the best possible quality, automated approaches can speed digitization of herbarium specimen labels and are likely to be broadly usable for all natural history collection types. [ABSTRACT FROM AUTHOR]

Tulving's introduction of episodic memory and the metaphor of mental time travel has immensely enriched our understanding of human cognition. However, his focus on human psychology, with limited consideration of evolutionary perspectives, led to the entrenched notion that mental time travel is uniquely human. We contend that adopting a phylogenetic perspective offers a deeper insight into cognition, revealing it as a continuous evolutionary process. Adherence to the uniqueness of pre-defined psychological concepts obstructs a more complete understanding. We offer a concise natural history to elucidate how events that occurred hundreds of millions of years ago have been pivotal for our ability to mentally time travel. We discuss how the human brain, utilizing parts with ancient origins in a networked manner, enables mental time travel. This underscores that episodic memories and mental time travel are not isolated mental constructs but integral to our perception and representation of the world. We conclude by examining recent evidence of neuroanatomical correlates found only in great apes, which show great variability, indicating the ongoing evolution of mental time travel in humans. This article is part of the theme issue 'Elements of episodic memory: lessons from 40 years of research'. [ABSTRACT FROM AUTHOR]

WWOX developmental and epileptic encephalopathy is characterised by drug-resistant epilepsy with onset within the first year of life and severe psychomotor developmental delay. This report presents for the first time a clinical case of an adult patient with a homozygous likely pathogenic variant (p.Thr12Met) in the WWOX gene, with more than 40 years of follow-up. The patient had refractory epilepsy with various types of seizures during his life: mainly epileptic spasms, autonomic, myoclonic, tonic seizures, and absences. The patient had a prominent developmental delay with a lack of expressive speech, but by the age of 3, he had acquired the skills to sit, crawl, and walk with support. In adolescence, there was an acute regression of acquired skills to a total absence of independent motor activity. The patient had dysmorphic features, such as upslanting palpebral fissures, arched eyebrows, and hypertelorism. For many years, the patient was given a diagnosis of cerebral palsy; 38 years after the onset of the disease, he was given a molecular genetic diagnosis of WWOX -associated developmental and epileptic encephalopathy. Our observation illustrates the natural history of WWOX -DEE and the high clinical significance of early genetic diagnostics for identifying the cause of developmental delay and resistant epilepsy. [ABSTRACT FROM AUTHOR]

The hepatitis C virus (HCV) infection continues to represent a significant public health threat and is a leading cause of liver cirrhosis, liver cancer, and liver-related mortality. The World Health Organization (WHO) has set a goal for 2030: to eliminate HCV infection as a public health threat by reducing new HCV infections by 90% and mortality by 65%. The early phase of HCV infection represents a pivotal point in the evolution of hepatitis C. Despite a favourable course in the majority of patients, approximately 50–70% of individuals with recently acquired hepatitis C will develop a chronic infection, defined as the persistence of viremia for a period exceeding six months. The diagnosis and treatment of a recent HCV infection should facilitate engagement in multidisciplinary care, prevent the development and complications of chronic liver disease, and reduce ongoing transmission in key populations. Therefore, early treatment in the early phase of infection compared with deferring treatment until the chronic infection remains a valid approach in the era of direct antiviral agents (DAAs). This approach is supported by a cost-effectiveness analysis. The aim of this review is to synthesise the existing knowledge on the early phase of hepatitis C virus infection, with a particular focus on the current risk factors, natural history, therapeutic management, and future perspectives. [ABSTRACT FROM AUTHOR]

