bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantum tunnelling in hafnia-based metal-insulator-metal diodes: atomistic-to-continuum modelling approach and experimental validation
Authors: Pavoni Eleonora , Laudadio Emiliano , Joseph Christopher Hardly , Zampa Gian Marco , Russo Paola , Mohebbi Elaheh , Mencarelli Davide , Dragoman Mircea , Stipa Pierluigi , Pierantoni Luca , Aldrigo Martino 
Published: December 2023

Abstract
In this work, we present a metal-insulator-metal (MIM) diode, based on quantum tunnelling phenomena. Its model is based on a multilevel modelling approach consisting of atomistic and continuum simulations, fully validated by extensive measurements. The MIM structure comprises a hafnium oxide (or hafnia, HfO2) dielectric layer, less than 4 nm thick and a square contact area of only 4 μm2, placed between two metallic electrodes, namely platinum as the source and titanium as the drain. The current–voltage (I–V) curve has been estimated by Density Functional Theory (DFT) calculations through an optimisation of the interfaces between metals and monoclinic HfO2. The dielectric parameters arising from ab initio computations have then been used as inputs for the successive circuit and electromagnetic simulations. Finally, the multilevel model has been validated with great accuracy, first measuring the I–V characteristics by applying a drain-source voltage between −1 V and +1 V, and then extracting the scattering parameters up to 40 GHz, thus demonstrating that DFT and circuit/electromagnetic simulations match almost perfectly the experimental ones. These outcomes represent the first study of such nanoscale devices investigated by means of a rigorous atomistic-to-continuum approach, providing invaluable information in order to improve fabrication and correctly assess the macroscale performance of nanoelectronics systems.
Quantum super-resolution with balanced homodyne detection in low-earth-orbit
Authors: Gosalia Ronakraj K , Malaney Robert , Aguinaldo Ryan , Green Jonathan 
Published: December 2023

Abstract
Quantum super-resolution involves resolving two sources below the Rayleigh limit using quantum optics. Such a technique would allow high-precision inter-satellite positioning and tracking on communication and navigation constellations. Due to the size, weight and power constraints typical of low-earth-orbit (LEO) satellites, a simple solution is often preferred. Here, we show that a balanced homodyne detection (BHD) setup using a shaped single-mode local oscillator can achieve super-resolution despite typical photonic losses. We further analyze the impact of a fluctuating and fixed centroid misalignment due to satellite pointing issues, and find that fixed misalignment is comparatively more detrimental to the performance of a BHD setup. Thus, our study provides a practical assessment of BHD to achieve super-resolution on a modern LEO satellite platform. Finally, we discuss how our analysis can be extended to stellar sources for astronomical applications.
Resilience of Amazon rainfall to CO2 removal forcing
Authors: Zhang Suqin , Qu Xia , Huang Gang , Hu Peng , Yang Xianke , Wang Ya , Wu Liang 
Published: December 2023

Abstract
Over the Amazon region, rainfall-induced changes to CO2 pathways significantly impact humans and multiple ecosystems. Its resilience is of vital importance, and idealized CO2 removal experiments indicate that declining trends in rainfall amounts are irreversible and exhibit a deficiency when the CO2 concentration returns to the pre-industrial level. The irreversible decline in Amazon rainfall is mainly due to the weakened ascent, further led by two main causes. (1) Enhanced tropospheric warming and a wetter atmospheric boundary layer over the tropics during CO2 removal generate a strong meridional gradient of temperature and specific humidity; driven by prevailing northeasterly winds, negative moist enthalpy advection occurs, which in turn weakens the ascent over the Amazon and results in anomalous drought. (2) The enhanced radiative cooling of atmospheric column. Driven by the negative lapse-rate feedback, the outgoing longwave radiative flux increases in the clear-sky atmosphere. As a result, the anomalous diabatic descent generates to maintain the energy balance of the atmospheric column. This result implies that the symmetric removal of CO2 does not guarantee full recovery of regional precipitation.
Applying polygenic risk score methods to pharmacogenomics GWAS: challenges and opportunities
Authors: Zhai Song , Mehrotra Devan V , Shen Judong 
Published: December 2023

