bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anxiety and sleep disorders
Authors: Ebzeeva E. Yu. , Polyakova O. A. 
Published: July 2022

Anxiety disorders are widespread among patients of primary care physicians and are the cause of increased morbidity and access to healthcare. Anxiety is a reaction of the body to the effects of stress and is manifested by the development of psychovegetative syndrome. In the general population, 5 to 7% of people have clinically significant anxiety, and in the practice of primary care physicians, these disorders are detected in every fourth patient. Anxiety disorder contributes to the development of psychogenic somatic pathology and/or negatively affects the course of background disease. Most patients with anxiety disorders suffer from various sleep disorders. In general practice, the frequency of sleep disorders reaches 73%. Chronic sleep disorder can act as a stressor that contributes to the development of pathophysiological changes in the body and increases anxiety. The above determines the need for early detection of sleep disorders and its timely treatment. The current treatment strategy for patients with sleep disorders involves an individualized approach to insomnia therapy. The existing arsenal of drugs used to treat sleep disorders allows this principle to be applied taking into account concomitant diseases (including anxiety disorders). The choice of product is also determined by good tolerability, efficacy and high safety profile. The optimal drug that answers the above requirements is doxylamine succinate, which allows you to effectively stop both anxiety symptoms and sleep disorders. Due to its high safety profile, doxylamine succinate can be used in the treatment of insomnia in pregnant women. The release form determines the convenience of use and the possibility of selecting an individual dose of the drug.
Association between marital status and age dynamics of cognitive functions in ageing in a Russian population sample
Authors: Titarenko A. V. , Shishkin S. V. , Shcherbakova L. V. , Verevkin E. G. , Hubacek J. A. , Bobak M. , Malyutina S. K. 
Published: July 2022

Introduction. The identification of risk factors for cognitive decline during ageing is of great importance for prevention of dementia. Being married or cohabited is considered a protective factor for health. The impact of marital status on age-related decrease of cognitive functions (CF) is understudied.The aim of the study was to investigate the relationship between the indicators of CF and marital status in a cross-sectional analysis and in 2 serial measurements over 9 years in a population sample of middle to older age in Russia.Materials and methods. The study was based on a random population sample of men and women aged 45–69 years old examined at baseline in 2003–2005 in Novosibirsk (n = 9360, HAPIEE project). Present analysis included a subsample of persons with repeated serial measurements – 3153 people. The average follow-up period was 9.2 (SD = 0.7) years. CF was assessed using standard validated methods, including immediate and delayed recall of 10 words, semantic verbal fluency and letter cancellation test. Marital status was determined by standardized questionnaires, groups of single and married/cohabiting participants were identified.Results. In studied population sample (n = 3153, 62% of women), the mean age of participants at baseline examination was 60.3 ± 6.8 years old, and at follow-up examination – 69.5 ± 6.9 years old. During the 9-year follow-up, a significant negative dynamics of the studied cognitive domains (p < 0.001) was revealed in single for both sexes. In multivariable-adjusted models, the rate of CF regress per year did not differ by marital status in both sexes, except for increased rate of decline in semantic verbal fluency in women, partly it was explained by high baseline level. Married or cohabiting women had faster rate of decline in this indicator (p = 0.007) compared with single, regardless of age and other risk factors.Conclusion. The findings obtained in this population sample in Novosibirsk support a potential protective effect of marriage or cohabitation on CF preservation during ageing.
Joint pathology in musculoskeletal lumbar pain: a dialogue between a neurologist and a rheumatologist
Authors: Editorial Article 
Published: July 2022

Skeletal-muscular (nonspecific) lumbar pain (lumbodynia), often with spread to the leg (lumboishialgia), is one of the most common causes of consultations with a physician and temporary disability in the population. In many cases, the development of pain is associated with lesions of the lumbar facet joints (LFJ) and sacroiliac joint (SI). What are the causes, clinical features, and diagnosis of lumbar pain caused by lesions of the LFJ and SI? What should be the medical tactics for lumbar pain caused by LFJ and SI lesions? What is the actual practice of treating such patients? Leading experts discuss the problem of managing patients with lumbar musculoskeletal pain:Parfenov Vladimir Anatolievich – Dr. Sci. (Med.), Professor, Neurologist, Head of the Department of Nervous Diseases and Neurosurgery, Sklifosovskiy Institute of Clinical Medicine? First Moscow State Medical University (Sechenov University)Karateev Andrey Evgenyevich – Dr. Sci. (Med.), Head of the Laboratory of Pathophysiology of Pain and Clinical Polymorphism of Musculoskeletal Diseases Nasonova Research Institute of Rheumatology.
Evaluation Criteria and Algorithm for Calculating the Environmental Quality Index of Rural Areas
Authors: Lavrentieva I. V. , Javakhia V. V. , Sedova N. V. 
Published: July 2022

