bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microcephaly and Its Related Syndromes: Classification, Genetic, Clinical, and Rehabilitative Considerations
Authors: Di Nora Alessandra , La Cognata Daria , Zanghì Antonio , Vecchio Michele , Chiaramonte Rita , Marino Francesco , Palmucci Stefano , Belfiore Giuseppe , Polizzi Agata , Praticò Andrea D. 
Published: May 2024

AbstractMicrocephaly, a form of cortical cortex malformation, results from abnormal cellular production and proliferation, identified when the occipital frontal head circumference (OFC) falls two or more standard deviations (SDs) below the expected average for age, gender, and population. Severity is classified based on SD: mild (OFC < 2 SD) or severe (OFC < 3 SD). While microcephaly can lead to developmental delay, intellectual disability, epilepsy, and cerebral palsy, not all cases exhibit these issues. Classified as primary/congenital or secondary/postnatal, microcephaly can stem from genetic or acquired factors in both types. Congenital microcephaly origins vary, while secondary microcephaly is characterized by normal OFC at birth, followed by a decrease within the first year, often associated with progressive cognitive and motor impairments. Primary hereditary microcephaly (MCPH), or microcephaly vera, is genetically diverse, with 28 related genes (MCPH1 to MCPH28) encoding proteins linked to centrosomes and progenitor cell mitosis in the brain ventricle's neuroepithelium. Defects in deoxyribonucleic acid (DNA) repair pathways (e.g., NBN, FANCA, ATR, ATM genes) can lead to microcephaly by impairing DNA repair. Enzyme deficiencies in metabolic pathways may also contribute, causing toxic metabolite accumulation or essential metabolite loss (microcephaly of metabolic origin). Acquired congenital microcephaly may result from ischemic or infectious processes, drugs, radiation, maternal diseases during pregnancy, with damage influenced by fetal genetics, environmental interactions, developmental stage, and exposure intensity/duration. Diagnostic workup includes electroencephalogram, ophthalmological, auditory, magnetic resonance imaging, metabolic, echocardiogram, and infection screening tests, alongside genetic evaluations like cytogenetic studies, fluorescence in situ hybridization, comparative genomic microarray-hybridization, single-nucleotide microarray-polymorphism, and exome sequencing. Symptomatic treatment is available, and genetic counseling is crucial for affected families.
Introduction: A Practical Guide to Central Nervous System Malformations—From Genetics, to Diagnosis and Treatment
Authors: Praticò Andrea D. , Polizzi Agata , Ruggieri Martino 
Published: May 2024

AbstractCentral nervous system (CNS) malformations encompass diverse congenital anomalies impacting brain and spinal cord development, profoundly affecting neurological function. They arise from disruptions in embryonic neural tube formation, neuronal migration, and cortical organization. This abstract provides a comprehensive overview of CNS malformations, covering classification, etiology, clinical manifestations, and diagnostic challenges. CNS malformations fall into distinct groups: neural tube defects (e.g., anencephaly, spina bifida), resulting from incomplete neural tube closure; malformations of cortical development (e.g., lissencephaly, polymicrogyria), featuring irregularities in cortical folding; and anomalies affecting structures like the corpus callosum, cerebellum, and CNS vasculature, alongside conditions such as hydrocephalus and Chiari malformations. Genetic factors, including mutations in LIS1, DCX, and RELN, contribute significantly, while environmental factors like maternal folic acid deficiency also play a role. Some malformations occur in genetic syndromes (e.g., tuberous sclerosis, neurofibromatosis). Clinical presentations vary, with neural tube defects typically presenting severe deficits at birth, while cortical malformations manifest as intellectual disabilities, seizures, and motor deficits. Hydrocephalus elevates intracranial pressure, and Chiari malformations cause headaches and neurological symptoms. Diagnosis necessitates a multidisciplinary approach involving clinical evaluation, neuroimaging, genetic testing, and histopathological analysis. Prenatal diagnosis via ultrasound and magnetic resonance imaging is crucial for planning interventions, while postnatal diagnosis relies on clinical and imaging findings.Understanding CNS malformations is vital for early detection, intervention, and comprehensive care provision. Advances in genetics and neuroimaging offer hope for improved outcomes and better quality of life for affected individuals.
At the Basis of Brain Malformations: Brain Plasticity, Developmental Neurobiology, and Considerations for Rehabilitation
Authors: Polizzi Agata , Ruggieri Martino , Praticò Andrea D. , Leotta Michela , Cavallaro Paola , Sciuto Laura , Vecchio Michele , Di Napoli Claudia 
Published: May 2024

