Miracle-dz/UniFAR-FTUs huggingface dataset:
Nuclear factor kappa B regulated monocyte chemoattractant protein-1/chemokine CC motif receptor-2 expressing in spinal cord contributes to the maintenance of cancer-induced bone pain in rats

Background: Chemokine, monocyte chemoattractant protein-1 (MCP-1), is a potential factor to cause cancer-induced bone pain (CIBP). NF-κB signaling is very important in mediating the expression of chemokines and may have a role in CIBP. However, the mechanism is still unclear. This study investigates the role of NF-κB in CIBP by regulating MCP-1/chemokine CC motif receptor-2 (CCR2) signaling pathway. Methods: A rat CIBP model was established by injecting Walker-256 cells into the tibia medullary cavity. Nine days later, animals were intrathecally administrated with MCP-1 neutralizing antibody, CCR2 antagonist (RS504393), or NF-кB inhibitor (BAY11–7081). Mechanical paw withdrawal threshold was used to assess pain behavior and sciatic functional index, and radiographic images were adopted to evaluate the damage of nerve and bone. The spinal cords were harvested for Western blot and quantitative reverse transcription polymerase chain reaction. The distribution of MCP-1, CCR2, and NF-кB was detected by double immunofluorescent staining. Results: CIBP caused remarkable bone destruction, injury of sciatic and femoral nerve, and persistent (>15 days) mechanical allodynia in rats. Tumor cell inoculation upregulate MCP-1 and NF-кB in activated neurons as well as CCR2 in neurons and microglia of the spinal cord. MCP-1 antibody, RS504393, and BAY11–7081 partially reversed CIBP-induced mechanical allodynia, and CIBP regulated the expression levels of pro-inflammatory cytokines, tumor necrosis factor-α and interferon-γ, and anti-inflammatory cytokine, interleukin 4, and BAY11–7081 lowered CIBP-induced MCP-1 and CCR2 expressions in a dose-dependent manner. Conclusion: In conclusion, NF-кB signaling pathway regulates the expressions of MCP-1/CCR2-induced inflammatory factors in the spinal cord of CIBP rats.
Regional Subclinical Cerebrovascular Disease Is Associated with Balance in an Elderly Multi-Ethnic Population

Introduction: White matter hyperintensity volume (WMHV) and subclinical brain infarcts (SBI) are associated with impaired mobility, but less is known about the association of WMHV in specific brain regions. We hypothesized that anterior WMHV would be associated with lower scores on the Short Physical Performance Battery (SPPB), a well-validated mobility scale. Methods: The SPPB was measured a median of 5 years after enrollment into the Northern Manhattan MRI sub study. Volumetric distributions for WMHV in 14 brain regions as a proportion of total cranial volume were determined. Multi-variable linear regression was performed to examine the association of SBI and regional log-WMHV with the SPPB score. Results: Among 668 participants with SPPB measurements (mean 74 ± 9 years, 37% male and 70% Hispanic), the mean SPPB score was 8.2 ± 2.9. Total (beta = –0.3 per SD, p = 0.001), anterior periventricular (beta = –0.4 per SD, p = 0.001), parietal (beta = –0.2 per SD, p = 0.02) and frontal (beta = –0.3 per SD, p = 0.002) WMHVs were associated with SPPB; other WMHV and SBI were not associated with the SPPB. Conclusions: WMHV, especially in the anterior cerebral regions, is associated with a lower SPPB. Prevention of subclinical cerebrovascular disease is a potential target to prevent physical decline in the elderly.
Cerebral Concussion Primes the Lungs for Subsequent Neutrophil-Mediated Injury