In the context of the implementation of the state program for the integrated development of rural areas, the issue of assessing the quality of the environment of rural areas remains particularly relevant in order to determine priority areas of development and allocation of budget funds. Until now, there was no such methodology, at the same time there was a methodology for assessing the quality of the urban environment, which is not applicable in rural territories, since it does not take into account the specifics of their development. The article presents a methodology for calculating the quality of rural areas. The authors emphasize in their research the relevance of the development of this methodology, as it will allow to assess the quality of rural areas and on its basis to propose directions for improving the policy of state regulation within the framework of existing regulatory legal acts. The authors identified the key areas of rural environment development, 11 assessment groups and the assessment is carried out by 30 indicators for each object of assessment. A point system has been developed for the transition from absolute values of indicators by indicators to a single calculation system. As part of the assessment, integral indices are also formed that allow assessing the quality of the environment at the level of the whole country, individual regions, municipalities and settlements. At each level of assessment, it is possible to identify key areas of improvement, work in which will ensure maximum effect for the growth of the quality of the rural environment at various levels of management.
Characterization of Pili Protein 67 kDa Streptococcus pneumoniae: New
Candidate for Virulence Factor-Based Pneumococcal Antigen Vaccine
Authors: Mufida Diana C. , Perwitasari Rahma , Agustina Dini , Shodikin Muhammad A. , Suswati Enny 
Published: July 2022

Introduction:
Streptococcus pneumoniae is a Gram-positive diplococci bacteria that cause infectious diseases such as otitis, meningitis, and pneumonia. Streptococcus pneumoniae has various virulence factors, one of which is pilus. In addition to being immunogenic, pilus S. pneumoniae also plays a role in bacterial adhesion to host cells and biofilm formation. The S. pneumoniae pilus found in this study consisted of several proteins with various molecular weights, one of which was a 67 kDa protein. Objective: This study aimed to determine the characteristics of the 67 kDa pilus protein, including Its ability as hemagglutinin and adhesin and its amino acid composition (AA).

Methods:
The LCMS/MS method is used to determine the AA composition of the 67 kDa pilus protein. The AA structure was analyzed through BLASTP by matching it with the sequence of the protein data bank of S. pneumoniae (taxid: 1313). The Protparam tool from ExPASy is used to calculate various physical and chemical parameters of the protein, while for evaluating its immunogenicity, it uses the VaxiJen V2.0 online server.

Results:
The results of this study indicate that the 67 kDa pilus protein is an anti-hemagglutinin protein and has a role as an adhesin protein. Adhesion tests show the action between protein concentration and the number of bacteria attached to enterocyte cells. LCMS/MS test results continued by BLASTP showed that the 67 kDa pilus protein had three AA sequences (ITYMSPDFAAPTLAGLDDATK, AEFVEVTK, and LVVSTQTALA), which had similarities with the A backbone chain of S. pneumoniae pilus. The physicochemical test shows that the protein is hydrophilic and nonpolar, while the antigenicity test shows that the protein is antigenic.

Conclusion:
Based on these characteristics, it can be concluded that the 67 kDa S. pneumoniae pilus protein can be used as a vaccine candidate for pneumococcus.
Mesenchymal Stem Cell Therapy for ALI/ARDS: Therapeutic Potential and
Challenges
Authors: Wang Zhenxing , Yu Tong , Hou Yapeng , Zhou Wei , Ding Yan , Nie Hongguang 
Published: July 2022

