bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical features and mechanisms of the development of cognitive impairment in children with obstructive sleep apnoea syndrome
Authors: Kalashnikova Tatyana P. , Yastrebova Anna V.
Published: January 2025

The article reviews clinical features and mechanisms of the development of cognitive impairment in children with obstructive sleep apnoea/hypopnea syndrome (OSAHS). Short-term and long-term consequences of sleep apnoea along with the pathogenetic similarity of OSAHS and neurodynamic disturbances and concomitant conditions are discussed. The role of ENT conditions in children with OSAHS is reviewed as well. Data on the genetic features that affect the risk of developing OSAHS in children are presented.
Chronic disorders of consciousness: terminology and diagnostic criteria. The results of the first meeting of the Russian Working Group for Chronic Disorders of Consciousness
Authors: Piradov Mikhail A. , Suponeva Natalya A. , Voznyuk Igor A. , Kondratyev Anatoly N. , Shchegolev Alexey V. , Belkin Andrey A. , Zaitsev Oleg S. , Pryanikov Igor V. , Petrova Marina V. , Ivanova Natalia E. , Gnedovskaya Elena V. , Ryabinkina Yulia V. , Sergeev Dmitry V. , Yazeva Elizaveta G. , Legostaeva Liudmila A. , Fufaeva Ekaterina V. , Petrikov Sergey S.
Published: January 2025

Introduction. To date, patients with chronic disorders of consciousness (CDC) represent a serious problem from the medical, social, and economic points of view. Because of the relatively small incidence of this condition, accumulation of the sufficient experience in its diagnosis and treatment remains a complex task, while the lack of a unified approach among Russian specialists to classification of the CDC makes it even harder to solve. At the same time, there are widely used terms overseas that are accepted by the medical community and used in current recommendations.
Aim. Specialists of the Federal State Funded Research Institution, Research Centre of Neurology, have put forward an initiative to create a Russian Working Group for Chronic Disorders of Consciousness, to discuss and approve unified Russian terminology for CDC and criteria for classifying CDC, and to then develop clinical recommendations for the diagnosis and treatment of patients with CDC.
Results. The first roundtable meeting on the issues related to CDC took place at the ХI Russian Congress of Neurologists in June 2019. The attendees included staff members from the FSFRI Research Centre of Neurology, FSFRI Federal Research and Clinical Centre of Intensive Care Medicine and Rehabilitation Medicine, the Polenov Neurosurgical Institute - Branch of the FSFI Almazov National Medical Research Centre, FSFEI HE Ural State Medical University, SFI Saint PetersburgI.I.Dzhanelidze Research InstituteofEmergency Medicine, FSAEI HE Pirogov RussianNationalResearch Medical University, SFHI Research Institute of Emergency Paediatric Surgery and Traumatology of the Moscow Department of Health, and the SFHI N.I. Sklifosovsky Research Institute of Emergency Medicine of the Moscow Department of Health. Based on the results of the meeting and voting, a list of terms was composed to describe CDC and the corresponding diagnostic criteria were approved. The roundtable discussion also included the working groups future plans, and the development of a plan for Russian recommendations for the diagnosis and treatment of the CDC.
Conclusion. The terms and criteria mentioned in the article are recommended for use in clinical practice and research in Russia, for patients with CDC.
The use of a pharmabiotic based on the Lactobacillus fermentum U-21 strain to modulate the neurodegenerative process in an experimental model of Parkinson disease
Authors: Danilenko Valery N. , Stavrovskaya Alla V. , Voronkov Dmitriy N. , Gushchina Anastasiya S. , Marsova Maria V. , Yamshchikova Nina G. , Ol'shansky Аrtyem S. , Ivanov M. V. , Illarioshkin Sergey N.
Published: January 2025

Introduction. Experimental and clinical studies have repeatedly shown the interplay between the intestinal microbiota properties and the nervous system, with a clear link established between changes in microbiota and the development of a neurodegenerative process. It is thought that inflammation and microbiota disturbances provoke the spread of pathological forms of a-synuclein in the nervous system, which is recognized as the main cause of neurodegeneration in Parkinson disease (PD).
Aim of the study: to identify the effect of a pharmabiotic based on a Lactobacillus fermentum U-21 strain in Wistar rats with paraquat-induced parkinsonism.
Materials and methods. Two groups of animals received intra-abdominal paraquat injections (8 doses of 10 mg/kg, every second day for 15 days) and then received orally either a 0.9% NaCl solution, or the U-21 preparation daily for 15 days. The control groups received 0.9% NaCl injections and either a U-21 preparation, or a 0.9% NaCl solution orally under the same regimen. Motor activity was tested in the open field and narrowing beam walking tests. Changes in tyrosine hydroxylase positive enteric plexus fibers and the in quantity of intestinal villi goblet cells were measured morphologically.
Results. Paraquat administration led to a gradual animal death, however, administration of the U-21 increased their survival rate and preserved their motor activity at the level of the control rats. Oral administration of the pharmabiotic only did not alter the animals motor activity. Paraquat reduced density of the tyrosine hydroxylase positive fibers and increased the number of goblet cells, while the study drug partially diminished the changes induced by paraquat.
Conclusion. The U-21 preparation demonstrated high biological activity in the neurotoxin-induced model of PD, which justifies further, extended studies of its effects.
Transcranial Direct Current Stimulation in Poststroke Hemianopia
Authors: Bakulin Ilya S. , Lagoda Dmitry Yu. , Poydasheva Alexandra G. , Kremneva Elena I. , Suponeva Natalia A. , Piradov Mikhail A.
Published: January 2025