Abstract
Polygenic risk scores (PRSs) have emerged as promising tools for the prediction of human diseases and complex traits in disease genome-wide association studies (GWAS). Applying PRSs to pharmacogenomics (PGx) studies has begun to show great potential for improving patient stratification and drug response prediction. However, there are unique challenges that arise when applying PRSs to PGx GWAS beyond those typically encountered in disease GWAS (e.g. Eurocentric or trans-ethnic bias). These challenges include: (i) the lack of knowledge about whether PGx or disease GWAS/variants should be used in the base cohort (BC); (ii) the small sample sizes in PGx GWAS with corresponding low power and (iii) the more complex PRS statistical modeling required for handling both prognostic and predictive effects simultaneously. To gain insights in this landscape about the general trends, challenges and possible solutions, we first conduct a systematic review of both PRS applications and PRS method development in PGx GWAS. To further address the challenges, we propose (i) a novel PRS application strategy by leveraging both PGx and disease GWAS summary statistics in the BC for PRS construction and (ii) a new Bayesian method (PRS-PGx-Bayesx) to reduce Eurocentric or cross-population PRS prediction bias. Extensive simulations are conducted to demonstrate their advantages over existing PRS methods applied in PGx GWAS. Our systematic review and methodology research work not only highlights current gaps and key considerations while applying PRS methods to PGx GWAS, but also provides possible solutions for better PGx PRS applications and future research.
LncRNA CARD8-AS1 suppresses lung adenocarcinoma progression by enhancing TRIM25-mediated ubiquitination of TXNRD1
Authors: Pan Cheng , Wang Qi , Wang Hongshun , Deng Xiaheng , Chen Liang , Li Zhihua 
Published: December 2023

Abstract
Long non-coding RNAs (lncRNAs) play crucial roles in the tumorigenesis and progression of lung adenocarcinoma (LUAD). However, little was known about the role of lncRNAs in high-risk LUAD subtypes: micropapillary-predominant adenocarcinoma (MPA) and solid-predominant adenocarcinoma (SPA). In this study, we conducted a systematic screening of differentially expressed lncRNAs using RNA sequencing in 10 paired MPA/SPA tumor tissues and adjacent normal tissues. Consequently, 110 significantly up-regulated lncRNAs and 288 aberrantly down-regulated lncRNAs were identified (|Log2 Foldchange| ≥ 1 and corrected P &lt; 0.05). The top 10 lncRNAs were further analyzed in 89 MPA/SPA tumor tissues and 59 normal tissues from The Cancer Genome Atlas database. Among them, CARD8-AS1 showed the most significant differential expression, and decreased expression of CARD8-AS1 was significantly associated with a poorer prognosis. Functionally, CARD8-AS1 overexpression remarkably suppressed the proliferation, migration and invasion of LUAD cells both in vitro and in vivo. Conversely, inhibition of CARD8-AS1 yielded opposite effects. Mechanistically, CARD8-AS1 acted as a scaffold to facilitate the interaction between TXNRD1 and E3 ubiquitin ligase TRIM25, thereby promoting the degradation of TXNRD1 through the ubiquitin–proteasome pathway. Additionally, TXNRD1 was found to promote LUAD cell proliferation, migration and invasion in vitro. Furthermore, the suppressed progression of LUAD cells resulting from CARD8-AS1 overexpression could be significantly reversed by simultaneous overexpression of TXNRD1. In conclusion, this study revealed that the lncRNA CARD8-AS1 played a suppressive role in the progression of LUAD by enhancing TRIM25-mediated ubiquitination of TXNRD1. The CARD8-AS1-TRIM25-TXNRD1 axis may represent a promising therapeutic target for LUAD.
Partisan Effects of Information Campaigns in Competitive Authoritarian Elections: Evidence from Bangladesh
Authors: Ahmed Firoz , Hodler Roland , Islam Asad 
Published: December 2023

Abstract
To study the effects of non-partisan information and get-out-the-vote campaigns on the partisan composition of the voting population in competitive authoritarian elections, we conducted a large-scale field experiment prior to the 2018 Bangladeshi general election. Our two treatments highlight that high turnout increases the winning party’s legitimacy and that election outcomes matter for policy outcomes. Both treatments increase turnout (measured by ink marks) in government strongholds, but decrease turnout in opposition strongholds. We explain the withdrawal of treated opposition supporters and conclude that non-partisan information and get-out-the-vote campaigns can further tilt the uneven playing field in competitive authoritarian elections.
Introduction to the special issue on positive psychology and wellbeing
Authors: Resnik Pia , Mercer Sarah 
Published: December 2023

