Miracle-dz/UniFAR-FTUs huggingface dataset:
Double Color Lanthanide Metal-Organic Framework Based Logic Device and Visual Ratiometric Fluorescence Water Microsensor for Solid Pharmaceuticals.

Water is one of the most widespread impurities and contaminants for pharmaceuticals and chemical products. A simple, fast and reliable water assay method is of high significance for pharmaceutical and chemical manufacturing industry. In this work, lanthanide metal-organic framework Eu-dipicolinic acid/2-aminophthalic acid (Eu-DPA/PTA-NH2) was prepared as a double-color ratiometric fluorescent water sensor, which shows ultra-sensitive (limit of detection 0.01% v/v) and linear broad-range (0-100% v/v) response to water. An innovative analytical device based on one-to-two logic gate was constructed by using the water content and the two fluorescence responses as the input and output signals, respectively. The direct analysis of water content can be achieved by the four output types, NOT (0, 1), PASS 0 (0, 0), PASS 1 (1, 1) and YES (1, 0). Importantly, the MOF-loaded fiber paper was prepared as a microsensor, and a water assay tube was designed for rapid water detection of solid pharmaceuticals via ratiometric chromaticity, coupled with a portable visual determination device. The paper-based microsensor is response-rapid (20 s), long-term stable (at least 30 days), and can achieve the accurate (relative error < 9.8%) visual assay of trace water in solid pharmaceuticals. To our knowledge, this is the first time to report a MOF-based double-color ratiometric fluorescent water sensor, a water analytical logic device and a paper-based water microsensor for point-of-care visual water assay in solid samples via ratiometric chromaticity.
Chronic Obstructive Pulmonary Disease as a Predictor of Cardiovascular Risk: A Case-Control Study

Abstract Chronic obstructive pulmonary disease (COPD) is a complex multi-morbid disorder with significant cardiac mortality. Current cardiovascular risk prediction models do not include COPD. We investigated whether COPD modifies future cardiovascular risk to determine if it should be considered in risk prediction models. Case-control study using baseline data from two randomized controlled trials performed between 2012 and 2015. Of the 90 eligible subjects, 26 COPD patients with lung hyperinflation were propensity matched for 10-year global cardiovascular risk score (QRISK2) with 26 controls having normal lung function. Patients underwent cardiac magnetic resonance imaging, arterial stiffness and lung function measurements. Differences in pulse wave velocity (PWV), total arterial compliance (TAC) and aortic distensibility were main outcome measures. PWV (mean difference 1.0 m/s, 95% CI 0.02–1.92; p = 0.033) and TAC (mean difference –0.27 mL/m2/mmHg, 95% CI 0.39–0.15; p < 0.001) were adversely affected in COPD compared to the control group. The PWV difference equates to an age, sex and risk-factor adjusted increase in relative risk of cardiovascular events and mortality of 14% and 15%, respectively. There were no differences in aortic distensibility. In the whole cohort (n = 90) QRISK2 (β = 0.045, p = 0.005) was associated with PWV in multivariate analysis. The relationship between QRISK2 and PWV were modified by COPD, where the interaction term reached significance (p = 0.014). FEV1 (β = 0.055 (0.027), p = 0.041) and pulse (B = –0.006 (0.002), p = 0.003) were associated with TAC in multivariate analysis. Markers of cardiovascular outcomes are adversely affected in COPD patients with lung hyperinflation compared to controls matched for global cardiovascular risk. Cardiovascular risk algorithms may benefit from the addition of a COPD variable to improve risk prediction and guide management. HAPPY London ClinicalTrials.gov: NCT01911910 and HZC116601; ClinicalTrials.gov: NCT01691885
An International Exploration of the Effect of Media Portrayals of Postconcussion Management on Concussion Identification in the General Public.

BACKGROUND Concussion portrayal in media broadcasts of sporting events may contribute to lack of public understanding regarding concussion. METHODS In total, 828 participants from Australia, New Zealand, and the United Kingdom completed a questionnaire assessing concussion knowledge. Participants were randomly assigned to either receive sports return-to-play (RTP) guideline information (RTP group) or not (no-RTP group). Participants viewed 12 short clips from televised rugby games and indicated whether they believed the player in each clip had sustained a concussion. Participants were then informed whether the player was removed, returned, or stayed in the game and again asked whether they thought a concussion had occurred. RESULTS Probability of reporting a likely concussion over all videos was 65.6%. When told a player's possible concussion was managed by removal from the game, participants were more likely to change their response from "no" (no concussion) to "yes" (concussion) than from "yes" to "no." When told the player stayed or returned to the game, participants were more likely to change their response from "yes" (concussion) to "no" (no concussion) than from "no" to "yes. " There was no significant main effect for RTP guideline manipulation or interaction effect with RTP information. CONCLUSION Additional player's injury management information influenced participants' judgments of concussion occurrence. Results show that information provided via sports media broadcasts influenced viewers' perceptions of concussion and appropriate concussion management.
Incidence and Prevalence of Nontuberculous Mycobacterial Lung Disease in a Large U.S. Managed Care Health Plan, 2008–2015

