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The detection of limit cycles of differential equations poses a challenge due to the type of the nonlinear system, the regime of interest, and the broader context of applicable models. Consequently, attempts to solve Hilbert's sixteenth problem on the maximum number of limit cycles of polynomial differential equations have been uniformly unsuccessful due to failing results and their lack of consistency. Here, the answer to this problem is finally obtained through information geometry, in which the Riemannian metrical structure of the parameter space of differential equations is investigated with the aid of the Fisher information metric and its scalar curvature R. We find that the total number of divergences of |R| to infinity provides the maximum number of limit cycles of differential equations. Additionally, we demonstrate that real polynomial systems of degree n≥2 have the maximum number of 2(n-1)(4(n-1)-2) limit cycles. The research findings highlight the effectiveness of geometric methods in analyzing complex systems and offer valuable insights across information theory, applied mathematics, and nonlinear dynamics. These insights may pave the way for advancements in differential equations, presenting exciting opportunities for future developments.

Introduction: Rare disorders that are genetically and clinically heterogeneous, such as mitochondrial diseases (MDs), have a challenging diagnosis. Nuclear genes codify most proteins involved in mitochondrial biogenesis, despite all mitochondria having their own DNA. The development of next-generation sequencing (NGS) technologies has revolutionized the understanding of many genes involved in the pathogenesis of MDs. In this new genetic era, using the NGS approach, we aimed to identify the genetic etiology for a suspected MD in a cohort of 450 Portuguese patients. Methods: We examined 450 patients using a combined NGS strategy, starting with the analysis of a targeted mitochondrial panel of 213 nuclear genes, and then proceeding to analyze the whole mitochondrial DNA. Results and Discussion: In this study, we identified disease-related variants in 134 (30%) analyzed patients, 88 with nuclear DNA (nDNA) and 46 with mitochondrial DNA (mtDNA) variants, most of them being pediatric patients (66%), of which 77% were identified in nDNA and 23% in mtDNA. The molecular analysis of this cohort revealed 72 already described pathogenic and 20 novel, probably pathogenic, variants, as well as 62 variants of unknown significance. For this cohort of patients with suspected MDs, the use of a customized gene panel provided a molecular diagnosis in a timely and cost-effective manner. Patients who cannot be diagnosed after this initial approach will be further selected for whole-exome sequencing. Conclusion: As a national laboratory for the study and research of MDs, we demonstrated the power of NGS to achieve a molecular etiology, expanding the mutational spectrum and proposing accurate genetic counseling in this group of heterogeneous diseases without therapeutic options., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Nogueira, Pereira, Silva, Laranjeira, Lopes, Neiva, Rodrigues, Campos, Martins, Bandeira, Coelho, Magalhães, Damásio, Gaspar, Janeiro, Gomes, Ferreira, Jacinto, Vieira, Diogo, Santos, Mendonça and Vilarinho.)

Climate and anthropogenic stressors are frequent in coastal systems, affecting biological communities in different intensities and directions. When acting synergistically, their effects may be intensified. ENSO strongly affects the climate globally, being responsible for increased rainfall in the Atlantic Southwestern during El Niño and droughts during La Niña phases. Contrasting, human-made breakwaters have static influence in decreasing estuarine salinity. Using a 23-year of fish abundance dataset, we identified that intense El Niño events and breakwater extension decreased the marine fish abundance, with potential additive synergistic effects, whereas La Niña showed no influence. Species composition changes were observed after the breakwater extension, probably related to opportunistic habits of euryhaline species. Anthropogenic and natural climatic disturbances affect habitat use, and their synergic effects must be considered to evaluate ecosystem responses in the current climate change scenario, and constant human modification of coastal zones., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Overfishing constitutes a major threat affecting marine fish population worldwide, including mullet species that have been exploited by fisheries during the reproductive migration in temperate and tropical latitudes for millennia. In the present study, we investigated the relationship of fishing intensity of mullet Mugil liza during its reproductive migration and the abundance of their juveniles in an essential nursery ground for the species in the southwest Atlantic Ocean. To carry out this analysis, we used a 23-year standardized long-term time series (1997-2019) of monthly abundance of M. liza juveniles, local/regional (water temperature, salinity, water transparency and river discharge) and global (ENSO) environmental factors, along with compilations of fishing landing data for the species. Generalized Additive Models (GAM) revealed the negative effect of fishing adult populations on the abundance of juveniles when they reach the marine surf-zone and after recruiting into the estuary. Our results reinforce the importance of adequate conservation and fishery regulation policies to prevent the species' stock from collapsing., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: To analyze the factors associated with loss to follow-up in tuberculosis cases among adults in Brazil in 2020 and 2021., Method: Retrospective cohort with secondary data from the Brazilian Notifiable Diseases Information System. A total of 24,344 people diagnosed with tuberculosis whose information was complete in the database were included. Adjusted odds ratios and confidence intervals were estimated by binary logistic regression., Results: Higher odds of loss to follow-up were observed for males, non-white ethnicity/color, with lower education level, homeless or deprived of liberty, who used drugs, alcohol and/or tobacco, with admission due to recurrence or re-entry after abandonment, and with unknown or positive serology for HIV. On the other hand, older age, extrapulmonary tuberculosis, deprivation of libertyand supervised treatment were associated with lower odds of loss to follow-up., Conclusion: Demographic, socioeconomic and clinical-epidemiological factors were associated with the loss to follow-up in tuberculosis cases, which reiterates the various vulnerabilities intertwined with the illness and treatment of this disease. Therefore, there is a need to promote strategies aimed at adherence and linkage to the care for groups most vulnerable to loss to follow-up in tuberculosis treatment in Brazil.