Objectives: Mild traumatic brain injury in the form of concussion is extremely common, and the potential effects on pulmonary priming have been underestimated. The aim of this study was to characterize the pulmonary response following mild traumatic brain injury and assess the pulmonary susceptibility to lung injury after a subsequent innocuous pulmonary insult. Design: Experimental in vivo study. Setting: University research laboratory. Subjects: Male CD1 mice. Interventions: We developed a model of concussive traumatic brain injury in mice followed by pulmonary acid microaspiration. To assess the dependent role of neutrophils in mediating pulmonary injury, we specifically depleted neutrophils. Measurements and Main Results: Lateral fluid percussion to the brain resulted in neuronal damage and neutrophil infiltration as well as extensive pulmonary interstitial neutrophil accumulation but no alveolar injury. Following subsequent innocuous acid microaspiration, augmented alveolar neutrophil influx led to the development of pulmonary hemorrhage that was reduced following neutrophil depletion. Conclusions: This model shows for the first time that innocuous acid microaspiration is sufficient to induce neutrophil-mediated lung injury following mild concussion and that the extracranial effects of mild traumatic brain injury have been underestimated.
Synthesis, Biological Evaluation, and Molecular Docking of Novel Thiazoles and [1,3,4]Thiadiazoles Incorporating Sulfonamide Group as DHFR Inhibitors

2‐(1‐{4‐[(4‐Methylphenyl)sulfonamido]phenyl}ethylidene)thiosemicarbazide (3) was exploited as a starting material for the synthesis of two novel series of 5‐arylazo‐2‐hydrazonothiazoles 6a – 6j and 2‐hydrazono[1,3,4]thiadiazoles 10a – 10d, incorporating sulfonamide group, through its reactions with appropriate hydrazonoyl halides. The structures of the newly synthesized products were confirmed by spectral and elemental analyses. Also, the antimicrobial, anticancer, and DHFR inhibition potency for two series of thiazoles and [1,3,4]thiadiazoles were evaluated and explained by molecular docking studies and SAR analysis.
Brain, antibiotics, and microbiota – how do they interplay?

The microbiome and its cross‐talk with the brain have drawn increasing attention lately, since imbalances in the gut microbiota's composition may result in pathogenic dysfunctions affecting brain functioning up to development of neurodegenerative and mental diseases. The current Editorial discusses a study by Gao and coworkers in the current issue of the Journal of Neurochemistry in which the authors use a model of antibiotic‐induced dysbiosis ‐ targeted infusion of antibiotics into the gut ‐ to assess if microbiotic metabolites exert effects on local neurotransmitter expression or contribute to the gut‐brain axis. The authors mechanistically link distal ileal infusion of antibiotics with a change in the levels of microbial metabolites that affect the expression of neurotransmitters in the brain and thereby can participate in the fine‐tuning of the hypothalamic functions, including regulation of visceral and neuroendocrine processes, stress responses, mood and anxiety. Their study thus represents an important step towards our understanding of the brain‐gut axis, with the potential to advance therapeutics.
Delineating the Cellular Mechanisms Associated with Skin Electroporation.

The immune responses elicited following delivery of DNA vaccines to the skin has previously been shown to be significantly enhanced by the addition of electroporation (EP) to the treatment protocol. Principally, EP increases the transfection of plasmid DNA (pDNA) into the resident skin cells. In addition to increasing the levels of in vivo transfection, the physical insult induced by EP is associated with activation of innate pathways which are believed to mediate an adjuvant effect, further enhancing DNA vaccine responses. We investigated the possible mechanisms associated with this adjuvant effect, primarily focusing on the cell death pathways associated with the skin EP procedure independent of pDNA delivery. Using the minimally invasive CELLECTRA®-3P intradermal electroporation device that penetrates the epidermal and dermal layers of the skin, we have investigated apoptotic and necrotic cell death in relation to the vicinity of the electrode needles and electric field generated. Employing the well-established terminal deoxynucleotidyl transferase nick-end labeling assay, we detected apoptosis beginning as early as one hour after EP and peaking at the 4 h time point. The majority of the apoptotic events were detected in the epidermal region directly adjacent to the electrode needle. Using a novel propidium iodide in vivo necrotic cell death assay, we detected necrotic events concentrated in the epidermal region adjacent to the electrode. Furthermore, we detected upregulation of calreticulin expression on skin cells after EP, thus labeling these cells for uptake by dendritic cells and macrophages. These results allow us to delineate the cell death mechanisms occurring in the skin following intradermal EP independently of pDNA delivery. We believe these events contribute to the adjuvant effect observed following electroporation at the skin treatment site.
Relationship between the use of social media of the universities of Ecuador Vs. the consumption of millennials

