bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimising Healthcare Communication for People with Aphasia in Hospital: Key Directions for Future Research
Authors: Lamborn Edwina , Carragher Marcella , O’Halloran Robyn , Rose Miranda L.
Published: February 2024

Purpose of Review

People with aphasia and their healthcare workers have difficulty communicating, leaving people with aphasia at risk of poorer quality care, experiences and health outcomes. It is not yet known how best to optimise healthcare communication for this population. This literature review provides directions for future research regarding interventions aiming to optimise communication between healthcare workers and people with aphasia in hospital.

Findings

This paper offers four key foci to consider when planning or evaluating interventions: (1) individual and (2) systems-level environmental factors must be targeted to facilitate successful implementation, (3) reliable and feasible outcome measures must be developed to measure communication change in actual clinical interactions and (4) studies must be designed and reported adequately to ensure replicable and comparable research.

This paper provides direction for research on interventions to enhance patient-provider communication, and quality care for people with aphasia in hospital, to enable better participation and care outcomes for this population.
Design of acoustic coating for underwater stealth in low-frequency ranges
Authors: Ranjbar Mostafa , Bayer Muhammed Umar
Published: February 2024

In this study, it is aimed to protect underwater vehicles against active sonar systems by anechoic coating. A matrix material with close acoustic impedance to water, resistivity to hydrostatic pressure, suitability for the marine environment, and high material loss factor is selected. At low frequencies, the inclusions in different shapes and sizes are added to the matrix material. Since solid inclusions will increase the coating mass considerably, air cavities are preferred as inclusions. More attention is paid to low-frequency absorption, especially below 1 kHz, because of advancing sonar technology. The acoustic performance of the designed models is compared in three frequency ranges: low (below 3 kHz), middle (3–6 kHz), and high (6–10 kHz). The designed models are constructed by considering hydrostatic pressure; hence, volume of air cavities is tried to decrease, while absorption performance is aimed to increase. Therefore, a conical cavity which commonly used in the literature is optimized by chancing its dimensions and location. Also, novel approaches, gong shape cavity, and sandglass cavities are introduced. The results show that, not only cavity shape, but also its location and dimensions are highly influential on absorption performance. High-volume cavities increase the absorption performance at the low-frequency range, but they are not effective at high frequencies. The gong shape and sandglass air cavities show broadband absorption; also, gong shape cavity volume is less than literature models. Thus, its usability increases at deep waters. The results of this study provide novel underwater acoustic coating models for various applications.
Schweizer-Sklar power aggregation operators based on complex intuitionistic fuzzy information and their application in decision-making
Authors: Liu Peide , Ali Zeeshan , Mahmood Tahir
Published: February 2024

In 1960, Schweizer and Sklar introduced the novel Schweizer-Sklar t-norm and t-conorm which is used in the construction of aggregation operators. Schweizer-Sklar norms are more general than algebraic norms and Einstein norms. Additionally, computing the power operators based on the Schweizer-Sklar norms for complex Atanassov intuitionistic fuzzy (CA-IF) set is very awkward and complicated. In this manuscript, firstly, we propose the Schweizer-Sklar operational laws for CA-IF values, and secondly, we develop the CA-IF Schweizer-Sklar power averaging (CA-IFSSPA) operator, CA-IF Schweizer-Sklar power ordered averaging (CA-IFSSPOA) operator, CA-IF Schweizer-Sklar power geometric (CA-IFSSPG) operator, and CA-IF Schweizer-Sklar power ordered geometric (CA-IFSSPOG) operator. Some suitable and dominant properties for the above operators are also discussed. Furthermore, to simplify the above operators, we develop the procedure of decision-making technique, called multi-attribute decision-making (MADM) methods based on the proposed operators based on CA-IF values. Finally, we compare the proposed methods with some existing methods to describe the efficiency and capability of the discovered approaches by some examples.
On-Chip Micro Temperature Controllers Based on Freestanding Thermoelectric Nano Films for Low-Power Electronics
Authors: Jin Qun , Guo Tianxiao , Pérez Nicolás , Yang Nianjun , Jiang Xin , Nielsch Kornelius , Reith Heiko
Published: February 2024

Multidimensional integration and multifunctional component assembly have been greatly explored in recent years to extend Moore’s Law of modern microelectronics. However, this inevitably exacerbates the inhomogeneity of temperature distribution in microsystems, making precise temperature control for electronic components extremely challenging. Herein, we report an on-chip micro temperature controller including a pair of thermoelectric legs with a total area of 50 × 50 μm2, which are fabricated from dense and flat freestanding Bi2Te3-based thermoelectric nano films deposited on a newly developed nano graphene oxide membrane substrate. Its tunable equivalent thermal resistance is controlled by electrical currents to achieve energy-efficient temperature control for low-power electronics. A large cooling temperature difference of 44.5 K at 380 K is achieved with a power consumption of only 445 μW, resulting in an ultrahigh temperature control capability over 100 K mW−1. Moreover, an ultra-fast cooling rate exceeding 2000 K s−1 and excellent reliability of up to 1 million cycles are observed. Our proposed on-chip temperature controller is expected to enable further miniaturization and multifunctional integration on a single chip for microelectronics.
Real non-degenerate two-step nilpotent Lie algebras of dimension eight
Authors: Borovoi Mikhail , Dina Bodgan Adrian , de Graaf Willem A.
Published: February 2024

