bluuebunny/crossref_metadata_2025_split huggingface dataset:
SWOT analysis of the dental hygiene profession in Pakistan—past, present, and future
Authors: Damani Iqra , Taimoor Shazia , Umer Fahad , Sukhia Rashna Hoshang , Sadiq Ali 
Published: September 2024

Abstract
Background
Pakistan faces a significant burden of oral diseases, which can be effectively reduced through preventive measures. Dentistry in Pakistan predominantly focuses on corrective dental procedures, increasing the treatment costs and widens disparities in oral healthcare access. To address this gap and meet the country’s oral health needs, Aga Khan University initiated a Dental Hygiene program aimed to expand and diversify the oral health workforce and improving access to quality care in various healthcare settings. Due to limited awareness of this profession in the country, the program encounters significant challenges.

Aim
This article aims to present a SWOT analysis of the Dental Hygiene profession in Pakistan and propose evidence-based strategic changes to address these challenges and improve future outcomes.

Methods
A SWOT analysis was conducted to identify the internal strengths, weaknesses, external opportunities, and threats related to the Dental Hygiene profession, gathering both quantitative and qualitative data through a survey of relevant stakeholders (Consultants, Dental hygiene graduates, dental auxiliaries, fresh dental graduates, and prospective students) using Research Electronic Data Capture (REDCap).

Results
A total of 267 respondents participated in the survey, providing insights into the current state of the Dental Hygiene profession.

Conclusion
The analysis reveals that the Dental Hygiene profession in Pakistan requires robust advocacy, increased collaboration with dentists, opportunities for higher education, and the establishment of proper legislative frameworks to prevent professional transgression beyond the scope of practice.
Exploring the structural landscape of DNA maintenance proteins
Authors: Schou Kenneth Bødkter , Mandacaru Samuel , Tahir Muhammad , Tom Nikola , Nilsson Ann-Sofie , Andersen Jens S. , Tiberti Matteo , Papaleo Elena , Bartek Jiri 
Published: September 2024

Abstract
Evolutionary annotation of genome maintenance (GM) proteins has conventionally been established by remote relationships within protein sequence databases. However, often no significant relationship can be established. Highly sensitive approaches to attain remote homologies based on iterative profile-to-profile methods have been developed. Still, these methods have not been systematically applied in the evolutionary annotation of GM proteins. Here, by applying profile-to-profile models, we systematically survey the repertoire of GM proteins from bacteria to man. We identify multiple GM protein candidates and annotate domains in numerous established GM proteins, among other PARP, OB-fold, Macro, TUDOR, SAP, BRCT, KU, MYB (SANT), and nuclease domains. We experimentally validate OB-fold and MIS18 (Yippee) domains in SPIDR and FAM72 protein families, respectively. Our results indicate that, surprisingly, despite the immense interest and long-term research efforts, the repertoire of genome stability caretakers is still not fully appreciated.
Quantifying concentration distributions in redox flow batteries with neutron radiography
Authors: Jacquemond Rémy Richard , van der Heijden Maxime , Boz Emre Burak , Carreón Ruiz Eric Ricardo , Greco Katharine Virginia , Kowalski Jeffrey Adam , Muñoz Perales Vanesa , Brushett Fikile Richard , Nijmeijer Kitty , Boillat Pierre , Forner-Cuenca Antoni 
Published: September 2024

AbstractThe continued advancement of electrochemical technologies requires an increasingly detailed understanding of the microscopic processes that control their performance, inspiring the development of new multi-modal diagnostic techniques. Here, we introduce a neutron imaging approach to enable the quantification of spatial and temporal variations in species concentrations within an operating redox flow cell. Specifically, we leverage the high attenuation of redox-active organic materials (high hydrogen content) and supporting electrolytes (boron-containing) in solution and perform subtractive neutron imaging of active species and supporting electrolyte. To resolve the concentration profiles across the electrodes, we employ an in-plane imaging configuration and correlate the concentration profiles to cell performance with polarization experiments under different operating conditions. Finally, we use time-of-flight neutron imaging to deconvolute concentrations of active species and supporting electrolyte during operation. Using this approach, we evaluate the influence of cell polarity, voltage bias and flow rate on the concentration distribution within the flow cell and correlate these with the macroscopic performance, thus obtaining an unprecedented level of insight into reactive mass transport. Ultimately, this diagnostic technique can be applied to a range of (electro)chemical technologies and may accelerate the development of new materials and reactor designs.
Spatiotemporal dynamics of fast electron heating in solid-density matter via XFEL
Authors: Sawada H. , Yabuuchi T. , Higashi N. , Iwasaki T. , Kawasaki K. , Maeda Y. , Izumi T. , Nakagawa Y. , Shigemori K. , Sakawa Y. , Curry C. B. , Frost M. , Iwata N. , Ogitsu T. , Sueda K. , Togashi T. , Hu S. X. , Glenzer S. H. , Kemp A. J. , Ping Y. , Sentoku Y. 
Published: September 2024