Rationale: Estimating the annual incidence and prevalence of nontuberculous mycobacterial (NTM) lung disease may assist in improving understanding of the public health and economic impacts of this disease and its treatment. Objective: To estimate the yearly incidence and prevalence of administrative claims–based NTM lung disease between 2008 and 2015 in a U.S. managed care claims database. Methods: We used a national managed care claims database (Optum Clinformatics Data Mart) representing a geographically diverse population of approximately 27 million members annually. All medical claims from January 1, 2007, to June 30, 2016, were scanned for diagnosis codes for NTM lung disease (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] code 031.0 or ICD-10-CM code A31.0). We defined a case of NTM lung disease as having at least two medical claims with a code of 031.0 or A31.0 that were dated at least 30 days apart. Annual incidence and prevalence were estimated for each calendar year from 2008 to 2015. Results: From 2008 to 2015, the annual incidence of NTM lung disease increased from 3.13 (95% confidence interval [CI], 2.88–3.40) to 4.73 (95% CI, 4.43–5.05) per 100,000 person-years, and the annual prevalence increased from 6.78 (95% CI, 6.45–7.14) to 11.70 (95% CI, 11.26–12.16) per 100,000 persons. The average annual changes in incidence and prevalence were +5.2% (95% CI, 4.0–6.4%; P < 0.01) and +7.5% (95% CI, 6.7–8.2%; P < 0.01), respectively. For women, the annual incidence increased from 4.16 (95% CI, 3.76–4.60) to 6.69 (95% CI, 6.19–7.22) per 100,000 person-years, and the annual prevalence increased from 9.63 (95% CI, 9.08–10.22) to 16.78 (95% CI, 16.04–17.55) per 100,000 persons. For individuals aged 65 years or older, the annual incidence increased from 12.70 (95% CI, 11.46–14.07) to 18.37 (95% CI, 16.98–19.87) per 100,000 person-years, and the annual prevalence increased from 30.27 (95% CI, 28.41–32.24) to 47.48 (95% CI, 45.37–49.67) per 100,000 persons. The incidence and prevalence of NTM lung disease increased in most U.S. states and overall at the national level. Conclusions: The incidence and prevalence of NTM lung disease appears to be increasing in the United States, particularly among women and older age groups.
Total Protein Concentration and Tumor Necrosis Factor α in Tears of Nonproliferative Diabetic Retinopathy.

SIGNIFICANCE Total protein concentration (TPC) and tumor necrosis factor α (TNF-α) concentration in tears are correlated with severity of retinopathy. However, minimal data are available in the literature for investigating tear TPC and TNF-α concentrations in Asian individuals with different severity of nonproliferative diabetic retinopathy (NPDR). PURPOSE This study evaluated differences of TPC and TNF-α concentrations in tears at different severity of NPDR among participants with diabetes in comparison with normal participants. METHODS A total of 75 participants were categorized based on Early Treatment for Diabetic Retinopathy Study scale, with 15 participants representing each group, namely, normal, diabetes without retinopathy, mild NPDR, moderate NPDR, and severe NPDR. All participants were screened using McMonnies questionnaire. Refraction was conducted subjectively. Visual acuity was measured using a LogMAR chart. Twenty-five microliters of basal tears was collected using glass capillary tubes. Total protein concentration and TNF-α concentrations were determined using Bradford assay and enzyme-linked immunosorbent assay, respectively. RESULTS Mean ± SD age of participants (n = 75) was 57.88 ± 4.71 years, and participants scored equally in McMonnies questionnaire (P = .90). Mean visual acuity was significantly different in severe NPDR (P = .003). Mean tear TPC was significantly lower, and mean tear TNF-α concentration was significantly higher in moderate and severe NPDR (P < .001). Mean ± SD tear TPC and TNF-α concentrations for normal were 7.10 ± 1.53 and 1.39 ± 0.24 pg/mL; for diabetes without retinopathy, 6.37 ± 1.65 and 1.53 ± 0.27 pg/mL; for mild NPDR, 6.32 ± 2.05 and 1.60 ± 0.21 pg/mL; for moderate NPDR, 3.88 ± 1.38 and 1.99 ± 0.05 pg/mL; and for severe NPDR, 3.64 ± 1.26 and 2.21 ± 0.04 pg/mL, respectively. Tear TPC and TNF-α concentrations were significantly correlated (r = -0.50, P < .0001). Visual acuity was significantly correlated with tear TPC (r = -0.236, P = .04) and TNF-α concentrations (r = 0.432, P < .0001). CONCLUSIONS This cross-sectional study identified differences in tear TPC and TNF-α concentrations with increasing severity of NPDR.
VarGen: an R package for disease-associated variant discovery and annotation