Abstract:
Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a serious clinical common disease, which may be caused by a variety of pathological factors and can induce a series of serious complications. There is still no specific and effective method for the treatment of ALI/ARDS. Mesenchymal stem cells (MSCs) have been one of the treatment methods for ALI, which can regulate related signal pathways such as PI3K/AKT, Wnt, and NF-κB to reduce inflammation. MSCs exist in a variety of tissues and have the ability of self-renewal and differentiation, which can be activated by specific substances or environments and home to the site of tissue damage, where they differentiate into new tissue cells and repair the damage. Both exosomes and cytokines involving the paracrine mechanism of MSCs have benefits on the treatment of ALI. Lung organoids produced by 3D culture technology can simulate the characteristics of the lung and help to research the pathophysiological process of ALI. This review summarizes the mechanisms by which MSCs treat ALI/ARDS and expects to use 3D models for future challenges in this field.
U-Shaped Association Between Serum Uric Acid and Hemorrhagic Transformation
After Intravenous Thrombolysis
Authors: Chen Hongfang , Han Zhao , Cheng Zicheng , Zhan Zhenxiang , Fu Yaming , Zhang Wen Yuan , Xia Lingfan , Xu Tong 
Published: July 2022

Background:
Uric acid (UA) has both antioxidative and pro-oxidative properties. The
study aimed to investigate the relationship between serum UA and hemorrhagic transformation (HT)
after intravenous thrombolysis in patients with acute ischemic stroke.

Methods:
The patients undergoing intravenous thrombolysis from two hospitals in China were retrospectively
analyzed. HT was evaluated using computed tomography images reviewed within 24-
36h after thrombolysis. Symptomatic intracranial hemorrhage (sICH) was defined as HT accompanied
by worsening neurological function. Multivariate logistic regression and spline regression
models were performed to explore the relationship between serum UA levels and the risk of HT and
sICH.

Results:
Among 503 included patients, 60 (11.9%) were diagnosed with HT and 22 (4.4%) developed
sICH. Patients with HT had significant lower serum UA levels than those without HT (245
[214-325 vs. 312 [256-370] μmol/L, p < 0.001). Multivariable logistic regression analysis indicated
that patients with higher serum UA levels had a lower risk of HT (OR per 10-μmol/L increase 0.96,
95%CI 0.92–0.99, p = 0.015). Furthermore, multiple-adjusted spline regression models showed a Ushaped
association between serum UA levels and HT (p < 0.001 for non-linearity). Similar results
were present between serum UA and sICH. Restricted cubic spline models predicted the lowest risk
of HT and sICH when the serum UA levels were 386μmol/L.

Conclusion:
The data show the U-shaped relationship between serum UA levels and the risk of HT
and sICH after intravenous thrombolysis.
Prediction of Symptoms on Admission with Early Neurological Deterioration
in Single Small Subcortical Infarct
Authors: Gao Yuan , Zong Ce , Liu Hongbing , Zhang Ke , Yang Hongxun , Wang Anran , Wang Yunchao , Zhu Hanghang , Li Yapeng , Liu Kai , Song Bo , Xu Yuming 
Published: July 2022

Background:
Early neurological deterioration (END) often occurs during hospitalization
in single small subcortical infarct (SSSI). While, symptoms on admission were rarely reported about
its performance on predicting the risk of END.

Objectives:
The objective of this study is to explore the relationship between symptoms on admission
and END in SSSI.

Methods:
Patients with SSSI in the lenticulostriate artery (LSA) territory presenting within 72 hours
of stroke onset were screened prospectively. Clinical characteristics, including symptoms on admission,
laboratory tests and imaging findings, were collected. Based on the body regions involved
including spherical face (SF), upper limb (UL) or lower limb (LL), symptoms on admission were
classified into single spherical face (sSF) and any involvement of limbs (AL). END was defined as
≥2 points increase in total National Institutes of Health Stroke Scale (NIHSS) score or ≥ 1 point
increase in motor score within 72 hours after admission. Multivariate logistic regression was used to
analyze factors associated with END.

Results:
Out of 5,832 ischemic stroke patients in the database, 394 patients were finally enrolled in
analysis. 65 patients (16.5%) developed END. Multivariable logistic regression revealed that symptoms
with LL (OR 2.337, 95% CI 1.041-5.246), UL (OR 2.936, 95% CI 1.349-6.390) were both
associated with END, while the involvement of SF (OR 0.447, 95% CI 0.249-0.804) showed the
opposite result. Further analysis found that symptoms with AL (OR 3.958, 95% CI 1.355-11.565)
showed a higher risk of END compared to sSF after adjustment.