Introduction. Development of the new approaches to the rehabilitation of patients with poststroke hemianopia is of great importance, given the high prevalence of that disorder and its negative impact on patients quality of life.
This study aimed to investigate the effect of transcranial direct current stimulation (tDCS) on the quality of life and the quality of visual perception in patients with poststroke hemianopia, as well as to study the safety and tolerability of this technique.
Materials and methods. The study included ten patients with poststroke hemianopia. Patients underwent ten tDCS sessions (2 mA, 20 min with anode placed over Oz, cathode over Cz for a unilateral lesion, and anode over O1 and O2, cathode over Fp1 and Fp2 for bilateral lesions). The tolerability of tDCS was evaluated after each session using a standardized questionnaire. Clinical assessment before and after tDCS was performed using the Visual Function Questionnaire (VFQ-25) and the 36-item Short Form Survey (SF-36). Functional MRI using a visual paradigm was performed in 5 patients before and after the course of tDCS.
Results. Adverse effects were recorded during 9.9% of the sessions and had low severity in most cases. There was one withdrawal from the study because of increased pain in the hand and leg, in a patient with central post-stroke pain syndrome, which was likely unrelated to the biological effects of stimulation. Data of 9 patients were included in the analysis. There was a statistically significant increase in the overall score on the VFQ-25 (p = 0.02) after tDCS with improvements in the social activity (p = 0.02), mental health (p = 0.02), dependence on others (p = 0.04), and peripheral vision (p = 0.04) sections. A statistically significant improvement was also found in the psychological component of quality of life (p = 0.04), vitality (p = 0.03), social functioning (p = 0.02), role functioning due to physical health (p = 0.04), and general health (p = 0.008). In 3 cases, increased activation of the occipital cortex after tDCS was identified using functional MRI with a visual paradigm.
Conclusion. tDCS is a safe, well-tolerated, and potentially effective method in patients with poststroke hemianopia. Larger, controlled, and randomized studies are needed to clarify the efficacy of this method in hemianopia.
Sleep and Wakefulness Disorders in Vascular Cognitive Impairment
Authors: Merkulova Tatyana B. , Kovrov Gennadiy V. , Yakhno Nikolay N.
Published: January 2025

Dementia is a pathology that leads to disability and significantly affects the quality of life of patients and their relatives. The study and development of treatment methods for dementia is a priority in medicine, given the rate of growth in the number of patients. Vascular dementia is the second most common type of dementia in the world after Alzheimer disease. Poor sleep quality is a common feature of the neuropsychiatric profile in dementia patients. Sleep disorders are a modifiable and significant risk factor for cardiovascular disorders, in particular, vascular cognitive impairment. Several sleep disorders are more pronounced in patients with vascular dementia than in patients with dementia due to Alzheimer disease.
This review contains data on changes in the sleep-wake cycle, often found in vascular cognitive impairments. The likely mechanisms connecting sleep disorders and vascular cognitive impairments are described. The possibility of predicting the development of vascular cognitive impairment based on identified sleep disorders is shown, as well as the potential for studying and developing methods to treat sleep disturbances to prevent vascular cognitive impairment are presented.
Clinical and Epidemiological Aspects of Huntington Disease in the Republic of Tatarstan
Authors: Munasipova Sabina E. , Zalyalova Zuleykha A.
Published: January 2025

his study aimed to evaluate the epidemiological features ofHuntington disease (HD), based on data from the Centre for Extrapyramidal Pathology and Botulinum Toxin Therapy of theRepublic ofTatarstan.
Materials and methods. We examined 44 patients with HD (mean age 47.3 12.5 years). The study design included determining and comparing clinical data, genealogical and epidemiological data, and laboratory parameters.
Results. The highest prevalence of HD was found in the north-western and north-eastern parts of theRepublic ofTatarstan being 1.1 per 100,000 people, regardless of nationality. The phenomenon of anticipation in HD inheritance was observed, considering the instability and increasing expansion in subsequent generations along the paternal line. Psychiatric manifestations (apathy, irritability, anxiety, depression) were present in 61.4% of cases at disease onset. One male patient was presumably diagnosed with the Westphal variant. Manifest carriers of a CAG-expansion in the range of 3639 repeats in the mutant gene were found in 15.9% of cases and were predominantly represented by females (85.7%).
Cerebral Pathology in Hepatolenticular Degeneration (Wilson Disease)
Authors: Gulevskaya Tat'yana S. , Chaykovskaya Roxana P. , Anufriev Pavel L.
Published: January 2025