Background Spontaneous recovery of a birth brachial plexus disorder is difficult to predict. Although root avulsion and total plexus injury is indicated for surgical management, early nerve surgery is still doubtful. Hand motion is obviously an important indicator for predicting the function of an affected limb. However, the timing for diagnosing a transient or true total plexus injury from hand recovery is controversial. This study aimed to report the recovery time of total birth brachial plexus palsy in patients who did not undergo surgery due to various reasons. Methods In this 15-year retrospective chart review, 45 patients of total birth brachial plexus injury with a mean follow-up time of 34.5 months, were included. Although patients met surgical indications, surgical management was abandoned for a variety of reasons. Imaging was not performed routinely and, nerve conduction study and Horner's syndrome were not consistently recorded in the past. All patients were evaluated for clinical improvement by motor power grading. The recovery time was reported as the median and interquartile range. Results Forty-five patients were diagnosed with total birth brachial plexus injury. Out of 45 patients, 36 showed clinical evidence of recovering their hand motion within a median of 3 months. The median time for the recovery of elbow flexion and shoulder abduction was 4 months. The median for achieving antigravity or full motion recovery of elbow flexion, shoulder abduction, and hand flexion were 10, 10.5, and 7 months, respectively. Conclusion In this study, spontaneous recovery of shoulder, elbow and hand motion substantially occurred in the patient diagnosed with a total birth brachial plexus palsy. True total plexus palsy can be distinguished from transient palsy by the recovery of hand motion at 3 months. Most of the patients, who had spontaneous recovery, potentially achieved antigravity or full hand movement without surgery. [ABSTRACT FROM AUTHOR]

The article discusses the overlooked habitat of macroalgae in sand grains, specifically focusing on the life cycle of Monostroma angicava in northern Japan. The study reveals that microscopic codiolum sporophytes of M. angicava bore into calcareous sand grains during the summer, showcasing a unique endolithic lifestyle. The research highlights the ecological significance of sand grains as a seasonal habitat for macroalgal life cycle stages, shedding light on the adaptive strategies and dispersal modes of these organisms in coastal ecosystems. [Extracted from the article]

Limb‐girdle muscular dystrophy type 2G/R7 (LGMD2G/R7) is an ultra‐rare condition initially identified within the Brazilian population. We aimed to expand clinical and genetic information about this disease, including its worldwide distribution. A multicenter historical cohort study was performed at 13 centers in Brazil in which data from index cases and their affected relatives from consecutive families with LGMD2G/R7 were reviewed from July 2017 to August 2023. Additionally, a systematic literature review was conducted to identify case reports and series of the disease worldwide. Forty‐one LGMD2G/R7 cases were described in the Brazilian cohort, being all subjects homozygous for the c.157C>T/(p.Gln53*) variant in TCAP. Survival curves showed that the median disease duration before individuals required walking aids was 21 years. Notably, women exhibited a slower disease progression, requiring walking aids 13 years later than men. LGMD2G/R7 was frequently reported not only in Brazil but also in China and Bulgaria, with 119 cases identified globally, with possible founder effects in the Brazilian, Eastern European, and Asian populations. These findings are pivotal in raising awareness of LGMD2G/R7, understanding its progression, and identifying potential modifiers. This can significantly contribute to the development of future natural history studies and clinical trials for this disease. [ABSTRACT FROM AUTHOR]

Course‐based undergraduate research experiences (CUREs) can be a powerful tool in broadening participation in undergraduate research. In this paper, we review the benefits of and barriers to undergraduate research experiences and explore how CUREs can mitigate some of those issues. As a part of the NSF‐supported Biological Collections in Ecology and Evolution Network (BCEENET) activities, a series of network meetings produced a set of recommendations to increase the accessibility of CUREs for all students at all institution types. We use BCEENET CUREs that focus on digitized natural history collections data to illustrate how leveraging adaptable open educational resources that use freely available data and analysis tools can increase accessibility of undergraduate research. We also discuss how inclusive networks of educators and research collaborators can support broadening CURE implementation. [ABSTRACT FROM AUTHOR]

Background Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is increasingly being diagnosed incidentally on imaging. It has malignant potential, making it vital to establish the correct diagnosis, assess its malignant risk and follow a management strategy to prevent development of invasive carcinoma of the pancreas. Objective This review focuses on the epidemiology, natural history, risk factors, diagnosis and management of IPMN of the pancreas, and will provide practical points for general practitioners. Discussion IPMN of the pancreas can transform into invasive pancreatic carcinoma at a low rate of approximately 2%/year. Upon diagnosis of IPMN, it is risk stratified based on the presence of worrisome or high-risk stigmata, which guides further management. Management needs to be individualised based on IPMN and patient factors due to limitations with the current diagnostic tools. [ABSTRACT FROM AUTHOR]

