Miracle-dz/UniFAR-FTUs huggingface dataset:
Efficacy of [

Background Peptide receptor radionuclide therapy (PRRT) is one of the most promising therapeutic strategies in neuroendocrine neoplasms (NENs). Nevertheless, its role in certain tumor sites remains unclear. This study sought to elucidate the efficacy and safety of [177Lu]Lu-DOTATATE in NENs with different locations and evaluate the effect of the tumor origin, bearing in mind other prognostic variables. Advanced NENs overexpressing somatostatin receptors (SSTRs) on functional imaging, of any grade or location, treated at 24 centers were enrolled. The protocol consisted of four cycles of 177Lu-DOTATATE 7.4 GBq iv every 8 weeks (NCT04949282). Results The sample comprised 522 subjects with pancreatic (35%), midgut (28%), bronchopulmonary (11%), pheochromocytoma/ paraganglioma (PPGL) (6%), other gastroenteropancreatic (GEP) (11%), and other non-gastroenteropancreatic (NGEP) (9%) NENs. The best RECIST 1.1 responses were complete response, 0.7%; partial response, 33.2%; stable disease, 52.1%; and tumor progression, 14%, with activity conditioned by the tumor subtype, but with benefit in all strata. Median progression-free survival (PFS) was 31.3 months (95% CI, 25.7–not reached [NR]) in midgut, 30.6 months (14.4-NR) in PPGL, 24.3 months (18.0-NR) in other GEP, 20.5 months (11.8-NR) in other NGEP, 19.8 months (16.8–28.1) in pancreatic, and 17.6 months (14.4–33.1) in bronchopulmonary NENs. [177Lu]Lu-DOTATATE exhibited scant severe toxicity. Conclusion This study confirms the efficacy and safety of [177Lu]Lu-DOTATATE in a wide range of SSTR-expressing NENs, regardless of location, with clinical benefit and superimposable survival outcomes between pNENs and other GEP and NGEP tumor subtypes different from midgut NENs.
Synthesis and evaluation of modified lens using plasma treatment containing timolol-maleate loaded lauric acid-decorated chitosan-alginate nanoparticles for glaucoma

Abstract Reducing intraocular pressure (IOP) with eye drops is one of the most common ways to control glaucoma. Low bioavailability and high frequency of administration in eye drops are major challenges in ocular pharmacotherapy. Contact lenses have attracted the attention of scientists in recent decades as an alternative method. In this study, with the aim of long-term drug delivery and better patient compatibility, contact lenses with surface modification and nanoparticles were used. In this study, timolol-maleate was loaded into polymeric nanoparticles made of chitosan conjugate with lauric acid and sodium alginate. Then silicon matrix was mixed with a curing agent (10:1), and the suspension of nanoparticles was added to the precursor and cured. Finally, for surface modification, the lenses were irradiated with oxygen plasma at different exposure times (30, 60, and 150 s) and soaked in different BSA concentrations (1, 3, and 5% w/v). The results showed nanoparticles with a size of 50 nm and a spherical shape were synthesized. The best surface modification of the lenses was for 5 (% w/v) albumin concentration and 150 s exposure time, which had the highest increase in hydrophilicity. Drug release from nanoparticles continued for 3 days and this amount increased to 6 days after dispersion in the modified lens matrix. The drug model and kinetic study show the Higuchi model completely supported the release profile. This study represents the novel drug delivery system to control intra-ocular pressure as a candidate platform for glaucoma treatment. Improved compatibility and drug release from the designed contact lenses would prepare new insight into the mentioned disease treatment. Graphical Abstract
Epidemiology, management and outcomes of Cryptococcus gattii infections: A 22-year cohort

