Miracle-dz/UniFAR-FTUs huggingface dataset:
Phase IV clinical study to evaluate the effects of an intracameral combined mydriatic and anesthetic agent and standard topical mydriatics and anesthetics on the ocular surface after cataract surgery

Ocular surface damage was reduced by using intracameral compared with topical mydriatics and anesthetics. In addition, procedure time and patient satisfaction improved, suggesting a clinical advantage for intracameral administration. Purpose: To compare intracameral and topical mydriatics and anesthetics in cataract surgery. Setting: Institute of Ocular Microsurgery, Barcelona, Spain. Design: Phase IV, open-label, randomized, single-center study. Methods: Patients were randomized in a 1:1 ratio to receive intracameral mydriatic–anesthetic (Mydrane/Fydrane) and anesthetic eyedrops or control (topical eyedrops only). The other treatment was administered for the second cataract surgery. Assessments were performed at presurgery and immediately postsurgery, at 12 to 36 hours postsurgery (day 1), and 7 days postsurgery. The primary endpoint was the change from baseline in corneal/conjunctival surface staining. The secondary endpoints included assessments of epithelial alterations, point-spread function, ocular surface disease index, conjunctival hyperemia, vision breakup time, ocular symptoms/signs, adverse events (AEs), corrected distance visual acuity, intraocular pressure, patient/investigator satisfaction, and procedure time. Results: A total of 50 patients undergoing sequential cataract surgery in both eyes were included. Baseline assessments were similar in each group. The difference between Fydrane and control groups for the change from baseline at day 1 in corneal and conjunctival surface staining was not statistically significant. For Fydrane, postoperative epithelial alterations were fewer at day 1 (P < .005), folliculopapillary reaction was less frequent (P < .05), some ocular symptoms were less frequent and milder (P < .05), length of procedure was shorter (P < .001), and patient and investigator satisfaction were better (P < .05). There were few AEs in both groups. Conclusions: Fydrane reduced ocular surface damage by decreasing corneal epithelial and conjunctival toxicity with faster recovery of surface integrity compared with topical eyedrops, improved patient and investigator satisfaction, and reduced procedure time.
Enhanced Stability of the Pharmacologically Active Lactone Form of 10-Hydroxycamptothecin by Self-Microemulsifying Drug Delivery Systems

10-Hydroxycamptothecin (HCPT) is a DNA inhibitor of topoisomerase I and exerts antitumor activities against various types of cancer. However, reversible conversion from a pharmacologically active lactone form to an inactive carboxylate form of HCPT and poor water solubility hamper its clinical applications. To overcome these shortcomings, we designed a fine self-microemulsifying drug delivery system (SMEDDS) for HCPT to effectively protect HCPT in its active lactone form as well as improving dissolution rates. A formulation of HCPT-SMEDDS that contained ethyl oleate, D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS), and polyethylene glycol 400 (PEG400) was optimized by using the central composite design and response surface methodology. Following 1:100 aqueous dilution of the optimized HCPT-SMEDDS, the droplet size of resulting microemulsions was 25.6 ± 0.7 nm, and the zeta potential was − 15.2 ± 0.4 mV. The optimized HCPT-SMEDDS appeared to stabilize the lactone moiety of HCPT with 73.6% being present in the pharmacologically active lactone forms in simulated intestinal fluid, but only 45.7% for free HCPT. Furthermore, the physically stable formulation showed the active lactone form predominated in HCPT-SMEDDS (> 95%) for 6 months under the accelerated storage condition. Meanwhile, the optimized SMEDDS formulation also significantly improved dissolution rates and membrane permeability of the lactone form of HCPT. Therefore, HCPT-SMEDDS involved designing for the ease of manufacture, and provided a potent oral dosage form for preserving its active lactone form as well as enhancing the dissolution rate.
GP decisions to participate in emergencies: a randomised vignette study