The objectives of this study are A) To analyze the scope of the communication management strategies utilized in third lever academic institutions in Ecuador. B) To determine the need for a study that identifies and characterizes how the communication tools are used by these institutions. Additionally, it is important to highlight whether the strategies utilized have a positive effect on the target population. This investigation encompasses the analysis of communicational strategies and the use of the different media tools within the universities in Ecuador as well as the analysis of which media are preferred by the so-called millennials or Generation Y (target population). The study had 2 phases. Phase 1 was focused in identify the habits of media use of our target population. To accomplish this task, we gathered data from a survey of 8,000 college students as well as official information sources. Phase 2 was aimed to identify which digital communicational strategies are used in the different universities of Ecuador. For Phase two we used an actual metric tool known as fan page karma. The results of our study allowed us to identify and contrast the different social media the millennials prefer versus those utilized by the universities of Ecuador. The study also determined which variables were linked to the management of such social media by the different universities.
Human Biomarkers of Outcome Following Rift Valley Fever Virus Infection

Rift Valley fever virus is an arbovirus found in Africa and the Middle East. Most infected individuals experience a mild self-limiting illness; however, some develop severe disease including hepatitis, hemorrhagic fever, or encephalitis. The biological reasons for these marked differences in disease manifestation are unknown. In this study, we evaluate 32 biomarkers in serum of 26 patients from an outbreak that occurred in Saudi Arabia in 2000-2001. Eleven biomarkers correlated with viral RNA. Thirteen biomarkers were associated with a fatal outcome. No associations of biomarkers and hemorrhage or central nervous system disease were identified in this cohort.
Outcome of 449 adult patients with rhabdomyosarcoma: an observational ambispective nationwide study

Five‐year overall survival (OS) of localized RMS exceeds 70% in children (<18) but is very poor in adult patients. We analyzed the outcome and prognostic factors (PF) of a national series of adult patients with RMS in a large study. The study population consisted of two different cohorts: a retrospective cohort (157 adult patients treated in 13 reference centers between 05/1981 and 02/2010) and the prospective cohort (292 patients with RMS diagnosed and treated between 01/2010 and 12/2014 in France) included in the NetSarc database. A descriptive analysis of patients’ characteristics and prognostic factors was conducted on both series which were compared. In the retrospective series, histological subtypes were embryonal (E‐RMS) for 21% of patients, alveolar (A‐RMS) for 35% of patients, and “adult‐type” P‐RMS (pleomorphic, spindle cell RMS, not otherwise specified) (P) for 44% patients. This distribution significantly differed in the prospective cohort: A‐RMS: 18%; E‐RMS: 17%; and P‐RMS 65%. With a median follow‐up of 8.5 years, 5‐year OS for localized RMS and advanced RMS (with nodes and/or metastases) was 43% and 5%, respectively, (P < 0.0001), and median OS was 51, 33, and 16 months for E‐RMS, A‐RMS, and P‐RMS, respectively, in the retrospective cohort. The median OS was less than 40 months for the prospective nationwide cohort for the entire population. In a multivariate analysis of the retrospective study, independent prognostic factors for OS were A‐RMS, R0 resection, and adjuvant radiotherapy (RT). For localized RMS, age and use of pediatric chemotherapy (CT) regimen are independent prognostic factors. Adult patients with RMS have a poorer overall survival than pediatric patients, and survival varies considerably across histological subtypes.
Interactive Visual Exploration of the Regesta Imperii

The Academy of Sciences and Literature in Mainz provides online access to the Regesta Imperii a very extensive historical dataset based on documentary sources of German-Roman kings. About 125,000 regestae of emperors and popes are searchable and viewable in this online portal. The current user interface offers direct access to single documents through different form-based search facilities, as well as through a catalogue that directly reflects the structure of the regestae volumes as they have been created in this long-term project. In order to further improve access to this large data volume, we suggest an additional approach based on coordinated views. The usage of coordinated view approaches is very common in many domains (Stasko et al, 2008, Vuillemot et al, 2009, Koch et al, 2011). However, there is no publicly system available, which would provide a suitable access to this historical dataset. The motivation for this new approach is twofold. On the one hand, we improve the support for search and exploration tasks in this historical data set that are based on imprecise information needs or on a less deep understanding of the available information. In practice, such imprecise queries can quickly lead to an overwhelmingly large number of search results. Allowing users to create and refine queries in a visual way, while offering immediate feedback on the number of entries requested, can help to cope with underspecified queries and help refining them iteratively (Jänicke et al, 2012). On the other hand, we offer a powerful means for visually analyzing the available information and understanding complex relationships by providing different linked perspectives on subsets of the collections. These perspectives include views on historic persons and entities as well as temporal and spatial information contained in the regestae. A usage scenario shows successful application of the approach.
Contributions to the ontology of aging, the sensitive indicators of rehabilitation nursing care, in terms of self-care, in people with respiratory disorders

