bluuebunny/crossref_metadata_2025 huggingface dataset:
Crystal chemistry and ionic conductivity of garnet-type solid-state electrolyte, Li5-xLa3(NbTa)O12-y
Authors: Kafle Amrit P. , Wong-Ng Winnie , Oleshko Vladimir , Stafford Gery R. , Kaduk James A. , Eufrasio Andreza , Pegg Ian L. , Dutta Biprodas
Published: June 2024

Crystal structures, microtopography, morphologies, elemental compositions, and ionic conductivity have been investigated for Li5-xLa3(Nb,Ta)O12-y using X-ray diffraction (XRD), field-emission analytical scanning and transmission electron microscopies (S/TEM), and electrochemical impedance spectroscopy. Using Rietveld refinements with powder XRD patterns, we determined that the number of Li atoms in the formula is less than 5 and that Li5-xLa3(NbTa)O12-y crystallizes in the cubic garnet structure with a space group Ia-3d. Sintering at varying temperatures (750–1000 °C) for 5 h in an ambient atmosphere produced distinct outcomes. Rietveld refinements disclosed that the sample sintered at 1000 °C (Li3.43(2)La3Nb1.07(2)Ta0.93(2)O12-y, a = 12.8361(7) Å, V = 2114.96(3) Å3) exhibited the highest ionic conductivity, while the 850 °C sample had the lowest conductivity, characterized by lower Li concentration and impurity phases (Li(Nb,Ta)3O88, Li2CO3). Analyses, including XRD and electron microscopy, confirmed the 1000 °C sample as a relatively phase pure with enhanced Li content (Li/La = 1.2), larger grains (15 μm), and uniform crystallinity. The 1000 °C sample introduced additional partially filled Li3 (96h) sites, promoting Li migration, and enhancing ionic conductivity. The resulting XRD pattern at 1000 °C has been submitted to the Powder Diffraction File as a reference.
A simulation study to improve calcium intake through wheat flour fortification
Authors: Cormick Gabriela , Romero Iris B , Puchulu María B , Perez Surya M , Sosa Miriam , Garitta Lorena , Elizagoyen Eliana , Gugole Maria Fernanda , Belizán José M , Matamoros Natalia , Gibbons Luz
Published: June 2024

Objective:

To simulate the impact on calcium intake – effectiveness and safety – of fortifying wheat flour with 200, 400 and 500 mg of calcium per 100 g of flour.

Design:

Secondary analysis of cross-sectional data collected through repeated 24 h dietary recalls using the Iowa State University Intake Modelling, Assessment and Planning Program.

Setting:

Urban cities in the National Health and Nutrition Survey of Argentina (ENNyS 2018–2019).

Participants:

21 358 participants, including children, adolescents and adults.

Results:

Most individuals in all age groups reported consuming wheat flour. The prevalence of low calcium intake was above 80 % in individuals older than 9 years. Simulating the fortification of 500 mg of calcium per 100 g of wheat flour showed that the prevalence of low calcium intake could be reduced by more than 40 percentage points in girls and women aged 19 to less than 51 years and boys and men aged 4 to less than 71 years, while it remained above 65 % in older ages. The percentages above the upper intake level remained below 1·5 % in all age groups.

Conclusions:

Calcium flour fortification could be further explored to improve calcium intake. Subnational simulations could be performed to identify groups that might not be reached by this strategy that could be explored in Argentina. This analysis could be used to advocate for a strategy to fortify wheat flour.
Bi-environmental evaluation of oat (Avena sativa L.) genotypes for yield and nutritional traits under cold stress conditions using multivariate analysis
Authors: Nabi Saika , Hussan Shamshir ul , Nabi Tawqeer , Shikari Asif B. , Dar Zahoor Ahmad , Khuroo N. S. , Lone Ajaz Ahmad , Sofi P. A. , Amin Rahila , Wani M. Altaf
Published: June 2024

Oat being a rabi/winter crop in Kashmir, experiences extremely low temperatures which has detrimental effects on its growth and development. Therefore, this study was designed to evaluate a set of 130 oat genotypes in multi-location trials across temperate conditions of Kashmir valley from 2018 to 2022. From the preliminary data of 56 genotypes, including five checks, were selected and evaluated for nutritional and yield attributing traits under cold stress conditions at two locations. The results demonstrated significant genetic variation and high heritability for majority of traits, except for days to 50% flowering, days to maturity and dry fodder. Positive correlations were observed between green fodder yield and other traits, indicating their potential for enhancing yield. Principal component analysis identified four principal components that accounted for 69.87% of the total variation. Cluster analysis categorized the genotypes into two main clusters and six sub-clusters. Frost damage assessment was conducted at tillering stage after the snow melted in late January 2021 and 2022 using cold tolerance rating scale and subsequently tested for chilling injury through an electrolyte leakage test. From field and lab data analysis, five most promising cold tolerant, nutritious and high-yielding genotypes were identified. These genotypes have significant potential for utilization in future breeding programmes to improve cold tolerance in cultivated oats within the Kashmir valley thus promoting agricultural productivity and sustainability. The outcomes also provide valuable insights into the genetic variation, heritability, genotype-by-environment interactions, correlations and cold tolerance of oat genotypes in Kashmir.
Understanding the Fate of H2S Injected in Basalts by Means of Time‐Domain Induced Polarization Geophysical Logging
Authors: Lévy L. , Ciraula D. A. , Legros B. , Martin T. , Weller A.
Published: June 2024

