bluuebunny/crossref_metadata_2025_split huggingface dataset:
Simulation-guided, application-specific manufacturing of gecko-inspired adhesives
Authors: Hajj-Ahmad Amar , Gharibi Armin , Lanzetta Michele , Cutkosky Mark R. 
Published: February 2025

Abstract
We introduce a simulation-based approach to specify tool trajectories for micromachining the molds used to create directional gecko-inspired adhesives. A challenge is that the final feature geometries are different from the corresponding tool-paths. Therefore, the process of designing molds for different applications has previously required empirical iteration. Large plastic strains and sensitivity to material parameters and friction also make it difficult to apply conventional finite element analyses, with only approximate agreement between predicted and observed cutting forces. The solution reported here uses a plane-strain FEA analysis specialized for metal working, with a customized material model to accommodate the strain rates and strain hardening effects. The analysis was conducted for wax and soft aluminum molds with a variety of wedge-shaped features. Predicted and measured microscopic feature geometries match to within 2.8%.
Nonlinear Complementary Strain Energy Formulation for Planar Beam Flexures Undergoing Intermediate Deflection
Authors: Ma Fulei , Bai Ruiyu , Chen Guimin , Awtar Shorya 
Published: February 2025

Abstract
The previously presented beam constraint model (BCM) successfully captures pertinent nonlinearities to predict the constraint characteristics of beam flexures. This has been followed by multiple attempts to construct a more comprehensive framework comprising strain energy (SE) principles and complementary strain energy (CSE) principles. However, comprehensive results are still lacking in the current literature, especially in the validation of the CSE definition, fundamental relations between beam coefficients, further relationships between the SE and the CSE, and suitable examples. This article addresses all these gaps. The nonlinear CSE is derived using the principle of complementary virtual work for a planar beam undergoing intermediate deflections. This result is shown to be consistent with the load—displacement relations and the nonlinear strain energy formulation in the BCM. Furthermore, the current article also demonstrates for the first time that the SE and the CSE are interrelated through the gap energy, which is derived and formulated in terms of tip loads. Finally, this CSE expression is employed in the analysis of a fixed-guided mechanism. All results are validated to a high degree of accuracy via nonlinear finite element analysis.
Innovative Designs of 3D Heat Sinks by Topology Optimization
Authors: Wang Dingbiao , Yang Chongrui , Wang Guanghui , Li Yi , Dbouk Talib 
Published: February 2025

Abstract
The topology optimization (TO) method is developed and applied to 3D heat sink design optimization using the finite element method (FEM). To go from theory to practical application of optimized heat sink designs, the impact of the ratio between fin height (Hc) and substrate thickness (Hb) on the performance of heat sinks was investigated, studying the critical role of geometric parameters in heat dissipation performance, focusing on optimizing the internal fluid channels to enhance the overall hydraulic and thermal efficiencies under various operating conditions. Optimal flow conditions vary across TO designs; notably, structures with near-equal (Hc) and (Hb) ratios demonstrated superior energy and fluid flow overall performances. At high Reynolds numbers, the optimized heat sink designs showed an enhancement in the overall performance up to 41.2%, showcasing the effectiveness of the present TO method. The new 3D optimal designs can be applied to different applications such as the cooling of CPU, GPU, and different electronic chips.
Unsteady Flow Development and Reynolds Stress Measurements in a Centrifugal Compressor Vaned Diffuser
Authors: Meier Matthew A. , Gooding William J. , Key Nicole L. 
Published: February 2025