Introduction. Hepatolenticular degeneration (HLD), or Wilson disease, is one of the severe progressive hereditary disorders of the nervous system. A number of questions regarding its pathogenesis and pathology are the subject of in-depth research.
The aim of the study was to examine cerebral pathology and determine the leading factors in its pathogenesis in the autopsy cases of HLD.
Materials and methods. A postmortem study was carried out in 15 deceased patients (1435 years old) with HLD. In all cases, clinical diagnosis was based on the characteristic signs of CNS and liver damage, presence of the KayserFleischer corneal ring, and specific biochemical abnormalities in copper and protein metabolism. A set of histological, neurohistological, and histochemical staining methods was used, including the histochemical study of copper after the fixation of brain slices in rubeanic acid.
Results. In all cases, severe microcirculatory changes were found in the brain, characteristic of the angiotoxic component of HLD, with impaired vessel permeability and the development of persistent edema and spongiform changes in brain tissue. Changes were more often found in the basal nuclei area, as well as in the white matter of the cerebral hemispheres, cerebellum, and pons. The cytotoxic component of HLD was evident in the same regions of the brain, represented by degenerative changes in astrocytes and neurons, often ending in their death. The most frequent form of pathology was the appearance of Alzheimer type II glia with naked nuclei, and much less frequently, Alzheimer type I glia. The histochemical study showed deposits of copper granules in the endothelial cells of microvessels, Alzheimer type II glia, and neurons predominantly in the globus pallidus and the caudate nucleus.
Conclusion. A set of pathogenic factors plays an essential role in the pathogenesis of the brain damage in HLD: the toxic effect of copper on the brain, the damage to and impaired permeability of the blood-brain barrier, severe metabolic disturbances caused by liver failure, and brain hypoxia.
The World Stroke Organization’s Declaration for worldwide primary stroke and dementia prevention
Authors: Brainin Michael , Feigin Valery L , Norrving Bo , Martins Sheila C.O. , Hankey Graeme J. , Hachinski Vladimir
Published: January 2025

Сurrent strategies of primary stroke and cardiovascular disease prevention are aimed at addressing the main risk factors primarily in patients with higher cardiovascular disease risk. Since the number of people with incident stroke and ischaemic heart disease cases is rapidly growing across all countries of the world, this preventive strategy appears to be not sufficiently effective. World Stroke Organization recently (2020) endorsed a different concept of stroke and dementia prevention based on a population-wide approach to dealing with risk factors, which involves all individuals regardless of their cardiovascular disease risk level. This article describes four main primary prevention strategies suggested by the World Stroke Organization to effectively reduce stroke and dementia incidence by 50% and 30% respectively. These strategies include (1) population-wide prevention; (2) polypill therapy; (3) free e-Health application Stroke Riskometer; and active engagement of community health workers.
Bilateral hypertrophic olivary degeneration in genetic neurological disorders
Authors: Suslin Aleksander S. , Seliverstov Yury A. , Kremneva Elena I. , Krotenkova Marina V.
Published: January 2025

Hypertrophic olivary degeneration (HOD) is a rare variant of transsynaptic degeneration in the inferior olivary nuclei due to a lesion within the dentato-rubro- olivary pathway, also known as the GuillainMollaret triangle. Bilateral HOD can be identified on MRI in patients with not only acquired but also genetic neurological disorders. The article describes patients with both common and rare genetic causes of the bilateral HOD. The pathophysiology of HOD is also briefly reviewed.
Magnetic resonance imaging in patients with migraine: the results of unsubstantiated referral
Authors: Pozhidaev Kirill A. , Parfenov Vladimir A.
Published: January 2025

Introduction.Magnetic resonance imaging (MRI) in patients with migraines often reveals structural brain changes of an unclear aetiology. The effect of these changes on the patients management plan requires further investigation.
Theaimof the study was to analyse the management of patients with migraine, in whom structural brain changes were detected on MRI and the validity of MRI referral for migraine.
Materials and methods.We examined 50 patients (8 men and 42 women, average age 41.9 11.9 years) with migraine (mainly chronic) and changes on brain MRI. We compared clinical and MRI data, analysed typical medical practice, and conducted a prospective follow-up of the patients for 6 months, during which preventive therapy was administered.
Results.Most patients (78%) had predominantly white matter damage of the cerebral hypoperfusion type. None of the patients had indications for MRI. Misinterpretation of the changes on MRI led to most patients (86%) being mistakenly diagnosed with another disease (mainly chronic brain ischaemia) and prescribed inappropriate treatment. Six months of patient follow-up showed the effectiveness of preventive migraine therapy, with a reduction in headache frequency from 19.4 2.9 to 12.6 4.4 days per month (p 0.05).
Conclusion. We found unreasonable referrals for brain MRI because of migraine, widespread misinterpretation of MRI changes, and an erroneous diagnosis of cerebrovascular changes as the cause of the migraines.
LYVE-1 expression in the endothelium of newly formed vessels of carotid atherosclerotic plaque
Authors: Evdokimenko Anna N. , Kulichenkova Ksenia N. , Gulevskaya Tatiana S.
Published: January 2025