To help meet emission standards, hydrogen sulfide (H2S) from geothermal production may be injected back into the subsurface, where basalt offers, in theory, the capacity to mineralize H2S into pyrite. Ensuring the viability of this pollution mitigation technology requires information on how much H2S is mineralized, at what rate and where. To date, monitoring efforts of field‐scale H2S reinjection have mostly occurred via mass balance calculations, typically capturing less than 5% of the injected fluid. While these studies, along with laboratory experiments and geochemical models, conclude effective H2S mineralization, their extrapolation to quantify mineralization and its persistence over time leads to considerable uncertainty. Here, a geophysical methodology, using time‐domain induced polarization (TDIP) logging in two of the injection wells (NN3 and NN4), is developed as a complementary tool to follow the fate of H2S re‐injected at Nesjavellir geothermal site (Iceland). Results show a strong chargeability increase at +40 days, interpreted as precipitation of up to 2 vol.% based on laboratory relationships. A uniform increase is observed along NN4, whereas it is localized below 450 m in NN3. Changes are more pronounced with larger electrode spacing, indicating that pyrite precipitation takes place away from the wells. Furthermore, a chargeability decrease is observed at later monitoring rounds in both wells, suggesting that pyrite is either passivated or re‐dissolved after precipitating. These results highlight that a sequence of overlapping reactive processes (pyrite precipitation, passivation, pore clogging and possibly pyrite re‐dissolution) results from H2S injection and that TDIP monitoring is sensitive to this sequence.
Pathways of Inter‐Basin Exchange From the Bellingshausen Sea to the Amundsen Sea
Authors: Flexas M. Mar , Thompson Andrew F. , Robertson Megan L. , Speer Kevin , Sheehan Peter M. F. , Heywood Karen J.
Published: June 2024

The West Antarctic Ice Sheet is experiencing rapid thinning of its floating ice shelves, largely attributed to oceanic basal melt. Numerical models suggest that the Bellingshausen Sea has a key role in setting water properties in the Amundsen Sea and further downstream. Yet, observations confirming these pathways of volume and tracer exchange between coast and shelf break and their impact on inter‐sea exchange remain sparse. Here we analyze the circulation and distribution of glacial meltwater at the boundary between the Bellingshausen Sea and the Amundsen Sea using a combination of glider observations from January 2020 and hydrographic data from instrumented seals. Meltwater distributions over previously unmapped western regions of the continental shelf and slope reveal two distinct meltwater cores with different optical backscatter properties. At Belgica Trough, a subsurface meltwater peak is linked with hydrographic properties from Venable Ice Shelf. West of Belgica Trough, the vertical structure of meltwater concentration changes, with peak values occurring at greater depths and denser isopycnals. Hydrographic analysis suggests that the western (deep) meltwater core is supplied from the eastern part of Abbot Ice Shelf, and is exported to the shelf break via a previously‐overlooked bathymetric trough (here named Seal Trough). Hydrographic sections constructed from seal data reveal that the Antarctic Coastal Current extends west past Belgica Trough, delivering meltwater to the Amundsen Sea. Each of these circulation elements has distinct dynamical implications for the evolution of ice shelves and water masses both locally and downstream, in the Amundsen Sea and beyond.
In the Wake of Deeper Convection: Nonsteady State Anthropogenic Carbon in the Greenland Sea
Authors: Olsen Are , Rajasakaren Balamuralli , Jeansson Emil , Lauvset Siv K. , Omar Abdirahman M. , Becker Meike
Published: June 2024

We evaluate changes in dissolved inorganic carbon (DIC) in the Greenland Sea between 2002 and 2016, a period characterized by increasing convection depths. We find a mid‐depth maximum in anthropogenic carbon (Cant) accumulation that occurred as waters at these depths were rejuvenated by deeper reaching convection; broadly, these waters have caught up with the atmospheric CO2 rise that had happened between the last time they were ventilated and 2002 and also tracked the atmospheric CO2 rise 2002–2016. The overlying waters only tracked the atmospheric CO2 rise 2002–2016. The mid‐depth maximum in Cant accumulation was not evident in estimates generated with commonly used multiple linear regression (MLR) methods. We analyze the reasons why and show that the eMLR(C*) method may not fully capture nonsteady state changes in Cant when applied along a single hydrographic section as done here. This nonsteady component equates to redistribution of C*, whose spatial gradients in the Greenland Sea are dominated by Cant. We also show that the regular extended multiple linear regression method is sensitive to loss of spatial DIC gradients, which now happens as more and more Cant enters the ocean. Our findings demonstrate that MLR‐based estimates of the Cant accumulation rate should not be taken at face value in highly dynamical ocean regions, such as the Greenland Sea, and the need for also considering the total change in DIC and how this is affected by natural processes. Further investigations into the ability of MLR methods to reproduce nonsteady state changes in Cant are encouraged.
Stagnation of Eddy Kinetic Energy After Summer Monsoon Onset in the South China Sea
Authors: Lin Junshu , Wang Minyang , Wu Wei , Wang Xiangpeng , Du Yan
Published: June 2024