Background Cryptococcus gattii is a globally endemic pathogen causing disease in apparently immune-competent hosts. We describe a 22-year cohort study from Australia’s Northern Territory to evaluate trends in epidemiology and management, and outcome predictors. Methods A retrospective cohort study of all C. gattii infections at the northern Australian referral hospital 1996–2018 was conducted. Cases were defined as confirmed (culture-positive) or probable. Demographic, clinical and outcome data were extracted from medical records. Results 45 individuals with C. gattii infection were included: 44 Aboriginal Australians; 35 with confirmed infection; none HIV positive out of 38 tested. Multifocal disease (pulmonary and central nervous system) occurred in 20/45 (44%). Nine people (20%) died within 12 months of diagnosis, five attributed directly to C. gattii. Significant residual disability was evident in 4/36 (11%) survivors. Predictors of mortality included: treatment before the year 2002 (4/11 versus 1/34); interruption to induction therapy (2/8 versus 3/37) and end-stage kidney disease (2/5 versus 3/40). Prolonged antifungal therapy was the standard approach in this cohort, with median treatment duration being 425 days (IQR 166–715). Ten individuals had adjunctive lung resection surgery for large pulmonary cryptococcomas (median diameter 6cm [range 2.2-10cm], versus 2.8cm [1.2-9cm] in those managed non-operatively). One died post-operatively, and 7 had thoracic surgical complications, but ultimately 9/10 (90%) treated surgically were cured compared with 10/15 (67%) who did not have lung surgery. Four patients were diagnosed with immune reconstitution inflammatory syndrome which was associated with age <40 years, brain cryptococcomas, high cerebrospinal fluid pressure, and serum cryptococcal antigen titre >1:512. Conclusion C. gattii infection remains a challenging condition but treatment outcomes have significantly improved over 2 decades, with eradication of infection the norm. Adjunctive surgery for the management of bulky pulmonary C. gattii infection appears to increase the likelihood of durable cure and likely reduces the required duration of antifungal therapy.
From dyspepsia to complicated peptic ulcer: new markers in diagnosis and prognosis.

OBJECTIVE Peptic ulcer disease (PUD) may present with different clinical findings, ranging from mild dyspeptic complaints to mortal complications, such as gastrointestinal system perforation. The aim of this study was to investigate the potential blood parameters that can be used in the diagnosis of PUD and prediction of complications. PATIENTS AND METHODS A total of 80 patients with dyspeptic complaints, 83 patients with PUD, and 108 patients with peptic ulcer perforation (PUP) who were treated in our hospital between January 2017 and December 2020 were included in the study. Clinical findings, laboratory data, and imaging methods were reviewed retrospectively. RESULTS The mean age of 271 (154 men, 117 women) patients included in the study was 56.04 ± 17.98 (mean ± standard deviation) years. The neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), mean platelet volume, white blood cell, C-reactive protein, and neutrophil values were higher in patients with PUP compared to other groups (p < 0.001 for all). In the PUD group, only red blood cell distribution width was significantly higher compared to the patient group with dyspeptic complaints. In the postoperative period, NLR and PLR were significantly higher in patients who developed severe complications according to the Clavien-Dindo classification compared to patients who developed mild complications. CONCLUSIONS This study showed that simple blood parameters can be used as diagnostic markers at different stages of PUD. NLR and PLR can be helpful in the diagnosis of PUP and red blood cell distribution width can be used to differentiate patients with peptic ulcer from dyspeptic patients. Additionally, NLR and PLR can be used to predict serious postoperative complications after PUP surgery.
Sheared flows and small‐scale Alfvén wave generation in the auroral acceleration region

Coincident particle and optical measurements from the Reimei spacecraft suggest that sheared flows through an inverted‐V arc may be unstable to the emission of Alfvén waves. The particle measurements reveal time dispersed field‐aligned electron bursts typical of low energy electrons accelerated by inertial Alfvén waves (IAWs). These Alfvén wave accelerated electrons are embedded within multi‐keV inverted‐V electron structures. The optical measurements at the footprint of the inverted‐V structures reveal counter propagating and folded/vortical discrete auroral forms moving with speeds of ∼14–18 km/s. We show that the flow shear inferred from this motion exceeds that required for instability to the emission of Alfvén waves on scales of the order of an electron inertial length. The emission of these waves provides a likely means for driving the low energy dispersed electron bursts we observe.
DIMENSIONAL CHARACTERISTICS OF THE NONWANDERING SETS OF OPEN BILLIARDS

