bluuebunny/crossref_metadata_2025_split huggingface dataset:
Homology modeling, virtual screening, molecular docking, and dynamics studies for discovering Staphylococcus epidermidis FtsZ inhibitors
Authors: Vemula Divya , Maddi Dhanashri Ramesh , Bhandari Vasundhra 
Published: March 2023

Staphylococcus epidermidis is the most common cause of medical device-associated infections and is an opportunistic biofilm former. Among hospitalized patients, S. epidermidis infections are the most prevalent, and resistant to most antibiotics. In order to overcome this resistance, it is imperative to treat the infection at a cellular level. The present study aims to identify inhibitors of the prokaryotic cell division protein FtsZ a widely conserved component of bacterial cytokinesis. Two substrate binding sites are present on the FtsZ protein; the nucleotide-binding domain and the inter-domain binding sites. Molecular modeling was used to identify potential inhibitors against the binding sites of the FtsZ protein. One hundred thirty-eight chemical entities were virtually screened for the binding sites and revealed ten molecules, each with good binding affinities (docking score range −9.549 to −4.290 kcal/mol) compared to the reference control drug, i.e., Dacomitinib (−4.450 kcal/mol) and PC190723 (−4.694 kcal/mol) at nucleotide and inter-domain binding sites respectively. These top 10 hits were further analyzed for their ADMET properties and molecular dynamics simulations. The Chloro-derivative of GTP, naphthalene-1,3-diyl bis(3,4,5-trihydroxybenzoate), Guanosine triphosphate (GTP), morpholine and methylpiperazine derivative of GTP were identified as the lead molecules for nucleotide binding site whereas for inter-domain binding site, 1-(((amino(iminio)methyl)amino)methyl)-3-(3-(tert-butyl)phenyl)-6,7-dimethoxyisoquinolin-2-ium, and Chlorogenic acidwere identified as lead molecules. Molecular dynamics simulation and post MM/GBSA analysis of the complexes revealed good protein-ligand stability predicting them as potential inhibitors of FtsZ (Figure 1). Thus, identified FtsZ inhibitors are a promising lead compounds for S. epidermidis related infections.
Serum miRNA modulations indicate changes in retinal morphology
Authors: Aggio-Bruce Riemke , Schumann Ulrike , Cioanca Adrian V. , Chen Fred K. , McLenachan Samuel , Heath Jeffery Rachael C. , Das Shannon , Natoli Riccardo 
Published: March 2023

BackgroundAge-related macular degeneration (AMD) is the leading cause of vision loss in the developed world and the detection of its onset and progression are based on retinal morphological assessments. MicroRNA (miRNA) have been explored extensively as biomarkers for a range of neurological diseases including AMD, however differences in experimental design and the complexity of human biology have resulted in little overlap between studies. Using preclinical animal models and clinical samples, this study employs a novel approach to determine a serum signature of AMD progression.MethodsSerum miRNAs were extracted from mice exposed to photo-oxidative damage (PD; 0, 1, 3 and 5 days), and clinical samples from patients diagnosed with reticular pseudodrusen or atrophic AMD. The expression of ~800 miRNAs was measured using OpenArray™, and differential abundance from controls was determined using the HTqPCR R package followed by pathway analysis with DAVID. MiRNA expression changes were compared against quantifiable retinal histological indicators. Finally, the overlap of miRNA changes observed in the mouse model and human patient samples was investigated.ResultsDifferential miRNA abundance was identified at all PD time-points and in clinical samples. Importantly, these were associated with inflammatory pathways and histological changes in the retina. Further, we were able to align findings in the mouse serum to those of clinical patients.ConclusionIn conclusion, serum miRNAs are a valid tool as diagnostics for the early detection of retinal degeneration, as they reflect key changes in retinal health. The combination of pre-clinical animal models and human patient samples led to the identification of a preliminary serum miRNA signature for AMD. This study is an important platform for the future development of a diagnostic serum miRNA panel for the early detection of retinal degeneration.
Exploring barriers of childhood full vaccination among children living in Siraro District, West Arsi Zone, Oromia region, Ethiopia: A qualitative study
Authors: Guye Ararso Hordofa , Nigussie Tadesse , Tesema Mengistu , Shambi Dame Banti , Diriba Berhanu Senbeta , Tefera Esayas Mekonen , Girma Yeabsira 
Published: March 2023