Abstract
This introduction to the Special Issue on ‘Positive Psychology and Wellbeing’ begins by outlining the history and relevance of Positive Psychology (PP) for ELT. A key construct in PP is wellbeing, which all the papers in this Special Issue focus on. In this introductory article, we describe how the term wellbeing has been used and how it is defined in this collection. We discuss why wellbeing matters in language learning and teaching and point out some of the key controversies surrounding this term. We then introduce the nine articles highlighting their unique contributions to furthering our understandings in this field. We conclude by reflecting on key practical implications derived from the contributions and by presenting possible avenues for future research in this area. Our hope is that this collection of papers will serve as an impetus for innovations in practice, research, and theoretical thinking about this vitally important topic.
Anisotropic tomography and mantle dynamics of the North China Craton
Authors: Guo Huili , Zhao Dapeng , Ding Zhifeng 
Published: December 2023

SUMMARY
We present high-resolution 3-D images of isotropic P-wave velocity (Vp), azimuthal anisotropy (AAN) and radial anisotropy (RAN) down to 700 km depth beneath the North China Craton (NCC) and adjacent areas, which are obtained by inverting a great number of high-quality arrival time data recorded at 1374 portable seismic stations and 635 permanent stations in the study region. Our results reveal new and detailed features of the upper mantle structure beneath the NCC. Varying structural heterogeneities are revealed beneath different tectonic blocks, and differences also exist between northern and southern parts of each block. The fast velocity directions (FVDs) of azimuthal anisotropy are mainly NW–SE under the Alaxa block, and NE–SW beneath the Tibetan Plateau. The FVDs present an arc transition along the boundary faults separating the Tibetan Plateau, the Alaxa block, the western NCC, and the Sichuan basin. Low-Vp anomalies with positive RANs (i.e. horizontal Vp &gt; vertical Vp) are revealed at 100–200 km depths under the Tibetan Plateau, reflecting frozen-in anisotropy in the thick lithosphere. Significant low-Vp anomalies with a circular AAN pattern exist at 0–700 km depths beneath the Datong volcano. In addition, negative RAN occurs right below the volcano, whereas positive RANs appear around it, suggesting that the Datong volcano is fed by hot upwelling flow from the lower mantle associated with collapsing of subducted slab materials down to the lower mantle. The eastern NCC shows complex Vp AANs and RANs. Seismic anisotropy exhibits east–west variations in the upper mantle across the Tanlu fault zone. The west of the Tanlu fault shows negative RANs (vertical Vp &gt; horizontal Vp), whereas its east shows positive RANs at 300–500 km depths. The low-Vp anomaly under the Datong volcano is connected with a large low-Vp anomaly beneath the eastern NCC above ∼250 km depth, suggesting that the hot upwelling flow under Datong may migrate laterally to the asthenosphere under the eastern NCC and contribute to the lithospheric delamination and destruction there.
A detailed characterization of drug resistance during darunavir/ritonavir monotherapy highlights a high barrier to the emergence of resistance mutations in protease but identifies alternative pathways of resistance
Authors: Abdullahi Adam , Diaz Ana Garcia , Fopoussi Olga Mafotsing , Beloukas Apostolos , Fokom Defo Victoire , Kouanfack Charles , Torimiro Judith , Geretti Anna Maria 
Published: December 2023

Abstract

Background
Maintenance monotherapy with ritonavir-boosted darunavir has yielded variable outcomes and is not recommended. Trial samples offer valuable opportunities for detailed studies. We analysed samples from a 48 week trial in Cameroon to obtain a detailed characterization of drug resistance.

Methods
Following failure of NNRTI-based therapy and virological suppression on PI-based therapy, participants were randomized to ritonavir-boosted darunavir (n = 81) or tenofovir disoproxil fumarate/lamivudine +ritonavir-boosted lopinavir (n = 39). At study entry, PBMC-derived HIV-1 DNA underwent bulk Protease and Reverse Transcriptase (RT) sequencing. At virological rebound (confirmed or last available HIV-1 RNA ≥ 60 copies/mL), plasma HIV-1 RNA underwent ultradeep Protease and RT sequencing and bulk Gag-Protease sequencing. The site-directed mutant T375A (p2/p7) was characterized phenotypically using a single-cycle assay.

