Miracle-dz/UniFAR-FTUs huggingface dataset:
Clinical quality and efficiency of monolithic glass ceramic crowns in the posterior area: digital compared with conventional workflows.

PURPOSE The aim of this clinical study was to test whether or not digital workflows for the fabrication of crowns render different clinical outcomes from the conventional pathway with respect to (1) crown quality, and (2) time efficiency. MATERIAL AND METHODS For each of the 10 patients in need of one tooth-supported crown, five monolithic crowns were produced out of lithium disilicate reinforced glass ceramic. Four different optical impression and associated computer-aided design/computer-aided manufacturing (CAD/CAM) systems were used for crown fabrication (digital workflows): (1) Lava C.O. S. scanner and Lava C.O. S. and CARES CAD software, centralized CAM (group L); (2) Cadent iTero scanner, CARES CAD software and centralized CAM (group iT); (3) Cerec Bluecam, Cerec Connect CAD software, followed by laboratory-based CAM (group CiL); and (4) centralized CAM (group CiD). The conventional crown (group K) was fabricated based on a conventional silicone impression followed by a conventional wax-up and heat press technique. The examiners were blinded and evaluated the crowns clinically at the bisque-bake stage (initial try-in), and subsequently after finalization by a dental technician (final try-in). For the assessment of crown quality, modified United States Public Health Service (USPHS) criteria were used. Treatment times were recorded for clinical evaluation and adjustment. The quality ratings were analyzed descriptively. For both the continuous and ordinal outcomes, the non-parametric paired Wilcoxon test was applied, together with an appropriate Bonferroni correction to evaluate the differences between treatment groups. The results of the statistical analysis were interpreted globally at the significance level P = 0.05. RESULTS The clinical evaluation during the initial and final try-ins demonstrated similar clinical outcome measures for crowns generated with the four digital workflows and the conventional workflow. No statistically significant differences of crown quality in any state were found between groups (P > 0.005). The total clinical treatment times measured were: 456 ± 240 s for L; 655 ± 374 s for iT; 783 ± 403 s for CiL; 556 ± 285 s for CiD; and 833 ± 451 s for K. No statistically significant differences in treatment times were found between the groups (P > 0.05). CONCLUSIONS Within the limitations of the present study, the monolithic ceramic crowns resulting from the four different CAD/CAM systems did not differ from the conventionally produced crowns with respect to the clinical quality rating and the treatment time efficiency.
High-Intensity Interval Training Is Associated With Alterations in Blood Biomarkers Related to Brain Injury

Purpose: Blood biomarkers are a useful tool to study concussion. However, their interpretation is complicated by a number of potential biological confounds, including exercise. This is particularly relevant in military and athletic settings where injury commonly occurs during physical exertion. The impact of high-intensity interval training (HIIT) on putative brain injury biomarkers remains under-examined. The purpose of this study was to observe the effects of HIIT on a panel of blood biomarkers associated with brain injury. Methods: Eleven healthy, recreationally active males (median age = 29.0, interquartile range = 26.0–31.5) performed HIIT on a bicycle ergometer (8-12 × 60-s intervals at 100% of peak power output, interspersed by 75-s recovery at 50 W) three times/week for 2 weeks. Peripheral blood samples were collected before and immediately after HIIT during the first and last training sessions. Plasma concentrations of s100 calcium-binding protein beta (S100B), glial fibrillary acidic protein (GFAP), neuron-specific enolase (NSE), brain-derived neurotrophic factor (BDNF), neurogranin (NRGN), peroxiredoxin (PRDX)-6, creatine kinase-BB isoenzyme (CKBB), visinin-like protein (VILIP)-1, von Willebrand factor (vWF), monocyte chemoattractant protein (MCP)-1, matrix metalloproteinase (MMP)-9, and total tau (T-tau) were quantitated by high-sensitivity MULTI-SPOT® immunoassay, on the MesoScale Diagnostics electrochemiluminescence detection platform. Differences in biomarker concentrations in response to HIIT were evaluated by partial least squares discriminant analysis (PLSDA) within a repeated-measures bootstrapped framework. Results: Ten of 12 biomarkers were increased pre-to-post HIIT; VILIP-1 remained unchanged, and GFAP was not statistically evaluated due to insufficient detectability. After 2 weeks of HIIT, T-tau was no longer significantly elevated pre-to-post HIIT, and significant attenuation was noted in the acute responses of NRGN, PRDX-6, MMP-9, and vWF. In addition, compared to session 1, session 6 pre-exercise concentrations of NSE and VILIP-1 were significantly lower and higher, respectively. Conclusion: Blood biomarkers commonly associated with brain injury are significantly elevated in response to a single bout of HIIT. After a 2-week, six-session training protocol, this response was attenuated for some, but not all markers. While biomarkers continue to provide promise to concussion research, future studies are necessary to disentangle the common biological sequelae to both exercise and brain injury.
Lung transplantation in scleroderma: recent advances and lessons