SUMMARY Over the past decade, there has been an exponential increase in the amount of disease-related genomic data available in public databases. However, this high-quality information is spread across independent sources and researchers often need to access these separately. Hence, there is a growing need for tools that gather and compile this information in an easy and automated manner. Here we present "VarGen", an easy to use, customisable R package that fetches, annotates and rank variants related to diseases and genetic disorders, using a collection public databases (viz. OMIM, FANTOM5, GTEx and the GWAS catalog). This package is also capable of annotating these variants to identify the most impactful ones. We expect that this tool will benefit the research of variant-disease relationships. AVAILABILITY AND IMPLEMENTATION VarGen is open-source and freely available via GitHub: https://github.com/MCorentin/VarGen. The software is implemented as an R package and is supported on Linux, MacOS and Windows. SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.
A Phase Ib Study of Preoperative, Locoregional IRX-2 Cytokine Immunotherapy to Prime Immune Responses in Patients with Early-Stage Breast Cancer

Purpose: To evaluate the safety and feasibility of preoperative locoregional cytokine therapy (IRX-2 regimen) in early-stage breast cancer, and to evaluate for intratumoral and peripheral immunomodulatory activity. Patients and Methods: Sixteen patients with stage I–III early-stage breast cancer (any histology type) indicated for surgical lumpectomy or mastectomy were enrolled to receive preoperative locoregional immunotherapy with the IRX-2 cytokine biological (2 mL subcutaneous × 10 days to periareolar skin). The regimen also included single-dose cyclophosphamide (300 mg/m2) on day 1 to deplete T-regulatory cells and oral indomethacin to modulate suppressive myeloid subpopulations. The primary objective was to evaluate feasibility (i.e., receipt of therapy without surgical delays or grade 3/4 treatment–related adverse events). The secondary objective was to evaluate changes in stromal tumor–infiltrating lymphocyte score. The exploratory objective was to identify candidate pharmacodynamic changes for future study using a variety of assays, including flow cytometry, RNA and T-cell receptor DNA sequencing, and multispectral immunofluorescence. Results: Preoperative locoregional cytokine administration was feasible in 100% (n = 16/16) of subjects and associated with increases in stromal tumor–infiltrating lymphocytes (P < 0.001). Programmed death ligand 1 (CD274) was upregulated at the RNA (P < 0.01) and protein level [by Ventana PD-L1 (SP142) and immunofluorescence]. Other immunomodulatory effects included upregulation of RNA signatures of T-cell activation and recruitment and cyclophosphamide-related peripheral T-regulatory cell depletion. Conclusions: IRX-2 is safe in early-stage breast cancer. Potentially favorable immunomodulatory changes were observed, supporting further study of IRX-2 in early-stage breast cancer and other malignancies.
Drip and ship for mechanical thrombectomy within the Neurovascular Network of Southwest Bavaria

Objective To determine feasibility and safety of stroke care organization within our Neurovascular Network of Southwest Bavaria (NEVAS) in a rural area with distances of up to 100 kilometers, we compared patients who underwent mechanical thrombectomy (MT) in large vessel occlusion admitted directly to our center (direct to center [DTC]) to patients who were transferred for MT via NEVAS (drip and ship [DS]). Methods This is a retrospective analysis of prospectively collected data of all MT patients between January 2015 and May 2018. Successful recanalization was defined as a thrombolysis in cerebral infarction score of 2b-3. Symptomatic intracerebral hemorrhage (sICH) was defined according to European Cooperative Acute Stroke Study 3. Modified Rankin Scale (mRS) score of 0–2 at 3 months indicated good outcome. Results MT was performed in 410 patients: 221 DTC and 189 DS. Median NIH Stroke Scale (NIHSS) score was 16 and premorbid mRS score was 0. Thrombolysis was applied in 62.2% with the same time from symptom onset in both groups (94.5 vs 95 minutes). Successful recanalization (79.3% vs 77.8%) and NIHSS score reduction from admission to discharge (16–7 vs 17–6) were comparable. Time delay from onset to revascularization was 96 minutes in DS (212 vs 308 minutes, p = 0.001). At follow-up, DTC patients had a trend to better outcome (33.5% vs 24.3%, p = 0.056). Neither sICH (6.3% vs 5.9%, p = 0.840) nor mortality (31.2% vs 34.4%, p = 0.387) differed between the groups. Conclusion DS patients benefit from MT without relevant safety concerns, but with a trend to unfavorable outcome compared to DTC patients. These results suggest that DS is suitable to provide MT in rural areas where DTC is not possible.
Nearly quantized conductance plateau of vortex zero mode in an iron-based superconductor