We classify the non-degenerate two-step nilpotent Lie algebras of dimension 8 over the field of real numbers, using known results over complex numbers. We write explicit structure constants for these real Lie algebras.
A spectroscopic study on the effect of acid concentration on the physicochemical properties of calcined halloysite nanotubes
Authors: Aydın Meryem Türkay Aytekin
Published: February 2024

Halloysite nanotubes a naturally occurring type of clay with unique properties. This research intends to investigate of the effects of hydrochloric acid treatment on the physicochemical and pore properties of halloysite nanotubes. X-ray diffraction (XRD), field emission scanning electron microscopy (SEM), Fourier-transform infrared (FT-IR) spectroscopy, the nitrogen adsorption-desorption isotherm (BET), thermogravimetric analyses (TGA-DTA) and X-ray photoelectron spectroscopy (XPS) were used to analyze the structure of natural, calcined, and acid-treated calcined halloysite nanotubes. From the analysis of XRD, SEM, FT-IR, BET, and TGA-DTA, it was possible to infer that activation with HCl on the calcined nanotubes allowed for an increase in the specific surface area and the volume of pores while maintaining the tubular structure of these materials. Because the samples’ tubular structure was preserved, the study’s goal was to evaluate the effects of acid treatment on calcined halloysite nanotubes for use as potential adsorbents. The influence of treatment with hydrochloric acid on the structure of halloysite nanotubes calcinated at different temperatures was investigated using a surface sensitive XPS method.
New 1,2,4-triazole based eugenol derivatives as antiCOX-2 and anticancer agents
Authors: Alam Mohammad Mahboob
Published: February 2024

Due to chronic inflammation, elevated cyclooxygenase (COX-2) level leads to tumorigenesis, proliferation, invasion, angiogenesis and metastasis. Therefore, suppression of COX-2 enzyme is a fascinating approach in cancer treatment. In the present study, natural product eugenol was modified to develop new 1,2,4-triazole derivatives as antiCOX-2 and antiproliferative agents. The structures of newly prepared derivatives were established using sophisticated analytical techniques. The antiproliferative result showed compound 10 to be equipotent to doxorubicin towards MDA-MB 231 and PC-3 cancer cells with IC50 1.42 and 5.69 μM, respectively and potent COX-2 inhibitor with IC50 0.28 μM. Compound 10 was also non carcinogenic, non mutagenic with good drug likeness property as depicted by in silico physicochemical and pharmacokinetic studies. The docking results against COX-2 protein showed highest binding energy for compound 10 which was found to be in consistent with the cytoxicity and COX-2 results. In conclusion, compound 10 could harness COX-2 and cell proliferation and could be a promising candidate in cancer therapy.
Music Generations in the Digital Age
Authors: Zaborowski Rafal
Published: February 2024

What do we do when we listen? The act of engagement with music in everyday life may seem simple on the surface but participation, interpretation, circulation and cultural production in the digital age are more complex and entangled than ever before. It is especially so in Japan, with its vast multimedia idol and vocaloid industries. This unique ethnographic work at the intersection of cultural, media and music studies covers a wide spectrum of music-related activities embedded in the daily lives of two Japanese cohorts. The varied case studies, including teen idol groups and virtual idols, aid the detailed examination of the relation between music, generation, and society.
Gender-Transformative Remedies for Women Human Rights Defenders
Authors: Nissen Aleydis
Published: February 2024

In its 2019 report to the Human Rights Council, the United Nations (UN) Working Group on business and human rights emphasized that ‘gender-transformative’ remedies can bring ‘change to patriarchal norms and unequal power relations that underpin discrimination, gender-based violence and gender stereotyping’. This article aims to deepen our knowledge of such remediation for women human rights defenders who fight against corporate human rights abuses. Human rights remediation is highly fragmented. This has the advantage that remedies at one level can offer sources of learning for remedies at other levels. This article uses relevant communications that the UN Special Rapporteur on the situation of human rights defenders sent to states and corporations jointly with other Special Procedures (including the UN Special Rapporteur on violence against women and girls, its causes and consequences and the UN Working Group on discrimination against women and girls in law and practice) between 2011 and 2020 as a source of learning.
Translation of the Preference-Based Amyotrophic Lateral Sclerosis Scale into French
Authors: Mehdipour Ava , Teshler Lizabeth , Dal Bello-Haas Vanina , Bouchard Vanessa , Kuspinar Ayse
Published: February 2024

The objective of this study was to translate the Preference-Based Amyotrophic Lateral Sclerosis Scale to French-Canadian. After the scale underwent forward and back translations, the expert committee examined the translated versions and found minor grammatical errors and suggested idioms to be changed to better represent French-Canadian language. Cognitive debriefing interviews were carried out to assess the pre-final version for clarity, and minor changes were made. Consensus from the expert committee and people with amyotrophic lateral sclerosis on the measure’s clarity, word choice, and meaning were achieved, resulting in the final French version of the Preference-Based Amyotrophic Lateral Sclerosis Scale.
Description of an intramonocytic haemoparasite, Hepatozoon lainsoni sp. nov. (Apicomplexa: Adeleorina: Hepatozoidae), infecting Ameiva ameiva lizard (Reptilia: Squamata: Teiidae) in northern Brazil
Authors: Morais Rafaela A. P. B. , Rodrigues Ana Paula D. , Diniz José Antonio P. , Úngari Letícia Pereira , O'Dwyer Lucia Helena , de Souza Wanderley , DaMatta Renato A. , Silva Edilene O.
Published: February 2024