The article "Unveiling the enigmatic cone snails along the coastal environments of the South Andaman Islands: diversity, distribution and their habitat preference" published in Frontiers in Marine Science explores the diversity, distribution, and habitat preferences of cone snails in the South Andaman Islands. The study reveals that Conus ebraeus is the predominant species among the nine study sites, with Conus litteratus and Conus leopardus found exclusively in specific locations with soft, muddy substrates. The research highlights the importance of substrate type, waterline zones, and habitat characteristics in shaping the distribution patterns of cone snails, emphasizing the need for responsible management and conservation practices. [Extracted from the article]

Background: Haemophilus influenzae is prevalent within the airways of persons with cystic fibrosis (pwCF). H. influenzae is often associated with pulmonary exacerbations (PEx) in pediatric cohorts, but in adults, studies have yielded conflicting reports around the impact(s) on clinical outcomes such as lung function decline. Accordingly, we sought to discern the prevalence, natural history, and clinical impact of H. influenzae in adult pwCF. Methods: This single-centre retrospective cohort study reviewed all adult pwCF with H. influenzae sputum cultures between 2002 and 2016. From this cohort, persistently infected subjects (defined as: ≥2 samples with the same pulsotype and > 50% sputum culture-positive for H. influenzae in each year) were matched (1:2) to controls without H. influenzae. Demographic and clinical status (baseline health or during periods of PEx) were obtained at each visit that H. influenzae was cultured. Yearly biobank isolates were typed using pulsed-field gel electrophoresis (PFGE) to assess relatedness. Results: Over the study period, 30% (n = 70/240) of pwCF were culture positive for H. influenzae, of which 38 (54%) were culture-positive on multiple occasions and 12 (17%) had persistent infection. One hundred and thirty-seven isolates underwent PFGE, with 94 unique pulsotypes identified. Two (1.5%) were serotype f with the rest non-typeable (98.5%). H. influenzae isolation was associated with an increased risk of PEx (RR = 1.61 [1.14–2.27], p = 0.006), however, this association was lost when we excluded those who irregularly produced sputum (i.e. only during a PEx). Annual lung function decline did not differ across cohorts. Conclusions: Isolation of H. influenzae was common amongst adult pwCF but often transient. H. influenzae infection was not associated with acute PEx or chronic lung function decline. [ABSTRACT FROM AUTHOR]

Background: SELENON-related myopathy (SELENON-RM) is a rare congenital myopathy characterized by slowly progressive axial muscle weakness, rigidity of the spine, scoliosis, and respiratory insufficiency. Laminin-a2-related muscular dystrophy (LAMA2-MD) has a similar clinical phenotype, which ranges from severe, early-onset congenital muscular dystrophy type 1A (MDC1A) to milder forms presenting as childhood- or adult-onset limb-girdle type muscular dystrophy. The first 1.5-year natural history follow-up showed that 90% of the patients had low bone quality, respiratory impairments were found in all SELENON-RM and most of the LAMA2-MD patients, and many had cardiac risk factors. However, further extensive knowledge on long-term natural history data, and clinical and functional outcome measures is needed to reach trial readiness. Therefore, we extended the natural history study with 3- and 5-year follow-up visits (Extended LAST STRONG). Methods: The Extended LAST STRONG is a long-term natural history study in Dutch-speaking patients of all ages diagnosed with genetically confirmed SELENON-RM or LAMA2-MD, starting in September 2023. Patients visit our hospital twice over a period of 2 years to complete a 5-year follow up from the initial LAST-STRONG study. At both visits, they undergo standardized neurological examination, hand-held dynamometry (age ≥ 5 years), functional measurements, muscle ultrasound, respiratory assessments (spirometry, maximal inspiratory and expiratory pressure, sniff nasal inspiratory pressure; age ≥ 5 years), Dual-energy X-ray absorptiometry (DEXA-)scan (age ≥ 2 years), X-ray of the left hand (age ≤ 17 years), lower extremity MRI (age ≥ 10 years), accelerometry for 8 days (age ≥ 2 years), and questionnaires (patient report and/or parent proxy; age ≥ 2 years). All examinations are adapted to the patient's age and functional abilities. Disease progression between all subsequent visits and relationships between outcome measures will be assessed. Discussion: This study will provide valuable insights into the 5-year natural history of patients with SELENON-RM and LAMA2-MD and contribute to further selecting relevant and sensitive to change clinical and functional outcome measures. Furthermore, this data will help optimize natural history data collection in clinical care and help develop clinical care guidelines. Trial registration: This study protocol including the patient information and consent forms has been approved by medical ethical reviewing committee ('METC Oost-Nederland'; https://www.ccmo.nl/metcs/erkende-metcs/metc-oost-nederland, file number: 2023–16401). It is registered at ClinicalTrials.gov (NCT06132750; study registration date: 2023-10-05; study first passed date: 2023-11-15). [ABSTRACT FROM AUTHOR]