Reaching a conductance plateau The surface of the iron-based superconductor FeTe0.55Se0. 45 satisfies the necessary conditions to support topological superconductivity. Under the application of a magnetic field, vortices with zero-bias peaks that are consistent with Majorana bound states have been observed. Using scanning tunneling spectroscopy, Zhu et al. studied the conductance of these states as the tip-sample distance was reduced (see the Perspective by Sau). The researchers found that the value of the conductance increased and eventually saturated. For one of the vortices they studied, the conductance reached a quantized value that is characteristic of the Majorana bound states. Science, this issue p. 189; see also p. 145 Scanning tunneling spectroscopy is used to study the conductance of zero bias states in vortices on FeTe0.55Se0. 45. Majorana zero modes (MZMs) are spatially localized, zero-energy fractional quasiparticles with non-Abelian braiding statistics that hold promise for topological quantum computing. Owing to the particle-antiparticle equivalence, MZMs exhibit quantized conductance at low temperature. By using variable-tunnel–coupled scanning tunneling spectroscopy, we studied tunneling conductance of vortex bound states on FeTe0.55Se0. 45 superconductors. We report observations of conductance plateaus as a function of tunnel coupling for zero-energy vortex bound states with values close to or even reaching the 2e2/h quantum conductance (where e is the electron charge and h is Planck’s constant). By contrast, no plateaus were observed on either finite energy vortex bound states or in the continuum of electronic states outside the superconducting gap. This behavior of the zero-mode conductance supports the existence of MZMs in FeTe0.55Se0. 45.
Outcomes of stent optimisation in intravascular ultrasound-guided intervention for long or chronic totally occluded coronary lesions.

AIMS We sought to investigate the incidence, predictors, and clinical outcomes of stent optimisation on intravascular ultrasound (IVUS) in long coronary lesions treated with new-generation drug-eluting stents (DESs). METHODS AND RESULTS From four randomised trials comparing IVUS and angiography guidance in long (≥26 mm) or chronic total occlusion coronary lesions, a total of 1,396 patients who underwent IVUS-guided intervention were classified into two groups (Stent-optimisation and Non-optimisation) according to optimisation criteria [minimal stent area (MSA) ≥5.5 mm2 or 80% of mean reference lumen area (MLA)]. Major adverse cardiac event (MACE) occurrence, defined as a composite of cardiac death, myocardial infarction, stent thrombosis, or target-vessel revascularisation, was compared. Stent optimisation was not met in 578 (41%) patients. Predictors of non-optimisation were older age, longer lesion length, and smaller stent diameter. MACE rate was significantly higher in the Non-optimisation vs. the Stent-optimisation group (4.8% vs. 1.9%, log-rank P=0.002; adjusted hazard ratio=2.95, 95% confidence interval=1.43-6.06). Among possible combinations of absolute and relative expansion criteria, the combination best predicting MACE was MSA ≥5.4 mm2 or 80% of MLA (Youden index=0.264). CONCLUSIONS Achieving stent optimisation on IVUS evaluation was associated with favourable outcomes in IVUS-guided, new-generation DES implantation for long coronary lesions including CTO.
Factors associated with repeat rectal Neisseria gonorrhoeae and Chlamydia trachomatis screening following inconclusive nucleic acid amplification testing: A potential missed opportunity for screening