The monsoon is the primary force behind the upper‐layer circulation system and regulates eddy activity in the South China Sea (SCS). Using satellite observations and a state‐of‐the‐art oceanic reanalysis, this study examines transferring processes of eddy kinetic energy (EKE) during the SCS Summer Monsoon (SCSSM) onset (20th May on average). The SCSSM onset transforms surface winds from easterly to southwesterly, increasing EKE in the southwestern SCS by surface wind work. Despite the persistent energy input from wind work, EKE growth ceases during the first 20 days after SCSSM onset. An EKE budget analysis suggests that most energy input dissipates in the mixed layer due to the high wind speed, which explains the EKE stagnation. Additionally, eddy‐mean flow interactions transfer kinetic energy from eddies to mean flows during the SCSSM onset. The Vietnam coastal upwelling system provides available potential energy to EKE on the offshore side through buoyancy work. Our study reveals energy‐transferring processes from the summer monsoon to eddy activity and dissipation in the SCS, with implications for understanding multiscale dynamic evolutions during the monsoon transition.
Evolving Particles in the 2022 Hunga Tonga—Hunga Ha'apai Volcano Eruption Plume
Authors: Kahn Ralph A. , Limbacher James A. , Junghenn Noyes Katherine T. , Flower Verity J. B. , Zamora Lauren M. , McKee Kathleen F.
Published: June 2024

The Multi‐angle Imaging SpectroRadiometer (MISR) aboard NASA's Terra satellite observed the Hunga Tonga—Hunga Ha'apai (HTHH) 15 January eruption plume on eight occasions between 15 and 23 January 2022. From the MISR multi‐angle, multi‐spectral imagery we retrieve aerosol plume height geometrically, along with plume‐level motion vectors, and derive radiometrically constraints on particle effective size, shape, and light‐absorption properties. Parts of two downwind aerosol layers were observed in different places and times, one concentrated in the upper troposphere (11–18 km ASL), and a mid‐stratosphere layer ∼23–30+ km ASL. After the initial day (1/15), the retrievals identified only spherical, non‐light‐absorbing particles, typical of volcanic sulfate/water particles. The near‐tropopause plume particles show constant, medium‐small (several tenths of a micron) effective size over 4 days. The mid‐stratosphere particles were consistently smaller, but retrieved effective particle size increased between 1/17 and 1/23, though they might have decreased slightly on 1/22. As a vast amount of water was also injected into the stratosphere by this eruption, models predicted relatively rapid sulfate particle growth from the modest amounts of SO2 gas injected by the eruption to high altitudes along with the water (Zhu et al., 2022, https://doi.org/10.5194/acp‐22‐10267‐2022). MISR observations up to 10 days after the eruption are consistent with these model predictions. The possible decrease in stratospheric particle size after initial growth was likely caused by evaporation, as the plume mixed with drier, ambient air. Particles in the lower‐elevation plume observed on 1/15 were larger than all the downwind aerosols and contained significant non‐spherical (likely ash) particles.
Increasing Methane Emissions and Widespread Cold‐Season Release From High‐Arctic Regions Detected Through Atmospheric Measurements
Authors: Ward Rebecca H. , Sweeney Colm , Miller John B. , Goeckede Mathias , Laurila Tuomas , Hatakka Juha , Ivakov Viktor , Sasakawa Motoki , Machida Toshinobu , Morimoto Shinji , Goto Daisuke , Ganesan Anita L.
Published: June 2024

Rising Arctic temperatures pose a threat to the large carbon stores trapped in Arctic permafrost. To assess methane emissions in high‐Arctic regions, we analyzed atmospheric data from Alaska and Siberia using two methods: (a) a wind sector approach to calculate emission changes based on concentration enhancements using wind direction, and (b) an inversion method utilizing a high‐resolution atmospheric transport model. Incorporating data after 2015, we observed a significant rise in methane emissions (0.018 ± 0.005 Tg yr−2 from 2000 to 2021) from Alaska's North Slope, indicating a shift from previous analyses. We find 34%–50% of yearly emissions occurred in the late season (September–December) consistently across multiple years and regions, which is historically underestimated in models and inventories. Our findings reveal significant changes occurring in the Arctic, highlighting the crucial role of long‐term atmospheric measurements in monitoring the region, especially during the cold season.
The m6A writer RBM15 drives the growth of triple-negative breast cancer cells through the stimulation of serine and glycine metabolism
Authors: Park Su Hwan , Ju Jin-Sung , Woo Hyunmin , Yun Hye Jin , Lee Su Bin , Kim Seok-Ho , Győrffy Balázs , Kim Eun-jeong , Kim Ho , Han Hee Dong , Eyun Seong-il , Lee Jong-Ho , Park Yun-Yong
Published: June 2024