With the increase in the average life expectancy, the appearance of chronic diseases and, in particular, in the respiratory forum and its disadvantages in the autonomy and self-care of patients, brought an important paradigm for health care and, in particular, rehabilitation nursing, with implications for the development of ontologies of aging. Thus, it is imperative to systematize them in scientifically measurable indicators to demonstrate the benefit that rehabilitation nursing brings to improve patients' quality of life, thus ensuring excellence. Each area of scientific health should contribute to the construction of aging ontology. Objective: to identify indicators sensitive to nursing care of rehabilitation, in terms of self-care, in relation to those with respiratory pathology, to be integrated into the ontology of aging. Methods: A systematic review of the literature was performed using the EBSCO (full-text MEDLINE, CINAHL, Full-Text Plus, British Nursing Index), using the PI [C] O method with 6 emergent articles. Results: A total of 20 indicators were identified, including: Ability to perform activities, increase physical and functional independence, symptom management, reduction of complications, increase in quality of life, which can be allocated as a proposal for classes of the aging ontology. Conclusion: Knowledge of indicators sensitive to nursing care recognition of the importance of rehabilitation nursing in increasing self-care and autonomy for people with respiratory pathology, and research in this area is fundamental for its effectiveness and efficiency, and its integration in the ontologies of aging is fundamental.
Imaging Cardiovascular Calcification

C ardiovascular disease is the leading cause of morbidity and mortality worldwide. Atherosclerosis is a complex and multifactorial process, characterized by early asymptomatic formation of plaque in the arterial walls, silent plaque progression that poses flow limitation, and risk of sudden rupture and subsequent thrombotic occlusion. The early assessment and predictive value of atherosclerotic plaque development and rupture are critically important to prevent clinical consequences. Inflammation and calcification play important roles in the pathophysiological progression of atherosclerosis. In the early stage, inflammation is the predominant process involved that promotes plaque progression and calcification. The repeated cycles of inflammatory damage and repair ultimately lead to calcification of the vessel walls, whose extent provides an important estimate of atherosclerotic progression and clinical prognosis. Macrocalcification is considered the stable stage of vascular disease, whereas the dynamic process of microcalcification may increase the risk of plaque rupture and adverse clinical events. Therefore, imaging early calcification is important to identify individuals with enhanced risk of cardiovascular events. Furthermore, many studies have demonstrated coronary artery calcification as a marker for the extent of atherosclerosis and overall plaque burden, and as an important independent predictor of cardiovascular events, mortality, and morbidity. Over the past few decades, advanced imaging methods have improved our assessment of atherosclerotic calcification and have provided insights into cardiovascular risk and have contributed to the understanding of the underlying pathophysiologic mechanisms of atherosclerosis. This review aims to summarize current imaging techniques for vascular calcification (Table) and their applications in clinical research.
Targeting Tropomyosin Receptor Kinase in Cutaneous CYLD Defective Tumors With Pegcantratinib