Purpose of review The purpose of this review is to highlight recent data regarding feasibility and outcomes following lung transplantation for patients with systemic sclerosis related pulmonary disease as well as to emphasize areas of uncertainly in need of further study. We include a description of our centre's approach to lung transplant evaluation and posttransplant management in this complex patient population. Recent findings Historical data have demonstrated that patients with scleroderma have an increased risk of complications following lung transplantation owing to the multisystem nature of disease, particularly concurrent gastrointestinal, cardiac and renal involvement. Emerging data support the safety of lung transplant in appropriately selected patients with scleroderma-related interstitial lung disease and pulmonary arterial hypertension. Summary Accumulating evidence validates that a diagnosis of scleroderma is not a priori a contraindication to lung transplant. In the carefully selected patient, both short-term and long-term outcomes following lung transplantation are comparable to counterparts with fibrotic lung disease or pulmonary arterial hypertension. However, further prospective study to detail how these patients should be evaluated and managed posttransplant is definitely needed. Cardiac disease is an emerging cause of morbidity and mortality in the scleroderma population and deserves particular attention during the pre and posttransplant period.
“Living in a foreign country”: experiences of staff–patient communication in inpatient stroke settings for people with post-stroke aphasia and those supporting them

Abstract Purpose: Staff–patient communication in in-patient stroke settings is viewed as challenging for stroke survivors with aphasia and those supporting them. This study sought to explore these experiences from the perspectives of stroke survivors, their carers and healthcare professionals. Methods: A qualitative study where stroke survivors with aphasia, carers and healthcare professionals were interviewed (audio-recorded) one-to-one or via focus group. Stroke survivors were at least 6 months post-stroke and had a self-reported mild to moderate level of post-stroke aphasia. Transcripts for each group were analysed separately using inductive thematic analysis; followed by an integrative analysis. Results: Six stroke survivors with aphasia, 10 carers, and six healthcare professionals were recruited. Three overarching themes were identified: “being in a foreign country”, “finding a voice”, and “you’re just a number”. A dynamic model of communication is proposed offering a framework for understanding the relationships between “the context”, “the people” and “the interactions”. Conclusions: Communication was viewed as important but challenging by all three groups. To maximise staff–patient interactions in the future, attention needs to be paid to: the psychosocial needs of stroke survivors and their carers, ongoing staff training and support for the healthcare professionals supporting them, and the provision of an aphasia-friendly and a communicatively stimulating ward environment. Implications for Rehabilitation Effective staff–patient communication is viewed as fundamental to stroke rehabilitation but challenging by patients with aphasia, their carers and the healthcare professionals supporting them. To maximise staff–patient communication three key areas must be considered and targeted: those involved/affected by staff–patient communication (“the people”), factors within the “hospital context”, and “the interactions” between “the people”. Tailoring and being consistent with communication and care is paramount to avoid repeated negative communication encounters which can result in disengagement from care. Stroke rehabilitation which currently focuses on the physical fails to address the psychological/emotional and social needs of the patients and those supporting them.
Sex Differences in the Association Between Cannabis Use and Suicidal Ideation and Attempts, Depression, and Psychological Distress Among Canadians