Background GPs use their judgement on whether to participate in emergencies; however, little is known about how GPs make their decisions on emergency participation. Aim To test whether GPs' participation in emergencies is associated with cause of symptoms, distance to the patient, other patients waiting, and out-of-hours (OOH) clinic characteristics. Design & setting An online survey was sent to all GPs in Norway (n = 4701). Method GPs were randomised to vignettes describing a patient with acute shortness of breath and asked whether they would participate in a callout. The vignettes varied with respect to cause of symptoms (trauma versus illness), distance to the patient (15 minutes versus 45 minutes), and other patients waiting at the OOH clinic (crowding versus no crowding). The survey included questions about OOH clinic characteristics. Results Of the 1013 GPs (22%) who responded, 76% reported that they would participate. The proportion was higher in trauma (83% versus 69%, χ2 24.8, P<0.001), short distances (80% versus 71%, χ2 9.5, P=0.002), and no crowding (81% versus 70% χ2 14.6, P<0.001). Participation was associated with availability of a manned-response vehicle (adjusted odds ratio [OR] 2.06, 95% confidence interval [CI] = 1.25 to 3.41), and team training at the OOH clinic once a year (OR = 1.78, 95% CI = 1.12 to 2.82) or more than once a year (OR = 3.78, 95% CI = 1.64 to 8.68). Conclusion GPs were less likely to participate in emergencies when the incident was not owing to trauma, was far away, and when other patients were waiting. A manned-response vehicle and regular team training were associated with increased participation.
Husbandry Conditions and Welfare Outcomes in Organic Egg Production in Eight European Countries

Simple Summary An important challenge for the further development of organic egg production is to reach and maintain a high level of animal welfare. In a European research project including eight countries, the welfare state in 107 laying hen flocks as well as their housing and management were recorded during two farm visits at peak and end of lay. Data analysis aimed to reveal factors that may help to prevent or reduce welfare problems. Large variation between flocks indicated options for improvement with regard to mortality, feather and injurious pecking, parasitic infestation and keel bone damage. Results of the project indicate that (i) decreasing mite and worm infestation and (ii) providing an attractive covered veranda help to decrease mortality; (iii) maximising access to the free-range to decrease injurious pecking and Ascaridia galli infection; (iv) feeding sufficient protein levels and (v) providing adequate litter is preventive against feather pecking and cannibalism; (vi) ensuring that the birds have sufficient weight and (vii) preventing accidents by adequate hen house facilities and light conditions contributes to reduced keel bone damage. These primarily management-based measures have the potential to improve bird welfare both in terms of behavioural and health aspects in organic egg production systems. Abstract In the European research project HealthyHens, welfare indicators as well as husbandry and management conditions were recorded in 107 organic laying hen farms in eight countries. Farms were visited at peak and end of lay. Egg production was on average comparable to breeder specifications. A mean mortality of 5.7% and mean prevalences of footpad lesions of 30.5%, keel bone damage of 44.5%, 57.3% of flocks with on average >200 Ascarid eggs per gram faeces and 28.2% of flocks with >100 mites/trap were recorded. A large variation between flocks indicated options for improvement. Based on the results, the following measures can be recommended: (i) decreasing mite and worm infestation and (ii) providing an attractive covered veranda, because of their association with decreased mortality; (iii) maximising access to the free range, because of its relation to decreased A. galli infection and less injurious pecking; (iv) feeding sufficient protein levels and (v) providing adequate litter as preventive measure against feather pecking and cannibalism; (vi) ensuring that the birds have sufficient weight and (vii) preventing accidents by adequate hen house facilities and light conditions to reduce keel bone damage. These primarily management-based measures have the potential to improve bird welfare both in terms of behavioural and health aspects.
Post-Flood Impacts on Occurrence and Distribution of Mycotoxin-Producing Aspergilli from the Sections Circumdati, Flavi, and Nigri in Indoor Environment