BackgroundChildhood immunization is one of the most effective global public health interventions to reduce childhood morbidity and mortality. However, some children remain not fully vaccinated in developing countries due to defaulting from full vaccination, which can put them at risk of acquiring vaccine-preventable disease outbreaks. The barriers to full vaccination were well explored in Ethiopia using a qualitative approach. The study aimed to explore barriers to full childhood vaccination in Siraro District, West Arsi Zone, Oromia, Ethiopia.MethodsA qualitative study was conducted in Siraro District through 15 key informant health workers interviews and 6 in-depth interviews with children’s mothers from April 20 to May 15, 2022. Data were collected by semi-structured questionnaires and captured using audio tape recorders and field note-taking. A heterogeneous purposive sampling technique was used to select representative study participants. Data transcription and translation were done according to the respondents’ verbatim from the local language to English. Data coding and key categories were identified and analyzed using thematic analysis. Finally, data were presented in narrative forms using respondents' own words as an illustration.ResultTwenty-one study participants were interviewed and included in this study. Of the explored barriers to full childhood vaccination, the evidence from the respondents was integrated from subcategories and presented as a whole within each thematic area. Five thematic areas emerged from interviews of the participants through thematic analysis of the data. The identified barriers were forgetting the next vaccination schedule, migration of parents, work overload, lack of knowledge and awareness, rumors, and misinformation. Additionally, vaccination service delivery-related barriers such as vaccine vials not being opened for a few children, fear of vaccine side effects, closed health posts during visits by mothers for vaccination, and absence of health extension workers at health posts were the key barriers to full childhood vaccination.ConclusionForgetting vaccination schedule, migration of parents, work overload, rumors, and misinformation, fear of vaccine side effects, vaccine vial not opened for few children, closed health posts during visiting by mothers, absence of health extension workers from health posts were the key barriers to the full vaccination status of children. Thus, the district health office should work on barriers to full vaccination by strengthening vaccination service delivery and improving vaccination awareness through a health extension program.
Case report: Pediatric anti-gamma aminobutyric acid-B receptor encephalitis with benign prognosis
Authors: Wang Yeping , Ren Xiaoyan , Shen Yu , Hua Yi , Xu Lu , Zhang Weiran , Sheng Guoxia , Jiang Peifang , Yuan Zhefeng , Liu Liu , Gao Feng 
Published: March 2023

ObjectiveTo explore the clinical characteristics of pediatric anti-gamma-aminobutyric acid-B receptor (GABABR) encephalitis to enhance the understanding and improve the diagnostic and therapeutic strategies for this disease.MethodsWe report a rare case of a female pediatric patient with anti-GABABR encephalitis who was treated at the Children's Hospital of Zhejiang University School of Medicine. Literature search was performed to explore the clinical characteristics of pediatric anti-GABABR encephalitis.ResultsThe patient exhibited recurrent epileptic seizure, status epilepticus, and psychiatric symptoms at the age of 11 years and 10 months. Anti-GABABR antibodies were positive in cerebrospinal fluid and serum. Brain magnetic resonance imaging (MRI) exhibited abnormal signals in the left hippocampus. Symptoms and abnormality of brain MRI were improved after administration of immunosuppressants, anti-seizure and antipsychotic drugs. Two of pediatric anti-GABABR encephalitis with clinical data were identified through literature search. Analysis of these three cases suggested that the pediatric patients primarily experienced limbic encephalitis, with no tumor incidence. A favorable immunotherapy response was demonstrated with a superior prognosis in all the cases.ConclusionsWe reported a pediatric anti-GABABR encephalitis case with early age of onset. Promt autoimmune antibody testing and tumor screening, as well as immunomodulatory treatment immediately after a definitive diagnosis are warranted to improve prognosis.
The relation between radiographic manifestation and clinical characteristics of congenital radioulnar synostosis in children: A retrospective study from multiple centers
Authors: Hong Pan , Tan Wei , Zhou Wei-Zheng , Zheng Yu , Li Jin , Zheng PengFei , Tang Xin 
Published: March 2023