Haemogregarine (Apicomplexa: Adeleorina) parasites are considered to be the most common and widespread haemoparasites in reptiles. The genus Hepatozoon (Apicomplexa: Adeleorina: Hepatozoidae) can be found parasitizing a broad range of species and, in reptiles, they infect mainly peripheral blood erythrocytes. The present study detected and characterized a haemogregarine isolated from the lizard species, Ameiva ameiva, collected from the municipality of Capanema, Pará state, north Brazil. Blood smears and imprints from lungs, brain, heart, kidney, liver, bone marrow and spleen were observed using light microscopy and the parasite was genetically identified by molecular analysis. Morphological, morphometric and molecular data were obtained. Parasite gamonts were found in 49.5% (55/111) of the blood smears from A. ameiva, and were characterized as oval, averaging 12.0 ± 0.8 × 5.9 ± 0.6 μm2 in size, which displaced the nuclei of parasitized monocytes laterally. Parasite forms resembling immature gamonts were observed in the spleen and bone marrow of the lizards. Furthermore, phylogenetic analyses of 18S rRNA sequences did not reveal gene similarity with other Hepatozoon spp. sequences from reptiles. Thus, morphological and molecular analyses have identified a new species of Hepatozoon parasite, Hepatozoon lainsoni sp. nov., which infects monocytes of the A. ameiva lizard.
Optimization of a Tsunami Gauge Configuration for Pseudo‐Super‐Resolution of Wave Height Distribution
Authors: Fujita Saneiki , Nomura Reika , Moriguchi Shuji , Otake Yu , Koshimura Shunichi , LeVeque Randall J. , Terada Kenjiro
Published: February 2024

In this study, we present an optimization method for determining a cost‐effective sparse configuration for tsunami gauges to realize the reconstruction of high‐resolution wave height distribution throughout the target region based on the concept of super‐resolution. This optimization method consists of three procedures. First, we generate time series data of tsunami wave heights at synthetic gauges by conducting numerical simulations of various earthquake and tsunami scenarios at the target site. Next, we apply proper orthogonal decomposition to the synthetic tsunami data to extract the spatial features of the wave height distribution. Finally, according to these spatial features, an optimization process is performed to determine a sparse configuration of synthetic gauges. In the optimization, the optimal gauges are sequentially selected from the set of synthetic gauges to reconstruct the wave height distribution with the highest accuracy. Targeting hypothetical Nankai Trough earthquakes and tsunamis, we determine the optimal configuration near Shikoku and demonstrate the wave height reconstruction capability of the approach by comparing the performance of networks with optimally and randomly placed gauges. The results indicate that coastal gauges contribute more to improving the reconstruction accuracy and that a configuration with 21 optimal gauges has satisfactory performance. In addition, we assess the performance of the existing NOWPHAS network installed in the Shikoku region and find that the reconstruction performance of the existing network is equivalent to that of the optimal gauge network.
Correcting Projection Effects in CMEs Using GCS‐Based Large Statistics of Multi‐Viewpoint Observations
Authors: Gandhi Harshita , Patel Ritesh , Pant Vaibhav , Majumdar Satabdwa , Pal Sanchita , Banerjee Dipankar , Morgan Huw
Published: February 2024

This study addresses the limitations of single‐viewpoint observations of Coronal Mass Ejections (CMEs) by presenting results from a 3D catalog of 360 CMEs during solar cycle 24, fitted using the Graduated Cylindrical Shell (GCS) model. The data set combines 326 previously analyzed CMEs and 34 newly examined events, categorized by their source regions into active region (AR) eruptions, active prominence (AP) eruptions, and prominence eruptions (PE). Estimates of errors are made using a bootstrapping approach. The findings highlight that the average 3D speed of CMEs is ∼1.3 times greater than the 2D speed. PE CMEs tend to be slow, with an average speed of 432 km s−1. AR and AP speeds are higher, at 723 and 813 km s−1, respectively, with the latter having fewer slow CMEs. The distinctive behavior of AP CMEs is attributed to factors like overlying magnetic field distribution or geometric complexities leading to less accurate GCS fits. A linear fit of projected speed to width gives a gradient of ∼2 km s−1 deg−1, which increases to 5 km s−1 deg−1when the GCS‐fitted ‘true’ parameters are used. Notably, AR CMEs exhibit a high gradient of 7 km s−1 deg−1, while AP CMEs show a gradient of 4 km s−1 deg−1. PE CMEs, however, lack a significant speed‐width relationship. We show that fitting multi‐viewpoint CME images to a geometrical model such as GCS is important to study the statistical properties of CMEs, and can lead to a deeper insight into CME behavior that is essential for improving future space weather forecasting.
28 NICUs participating in a quality improvement collaborative targeting early-onset sepsis antibiotic use
Authors: Payton Kurlen S. E. , Bennett Mihoko V. , Schulman Joseph , Benitz William E. , Stellwagen Lisa , Darmstadt Gary L. , Quinn Jenny , Kristensen-Cabrera Alexandria I. , Breault Courtney C. , Bolaris Michael , Lefrak Linda , Merrill Jeff , Sharek Paul J.
Published: February 2024

Objective

There is widespread overuse of antibiotics in neonatal intensive care units (NICUs). The objective of this study was to safely reduce antibiotic use in participating NICUs by targeting early-onset sepsis (EOS) management.

Study design

Twenty-eight NICUs participated in this statewide multicenter antibiotic stewardship quality improvement collaborative. The primary aim was to reduce the total monthly mean antibiotic utilization rate (AUR) by 25% in participant NICUs.

