Miracle-dz/UniFAR-FTUs huggingface dataset:
The Diadenylate Cyclase CdaA Is Critical for Borrelia turicatae Virulence and Physiology

Relapsing fever (RF), caused by spirochetes of the genus Borrelia, is a globally distributed, vector-borne disease with high prevalence in developing countries. To date, signaling pathways required for infection and virulence of RF Borrelia spirochetes are unknown. Cyclic di-AMP (c-di-AMP), synthesized by diadenylate cyclases (DACs), is a second messenger predominantly found in Gram-positive organisms that is linked to virulence and essential physiological processes. ABSTRACT Relapsing fever (RF), caused by spirochetes of the genus Borrelia, is a globally distributed, vector-borne disease with high prevalence in developing countries. To date, signaling pathways required for infection and virulence of RF Borrelia spirochetes are unknown. Cyclic di-AMP (c-di-AMP), synthesized by diadenylate cyclases (DACs), is a second messenger predominantly found in Gram-positive organisms that is linked to virulence and essential physiological processes. Although Borrelia is Gram-negative, it encodes one DAC (CdaA), and its importance remains undefined. To investigate the contribution of c-di-AMP signaling in the RF bacterium Borrelia turicatae, a cdaA mutant was generated. The mutant was significantly attenuated during murine infection, and genetic complementation reversed this phenotype. Because c-di-AMP is essential for viability in many bacteria, whole-genome sequencing was performed on cdaA mutants, and single-nucleotide polymorphisms identified potential suppressor mutations. Additionally, conditional mutation of cdaA confirmed that CdaA is important for normal growth and physiology. Interestingly, mutation of cdaA did not affect expression of homologs of virulence regulators whose levels are impacted by c-di-AMP signaling in the Lyme disease bacterium Borrelia burgdorferi. Finally, the cdaA mutant had a significant growth defect when grown with salts, at decreased osmolarity, and without pyruvate. While the salt treatment phenotype was not reversed by genetic complementation, possibly due to suppressor mutations, growth defects at decreased osmolarity and in media lacking pyruvate could be attributed directly to cdaA inactivation. Overall, these results indicate CdaA is critical for B. turicatae pathogenesis and link c-di-AMP to osmoregulation and central metabolism in RF spirochetes.
Characterization of the Early Years of Bevacizumab Use for First-Line Treatment of Ovarian Cancer in the United States

PURPOSE: To quantify early dissemination patterns, factors influencing use, and costs of bevacizumab (BEV) for the treatment of newly diagnosed ovarian cancer (OC) in the United States before its regulatory approval for this indication (off-label use). METHODS: We identified women 18-65 years of age with newly diagnosed OC treated with surgery and platinum-based chemotherapy from 2008 to 2016 through the MarketScan database (N = 8,109). The proportion of women receiving BEV over time was calculated, multivariate logistic regression used to determine factors associated with BEV use, and total costs per cycle of chemotherapy with and without BEV abstracted. RESULTS: BEV utilization rose 1.8-fold during the study period, from 4.1% (2008) to 7.4 % (2016). BEV was used with non–platinum/taxane regimens over a third of the time (37.2%). Physician specialty (medical oncology v gyn oncology) and geography (southeast region) were significantly associated with higher rates of use. Clinical factors associated with BEV use were metastatic disease and presence of ascites. The median cost of one cycle of platinum/taxane chemotherapy plus BEV was $10,897 in US dollars (USD) (interquartile range $7,573-$18,133 USD), compared with $1,629 USD (interquartile range, $683.0-$4,461 USD) for platinum/taxane alone. CONCLUSION: Off-label use of BEV for newly diagnosed OC was rare (< 10%), but doubled following presentation of phase II and III data at international meetings. Both clinical (ascites, metastatic disease, and age) and nonclinical (specialty and region) factors were associated with BEV use, and its use was accompanied by a six-fold increase in the cost of one cycle of treatment.
Aging and technology: understanding the issues and creating a base for technology designers