Ocean warming is associated with the tropicalization of fish towards higher latitudes. However, the influence of global climatic phenomena like the El Niño Southern Oscillation (ENSO) and its warm (El Niño) and cold (La Niña) phases on tropicalization has been overlooked. Understanding the combined effects of global climatic forces together with local variability on the distribution and abundance of tropical fish is essential for building more accurate predictive models of species on the move. This is particularly important in regions where ENSO-related impacts are known to be major drivers of ecosystem change, and is compounded by predictions that El Niño is becoming more frequent and intense under current ocean warming. In this study, we used long-term time series of monthly standardized sampling (August 1996 to February 2020) to investigate how ocean warming, ENSO and local environmental variability influence the abundance of an estuarine dependent tropical fish species (white mullet Mugil curema) at subtropical latitudes in the southwestern Atlantic Ocean. Our work revealed a significant increasing trend in surface water temperature in shallow waters (<1.5 m) at estuarine and marine sites. However, against our initial expectation, we did not observe an increasing trend in the abundance of this tropical mullet species. Generalized Additive Models revealed complex, non-linear relationships between species abundance and environmental factors operating at large (ENSO's warm and cold phases), regional (freshwater discharge in the coastal lagoon's drainage basin) and local (temperature and salinity) scales across the estuarine marine gradient. These results demonstrate that fish responses to global climate change can be complex and multifaceted. More specifically, our findings suggested that the interaction among global and local driving forces dampen the expected effect of tropicalization for this mullet species in a subtropical seascape., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Introduction: Metabolic myopathies (MM) are a heterogeneous group of genetic disorders affecting metabolic pathways involved in energy production during rest, exercise and physiologic stress (fever, fasting, …). Impairments in the pathways of glycolysis/ glycogenolysis, fatty acid transport/oxidation or in the mitochondrial respiratory chain present primarily with exercise intolerance, myalgias, weakness, cramps, or rhabdomyolysis. Depending on aetiology, the diagnosis can be made through neonatal screening, pre-symptomatic or in the set of clinical manifestations for which a high level of suspicion is important., Methods: Retrospective descriptive study of the clinical, biochemical, and molecular features of patients with a confirmed diagnosis of MM followed by the multidisciplinary team of the Reference Center of Inherited Metabolic Diseases of Centro Hospitalar Universitário de Lisboa Central from 2009 to 2022., Results: Twenty-three patients with MM were included: 9 (39%) glycogen storage diseases (7 McArdle and 2 Pompe), 7 (30%) fatty acid oxidation disorders (3 CPT2, 3 LCHAD and 1 MAD deficiencies), 6 (26%) mitochondrial disease with significant muscle involvement (2 Pearson, 1 Kearns Sayre, 1 VARS2, 1 SUCLA2 and 1 MT-TL1 deficiencies), and 1 myoadenylate deaminase deficiency. Ages varied from 15 months to 35 years. Eighteen (78%) patients were diagnosed by clinical symptoms, 3 by newborn screening (LCHAD) and 2 were asymptomatic (1 Pompe and 1 McArdle). Frequent symptoms were rhabdomyolysis triggered by illness or exercise 12 (52%), fatigue 11 (48%), exercise intolerance 10 (43%), and myalgia 9 (43%). Eight (35%) patients (LCHAD and mitochondrial) had multisystemic involvement. In 20 (87%) patients, the diagnosis was confirmed by biochemical and/or genetic analysis and 3 (McArdle) by muscle biopsy., Conclusion: MM are a heterogeneous set of disorders, but a careful history may guide the differential diagnosis among biochemical pathways and other etiologies. Nowadays, molecular testing has become a powerful tool for diagnosis confirmation, surpassing muscular biopsy in most cases. Accurate diagnosis is important to identify who may benefit from specific therapeutic options, such as enzyme replacement therapy, restricted diets, emergency regime and cofactors. All patients benefit from adequate lifestyle modifications, individualized exercise prescription, nutritional intervention, and genetic counselling., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Aortic coarctation is characterized by a segmental narrowing of the aortic lumen, usually diagnosed and treated in the neonatal period or early childhood, but can remain undiagnosed until adulthood. It manifests as a broad spectrum of signs and symptoms, ranging from mild to severe, of which arterial hypertension is one of the most common. In this article, the authors describe the clinical case of a 9-year-old child under investigation in the Pediatric Department for secondary causes of arterial hypertension. A renal Doppler ultrasound study revealed the presence of bilateral parvus et tardus waveform morphology in renal and intrarenal arteries and the proximal abdominal aorta. These findings were suspicious for diagnosing aortic coarctation, which thoracic CTangio confirmed.