Importance There are no medical interventions for the orphan disease CYLD cutaneous syndrome (CCS). Transcriptomic profiling of CCS skin tumors previously highlighted tropomyosin receptor kinases (TRKs) as candidate therapeutic targets. Objective To investigate if topical targeting of TRK with an existing topical TRK inhibitor, pegcantratinib, 0.5% (wt/wt), is safe and efficacious in CCS. Design, Setting, and Participants A phase 1b open-label safety study, followed by a phase 2a within-patient randomized (by tumor), double-blind, placebo-controlled trial (the Tropomyosin Receptor Antagonism in Cylindromatosis [TRAC] trial). The setting was a single-center trial based at a tertiary dermatogenetics referral center for CCS (Royal Victoria Infirmary, Newcastle, United Kingdom). Patients who had germline mutations in CYLD or who satisfied clinical diagnostic criteria for CCS were recruited between March 1, 2015, and July 1, 2016. Interventions In phase 1b, patients with CCS applied pegcantratinib for 4 weeks to a single skin tumor. In phase 2a, allocation of tumors was to either receive active treatment on the right side and placebo on the left side (arm A) or active treatment on the left side and placebo on the right side (arm B). Patients were eligible if they had 10 small skin tumors, with 5 matched lesions on each body side; patients were randomized to receive active treatment (pegcantratinib) to one body side and placebo to the other side once daily for 12 weeks. Main Outcomes and Measures The primary outcome measure was the number of tumors meeting the criteria for response in a prespecified critical number of pegcantratinib-treated tumors. Secondary clinical outcome measures included an assessment for safety of application, pain in early tumors, and compliance with the trial protocol. Results In phase 1b, 8 female patients with a median age of 60 years (age range, 41-80 years) were recruited and completed the study. None of the participants experienced any adverse treatment site reactions. Three patients reported reduced pain in treated tumors. In phase 2a (15 patients [13 female; median age, 51 years], with 150 tumors), 2 tumors treated with pegcantratinib achieved the primary outcome measure of response compared with 6 tumors treated with placebo. The primary prespecified number of responses was not met. The incidence of adverse events was low. Conclusions and Relevance In this study, pegcantratinib, 0.5% (wt/wt), applied once daily appeared to be well tolerated and to penetrate the tumor tissue; however, the low tumor drug concentrations demonstrated are likely to account for the lack of response. Dose-escalation studies to assess the maximal tolerated dose may be beneficial in future studies of CCS. Trial Registration isrctn.org Identifier: ISRCTN75715723
Cardiologists' experiences and perceptions of patient involvement and communication related to shared decision-making regarding atrial fibrillation treatment.

OBJECTIVE To feel involved in decisions about atrial fibrillation (AF) treatment, patients need supportive communication from cardiologists. Shedding light on cardiologists' perceptions of patient involvement in AF care settings is thus of importance. We examine (1) how cardiologists describe patient involvement and communication related to shared decisionmaking regarding AF treatment, and (2) their perceptions of efforts to involve patients in the treatment decisions. METHODS Ten cardiologists were interviewed in four Swedish hospitals. A qualitative content analysis was performed on the interview data. RESULTS Cardiologists' perceptions of patient involvement in treatment decisions are framed in terms of (1) ideology, (2) experience, and (3) responsibility. CONCLUSION By taking into account patients' feelings in the consultations, and by actively encouraging patients to be involved, the cardiologists contributed to patient involvement. PRACTICE IMPLICATIONS One key to improving compliance with legislation aimed at increasing patient involvement in treatment decisions could lie in paying attention to physician-patient communication and the conditions for patient involvement in decision-making about treatment.
MBNL splicing activity depends on RNA binding site structural context

Abstract Muscleblind-like (MBNL) proteins are conserved RNA-binding factors involved in alternative splicing (AS) regulation during development. While AS is controlled by distribution of MBNL paralogs and isoforms, the affinity of these proteins for specific RNA-binding regions and their location within transcripts, it is currently unclear how RNA structure impacts MBNL-mediated AS regulation. Here, we defined the RNA structural determinants affecting MBNL-dependent AS activity using both cellular and biochemical assays. While enhanced inclusion of MBNL-regulated alternative exons is controlled by the arrangement and number of MBNL binding sites within unstructured RNA, when these sites are embedded in a RNA hairpin MBNL binds preferentially to one side of stem region. Surprisingly, binding of MBNL proteins to RNA targets did not entirely correlate with AS efficiency. Moreover, comparison of MBNL proteins revealed structure-dependent competitive behavior between the paralogs. Our results showed that the structure of targeted RNAs is a prevalent component of the mechanism of alternative splicing regulation by MBNLs.