Background: Depression, anxiety, and substance use disorders are leading causes of morbidity worldwide. The most commonly used illicit substance is cannabis and there is some evidence that the association between cannabis use and poor mental health is more pronounced among females compared with males. This analysis examines sex differences in the association between cannabis use and major depressive episode (MDE), suicidal thoughts and attempts, and psychological distress. Methods: This study uses data from the 2002 and 2012 Canadian Community Health Survey’s Mental Health Component, repeated cross-sectional surveys of nationally representative samples of Canadians 15 years of age and older (n = 43,466). Linear and binary logistic regressions were performed, applying weighting and bootstrapping. Results: There were significant sex differences in the strength of the association between cannabis use and suicidal thoughts and attempts and psychological distress, but not MDE. Females who reported using cannabis occasionally (defined as 1 to 4 times a month) reported higher levels of psychological distress than their male counterparts. Females who reported using regularly (defined as more than once per week) reported higher levels of psychological distress and were more likely to report suicidal thoughts and attempts. Conclusions: Future research is needed to further our understanding of the nature of these sex differences. Public health messaging should incorporate being female as a potential risk factor for the co-occurrence of cannabis use and emotional problems, particularly at higher frequencies of use. Clinicians should also be aware of this association to better inform integrated mental health and substance use screening, discussions, and care, particularly for female patients.
Aplastic anemia in the elderly: a nationwide survey on behalf of the French Reference Center for Aplastic Anemia

Aplastic anemia is a rare but potentially life-threatening disease that may affect older patients. Data regarding the treatment of aplastic anemia in this ageing population remains scarce. We conducted a retrospective nationwide multicenter study in France to examine current treatments for aplastic anemia patients over 60 years old. Our aims were to evaluate efficacy and tolerance, and to analyze predictive factors for response and survival. Over the course of a decade, 88 patients (median age 68.5 years) were identified in 19 centers, with a median follow up of 2.7 years; 21% had very severe and 36% severe aplastic anemia. We analyzed 184 treatment lines, mostly involving the standard combination of anti-thymocyte globulin and cyclosporine-A (33%), which was also the most frequent first-line treatment (50%). After first-line therapy, 32% of patients achieved a complete response, and 15% a partial response. Responses were significantly better in first line and in patients with good performance status, as well as in those that had followed an anti-thymocyte globulin and cyclosporine-A regimen (overall response rate of 70% after first-line treatment). All treatments were well tolerated by patients, including over the age of 70. Three-year survival was 74.7% (median 7.36 years). Age, Charlson comorbidity index and very severe aplastic anemia were independently associated with mortality. Age, per se, is not a limiting factor to aplastic anemia treatment with anti-thymocyte globulin and cyclosporine-A; this regimen should be used as a first-line treatment in elderly patients if they have a good performance status and low comorbidity index score.
On the Extraction and Analysis of Graphs From Resting-State fMRI to Support a Correct and Robust Diagnostic Tool for Alzheimer's Disease