Result

Aggregate AUR was reduced by 15.3% (p < 0.001). There was a wide range in improvement among participant NICUs. There were no increases in EOS rates or nosocomial infection rates related to the intervention.

Conclusion

Participation in this multicenter NICU antibiotic stewardship collaborative targeting EOS was associated with an aggregate reduction in antibiotic use. This study informs efforts aimed at sustaining improvements in NICU AURs.
A WHO digital intervention to address depression among young Chinese adults: a type 1 effectiveness-implementation randomized controlled trial
Authors: Li Gen , Sit Hao Fong , Chen Wen , Wu Kunpeng , Sou Elvo Kuai Long , Wong Mek , Chen Ze , Burchert Sebastian , Hong Ieng Wai , Sit Ho Yi , Lam Agnes Iok Fong , Hall Brian J.
Published: February 2024

Common mental disorders among young people are rising globally. Current university-based interventions are inadequate to address the need for evidence-based interventions. We investigated the effectiveness and implementation of Step-by-Step (SbS), a WHO digital intervention to address depression, among Chinese university students with depressive symptoms. In this paper, we report a type 1 hybrid effectiveness-implementation randomized controlled trial conducted between September 2021 and September 2022. The control condition was enhanced treatment as usual (ETAU, psychoeducation). The primary outcome was improvement in depression symptoms. Secondary outcomes were improvements in psychological well-being, anxiety symptoms, and self-identified psychosocial problems. Effectiveness of the intervention was evaluated using generalized linear mixed models. Implementation outcomes were evaluated by thematic analysis of participant interviews. A total of 371 participants were enrolled to two treatment conditions in a 1:1 ratio. SbS resulted in a greater reduction in depressive symptoms at posttreatment (p = 0.004, Hedges’ g = 0.35), but no significant difference between SbS and ETAU was observed at three-month follow-up (p = 0.179, Hedges’ g = 0.16). The treatment effect was larger among those who adhered to the treatment (Hedges’ gs = 0.59 and 0.30). Subjective well-being also improved for SbS at both time points (Hedges’ gs = 0.31 and 0.30). In addition, SbS resulted in more improvement in anxiety symptoms at posttreatment (p = 0.029, Hedges’ g = 0.26), but not at three-month follow-up (p = 0.265, Hedges’ g = 0.13). The qualitative results demonstrated that the intervention was well-implemented as a self-help mental health service, with minimal support from peer supporters. In conclusion, Step-by-Step, a digital intervention developed by WHO, was effective in reducing depressive symptoms in the short term and improving psychological well-being in a longer term. The sustained effect on depression needs further investigation. Improving uptake and engagement in the program is needed for its scale-up implementation as a university-based mental health service for Chinese young adults. Trial registration: ChiCTR2100050214.
Multi-level profiling of the Fmr1 KO rat unveils altered behavioral traits along with aberrant glutamatergic function
Authors: Ntoulas George , Brakatselos Charalampos , Nakas Gerasimos , Asprogerakas Michail-Zois , Delis Foteini , Leontiadis Leonidas J. , Trompoukis George , Papatheodoropoulos Costas , Gkikas Dimitrios , Valakos Dimitrios , Vatsellas Giannis , Politis Panagiotis K. , Polissidis Alexia , Antoniou Katerina
Published: February 2024

Fragile X syndrome (FXS) is the most common cause of inherited intellectual disabilities and the most prevalent monogenic cause of autism. Although the knockout (KO) of the Fmr1 gene homolog in mice is primarily used for elucidating the neurobiological substrate of FXS, there is limited association of the experimental data with the pathophysiological condition in humans. The use of Fmr1 KO rats offers additional translational validity in this regard. Therefore, we employed a multi-level approach to study the behavioral profile and the glutamatergic and GABAergic neurotransmission status in pathophysiology-associated brain structures of Fmr1 KO rats, including the recordings of evoked and spontaneous field potentials from hippocampal slices, paralleled with next-generation RNA sequencing (RNA-seq). We found that these rats exhibit hyperactivity and cognitive deficits, along with characteristic bidirectional glutamatergic and GABAergic alterations in the prefrontal cortex and the hippocampus. These results are coupled to affected excitability and local inhibitory processes in the hippocampus, along with a specific transcriptional profile, highlighting dysregulated hippocampal network activity in KO rats. Overall, our data provide novel insights concerning the biobehavioral profile of FmR1 KO rats and translationally upscales our understanding on pathophysiology and symptomatology of FXS syndrome.
Cortical signatures of sleep are altered following effective deep brain stimulation for depression
Authors: van Rheede Joram J. , Alagapan Sankaraleengam , Denison Timothy J. , Riva-Posse Patricio , Rozell Christopher J. , Mayberg Helen S. , Waters Allison C. , Sharott Andrew
Published: February 2024