Introduction.The discovery of specific markers of lymphatic endothelium, including LYVE-1, has led to a much better understanding of the structure and function of the lymphatic system. It has been shown that lymphatic system regulates immune responses, reverse cholesterol transport, and inflammation in atherosclerosis. LYVE-1 plays an important role in activating the function of the lymphatic system and is also one of the first markers of lymphangiogenesis. There are few morphological studies of lymphatic vessels in atherosclerotic plaques, and the obtained data are contradictory.
The aim of the study was to characterize the LYVE-1 receptor expression in the endothelium of newly formed vessels in carotid atherosclerotic plaques and to evaluate its relationship with the plaque structure.
Materials and methods. 34 carotid atherosclerotic plaques obtained during carotid endarterectomies were investigated using histological and immunohistochemical techniques. The density of LYVE-1+ vessels per 1 cm2 of plaque, combined expression of LYVE-1 and CD34, proportion of atheromatosis and calcifications, as well as severity of dust-like calcification, haemorrhage, overall macrophage response (CD68+), and plaque infiltration by M2 macrophage (CD206+) were evaluated.
Results. LYVE-1+ vessels were detected in 32 carotid atherosclerotic plaques, with a range of 5.71698 per 1 cm2 of the plaque (37.4 [15.3; 76]). Marker expression was heterogeneous: it was observed in all or only some endothelial cells of the newly formed vessel, and the expression intensity varied from weak to strong. Both CD34+LYVE-1+ and CD34+LYVE-1 vessel phenotypes were identified. A relationship between endothelial LYVE-1 expression and the structure or type of plaque was not established, except for the macrophage response. The density of LYVE-1+ vessels in atherosclerotic plaques correlated weakly with the overall macrophage response (r = 0.37; p = 0.03), more significantly with the number of anti-inflammatory M2 macrophages (r = 0.47; p = 0.005), especially for vessels with moderate and strong marker expression (r = 0.56; p = 0.0006).
Conclusion. The combined expression of LYVE-1 and CD34 in the endothelium of plaque neovessels was demonstrated for the first time, and a possible association between endothelial LYVE-1 expression in newly formed vessels and the reparative processes in atherosclerotic plaques was shown.
Rehabilitation of elderly patients at risk of falling: the value of psychophysiological parameters and cognitive-motor training using virtual reality
Authors: Klochkov Anton S. , Khizhnikova Anastasia E. , Fuks Anna A. , Kotov-Smolenskiy Artem M. , Suponeva Natalia A. , Piradov Mikhail A.
Published: January 2025

Due to the slowing of the neurodynamic and cognitive processes, as well as changes in the musculoskeletal system that accompany aging, attention, reaction, and movement coordination are impaired in elderly patients. Decreased overall brain adaptability leads to an increased risk of falls and disability, thus reducing the age of active aging. According to the World Health Organization, 37.3 million falls occur annually that are not fatal but have serious consequences requiring medical attention. These falls are most common among people over the age of 65 years. An objective assessment of psychophysiological characteristics identified a correlation between the duration of simple and complex reactions and the risk of falls and served as a tool for evaluating the effectiveness of balance retraining. Studies have shown that cognitive-motor training improves postural stability and functional performance in daily life. This type of training is widely used to rehabilitate patients with balance disorders, and virtual reality systems are increasingly being used in its implementation. There is a theory that the virtual environment can improve responses to rapid environmental changes, as well as modulate various characteristics of attention, spatiotemporal memory, and planning, which favorably affects postural function. This review describes the changes in psychophysiological parameters in the elderly, as well as balance retraining techniques using cognitive-motor training, including the use of virtual reality technology.
The diagnostic significance of neurofilament heavy chains in cerebrospinal fluid in amyotrophic lateral sclerosis
Authors: Vladykina Anastasia V. , Nazarov Vladimir D. , Krasnov Vladimir S. , Koroleva Ekaterina I. , Fedorova Polina A. , Moshnikova Anna N. , Mazing Aleksandra V. , Lapin Sergey V. , Emanuel Vladimir L. , Rudenko Dmitriy I. , Stuchevskaya Fatima R. , Zatakovenko Sergey M. , Pavlova Tatyana A. , Alekseeva Tatyana M. , Goldobin Vitaliy V.
Published: January 2025

Introduction. Early diagnosis of amyotrophic lateral sclerosis (ALS) is difficult because of the low sensitivity of clinical criteria at the early stages of the disease and the lack of reliable laboratory biomarkers. Neuron destruction leads to the release of excessively accumulated phosphorylated neurofilament heavy chains(pNFH) in the cerebrospinal fluid (CSF) and may potentially be used for early diagnosis of ALS. In addition, pNFH may have predictive significance.
Aim. To investigate the clinical significance of elevated neurofilament heavy chain levels in the CSF in ALS.
Materials and methods. The study included 33 patients with ALS diagnosed using the El Escorial criteria, 30 patients in the control group (post phlebectomy), as well as 28 patients in the comparison group: 16 patients with multiple sclerosis, 5 with autoimmune encephalitis, 1 with tick-borne encephalitis, 2 with primary lateral sclerosis, 1 with progressive muscle atrophy and 3 with other conditions (restless leg syndrome, compressive myelopathy and paraneoplastic cerebellar degeneration). All patients underwent a lumbar puncture, with pNFH levels measured using ELISA.
Results. A statistically significant difference in pNFH concentration was found between ALS patients and patients in the comparison group (p 0.0001). At a threshold pNFH level, which was taken to be 0.785 ng/ml, the test sensitivity and specificity were 94% and 86%, respectively. Elevated pNFH levels in the CSF of patients with confirmed ALS were found in 94% of cases, compared with only 14% of patients in the comparison group. A statistically significant difference in pNFH concentration was found between the group with ALS and the control group (p 0.0001). A negative correlation was found between pNFH level in the CSF and disease duration (r = 0.5172; p = 0.0029). A positive correlation was also found between the speed of disease progression and pNFH concentration (r = 0.5480; p = 0.001).
Conclusion. The results of this study demonstrate the high clinical significance of pNFH in the CSF in ALS.
The effect of reactive Bergmann glia on short-term synaptic plasticity in cerebellar neurodegenerative models, caused by chronic activation of ChR2 and expression of the mutant ataxin-1
Authors: Shuvaev Аnton N. , Belozor Оlga S. , Mozjei Oleg I. , Yakovleva Daria A. , Shuvaev Аndrey N. , Smolnikova Marina V. , Pozhilenkova Еlena A. , Каsparov S. . , Salmin Vladimir V. , Salmina Аlla B.
Published: January 2025