The diagnosis of Alzheimer's disease (AD), especially in the early stage, is still not very reliable and the development of new diagnosis tools is desirable. A diagnosis based on functional magnetic resonance imaging (fMRI) is a suitable candidate, since fMRI is non-invasive, readily available, and indirectly measures synaptic dysfunction, which can be observed even at the earliest stages of AD. However, the results of previous attempts to analyze graph properties of resting state fMRI data are contradictory, presumably caused by methodological differences in graph construction. This comprises two steps: clustering the voxels of the functional image to define the nodes of the graph, and calculating the graph's edge weights based on a functional connectivity measure of the average cluster activities. A variety of methods are available for each step, but the robustness of results to method choice, and the suitability of the methods to support a diagnostic tool, are largely unknown. To address this issue, we employ a range of commonly and rarely used clustering and edge definition methods and analyze their graph theoretic measures (graph weight, shortest path length, clustering coefficient, and weighted degree distribution and modularity) on a small data set of 26 healthy controls, 16 subjects with mild cognitive impairment (MCI) and 14 with Alzheimer's disease. We examine the results with respect to statistical significance of the mean difference in graph properties, the sensitivity of the results to model and parameter choices, and relative diagnostic power based on both a statistical model and support vector machines. We find that different combinations of graph construction techniques yield contradicting, but statistically significant, relations of graph properties between health conditions, explaining the discrepancy across previous studies, but casting doubt on such analyses as a method to gain insight into disease effects. The production of significant differences in mean graph properties turns out not to be a good predictor of future diagnostic capacity. Highest predictive power, expressed by largest negative surprise values, are achieved for both atlas-driven and data-driven clustering (Ward clustering), as long as graphs are small and clusters large, in combination with edge definitions based on correlations and mutual information transfer.
Extraction and Standardization of Patient Complaints from Electronic Medication Histories for Pharmacovigilance: Natural Language Processing Analysis in Japanese

Background Despite the growing number of studies using natural language processing for pharmacovigilance, there are few reports on manipulating free text patient information in Japanese. Objective This study aimed to establish a method of extracting and standardizing patient complaints from electronic medication histories accumulated in a Japanese community pharmacy for the detection of possible adverse drug event (ADE) signals. Methods Subjective information included in electronic medication history data provided by a Japanese pharmacy operating in Hiroshima, Japan from September 1, 2015 to August 31, 2016, was used as patients’ complaints. We formulated search rules based on morphological analysis and daily (nonmedical) speech and developed a system that automatically executes the search rules and annotates free text data with International Classification of Diseases, Tenth Revision (ICD-10) codes. The performance of the system was evaluated through comparisons with data manually annotated by health care workers for a data set of 5000 complaints. Results Of 5000 complaints, the system annotated 2236 complaints with ICD-10 codes, whereas health care workers annotated 2348 statements. There was a match in the annotation of 1480 complaints between the system and manual work. System performance was . 66 regarding precision, . 63 in recall, and . 65 for the F-measure. Conclusions Our results suggest that the system may be helpful in extracting and standardizing patients’ speech related to symptoms from massive amounts of free text data, replacing manual work. After improving the extraction accuracy, we expect to utilize this system to detect signals of possible ADEs from patients’ complaints in the future.
Oleocanthal Inhibits Catabolic and Inflammatory Mediators in LPS-Activated Human Primary Osteoarthritis (OA) Chondrocytes Through MAPKs/NF-κB Pathways

Background/Aims: Oleocanthal (OC), a phenolic compound present in extra virgin olive oil (EVOO), has attracted attention since its discovery for its relevant pharmacological properties in different pathogenic processes, including inflammation. Here, we investigated the involvement of OC in LPS-activated osteoarthritis (OA) human primary chondrocytes. Methods: Human primary chondrocytes were harvested from articular cartilage samples obtained from OA patients. The effects of OC on the viability of chondrocytes were tested by MTT assay. Protein and mRNA expression of several catabolic and pro-inflammatory factors after OC treatment were measured by RT-qPCR and western blot respectively. Moreover, we analysed the NO production by Griess reaction. Finally, several pathways mediators were analysed by western blot. Results: We demonstrated that OC did not have any cytotoxic effect. Oleocanthal inhibited NO production and strongly decreased NOS2 and COX-2 protein and mRNA expression in LPS-activated human primary OA chondrocytes. Interestingly, OC also inhibits MMP-13 and ADAMTS-5. In addition, OC downregulates several pro-inflammatory factors, such as IL-6, IL-8, CCL3, LCN2 and TNF-α induced by LPS in human primary OA chondrocytes. Finally, we demonstrated that OC exerts its effects through the MAPK/P38/NF-kB pathways. Conclusion: These data show that OC is able to block LPS-mediated inflammatory response and MMP-13 and ADAMTS-5 induction in human primary OA chondrocytes via MAPKs/NF-kB pathways, suggesting that OC may be a promising agent for the treatment of inflammation in cartilage and a potential molecule to prevent disease progression by inhibiting metalloproteases and aggrecanases.
Large-scale health disparities associated with Lyme disease and human monocytic ehrlichiosis in the United States, 2007–2013