N6-adenosine methylation (m6A) is critical for controlling cancer cell growth and tumorigenesis. However, the function and detailed mechanism of how m6A methyltransferases modulate m6A levels on specific targets remain unknown. In the current study, we identified significantly elevated levels of RBM15, an m6A writer, in basal-like breast cancer (BC) patients compared to nonbasal-like BC patients and linked this increase to worse clinical outcomes. Gene expression profiling revealed correlations between RBM15 and serine and glycine metabolic genes, including PHGDH, PSAT1, PSPH, and SHMT2. RBM15 influences m6A levels and, specifically, the m6A levels of serine and glycine metabolic genes via direct binding to target RNA. The effects of RBM15 on cell growth were largely dependent on serine and glycine metabolism. Thus, RBM15 coordinates cancer cell growth through altered serine and glycine metabolism, suggesting that RBM15 is a new therapeutic target in BC.
Alleviation of preeclampsia-like symptoms through PlGF and eNOS regulation by hypoxia- and NF-κB-responsive miR-214-3p deletion
Authors: Kim Suji , Shim Sungbo , Kwon Jisoo , Ryoo Sungwoo , Byeon Junyoung , Hong Jungwoo , Lee Jeong-Hyung , Kwon Young-Guen , Kim Ji-Yoon , Kim Young-Myeong
Published: June 2024

Preeclampsia is caused by placental hypoxia and systemic inflammation and is associated with reduced placental growth factor (PlGF) and endothelial nitric oxide synthase (eNOS) levels. The molecular signaling axes involved in this process may play a role in the pathogenesis of preeclampsia. Here, we found that hypoxic exposure increased hypoxia-inducible factor-1α (HIF-1α)/Twist1-mediated miR-214-3p biogenesis in trophoblasts, suppressing PlGF production and trophoblast invasion. TNF-α stimulation increased NF-κB-dependent miR-214-3p expression in endothelial cells, impairing eNOS expression and causing endothelial dysfunction. Synthetic miR-214-3p administration to pregnant mice decreased PlGF and eNOS expression, resulting in preeclampsia-like symptoms, including hypertension, proteinuria, and fetal growth restriction. Conversely, miR-214-3p deletion maintained the PlGF and eNOS levels in hypoxic pregnant mice, alleviating preeclampsia-like symptoms and signs. These findings provide new insights into the role of HIF-1/Twist1- and NF-κB-responsive miR-214-3p-dependent PlGF and eNOS downregulation in the pathogenesis of preeclampsia and establish miR-214-3p as a therapeutic or preventive target for preeclampsia and its complications.
Regulation of metaplasia and dysplasia in the stomach by the stromal microenvironment
Authors: Rhodes Jared D. , Goldenring James R. , Lee Su-Hyung
Published: June 2024

Research on the microenvironment associated with gastric carcinogenesis has focused on cancers of the stomach and often underestimates premalignant stages such as metaplasia and dysplasia. Since epithelial interactions with T cells, macrophages, and type 2 innate lymphoid cells (ILC2s) are indispensable for the formation of precancerous lesions in the stomach, understanding the cellular interactions that promote gastric precancer warrants further investigation. Although various types of immune cells have been shown to play important roles in gastric carcinogenesis, it remains unclear how stromal cells such as fibroblasts influence epithelial transformation in the stomach, especially during precancerous stages. Fibroblasts exist as distinct populations across tissues and perform different functions depending on the expression patterns of cell surface markers and secreted factors. In this review, we provide an overview of known microenvironmental components in the stroma with an emphasis on fibroblast subpopulations and their roles during carcinogenesis in tissues including breast, pancreas, and stomach. Additionally, we offer insights into potential targets of tumor-promoting fibroblasts and identify open areas of research related to fibroblast plasticity and the modulation of gastric carcinogenesis.
IL-33 and IL-33-derived DC-based tumor immunotherapy
Authors: Kang Myeong-Ho , Bae Yong-Soo
Published: June 2024

Interleukin-33 (IL-33), a member of the IL-1 family, is a cytokine released in response to tissue damage and is recognized as an alarmin. The multifaceted roles of IL-33 in tumor progression have sparked controversy within the scientific community. However, most findings generally indicate that endogenous IL-33 has a protumor effect, while exogenous IL-33 often has an antitumor effect in most cases. This review covers the general characteristics of IL-33 and its effects on tumor growth, with detailed information on the immunological mechanisms associated with dendritic cells (DCs). Notably, DCs possess the capability to uptake, process, and present antigens to CD8+ T cells, positioning them as professional antigen-presenting cells. Recent findings from our research highlight the direct association between the tumor-suppressive effects of exogenous IL-33 and a novel subset of highly immunogenic cDC1s. Exogenous IL-33 induces the development of these highly immunogenic cDC1s through the activation of other ST2+ immune cells both in vivo and in vitro. Recognizing the pivotal role of the immunogenicity of DC vaccines in DC-based tumor immunotherapy, we propose compelling methods to enhance this immunogenicity through the addition of IL-33 and the promotion of highly immunogenic DC generation.
Association between solar radiation and mood disorders among Gulf Coast residents
Authors: Deng Xinlei , Launer Lenore J. , Lawrence Kaitlyn G. , Werder Emily J. , Buller Ian D. , Jackson William Braxton , Sandler Dale P.
Published: June 2024

Background

Climate factors such as solar radiation could contribute to mood disorders, but evidence of associations between exposure to solar radiation and mood disorders is mixed and varies by region.