Natural history collections are invaluable reference collections. Digitizing these collections is a transformative process that improves the accessibility, preservation, and exploitation of specimens and associated data in the long term. Arthropods make up the majority of zoological collections. However, arthropods are small, have detailed color textures and share small, complex and shiny structures, which poses a challenge to conventional digitization methods. Sphaeroptica is a multi-images viewer that uses a sphere of oriented images. It allows the visualization of insects including their tiniest features, the positioning of landmarks, and the extraction of 3D coordinates for measuring linear distances or for use in geometric morphometrics analysis. The quantitative comparisons show that the measures obtained with Sphaeroptica are similar to the measurements derived from 3D μCT models with an average difference inferior to 1%, while featuring the high resolution of color stacked pictures with all details like setae, chaetae, scales, and other small and/or complex structures. Shaeroptica was developed for the digitization of small arthropods but it can be used with any sphere of aligned images resulting from the digitization of objects or specimens with complex surface and shining, black, or translucent texture which cannot easily be digitized using structured light scanner or Structure-from-Motion (SfM) photogrammetry. [ABSTRACT FROM AUTHOR]

Purpose Methods Results Conclusion To describe clinical characteristics in Finnish patients with X‐linked retinoschisis (XLRS) longitudinally with emphasis on retinal morphology and genotype–phenotype correlations.A retrospective cohort study reviewed medical records from patients with genetically confirmed XLRS from the Department of Ophthalmology, Helsinki University Hospital. Best‐corrected visual acuity (BCVA), refraction, colour fundus photography, spectral‐domain optical coherence tomography and genetic information were collected.Fifty‐two males were diagnosed at the median age of 7 years (range 1–57) and followed for a median of 8 years (range, 1–49). Baseline findings included macular retinoschisis in 92 (89%), macular atrophy in 25 (24%) and peripheral retinoschisis in 22 (21%) eyes. Vitreous haemorrhage occurred in 10 (10%) eyes, more frequently with peripheral schisis (p < 0.001). Nearly half of the patients, 22 (42%) were classified as visually impaired according to WHO. Median central retinal thickness was similar between initial (355 μm) and latest visits (360 μm) (p = 0.781). Low BCVA was associated with macular atrophy (p < 0.001), ellipsoid zone disruption (p = 0.007) and peripheral retinoschisis (p = 0.006). The three Finnish founder mutations c.214G >A, c.221G >T, and c.325G >C in exon 4 of retinoschisin 1 (RS1) were identified in 40 patients (77%). No associations were found between the genotypes and phenotypes.Three‐fourths of the patients carried the Finnish founder mutations in RS1, but we did not detect any genotype–phenotype association. Macular atrophy was associated with the poorest visual acuity. Ocular compilations were associated with peripheral retinoschisis, suggesting that these patients should be followed more frequently. [ABSTRACT FROM AUTHOR]