Abstract
Modern aeroengine designers face the challenge of reducing fuel consumption, which is pushing compressor technology into new design spaces. To optimize these design spaces, high-fidelity computational models are crucial to the compressor design process. It is important to validate these models with experimental data. Nonintrusive measurement techniques allow for the acquisition of data well suited for this comparison, as they do not lead to local disruptions of the flow field. This investigation utilized three-component laser Doppler velocimetry to acquire a unique dataset of detailed unsteady velocity measurements in the vaned diffuser of an aeroengine centrifugal compressor. These measurements allowed for a thorough study of the flow development in the vaneless and semivaneless space of the diffuser as well as through the diffuser passage. The components of the Reynolds stress tensor were also determined at multiple locations in the diffuser flow field. These data are used to study the jet and wake propagation from the impeller exit flow field into the diffuser passage and the resulting secondary flow structures. Predictions from unsteady computational fluid dynamics (CFD) simulations using the shear stress transport (SST) and baseline k–ω explicit algebraic Reynolds stress model (BSL-EARSM) turbulence models are also compared with these experimental data. Both turbulence models yielded results that qualitatively agreed with the experimental radial velocity profile through the vaneless and semivaneless space. With the experimentally determined Reynolds stress tensor, the turbulent kinetic energy (TKE) is calculated at multiple points through the flow field and is compared to the TKE at the same geometric locations in the computational flow field. This comparison highlights the difference in dissipation and production of turbulence between the experimental data and the computational predictions. Investigating the differences in TKE throughout the diffuser helps elucidate the differences in predicted flow structures in the diffuser passage.
Persistence in time: the hunt for
Bacillus anthracis
at a historic tannery site in Austria reveals genetic diversity thought extinct
Authors: Mayerhofer-Rochel Maximilian F. , Himmelbauer Florian , Reinprecht Pierre , Herndler Sebastian , Weidinger Hugo , Hellinger Hans-Jörg , Szostak Michael P. , Grass Gregor , Ehling-Schulz Monika 
Published: February 2025

ABSTRACT

Identifying and analyzing historic anthrax loci may provide a treasure trove to fill in the gaps of persistence in time and genetic diversity of
Bacillus anthracis
. In countries where anthrax has become a disease of the past, detailed knowledge of the exact location and stability of spores in soil reservoirs is limited. Reviewing archival records may provide valuable clues to unearthing such forgotten sites. Knowledge of anthrax diversity in Austria is scarce, as the only available isolates—originating from the last outbreak in Austria in 1988—cluster in the B.Br.004 (CNEVA) canonical single-nucleotide polymorphism (canSNP) group. Thus, we analyzed archival records on anthrax incidents in Austria to locate historic
B. anthracis
soil reservoirs. In parallel, we tested the performance of different soil processing protocols for the isolation of
B. anthracis
spores to establish a suitable workflow for screening historical anthrax loci. Using an optimized workflow, we were able to isolate viable
B. anthracis
spores 80 years after the last occurrence of anthrax at an abandoned tannery identified through our archival work. Genome analysis of the isolated strains allowed to improve the phylogeographic resolution within the hitherto poorly covered A.Br.064 (V770) canSNP group by linking historical records to genetic information. Furthermore, our results re-emphasize that
B. anthracis
can survive for decades at historic sites and may pose a health threat when such sites are eventually reactivated by climatic factors or human intervention.

IMPORTANCE

Bacillus anthracis
is a continuing threat from a One Health perspective since it leads to severe infections in animals and humans. Ongoing climate change or human activities can reactivate historical
B. anthracis
loci, previously considered inactive or forgotten. Therefore, knowledge of historic anthrax incidents at abandoned animal processing facilities, such as tanneries or farmyards, along with robust detection protocols, is of prime interest when monitoring this important zoonosis. As shown here, archival records of possible origins of anthrax-contaminated goods received at tanneries are valuable sources and support these efforts. Investigation for viable spores at such historical sites could not only provide new insights into the past genetic diversity and population structure of
B. anthracis
but also provide important information for taking appropriate measures to prevent future outbreaks originating from these sites.
Candida albicans
enhances iron uptake to maintain fluconazole resistance
Authors: Sharma Rishabh , Nahar Anubhav , Puri Sumant 
Published: February 2025