AbstractHigh-intensity, short-pulse lasers are crucial for generating energetic electrons that produce high-energy-density (HED) states in matter, offering potential applications in igniting dense fusion fuels for fast ignition laser fusion. High-density targets heated by these electrons exhibit spatially non-uniform and highly transient conditions, which have been challenging to characterize due to limitations in diagnostics that provide simultaneous high spatial and temporal resolution. Here, we employ an X-ray Free Electron Laser (XFEL) to achieve spatiotemporally resolved measurements at sub-micron and femtosecond scales on a solid-density copper foil heated by laser-driven fast electrons. Our X-ray transmission imaging reveals the formation of a solid-density hot plasma localized to the laser spot size, surrounded by Fermi degenerate, warm dense matter within a picosecond, and the energy relaxation occurring within the hot plasma over tens of picoseconds. These results validate 2D particle-in-cell simulations incorporating atomic processes and provide insights into the energy transfer mechanisms beyond current simulation capabilities. This work significantly advances our understanding of rapid fast electron heating and energy relaxation in solid-density matter, serving as a key stepping stone towards efficient high-density plasma heating and furthering the fields of HED science and inertial fusion energy research using intense, short-pulse lasers.
Second harmonic generation at a time-varying interface
Authors: Tirole Romain , Vezzoli Stefano , Saxena Dhruv , Yang Shu , Raziman T. V. , Galiffi Emanuele , Maier Stefan A. , Pendry John B. , Sapienza Riccardo 
Published: September 2024

AbstractTime-varying metamaterials rely on large and fast changes of the linear permittivity. Beyond the linear terms, however, the effect of a non-perturbative modulation of the medium on harmonic generation remains largely unexplored. In this work, we study second harmonic generation at an optically pumped time-varying interface between air and a 310 nm Indium Tin Oxide film. We observe a modulation contrast at the second harmonic wavelength up to 93% for a pump intensity of 100 GW/cm2, leading to large frequency broadening and shift. We experimentally demonstrate that a significant contribution to the enhancement comes from the temporal modulation of the second order nonlinear susceptibility. Moreover, we show the frequency-modulated spectra resulting from single and double-slit time diffraction could be exploited for enhanced optical computing and sensing, enabling broadband time-varying effects on the harmonic signal and extending the application of Epsilon-Near-Zero materials to the visible range.
Quantitative localisation of titanium in the framework of titanium silicalite-1 using anomalous X-ray powder diffraction
Authors: Rzepka Przemyslaw , Signorile Matteo , Huthwelker Thomas , Checchia Stefano , Rosso Francesca , Bordiga Silvia , van Bokhoven Jeroen A. 
Published: September 2024