Objective

To evaluate the association of solar radiation with depression and distress among residents living in U.S. Gulf states.

Methods

We enrolled home-visit participants in the Gulf Long-Term Follow-up Study who completed validated screening questionnaires for depression (Patient Health Questionnaire-9, N = 10,217) and distress (Kessler Psychological Distress Questionnaire, N = 8,765) for the previous 2 weeks. Solar radiation estimates from the Daymet database (1-km grid) were linked to residential addresses. Average solar radiation exposures in the seven (SRAD7), 14 (SRAD14), and 30 days (SRAD30) before the home visit were calculated and categorized into quartiles (Q1-Q4). We used generalized linear mixed models to estimate prevalence ratios (PR) and 95% confidence intervals (CI) for associations between solar radiation and depression/distress.

Results

Higher levels of SRAD7 were non-monotonically inversely associated with depression [PRVs.Q1 (95%CI): Q2 = 0.81 (0.68, 0.97), Q3 = 0.80 (0.65, 0.99), Q4 = 0.88 (0.69, 1.15)] and distress [PRVs.Q1 (95%CI): Q2 = 0.76 (0.58, 0.99), Q3 = 0.77 (0.57, 1.06), Q4 = 0.84 (0.58, 1.22)]. Elevated SRAD14 and SRAD30 appeared to be associated with decreasing PRs of distress. For example, for SRAD14, PRs were 0.86 (0.63–1.19), 0.80 (0.55–1.18), and 0.75 (0.48–1.17) for Q2-4 versus Q1. Associations with SRAD7 varied somewhat, though not significantly, by season with increasing PRs of distress in spring and summer and decreasing PRs of depression and distress in fall.

Impact Statement

Previous research suffered from exposure misclassification, which impacts the validity of their conclusions. By leveraging high-resolution datasets and Gulf Long-term Follow-up Cohort, our findings support an association between increased solar radiation and fewer symptoms of mood disorders.
High-precision all-in-one dual robotic arm strategy in oral implant surgery
Authors: Tang Gang , Liu Shibo , Sun Meng , Wang Yide , Zhu Weidong , Wang Dongmei , Li Xiang , Wu Hao , Men Shaoyang , Zhang Liangbin , Feng Changfen , Wang Yingfu , Ding Yuehua
Published: June 2024

Introduction

Dental implantation has emerged as an efficient substitute for missing teeth, which is essential for restoring oral function and aesthetics. Compared to traditional denture repair approaches, dental implants offer better stability and sustainability. The position, angle, and depth of dental implants are crucial factors for their long-term success and necessitate high-precision operation and technical support.

Method

We propose an integrated dual-arm high-precision oral implant surgery navigation positioning system and a corresponding control strategy. Compared with traditional implant robots, the integrated dual-arm design greatly shortens the preparation time before surgery and simplifies the operation process. We propose a novel control flow and module for the proposed structure, including an Occluded Target Tracking Module (OTTM) for occlusion tracking, a Planting Plan Development Module (PPDM) for generating implant plans, and a Path Formulation Module (PFM) for controlling the movement path of the two robot arms.

Result

Under the coordinated control of the aforementioned modules, the robot achieved excellent accuracy in clinical trials. The average angular error and entry point error for five patients who underwent implant surgery using the proposed robot were 2.1° and 0.39 mm, respectively.

Conclusion

In essence, our study introduces an integrated dual-arm high-precision navigation system for oral implant surgery, resolving issues like lengthy preoperative preparation and static surgical planning. Clinical results confirm its efficacy, emphasizing its accuracy and precision in guiding oral implant procedures.
Clinical landscape of macrophage-reprogramming cancer immunotherapies
Authors: Rannikko Jenna H. , Hollmén Maija
Published: June 2024

Tumour-associated macrophages (TAMs) sustain a tumour-supporting and immunosuppressive milieu and therefore aggravate cancer prognosis. To modify TAM behaviour and unlock their anti-tumoural potential, novel TAM-reprogramming immunotherapies are being developed at an accelerating rate. At the same time, scientific discoveries have highlighted more sophisticated TAM phenotypes with complex biological functions and contradictory prognostic associations. To understand the evolving clinical landscape, we reviewed current and past clinically evaluated TAM-reprogramming cancer therapeutics and summarised almost 200 TAM-reprogramming agents investigated in more than 700 clinical trials. Observable overall trends include a high frequency of overlapping strategies against the same therapeutic targets, development of more complex strategies to improve previously ineffective approaches and reliance on combinatory strategies for efficacy. However, strong anti-tumour efficacy is uncommon, which encourages re-directing efforts on identifying biomarkers for eligible patient populations and comparing similar treatments earlier. Future endeavours will benefit from considering the shortcomings of past treatment strategies and accommodating the emerging complexity of TAM biology.
The trends of antihypertensive drug prescription based on the Japanese national data throughout the COVID-19 pandemic period
Authors: Natsume Shotaro , Satoh Michihiro , Murakami Takahisa , Sasaki Masato , Metoki Hirohito
Published: June 2024