Conclusion:
Our results discovered that symptoms with AL carried a higher risk of END than those
involving sSF in SSSI.
What Happens in TBI? A Wide Talk on Animal Models and Future Perspective
Authors: Kundu Satyabrata , Singh Shamsher 
Published: July 2022

Abstract:
Traumatic brain injury (TBI) is a global healthcare concern and a leading cause of death.
The most common causes of TBI include road accidents, sports injuries, violence in warzones, and
falls. TBI induces neuronal cell death independent of age, gender, and genetic background. TBI survivor
patients often experience long-term behavioral changes like cognitive and emotional changes. TBI
affects social activity, reducing the quality and duration of life. Over the last 40 years, several rodent
models have been developed to mimic different clinical outcomes of human TBI for a better understanding
of pathophysiology and to check the efficacy of drugs used for TBI. However, promising
neuroprotective approaches that have been used preclinically have been found to be less beneficial in
clinical trials. So, there is an urgent need to find a suitable animal model for establishing a new therapeutic
intervention useful for TBI. In this review, we have demonstrated the etiology of TBI and post-
TBI social life alteration, and also discussed various preclinical TBI models of rodents, zebrafish, and
drosophila.
Comparative Analysis of the Pre- and Post-Medication Effects of Antipsychotic Agents on the Blood-Based Oxidative Stress Biomarkers in Patients with Schizophrenia: A Meta-Analysis
Authors: Yang Mi , Wang Chunzhi , Zhao Guocheng , Kong Di , Liu Liju , Yuan Shuai , Chen Wei , Feng Can , Li Zezhi 
Published: July 2022

Objectives:Studies have shown that oxidative stress (OS) is related to the pathophysiology of schizophrenia (SCZ), but whether antipsychotics can induce OS has not been investigated well. Moreover, antipsychotics have differential effects on the OS level modulation, i.e., different types of antipsychotics have different effects on the cellular antioxidants or pro-oxidants.Methods:We followed the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines and investigated the OS indicators including both enzymatic and nonenzymatic markers, such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), malondialdehyde (MDA), glutathione (GSH), vitamin C, etc., of SCZ patients at baseline and follow-up of mono-medication.Results:Twenty studies met the inclusion criteria, with a total of 1162 patients enrolled at baseline, and 1105 patients completed the follow-up. OS markers were changed after a period of antipsychotic treatment in SCZ patients. The GPx activity and MDA level decreased in the whole blood (P<0.05), also the serum MDA level decreased (P<0.05). For the first-episode SCZ patients, the activity of GPx and the level of MDA decreased, while the level of vitamin C increased (all P<0.05). The levels of MDA in patients receiving atypical antipsychotics decreased (P<0.05), while the level of GSH in patients with typical antipsychotics decreased (P=0.05).Conclusion:Antipsychotic medication may cause changes in the levels of OS markers in different blood samples of SCZ patients. However, the available studies might not be sufficient to reveal the underlying facts accurately due to the poor quality of experimental designs in the published literature.
Epilepsy and Cognitive Impairment in Childhood and Adolescence: A
Mini-Review
Authors: Operto Francesca Felicia , Pastorino Grazia Maria Giovanna , Viggiano Andrea , Dell'Isola Giovanni Battista , Dini Gianluca , Verrotti Alberto , Coppola Giangennaro 
Published: July 2022

Abstract:
Managing epilepsy in people with an intellectual disability remains a therapeutic challenge
and must take into account additional issues such as diagnostic difficulties and frequent drug
resistance. Advances in genomic technologies improved our understanding of epilepsy and raised
the possibility to develop patients-tailored treatments acting on the key molecular mechanisms involved
in the development of the disease. In addition to conventional antiseizure medications
(ASMs), ketogenic diet, hormone therapy and epilepsy surgery play an important role, especially in
cases of drugresistance. This review aims to provide a comprehensive overview of the mainfactors
influencing cognition in children and adolescents with epilepsy and the main therapeutic options
available for the epilepsies associated with intellectual disability.
Antimicrobial Activities of Substituted 4-N-alkylated-2-trifluoromethylquinoline
Analogs Against Nontuberculous Mycobacteria
Authors: da Silva Emerson Teixeira , de Andrade Gabriel Fernandes , Silva Lourenço Maria Cristina , de Souza Marcus Vinícius Nora 
Published: July 2022

Background:
Many contagious diseases have been caused by a variety of nontuberculous mycobacteria,
opportunistic pathogens that can cause disseminated or localized diseases, particularly pulmonary,
skin, and soft tissue infections.

