bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of the comorbid seizure/epilepsy on the health related quality of life in people with multiple sclerosis: an international multicentric study
Authors: Drulovic Jelena , Pekmezovic Tatjana , Tamas Olivera , Adamec Ivan , Aleksic Dejan , Andabaka Marko , Basic Kes Vanja , Butkovic Soldo Silva , Cukic Mirjana , Despinic Livija , Dincic Evica , Djelilovic Vranic Jasminka , Grgic Sanja , Habek Mario , Hristova Sonya Ivanova , Ivanovic Jovana , Jovanovic Aleksa , Jovicevic Vanja , Krbot Skoric Magdalena , Kuzmanovski Igor , Maric Gorica , Mesaros Sarlota , Milanov Ivan Gospodinov , Miletic Drakulic Svetlana , Sinanovic Osman , Skarpa Prpic Ingrid , Sremec Josip , Tadic Daliborka , Toncev Gordana , Sokic Dragoslav 
Published: November 2023

IntroductionThe health-related quality of life (HRQoL) of people with (Pw) multiple sclerosis (MS) is usually deteriorated. It has been recently suggested that comorbidities may have the negative influence on the quality of life of the PwMS, but according to the best of our knowledge, only one study investigated, although in a very small cohort, the impact of individual comorbidity on the quality of life of PwMS. The aim of our investigation was to assess, in an international, multicentric study, the impact of comorbid seizure/epilepsy on the HRQoL in PwMS.MethodsWe conducted cross-sectional study at numerous neurological centers in Serbia, Croatia, Bulgaria, Montenegro, Northern Macedonia, and Bosnia and Herzegovina (Federation of Bosnia and Herzegovina and Republic of Srpska). For each patient, demographic and clinical data were collected, including Expanded disability status scale (EDSS) score. Beck Depression Inventory (BDI) and the 36-Item Short Form Health Survey (SF-36) questionnaires were administered to all patients.ResultsThe study comprised 326 PwMS in total, 127 PwMS with seizure/epilepsy and 209 PwMS without. Both mean Physical health composite (PHC) and mental health composite (MHC) scores, were statistically significantly higher in PwMS without seizure/epilepsy, implicating worse quality of life in PwMS with comorbid seizure/epilepsy. Presence of seizure/epilepsy in pwMS was statistically significant independent predictor of both PHC and MHC, in multivariate linear regression model after adjustment for potential confounding variables. The hierarchical multivariate regression analysis was performed in order to establish the most important predictors of the PHC and MHC of the SF-36, in PwMS with seizure/epilepsy; older age, higher level of disability, as measured by EDSS, higher depression score, drug-resistant epilepsy and shorter time since last seizure were found to significantly predict worse MHC score in PwMS with seizure/epilepsy.DiscussionOur results point to the possible role of theinterventions related to the adequate control of epilepsy along with improvement of the mental health status to be important in order to reduce MS burden in the PwMS with comorbid seizure/epilepsy.
In-silico and in-vitro functional validation of imidazole derivatives as potential sirtuin inhibitor
Authors: Dindi Uma Maheswara Rao , Sadiq Suhadha Parveen , Al-Ghamdi Sameer , Alrudian Naif Abdurhman , Dayel Salman Bin , Abuderman Abdulwahab Ali , Shahid Mohammad , Ramesh Thiyagarajan , Vilwanathan Ravikumar 
Published: November 2023