Deep brain stimulation (DBS) of the subcallosal cingulate cortex (SCC) is an experimental therapy for treatment-resistant depression (TRD). Chronic SCC DBS leads to long-term changes in the electrophysiological dynamics measured from local field potential (LFP) during wakefulness, but it is unclear how it impacts sleep-related brain activity. This is a crucial gap in knowledge, given the link between depression and sleep disturbances, and an emerging interest in the interaction between DBS, sleep, and circadian rhythms. We therefore sought to characterize changes in electrophysiological markers of sleep associated with DBS treatment for depression. We analyzed key electrophysiological signatures of sleep—slow-wave activity (SWA, 0.5–4.5 Hz) and sleep spindles—in LFPs recorded from the SCC of 9 patients who responded to DBS for TRD. This allowed us to compare the electrophysiological changes before and after 24 weeks of therapeutically effective SCC DBS. SWA power was highly correlated between hemispheres, consistent with a global sleep state. Furthermore, SWA occurred earlier in the night after chronic DBS and had a more prominent peak. While we found no evidence for changes to slow-wave power or stability, we found an increase in the density of sleep spindles. Our results represent a first-of-its-kind report on long-term electrophysiological markers of sleep recorded from the SCC in patients with TRD, and provides evidence of earlier NREM sleep and increased sleep spindle activity following clinically effective DBS treatment. Future work is needed to establish the causal relationship between long-term DBS and the neural mechanisms underlying sleep.
Optical behavior and marginal discoloration of a single shade resin composite with a chameleon effect: a randomized controlled clinical trial
Authors: Anwar Ruba Salah , Hussein Yasser Fathi , Riad Mona
Published: February 2024

Objective/aim

Evaluating the optical behavior and marginal discoloration of a Single-shade universal resin composite over 12 months. To achieve this, a split-mouth with a double-blinded randomized strategy was employed.

Materials and methods

Twenty adult patients, each presenting with at least two caries lesions in their posterior teeth, were selected and randomly subdivided into two identical groups: Group I received Single-shade universal resin composite (Omnichroma), and Group II received multi-shade nanohybrid resin composite (Tetric®N-Ceram). Color measurements and marginal discoloration were assessed visually by three blinded operators at baseline followed after 1,3,6,9, and 12‑month periods utilizing the Modified United States Public Health Services (USPHS) criteria. Statistical analysis was adopted utilizing the Wilcoxon test with a 0.05 significance level.

Results

The two groups revealed non-statistically significant differences up to 6 months regarding color match and color stability. After 9 and 12 months, the multi-shade group demonstrated a statistically significant higher prevalence of color match (Alpha) scores than the single-shade universal group. Regarding marginal discoloration, all restorations in the two groups had no discoloration (Alpha scores).

Discussion/conclusion

Since the percentage of Alpha and Bravo scores was considered clinical success, both the single-shade universal and the multi-shade nanohybrid resin composites demonstrated satisfactory optical performance and marginal discoloration as posterior restorations after a 12-month follow-up period.
RANKL inhibition reduces lesional cellularity and Gαs variant expression and enables osteogenic maturation in fibrous dysplasia
Authors: de Castro Luis F. , Whitlock Jarred M. , Michel Zachary , Pan Kristen , Taylor Jocelyn , Szymczuk Vivian , Boyce Brendan , Martin Daniel , Kram Vardit , Galisteo Rebeca , Melikov Kamran , Chernomordik Leonid V. , Collins Michael T. , Boyce Alison M.
Published: February 2024

Fibrous dysplasia (FD) is a rare, disabling skeletal disease for which there are no established treatments. Growing evidence supports inhibiting the osteoclastogenic factor receptor activator of nuclear kappa-B ligand (RANKL) as a potential treatment strategy. In this study, we investigated the mechanisms underlying RANKL inhibition in FD tissue and its likely indirect effects on osteoprogenitors by evaluating human FD tissue pre- and post-treatment in a phase 2 clinical trial of denosumab (NCT03571191) and in murine in vivo and ex vivo preclinical models. Histological analysis of human and mouse tissue demonstrated increased osteogenic maturation, reduced cellularity, and reduced expression of the pathogenic Gαs variant in FD lesions after RANKL inhibition. RNA sequencing of human and mouse tissue supported these findings. The interaction between osteoclasts and mutant osteoprogenitors was further assessed in an ex vivo lesion model, which indicated that the proliferation of abnormal FD osteoprogenitors was dependent on osteoclasts. The results from this study demonstrated that, in addition to its expected antiosteoclastic effect, denosumab reduces FD lesion activity by decreasing FD cell proliferation and increasing osteogenic maturation, leading to increased bone formation within lesions. These findings highlight the unappreciated role of cellular crosstalk between osteoclasts and preosteoblasts/osteoblasts as a driver of FD pathology and demonstrate a novel mechanism of action of denosumab in the treatment of bone disease.

TRIAL REGISTRATION: ClinicalTrials.gov NCT03571191
Deep learning models incorporating endogenous factors beyond DNA sequences improve the prediction accuracy of base editing outcomes
Authors: Yuan Tanglong , Wu Leilei , Li Shiyan , Zheng Jitan , Li Nana , Xiao Xiao , Zhang Haihang , Fei Tianyi , Xie Long , Zuo Zhenrui , Li Di , Huang Pinzheng , Feng Hu , Cao Yaqi , Yan Nana , Wei Xinming , Shi Lei , Sun Yongsen , Wei Wu , Sun Yidi , Zuo Erwei
Published: February 2024