AbstractFrom early age in the human brain occurs plasticity process that influences its development. The functioning of the brain is governed by its neuronal connectivity and the synaptic dynamics of these connections. A neuron, over thousands of synapses, can receive a large number of inputs and produce different outputs leading to the consolidation and integration of memory. Synaptic plasticity is the set of experience-dependent changes in neuronal pathways that support acquired habits. It is the ability of the nervous system to reshape connectivity between neurons, changing the functional and structural organization of neuronal circuits that allows us to adapt to the multiple and continuous changes in the environment and leading to processes such as cognitive development and the ability to learn. Synaptic plasticity is mainly due to short- and long-term mechanisms. Short-term synaptic plasticity refers to changes in synaptic strength that occurs very quickly (from one-thousandth of a second to 5 minutes) and are temporary and decay over minutes (maximum 30 minutes). Long-term synaptic plasticity is defined by a long-lasting, activity-dependent change in synaptic efficacy, last from hours up to a lifetime (from 30 minutes to weeks, months, and years) and is thought to constitute the basis of learning and memory. A significant difference occurs in the nature of the change; short-term plasticity adds only a functional change, whereas long-term plasticity causes not only functional but also structural changes. Aside from genetic factors and metabolic processes, brain development is mediated also by environmental factors. Interaction with the environment plays a key role in the development and growth of neural networks and neuroplasticity. Environmental interactions that can modify and increase the development of neural networks and intelligence in children are several and are herein discussed.
Megalencephaly: Classification, Genetic Causes, and Related Syndromes
Authors: Leonardi Roberta , Licciardello Laura , Zanghì Antonio , La Cognata Daria , Maniaci Antonino , Vecchio Michele , Polizzi Agata , Falsaperla Raffaele , Praticò Andrea D. 
Published: May 2024

AbstractMegalencephaly is a developmental disorder due to an abnormal neuronal proliferation and migration during intrauterine or postnatal brain development that leads to cerebral overgrowth and neurological dysfunction. This cerebral overgrowth may affect the whole encephalon or only a region; when it involves one hemisphere it is referred to as hemimegalencephaly. Megalencephaly presents with a head circumference measurement of 2 standard deviations above the average measure for age. This group of disorders is clinically characterized by early onset and refractory to therapy epilepsy, neurodevelopmental disorders, behavioral problems, and autism spectrum disorder. Syndromic forms of megalencephaly should be considered when associated with other congenital abnormalities. Megalencephaly in fact could be associated with segmental overgrowth and cutaneous/vascular abnormalities (i.e., Proteus syndrome, CLOVES [congenital lipomatous overgrowth, vascular malformations, epidermal naevi, scoliosis, and/ or skeletal abnormalities] syndrome, Klippel-Trenaunay syndrome, megalencephaly-capillary malformation-polymicrogyria syndrome , megalencephaly-postaxial polydactyly-polymicrogyria-hydrocephalus syndrome, etc.) or generalized overgrowth (i.e., Weaver or Beckwith-Wiedemann syndrome) as well as with nanism in achondroplasia where megalencephaly is associated with disproportionate short stature, primary skeletal dysplasia, characteristic facies (prominent forehead, flat nasal bridge), narrow chest, and normal intelligence. It is possible to identify three main groups of disorders associated with megalencephaly: idiopathic or benign, metabolic, and anatomic. The idiopathic (benign) form indicates an abnormal increased head circumference in absence of neurological impairment, such as in benign familial megalencephaly. In metabolic megalencephaly (such as in organic acid disorders, metabolic leukoencephalopathies, or lysosomal diseases) there is an increase of different constituents that increase the size of the brain, whereas in the anatomical form there are underlying genetic causes. Neuroimaging is crucial for diagnosis, as it can reveal a generalized brain growth or a segmental one and possible specific frameworks associated. In all these conditions it is necessary to identify possible microdeletion-microduplication by chromosomal arrays.
Lissencephaly, Pachygyrias, Band Heterotopias, RELN Pathway, and ARX Mutations (Incomplete Neuron Migration)
Authors: Sciuto Laura , Fichera Valeria , Zanghì Antonio , Vecchio Michele , Falsaperla Raffaele , Galioto Sebastiano , Palmucci Stefano , Belfiore Giuseppe , Di Napoli Claudia , Polizzi Agata , Praticò Andrea D. 
Published: May 2024