Abstract The world's population continues to increase, and now we have more aged and aging people than ever before. As people age, many of them develop health problems that impede their independence. Fortunately, the fast pace of contemporary technology provides new ways to overcome health barriers faced by the aged. Considering the countless number of efforts made in aging and technology, the time has come to reorganise and combine the two fields and reveal the most disciplined and innovative technological approaches in a partnership designed to help the elderly. In this paper, age-related health issues are discussed and organised. Then, each health issue is examined in terms of what technological solutions are available to improve the health of the elderly. As a result, a solid base for technology designers is established to encourage them, direct their effort, and enrich their knowledge on solutions for ever-increasing practical applications in the field.
Bimodular thrombin aptamers with two types of non-covalent locks

Abstract Aptamers are structured oligonucleotides that specifically bind their targets. Oligonucleotides can be assembled in large nanostructures via intermolecular duplexes or G-quadruplexes. Addition of aptamers can be used to create nanostructures that bind specifically certain targets. Here two types of self-assembling locks were used to create bimodular aptamer constructions. Well-known aptamer to thrombin was chosen as a model object. The assembly of duplex locks was more efficient at low concentrations. The functional activity of aptamer modules was nearly the same as in HD1. However, the affinity of bimodular aptamers with G-quadruplex locks to immobilized thrombin was 5-10 times higher.
Powerful Effects of Diagnostic Information on Automatic and Self-Reported Evaluation: The Moderating Role of Memory Recall

We sometimes learn about certain behaviors of others that we consider diagnostic of their character (e.g., that they did immoral things). Recent research has shown that such information trumps the impact of other (less diagnostic) information both on self-reported evaluations and on more automatic evaluations as probed with indirect measures such as the Affect Misattribution Procedure (AMP). We examined whether facilitating memory recall of alternative information moderates the impact of diagnostic information on evaluation. In Experiments 1 and 2, participants learned one diagnostic positive and one diagnostic negative behavior of two unfamiliar people. Presenting a cue semantically related to this information during evaluation influenced AMP scores but not self-reported liking scores. Experiments 3 and 4 showed that elaborative rehearsal of low diagnostic information eliminated diagnosticity effects on AMP scores and reduced them on self-reported liking scores. These findings help elucidate the role of memory recall and diagnosticity in evaluation.
Influence of Boiling, Temperature and Thickness on Drying Time of Aerial Yam (Dioscorea bulbifera bulbis)

This Article was published by Scholars Journal of Engineering and Technology (SJET) ISSN 2321-435X (Online) Sch. J. Eng. Tech., 2015; 3(8):701-706 ISSN 2347-9523 (Print) ©Scholars Academic and Scientific Publisher (An International Publisher for Academic and Scientific Resources)
Vedolizumab Clinical Decision Support Tool Predicts Efficacy of Vedolizumab But Not Ustekinumab in Refractory Crohn's Disease.

INTRODUCTION Vedolizumab clinical decision support tool (VDZ-CDST) predicts response to vedolizumab, but whether this tool also predicts efficacy of other drugs in Crohn's disease (CD) is unknown. This study aimed to assess the value of VDZ-CDST to predict vedolizumab and ustekinumab efficacy in patients with CD. PATIENTS AND METHODS We included consecutive CD patients refractory or intolerant to anti-TNF who started either vedolizumab or ustekinumab in 5 university hospitals between May 2014 and August 2018. The main end points were the rates of clinical remission and steroid-free clinical remission (SFCR) in each group of VDZ-CDST at week 48. RESULTS One hundred eighty patients were included; 94 received vedolizumab (VDZ-CDST ≤13: 32; VDZ-CDST >13 and ≤19: 52; VDZ-CDST >19: 10), and 86 received ustekinumab (VDZ-CDST ≤13: 16; VDZ-CDST >13 and ≤19: 60; VDZ-CDST >19: 10). At week 48 in the vedolizumab group, clinical remission and SFCR were reached in 9.4% with a VDZ-CDST ≤13, in 38.5% and 28.8% with a VDZ-CDST >13 and ≤19, respectively, and in 80.0% with a VDZ-CDST >19 (P < 0.0001 and P < 0.0001, respectively). In the ustekinumab cohort, clinical remission and SFCR were reached in 43.8% and 37.5% with a VDZ-CDST ≤13, in 55.0% and 50.0% with a VDZ-CDST >13 and ≤19, and 50.0% with a VDZ-CDST >19, respectively (P = 0.65 and P = 0.46, respectively). VDZ-CDST identified SFCR with an area under the curve of 0.69 (95% CI, 0.57-0.82) for vedolizumab and 0.52 (95% CI, 0.40-0.65) for ustekinumab. CONCLUSION The VDZ-CDST predicts clinical remission and SFCR at week 48 for vedolizumab but not for ustekinumab in CD patients refractory or intolerant to anti-TNF.
Factors affecting clinicians’ adherence to principles of diagnosis documentation: A concept mapping approach for improved decision-making