In 2020, concerns arose about the potential adverse effects of angiotensin II type 1 receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs) on patients with the Coronavirus Disease 2019 (COVID-19). However, there is no national data on antihypertensive prescriptions during the COVID-19 pandemic in Japan. This study aimed to explore the trends in antihypertensive drug prescriptions in Japan throughout COVID-19 pandemic period. This study used data from the National Database (NDB) Open Data in Japan, an annual publication by the Ministry of Health, Labour and Welfare. To capture changes before and after social activity restrictions, the present study focused on extracting the number of prescribed oral medicine tablets for outpatients from the NDB Open Data from 2018 to 2021. The fiscal year 2020 exhibited the lowest for both outpatient claims and prescribed drugs. In contrast, all categories of antihypertensive drug prescription showed annual increases, and no specific changes in the prescription patterns of ARBs and ACEIs around fiscal year 2020 were observed. This study implies that antihypertensive drug prescriptions were adequately maintained throughout the COVID-19 pandemic in Japan.
Fate of telomere entanglements is dictated by the timing of anaphase midregion nuclear envelope breakdown
Authors: Nageshan Rishi Kumar , Ortega Raquel , Krogan Nevan , Cooper Julia Promisel
Published: June 2024

Persisting replication intermediates can confer mitotic catastrophe. Loss of the fission yeast telomere protein Taz1 (ortholog of mammalian TRF1/TRF2) causes telomeric replication fork (RF) stalling and consequently, telomere entanglements that stretch between segregating mitotic chromosomes. At ≤20 °C, these entanglements fail to resolve, resulting in lethality. Rif1, a conserved DNA replication/repair protein, hinders the resolution of telomere entanglements without affecting their formation. At mitosis, local nuclear envelope (NE) breakdown occurs in the cell’s midregion. Here we demonstrate that entanglement resolution occurs in the cytoplasm following this NE breakdown. However, in response to taz1Δ telomeric entanglements, Rif1 delays midregion NE breakdown at ≤20 °C, in turn disfavoring entanglement resolution. Moreover, Rif1 overexpression in an otherwise wild-type setting causes cold-specific NE defects and lethality, which are rescued by membrane fluidization. Hence, NE properties confer the cold-specificity of taz1Δ lethality, which stems from postponement of NE breakdown. We propose that such postponement promotes clearance of simple stalled RFs, but resolution of complex entanglements (involving strand invasion between nonsister telomeres) requires rapid exposure to the cytoplasm.
Cooperative growth in microbial communities is a driver of multistability
Authors: Lopes William , Amor Daniel R. , Gore Jeff
Published: June 2024

Microbial communities often exhibit more than one possible stable composition for the same set of external conditions. In the human microbiome, these persistent changes in species composition and abundance are associated with health and disease states, but the drivers of these alternative stable states remain unclear. Here we experimentally demonstrate that a cross-kingdom community, composed of six species relevant to the respiratory tract, displays four alternative stable states each dominated by a different species. In pairwise coculture, we observe widespread bistability among species pairs, providing a natural origin for the multistability of the full community. In contrast with the common association between bistability and antagonism, experiments reveal many positive interactions within and between community members. We find that multiple species display cooperative growth, and modeling predicts that this could drive the observed multistability within the community as well as non-canonical pairwise outcomes. A biochemical screening reveals that glutamate either reduces or eliminates cooperativity in the growth of several species, and we confirm that such supplementation reduces the extent of bistability across pairs and reduces multistability in the full community. Our findings provide a mechanistic explanation of how cooperative growth rather than competitive interactions can underlie multistability in microbial communities.
Climate extremes in Svalbard over the last two millennia are linked to atmospheric blocking
Authors: Lapointe Francois , Karmalkar Ambarish V. , Bradley Raymond S. , Retelle Michael J. , Wang Feng
Published: June 2024

Arctic precipitation in the form of rain is forecast to become more prevalent in a warmer world but with seasonal and interannual changes modulated by natural modes of variability. Experiencing rapid hydroclimatic changes in the Arctic, Svalbard serves as an ideal study location due to its exposure to oceanic and atmospheric variability in the North Atlantic region. Here we use climate data from paleoproxies, observations, and a climate model to demonstrate that wet and warm extremes in Svalbard over the last two millennia are linked to the presence of atmospheric blocking regimes over Scandinavia and the Ural mountain region. Rainfall episodes lead to the deposition of coarse sediment particles and high levels of calcium in Linnévatnet, a lake in southwest Svalbard, with the coarsest sediments consistently deposited during atmospheric blocking events. A unique annually resolved sediment record from Linnévatnet confirms that this linkage has been persistent over the past 2000 years. Our record also shows that a millennial-scale decline in Svalbard precipitation ended around the middle of the 19th century, followed by several unprecedented extreme events in recent years. As warming continues and sea ice recedes, future Svalbard floods will become more intense during episodes of Scandinavian and Ural blocking.
Neutrophils and galectin-3 defend mice from lethal bacterial infection and humans from acute respiratory failure
Authors: Das Sudipta , Kaminski Tomasz W. , Schlegel Brent T. , Bain William , Hu Sanmei , Patel Akruti , Kale Sagar L. , Chen Kong , Lee Janet S. , Mallampalli Rama K. , Kagan Valerian E. , Rajasundaram Dhivyaa , McVerry Bryan J. , Sundd Prithu , Kitsios Georgios D. , Ray Anuradha , Ray Prabir
Published: June 2024