An open billiard is a dynamical system in which a pointlike particle moves at constant speed in an unbounded domain, reflecting off a boundary according to the classical laws of optics [4]. This thesis is an investigation of dimensional characteristics of the nonwandering set of an open billiard in the exterior of three or more strictly convex bodies satisfying Ikawa’s no-eclipse condition [5, 11]. The billiard map for these systems is an axiom A diffeomorphism with a finite Markov partition. The nonwandering set is a hyperbolic set with stable and unstable manifolds satisfying a certain reflection property. The characteristics we investigate include the topological and measure-theoretic entropy, topological pressure, Lyapunov exponents, lower and upper box dimensions and the Hausdorff dimension of the nonwandering set. In particular, we investigate the dependence of the Hausdorff dimension on deformations to the boundary of the billiard obstacles. While the dependence of dimensional characteristics on perturbations of a system has been studied before [6, 9], this is the first time this question has been answered for dynamical billiards. We find upper and lower bounds for the Hausdorff dimension using two different methods: one involving bounding the size of curves on convex fronts and the other using Bowen’s equation and the variational principle for topological pressure. Both methods lead to the same upper and lower bounds. In the first method, we use a wellknown recurrence relation for the successive curvatures of convex fronts to find bounds on the size of the fronts. This allows us to construct Lipschitz (but not bi-Lipschitz) homeomorphisms between the nonwandering set and the one-sided symbol space. From there we obtain estimates of the dimension. Kenny [7] used this method for open billiards in the plane. We extend it to higher dimensions and make improvements to the results in the plane. This work has been published in [13].
Molecular Mechanisms of Resistance to Ceftazidime/Avibactam in Clinical Isolates of Enterobacterales and Pseudomonas aeruginosa in Latin American Hospitals

In this manuscript, we determine the molecular mechanisms of ceftazidime-avibactam resistance in Enterobacterales and P. aeruginosa isolates from five Latin American countries. Our results reveal a low rate of resistance to ceftazidime-avibactam among Enterobacterales; in contrast, resistance in P. aeruginosa has proven to be more complex, as it might involve multiple known and possibly unknown resistance mechanisms. ABSTRACT Ceftazidime-avibactam (CZA) is the combination of a third-generation cephalosporin and a new non-β-lactam β-lactamase inhibitor capable of inactivating class A, C, and some D β-lactamases. From a collection of 2,727 clinical isolates of Enterobacterales (n = 2,235) and P. aeruginosa (n = 492) that were collected between 2016 and 2017 from five Latin American countries, we investigated the molecular resistance mechanisms to CZA of 127 (18/2,235 [0.8%] Enterobacterales and 109/492 [22.1%] P. aeruginosa). First, by qPCR for the presence of genes encoding KPC, NDM, VIM, IMP, OXA-48-like, and SPM-1 carbapenemases, and second, by whole-genome sequencing (WGS). From the CZA-resistant isolates, MBL-encoding genes were detected in all 18 Enterobacterales and 42/109 P. aeruginosa isolates, explaining their resistant phenotype. Resistant isolates that yielded a negative qPCR result for any of the MBL encoding genes were subjected to WGS. The WGS analysis of the 67 remaining P. aeruginosa isolates showed mutations in genes previously associated with reduced susceptibility to CZA, such as those involved in the MexAB-OprM efflux pump and AmpC (PDC) hyperproduction, PoxB (blaOXA-50-like), FtsI (PBP3), DacB (PBP4), and OprD. The results presented here offer a snapshot of the molecular epidemiological landscape for CZA resistance before the introduction of this antibiotic into the Latin American market. Therefore, these results serve as a valuable comparison tool to trace the evolution of the resistance to CZA in this carbapenemase-endemic geographical region. IMPORTANCE In this manuscript, we determine the molecular mechanisms of ceftazidime-avibactam resistance in Enterobacterales and P. aeruginosa isolates from five Latin American countries. Our results reveal a low rate of resistance to ceftazidime-avibactam among Enterobacterales; in contrast, resistance in P. aeruginosa has proven to be more complex, as it might involve multiple known and possibly unknown resistance mechanisms.
Piezoelectricity and related properties of vinylidene fluoride and trifluoroethylene copolymers

The piezoelectric properties and ferroelectric transition behaviors of vinylidene fluoride and trifluoroethylene copolymers, P(VDFx−TrFE1−x), were studied as a function of x in the range of x=0.37–0.94. The electromechanical coupling factor kt and piezoelectric constant d31 are strongly dependent on both x and annealing temperature. In the copolymers of 0.65≲x≲0.82, a large kt value of 0.27–0.3 has been found when annealed above ferroelectric‐to‐paraelectric transition temperature Tc. The large kt is attributable to their high remanent polarization (∼110 mC/m2) which arises from high degrees of crystallinity and preferred orientation of well‐grown crystallites. Structural and morphological changes induced by annealing and poling were characterized by SEM, DSC, and x‐ray diffraction studies. Phase diagram of the copolymers were obtained by DSC measurements. Tc increases with increase of x and coincides with melting temperture Tm at x≂0.82. In the range of x≳0.82, Tc=Tm.
Aeroelastic Stability of Welded-in-Pair Low Pressure Turbine Rotor Blades: A Comparative Study Using Linear Methods