ObjectiveTo review the radiographic manifestation and clinical appearance of children with congenital radioulnar synostosis (CRUS) retrospectively.Study designRetrospective cohort study of children with CRUS from multiple medical centers.ResultsA total of 329 patients (male 259, female 70) with an average age of 5.4 years (0.5–16 years old), were included in this study. In particular, 145 patients (145/329, 44.1%) demonstrated bilateral involvement, and 184 patients (left 123, right 61) demonstrated unilateral involvement. As for Clear and Omery (C&amp;O) classification, most patients belonged to Type III, and then followed by Type IV. As for Chinese Multi-center Pediatric Orthopedic Study Group (CMPOS) classification, most patients belonged to Type III, and then followed by Type II and Type I. In C&amp;O Type III, 92.03% patients demonstrated severe pronation. According to CMPOS classification, 92.98% Type I patients demonstrated neutral to mild pronation, 72.17% Type II patients demonstrated moderate pronation, and 92.03% Type III patients demonstrated severe pronation. The age distribution showed no significant difference between C&amp;O Type II and IV (P = 0.96); the pronation ankylosis severity showed no significant difference between C&amp;O Type II and IV (P = 0.387).ConclusionAlthough CRUS is a rare forearm deformity, there are certain relation between radiographic manifestation and clinical forearm functional restriction. CRUS patients of C&amp;O or CMPOS Type III classification might suffer severe pronation deformity and warrant early intervention.
Potential of natural flavonols and flavanones in the treatment of ulcerative colitis
Authors: Li Cailan , Tang Ying , Ye Yonghao , Zuo Manhua , Lu Qiang 
Published: March 2023

Ulcerative colitis (UC) is an inflammatory bowel disease generally characterized by chronic, persistent, recurrent, and non-specific ulcers of the intestine. Its main clinical manifestations include abdominal pain, diarrhea, and bloody stools. This disease is difficult to cure and even carries the risk of canceration. It has been listed as a modern refractory disease by the World Health Organization. Though a large amount of drugs are available for the inhibition of UC, the conventional treatment such as aminosalicylic acids, glucocorticoids, immunosuppressors, and biological agents possess certain limitations and serious side effects. Therefore, it is urgently needed for safe and effective drugs of UC, and natural-derived flavonols and flavanones showed tremendous potential. The present study concentrated on the progress of natural-derived flavonols and flavanones from edible and pharmaceutical plants for the remedy of UC over the last two decades. The potential pharmaceutical of natural-derived flavonols and flavanones against UC were closely connected with the modulation of gut microflora, gut barrier function, inflammatory reactions, oxidative stress, and apoptosis. The excellent efficacy and safety of natural flavonols and flavanones make them prospective drug candidates for UC suppression.
Emerging trends and research foci of berberine on tumor from 2002 to 2021: A bibliometric article of the literature from WoSCC
Authors: Yuan Runzhu , Tan Yao , Sun Ping-Hui , Qin Bo , Liang Zhen 
Published: March 2023

Background: Cancer, also known as a malignant tumor, is caused by the activation of oncogenes, which leads to the uncontrolled proliferation of cells that results in swelling. According to the World Health Organization (WHO), cancer is one of the main causes of death worldwide. The main variables limiting the efficacy of anti-tumor treatments are side effects and drug resistance. The search for natural, safe, low toxicity, and efficient chemical compounds in tumor research is essential. Berberine is a pentacyclic isoquinoline quaternary ammonium alkaloid isolated from Berberis and Coptis that has long been used in clinical settings. Studies in recent years have reported the use of berberine in cancer treatment. In this study, we performed a bibliometric analysis of berberine- and tumor-related research.Materials and methods: Relevant articles from January 1, 2002, to December 31, 2021, were identified from the Web of Science Core Collection (WOSCC) of Clarivate Analytics. Microsoft Excel, CiteSpace, VOSviewer, and an online platform were used for the literary metrology analysis.Results: A total of 1368 publications had unique characteristics. Publications from China were the most common (783 articles), and Y. B. Feng (from China) was the most productive author, with the highest total citations. China Medical University (Taiwan) and Sun Yat-sen University (China) were the two organizations with the largest numbers of publications (36 each). Frontiers in Pharmacology was the most commonly occurring journal (29 articles). The present body of research is focused on the mechanism, molecular docking, and oxidative stress of berberine in tumors.Conclusion: Research on berberine and tumors was thoroughly reviewed using knowledge map and bibliometric methods. The results of this study reveal the dynamic evolution of berberine and tumor research and provide a basis for strategic planning in cancer research.
Development of a computerized 2D rating scale for continuous and simultaneous evaluation of two dimensions of a sensory stimulus
Authors: Hoeppli Marie-Eve , Thurston Taylor S. , Roy Mathieu , Light Alan R. , Amann Markus , Gracely Richard H. , Schweinhardt Petra 
Published: March 2023