Objective:
In this study fifty-five substituted 4-N-alkylated-2-trifluoromethylquinolines were evaluated
against five species of nontuberculous mycobacteria: Mycobacterium fortuitum, Mycobacterium chelonae,
Mycobacterium abscessus, Mycobacterium kansasii, and Mycobacterium avium.

Methods:
The antimycobacterial activities of all tested compounds were assessed using the microplate
procedure with broth microdilution assay. The most actives were selected for their potential cytotoxic
activity against Vero cells.

Results:
Most of the compounds displayed some activity against M. kansaii, of which 12, 15, 34, 37 and
48 were the most active at 3.12 μg/mL. The derivative 8 was the most active against M. fortuitum at 6.25
μg/mL and the most active against M. chelonae at 3.12 μg/mL. The derivative 2 was the most active
against M. avium at 12.5 μg/mL, and 9 the most active against M. abscessus at 12.5 μg/mL. All the most
active compounds showed MIC values similar to the references drugs used against these species.

Conclusion:
47 compounds displayed some activity against some of the species analyzed, highlighting
derivatives 12, 15, 34, 37, and 48, which presented the lower MIC values. Compounds 34 and 37 displayed
the highest activity and did not show cytotoxicity against Vero cells. These findings have opened
new perspectives for the research of new drugs against these mycobacterial species based on the quinoline
nucleus.
In Vitro Inhibitory Effects of Agarwood Tea (Aquilaria malaccensis Lamk) Aqueous Extract on Human Cytochrome P450 (CYP) Enzyme Activities
Authors: Yan Pan , Tze Ung Yee , Jagadish Premika A P R , Hon Lim Kuan , Chowdhury Lamia Noushin Sadeque , Tao Shang , Eng Ong Chin 
Published: July 2022

Background:Agarwood tea derived from Aquilaria malaccensis Lamk is becoming an increasingly popular herbal drink that is said to have multiple health benefits. Co-administration of this tea and clinical used drugs is possible, but it increases the risk of drug-herb interactions.Objectives:This in vitro study investigated the inhibitory effects of agarwood tea aqueous extract on the eight major human drug-metabolising cytochrome P450 (CYP) enzyme activities.Methods:High-throughput fluorescence-based Vivid® CYP450 screening kits were employed to obtain the enzyme activities before and after incubation with agarwood tea aqueous extract.Results:Agarwood aqueous extract potently inhibited CYP2C9, CYP2D6, and CYP3A4 activities with Ki values of 5.1, 34.5, and 20.3μg/ml, respectively. The most likely inhibition mode responsible for these inhibitions was non-competitive inhibition. On the other hand, at 1000μg/ml, agarwood tea aqueous extract negligibly inhibited CYP1A2, CYP2B6, CYP2C19, CYP2E1, and CYP3A5 activities.Conclusion:These findings can be used to design additional in vitro investigations using clinical relevant drug substrates for CYP2C9, CYP2D6, and CYP3A4. Subsequently, future studies can be conducted to determine potential interactions between agarwood tea aqueous extract and CYP using in vivo models.
Differential Drug Release Kinetics from Paclitaxel-Loaded Polydioxanone
Membranes and Capsules
Authors: Padmakumar Smrithi , Varghese Merin Mary , Menon Deepthy 
Published: July 2022

Background:
Drug laden implantable systems can provide drug release over several hours
to years, which eventually aid in the therapy of both acute and chronic diseases. The present study focuses
on a fundamental evaluation of the influence of implant properties such as morphology, architecture,
porosity, surface area, and wettability in regulating the drug release kinetics from drug-loaded
polymeric matrices.

Methods:
For this, Polydioxanone (PDS) was selected as the polymer and Paclitaxel (Ptx) as the model
drug. Two different forms of the matrix implants, viz., reservoir type capsules developed by dip
coating and matrix type membranes fabricated by phase inversion and electrospinning, were utilized
for the study. Drug release from all the four different matrices prepared by simple techniques was
evaluated in vitro in PBS and ex vivo in peritoneal wash fluid for ~4 weeks. The drug release profiles
were thereafter correlated with the physicochemical parameters of the polymeric implants.

Results:
Reservoir-type capsules followed a slow and steady zero-order kinetics, while matrix-type
electrospun and phase inversion membranes displayed typical biphasic kinetics.

Conclusion:
It was inferred that the slow degradation rate of PDS polymer as well as the implant
properties like porosity and wettability play an important role in controlling the drug release rates.