Background: The quality of data in electronic health records (EHRs) depends on adherence of clinicians to principles of diagnosis documentation. Objective: A concept mapping (CM) approach was used to extract factors related to quality of clinicians’ documentation that govern EHR data quality. Method: Influential factors extracted from brainstorming sessions were sorted by individual participants, followed by a quantitative analysis using multidimensional scaling and cluster analysis to categorise sorted factors. Finally, a questionnaire was used to elicit the importance-feasibility of the extracted factors. Results were visualised by cluster maps and Go-Zone plots. Result: Factors were classified into seven clusters: “knowledge about International Classification of Diseases and clinical coding,” “need for facilitators and guidelines,” “explaining the importance of the issue and defining responsibilities,” “cooperation of other personnel,” “codify legal requirements,” “workload” and “clinical obstacles,” as ranked by importance. Conclusion: To enhance the quality of EHR data, a collaboration between physicians, nurses, managers and EHR developers is required. CM is an acceptable approach to meet this objective. Our findings highlight the significance of clinical coding knowledge, awareness about its importance and applicability and use of well-structured information systems. In combination, these three factors can have a strong positive impact on the quality of EHR data. Implications: A list of solutions is provided for policymakers, and two interventions suggested, based on the findings of this study, including the adoption of EHRs that incorporate documentation guidelines. We further propose updated clinical training programs and a monitoring and feedback mechanism to facilitate the EHR documentation process.
The emergence of a complex pore‐canal system in the dermal skeleton of Tremataspis (Osteostraci)

Thyestiids are a group of osteostracans (sister‐group to jawed vertebrates) ranging in time from the early Silurian to Middle Devonian. Tremataspis is unique among thyestiids in having a continuous mesodentine and enameloid cover on its dermal elements, and an embedded pore‐canal system divided into lower and upper parts by a perforated septum. The origin of this upper mesh canal system and its potential homology to similar canal systems of other osteostracans has remained a matter of debate. To investigate this, we use synchrotron radiation microtomography data of four species of Tremataspis and three other thyestiid genera. Procephalaspis oeselensis lacks an upper mesh canal system entirely, but Aestiaspis viitaensis has partially enclosed upper canals formed between slightly modified tubercles that generally only cover separate pore fields. Further modification of tubercles in Dartmuthia gemmifera forms a more extensive, semi‐enclosed upper mesh canal system that overlies an extensive perforated septum, similar to that found in Tremataspis. Lower mesh canals in P. oeselensis are radially arranged and buried tubercles indicate a continuous growth and addition of dermal hard tissues. These features are lacking to varying degrees in the other investigated thyestiids, and Tremataspis probably had a determinate growth accompanied by a single mineralization phase of its dermal hard tissues. The previously proposed homology between the semi‐enclosed upper canal system in Dartmuthia to the pore‐canal system in Tremataspis is supported in this study, but the suggested homologies between these canals and other parts of the thyestiid vasculature to those in non‐thyestiid osteostracans remain unclear. This study shows that three‐dimensional modeling of high‐resolution data can provide histological and structural details that can help clarify homology issues and elucidate the evolution of dermal hard tissues in osteostracans. In extension, this can give insights into how these tissues relate to those found among jawed vertebrates.
Heterozygous variants in SPTBN1 cause intellectual disability and autism