ABSTRACT

Widespread use of fluconazole has led to the emergence of fluconazole-resistant (FR)
Candid
a spp. causing challenges in clinical treatment. Iron, an essential nutrient, affects the levels of ergosterol (a fluconazole target) in fungal membranes. Our lab-generated FR strain (fluconazole minimum inhibitory concentration [MIC] >125 µg/mL) showed a twofold lower MIC (4.66 µg/mL) for the iron chelator deferasirox (DFX), compared to its patent strain CAI4 (DFX MIC 9.34 µg/mL), suggesting a greater sensitivity to iron chelation. A sublethal dose of DFX (2.33 µg/mL) was able to effectively synergize with 125 µg/mL fluconazole to kill the FR strain. Iron estimation revealed significantly enhanced intracellular iron accumulation in the FR strain compared to CAI4. Expression of iron-uptake genes (
FRP1
,
FRE10
, and
RBT5
) was also significantly upregulated in the FR strain, particularly under high iron. FR strain also showed an increase in the levels of cellular ergosterol, along with an increase in the expression of ergosterol biosynthesis genes (
ERG11
and
ERG9
), compared to CAI4, under both low and high iron. The strain further showed increased β-glucan levels and exposure. Additionally, FR strain showed significantly higher survival in high-iron mice compared to low-iron mice, during fluconazole treatment. Finally, we observed a synergistic fungicidal response between 2.33 µg/mL DFX and 125 µg/mL fluconazole, for FR clinical strains. Overall, this suggests that FR
C. albicans
actively uptakes more iron to maintain cellular conditions needed to support its resistance against fluconazole; and that DFX alone or in conjugation with fluconazole has the potential to overcome fluconazole drug resistance.
Chlamydia
plasmid-encoded protein Pgp2 is a replication initiator with a unique β-hairpin necessary for iteron-binding and plasmid replication
Authors: Wan Danny , Pan Matthew , Zhong Guangming , Fan Huizhou 
Published: February 2025

ABSTRACT

The virulence plasmid of the obligate intracellular bacterium
Chlamydia
encodes eight proteins. Among these, Pgp3 is crucial for pathogenicity, and Pgp4 functions as a transcriptional regulator of both plasmid and chromosomal genes. The remaining proteins, Pgp1, Pgp5, Pgp6, Pgp7, and Pgp8, are predicted to play various roles in plasmid replication or maintenance based on their amino acid sequences. However, the function of Pgp2 remains unknown, even though it is required for transformation. In this study, we utilized AlphaFold to predict the three-dimensional (3-D) structure of
Chlamydia trachomatis
Pgp2. Despite a lack of apparent sequence homology, the AlphaFold structure exhibited high similarity to experimentally determined structures of several plasmid replication initiators. Notably, Pgp2 features a unique β-hairpin motif near the DNA-binding domain, absent in other plasmid replication initiators with overall 3-D structures similar to Pgp2. This β-hairpin motif is also present in AlphaFold models of Pgp2s across all 13
Chlamydia
species. To assess its significance, we engineered a plasmid lacking the 11 amino acids constituting the β-hairpin motif in
C. trachomatis
Pgp2. Although this deletion did not alter the overall structure of Pgp2, the mutated plasmid failed to transform plasmid-free
C. trachomatis
. These findings reveal that Pgp2 is a plasmid replication initiator, with the β-hairpin motif playing a critical role in binding to its cognate iteron sequences in the replication origin of the chlamydial plasmid.
Mecillinam activity against multidrug-resistant
Shigella sonnei
and
Shigella flexneri
Authors: Stefanovic Aleksandra , Gowland Leah , Ritchie Gordon , Lee Colin , Chorlton Sam , Matic Nancy , Leung Victor , Payne Michael , Lowe Christopher F. , Romney Marc G. 
Published: February 2025

ABSTRACT

We performed phenotypic susceptibility testing and whole-genome sequencing to investigate
in vitro
mecillinam activity against multidrug-resistant (MDR)
Shigella
. Ninety-five isolates (53 [56%]
Shigella sonnei
and 42 [44%]
Shigella flexneri
) were included. The MIC
50
and MIC
90
were 1 and 2 µg/mL, respectively, by agar dilution, and all zone diameters were ≥15 mm by disc diffusion testing. No known clinically relevant mecillinam resistance mutations (including
cys
B) were detected. The favorable MIC profile and absence of resistance markers make pivmecillinam an agent worth considering for the treatment of infections caused by MDR
Shigella
. Clinically feasible susceptibility testing methods and standardized interpretations for mecillinam and
Shigella
spp. are needed to guide therapy.