IntroductionOne-dimensional rating scales are widely used in research and in the clinic to assess individuals’ perceptions of sensory stimuli. Although these scales provide essential knowledge of stimulus perception, their limitation to one dimension hinders our understanding of complex stimuli.MethodsTo allow improved investigation of complex stimuli, a two-dimensional scale based on the one-dimensional Gracely Box Scale was developed and tested in healthy participants on a visual and an auditory task (rating changes in brightness and size of circles and rating changes in frequency and sound pressure of sounds, which was compared to ratings on one-dimensional scales). Before performing these tasks, participants were familiarized with the intensity descriptors of the two-dimensional scale by completing two tasks. First, participants sorted the descriptors based on their judgment of the intensity of the descriptors. Second, participants evaluated the intensity of the descriptors by pressing a button for the duration they considered matching the intensity of the descriptors or squeezing a hand grip dynamometer as strong as they considered matching the intensity of the descriptors.ResultsResults from these tasks confirmed the order of the descriptors as displayed on the original rating scale. Results from the visual and auditory tasks showed that participants were able to rate changes in the physical attributes of visual or auditory stimuli on the two-dimensional scale as accurately as on one-dimensional scales.DiscussionThese results support the use of a two-dimensional scale to simultaneously report multiple dimensions of complex stimuli.
Treatment patterns, adherence to international guidelines, and financial mechanisms of the market access of advanced breast cancer therapy in Bulgaria
Authors: Karanyotova Stephanie , Topova Branimira , Petrova Elina , Doychev Peter , Kapitanska Eliana , Petrova Guenka , Mitkova Zornitsa , Dimitrova Maria 
Published: March 2023

IntroductionBreast cancer is the most common type of cancer affecting women in Europe. Advanced breast cancer (ABC) poses a significant therapeutic challenge, and therefore, timely access to treatment is crucial. The aim of the present study was to evaluate the treatment patterns and patients' access to new therapies for ABC in Bulgaria.MethodsWe conducted a retrospective study in the period 2008–2021. Based on the European Medicines Agency (EMA) database, we analyzed a number of medicinal products with marketing authorization for ABC in the last 13 years. Time to market access was evaluated as the degree of availability, which is measured by the number of medicines that are available to patients (availability index, AI), and the average time elapsed between obtaining a marketing authorization and time to inclusion in the Positive Drug List. Data were analyzed through descriptive statistics via Microsoft Excel version 10.ResultsThe average time to access was 564 days for targeted therapy. The availability and compliance index for chemotherapy and hormonal therapy in advanced breast cancer was 1, while the average AI for targeted therapy was 0.67. Patient access to targeted oncology therapy of ABC is above average for Europe and takes 1–2 years.ConclusionFaster access is more evident for biosimilars. National regulatory requirements for pricing and reimbursement have a major impact on market access.
Case report: The gait deviation index may predict neurotherapeutic effects of FES-assisted gait training in children with cerebral palsy
Authors: Behboodi Ahad , Sansare Aswhini , Zahradka Nicole , Lee Samuel C. K. 
Published: March 2023