AbstractLissencephaly (LIS) is a group of malformations of cortical development consisting of a defective neuronal migration that results in lack of formation of the normal cerebral convolutions. It includes a spectrum of defect with varying degrees of severity, from agyria and pachygyria to subcortical band heterotopia. The etiopathogenesis of LIS includes both genetic and environmental factors. Although nongenetic forms of LIS have been reported, genetic causes are certainly more frequent and to date 19 LIS-SBH-associated genes have been identified. Most common mutations involve LIS1, DCX, ARX, and RELN genes. Clinically affected individuals present with early hypotonia, which can progress to limb spasticity, seizures, and psychomotor retardation. Convulsive episodes usually appear early (first months of life) and include infantile spasms, akinetic or myoclonic seizures, up to the development of complex epileptic syndromes, including atypical absences, myoclonia, and partial or tonic–clonic seizures. Several clinical entities are associated with classical LIS, including the following: isolated lissencephaly sequence (ILS); Miller–Dieker syndrome (MDS; OMIM 247200); subcortical band heterotopia (OMIM 300067); X-linked LIS with abnormal genitalia; and LIS with cerebellar hypoplasia. Diagnosis primarily depends on genetic and neuroimaging. Magnetic resonance imaging (MRI) is the gold standard, and it detects the presence of thick cortical cortex, its location, and the layers' architecture. Based on neuroimaging, it is possible to distinguish six subtypes of gyral malformations. Clinical and therapeutic management of these patients is challenging, considering the necessity to face drug-resistant epilepsy, intellectual disability, spasticity, and dysphagia and feeding problems. At the present moment, no gene-specific treatment for LIS is available.
Anomalies of the Mesenchyme (Meninges and Skull)—Defects of Neural Tube Closure: Cephalocele and Other Calvarial and Skull Base Defects; Intracranial Lipomas; Arachnoid Cysts; Nonsyndromic and Syndromic Craniosynostoses
Authors: Carnazzo Salvatore , La Cognata Daria , Zanghì Antonio , Marino Francesco , Palmucci Stefano , Belfiore Giuseppe , Basile Antonio , Vecchio Michele , Di Napoli Claudia , Polizzi Agata , Praticò Andrea D. 
Published: May 2024

AbstractWithin the embryonic head, a layer of mesenchyme envelops the brain beneath the surface ectoderm. This cranial mesenchyme is responsible for the formation of the meninges, the calvaria (upper portion of the skull), and the scalp's dermis. Irregular development of these structures, particularly the meninges and the calvaria, is associated with notable congenital defects in humans, such as defects in neural tube closure. Anencephaly is the most common neural tube defect (NTD) and one of the most severe malformations of the central nervous system; it consists in the complete or partial absence of the brain, associated with the absence of the bones of the cranial vault. Iniencephaly is an uncommon congenital NTD characterized by abnormalities in the occipital region, including rachischisis of the cervicothoracic spine and a fixed retroflexion deformity of the head. Unlike anencephaly, in iniencephaly, there is a skull cavity and a normal-looking skin that entirely covers the head and the medullary retroflex area. Cephaloceles are congenital abnormalities distinguished by the protrusion of meninges and/or brain tissue through a naturally occurring defect in the skull bone. This anomaly is typically covered by skin or mucous membrane. Intracranial lipoma is a relatively uncommon and generally benign tumor that occurs in an abnormal location within the brain; it probably represents a disturbance of the differentiation of the primordial meninges: for unknown causes, the meningeal mesenchyme can differentiate into adipose tissue. Arachnoid cysts are sacs filled with cerebrospinal fluid (CSF) situated between the brain or spinal cord and the arachnoid membrane. Typically, these cysts originate within CSF cisterns and gradually expand their boundaries. Craniosynostosis is the early fusion of one or more cranial sutures. It can occur spontaneously, be associated with a syndrome, or have a familial connection. It can involve one or multiple cranial sutures. Pfeiffer's, Crouzon's, and Apert's syndromes are among the more prevalent syndromic craniosynostoses.
Schizencephaly: Etiopathogenesis, Classification, Therapeutic, and Rehabilitative Approach
Authors: Tosto Monica , Fichera Valeria , Zanghì Antonio , Praticò Andrea D. , Vecchio Michele , Palmucci Stefano , Belfiore Giuseppe , Foti Pietro , Di Napoli Claudia , Polizzi Agata 
Published: May 2024