Mycotoxin-producing Aspergilli (Circumdati, Flavi, and Nigri), usually associated with contaminated food, may also cause respiratory disorders and are insufficiently studied in water-damaged indoor environments. Airborne (N = 71) and dust borne (N = 76) Aspergilli collected at post-flood and control locations in Croatia resulted in eleven different species based on their calmodulin marker: A. ochraceus, A. ostianus, A. pallidofulvus, A. sclerotiorum, and A. westerdijkiae (Circumdati); A. flavus (Flavi); and A. tubingensis, A. welwitschiae, A. niger, A. piperis, and A. uvarum (Nigri). Most of the airborne (73%) and dust borne (54%) isolates were found at post-flood locations, and the highest concentrations measured in indoor air (5720 colony-forming units (CFU)/m3) and dust (2.5 × 105 CFU/g) were up to twenty times higher than in the control locations. A. flavus dominated among airborne isolates (25%) at the unrepaired locations, while 56% of the dust borne Aspergilli were identified as A. tubingensis and A. welwitschiae. The ability of identified isolates to produce mycotoxins aflatoxin B1 (AFB1), fumonisin B2 (FB2), and ochratoxin A were assessed by LC-MS analysis. All ochratoxin A (OTA)-producing Circumdati belonged to A. westerdijkiae (13.7 ± 15.81 µg/mL); in the section, Flavi A. flavus produced AFB1 (2.51 ± 5.31 µg/mL), while A. welwitschiae and A. niger (section Nigri) produced FB2 (6.76 ± 13.51 µg/mL and 11.24 ± 18.30 µg/mL, respectively). Water damage dominantly supported the occurrence of aflatoxigenic A. flavus in indoor environments. Yet unresolved, the causal relationship of exposure to indoor Aspergilli and adverse health effects may support the significance of this research.
Imaging markers for the characterization of grey and white matter changes from acute to chronic stages after experimental traumatic brain injury.

Despite clinical symptoms, a large majority of people with mild traumatic brain injury (TBI) has normal CT and MRI scans. As such present-day neuroimaging tools are insufficient to diagnose or classify low grades of TBI. Advanced neuroimaging techniques, like diffusion-weighted and functional MRI, may yield novel biomarkers that may aid in the diagnosis of TBI. Therefore, the present study had two aims. First, to characterize the development of MRI-based measures of structural and functional changes in grey and white matter regions from acute to chronic stages after mild and moderate TBI. Second, to identify imaging markers that can most accurately predict outcome after TBI. To these aims, fifty-two rats underwent serial functional (resting-state) and structural (T1-, T2-, and diffusion-weighted) MRI before and 1 hour, 1 day, 1 week, 1 month and 3-4 months after mild or moderate experimental TBI. All rats underwent behavioral testing. Histology was performed in subgroups of rats at different time-points. Early after moderate TBI, axial and radial diffusivities were increased, and fractional anisotropy was reduced in the corpus callosum and bilateral hippocampi, which normalized over time and was paralleled by recovery of sensorimotor function. Correspondingly, histology revealed decreased myelin staining early after TBI, which was not detected at chronic stages. No significant changes in individual outcome measures were detected after mild TBI. However, multivariate analysis showed a significant additive contribution of diffusion parameters in the distinction between control and different grades of TBI-affected brains. Therefore, combining multiple imaging markers may increase the sensitivity for TBI-related pathology.
Distribution of contemporary sensitivity troponin in the emergency department and relationship to 30-day mortality: The CHARIOT-ED substudy.

BACKGROUND Contemporary sensitivity troponin (cs-cTn) concentrations above the upper limit of normal (ULN) are seen in a wide range of clinical conditions and evidence is growing that suggests cs-cTn may be a biomarker of future morbidity and mortality. OBJECTIVES Our aim was to test the hypothesis that cs-cTn, measured in the emergency department, may be a biomarker for 30-day mortality, irrespective of the patient's presentation. METHOD In all 5,708 consecutive cases, contemporary sensitivity troponin I (cs-cTnI) was measured either as requested by the clinical team or as part of the study, in which case both the clinical team and the patient were unaware of the result. Basic demographics were available from the original study and 30-day mortality was derived from NHS Digital data. RESULTS In patients whose cs-cTnI test was requested solely as part of the study, 30-day mortality increased with increasing cs-cTnI concentrations (0% with undetectable concentrations to 14.7% with concentrations above the ULN). Multivariable Cox regression analysis showed that log(10)cs-cTnI concentration was independently associated with 30-day mortality. CONCLUSION Increasing cs-cTnI concentrations are associated with higher short-term mortality as well as length of stay. As such, cs-cTnI measurements may provide useful prognostic information.
Liver Transplantation for Intrahepatic Cholangiocarcinoma: A Meta-analysis and Meta-regression of Survival Rates