Digitization of Natural History Collections (NHCs) and mobilization of their data are pivotal for their study, preservation, and accessibility. Furthermore, thanks to digitization and mobilization, Natural History Museums can better showcase their collections, potentially attracting more visitors. However, the optimization of digitization workflows, especially when addressing small and/or historical NHCs, remains a challenge. Starting from a practical example, this contribution aims at providing a general guideline for the digitization of historical NHCs, with a particular focus on pre-digitization planning, during which some decisions should be made for ensuring a smooth, cost- and time-effective digitization process. The digitization of the algarium by Aristocle Vatova and Victor Schiffner was carried out following an image-to-data workflow, which allowed for reducing the handling of the specimens. The metadata were organized according to the Darwin Core standard scheme, and, together with the digital images of the specimens, have been made available to the scientific community and to the general public via an online portal. Thanks to the application of digital technologies and standardized methods, the accessibility of the collection has been enhanced, and its integration with historical data is possible, highlighting the relevance of shared experiences and protocols in advancing the digital transformation of natural history heritage. [ABSTRACT FROM AUTHOR]

Background: Pain is common in the genetic skin fragility disorder epidermolysis bullosa (EB), from skin and mucosal injury and inflammation as well as extra-mucocutaneous sites. Individuals living with EB have identified pain as a priority for better treatments. Objectives: The Prospective EB Longitudinal Evaluation Study (PEBLES) is a prospective register study exploring the natural history of RDEB across all ages from birth to death. Here, we investigated the characteristics and treatment of pain in different RDEB subtypes. Methods: Information was collected from individuals with different RDEB subtypes over an 8-year period. Data included visual analogue scale (VAS) ratings of background and procedural pain, its location, intensity and impact on sleep, as well as pain medication. Disease severity scores and quality of life measures were correlated to pain scores. Results: Sixty-one participants (13 children, 48 adults) completed a total of 361 reviews. Pain was common, experienced by 93% of participants at index review, with 80% suffering both background and procedural pain. Across all RDEB patients, the median VAS for background pain was 40 (out of 100) [interquartile range 20,60] and for those having regular dressing changes, median procedural pain was 52 [40,80]. Severe (RDEB-S) and pruriginosa (RDEB-Pru) groups had the greatest increase in procedural compared to background pain of 20 and 22 VAS points, respectively. Correlations between disease severity and quality of life impairment were observed across most groups, particularly RDEB-S. Over half of those studied experienced pain frequently or constantly, and in one third pain disturbed sleep at least 4 nights per week. Skin was the commonest source of pain in all subtypes except inversa RDEB where the mouth was the main site. Despite frequent and severe pain, one third of participants used no medication for pain and, in those that did, pain levels remained high suggesting ineffectiveness of current pain management approaches and a significant unmet need in RDEB. Conclusion: The frequency, severity, and impact of pain in all RDEB patients is significant, particularly in RDEB-S and RDEB-Pru. Our findings highlight that current RDEB pain management is poorly effective and that further research is needed to address this symptom. [ABSTRACT FROM AUTHOR]

Aim Method Results Interpretation To assess a group of ambulant, untreated children with bilateral spastic cerebral palsy, in a resource‐poor setting, who had never been assessed by a health care professional or received any treatment, to help establish the natural history of gait patterns in this condition.At CURE Children's Hospital of Ethiopia, 46 children with no prior health care contact were assessed in a cross‐sectional cohort study, through a detailed history, clinical examination, and instrumented gait analysis using a motion capture system.There was a large spread in the data reflecting the high natural heterogeneity in this population. The severity of gait pathology did not correlate with age; however, a small but significant reduction in sagittal hip and knee range of motion with increasing age was observed. There was also a trend towards reduced passive knee extension with age.Improved understanding of the aspects of gait that are likely to naturally improve, deteriorate, or remain stable over time helps guide treatment decisions in this population. [ABSTRACT FROM AUTHOR]