AbstractOne of the biggest obstacles to developing better zeolite-based catalysts is the lack of methods for quantitatively locating light heteroatoms on the T-sites in zeolites. Titanium silicalite-1 (TS-1) is a Ti-bearing zeolite-type catalyst commonly used in partial oxidation reactions with H2O2, such as aromatic hydroxylation and olefin epoxidation. The reaction mechanism is controlled by the configuration of titanium sites replacing silicon in the zeolite framework, but these sites remain unknown, hindering a fundamental understanding of the reaction. This study quantitatively determines heteroatoms within the zeolite-type framework using anomalous X-ray powder diffraction (AXRD) and the changes in the titanium X-ray scattering factor near the Ti K-edge (4.96 keV). Two TS-1 samples, each with approximately 2 Ti atoms per unit cell, were examined. Half of the titanium atoms are primarily split between sites T3 and T9, with the remainder dispersed among various T-sites within both MFI-type frameworks. One structure showed significant non-framework titanium in the micropores of a more distorted lattice. In both samples, isolated titanium atoms were more prevalent than dinuclear species, which could only potentially arise at site T9, but with a significant energy penalty and were not detected.
The scaffolding function of LSD1 controls DNA methylation in mouse ESCs
Authors: Malla Sandhya , Kumari Kanchan , García-Prieto Carlos A. , Caroli Jonatan , Nordin Anna , Phan Trinh T. T. , Bhattarai Devi Prasad , Martinez-Gamero Carlos , Dorafshan Eshagh , Stransky Stephanie , Álvarez-Errico Damiana , Saiki Paulina Avovome , Lai Weiyi , Lyu Cong , Lizana Ludvig , Gilthorpe Jonathan D. , Wang Hailin , Sidoli Simone , Mateus Andre , Lee Dung-Fang , Cantù Claudio , Esteller Manel , Mattevi Andrea , Roman Angel-Carlos , Aguilo Francesca 
Published: September 2024

AbstractLysine-specific histone demethylase 1 (LSD1), which demethylates mono- or di- methylated histone H3 on lysine 4 (H3K4me1/2), is essential for early embryogenesis and development. Here we show that LSD1 is dispensable for mouse embryonic stem cell (ESC) self-renewal but is required for mouse ESC growth and differentiation. Reintroduction of a catalytically-impaired LSD1 (LSD1MUT) recovers the proliferation capability of mouse ESCs, yet the enzymatic activity of LSD1 is essential to ensure proper differentiation. Indeed, increased H3K4me1 in Lsd1 knockout (KO) mouse ESCs does not lead to major changes in global gene expression programs related to stemness. However, ablation of LSD1 but not LSD1MUT results in decreased DNMT1 and UHRF1 proteins coupled to global hypomethylation. We show that both LSD1 and LSD1MUT control protein stability of UHRF1 and DNMT1 through interaction with HDAC1 and the ubiquitin-specific peptidase 7 (USP7), consequently, facilitating the deacetylation and deubiquitination of DNMT1 and UHRF1. Our studies elucidate a mechanism by which LSD1 controls DNA methylation in mouse ESCs, independently of its lysine demethylase activity.
Advancing EDGE Zones to identify spatial conservation priorities of tetrapod evolutionary history
Authors: Pipins Sebastian , Baillie Jonathan E. M. , Bowmer Alex , Pollock Laura J. , Owen Nisha , Gumbs Rikki 
Published: September 2024

AbstractThe biodiversity crisis is pruning the Tree of Life in a way that threatens billions of years of evolutionary history and there is a need to understand where the greatest losses are predicted to occur. We therefore present threatened evolutionary history mapped for all tetrapod groups and describe patterns of Evolutionarily Distinct and Globally Endangered (EDGE) species. Using a complementarity procedure with uncertainty incorporated for 33,628 species, we identify 25 priority tetrapod EDGE Zones, which are insufficiently protected and disproportionately exposed to high human pressure. Tetrapod EDGE Zones are spread over five continents, 33 countries, and 117 ecoregions. Together, they occupy 0.723% of the world’s surface but harbour one-third of the world’s threatened evolutionary history and EDGE tetrapod species, half of which is endemic. These EDGE Zones highlight areas of immediate concern for researchers, practitioners, policymakers, and communicators looking to safeguard the tetrapod Tree of Life.
An artificial intelligence accelerated virtual screening platform for drug discovery
Authors: Zhou Guangfeng , Rusnac Domnita-Valeria , Park Hahnbeom , Canzani Daniele , Nguyen Hai Minh , Stewart Lance , Bush Matthew F. , Nguyen Phuong Tran , Wulff Heike , Yarov-Yarovoy Vladimir , Zheng Ning , DiMaio Frank 
Published: September 2024