Supplemental Digital Content is available in the text. Background. Intrahepatic cholangiocarcinoma (iCCA) is a contraindication to liver transplantation in most centers worldwide. Therefore, only a few such cases have been performed in each individual center, and the need for a systematic review and meta-analysis to cumulatively pool these results is apparent. Methods. A systematic literature review was conducted using the MEDLINE and Cochrane Library databases according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement (end-of-search date: May 29, 2020). Meta-analyses of proportions were conducted to pool the overall survival (OS), recurrence-free survival (RFS), and overall recurrence rates using the random-effects model. Meta-regression was used to examine cirrhosis and incidental diagnosis as confounders on OS and RFS. Results. Eighteen studies comprising 355 patients and a registry study of 385 patients were included. The pooled 1-, 3-, and 5-y OS rates were 75% (95% CI, 64%-84%), 56% (95% CI, 46%-67%), and 42% (95% CI, 29%-55%), respectively. The pooled 1-, 3-, and 5-y RFS rates were 70% (95% CI, 63%-75%), 49% (95% CI, 41%-57%), and 38% (95% CI, 27%-50%), respectively. Cirrhosis was positively associated with RFS, while incidental diagnosis was not. Neither cirrhosis nor incidental diagnosis was associated with OS. The pooled overall recurrence rate was 43% (95% CI, 33%-53%) over a mean follow-up of 40.6 ± 37.7 mo. Patients with very early (single ≤2 cm) iCCA exhibited superior pooled 5-y RFS (67%; 95% CI, 47%-86%) versus advanced iCCA (34%; 95% CI, 23%-46%). Conclusions. Cirrhotics with very early iCCA or carefully selected patients with advanced iCCA after neoadjuvant therapy may benefit from liver transplantation under research protocols.
The inflammatory biomarker YKL-40 is elevated in the serum, but not the sputum, of E-cigarette users

Abstract Rationale: E-cigarettes are popular among youth and young adults and have been shown to be associated with pulmonary conditions such as asthma and COPD. YKL-40 may serve as a biomarker of pulmonary diseases and may predict the loss of pulmonary function among smokers. We hypothesized that similar to cigarette smokers, e-cigarette users will have higher levels of YKL-40 compared to non-tobacco users. Methods We conducted a cross-sectional study of adults between 18 and 55 years old. Inclusion criteria were: exclusive e-cigarette use or cigarette smoking for ≥ 1 year or no history of tobacco use. Participants with a history of pulmonary illness, atopy, medications (except birth control pills), marijuana, and illegal substance use were excluded. Custom Multiplex ELISA was used to measure YKL-40 and other biomarker levels in the serum and induced sputum of the participants. Multivariable linear regression was used to compare the levels of YLK-40 in healthy participants, e-cigarette, and cigarette users after adjusting for age, sex, and BMI. Results We recruited 20 healthy controls, 23 cigarette smokers, and 22 exclusive e-cigarette users. Serum YKL-40 (ng/ml) was significantly higher in e-cigarette users (Median 21.2 [IQR 12.1-24.0] ng/ml) when compared to controls (12.2 [IQR 8.7-18.1] ng/ml, p = 0.016) but comparable to cigarette smokers (21.6 [IQR 11.62-51.7] ng/ml, p = 0.31). No significant differences were found in the serum or sputum of the other biomarkers tested. Conclusion The inflammatory biomarker, YKL-40 is elevated in the serum but not the sputum of e-cigarette users with no reported pulmonary disease. Further research is necessary to characterize this association.
Systematic Review on the Creep of Fiber-Reinforced Concrete