Adenine base editors (ABEs) and cytosine base editors (CBEs) enable the single nucleotide editing of targeted DNA sites avoiding generation of double strand breaks, however, the genomic features that influence the outcomes of base editing in vivo still remain to be characterized. High-throughput datasets from lentiviral integrated libraries were used to investigate the sequence features affecting base editing outcomes, but the effects of endogenous factors beyond the DNA sequences are still largely unknown. Here the base editing outcomes of ABE and CBE were evaluated in mammalian cells for 5012 endogenous genomic sites and 11,868 genome-integrated target sequences, with 4654 genomic sites sharing the same target sequences. The comparative analyses revealed that the editing outcomes of ABE and CBE at endogenous sites were substantially different from those obtained using genome-integrated sequences. We found that the base editing efficiency at endogenous target sites of both ABE and CBE was influenced by endogenous factors, including epigenetic modifications and transcriptional activity. A deep-learning algorithm referred as BE_Endo, was developed based on the endogenous factors and sequence information from our genomic datasets, and it yielded unprecedented accuracy in predicting the base editing outcomes. These findings along with the developed computational algorithms may facilitate future application of BEs for scientific research and clinical gene therapy.
Effect of adalimumab on choroidal thickness and choroidal vascularity index in eyes with non-infectious uveitis using enhanced-depth imaging optical coherence tomography
Authors: Evereklioglu Cem , Er Arslantas Elif , Sener Hidayet , Akkul Zeynep , Gahramanov Kamran , Gulmez Sevim Duygu , Polat Osman Ahmet , Horozoglu Fatih
Published: February 2024

Objective

To evaluate the effect of adalimumab (ADA) on choroidal thickness (ChT) and choroidal vascularity index (CVI) in eyes with non-infectious uveitis (NIU).

Methods

Thirty-seven eyes with NIU including Behçet disease (BD), sarcoidosis, ankylosing spondylitis (AS), juvenile idiopathic arthritis and idiopathic arthritis, 38 eyes of non-uveitic (NU) patients including BD, AS and rheumatoid arthritis, and 40 healthy control eyes were included. ADA was used for anti-TNF-naive adult (80 mg) or paediatric (40 mg) patients with refractory NIU, then 40 mg every 2-week (20 mg in children<30 kg) with controls at weeks 1, 4, 12, and 24. Images were used to measure central, nasal, and temporal ChT, and the luminal area (LA), stromal area, and total choroidal area (TCA) were analysed using enhanced-depth imaging optical coherence tomography (EDI-OCT) by ImageJ software. The CVI was then calculated as the ratio of LA to TCA.

Results

Mean ages were similar between the groups. Mean (SE) subfoveal ChT measurements for each location were also similar (for each, p > 0.05). However, calculated CVI values in eyes with NIU (0.63 ± 0.007) were significantly (p < 0.001) lower than NU eyes (0.66 ± 0.006) and controls (0.70 ± 0.007) (p < 0.001). Moreover, CVI was significantly lower in NU eyes compared to controls (p < 0.001). There were no significant CVI changes between the consecutive visits after ADA therapy in eyes with NIU (for each, p > 0.05).

Conclusions

Decreased CVI in NIU and NU eyes indicates that systemic inflammation affects the choroidal vasculature and perfusion both in the presence and absence of ocular involvement. Although CVI may be used as a possible novel tool in monitoring ocular involvement and progression of NIU, CVI does not seem to be a biomarker for treatment monitoring in NIU.
Regulatory T cells use heparanase to access IL-2 bound to extracellular matrix in inflamed tissue
Authors: Martinez Hunter A. , Koliesnik Ievgen , Kaber Gernot , Reid Jacqueline K. , Nagy Nadine , Barlow Graham , Falk Ben A. , Medina Carlos O. , Hargil Aviv , Zihsler Svenja , Vlodavsky Israel , Li Jin-Ping , Pérez-Cruz Magdiel , Tang Sai-Wen , Meyer Everett H. , Wrenshall Lucile E. , Lord James D. , Garcia K. Christopher , Palmer Theo D. , Steinman Lawrence , Nepom Gerald T. , Wight Thomas N. , Bollyky Paul L. , Kuipers Hedwich F.
Published: February 2024

Although FOXP3+regulatory T cells (Treg) depend on IL-2 produced by other cells for their survival and function, the levels of IL-2 in inflamed tissue are low, making it unclear how Treg access this critical resource. Here, we show that Treg use heparanase (HPSE) to access IL-2 sequestered by heparan sulfate (HS) within the extracellular matrix (ECM) of inflamed central nervous system tissue. HPSE expression distinguishes human and murine Treg from conventional T cells and is regulated by the availability of IL-2. HPSE-/-Treg have impaired stability and function in vivo, including in the experimental autoimmune encephalomyelitis (EAE) mouse model of multiple sclerosis. Conversely, endowing monoclonal antibody-directed chimeric antigen receptor (mAbCAR) Treg with HPSE enhances their ability to access HS-sequestered IL-2 and their ability to suppress neuroinflammation in vivo. Together, these data identify a role for HPSE and the ECM in immune tolerance, providing new avenues for improving Treg-based therapy of autoimmunity.
Historical changes in wind-driven ocean circulation drive pattern of Pacific warming
Authors: Fu Shuo , Hu Shineng , Zheng Xiao-Tong , McMonigal Kay , Larson Sarah , Tian Yiqun
Published: February 2024

The tropical Pacific warming pattern since the 1950s exhibits two warming centers in the western Pacific (WP) and eastern Pacific (EP), encompassing an equatorial central Pacific (CP) cooling and a hemispheric asymmetry in the subtropical EP. The underlying mechanisms of this warming pattern remain debated. Here, we conduct ocean heat decompositions of two coupled model large ensembles to unfold the role of wind-driven ocean circulation. When wind changes are suppressed, historical radiative forcing induces a subtropical northeastern Pacific warming, thus causing a hemispheric asymmetry that extends toward the tropical WP. The tropical EP warming is instead induced by the cross-equatorial winds associated with the hemispheric asymmetry, and its driving mechanism is southward warm Ekman advection due to the off-equatorial westerly wind anomalies around 5°N, not vertical thermocline adjustment. Climate models fail to capture the observed CP cooling, suggesting an urgent need to better simulate equatorial oceanic processes and thermal structures.
Phage-plasmids promote recombination and emergence of phages and plasmids
Authors: Pfeifer Eugen , Rocha Eduardo P. C.
Published: February 2024