Results
NRTI and NNRTI resistance-associated mutations (RAMs) were detected in 52/90 (57.8%) and 53/90 (58.9%) HIV-1 DNA samples, respectively. Prevalence in rebound HIV-1 RNA (ritonavir-boosted darunavir, n = 21; ritonavir-boosted lopinavir, n = 2) was 9/23 (39.1%) and 10/23 (43.5%), respectively, with most RAMs detected at frequencies ≥15%. The resistance patterns of paired HIV-1 DNA and RNA sequences were partially consistent. No darunavir RAMs were found. Among eight participants experiencing virological rebound on ritonavir-boosted darunavir (n = 12 samples), all had Gag mutations associated with PI exposure, including T375N, T375A (p2/p7), K436R (p7/p1) and substitutions in p17, p24, p2 and p6. T375A conferred 10-fold darunavir resistance and increased replication capacity.

Conclusions
The study highlights the high resistance barrier of ritonavir-boosted darunavir while identifying alternative pathways of resistance through Gag substitutions. During virological suppression, resistance patterns in HIV-1 DNA reflect treatment history, but due to technical and biological considerations, cautious interpretation is warranted.
Resistance to first-line antibiotic therapy among patients with uncomplicated acute cystitis in Melbourne, Australia: prevalence, predictors and clinical impact
Authors: Curtis Stephanie J , Kwong Jason C , Chaung Yee Lin , Mazza Danielle , Walsh Calum J , Chua Kyra Y , Stewardson Andrew J 
Published: December 2023

Abstract

Background
Australian guidelines recommend trimethoprim or nitrofurantoin as first-line agents for uncomplicated urinary tract infections (UTIs). Laboratory surveillance indicates high rates of trimethoprim resistance among urinary bacterial isolates, but there are scant local clinical data about risk factors and impact of trimethoprim resistance.

Objectives
To determine the prevalence, risk factors, mechanism and impact of resistance to first-line antibiotic therapy for uncomplicated UTIs in the community setting.

Methods
A prospective observational study from October 2019 to November 2021 in four general practices in Melbourne, Australia. Female adult patients prescribed an antibiotic for suspected or confirmed uncomplicated acute cystitis were eligible. Primary outcome was urine isolates with resistance to trimethoprim and/or nitrofurantoin.

Results
We recruited 87 participants across 102 UTI episodes with median (IQR) age of 63 (47–76) years. Escherichia coli was the most common uropathogen cultured (48/62; 77%); 27% (13/48) were resistant to trimethoprim (mediated by a dfrA gene) and none were resistant to nitrofurantoin. Isolates with resistance to a first-line therapy were more common among patients reporting a history of recurrent UTIs [risk ratio (RR): 2.08 (95% CI: 1.24–3.51)] and antibiotic use in the previous 6 months [RR: 1.89 (95% CI: 1.36–2.62)]. Uropathogen resistance to empirical therapy was not associated with worse clinical outcomes.

Conclusions
Resistance to trimethoprim is common in uncomplicated UTIs in Australia but may not impact clinical outcomes. Further research is warranted on the appropriateness of trimethoprim as empirical therapy, particularly for patients with antimicrobial resistance risk factors.
Prevalence of piperacillin/tazobactam resistance in invasive Haemophilus influenzae in Germany
Authors: Duske Helene , Claus Heike , Krone Manuel , Lâm Thiên-Trí 
Published: December 2023

Abstract

Background
Haemophilus influenzae (Hi) is a Gram-negative bacterium that may cause sepsis or meningitis, treatment of which mainly includes β-lactam antibiotics. Since 2019 EUCAST breakpoints for piperacillin/tazobactam have been available. Little is known about the prevalence and mechanisms of piperacillin/tazobactam resistance in Hi.

Objectives
To provide reliable prevalence data for piperacillin/tazobactam resistance in Hi in Germany, to evaluate different antibiotic susceptibility testing methods and to examine possible resistance mechanisms.

Methods
According to EUCAST breakpoints, the MIC for piperacillin/tazobactam resistance is &gt;0.25 mg/L. All invasive Hi in Germany from 2019 were examined by gradient agar diffusion (GAD) for piperacillin/tazobactam susceptibility. Piperacillin/tazobactam broth microdilution (BMD), piperacillin GAD on tazobactam-containing agar [piperacillin GAD on Mueller–Hinton agar with horse blood (MH-F)/tazobactam) and piperacillin/tazobactam agar dilution (AD) were used for confirmation. Phenotypic testing was complemented by ftsI sequencing.