AbstractStructure-based virtual screening is a key tool in early drug discovery, with growing interest in the screening of multi-billion chemical compound libraries. However, the success of virtual screening crucially depends on the accuracy of the binding pose and binding affinity predicted by computational docking. Here we develop a highly accurate structure-based virtual screen method, RosettaVS, for predicting docking poses and binding affinities. Our approach outperforms other state-of-the-art methods on a wide range of benchmarks, partially due to our ability to model receptor flexibility. We incorporate this into a new open-source artificial intelligence accelerated virtual screening platform for drug discovery. Using this platform, we screen multi-billion compound libraries against two unrelated targets, a ubiquitin ligase target KLHDC2 and the human voltage-gated sodium channel NaV1.7. For both targets, we discover hit compounds, including seven hits (14% hit rate) to KLHDC2 and four hits (44% hit rate) to NaV1.7, all with single digit micromolar binding affinities. Screening in both cases is completed in less than seven days. Finally, a high resolution X-ray crystallographic structure validates the predicted docking pose for the KLHDC2 ligand complex, demonstrating the effectiveness of our method in lead discovery.
BRCA genetic testing and counseling in breast cancer: how do we meet our patients’ needs?
Authors: Dubsky Peter , Jackisch Christian , Im Seock-Ah , Hunt Kelly K. , Li Chien-Feng , Unger Sheila , Paluch-Shimon Shani 
Published: September 2024

AbstractBRCA1 and BRCA2 are tumor suppressor genes that have been linked to inherited susceptibility of breast cancer. Germline BRCA1/2 pathogenic or likely pathogenic variants (gBRCAm) are clinically relevant for treatment selection in breast cancer because they confer sensitivity to poly(ADP-ribose) polymerase (PARP) inhibitors. BRCA1/2 mutation status may also impact decisions on other systemic therapies, risk-reducing measures, and choice of surgery. Consequently, demand for gBRCAm testing has increased. Several barriers to genetic testing exist, including limited access to testing facilities, trained counselors, and psychosocial support, as well as the financial burden of testing. Here, we describe current implications of gBRCAm testing for patients with breast cancer, summarize current approaches to gBRCAm testing, provide potential solutions to support wider adoption of mainstreaming testing practices, and consider future directions of testing.
DeepMIP-Eocene-p1: multi-model dataset and interactive web application for Eocene climate research
Authors: Steinig Sebastian , Abe-Ouchi Ayako , de Boer Agatha M. , Chan Wing-Le , Donnadieu Yannick , Hutchinson David K. , Knorr Gregor , Ladant Jean-Baptiste , Morozova Polina , Niezgodzki Igor , Poulsen Christopher J. , Volodin Evgeny M. , Zhang Zhongshi , Zhu Jiang , Evans David , Inglis Gordon N. , Meckler A. Nele , Lunt Daniel J. 
Published: September 2024

AbstractPaleoclimate model simulations provide reference data to help interpret the geological record and offer a unique opportunity to evaluate the performance of current models under diverse boundary conditions. Here, we present a dataset of 35 climate model simulations of the warm early Eocene Climatic Optimum (EECO; ~ 50 million years ago) and corresponding preindustrial reference experiments. To streamline the use of the data, we apply standardised naming conventions and quality checks across eight modelling groups that have carried out coordinated simulations as part of the Deep-Time Model Intercomparison Project (DeepMIP). Gridded model fields can be downloaded from an online repository or accessed through a new web application that provides interactive data exploration. Local model data can be extracted in CSV format or visualised online for streamlined model-data comparisons. Additionally, processing and visualisation code templates may serve as a starting point for advanced analysis. The dataset and online platform aim to simplify accessing and handling complex data, prevent common processing issues, and facilitate the sharing of climate model data across disciplines.
Temporal stability of the rumen microbiome and its longitudinal associations with performance traits in beef cattle
Authors: Lima Joana , Martínez-Álvaro Marina , Mattock Jennifer , Auffret Marc D. , Duthie Carol-Anne , Cleveland Matthew A. , Dewhurst Richard J. , Watson Mick , Roehe Rainer 
Published: September 2024