Respiratory infection byPseudomonas aeruginosa, common in hospitalized immunocompromised and immunocompetent ventilated patients, can be life-threatening because of antibiotic resistance. This raises the question of whether the host’s immune system can be educated to combat this bacterium. Here we show that prior exposure to a single low dose of lipopolysaccharide (LPS) protects mice from a lethal infection byP. aeruginosa. LPS exposure trained the innate immune system by promoting expansion of neutrophil and interstitial macrophage populations distinguishable from other immune cells with enrichment of gene sets for phagocytosis- and cell-killing-associated genes. The cell-killing gene set in the neutrophil population uniquely expressedLgals3, which encodes the multifunctional antibacterial protein, galectin-3. Intravital imaging for bacterial phagocytosis, assessment of bacterial killing and neutrophil-associated galectin-3 protein levels together with use of galectin-3-deficient mice collectively highlight neutrophils and galectin-3 as central players in LPS-mediated protection. Patients with acute respiratory failure revealed significantly higher galectin-3 levels in endotracheal aspirates (ETAs) of survivors compared to non-survivors, galectin-3 levels strongly correlating with a neutrophil signature in the ETAs and a prognostically favorable hypoinflammatory plasma biomarker subphenotype. Taken together, our study provides impetus for harnessing the potential of galectin-3-expressing neutrophils to protect from lethal infections and respiratory failure.
Early warning and proactive control strategies for power blackouts caused by gas network malfunctions
Authors: Yu Fengshuo , Guo Qinglai , Wu Jianzhong , Qiao Zheng , Sun Hongbin
Published: June 2024

There is growing consensus that gas-fired generators will play a crucial role during the transition to net-zero energy systems, both as an alternative to coal-fired generators and as a flexibility service provider for power systems. However, malfunctions of gas networks have caused several large-scale power blackouts. The transition from coal and oil to gas fuels significantly increases the interdependence between gas networks and electric power systems, raising the risks of more frequent and widespread power blackouts due to the malfunction of gas networks. In a coupled gas–electricity system, the identification and transmission of gas network malfunction information, followed by the redispatch of electric power generation, occur notably faster than the propagation and escalation of the malfunction itself, e.g., significantly diminished pressure. On this basis, we propose a gas-electric early warning system that can reduce the negative impacts of gas network malfunctions on the power system. A proactive control strategy of the power system is also formulated based on the early warning indicators. The effectiveness of this method is demonstrated via case studies of a real coupled gas–electricity system in China.
Instantly adhesive and ultra-elastic patches for dynamic organ and wound repair
Authors: Chansoria Parth , Chaudhari Ameya , Etter Emma L. , Bonacquisti Emily E. , Heavey Mairead K. , Le Jiayan , Maruthamuthu Murali Kannan , Kussatz Caden C. , Blackwell John , Jasiewicz Natalie E. , Sellers Rani S. , Maile Robert , Wallet Shannon M. , Egan Thomas M. , Nguyen Juliane
Published: June 2024

Bioadhesive materials and patches are promising alternatives to surgical sutures and staples. However, many existing bioadhesives do not meet the functional requirements of current surgical procedures and interventions. Here, we present a translational patch material that exhibits instant adhesion to tissues (2.5-fold stronger than Tisseel, an FDA-approved fibrin glue), ultra-stretchability (stretching to >300% its original length without losing elasticity), compatibility with rapid photo-projection (<2 min fabrication time/patch), and ability to deliver therapeutics. Using our established procedures for the in silico design and optimization of anisotropic-auxetic patches, we created next-generation patches for instant attachment to tissues while conforming to a broad range of organ mechanics ex vivo and in vivo. Patches coated with extracellular vesicles derived from mesenchymal stem cells demonstrate robust wound healing capability in vivo without inducing a foreign body response and without the need for patch removal that can cause pain and bleeding. We further demonstrate a single material-based, void-filling auxetic patch designed for the treatment of lung puncture wounds.
ChatMOF: an artificial intelligence system for predicting and generating metal-organic frameworks using large language models
Authors: Kang Yeonghun , Kim Jihan
Published: June 2024

ChatMOF is an artificial intelligence (AI) system that is built to predict and generate metal-organic frameworks (MOFs). By leveraging a large-scale language model (GPT-4, GPT-3.5-turbo, and GPT-3.5-turbo-16k), ChatMOF extracts key details from textual inputs and delivers appropriate responses, thus eliminating the necessity for rigid and formal structured queries. The system is comprised of three core components (i.e., an agent, a toolkit, and an evaluator) and it forms a robust pipeline that manages a variety of tasks, including data retrieval, property prediction, and structure generations. ChatMOF shows high accuracy rates of 96.9% for searching, 95.7% for predicting, and 87.5% for generating tasks with GPT-4. Additionally, it successfully creates materials with user-desired properties from natural language. The study further explores the merits and constraints of utilizing large language models (LLMs) in combination with database and machine learning in material sciences and showcases its transformative potential for future advancements.
Tailoring the quantum anomalous layer Hall effect in multiferroic bilayers through sliding
Authors: Liu Kehan , Ma Xikui , Li Yangyang , Zhao Mingwen
Published: June 2024