IntroductionEpigenetic enzymes can interact with a wide range of genes that actively participate in the progression or repression of a diseased condition, as they are involved in maintaining cellular homeostasis. Sirtuins are a family of Class III epigenetic modifying enzymes that regulate cellular processes by removing acetyl groups from proteins. They rely on NAD+ as a coenzyme in contrast to classical histone deacetylases (HDACs) (Class I, II, and IV) that depend on Zn+ for their activation, linking their function to cellular energy levels. There are seven mammalian sirtuin isoforms (Sirt1-7), each located in different subcellular compartments. Sirtuins have emerged as a promising target, given that inhibitors of natural and synthetic sources are highly warranted. Imidazole derivatives are often investigated as sirtuin regulators due to their ability to interact with the binding site and modulate their activity. Imidazole bestows many possible substitutions on its ring and neighboring atoms to design and synthesize derivatives with specific target selectivity and improved pharmacokinetic properties, optimizing drug development.Materials and methodsLigand preparation, protein preparation, molecular docking, molecular dynamics, density function theory (DFT) analysis, and absorption, distribution, metabolism, and excretion (ADME) analysis were performed to understand the interacting potential and effective stability of the ligand with the protein. RT-PCR and Western blot analyses were performed to understand the impact of ligands on the gene and protein expression of Class III HDAC enzymes.Results and discussionWe evaluated the sirtuin inhibition activity of our in-house compound comprised of imidazole derivatives by docking the molecules with the protein data bank. ADME properties of all the compounds used in the study were evaluated, and it was found that all fall within the favorable range of being a potential drug. The molecule with the highest docking score was analyzed using DFT, and the specific compound was used to treat the non-small cell lung cancer (NSCLC) cell lines A549 and NCI-H460. The gene and protein expression data support the in-silico finding that the compound Ethyl 2-[5-(4-chlorophenyl)-2-methyl-1-H-Imidazole-4-yl) acetate has an inhibitory effect on nuclear sirtuins. In conclusion, targeting sirtuins is an emerging strategy to combat carcinogenesis. In this study, we establish that Ethyl 2-[5-(4-chlorophenyl)-2-methyl-1-H-Imidazole-4-yl) acetate possesses a strong inhibitory effect on nuclear sirtuins in NSCLC cell lines.
Diagnosis of Alzheimer’s disease via resting-state EEG: integration of spectrum, complexity, and synchronization signal features
Authors: Zheng Xiaowei , Wang Bozhi , Liu Hao , Wu Wencan , Sun Jiamin , Fang Wei , Jiang Rundong , Hu Yajie , Jin Cheng , Wei Xin , Chen Steve Shyh-Ching 
Published: November 2023

BackgroundAlzheimer’s disease (AD) is the most common neurogenerative disorder, making up 70% of total dementia cases with a prevalence of more than 55 million people. Electroencephalogram (EEG) has become a suitable, accurate, and highly sensitive biomarker for the identification and diagnosis of AD.MethodsIn this study, a public database of EEG resting state-closed eye recordings containing 36 AD subjects and 29 normal subjects was used. And then, three types of signal features of resting-state EEG, i.e., spectrum, complexity, and synchronization, were performed by applying various signal processing and statistical methods, to obtain a total of 18 features for each signal epoch. Next, the supervised machine learning classification algorithms of decision trees, random forests, and support vector machine (SVM) were compared in categorizing processed EEG signal features of AD and normal cases with leave-one-person-out cross-validation.ResultsThe results showed that compared to normal cases, the major change in EEG characteristics in AD cases was an EEG slowing, a reduced complexity, and a decrease in synchrony. The proposed methodology achieved a relatively high classification accuracy of 95.65, 95.86, and 88.54% between AD and normal cases for decision trees, random forests, and SVM, respectively, showing that the integration of spectrum, complexity, and synchronization features for EEG signals can enhance the performance of identifying AD and normal subjects.ConclusionThis study recommended the integration of EEG features of spectrum, complexity, and synchronization for aiding the diagnosis of AD.
Treatment efficacy of repositioning maneuvers in multiple canal benign paroxysmal positional vertigo: a systematic review and meta-analysis
Authors: Alfarghal Mohamad , Singh Niraj Kumar , Algarni Mohammed Abdullah , Jagadish Nirmala , Raveendran Rajesh Kumar 
Published: November 2023

IntroductionBenign paroxysmal positional vertigo (BPPV) involving the posterior canal is more common than other canals; however, simultaneous involvement of multiple canals can be seen up to 20% of all BPPV cases. The diagnosis and management of multiple canal BPPV can be quite challenging due to the complexity of findings. Therefore, this systematic review and meta-analysis aimed at unveiling the most effective repositioning strategy for the treatment of multiple canal BPPV.MethodsA literature search through PubMed, Scopus, and Web of Science databases was conducted using search terms such as BPPV, multiple canals, bilateral BPPV, repositioning maneuvers etc. After duplicate removal, the retained articles underwent various stages of elimination by two independent reviewers, and a third reviewer resolved the discrepancy between them.ResultsA total of 22 articles were included in the systematic review. These publications documented 5,196 patients diagnosed with BPPV, of which 513 had multiple canal BPPV. Of 295 individuals with multiple canal BPPV, 58.9% were effectively treated in 1 session, whereas 18.3 and 4.4% achieved a symptom-free state after two and three sessions, respectively. Failure of treatment using repositioning maneuvers was found in 18.4%.Possible implicationsThis study offers insight into the real world of BPPV management in single and multiple canal BPPV. It is evident that repositioning maneuvers provide rapid and long-lasting relief of BPPV in most single canal BPPV patients; however, multiple canal BPPV often requires repeated treatment, and the risk of recurrence is higher in this variety than the single canal BPPV.
Prominent elevation of extracellular matrix molecules in intracerebral hemorrhage
Authors: Li Hongmin , Ghorbani Samira , Zhang Ruiyi , Ebacher Vincent , Stephenson Erin L. , Keough Michael B. , Yong V. Wee , Xue Mengzhou 
Published: November 2023