BackgroundChildren with cerebral palsy (CP) show progressive loss of ambulatory function characterized by kinematic deviations at the hip, knee, and ankle. Functional electrical stimulation (FES) can lead to more typical lower limb kinematics during walking by eliciting appropriately timed muscle contractions. FES-assisted walking interventions have shown mixed to positive results in improving lower limb kinematics through immediate correction of gait during the application of FES, or long-term, persisting effects of non-FES-assisted gait improvements following multi-week FES-assisted gait training, at the absence of stimulation, i.e., neurotherapeutic effects. It is unknown, however, if children with CP will demonstrate a neurotherapeutic response following FES-assisted gait training because of the CP population's heterogeneity in gait deviations and responses to FES. Identifying the neurotherapeutic responders is, therefore, important to optimize the training interventions to those that have higher probability of benefiting from the intervention.ObjectiveThe purpose of this case study was to investigate the relationship between immediate and neurotherapeutic effects of FES-assisted walking to identify responders to a FES-assisted gait training protocol.MethodsThe primary outcome was Gait Deviation Index (GDI) and secondary outcome was root mean squared error (RMSE) of the lower extremity joint angles in the sagittal plane between participants with CP and a typically developing (TD) dataset. Potential indicators were defined as immediate improvements from baseline during FES-assisted walking followed by neurotherapeutic improvements at the end of training.Case descriptionGait analysis of two adolescent female participants with spastic diplegia (Gross Motor Function Classification System level II and III) was conducted at the start and end of a 12-week FES-assisted treadmill training protocol. Participant 1 had scissoring crouch gait, while participant 2 had jump gait.OutcomesThe GDI showed both immediate (presence of FES) and neurotherapeutic (absence of FES after training period) improvements from baseline in our two participants. Joint angle RMSE showed mixed trends between immediate and neurotherapeutic changes from baseline. The GDI warrants investigation in a larger sample to determine if it can be used to identify responders to FES-assisted gait training.
Effects of an 8-week multimodal program on thoracic posture, glenohumeral range of motion and serve performance in competitive young tennis players
Authors: Le Solliec Tom , Blache Yoann , Rogowski Isabelle 
Published: March 2023

IntroductionIntensive tennis practice is known to generate sport-specific adaptations at the shoulder region and influence the sagittal spinal curvature. However, increased thoracic kyphosis decreases the shoulder functional capacity, which could limit tennis performance. Therefore, the aim of this study was to investigate the effects of an 8-week multimodal program on thoracic posture, glenohumeral range of motion, and serve performance in competitive young tennis players.MethodsEighteen male and four female players (age: 16.0 ± 2.4 years, height: 170.7 ± 11.0 cm; mass: 62.1 ± 11.5 kg; International Tennis Number: 3–4) performed their regular training during 8 weeks, which was used as a reference period, and implemented a multimodal program including stretching, strengthening, and myofascial release exercises, four times per week during 8 additional weeks, which corresponded to the intervention period. The thoracic curvature angle and mobility, the biacromial and interscapular distances, the glenohumeral range of motion and the tennis serve performance were assessed three times, i.e., before and after the regular training and after the 8-week multimodal program.ResultsThe results showed that the 8-week regular training had no significant effects on thoracic curvature angle [effect size (ES) = 0.02–0.36, p = 0.06–0.46] and mobility (ES = 0.05–0.26, p = 0.13–0.42), biacromial (ES = 0.05, p = 0.18) and interscapular distances (ES = 0.03, p = 0.45), ranges of motion in glenohumeral internal (ES = 0.04, p = 0.43) and external rotation (ES = 0.43, p = 0.06), and tennis serve accuracy (ES = 0.33, p = 0.07) and velocity (ES = 0.09, p = 0.35). The 8-week multimodal program increased moderately the thoracic mobility (ES = 0.55, p = 0.01), moderately to strongly the serve accuracy and velocity (ES = 0.65, p = 0.003, for both), strongly decreased the interscapular distance (ES = 1.02, p &lt; 0.001), and strongly increased the range of motion in glenohumeral internal (ES = 0.90, p &lt; 0.001) and external rotation (ES = 1.49, p &lt; 0.001).DiscussionThese findings indicated that an 8-week multimodal program, including spine and glenohumeral mobility and shoulder girdle strength exercises, performed four times per week during 8 weeks, is moderately relevant to rectify the sagittal thoracic curvature in competitive tennis players, while such a program may help regain the range of motion in glenohumeral rotation without tennis serve performance impairment.