Spectrins are common components of cytoskeletons, binding to cytoskeletal elements and the plasma membrane, allowing proper localization of essential membrane proteins, signal transduction, and cellular scaffolding. Spectrins are assembled from α and β subunits, encoded by SPTA1 and SPTAN1 (α) and SPTB, SPTBN1, SPTBN2, SPTBN4, and SPTBN5 (β). Pathogenic variants in various spectrin genes are associated with erythroid cell disorders (SPTA1, SPTB) and neurologic disorders (SPTAN1, SPTBN2, and SPTBN4), but no phenotypes have been definitively associated with variants in SPTBN1 or SPTBN5. Through exome sequencing and case matching, we identified seven unrelated individuals with heterozygous SPTBN1 variants: two with de novo missense variants and five with predicted loss‐of‐function variants (found to be de novo in two, while one was inherited from a mother with a history of learning disabilities). Common features include global developmental delays, intellectual disability, and behavioral disturbances. Autistic features (4/6) and epilepsy (2/7) or abnormal electroencephalogram without overt seizures (1/7) were present in a subset. Identification of loss‐of‐function variants suggests a haploinsufficiency mechanism, but additional functional studies are required to fully elucidate disease pathogenesis. Our findings support the essential roles of SPTBN1 in human neurodevelopment and expand the knowledge of human spectrinopathy disorders.
Single-Crystalline Body Centered FeCo Nano-Octopods: From One-Pot Chemical Growth to a Complex 3D Magnetic Configuration.

Single crystalline magnetic FeCo nanostars were prepared using an organometallic approach under mild conditions. The fine-tuning of the experimental conditions allowed the direct synthesis of these nano-octopods with body-centered cubic (bcc) structure through a one-pot reaction, contrarily to the seed-mediated growth classically used. The FeCo nanostars consist of 8 tetrahedrons exposing {311} facets, as revealed by high resolution transmission electron microscopy (HRTEM) imaging and electron tomography (ET), and exhibit a high magnetization comparable with the bulk one (Ms = 235 A·m2·kg-1). Complex 3D spin configurations resulting from the competition between dipolar and exchange interactions are revealed by electron holography. This spin structures are stabilized by the high aspect ratio tetrahedral branches of the nanostars, as confirmed by micromagnetic simulations. This illustrates how magnetic properties can be significantly tuned by nanoscale shape control.
A New SOFA Score Calculation to Improve the Predictive Performance for Mortality

Background: The sequential organ failure assessment (SOFA) is one of the most commonly used scoring systems to evaluate organ failure in sepsis. The trajectory of the SOFA score, a delta-SOFA (SOFAΔ), is proposed as a better indicator for predicting mortality, and potentially as an endpoint in exploratory clinical trials. However, there are some concerns about the use of SOFAΔ. For example, SOFAΔ represents only the changes in the score, and the potential value of the absolute SOFA score has not been considered. Therefore, we hypothesized that the addition of the absolute SOFA score to the SOFAΔ would improve the predictive performance for patient outcomes. Based on this theory, a new indicator, SOFAComb calculated by SOFAΔ + absolute SOFA score, was examined in this study. Methods: Data obtained from 297 patients in multiinstitutional post-marketing surveys performed during June 2014, and May 2016 were retrospectively analyzed. All patients were diagnosed as having sepsis-associated disseminated intravascular coagulopathy (DIC) and treated with antithrombin concentrate. The SOFAComb and SOFAΔ were calculated on days 2, 4, and 7, and the performance was analyzed in terms of predictive ability for 28-day mortality.Results: Of the 297 patients included in the analysis, 214 patients survived (72.1%), while 83 patients (27.9%) died. The area under the receiver operating curve (AUC) of SOFA at baseline for predicting 28-mortality was 0.679. The AUCs of SOFAΔ on day 2, 4, 7 were 0.662, 0.769, 0.815, respectively, and those of SOFAComb on day 2, 4, 7 were 0.765, 0.830, 0.866, respectively. The AUCs of SOFAComb were significantly greater at all time points compared to SOFAΔ (day 2: P <0.001, day 4: P =0.002, day 7: P <0.001). In addition, the accuracy of SOFAComb was better than that of SOFAΔ (day 2: P <0.001, day 4: P =0.067, day 7: P =0.049). Conclusions: SOFAComb is simple to calculate and provides better predictive performance compared to SOFAΔ for predicting mortality. Additional studies are needed to confirm these findings.
Potential reversal of epigenetic age using a diet and lifestyle intervention: a pilot randomized clinical trial