The aerodynamic damping of a modern low pressure turbine bladed-disk with interlock rotor blades is compared for the first time to that obtained when the rotor blades are welded in pairs through the lateral face of the shroud. The damping is computed solving the linearized Reynolds averaged Navier-Stokes equations on a moving grid. First the basics of the stabilising mechanism of welding the rotor blades in pairs is investigated using two-dimensional analyzer and the Panovsky and Kielb method. It is concluded that the stabilizing effect is due to the suppression of unsteady perturbations in one out of the two passages providing for the first time a physical explanation to engine data. Three-dimensional effects are then studied using the actual mode shapes of two bladed disks differing solely in the shroud boundary conditions. It is concluded that the increase in the aerodynamic damping, due to the modification of the mode shapes caused by welding the rotor blades in pairs, is smaller than that due to the overall raise of the reduced frequencies of a bladed disk with an interlock design. The modification of the flutter boundaries due to mistiming effects is assessed using the reduced order model known as the Fundamental Mistuning Model. A novel extension of the critical reduced frequency stability maps accounting for mistiming effects is derived and applied for both, the freestanding and welded-in-pair airfoils. The stabilizing effect of mistuning is clearly seen in these maps. Finally, the effect of mistuning on low-pressure-turhine bladed disks is studied. It is shown that the modification on the stability limit of the interlock bladed disk is negligible, while for the welded-in-pair configuration a 0.15% increase of the damping relative to the critical damping is found. This qualitative difference between both configurations had not been reported before.
Consensual eye intra-ocular pressure rise following unilateral glaucoma surgery

Purpose: Consensual eye intra-ocular pressure (IOP) increase has been reported following ipsilateral glaucoma surgery. The study evaluated the need for increase in anti-glaucoma medications (AGM) ± glaucoma surgery to control the IOP in consensual eye following unilateral glaucoma surgery. Methods: Data of 187 consecutive patients who underwent either trabeculectomy or AGV implant were collected. Index (IE) and fellow eye (FE) IOP (baseline, follow-up day 1, week 1, months 1 and 3), acetazolamide and AGM use, FE surgery, glaucoma status, and relevant ophthalmological data were collected. Results: A significant increase from a baseline IOP of 14.4 mmHg was noted at week 1 (15.8 mmHg, p-0.005) and month 1 (15.62 mmHg, p-0.007) in FE (n-187). Among the 61 patients (33%, n-187) who needed additional intervention to reduce FE IOP, 27 (14.4%) underwent FE trabeculectomy. In the IE trabeculectomy group (n-164), significant increase in FE IOP was noted in week 1 (15.87 mmHg, p-0.014) and month 1 (15.61 mmHg, p-0.02), and in the IE AGV group (n-23) at day 1 (15.91 mmHg, p-0.06). Pre-operative acetazolamide resulted in significant increase in FE IOP at week 1 and month 1. Maximum increase in FE IOP of nearly 3.5 mm Hg was noted when IE IOP was persistently <5 mmHg at one month following surgery. Mean FE IOP remained elevated at all visits. Conclusion: An increase in fellow eye IOP needing any additional intervention in a third and surgical intervention in nearly a sixth meant that FE IOP be strictly monitored and addressed following unilateral glaucoma surgery.
CONSISTENCY AND ASYMPTOTIC NORMALITY OF SIEVE ML ESTIMATORS UNDER LOW-LEVEL CONDITIONS

This paper considers sieve maximum likelihood estimation of seminonparametric (SNP) models with an unknown density function as non-Euclidean parameter, next to a finite-dimensional parameter vector. The density function involved is modeled via an infinite series expansion, so that the actual parameter space is infinite-dimensional. It will be shown that under low-level conditions the sieve estimators of these parameters are consistent, and the estimators of the Euclidean parameters are $\sqrt N$ asymptotically normal, given a random sample of size N. The latter result is derived in a different way than in the sieve estimation literature. It appears that this asymptotic normality result is in essence the same as for the finite dimensional case. This approach is motivated and illustrated by an SNP discrete choice model.
From proposal to action: evaluating the results of a nursing student project to promote student-community engagement