Introduction. Synaptic plasticity is impaired in the early stages of a neurodegenerative process but is potentially reversible. The study of mechanisms associated with synaptic plasticity in neurodegenerative cerebellar conditions has enabled the search for potential therapeutic agents.
This study aimed to investigate the effect of the astrocytic link on paired-pulse facilitation (PPF) in cerebellar cortical synapses of mice, using a set of immunohistochemical, optogenetic, and electrophysiological analysis methods.
Materials and methods. Experiments were conducted on 12-week-old CD-1 mice. The model of murine cerebellar astrogliosis was created using chronic activation of light-sensitive ChR2 channels in Bergmann glia and after they expressed the mutant ataxin-1. To model astrocyte-mediated neurodegeneration, these mice were intracortically administered AVV GFAP-ChR2-mKate vector constructions with subsequent chronic 4-day light stimulation in vivo and LVV GFAP-ATXN1[Q85]-Flag without light stimulation. Mice in the control group were administered normal saline or LVV GFAP-ATXN1[Q2]-Flag. Changes in the PFF-excitatory postsynaptic currents in Purkinje cells were registered using the patch-clamp technique. Immunohistochemistry was used to examine anti-GFAP, mKate, and anti-ataxin-1 expression in the cerebellar cortex.
Results. For the reactive glia in the cerebellar cortex after chronic photostimulation, increased anti-GFAP immune reactivity and morphology changes in the form of process tortuosity were common. In Purkinje cell synapses with parallel fibers in these animals, the PPF coefficient was significantly increased because of impaired glutamate reuptake and presynaptic overexcitation with this neuromediator. However, photoactivation of reactive Bergmann glia led to a sharp slowing down of the glutamate-glutamine cycle and glutamate pool depletion in the presynapse, with a subsequent gradual reduction in the PPF coefficient. Such pathological mechanisms were found in the neurodegenerative model with selective damage to Bergmann glia by the mutant ataxin-1.
Conclusion. Astrocytes affect short-term synaptic plasticity such as PPF. In cerebellar astrogliosis, the PPF disturbance is multilevel: the high baseline level of PPF is significantly reduced after Bergmann glial activation, which is related to impaired glutamate reuptake by reactive glial cells.
The pharmacogenomics of lamotrigine (a literature review)
Authors: Azhigova Asya M. , Broutian Amayak G. , Vlasov Pavel N.
Published: January 2025

Pharmacogenomics aims to optimize drug therapy with respect to genetic variations in various human genes, whose products affect drug pharmacokinetics and pharmacodynamics. Among neurological diseases, selecting effective drug therapy is especially important in epilepsy since recurrent epileptic seizures can lead to persistent epileptic brain activity and patient traumatization.
Lamotrigine is a new generation broad-spectrum antiepileptic drug and is recommended as the drug of choice in focal and generalized epilepsy. By genotyping single-nucleotide polymorphisms (SNPs) associated with decreased or increased lamotrigine blood concentration, predicting the drug dose that will achieve the therapeutic serum concentration is possible. Selecting an appropriate individual drug dose avoids the development of dose-dependent side effects, which occur when the serum drug concentration is exceeded and drug discontinuation due to a lack of the expected effect because of insufficient blood levels.
This review presents the results of studies of the polymorphism in genes that directly or indirectly alter lamotrigine serum levels. These include genes that encode the UGT enzymes, responsible for the conjugation and elimination of lamotrigine from the body; genes that encode transport proteins (P-glycoprotein, organic cation transporter, multidrug resistance protein, and breast cancer resistance protein); genes that encode the transcription factors HNF4 and pregnane X receptor, which regulate the expression of several liver transport proteins and enzymes. The reviewed data demonstrate the relationship between polymorphisms in these genes and changes in lamotrigine concentration.
Highly Z-selective Julia–Kocienski Olefination Using N-sulfonylimines and Its Mechanistic Insights from DFT Calculations
Authors: Chizaki Takuma , Fujiwara Koichi , Fujimoto Junko , Narumi Tetsuo , Shuto Satoshi , Watanabe Mizuki
Published: January 2025

The Julia–Kocienski (JK) olefination is a powerful and widely used method for alkene synthesis, particularly favoring E-selective olefination. However, highly Z-selective variants remain underexplored. In this study, we report a highly Z-selective JK olefination (Z ratio >99:1) using N-sulfonylimines as electrophilic partners instead of traditional aldehydes. This approach exhibits broad substrate compatibility, accommodating a variety of sulfones and N-sulfonylimines with functional groups such as electron-donating and electron-withdrawing substituents, amides, halogens, carboxylic acids, and hydroxyls. The reaction enables efficient synthesis of valuable Z-alkenes, including (Z)-α,β-unsaturated amides, Z-alkenyl halides, and Z-trisubstituted alkenes, under mild and general conditions. Mechanistic investigations using DFT calculations revealed that Z-selectivity is established during the 1,2-addition step, contrasting with conventional Z-selective JK olefination, where the Smiles rearrangement step governs selectivity. This study not only expands the synthetic arsenal for stereoselective olefin synthesis but also provides a versatile and general method for constructing Z-olefins with high precision and efficiency.
DiffractGPT: Atomic Structure Determination from X-ray Diffraction Patterns using Generative Pre-trained Transformer
Authors: Choudhary Kamal
Published: January 2025