IMPORTANCE

Rapidly emerging resistance in
Shigella
species leaves few antibiotic treatment options. The World Health Organization recommends pivmecillinam, a prodrug of mecillinam, for the treatment of
Shigella
infections. However, little is known about the susceptibility of
Shigella
spp. to mecillinam in North America. We performed mecillinam susceptibility testing on our collection of resistant
Shigella
isolates and investigated genetic mechanisms of resistance using whole-genome sequencing. We observed a favorable mecillinam susceptibility profile and a lack of known genetic mechanisms of resistance. However, in the absence of standardized laboratory guidelines for mecillinam susceptibility testing, interpreting susceptibility test results is challenging. We propose that further studies are needed to correlate susceptibility testing data with clinical outcomes, with the aim of establishing standardized clinical breakpoints for
Shigella
spp. and mecillinam.
Supplemental Material: Formation of talc in the subduction interface: Mg isotopes demonstrate Mg loss over Si gain
Authors: Easthouse Griffin , al. et 
Published: February 2025

<div>Detailed methods, plot of δ<sup>26</sup>Mg with distance from a reaction boundary, additional mass balance plots, Mg isotope and bulk geochemical data, and global exhumed subduction interface matrix compilation. </div>
Effectiveness and safety of the XEN45 gel stent compared to trabeculectomy in primary open-angle glaucoma: the Gold-Standard Pathway Study
Authors: Ahmed Iqbal K , Vera Vanessa , Stalmans Ingeborg , Fea Antonio Maria , Mansouri Kaweh , Gu Xuemin , Craven Earl Randy , Reitsamer Herbert A 
Published: February 2025

AimTo compare the gel stent to trabeculectomy in the Gold-Standard Pathway Study (GPS) patients with primary open-angle glaucoma (POAG).MethodsIn the GPS, patients with elevated intraocular pressure (IOP) poorly controlled with IOP-lowering medication were randomised (2:1, gel stent:trabeculectomy). Aggregate primary endpoint: patients (%) at month 12 achieving ≥20% IOP reduction from baseline without medication increase, clinical hypotony, vision loss to counting fingers or secondary surgical intervention (SSI). Secondary endpoints included changes in mean IOP and medication count from baseline; postoperative interventions; visual recovery; postoperative complications; and the Symptom and Health Problem Checklist (SHPC-18) questionnaire.ResultsOf 130 eyes with POAG treated/analysed (gel stent, n=88; trabeculectomy, n=42); 61.4% and 69.0% met the primary endpoint, respectively (p=0.394). At month 12, the change from baseline in mean IOP was statistically greater post-trabeculectomy (by 2.8 mm Hg; p=0.028) than post-gel stent. Postoperative intervention and postoperative complication rates were 39.8% and 75.0% (gel stent) versus 76.2% and 92.9% (trabeculectomy), respectively. Hypotony (IOP ≤6 mm Hg at two consecutive visits) rates were 14.8% (gel stent) and 28.6% (trabeculectomy). Visual recovery was faster/better (per the mean and time to first return to baseline best corrected visual acuity) and SHPC-18-related improvements were greater post-gel stent than post-trabeculectomy.ConclusionSimilar proportions of eyes with POAG achieved the primary endpoint post-gel stent and post-trabeculectomy. The mean IOP reduction was statistically greater post-trabeculectomy. The gel stent resulted in fewer postoperative interventions, faster/better visual recovery, favourable patient-reported outcomes and fewer specific adverse events, although more SSIs and IOP elevations were observed.
Uptake and 4-week outcomes of an ‘opt-out’ smoking cessation referral strategy in a London-based lung cancer screening setting
Authors: Bhamani Amyn , Katsampouris Evangelos , Bojang Fanta , Verghese Priyam , Creamer Andrew , Prendecki Ruth , Khaw Chuen R , Dickson Jennifer L , Horst Carolyn , Tisi Sophie , Hall Helen , McCabe John , Gyertson Kylie , Hacker Anne-Marie , Farrelly Laura , Navani Neal , Hackshaw Allan ,   The SUMMIT Consortium, Janes Samuel M , Quaife Samantha L 
Published: February 2025