Disruptions in the MBD5 gene have been linked with an array of clinical features such as global developmental delay, intellectual disability, autistic-like symptoms, and seizures, through unclear mechanisms. MBD5 haploinsufficiency has been associated with the disruption of primary cilium-related processes during early cortical development, and this has been reported in many neurodevelopmental disorders. In this study, we describe the clinical history of a 12-year-old child harboring a novel MBD5 rare variant and presenting psychomotor delay and seizures. To investigate the impact of MBD5 haploinsufficiency on neural primary cilia, we established a novel patient-derived cell line and used CRISPR-Cas9 technology to create an isogenic control. The patient-derived neural progenitor cells revealed a decrease in the length of primary cilia and in the total number of ciliated cells. This study paves the way to understanding the impact of MBD5 haploinsufficiency in brain development through its potential impact on neural primary cilia.

This paper estimates the impact of the COVID-19 on air travel demand and emissions in Brazil, the largest aviation market in Latin America. Combining detailed flight data and data on combustion emission factors, we estimate the CO 2 emissions of domestic flights. A Bayesian structural time-series model was used to estimate the impact of COVID-19 on daily trends of air travel demand and emissions. The COVID-19 caused a reduction of 68% in national passengers and 63% in total CO 2 emissions compared to what would have occurred if the pandemic had not happened. Despite such a sharp drop, fuel efficiency decreased after the COVID-19 outbreak, and passenger demand recovered to 64.2% of pre-pandemic levels by the end of 2020. The fast recovery in domestic flights by December 2020 indicates that the emissions could soon return to pre-pandemic levels, demonstrating the challenges of reducing emissions in the aviation sector in the short term., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 Elsevier Ltd. All rights reserved.)

The conventional local bifurcation theory (CBT) fails to present a complete characterization of the stability and general aspects of complex phenomena. After all, the CBT only explores the behavior of nonlinear dynamical systems in the neighborhood of their fixed points. Thus, this limitation imposes the necessity of non-trivial global techniques and lengthy numerical solutions. In this article, we present an attempt to overcome these problems by including the Fisher information theory in the study of bifurcations. Here, we investigate a Riemannian metrical structure of local and global bifurcations described in the context of dynamical systems. The introduced metric is based on the concept of information distance. We examine five contrasting models in detail: saddle-node, transcritical, supercritical pitchfork, subcritical pitchfork, and homoclinic bifurcations. We found that the metric imposes a curvature scalar R on the parameter space. Also, we discovered that R diverges to infinity while approaching bifurcation points. We demonstrate that the local stability conditions are recovered from the interpretations of the curvature R, while global stability is inferred from the character of the Fisher metric. The results are a clear improvement over those of the conventional theory.