Crystal structure determination from powder diffraction patterns is a complex challenge in materials science, often requiring extensive expertise and computational resources. This study introduces DiffractGPT, a generative pre-trained transformer model designed to predict atomic structures directly from X-ray diffraction (XRD) patterns. By capturing the intricate relationships between diffraction patterns and crystal structures, DiffractGPT enables fast and accurate inverse design. Trained on thousands of atomic structures and their simulated XRD patterns from the JARVIS-DFT dataset, we evaluate the model across three scenarios: (1) without chemical information, (2) with a list of elements, and (3) with an explicit chemical formula. The results demonstrate that incorporating chemical information significantly enhances prediction accuracy. Additionally, the training process is straightforward and fast, bridging gaps between computational, data science, and experimental communities. This work represents a significant advancement in automating crystal structure determination, offering a robust tool for data-driven materials discovery and design.
Machine Learning Reveals Amine Type in Polymer Micelles Determines mRNA Binding, In Vitro, and In Vivo Performance for Lung-Selective Delivery
Authors: Panda Sidharth , Eaton Ella , Muralikrishnan Praveen , Stelljes Erin , Seelig Davis , Leyden Michael , Gilkey Alexandria , Barnes Jackson , Morrissey David , Sarupria Sapna , Moriarity Branden , Reineke Theresa
Published: January 2025

Cationic micelles, composed of amphiphilic block copolymers with polycationic coronas, offer a customizable platform for mRNA delivery. Here, we present a library of 30 cationic micelle nanoparticles (MNPs) formulated from diblock copolymers with reactive poly(pentafluorophenol acrylate) backbones modified with a diverse set of amines. This library systematically varies in nitrogen-based cationic functionalities, exhibiting a spectrum of properties that encompass varied degrees of alkyl substitution (A1-A5), piperazine (A6), oligoamine (A7), guanidinium (A8), hydroxylation (A9-A10) that vary in sidechain volume, substitution pattern, hydrophilicity, and pKa to assess parameter impact on mRNA delivery. In vitro delivery assays using GFP+ mRNA across multiple cell lines reveal that amine sidechain bulk and chemical structure critically affect performance. Using machine learning analysis via SHapley Additive exPlanations (SHAP) on 3,780 experimental data points, we mapped key relationships between amine chemistry and performance metrics, finding that amine-specific binding efficiency was a major determinant of mRNA delivery efficacy, cell viability, and GFP intensity. Micelles with stronger mRNA binding capabilities (A1 and A7) have higher cellular delivery performance, whereas those with intermediate binding tendencies deliver a higher amount of functional mRNA per cell (A2 and A10). This indicates that balancing the binding strength is crucial for performance. Micelles with hydrophobic and bulky pendant groups (A3, A4, and A5) tend to induce necrosis during cellular delivery, highlighting the significance of chemical optimization. A cationic amphiphile identified as A7 displaying a primary and secondary amine, consistently demonstrates the highest GFP expression across various cell types and in vivo achieving high delivery specificity to lung tissue upon intravenous administration. Moreover, we established a strong correlation between in vitro and in vivo performance using Multitask Gaussian Process models, linking amine properties directly to both delivery efficacy and biodistribution. This correlation underscores the predictive power of in vitro models for anticipating in vivo outcomes and highlights chemical amine-dependent optimization as crucial for advancing mRNA delivery vehicle development. Overall, this innovative study integrates advanced data science with experimental design demonstrating the pivotal role of chemical amine identity for targeted mRNA delivery to the lungs.
Surface Induced Unfolding Reveals Unique Structural Features and Enhances Machine Learning Classification Models
Authors: Matney Rowan , Gadkari Varun
Published: January 2025

Native ion mobility-mass spectrometry combined with collision-induced unfolding (CIU) is a powerful analytical method for protein characterization, offering insights into structural stability, and enabling the differentiation of analytes of similar mass and mobility. A surface induced dissociation (SID) device was recently commercialized, enabling broader adoption of SID measurements and surface induced folding (SIU). This study evaluates SIU, benchmarking its reproducibility and performance against CIU on a Waters CyclicIMS ion mobility-mass spectrometer. Reproducibility studies were conducted on model proteins, including β-lactoglobulin (β-lac), bovine serum albumin (BSA), and immunoglobulin G1 kappa (IgG1κ). SIU and CIU exhibited comparable reproducibility, with root-mean-square deviation (RMSD) values averaging less than 4% across multiple charge states. Notably, SIU achieved unfolding transitions at lower activation thresholds, enhancing sensitivity to subtle structural differences and providing additional analytical information content such as unique high arrival time unfolding features and additional unfolding transitions. Furthermore, the differentiation of closely related protein subclasses, such as IgG1κ and IgG4κ, was improved with SIU, as evidenced by the f enhancement of supervised machine learning models for IgG subclass classifications. SIU-trained models outperformed or matched CIU-trained models, achieving high cross-validation accuracies (>90%) and robust classifications of biotherapeutics Adalimumab and Nivolumab. This work establishes SIU as a complementary and efficient alternative to CIU, offering improved sensitivity, and analytical depth without loss in reproducibility. This work highlights the benefits of including SIU in protein characterization workflows, particularly in high-throughput and machine learning-guided applications.
Synthesis, characterisation, in silico & in vitro anti-cholinesterase activity of some novel 2 amino 5-substituted oxadiazoles
Authors: Suchitra M. , Kiranmai A. , Deepika P. , Joshna K.
Published: January 2025