Season length and its associated variables can influence the expression of social behaviours, including the occurrence of eusociality in insects. Eusociality can vary widely across environmental gradients, both within and between different species. Numerous theoretical models have been developed to examine the life history traits that underlie the emergence and maintenance of eusociality, yet the impact of seasonality on this process is largely uncharacterized. Here, we present a theoretical model that incorporates season length and offspring development time into a single, individual-focused model to examine how these factors can shape the costs and benefits of social living. We find that longer season lengths and faster brood development times are sufficient to favour the emergence and maintenance of a social strategy, while shorter seasons favour a solitary one. We also identify a range of season lengths where social and solitary strategies can coexist. Moreover, our theoretical predictions are well matched to the natural history and behaviour of two flexibly eusocial bee species, suggesting that our model can make realistic predictions about the evolution of different social strategies. Broadly, this work reveals the crucial role that environmental conditions can have in shaping social behaviour and its evolution and it underscores the need for further models that explicitly incorporate such variation to study the evolutionary trajectories of eusociality. [ABSTRACT FROM AUTHOR]

Movement is a key means by which animals cope with variable environments. As they move, animals construct individual niches composed of the environmental conditions they experience. Niche axes may vary over time and covary with one another as animals make tradeoffs between competing needs. Seasonal migration is expected to produce substantial niche variation as animals move to keep pace with major life history phases and fluctuations in environmental conditions. Here, we apply a time-ordered principal component analysis to examine dynamic niche variance and covariance across the annual cycle for four species of migratory crane: common crane (Grus grus, n = 20), demoiselle crane (Anthropoides virgo, n = 66), black-necked crane (Grus nigricollis, n = 9), and white-naped crane (Grus vipio, n = 9). We consider four key niche components known to be important to aspects of crane natural history: enhanced vegetation index (resources availability), temperature (thermoregulation), crop proportion (preferred foraging habitat), and proximity to water (predator avoidance). All species showed a primary seasonal niche "rhythm" that dominated variance in niche components across the annual cycle. Secondary rhythms were linked to major species-specific life history phases (migration, breeding, and nonbreeding) as well as seasonal environmental patterns. Furthermore, we found that cranes' experiences of the environment emerge from time-dynamic tradeoffs among niche components. We suggest that our approach to estimating the environmental niche as a multidimensional and time-dynamical system of tradeoffs improves mechanistic understanding of organism-environment interactions. [ABSTRACT FROM AUTHOR]

Evolutionary biology is poised for a third major synthesis. The first presented Darwin's evidence from natural history. The second incorporated genetic mechanisms. The third will be based on energy and biophysical processes. It should include the equal fitness paradigm (EFP), which quantifies how organisms convert biomass into surviving offspring. Natural selection tends to maximise energetic fitness, E=PcohGFQ$$ E={P}_{\mathrm{coh}}\mathrm{GFQ} $$, wherePcoh$$ {P}_{\mathrm{coh}} $$ is mass‐specific rate of cohort biomass production, G$$ G $$ is generation time, F$$ F $$ is fraction of cohort production that is passed to surviving offspring, and Q$$ Q $$ is energy density of biomas. At steady state, parents replace themselves with offspring of equal mass‐specific energy content, E$$ E $$ ≈ 22.4 kJ/g, and biomass, M$$ M $$ ≈ 1 g/g. The EFP highlights: (i) the energetic basis of survival and reproduction; (ii) how natural selection acts directly on the parameters of M$$ M $$; (iii) why there is no inherent intrinsic fitness advantage for higher metabolic power, ontogenetic or population growth rate, fecundity, longevity, or resource use efficiency; and (iv) the role of energy in animals with a variety of life histories. Underlying the spectacular diversity of living things is pervasive similarity in how energy is acquired from the environment and used to leave descendants offspring in future generations. [ABSTRACT FROM AUTHOR]