AbstractSchizencephaly is an uncommon anomaly in neuronal migration characterized by complete clefts that extend from the pia mater to the ependymal surface of the ventricular system. These clefts are encompassed by displaced gray matter and filled with cerebrospinal fluid. Typically, they are found most often in the frontal lobe or the area around the lateral sulcus and can occur on one or both sides. The size, location, and type of these clefts carry significant clinical and prognostic implications. Moreover, they are frequently associated with other central nervous system malformations, including the absence of the septum pellucidum, septo-optic dysplasia, optic nerve hypoplasia, pachygyria, polymicrogyria, cortical dysplasia, heterotopia, and dysplasia of the corpus callosum. Occurrence of schizencephaly is almost always sporadic but its etiopathogenesis is yet to be fully understood. Most likely environmental factors, including exposure to teratogens, viral infections, and maternal factors, operate jointly with genetic defects. To date COL4A1, EMX2, SHH, and SIX3 are the genes identified as possible pathogenetic target. It is interesting to notice that schizencephaly is commonly seen in abandoned or adopted children, as proof of causative effect of intrautero insults. Clinical presentations widely vary and symptoms include a spectrum of cognitive impairment, limb paresis/tetraparesis, and epileptic seizures either with early or late onset; anyway, none of these symptoms is ever-present and patients with schizencephaly can also have normal neurocognitive and motor development. Diagnostic gold standard for schizencephaly is magnetic resonance imaging, which allows to identify and characterize typical clefts. Treatment of schizencephaly is symptomatic and supportive and depends on the severity of morbidity resulting from the malformation. Therapy includes antiepileptic drugs, psychomotor rehabilitation, and in selected cases surgical approach.
Thrombophilia Screening: Not So Straightforward
Authors: Moore Gary W. 
Published: May 2024

AbstractAlthough inherited thrombophilias are lifelong risk factors for a first thrombotic episode, progression to thrombosis is multifactorial and not all individuals with inherited thrombophilia develop thrombosis in their lifetimes. Consequently, indiscriminate screening in patients with idiopathic thrombosis is not recommended, since presence of a thrombophilia does not necessarily predict recurrence or influence management, and testing should be selective. It follows that a decision to undertake laboratory detection of thrombophilia should be aligned with a concerted effort to identify any significant abnormalities, because it will inform patient management. Deficiencies of antithrombin and protein C are rare and usually determined using phenotypic assays assessing biological activities, whereas protein S deficiency (also rare) is commonly detected with antigenic assays for the free form of protein S since available activity assays are considered to lack specificity. In each case, no single phenotypic assay is capable of detecting every deficiency, because the various mutations express different molecular characteristics, rendering thrombophilia screening repertoires employing one assay per potential deficiency, of limited effectiveness. Activated protein C resistance (APCR) is more common than discrete deficiencies of antithrombin, protein C, and protein S and also often detected initially with phenotypic assays; however, some centres perform only genetic analysis for factor V Leiden, as this is responsible for most cases of hereditary APCR, accepting that acquired APCR and rare F5 mutations conferring APCR will go undetected if only factor V Leiden is evaluated. All phenotypic assays have interferences and limitations, which must be factored into decisions about if, and when, to test, and be given consideration in the laboratory during assay performance and interpretation. This review looks in detail at performance and limitations of routine phenotypic thrombophilia assays.
Role of Retrograde Tibiopedal Access in Limb Salvage in Patients with Critical Lower Limb Ischemia
Authors: Ghoneim Baker M. , Elhindawy Khaled M. Abdo , Fouad Fouad S. , Ellil Mostafa H. Abo , Shaker Ahmed A. 
Published: May 2024