Objective Given rising incidence of Neisseria gonorrhoeae and Chlamydia trachomatis (GC/CT), development of efficacious screening strategies is critical to interruption of the infection cycle. However, a small proportion of nucleic acid amplification testing (NAAT) results are inconclusive—resulting in delays in diagnosis and treatment. As such, this study seeks to evaluate factors associated with inconclusive rectal GC/CT NAAT. Methods This is a retrospective chart review of individuals who received an inconclusive rectal GC/CT NAAT result at a single institution from 3/2016-6/2018. Inconclusive GC/CT NAAT was defined as presence of PCR amplification inhibitors using Roche Cobas v2.0 CT/NG assay. Clinical charts were abstracted for age, gender, HIV status, GC/CT (urogenital, rectal, pharyngeal) and syphilis screening results during the study period, clinic type (HIV clinic, university student health center, other), and whether repeat testing occurred within 6 months following an inconclusive result. Logistic regression analysis was used to calculate adjusted and unadjusted odds ratios of factors associated with receipt of repeat testing following an inconclusive rectal GC/CT NAAT result. Results During the study period, 6.1% (852/14,015) of rectal GC/CT NAAT were inconclusive for one or both of GC and CT. Among the 413 patients whose inconclusive rectal GC/CT NAAT results that were included in our analysis, 66.6% (275/413) received repeat testing within 6 months, of which 8.7% (24/275) were positive (compared to 5.4% positivity rate of all rectal samples). In multivariable analysis, individuals living with HIV had lower odds of receiving repeat testing following inconclusive rectal GC/CT NAAT compared to HIV uninfected individuals (adj OR 0.25; p = 0.001). Conclusions Despite being disproportionately affected by the STI epidemic, individuals living with HIV had 75% lower odds of receiving repeat testing following inconclusive rectal GC/CT NAAT compared to HIV-uninfected individuals, representing potentially missed opportunities for treatment and prevention of ongoing STI transmission.
Dynamics of photosynthetic responses in 10 rubber tree (Hevea brasiliensis) clones in Colombian Amazon: Implications for breeding strategies

The rubber tree [Hevea brasiliensis (Willd. Ex Adr. de Juss.) Muell. -Arg] is the main source of natural rubber in the world. However, in the Amazon region, its production is reduced by biotic and abiotic limitations, which have prompted breeding programs in order to identify desirable agronomic and physiological indicators. The objective of this study was to analyze the temporal dynamics of photosynthetic responses based on the parameters of leaf gas exchange and chlorophyll a fluorescence in 10 rubber tree clones during the immature phase (pre-tapping) in three large-scale clone trials, during daily cycles and under two climatic periods (dry and rainy) in the Caquetá region (Colombian Amazon). The variables A, LT, ΦPSII, ETR and qP were significantly higher in the dry period, where the highest values of PAR, AT and VPD were seen. In San Vicente del Caguán and Florencia, the highest averages were estimated for A, E and gs, as compared with Belén de los Andaquíes. In Florencia, the highest fluorescence parameters of chlorophyll a were recorded. At 9:00 h and 12:00 h, the highest means of A, E, ΦPSII and ETR were observed. The majority of the clones displayed the highest Fv/Fm mean (0.82–0.84) in the dry period. The clones FX 4098, FDR 4575, MDF 180, GU198 and FDR 5788 represent genotypes with the best photosynthetic performance (greater photosynthetic rates and better ability of the photosynthetic apparatus to capture, use and dissipate light energy). These desirable genotypes constitute a promising gene pool for expanding the genetic resource of rubber trees in the Colombian Amazon.
Context and number of noncanonical repeat variable diresidues impede the design of TALE proteins with improved DNA targeting

Transcription activator‐like effector (TALE) proteins have been used extensively for targeted binding of fusion proteins to loci of interest in (epi)genome engineering. Such approaches typically utilize four canonical TALE repeat variable diresidue (RVD) types, corresponding to the identities of two key amino acids, to target each nucleotide. Alternate RVDs with improved specificity are desired. Here, we focused on seven noncanonical RVDs that have been suggested to have improved specificity for their target nucleotides. We used custom protein binding microarrays to characterize the DNA‐binding activity of 65 TALEs containing these alternate or corresponding canonical RVDs at multiple positions to ~5,000 unique DNA sequences per protein. We found that none of the noncanonical thymine‐targeting RVDs displayed stronger preference for thymine than did the canonical RVD. Of the noncanonical RVDs with putatively improved specificity for guanine, only EN and NH showed greater discrimination of guanine over adenine. This improved specificity, however, comes at a cost: more substitutions of a noncanonical RVD for a canonical RVD generally decreased the protein's DNA‐binding activity. Our results highlight the need to investigate RVD‐nucleotide specificities in multiple protein contexts and suggest that a balance between canonical and noncanonical RVDs is needed to build TALEs with improved specificity.