BackgroundIntracerebral hemorrhage (ICH) is the predominant type of hemorrhagic stroke with high mortality and disability. In other neurological conditions, the deposition of extracellular matrix (ECM) molecules is a prominent obstacle for regenerative processes and an enhancer of neuroinflammation. Whether ECM molecules alter in composition after ICH, and which ECM members may inhibit repair, remain largely unknown in hemorrhagic stroke.MethodsThe collagenase-induced ICH mouse model and an autopsied human ICH specimen were investigated for expression of ECM members by immunofluorescence microscopy. Confocal image z-stacks were analyzed with Imaris 3D to assess the association of immune cells and ECM molecules. Sections from a mouse model of multiple sclerosis were used as disease and staining controls. Tissue culture was employed to examine the roles of ECM members on oligodendrocyte precursor cells (OPCs).ResultsAmong the lectican chondroitin sulfate proteoglycan (CSPG) members, neurocan but not aggrecan, versican-V1 and versican-V2 was prominently expressed in perihematomal tissue and lesion core compared to the contralateral area in murine ICH. Fibrinogen, fibronectin and heparan sulfate proteoglycan (HSPG) were also elevated after murine ICH while thrombospondin and tenascin-C was not. Confocal microscopy with Imaris 3D rendering co-localized neurocan, fibrinogen, fibronectin and HSPG molecules to Iba1+ microglia/macrophages or GFAP+ astrocytes. Marked differentiation from the multiple sclerosis model was observed, the latter with high versican-V1 and negligible neurocan. In culture, purified neurocan inhibited adhesion and process outgrowth of OPCs, which are early steps in myelination in vivo. The prominent expression of neurocan in murine ICH was corroborated in human ICH sections.ConclusionICH caused distinct alterations in ECM molecules. Among CSPG members, neurocan was selectively upregulated in both murine and human ICH. In tissue culture, neurocan impeded the properties of oligodendrocyte lineage cells. Alterations to the ECM in ICH may adversely affect reparative outcomes after stroke.
Analysis of the risk factors of radiation pneumonitis in patients after radiotherapy for esophageal squamous cell carcinoma
Authors: Sun Lu , Wang Yan , Zhu Lihua , Chen Jun , Chen Zhifu , Qiu Zhiyuan , Wu Chaoyang 
Published: November 2023

ObjectiveTo predict the risk factors of radiation pneumonitis (RP) in patients with esophageal squamous cell carcinoma (ESCC) who received radiotherapy.MethodsFrom January 2015 to October 2021, 477 ESCC patients were enrolled and were assessed retrospectively. All these patients received radiotherapy for primary lesions or mediastinal metastatic lymph nodes. Clinical efficacy and adverse events (AEs) were observed. Univariate analysis identified clinical and dosimetric factors associated with the development of RP, and multivariate logistic regression analysis identified independent potential risk factors associated with the development of RP. Nomograms were constructed to predict RP based on the results of multivariate logistic regression analysis.ResultsAmong the 477 ESCC patients, the incidence of RP was 22.2%, and the incidence of grade 4 or higher RP was 1.5%. Univariate analysis indicated that chronic obstructive pulmonary disease (COPD), pulmonary infection, leucopenia, PTV volume, V5, V20, V30 and MLD affected the occurrence of RP. The multivariate logistic regression analysis indicated that COPD (OR:1.821, 95%CI:1.111-2.985; P=0.017), pulmonary infection (OR:2.528, 95%CI:1.530-4.177; P&lt;0.001), higher V20 (OR: 1.129, 95% CI:1.006-1.266; P=0.029) were significant independent predictors of RP in ESCC patients. COPD, pulmonary infection, V20 have been integrated for the RP nomogram. The rate of RP was significantly reduced in the V20&lt;21.45% group. Further analysis indicated that the old age, diabetes, higher V20, and higher MLD were risk factors for grade 4 or higher RP. The area under the curve (AUC) value for V20 was 0.73 (95% CI, 0.567-0.893, P &lt; 0.05).ConclusionWe have determined the risk factors of RP and grade 4 or higher RP in ESCC patients after radiotherapy. MLD, V20, COPD were independent factors for RP. It was necessary to take measures to reduce or avoid the occurrence of RP for patients with these risk factors at the early stage.
Pediatric pituitary neuroendocrine tumors–a 13-year experience in a tertiary center
Authors: Li Xiaoxu , Deng Kan , Zhang Yi , Feng Ming , Xing Bing , Lian Wei , Yao Yong 
Published: November 2023