Phages and plasmids are regarded as distinct types of mobile genetic elements that drive bacterial evolution by horizontal gene transfer. However, the distinction between both types is blurred by the existence of elements known as prophage-plasmids or phage-plasmids, which transfer horizontally between cells as viruses and vertically within cellular lineages as plasmids. Here, we study gene flow between the three types of elements. We show that the gene repertoire of phage-plasmids overlaps with those of phages and plasmids. By tracking recent recombination events, we find that phage-plasmids exchange genes more frequently with plasmids than with phages, and that direct gene exchange between plasmids and phages is less frequent in comparison. The results suggest that phage-plasmids can mediate gene flow between plasmids and phages, including exchange of mobile element core functions, defense systems, and antibiotic resistance. Moreover, a combination of gene transfer and gene inactivation may result in the conversion of elements. For example, gene loss turns P1-like phage-plasmids into integrative prophages or into plasmids (that are no longer phages). Remarkably, some of the latter have acquired conjugation-related functions to became mobilisable by conjugation. Thus, our work indicates that phage-plasmids can play a key role in the transfer of genes across mobile elements within their hosts, and can act as intermediates in the conversion of one type of element into another.
A mutational atlas for Parkin proteostasis
Authors: Clausen Lene , Voutsinos Vasileios , Cagiada Matteo , Johansson Kristoffer E. , Grønbæk-Thygesen Martin , Nariya Snehal , Powell Rachel L. , Have Magnus K. N. , Oestergaard Vibe H. , Stein Amelie , Fowler Douglas M. , Lindorff-Larsen Kresten , Hartmann-Petersen Rasmus
Published: February 2024

Proteostasis can be disturbed by mutations affecting folding and stability of the encoded protein. An example is the ubiquitin ligase Parkin, where gene variants result in autosomal recessive Parkinsonism. To uncover the pathological mechanism and provide comprehensive genotype-phenotype information, variant abundance by massively parallel sequencing (VAMP-seq) is leveraged to quantify the abundance of Parkin variants in cultured human cells. The resulting mutational map, covering 9219 out of the 9300 possible single-site amino acid substitutions and nonsense Parkin variants, shows that most low abundance variants are proteasome targets and are located within the structured domains of the protein. Half of the known disease-linked variants are found at low abundance. Systematic mapping of degradation signals (degrons) reveals an exposed degron region proximal to the so-called “activation element”. This work provides examples of how missense variants may cause degradation either via destabilization of the native protein, or by introducing local signals for degradation.
General-purpose programmable photonic processor for advanced radiofrequency applications
Authors: Pérez-López Daniel , Gutierrez Ana , Sánchez David , López-Hernández Aitor , Gutierrez Mikel , Sánchez-Gomáriz Erica , Fernández Juan , Cruz Alejandro , Quirós Alberto , Xie Zhenyun , Benitez Jesús , Bekesi Nandor , Santomé Alejandro , Pérez-Galacho Diego , DasMahapatra Prometheus , Macho Andrés , Capmany José
Published: February 2024

A general-purpose photonic processor can be built integrating a silicon photonic programmable core in a technology stack comprising an electronic monitoring and controlling layer and a software layer for resource control and programming. This processor can leverage the unique properties of photonics in terms of ultra-high bandwidth, high-speed operation, and low power consumption while operating in a complementary and synergistic way with electronic processors. These features are key in applications such as next-generation 5/6 G wireless systems where reconfigurable filtering, frequency conversion, arbitrary waveform generation, and beamforming are currently provided by microwave photonic subsystems that cannot be scaled down. Here we report the first general-purpose programmable processor with the remarkable capability to implement all the required basic functionalities of a microwave photonic system by suitable programming of its resources. The processor is fabricated in silicon photonics and incorporates the full photonic/electronic and software stack.
Deglaciation-enhanced mantle CO2 fluxes at Yellowstone imply positive climate feedback
Authors: Clerc Fiona , Behn Mark D. , Minchew Brent M.
Published: February 2024

Mantle melt generation in response to glacial unloading has been linked to enhanced magmatic volatile release in Iceland and global eruptive records. It is unclear whether this process is important in systems lacking evidence of enhanced eruptions. The deglaciation of the Yellowstone ice cap did not observably enhance volcanism, yet Yellowstone emits large volumes of CO2 due to melt crystallization at depth. Here we model mantle melting and CO2 release during the deglaciation of Yellowstone (using Iceland as a benchmark). We find mantle melting is enhanced 19-fold during deglaciation, generating an additional 250–620 km3. These melts segregate an additional 18–79 Gt of CO2 from the mantle, representing a ~3–15% increase in the global volcanic CO2 flux (if degassed immediately). We suggest deglaciation-enhanced mantle melting is important in continental settings with partially molten mantle – including Greenland and West Antarctica – potentially implying positive feedbacks between deglaciation and climate warming.
Plasticity-induced repression of Irf6 underlies acquired resistance to cancer immunotherapy in pancreatic ductal adenocarcinoma
Authors: Kim Il-Kyu , Diamond Mark S. , Yuan Salina , Kemp Samantha B. , Kahn Benjamin M. , Li Qinglan , Lin Jeffrey H. , Li Jinyang , Norgard Robert J. , Thomas Stacy K. , Merolle Maria , Katsuda Takeshi , Tobias John W. , Baslan Timour , Politi Katerina , Vonderheide Robert H. , Stanger Ben Z.
Published: February 2024