The hypothalamus is the central regulator of energy homeostasis. Hypothalamic neuronal circuits are disrupted upon overfeeding, and play a role in the development of metabolic disorders. While mouse models have been extensively employed for understanding the mechanisms of hypothalamic dysfunction, functional magnetic resonance imaging (fMRI) on hypothalamic nuclei has been challenging. We implemented a robust glucose-induced fMRI paradigm that allows to repeatedly investigate hypothalamic responses to glucose. This approach was used to test the hypothesis that hypothalamic nuclei functioning is impaired in mice exposed to a high-fat and high-sucrose diet (HFHSD) for seven days. The blood oxygen level-dependent (BOLD) fMRI signal was measured from brains of mice under light isoflurane anaesthesia, during which a 2.6 g/kg glucose load was administered. The mouse hypothalamus responded to glucose but not saline administration with a biphasic BOLD fMRI signal reduction. Relative to controls, HFHSD-fed mice showed attenuated or blunted responses in arcuate nucleus, lateral hypothalamus, ventromedial nucleus and dorsomedial nucleus, but not in paraventricular nucleus. In sum, we have developed an fMRI paradigm that is able to determine dysfunction of glucose-sensing neuronal circuits within the mouse hypothalamus in a non-invasive manner.

Congenital cranial dysinnervation disorders (CCDDs) are a heterogeneous group of neurodevelopmental phenotypes caused by a primary disturbance of innervation due to deficient, absent, or misguided cranial nerves. Although some CCDDs genes are known, several clinical phenotypes and their aetiologies remain to be elucidated. We describe a 12-year-old boy with hypotonia, developmental delay, sensorineural hearing loss, and keratoconjunctivitis due to lack of corneal reflex. He had a long expressionless face, severe oromotor dysfunction, bilateral agenesis/severe hypoplasia of the VIII nerve with marked atresia of the internal auditory canals and cochlear labyrinth malformation. Trio-exome sequencing identified a homozygous loss of function variant in the NEUROG1 gene (NM&#95;006161.2: c.202G > T, p.Glu68*). NEUROG1 is considered a causal candidate for CCDDs based on (i) the previous report of a patient with a homozygous gene deletion and developmental delay, deafness due to absent bilateral VIII nerves, and severe oromotor dysfunction; (ii) a second patient with a homozygous NEUROG1 missense variant and corneal opacity, absent corneal reflex and intellectual disability; and (iii) the knockout mouse model phenotype which highly resembles the disorder observed in humans. Our findings support the growing compelling evidence that loss of NEUROG1 leads to a very distinctive disorder of cranial nerves development., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

It has been argued that the central nervous system relies on combining simple movement elements (i.e. motor primitives) to generate complex motor outputs. However, how movement elements are generated and combined during the acquisition of new motor skills is still a source of debate. Herein, we present results providing new insights into the role of movement elements in the acquisition of motor skills that we obtained by analysing kinematic data collected while healthy subjects learned a new motor task. The task consisted of playing an interactive game using a platform with embedded sensors whose aggregate output was used to control a virtual object in the game. Subjects learned the task over multiple blocks. The analysis of the kinematic data was carried out using a recently developed technique referred to as "movement element decomposition." The technique entails the decomposition of complex multi-dimensional movements in one-dimensional elements marked by a bell-shaped velocity profile. We computed the number of movement elements during each block and measured how closely they matched a theoretical velocity profile derived by minimizing a cost function accounting for the smoothness of movement and the cost of time. The results showed that, in the early stage of motor skill acquisition, two mechanisms underlie the improvement in motor performance: 1) a decrease in the number of movement elements composing the motor output and 2) a gradual change in the movement elements that resulted in a shape matching the velocity profile derived by using the above-mentioned theoretical model., (© 2019 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Background: Primary intrahepatic lithiasis is defined when the stones are formed in the liver and associated with local dilatation and biliary stricture. Liver resection is the ideal procedure., Aim: To evaluate the results of liver resection in the treatment of non-oriental intrahepatic lithiasis., Methods: Fifty-one patients with symptomatic benign non-oriental hepatolithiasis underwent surgical resection in six institutions in Brazil. Demography data, clinical symptoms, classification, diagnosis, management and postoperative course were analyzed., Results: Of the 51 patients, 28 were male (54.9%), with a mean age of 49.3 years. History of cholangitis was observed in 15 (29.4%). The types of intrahepatic lithiasis were type I in 39 (76.5%) and type IIb in 12 (23.5%), with additional type Ea in six (11.8%). Liver function test were normal in 42 patients (82.4%). Segmental atrophy was observed in 12 (23.5%). Treatments included left lateral sectionectomy in 24 (47.1%), left hepatectomy in 14 (27.5%) and right hepatectomy in eight (15.7%), with associated hepaticojejunostomy in four (7.8%). Laparoscopic liver resection was performed in eight (15.7%). Postoperative complications were observed in 20 (39.2%) with no mortality., Conclusion: Liver resection in patients with hepatolithiasis is the ideal procedure as it removes stones, stricture, atrophic parenchyma, and minimizes the risk of cholangiocarcinoma.