IntroductionPediatric pituitary neuroendocrine tumor is a rare condition, and despite previous research focusing on this specific group, the main factors influencing the surgical cure rate have not been identified.MethodsWe conducted a single-center retrospective study on pediatric pituitary neuroendocrine tumor patients who visited Peking Union Medical College Hospital between 2010 and 2023. We collected data on their clinical characteristics, imaging features, surgical outcomes, and follow-up information. Additionally, we used multiple-factor logistic regression to investigate the factors affecting the surgical cure rate of pediatric pituitary neuroendocrine tumor.Results232 patients were diagnosed with pediatric pituitary neuroendocrine tumors, with a higher incidence in females. The most common type was ACTH-secreting adenoma (90/232), followed by prolactin-secreting adenoma (63/232), and growth hormone-secreting adenoma (41/232). The majority of pediatric adenomas were macroadenomas (139/232), and some tumors were associated with cystic changes or hemorrhage (58/232), while a few exhibited invasion of the cavernous sinus (33/232). The results of the multivariate analysis indicated that the different hormone secretion types, macroadenoma or the presence of cystic changes or hemorrhage were not significant risk factors for the cure rate after the first surgery. However, the invasion of the cavernous sinus was found to be an important factor influencing the postoperative cure rate. Most pediatric pituitary neuroendocrine tumors with cavernous sinus invasion were macroadenomas, and some displayed characteristics of refractory pituitary neuroendocrine tumors, with some patients experiencing irreversible complications after surgery.ConclusionPediatric pituitary neuroendocrine tumors are complex, and the postoperative cure rate is particularly poor for tumors with cavernous sinus invasion. Although macroadenoma itself does not significantly impact the postoperative cure rate, it is still recommended to diagnose and treat early to avoid unnecessary surgery or surgical complications.
The impact of partnered pharmacist medication charting in the emergency department on the use of potentially inappropriate medications in older people
Authors: Atey Tesfay Mehari , Peterson Gregory M. , Salahudeen Mohammed S. , Wimmer Barbara C. 
Published: November 2023

Introduction: A process redesign, partnered pharmacist medication charting (PPMC), was recently piloted in the emergency department (ED) of a tertiary hospital. The PPMC model was intended to improve medication safety and interdisciplinary collaboration by having pharmacists work closely with medical officers to review and chart medications for patients. This study, therefore, aimed to evaluate the impact of PPMC on potentially inappropriate medication (PIM) use.Methods: A pragmatic concurrent controlled study compared a PPMC group to both early best-possible medication history (BPMH) and usual care groups. In the PPMC group, pharmacists initially documented the BPMH and collaborated with medical officers to co-develop treatment plans and chart medications in ED. The early BPMH group included early BPMH documentation by pharmacists, followed by traditional medication charting by medical officers in ED. The usual care group followed the traditional charting approach by medical officers, without a pharmacist-collected BPMH or collaborative discussion in ED. Included were older people (≥65 years) presenting to the ED with at least one regular medication with subsequent admission to an acute medical unit. PIM outcomes (use of at least one PIM, PIMs per patient and PIMs per medication prescribed) were assessed at ED presentation, ED departure and hospital discharge using Beers criteria.Results: Use of at least one PIM on ED departure was significantly lower for the PPMC group than for the comparison groups (χ2, p = 0.040). However, PIM outcomes at hospital discharge were not statistically different between groups. PIM outcomes on ED departure or hospital discharge did not differ from baseline within the comparison groups.Discussion: In conclusion, PIM use on leaving ED, but not at hospital discharge, was reduced with PPMC. Close interprofessional collaboration, as in ED, needs to continue on the wards.
Features and mechanisms of propofol-induced protein kinase C (PKC) translocation and activation in living cells
Authors: Noguchi Soma , Kajimoto Taketoshi , Kumamoto Takuya , Shingai Masashi , Narasaki Soshi , Urabe Tomoaki , Imamura Serika , Harada Kana , Hide Izumi , Tanaka Sigeru , Yanase Yuhki , Nakamura Shun-Ichi , Tsutsumi Yasuo M. , Sakai Norio 
Published: November 2023