Results
Piperacillin/tazobactam GAD resulted in 2.9% (21/726) resistant Hi. BMD did not confirm piperacillin/tazobactam resistance. Two strains were found resistant by AD, of which one was also resistant using piperacillin GAD on MH-F/tazobactam. Overall, we found two strains with a piperacillin/tazobactam MIC &gt;0.25 mg/L in at least two different tests (0.3%). Both were β-lactamase-producing amoxicillin/clavulanate-resistant with PBP3 mutations characterized as group III-like+. Relevant PBP3 mutations occurred in six strains without phenotypic piperacillin/tazobactam resistance. These mutations suggest a reduced efficacy of β-lactam antibiotics in these isolates.

Conclusions
Piperacillin/tazobactam resistance prevalence in invasive Hi is low in Germany. Reduced susceptibility was correlated with PBP3 mutations, in particular with group III mutations.
Rethinking c-Fos for understanding drug action in the brain
Authors: Sakurai Katsuyasu 
Published: December 2023

Abstract
Understanding the mechanisms of drug action in the brain, from the genetic to the neural circuit level, is crucial for the development of new agents that act upon the central nervous system. Determining the brain regions and neurons affected by a drug is essential for revealing its mechanism of action in the brain. c-Fos, a marker of neuronal activation, has been widely used to detect neurons activated by stimuli with high spatial resolution. In this review, the use of c-Fos for the visualization and manipulation of activated neurons is introduced. I also explain that a higher temporal resolution can be achieved by changing the staining method for visualization of c-Fos. Moreover, a new method that allows labeling and manipulating commonly activated neurons using two different stimuli is proposed.
Prevalence, intensity of infestation, and biomarker potential of the nemertean worm, Carcinonemertes carcinophila (Kölliker, 1845), on ovigerous blue crabs, Callinectes sapidus Rathbun, 1896 (Decapoda: Brachyura: Portunidae), in Chesapeake Bay, USA
Authors: Schneider Alexandra K , Pomroy Alexandria K , Shields Jeffrey D 
Published: December 2023

Abstract
The effect of individual and population-level egg mortality is important to quantify to maintain sustainable crustacean fisheries. The nemertean worm Carcinonemertes carcinophila (Kölliker, 1845) is an egg predator of the Atlantic blue crab, Callinectes sapidusRathbun, 1896; however, little is known about the impact this nemertean has on the reproduction of the blue crab. We assessed the prevalence and intensity of the infestation of nemerteans in ovigerous blue crabs using a fishery-independent trawl survey. During the primary spawning period of the crab, May–September 2022, 126 ovigerous females were collected and analyzed for worms. Prevalence over this time was 66.6% and mean brood infestation was 53.9 worms per infested crab host. Nemertean egg consumption was quantified with a six-day microcosm experiment. Of the 48 worms in the experiment, 71% actively fed on crab eggs and their consumption ranged 0.16–4.5 eggs day–1. Consumption rates were used to estimate population-level impact of nemertean feeding on crab brood mortality. Modeled proportions of brood loss per crab ranged 0–0.0044%. At the current prevalence and intensity of infestation, egg consumption by nemerteans has a negligible effect on blue crab reproductive output and batch fecundity in Chesapeake Bay. We also investigated the use of mature nemertean worms as a biomarker for establishing the spawning history of ovigerous female blue crabs and determined that the presence of worms in the clutch and in the gills can be used to indicate parity in ovigerous female crabs.
Mechanistic insights into the survival curve of HeLa cells with a short shoulder and their S phase-specific sensitivity
Authors: Komatsu Kenshi , Tauchi Hiroshi 
Published: December 2023

Abstract
HeLa cells are a cell line with two unique cellular features: a short-shouldered survival curve and two peaks of radioresistance during the cell cycle phase, while their underlying mechanisms remain unclear. We herein proposed that these radiobiological features are due to a common mechanism by which radiation suppresses homologous recombination repair (HRR) in a dose-dependent manner. This radio-suppression of HRR is mediated by an intra-S checkpoint and reduces survivals of cells in S phase, especially early S phase, resulting in both short shoulder and radioresistance with two peaks in the cell cycle. This new explanation may not be limited to HeLa cells since a similar close association of these features is also observed in other type of cells.