Fiber-reinforced concrete (FRC) is increasingly used in structural applications owing to its benefits in terms of toughness, durability, ductility, construction cost and time. However, research on the creep behavior of FRC has not kept pace with other areas such as short-term properties. Therefore, this study aims to present a comprehensive and critical review of literature on the creep properties and behavior of FRC with recommendations for future research. A transparent literature search and filtering methodology were used to identify studies regarding creep on the single fiber level, FRC material level, and level of structural behavior of FRC members. Both experimental and theoretical research are analyzed. The results of the review show that, at the single fiber level, pull-out creep should be considered for steel fiber-reinforced concrete, whereas fiber creep can be a governing design parameter in the case of polymeric fiber reinforced concrete subjected to permanent tensile stresses incompatible with the mechanical time-dependent performance of the fiber. On the material level of FRC, a wide variety of test parameters still hinders the formulation of comprehensive constitutive models that allow proper consideration of the creep in the design of FRC elements. Although significant research remains to be carried out, the experience gained so far confirms that both steel and polymeric fibers can be used as concrete reinforcement provided certain limitations in terms of structural applications are imposed. Finally, by providing recommendations for future research, this study aims to contribute to code development and industry uptake of structural FRC applications.
Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance.

Immune checkpoint inhibitors (ICIs) have made an indelible mark in the field of cancer immunotherapy. Starting with the approval of anti-cytotoxic T lymphocyte-associated protein 4 (anti-CTLA-4) for advanced-stage melanoma in 2011, ICIs-which now also include antibodies against programmed cell death 1 (PD-1) and its ligand (PD-L1)-quickly gained US Food and Drug Administration approval for the treatment of a wide array of cancer types, demonstrating unprecedented extension of patient survival. However, despite the success of ICIs, resistance to these agents restricts the number of patients able to achieve durable responses, and immune-related adverse events complicate treatment. Thus, a better understanding of the requirements for an effective and safe antitumor immune response following ICI therapy is needed. Studies of both tumoral and systemic changes in the immune system following ICI therapy have yielded insight into the basis for both efficacy and resistance. Ultimately, by building on these insights, researchers should be able to combine ICIs with other agents, or design new immunotherapies, to achieve broader and more durable efficacy as well as greater safety. Here, we review the history and clinical utility of ICIs, the mechanisms of resistance to therapy, and local and systemic immune cell changes associated with outcome. Expected final online publication date for the Annual Review of Pathology: Mechanisms of Disease, Volume 16 is January 25, 2021. Please see http://www.annualreviews. org/page/journal/pubdates for revised estimates.
Brain Development in Infants of Mothers With Gestational Diabetes Mellitus: A Diffusion Tensor Imaging Study.

OBJECTIVE The objective of this study was to investigate clinical neurocognitive performance and microstructural white matter (WM) alterations in infants of mothers with gestational diabetes mellitus (GDM) using diffusion tensor imaging. MATERIALS AND METHODS Infants (corrected gestational age, 33.42-36.00 weeks) of mothers with GDM (n = 31) and gestational age- and sex-matched unexposed controls (n = 31) accomplished 3-T diffusion tensor imaging scans and neurocognitive tests. Diffusion tensor imaging measures, mainly referring to fractional anisotropy (FA) values, were compared between 2 groups, and within-group analysis of correlation between FA values and neurocognitive testing outcomes in GDM-exposed infants was conducted subsequently. RESULTS Fractional anisotropy was significantly decreased in the splenium of corpus callosum, posterior limb of internal capsule, thalamus in infants of mothers with GDM when compared with controls (P < 0.05), reflecting microstructural WM abnormalities in the GDM group. Decreased FA was associated with worse neurocognitive performance in the exposed group (P < 0.05). CONCLUSIONS Individuals of mothers with GDM showed microstructural WM abnormalities in different brain regions, which were significantly related to worse neurocognitive performance. This might reveal that GDM directly insults the brain development of the offspring.