Acquired resistance to immunotherapy remains a critical yet incompletely understood biological mechanism. Here, using a mouse model of pancreatic ductal adenocarcinoma (PDAC) to study tumor relapse following immunotherapy-induced responses, we find that resistance is reproducibly associated with an epithelial-to-mesenchymal transition (EMT), with EMT-transcription factors ZEB1 and SNAIL functioning as master genetic and epigenetic regulators of this effect. Acquired resistance in this model is not due to immunosuppression in the tumor immune microenvironment, disruptions in the antigen presentation machinery, or altered expression of immune checkpoints. Rather, resistance is due to a tumor cell-intrinsic defect in T-cell killing. Molecularly, EMT leads to the epigenetic and transcriptional silencing of interferon regulatory factor 6 (Irf6), rendering tumor cells less sensitive to the pro-apoptotic effects of TNF-α. These findings indicate that acquired resistance to immunotherapy may be mediated by programs distinct from those governing primary resistance, including plasticity programs that render tumor cells impervious to T-cell killing.
Real space characterization of nonlinear hall effect in confined directions
Authors: Luo Sheng , Hsu Chuang-Han , Chang Guoqing , Bansil Arun , Lin Hsin , Liang Gengchiau
Published: February 2024

The nonlinear Hall effect (NLHE) is a phenomenon which could produce a transverse Hall voltage in a time-reversal-invariant material. Here, we report the real space characterizations of NLHE evaluated through quantum transport in TaIrTe4 nanoribbon without the explicit Berry curvature dipole (BCD) information. We first characterize the NLHE in both transverse confined directions in global-level measurement. The impact of quantum confinement in NLHE is evaluated by adjusting the width of nanoribbons. Then, the probing area is trimmed to the atomic scale to evaluate the local texture, where we discover its patterns differ among the probed neighboring atomic groups. The analysis of charge distribution reveals the connections between NLHE’s local patterns and its non-centrosymmetric nature, rendering nearly an order of Hall voltage enhancement through probe positioning. Our work paves the way to expand the range of NLHE study and unveil its physics in more versatile material systems.
Versatile spaceborne photonics with chalcogenide phase-change materials
Authors: Kim Hyun Jung , Julian Matthew , Williams Calum , Bombara David , Hu Juejun , Gu Tian , Aryana Kiumars , Sauti Godfrey , Humphreys William
Published: February 2024

Recent growth in space systems has seen increasing capabilities packed into smaller and lighter Earth observation and deep space mission spacecraft. Phase-change materials (PCMs) are nonvolatile, reconfigurable, fast-switching, and have recently shown a high degree of space radiation tolerance, thereby making them an attractive materials platform for spaceborne photonics applications. They promise robust, lightweight, and energy-efficient reconfigurable optical systems whose functions can be dynamically defined on-demand and on-orbit to deliver enhanced science or mission support in harsh environments on lean power budgets. This comment aims to discuss the recent advances in rapidly growing PCM research and its potential to transition from conventional terrestrial optoelectronics materials platforms to versatile spaceborne photonic materials platforms for current and next-generation space and science missions. Materials International Space Station Experiment-14 (MISSE-14) mission-flown PCMs outside of the International Space Station (ISS) and key results and NASA examples are highlighted to provide strong evidence of the applicability of spaceborne photonics.
Stretchable liquid metal based biomedical devices
Authors: Deng Yifan , Bu Fan , Wang Yujie , Chee Pei Song , Liu Xiangye , Guan Cao
Published: February 2024

Pursuit of improved living quality has stimulated great demand for high-performance conformal healthcare devices in modern human society. However, manufacturing of efficient, comfortable and stretchable biomedical apparatus faces huge challenges using traditional materials. Liquid metals (LMs) show remarkable potential to solve this problem due to their extraordinary biocompatibility, stretchability, thermal and electrical conductivity. In recent years, tremendous explorations have attempted to make stretchable biomedical devices with LMs. Herein, we review the stretchable LM-based biomedical devices on the topics of disease treatment and human function augmenting. The representative and up-to-date neural interfaces, alloy cement, e-vessels, soft heaters, exoskeletons, and e-skins are summarized. The existing issues of LMs applied for biomedical devices are also discussed. This review can provide guidance for the follow-up research in LM-based biomedical devices.
Better-than-classical Grover search via quantum error detection and suppression
Authors: Pokharel Bibek , Lidar Daniel A.
Published: February 2024

We report better-than-classical success probabilities for a complete Grover quantum search algorithm on the largest scale demonstrated to date, of up to five qubits, using two different IBM platforms. This is enabled by error suppression via robust dynamical decoupling. Further improvements arise after the use of measurement error mitigation, but the latter is insufficient by itself for achieving better-than-classical performance. For two qubits, we demonstrate a 99.5% success probability via the use of the [[4, 2, 2]] quantum error-detection (QED) code. This constitutes a demonstration of quantum algorithmic breakeven via QED. Along the way, we introduce algorithmic error tomography (AET), a method that provides a holistic view of the errors accumulated throughout an entire quantum algorithm, filtered via the errors detected by the QED code used to encode the circuit. We demonstrate that AET provides a stringent test of an error model based on a combination of amplitude damping, dephasing, and depolarization.