Background and purpose: In this study, we aimed to elucidate the action mechanisms of propofol, particularly those underlying propofol-induced protein kinase C (PKC) translocation.Experimental approach: Various PKCs fused with green fluorescent protein (PKC-GFP) or other GFP-fused proteins were expressed in HeLa cells, and their propofol-induced dynamics were observed using confocal laser scanning microscopy. Propofol-induced PKC activation in cells was estimated using the C kinase activity receptor (CKAR), an indicator of intracellular PKC activation. We also examined PKC translocation using isomers and derivatives of propofol to identify the crucial structural motifs involved in this process.Key results: Propofol persistently translocated PKCα conventional PKCs and PKCδ from novel PKCs (nPKCs) to the plasma membrane (PM). Propofol translocated PKCδ and PKCη of nPKCs to the Golgi apparatus and endoplasmic reticulum, respectively. Propofol also induced the nuclear translocation of PKCζ of atypical PKCs or proteins other than PKCs, such that the protein concentration inside and outside the nucleus became uniform. CKAR analysis revealed that propofol activated PKC in the PM and Golgi apparatus. Moreover, tests using isomers and derivatives of propofol predicted that the structural motifs important for the induction of PKC and nuclear translocation are different.Conclusion and implications: Propofol induced the subtype-specific intracellular translocation of PKCs and activated PKCs. Additionally, propofol induced the nuclear translocation of PKCs and other proteins, probably by altering the permeability of the nuclear envelope. Interestingly, propofol-induced PKC and nuclear translocation may occur via different mechanisms. Our findings provide insights into the action mechanisms of propofol.
Computer-aided drug design for virtual-screening and active-predicting of main protease (Mpro) inhibitors against SARS-CoV-2
Authors: Dai Renhui , Gao Hongwei , Su Ruiling 
Published: November 2023

Introduction: SARS-CoV-2 is a novel coronavirus with highly contagious and has posed a significant threat to global public health. The main protease (Mpro) is a promising target for antiviral drugs against SARS-CoV-2.Methods: In this study, we have used pharmacophore-based drug design technology to identify potential compounds from drug databases as Mpro inhibitors.Results: The procedure involves pharmacophore modeling, validation, and pharmacophore-based virtual screening, which identifies 257 compounds with promising inhibitory activity.Discussion: Molecular docking and non-bonding interactions between the targeted protein Mpro and compounds showed that ENA482732 was the best compound. These results provided a theoretical foundation for future studies of Mpro inhibitors against SARS-CoV-2.
Spending time in the forest or the field: qualitative semi-structured interviews in a randomized controlled cross-over trial with highly sensitive persons
Authors: Oomen-Welke Katja , Hilbich Tina , Schlachter Evelyn , Müller Alexander , Anton Andreas , Huber Roman 
Published: November 2023

IntroductionThe effects of spending time in forests have been subject to investigations in various countries around the world. Qualitative comparisons have been rarely done so far.MethodsSixteen healthy highly sensitive persons (SV12 score ≥ 18) aged between 18 and 70 years were randomly assigned to groups spending 1 h in the forest and in the field at intervals of one week. Semi-structured interviews were conducted after each intervention and analyzed using a mixed-methods approach of content analysis and grounded theory.ResultsBoth natural environments induced feelings of inner calmness, inner cleansing, joy, freedom, connectedness, strengthening qualities, and heightened body awareness. The forest environment additionally offered emotional shelter, and showed advantages in promoting inner strength and self-concentration.DiscussionPeople with previous negative experiences in the forest may feel safer in fields because of the wider view and better overview. Important preconditions are enough time and the absence of a judgmental authority. The two environments induced in part different but also similar emotions which might be useful to promote psychological well-being differentially.