Mangroves provide habitat for a diverse array of marine species, especially snails. We used a MaxEnt model to predict potential global suitable habitat for Cerithidea rhizophorarum and Telescopium telescopium in the family Potamididae. A total of 667 occurrence data were obtained from the Global Biodiversity Information Facility (GBIF) with the following sub‐data set contribution, "iNaturalist Research Grade Observations" (85%), "International Barcode of Life project (iBOL)" (7%), "FBIP: SeaKeys_SANBI: Marine images iSpot_2013" (1%), "A dataset of marine macroinvertebrate diversity from Mozambique and São Tomé and Príncipe" (1%), occurrence data of some marine invertebrates and freshwater crabs housed in the natural history collection at the National Museums of Kenya (1%), and Natural History Museum Rotterdam‐Specimens (1%). Our results showed that temperature with a contribution of above 80% in the present and future model is the most important driver of the distribution of mangrove snails. In the present and future models, the most potentially suitable habitats for C. rhizophorarum and T. telescopium were observed along coastal areas with a temperature between 20°C–21°C and 30°C, respectively. Our model predicts that by 2100, high‐suitability areas will shrink as a result of global warming. The vulnerability of mangrove snails under future climate conditions is evident in our results. Our findings contribute significant insights into the intricate relationship between mangrove habitats and mangrove snails, offering a valuable foundation for conservation initiatives aimed at safeguarding the biodiversity and ecological functions of these crucial coastal ecosystems in the face of changing global environmental conditions. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Benign ancient retroperitoneal schwannomas (BARS) exhibit abdominal masses and flank pain to incidental findings at more advanced stages. Histopathological and immunohistochemical analysis is essential for confirmation of benign nature. Our patient was misdiagnosed as ureteric colic, highlighting the need to consider BARS in differential diagnosis to prevent complications like hydronephrosis. Ancient schwannomas are usually benign neoplasms that originate from Schwann cells of peripheral nerves. We present a novel case of a 24‐year‐old young male with left flank pain and nausea which was initially thought to be left ureteric colic. However, in‐depth imaging and biopsy revealed a retroperitoneal mass. The definitive diagnosis was narrowed down to Benign Retroperitoneal Ancient Schwannoma (BARS) via immunohistochemistry and histopathological analysis. This often marble‐shaped S100 protein‐positive tumor is an under‐recognized and potential cause of hydronephrosis if localized near the renal structures. In addition, the retroperitoneal location with infrarenal abdominal aortic adherence is another rare peculiarity in the present case that demands prompt diagnosis and surgical excision to avoid any cardiovascular sequelae such as hypotension and abdominal pain, as indicated by the natural history of growth of this benign tumor. Therefore, timely excision of this benign tumor prior to its further proliferation is paramount. We initially planned laparoscopic removal but adopted excision via laparotomy because of the proximity of the vital structures. The postoperative course of the patient was uneventful and subsequently the patient's presenting complaint of left abdominal flank pain greatly improved. The patient was advised to undergo follow‐up computed tomography scan of kidney ureter bladder and RFT evaluation 6 months postsurgery which indicated no evidence of recurrence or iatrogenic complications. The diagnosis and management of the present case share valuable experiences for similar future cases worldwide. [ABSTRACT FROM AUTHOR]

The diversification of many lineages throughout natural history has frequently been associated with evolutionary changes in life cycle complexity. However, our understanding of the processes that facilitate differentiation in the morphologies and functions expressed by organisms throughout their life cycles is limited. Theory suggests that the expression of traits is decoupled across life stages, thus allowing for their evolutionary independence. Although trait decoupling between stages is well established, explanations of how said decoupling evolves have seldom been considered. Because the different phenotypes expressed by organisms throughout their life cycles are coded for by the same genome, trait decoupling must be mediated through divergence in gene expression between stages. Gene duplication has been identified as an important mechanism that enables divergence in gene function and expression between cells and tissues. Because stage transitions across life cycles require changes in tissue types and functions, we investigated the potential link between gene duplication and expression divergence between life stages. To explore this idea, we examined the temporal changes in gene expression across the monarch butterfly (Danaus plexippus) metamorphosis. We found that within homologous groups, more phylogenetically diverged genes exhibited more distinct temporal expression patterns. This relationship scaled such that more phylogenetically diverse homologous groups showed more diverse patterns of gene expression. Furthermore, we found that duplicate genes showed increased stage-specificity relative to singleton genes. Overall, our findings suggest an important link between gene duplication and the evolution of complex life cycles. [ABSTRACT FROM AUTHOR]