AbstractThe aim of this study was to assess the efficacy and safety of retrograde tibiopedal access as an alternative approach in cases of critical limb ischemia (CLI) when antegrade access has failed. A prospective study was conducted that included patients with CLI who underwent tibiopedal access after failed antegrade recanalization from January 2018 to June 2022. Follow-up was conducted at 6, 12, and 24 months. The primary outcomes evaluated were technical success rate and primary patency. Secondary outcomes included complication rate, mortality rate, and limb salvage rate (LSR). Forty-eight patients had CLI and Trans Atlantic Inter-Society Consensus infrainguinal lesions. The retrograde approach was used through the anterior tibial artery in 28 patients (58%), the posterior tibial artery in 18 patients (37.5%), and the peroneal artery in 2 patients (4.5%). Technical success was achieved in 90% of patients (43 patients). There was a significant increase in the anklebrachial index after the procedure with a mean follow-up of 22 months. Twenty-two months primary patency rate was 85.2%, while secondary patency rate was 100% and LSR was 96%, respectively. There was no mortality in the series. Retrograde tibiopedal approach is an alternative option for managing peripheral arterial disease and CLI. This method offers another means of crossing lesions when antegrade access failed, and the intervention can be completed either in an antegrade or retrograde approach. As the retrograde approach does not impact access site, considered a feasible safe treatment alternative which increase the success rate of endovascular treatment.
Obesity-Related Traits Mediate the Effects of Educational Attainment on the Risk of Varicose Veins, Venous Thromboembolism, and Phlebitis
Authors: Du Hong-Cheng , Deng Bai-Yang 
Published: May 2024

Background The extent to which educational attainment (EA) influences the risk of varicose veins (VVs), venous thromboembolism (VTE), and phlebitis occurrence, whether this pathway is mediated by obesity-related traits, and the proportion of their mediation is unknown.
Methods A Mendelian randomization (MR) design was used to genetically investigate the causal effects of EA on the risk of VV, VTE, and phlebitis and to assess the mediating effect of obesity-related traits. Causal effects were estimated using primarily the multiplicative random-effects inverse variance-weighted method. This was supplemented by Cochran's Q-statistic, MR–Egger regression, MR funnel plots, and leave-one-out test to evaluate the reliability of the results. For the individual mediation effect, the coefficient product method was mainly utilized to estimate.
Results An increase in genetically predicted EA was associated with a lower risk of VV, VTE, and phlebitis, as well as lower body mass index, basal metabolic rate, hip circumference, and waist circumference. As genetically predicted body mass index, basal metabolic rate, hip circumference, and waist circumference increased, the risk of developing VV, VTE, and phlebitis increased, respectively. Body mass index, basal metabolic rate, hip circumference, and waist circumference were identified as mediators of the protective effects of EA on VV, VTE, and phlebitis.
Conclusion The findings support a causal relationship between higher EA and lower risk of VV, VTE, and phlebitis. Obesity-related traits play a significant mediating role in these pathways, and there are interactions between them, with hip circumference mediating these pathways relatively independently from the other three.
On the running and the UV limit of Wilsonian renormalization group flows
Authors: László András , Tarcsay Zsigmond 
Published: May 2024

Abstract
In nonperturbative formulation of quantum field theory, the vacuum state is characterized by the Wilsonian renormalization group (RG) flow of Feynman type field correlators. Such a flow is a parametric family of ultraviolet (UV) regularized field correlators, the parameter being the strength of the UV regularization, and the instances with different strength of UV regularizations are linked by the renormalization group equation. Important RG flows are those which reach out to any UV regularization strengths. In this paper it is shown that for these flows a natural, mathematically rigorous generally covariant definition can be given, and that they form a topological vector space which is Hausdorff, locally convex, complete, nuclear, semi-Montel, Schwartz. That is, they form a generalized function space having favorable properties, similar to multivariate distributions. The other theorem proved in the paper is that for Wilsonian RG flows reaching out to all UV regularization strengths, a simple factorization formula holds in case of bosonic fields over flat (affine) spacetime: the flow always originates from a regularization-independent distributional correlator, and its running satisfies an algebraic ansatz. The conjecture is that this factorization theorem should generically hold, which is worth future investigations.