AbstractThe rumen microbiome is the focus of a growing body of research, mostly based on investigation of rumen fluid samples collected once from each animal. Exploring the temporal stability of rumen microbiome profiles is imperative, as it enables evaluating the reliability of findings obtained through single-timepoint sampling. We explored the temporal stability of rumen microbiomes considering taxonomic and functional aspects across the 7-month growing-finishing phase spanning 6 timepoints. We identified a temporally stable core microbiome, encompassing 515 microbial genera (e.g., Methanobacterium) and 417 microbial KEGG genes (e.g., K00856—adenosine kinase). The temporally stable core microbiome profiles collected from all timepoints were strongly associated with production traits with substantial economic and environmental impact (e.g., average daily gain, daily feed intake, and methane emissions); 515 microbial genera explained 45–83%, and 417 microbial genes explained 44–83% of their phenotypic variation. Microbiome profiles influenced by the bovine genome explained 54–87% of the genetic variation of bovine traits. Overall, our results provide evidence that the temporally stable core microbiome identified can accurately predict host performance traits at phenotypic and genetic level based on a single timepoint sample taken as early as 7 months prior to slaughter.
Biomechanical changes of tree shrew posterior sclera during experimental myopia, after retrobulbar vehicle injections, and crosslinking using genipin
Authors: Bianco Gianfranco , Girkin Christopher A. , Samuels Brian C. , Fazio Massimo A. , Grytz Rafael 
Published: September 2024

AbstractMyopia is a common ocular condition characterized by biomechanical weakening revealed by increasing creep rate, cyclic softening scleral thinning, change of collagen fibril crimping, and excessive elongation of the posterior sclera resulting in blurred vision. Animal studies support scleral crosslinking as a potential treatment for myopia control by strengthening the weakened sclera and slowing scleral expansion. While multiple studies investigated aspects of the biomechanical weakening and strengthening effects in myopia and after scleral crosslinking, a comprehensive analysis of the underlying mechanical changes including the effect of vehicle injections is still missing. The purpose of this study was to provide a comprehensive analysis of biomechanical changes by scleral inflation testing in experimental myopia, after retrobulbar vehicle injections and scleral crosslinking using genipin in tree shrews. Our results suggest that biomechanical weakening in myopia involves an increased creep rate and higher strain levels at which collagen fibers uncrimp. Both weakening effects were reduced after scleral crosslinking using genipin at doses that were effective in slowing myopia progression. Vehicle injections increased mechanical hysteresis and had a small but significant effect on slowing myopia progression. Also, our results support scleral crosslinking as a potential treatment modality that can prevent or counteract scleral weakening effects in myopia. Furthermore, vehicle solutions may cause independent biomechanical effects, which should be considered when developing and evaluating scleral crosslinking procedures.
A Gaussia luciferase reporter assay for the evaluation of coronavirus Nsp5/3CLpro activity
Authors: Vlachou Asimenia , Nchioua Rayhane , Regensburger Kerstin , Kirchhoff Frank , Kmiec Dorota 
Published: September 2024

AbstractHuman coronaviruses (hCoVs) infect millions of people every year. Among these, MERS, SARS-CoV-1, and SARS-CoV-2 caused significant morbidity and mortality and their emergence highlights the risk of possible future coronavirus outbreaks. Therefore, broadly-active anti-coronavirus drugs are needed. Pharmacological inhibition of the hCoV protease Nsp5 (3CLpro) is clinically beneficial as shown by the wide and effective use of Paxlovid (nirmatrelvir, ritonavir). However, further treatment options are required due to the risk of drug resistance. To facilitate the assessment of coronavirus protease function and its pharmacological inhibition, we developed an assay allowing rapid and reliable quantification of Nsp5 activity under biosafety level 1 conditions. It is based on an ACE2-Gal4 transcription factor fusion protein separated by a Nsp5 recognition site. Cleavage by Nsp5 releases the Gal4 transcription factor, which then induces the expression of Gaussia luciferase. Our assay is compatible with Nsp5 proteases from all hCoVs and allows simultaneous measurement of inhibitory and cytotoxic effects of the tested compounds. Proof-of-concept measurements confirmed that nirmatrelvir, GC376 and lopinavir inhibit SARS-CoV-2 Nsp5 function. Furthermore, the assay accurately predicted the impact of Nsp5 mutations on catalytic activity and inhibitor sensitivity. Overall, the reporter assay is suitable for evaluating viral protease activity.