Despite large differences in morphology, behavior and lek-mating strategies the birds-of-paradise are known to hybridize occasionally, even across different genera. Many of these bird-of-paradise hybrids were originally described as distinct species based on large morphological differences when compared to recognized species. Nowadays, these specimens are generally recognized as hybrids based on morphological assessments. Having fascinated naturalists for centuries, hybrid specimens of birds-of-paradise have been collected and the specimens kept in Natural History Collections. In the present study, we utilize this remarkable resource in a museomics framework and evaluate the genomic composition of most described intergeneric hybrids and some intrageneric hybrids. We show that the majority of investigated specimens are first-generation hybrids and that the parental species, in most cases, are in line with prior morphological assessments. We also identify two specimens that are the result of introgressive hybridization between different genera. Additionally, two specimens exhibit hybrid morphologies but have no identifiable signals of hybridization, which may indicate that minor levels of introgression can have large morphological effects. Our findings provide direct evidence of contemporary introgressive hybridization taking place between genera of birds-of-paradise in nature, despite markedly different morphologies and lek-mating behaviors. [ABSTRACT FROM AUTHOR]

Background: Multiple sclerosis (MS) presents a wide range of clinical symptoms, historically understood through long-term studies of earlier patient cohorts. However, due to improved diagnostic criteria, modern patients are diagnosed earlier and benefit from effective treatments, altering the disease's natural history. This study aimed to assess the clinical symptoms of MS patients in a modern population at various stages: before diagnosis, at diagnosis, during the disease course, and at the time of the survey. Methods: This was an observational study with retrospective and cross-sectional components; patients that fulfilled the 2017 revised McDonald criteria for MS completed a survey evaluating demographic and clinical data. Results: We included 163 patients, 69.9% female, with a mean age of 48.21 years; 87.1% had relapsing–remitting MS (RRMS), with a median EDSS of 2.0. Before diagnosis, 74.2% of patients experienced symptoms, mainly sensory issues (39.3%), fatigue (29.4%), and imbalance (27%). Motor and coordination symptoms were more common in progressive forms. At diagnosis, sensory (46.6%) and motor complaints (36.8%) were most prevalent. In RRMS and secondary progressive MS (SPMS), sensory and motor complaints predominated alongside imbalance, while primary progressive MS (PPMS) was characterized by motor, imbalance, and genitourinary symptoms. Throughout the disease, sensory symptoms were most common (76.1%), with fatigue (73%) and motor issues (62.6%) more prevalent in progressive forms. At the time of the survey, 50.7% of RRMS patients were asymptomatic, while progressive patients continued to experience motor symptoms, imbalance, and fatigue. Conclusions: The study reflects the modern spectrum of MS symptoms, consistent with previous research. [ABSTRACT FROM AUTHOR]

Pulmonary emphysema involves progressive destruction of alveolar walls, leading to enlarged air spaces and impaired gas exchange. While the precise mechanisms responsible for these changes remain unclear, there is growing evidence that the extracellular matrix plays a critical role in the process. An essential feature of pulmonary emphysema is damage to the elastic fiber network surrounding the airspaces, which stores the energy needed to expel air from the lungs. The degradation of these fibers disrupts the mechanical forces involved in respiration, resulting in distension and rupture of alveolar walls. While the initial repair process mainly consists of elastin degradation and resynthesis, continued alveolar wall injury may be associated with increased collagen deposition, resulting in a mixed pattern of emphysema and interstitial fibrosis. Due to the critical role of elastic fiber injury in pulmonary emphysema, preventing damage to this matrix component has emerged as a potential therapeutic strategy. One treatment approach involves the intratracheal administration of hyaluronan, a polysaccharide that prevents elastin breakdown by binding to lung elastic fibers. In clinical trials, inhalation of aerosolized HA decreased elastic fiber injury, as measured by the release of the elastin-specific cross-linking amino acids, desmosine, and isodesmosine. By protecting elastic fibers from enzymatic and oxidative damage, aerosolized HA could alter the natural history of pulmonary emphysema, thereby reducing the risk of respiratory failure. [ABSTRACT FROM AUTHOR]