An individual with Alzheimer's disease (AD) experiences cognitive decline, memory loss, and behavioral abnormalities. The complex condition known as AD is brought on by acetylcholinesterase (AChE), which breaks down acetylcholine. The current investigation aimed to evaluate synthetic AChE inhibitors that may be utilized to treat AD. To do this, synthetic two amino five substituted oxadiazole derivative compounds (1a-5e) were assessed and shown to be potential AChE inhibitors, with IC50 values ranging from 73 ± 0.67 to 98 ± 0.7 µmol/min/mg of tissue. In silico docking investigations were performed using Schrodinger, revealing that most of the compounds are held together by ?–? and hydrogen bonding and interact with the anionic subsite of AChE. Chem Bio Draw Ultra 12.0 (www.cambridgesoft.com) was used to create the 2D structures of each drug. 2. The RSC PDB (www.rscb.org) provided the crystallographic three-dimensional structure of AChE target receptors, with PDB ID: 4EY5 &604 w for AChE. The most potent compound is 5e; consequently, these compounds can potentially be used as therapeutic agents to treat AD and its related conditions because of their AChE inhibitory capacity cytotoxicity safe profile.
Os últimos 10 anos da Direção Executiva Nacional dos Estudantes de Medicina na defesa da Extensão Universitária Popular
Authors: Caetano George Luiz Neris , Oliveira Bruna Bau Segarra Garcia de , Pena Lorena Sampaio , Machado Bárbara Novais Prado , Broche Juan Sodré , Alcântara Laianne Barros Martins de
Published: January 2025

A Direção Executiva Nacional dos Estudantes de Medicina (DENEM), fundada em 1986, é a entidade máxima de representação estudantil de medicina no Brasil, cumprindo uma agenda político-social intensa. Dentre as suas pautas está a participação popular na produção de conhecimento científico e no desenho de um projeto de educação médica que dialogue com o Movimento por uma Universidade Popular (MUP), compreendendo a extensão popular como resposta à exigência de carga-horária de extensão universitária. Pretende-se sistematizar os últimos 10 anos de atuação da Coordenação de Extensão Universitária da DENEM, revelando os acúmulos teórico e práticos do Movimento Estudantil de Medicina para a obrigatoriedade da extensão universitária. A partir de metodologias próprias, a DENEM protagoniza a inclusão de pautas sociais e populares na educação médica, criando um modelo horizontal de participação social-popular na interação universidade-comunidade, em defesa da classe trabalhadora e no combate à mercantilização da educação em saúde. A proposta central do debate é refletir sobre as soluções que os próprios estudantes estão criando em parceria com os movimentos sociais e sobre as possibilidades de pensar, a partir da extensão popular, uma educação médica libertadora e formadora de uma sociedade mais justa e igual para todos.
Desdobramentos de atividades voltadas para a formação de leitores numa escola da educação básica do Distrito Federal por meio de um projeto de extensão
Authors: Moreira Lucas , Pedroza Marya Eduarda Mendonça , Moreira  Luciene Viana Guedes
Published: January 2025

Neste trabalho, são descritas as principais atividades promovidas durante o período de execução do projeto de extensão Leitureiros ao longo do ano de 2022. Estas iniciativas têm como objetivo principal promover vivências dialógicas e construtivas numa escola da Educação Básica do Distrito Federal. Principalmente, por meio da leitura coletiva de trechos de livros, explorando as várias interpretações que um texto pode oferecer. Os encontros promovidos ocorreram no formato de roda de leitura nas modalidades remota (síncrono) e presencial. Nas semanas que antecediam os eventos, a equipe do projeto promovia atividades formativas na comunidade escolar, no contexto da obra que seria abordada, em conformidade com as componentes curriculares correspondentes. Nesse sentido, a temática do texto selecionado era abordada nas aulas de Língua Portuguesa e Projeto Disciplinar 1 (PD1). A contextualização histórica do autor e da obra foram tratadas nas aulas de História e Geografia. O estímulo à confecção de painéis nas aulas de Artes. Com isso, uma grande parcela dos participantes das atividades formais de discussão coletiva de textos já estava bem apropriada da temática da ação realizada, o que enriquecia ainda mais estes momentos de trocas de saberes. Durante os eventos, os textos são apresentados de maneira a contextualizar a obra e autor. A leitura do texto é realizada de modo exploratório e lúdico, comtemplando as ações desenvolvidas no ambiente escolar. Pode-se evidenciar que as ações de extensão desenvolvidas durante a execução do projeto Leitureiros contribuíram, significativamente, para a obtenção de novos conhecimentos pelos integrantes. Consolidando a leitura coletiva como um campo reflexivo, formativo, afetivo e inclusivo nesta comunidade escolar.
De “Potencialidades dos 50+” a “Espaço Criativo das Poderosas”: Relato de Experiência sobre a inserção da Extensão em um CRAS
Authors: Moreno Ana Laura Pereira , Duarte Hítalo de Souza , Pinto Mariana da Cruz , Costa Pedro Henrique Antunes da , Diniz Silvia Beatriz Moreno , Machado Tainá Victoria
Published: January 2025