IntroductionLung cancer screening (LCS) enables the delivery of smoking cessation interventions to a population experiencing long-term tobacco dependence, but the optimal delivery method remains unclear. Here, we report uptake and short-term outcomes of an ‘opt-out’ smoking cessation referral strategy in an LCS cohort.MethodsIndividuals currently smoking tobacco who attended a face-to-face lung health check in the SUMMIT study (NCT03934866) were offered very brief advice on smoking cessation and where possible, an ‘opt-out’ referral to their local stop smoking service (SSS). Aggregate data on referral outcomes were obtained from each SSS individually.Results33.7% (n=2090/6203) of individuals currently smoking tobacco consented to a practitioner-made ‘opt-out’ smoking cessation referral. 42.7% (n=893/2090) of these individuals resided in boroughs where SSS were not present or required self-referral. Males (adjusted OR (aOR) 1.16), younger individuals (55–59: aOR 1.70, 60–64: aOR 1.71 and 65–69: aOR 1.78) and those of ethnic minority backgrounds (Asian: aOR 1.31, Black: aOR 1.71 and Mixed: aOR 1.72) were more likely to consent, while individuals from the most deprived socioeconomic quintile were less likely to do so (aOR 0.65).High level of motivation to quit within a defined time frame (aOR 1.92), previous quit attempts in the past 12 months (1–4: aOR 1.65 and ≥5: aOR 1.54) and time to first cigarette of ≤60 min (<5: aOR 2.07, 6–30: aOR 1.55 and 31–60: aOR 1.56) were measures of tobacco dependence associated with a higher likelihood of providing consent.Outcomes were available for 742 referrals. An appointment with the service was accepted by 47.3% (n=351/742) of individuals, following which 65.5% (n=230/351) set a quit date. The 4-week quit rate among those setting a quit date and all individuals referred was 57.4% (n=132/230) and 17.8% (n=132/742), respectively.ConclusionA proactive, ‘opt-out’ smoking cessation referral strategy for individuals currently smoking tobacco who interact with an LCS programme may be beneficial.
Phase II randomised, double-blind, placebo-controlled trial to assess the efficacy and safety of MLC1501 in patients with stroke: the MLC1501 study Assessing Efficacy in post-STrOke Subjects with mOtor deficits (MAESTOSO) study protocol
Authors: Chen Christopher P L H , Esagunde Romulo U , Escabillas Cyrus G , Hiyadan John Harold , Advincula Joel M , Co Christian Oliver C , Collantes Maria Epifania V , Lao Annabelle Y , Koh Yeow-Hoay , De Silva Deidre Anne , Tham Carol Huilian , Lokin Johnny K , Venketasubramanian Narayanaswamy 
Published: February 2025

BackgroundMLC1501, consisting of four herbs, that is,Radix Astragali,Radix Angelicae sinensis,Rhizoma Chuanxiong,Radix Polygalae, has the same pharmacological properties as its precursors MLC601 and MLC901 which contain extracts of nine herbs and showed neuroprotective, anti-inflammatory and neurorestorative properties in non-clinical models, as well as clinical benefits in improving functional and neurological recovery after brain injuries.AimsTo determine the efficacy of MLC1501 on motor recovery as measured by Fugl-Meyer motor Assessment (FMA) total score at 24 weeks in patients with ischaemic stroke (IS).DesignA total of 300 patients aged >18 years, diagnosed with IS in the prior 2–10 days, with National Institute of Health Stroke Scale (NIHSS) total score of 8–18 and a combined score of ≥3 on NIHSS motor items 5A, 5B, 6A and/or 6B, will be randomised in a 1:1:1 ratio to receive oral placebo, MLC1501 low dose or MLC1501 high dose for 6 months. The study is governed by a Steering Committee. An independent Data Monitoring Committee oversees patient safety.OutcomesThe primary outcome is mean change from baseline in FMA total score at 24 weeks. Efficacy outcomes evaluated in person at baseline, 12 weeks and 24 weeks include the FMA (total, upper extremity and lower extremity motor scores), modified Rankin Scale (mRS), Patient-Reported Outcomes Measurement Information System–Global Health (PROMIS-10) and NIHSS. Additionally, telephone assessment at week 4 includes the simplified mRS and PROMIS-10.Safety will be evaluated by standard assessments and occurrence of adverse events over the duration of the study.DiscussionInterventions that enhance recovery beyond the acute period of stroke are needed. MLC1501 has a good safety profile as well as potential to be a treatment for recovery after brain injury. The results of this study will provide objective level B evidence on the efficacy of MLC1501 on long-term recovery and safety of 24 weeks of treatment among patients with IS.Trial registration numberNCT05289947.