Promoting health equity is a fundamental public health objective, yet health disparities remain largely overlooked in studies of vectorborne diseases, especially those transmitted by ticks. We sought to identify health disparities associated with Lyme disease and human monocytic ehrlichiosis, two of the most pervasive tickborne diseases within the United States. We used general linear mixed models to measure associations between county-level disease incidence and six variables representing racial/ethnic and socioeconomic characteristics of counties (percent white non-Hispanic; percent with a bachelors degree or higher; percent living below the poverty line; percent unemployed; percent of housing units vacant; per capita number of property crimes). Two ecological variables important to tick demography (percent forest cover; density of white-tailed deer) were included in secondary analyses to contextualize findings. Analyses included data from 2,695 counties in 37 states and the District of Columbia during 2007–2013. Each of the six variables was significantly associated with the incidence of one or both diseases, but the direction and magnitude of associations varied by disease. Results suggested that the incidence of Lyme disease was highest in counties with relatively higher proportions of white and more educated persons and lower poverty and crime rates; the incidence of human monocytic ehrlichiosis was highest in counties with relatively higher proportions of white and less educated persons, higher unemployment rates and lower crime rates. The percentage of housing units vacant was a strong positive predictor for both diseases with a magnitude of association comparable to those between incidence and the ecological variables. Our findings indicate that racial/ethnic and socioeconomic disparities in disease incidence appear to be epidemiologically important features of Lyme disease and human monocytic ehrlichiosis in the United States. Steps to mitigate encroachment of wild flora and fauna into areas with vacant housing might be warranted to reduce disease risk.
Maximizing the Role of Physiologically Based Oral Absorption Modeling in Generic Drug Development

Physiologically based Oral Absorption Modeling has been gaining traction in the biopharmaceutics aspects of drug product development as a tool to guide formulation development, Quality by Design (QbD), food effect prediction, effect of acid reducing agents, SUPAC activities and influence label language. This opinion piece is intended to provide a perspective on the potential applications of oral absorption modeling in guiding formulation development, bioequivalence predictions and support regulatory interactions in development of generic drug products. This article is protected by copyright. All rights reserved.
Mapping the Contact Sites of the Escherichia coli Division-Initiating Proteins FtsZ and ZapA by BAMG Cross-Linking and Site-Directed Mutagenesis

Cell division in bacteria is initiated by the polymerization of FtsZ at midcell in a ring-like structure called the Z-ring. ZapA and other proteins assist Z-ring formation and ZapA binds ZapB, which senses the presence of the nucleoids. The FtsZ–ZapA binding interface was analyzed by chemical cross-linking mass spectrometry (CXMS) under in vitro FtsZ-polymerizing conditions in the presence of GTP. Amino acids residue K42 from ZapA was cross-linked to amino acid residues K51 and K66 from FtsZ, close to the interphase between FtsZ molecules in protofilaments. Five different cross-links confirmed the tetrameric structure of ZapA. A number of FtsZ cross-links suggests that its C-terminal domain of 55 residues, thought to be largely disordered, has a limited freedom to move in space. Site-directed mutagenesis of ZapA reveals an interaction site in the globular head of the protein close to K42. Using the information on the cross-links and the mutants that lost the ability to interact with FtsZ, a model of the FtsZ protofilament–ZapA tetramer complex was obtained by information-driven docking with the HADDOCK2.2 webserver.