We analysed the ratios Sr:Ca and Ba:Ca in the otoliths of 55 adults of the southern population of Mugil liza in Brazil (Paraná to Rio Grande do Sul) to investigate its coastal zone use and migratory behaviour. All individual M. liza analysed had Sr:Ca and Ba:Ca values indicating that their birth was in the marine environment, which is consistent with the southern population migration to spawn in the ocean,. Juveniles exhibited at least three coastal use and recruitment strategies (contingents): the majority (89%) of M. liza juveniles migrated toward brackish water. They entered the estuary before completing the first year of life (64%) or after (25%) their first year of life. The remaining 11% did not appear to enter brackish or freshwater water as a nursery or at any point in their life cycle. Some adults returned to the estuary after spawning in the ocean but others (of both sexes) never returned to the estuary after spawning, remaining in the marine environment. The pattern of juvenile habitat use in the Brazilian southern population of M. liza seems to be recurrent throughout the extent of its distribution as a consequence of the reproductive spawning aggregation behaviour, which mixes all contingents (with marine or estuarine preferences)., (© 2019 The Fisheries Society of the British Isles.)

Headache with neurologic deficits and cerebrospinal fluid lymphocytosis (HaNDL) is a rare headache syndrome included in the Classification of Headache of the International Headache Society as a "headache attributed to non-infectious inflammatory intracranial disease." We report one 15-year-old patient with clinical history and cerebrospinal fluid findings compatible with the diagnosis of HaNDL in whom Borrelia lusitaniae was identified in cerebrospinal fluid by polymerase chain reaction.

BACKGROUND Adenoid cystic carcinoma of trachea (ACCT) is an unusual low-grade tumor from the tracheal and bronchial wall glands. The histological structure and biological behavior of ACCT are similar to that of tumors found in the salivary glands. ACCT occurs most commonly in the upper trachea, being found in the articular cartilage in the posterior aspect of the trachea. CASE REPORT We describe the case of a 62-year-old male ex-smoker 25 years/pack (abstinence 20 years ago), who began with mild dyspnea 2 years ago, with intense evolution and cough. He was evaluated as an outpatient and was treated for sinusitis and later bronchitis after pulmonary function tests. With the worsening of the aforementioned symptoms, he sought prompt care, with hospitalization and computed tomography (CT) of the chest being indicated, showing an expansive lesion in the anterior wall of the trachea with an extension of approximately 3.1 cm, ending at the level of the carina, measuring 3.4×2.8 cm, with moderate stenosis of the tracheal lumen, with an exophytic component to the mediastinum. Bronchoscopy of the lesion was done, and later immunohistochemistry showed a probable pleomorphic adenoma. However, in a new analysis, after the removal of the surgical specimen, it was observed that it was a ACCT. CONCLUSIONS ACCT is a rare tumor that should be diagnosed as soon as possible in order to ensure its best prognosis. Moreover, it is evident that the analysis of the surgical specimen is sovereign to immunohistochemistry with regard to histological typing.

Mitochondrial diseases (MD) are a group of rare inherited disorders, characterized by phenotypic heterogeneity, with hitherto no effective therapeutic options. The aim of this study was to develop a next generation sequencing (NGS) strategy, by using a custom gene panel and whole mitochondrial genome, to identify the disease causing pathogenic variants in 146 patients suspicious of MD. The molecular analysis of this cohort revealed six novel and 15 described pathogenic variants, as well as 26 variants of unknown significance. Our findings are expanding the mutational landscape of these disorders and support the use of a NGS strategy for a higher diagnostic yield., (Copyright © 2019 Elsevier B.V. and Mitochondria Research Society. All rights reserved.)