Manipulations to slow biological aging and extend healthspan are of interest given the societal and healthcare costs of our aging population. Herein we report on a randomized controlled clinical trial conducted among 43 healthy adult males between the ages of 50-72. The 8-week treatment program included diet, sleep, exercise and relaxation guidance, and supplemental probiotics and phytonutrients. The control group received no intervention. Genome-wide DNA methylation analysis was conducted on saliva samples using the Illumina Methylation Epic Array and DNAmAge was calculated using the online Horvath DNAmAge clock (2013). The diet and lifestyle treatment was associated with a 3.23 years decrease in DNAmAge compared with controls (p=0.018). DNAmAge of those in the treatment group decreased by an average 1.96 years by the end of the program compared to the same individuals at the beginning with a strong trend towards significance (p=0.066). Changes in blood biomarkers were significant for mean serum 5-methyltetrahydrofolate (+15%, p=0.004) and mean triglycerides (-25%, p=0.009). To our knowledge, this is the first randomized controlled study to suggest that specific diet and lifestyle interventions may reverse Horvath DNAmAge (2013) epigenetic aging in healthy adult males. Larger-scale and longer duration clinical trials are needed to confirm these findings, as well as investigation in other human populations.
Synthesis and mesomorphism of modified 2,5-Di(4-dodecoxyphen-1-yl)-c-cyclopentene-pyridines

ABSTRACT Herein, we report on a new series of mesomorphic compounds synthesised by directional functionalisation of 2,5-di(4-dodecoxyphen-1-yl-c-cyclopentene-pyridine) on the c-cyclopentene moiety. The first functionalisation of the starting compound gave rise to a racemic product modified with a hydroxyl group on the fused cyclopentene ring. Further oxidation of this alcohol to a prochiral ketone and subsequent enantioselective reduction back to the alcohol afforded a new chiral alcohol. Further, the hydroxyl group of the chiral alcohol could be substituted by fluorine in a SN2 reaction, leading to a chiral compound with enantiomeric excess (ee) of 66% and chiral nematic liquid-crystalline (LC) phase. GRAPHICAL ABSTRACT
The number of biopsy specimens can influence the non-lifting sign in colorectal laterally spreading tumors

Abstract Background Although the problem of whether to perform a biopsy before endoscopic treatment for colorectal laterally spreading tumor (LST) troubles clinicians, about 50 % of lesions still undergo a preceding biopsy. We aimed to explore factors affecting the non-lifting sign in LST and examine the influence of “biopsy-related factors”, such as the number of biopsy specimens and the interval after biopsy on non-lifting sign in cases with a history of biopsy. Methods Clinical data of 159 LSTs regarding age, gender, history of biopsy, tumor location, tumor size, the depth of submucosal invasion, tumor configuration, histologic type, location with respect to the fold, and result of non-lifting sign testing were investigated retrospectively. For patients with a history of biopsy, the period after biopsy and the number of biopsy specimens also were analyzed. Results Among 159 cases of LST, 112 were positive and 47 were negative for lifting signs. Biopsy history (p = 0.008), tumor size (p = 0.010), and location with respect to the fold (p = 0.022) were identified as factors affecting the non-lifting sign in multivariate analyses. In 75 LST cases with a history of biopsy, only the number of biopsies (p = 0.003) was identified as a factor affecting the non-lifting sign in multivariate analyses. Conclusions For LST, lesions with larger size, being across the fold, and biopsy history were predictive factors for non-lifting signs. Reducing the number of biopsies would reduce the occurrence of non-lifting signs when biopsy is necessary. The impact of the interval after the biopsy on the non-lifting sign will require further study.