A experiência extensionista é imprescindível para a formação de universitários, sendo importante ação para contextualizar os conhecimentos trabalhados na universidade mediante a vivência na realidade cotidiana, inserindo a prática dos futuros profissionais em um contexto real e permitindo trocas de saberes desses com a comunidade. Nesse sentido, o projeto de extensão "Potencialidades 50+" é um esforço de fomento à saúde e ao bem-estar social para indivíduos com mais de 50 anos, residentes no Riacho Fundo 2, Distrito Federal. Realizado em parceria com o Centro de Referência da Assistência Social (CRAS) local, o projeto é construído por estudantes extensionistas de Psicologia da Universidade de Brasília (UnB) com apoio e supervisão docente. O projeto inclui oficinas práticas e eventos sociais, e tem por objetivo suscitar rodas de conversa e incentivo à comunidade na construção de laços com seus pares, além do fortalecimento das potencialidades individuais e do grupo. Os estudantes desempenham papel ativo na organização e execução das atividades, aprendendo a lidar com desafios e colaborando com profissionais de diferentes áreas, características essenciais para a prática condizente com a realidade. Como resultado, o projeto fortalece o envolvimento dos estudantes com a comunidade, permitindo o rompimento de uma lógica de hierarquia de saberes, preparando-os para futuras potencialidades e adversidades na área e destacando a importância da colaboração interdisciplinar e de políticas públicas.
Atividades extensionistas de conscientização ambiental e uso racional de energia: Projeto Catavento
Authors: Soares Paula Meyer , Avila Suzana Moreira , Shzu Maura Angélica Milfont , Carneiro Sérgio Henrique da Silva , Morais Marcus Vinicius Girao de
Published: January 2025

RESUMO: O aquecimento global e as emissões de gases de efeito estufa (GEE) têm sido um tema central de debate na agenda internacional das nações. O setor energético é um dos que mais emitem esses gases, daí a importância de se repensar e discutir as formas de uso e consumo dos insumos energéticos dentro dessa nova realidade. O Projeto Catavento é uma iniciativa extensionista da Universidade de Brasília, Faculdade do Gama-FGA, coordenada pela Profa. Paula Meyer, envolvendo alunos do curso de graduação em Engenharia de Energia e alunos do ensino médio da escola CEM 404 de Santa Maria-DF. Este artigo tem o objetivo de apresentar algumas das atividades extensionistas desenvolvidas no projeto Catavento no que tange a conscientização acerca do consumo e da produção sustentável de energia na atualidade. A apresentação das atividades e dinâmicas utilizadas pelo Projeto Catavento e seus resultados é salutar em um momento em que a transição energética e aquecimento global estão no centro da discussão atual na agenda internacional. O artigo apresenta essas atividades extensionistas desenvolvidas em conjunto com os alunos da escola CEM de Santa Maria -DF.O Projeto Catavento fará 10 anos em 2025 tendo acumulado experiências didáticas e desafios com o intuito de disseminar e conscientizar a comunidade acerca da importância em preservar tais recursos para que possamos garantir a sobrevivência e o futuro das demais gerações.
Construindo Pontes: Mulheres na Ciência disseminam a Universidade e a Ciência em Escolas Públicas do Distrito Federal através de visitas e gravação de Podcasts
Authors: Guarnieri Patrícia , Gomes Vanessa Cabral , Ferro Mariana Benchimol , Araujo Wanessa de Carvalho
Published: January 2025

Muito se tem produzido no âmbito das universidades inquestionavelmente, no entanto é importante se perguntar para quem chega esse conhecimento. Dessa forma iniciativas de disseminação científica e aproximação com a sociedade são necessárias a fim de tornar as universidades parte do cotidiano destas pessoas. Nesse sentido, o projeto teve como objetivo principal disseminar o papel e as pesquisas da universidade de forma a despertar o interesse e desejo dos estudantes, desde o ensino fundamental, para o ingresso na universidade pública por meio de visitas e podcast. A fim de atingir esse objetivo foi realizada uma pesquisa ação, na qual estudantes e professoras da Universidade de Brasília visitavam a escola Classe 01 do Guará, escola pública do Governo do Distrito Federal, de ensino fundamental a fim de disseminar o papel e pesquisas da universidade, de forma lúdica, por meio de brincadeiras, contação de história, teatro, visitas à universidade e gravação de podcasts. As atividades ocorreram no âmbito do projeto: Disseminando a ciência por meio de um podcast de meninas e mulheres em escolas do Governo do Distrito Federal. Com base nessa metodologia, foram realizadas 6 visitas à escola pela equipe, sendo uma delas a participação de um evento com as famílias dos alunos, que tinham de 6 a 12 anos, estudantes do 1º ao 5º ano do ensino fundamental. Também foi realizada uma visita de 280 estudantes na UnB, para conhecer projetos como o LabMat, Experimentoteca, Museu de Geociências e Memorial Darcy Ribeiro, na ocasião os estudantes tiveram contato com um aluno indígena que expôs seus costumes, cantos, danças e história, bem como com outros alunos da UnB de diversos cursos. Também foram gravados episódios para o quadro ‘Pergunte para um cientista’ do Podcast ‘Eu quero saber’ (@euquerosaberpodcast no Instagram). Constata-se que o projeto cumpriu o objetivo proposto e obteve resultados positivos em termos de interação, aceitação por parte das famílias e equipe da escola e engajamento das crianças envolvidas, além de aprendizado para a equipe da universidade formada por 6 alunas de graduação e 2 professoras coordenadoras, contribuindo para a popularização do papel, pesquisas e atividades da universidade, de forma a permitir o amplo acesso da sociedade.