Background A focus on community engagement is encouraged when educating nursing students on preventative care and advocacy. Students often struggle to connect theory to practice and benefit from real-world experiences. Aim This paper describes the effect of a student-led health project on student development. Methods A descriptive, correlational design was used to explore end of semester feedback from undergraduate nursing students (N = 174) completing a semester long community project. Chi-square analyses and thematic coding were performed to determine measures of association and student perceptions. Results Across 83 completed surveys (47.7%), self-efficacy was a key factor in project completion, development, bias awareness, and commitment to community. Conclusions Civic duty and professional responsibility are challenging concepts for students, thus, impacting transition to practice. Engagement in self-efficacious experiences is encouraged. Impact statement Community engagement influences undergraduate nursing students’ development. Enhanced support of student self-efficacy may promote attainment of nursing values and improved care delivery.
Antibiotic-induced accumulation of lipid II synergizes with antimicrobial fatty acids to eradicate bacterial populations

Antibiotic tolerance and antibiotic resistance are the two major obstacles to the efficient and reliable treatment of bacterial infections. Identifying antibiotic adjuvants that sensitize resistant and tolerant bacteria to antibiotic killing may lead to the development of superior treatments with improved outcomes. Vancomycin, a lipid II inhibitor, is a frontline antibiotic for treating methicillin-resistant Staphylococcus aureus and other Gram-positive bacterial infections. However, vancomycin use has led to the increasing prevalence of bacterial strains with reduced susceptibility to vancomycin. Here, we show that unsaturated fatty acids act as potent vancomycin adjuvants to rapidly kill a range of Gram-positive bacteria, including vancomycin-tolerant and resistant populations. The synergistic bactericidal activity relies on the accumulation of membrane-bound cell wall intermediates that generate large fluid patches in the membrane leading to protein delocalization, aberrant septal formation, and loss of membrane integrity. Our findings provide a natural therapeutic option that enhances vancomycin activity against difficult-to-treat pathogens, and the underlying mechanism may be further exploited to develop antimicrobials that target recalcitrant infection.
On the Accuracy of the Finite-Difference Schemes: The 1D Elastic Problem

We present a 1D finite-difference (fd) scheme that is based on the application of Geller and Takeuchi’s (1998) optimally accurate fd operators to the heterogeneous strong-form equation of motion developed by Moczo et al. (2002). We numerically compare the scheme with two other fd schemes that approximate the heterogeneous strong-form equation of motion, one using conventional 2nd-order fd operators, the other using staggered-grid 4th-order fd operators. The numerical comparison is based on the envelope and phase misfits between tested and reference solutions. We discuss the error due to internal interface (primarily controlled by the boundary condition and its numerical approximation) and error due to grid dispersion. We demonstrate the superior accuracy of the scheme based on the application of the optimally accurate operators.
Estimation of surgically induced astigmatism after small-incision cataract surgery done by junior residents

Purpose: To estimate the postoperative astigmatism after small-incision cataract surgery (SICS) done by junior residents at the end of 1 and 3 months. Methods: This observational longitudinal study was conducted at the Department of Ophthalmology of a tertiary eye care hospital and research center. 50 patients enrolled in the study underwent manual small incision cataract surgery by junior residents. Preoperative detailed ocular examination was done, which included keratometric estimation using autokeratometer (GR-3300K). Incision length, distance of incision from the limbus, and type of suturing technique were noted. Postoperatively, keratometric readings were noted at 1 and 3 months. Astigmatism (surgically induced astigmatism [SIA]) was estimated using Hill's SIA calculator version 2.0. All the analyses were performed using Statistical Package for the Social Sciences (SPSS) ver. 26.0 (IBM Corp., USA) software, and the statistical significance was tested at a 5% level. Results: Out of 50 patients, 54% had SIA between 1.5 and 2.5 D and 32% had SIA of more than 2.5 D. Only 14% had SIA less than 1.5 D at the end of 1 month. While 52% had SIA between 1.5 and 2.5 D, 22% had SIA between 1.5 and 2.5 D and 26% had SIA less than 1.5 D at the end of 3 months. Conclusion: The SIA in most of the SICS done by junior residents was above 1.5 D. It depended mainly on the incision length, its distance from the limbus, and the suturing technique.