Layer Hall effect (LHE), initially discovered in the magnetic topological insulator MnBi2Te4 film, expands the Hall effect family and opens a promising avenue for layertronics applications. In this study, we present an innovative ferroelectric bilayer model to attain a tunable quantum anomalous layer Hall effect (QALHE). This model comprises two ferromagnetic orbital-active Dirac monolayers stacked antiferromagnetically, accompanied by out-of-plane electric polarization. The interplay between the layer-locked Berry curvature monopoles and the intrinsic out-of-plane electric polarization leads to layer-polarized near-quantized anomalous Hall conductance. Using first-principles calculations, we have identified a promising material for this model, namely FeS bilayer. Our calculations demonstrate that the intrinsic out-of-plane electric polarization in the Bernal-stacked FeS bilayer can induce QALHE by regulating the layer-locked Berry curvature of FeS monolayers. Importantly, the intrinsic electric field can be reversed through interlayer sliding. The discovery of ferroelectrically modulated QALHE paves the way for the integrability and non-volatility of layertronics, offering exciting prospects for future applications.
Microwave-multiplexed qubit controller using adiabatic superconductor logic
Authors: Takeuchi Naoki , Yamae Taiki , Yamashita Taro , Yamamoto Tsuyoshi , Yoshikawa Nobuyuki
Published: June 2024

Cryogenic qubit controllers (QCs) are the key to build large-scale superconducting quantum processors. However, developing scalable QCs is challenging because the cooling power of a dilution refrigerator is too small (~10 μW at ~10 mK) to operate conventional logic families, such as complementary metal-oxide-semiconductor logic and superconducting single-flux-quantum logic, near qubits. Here we report on a scalable QC using an ultra-low-power superconductor logic family, namely adiabatic quantum-flux-parametron (AQFP) logic. The AQFP-based QC, referred to as the AQFP-multiplexed QC (AQFP-mux QC), produces multi-tone microwave signals for qubit control with an extremely small power dissipation of 81.8 pW per qubit. Furthermore, the AQFP-mux QC adopts microwave multiplexing to reduce the number of coaxial cables for operating the entire system. As a proof of concept, we demonstrate an AQFP-mux QC chip that produces microwave signals at two output ports through microwave multiplexing and demultiplexing. Experimental results show an output power of approximately −80 dBm and on/off ratio of ~40 dB at each output port. Basic mixing operation is also demonstrated by observing sideband signals.
Structure-guided discovery of highly efficient cytidine deaminases with sequence-context independence
Authors: Xu Kui , Feng Hu , Zhang Haihang , He Chenfei , Kang Huifang , Yuan Tanglong , Shi Lei , Zhou Chikai , Hua Guoying , Cao Yaqi , Zuo Zhenrui , Zuo Erwei
Published: June 2024

The applicability of cytosine base editors is hindered by their dependence on sequence context and by off-target effects. Here, by using AlphaFold2 to predict the three-dimensional structure of 1,483 cytidine deaminases and by experimentally characterizing representative deaminases (selected from each structural cluster after categorizing them via partitional clustering), we report the discovery of a few deaminases with high editing efficiencies, diverse editing windows and increased ratios of on-target to off-target effects. Specifically, several deaminases induced C-to-T conversions with comparable efficiency at AC/TC/CC/GC sites, the deaminases could introduce stop codons in single-copy and multi-copy genes in mammalian cells without double-strand breaks, and some residue conversions at predicted DNA-interacting sites reduced off-target effects. Structure-based generative machine learning could be further leveraged to expand the applicability of base editors in gene therapies.
Genetic variants in UNC93B1 predispose to childhood-onset systemic lupus erythematosus
Authors: Al-Azab Mahmoud , Idiiatullina Elina , Liu Ziyang , Lin Meng , Hrovat-Schaale Katja , Xian Huifang , Zhu Jianheng , Yang Mandy , Lu Bingtai , Zhao Zhiyao , Liu Yiyi , Chang Jingjie , Li Xiaotian , Guo Caiqin , Liu Yunfeng , Wu Qi , Chen Jiazhang , Lan Chaoting , Zeng Ping , Cui Jun , Gao Xia , Zhou Wenhao , Zhang Yan , Zhang Yuxia , Masters Seth L.
Published: June 2024

Rare genetic variants in toll-like receptor 7 (TLR7) are known to cause lupus in humans and mice. UNC93B1 is a transmembrane protein that regulates TLR7 localization into endosomes. In the present study, we identify two new variants in UNC93B1 (T314A, located proximally to the TLR7 transmembrane domain, and V117L) in a cohort of east Asian patients with childhood-onset systemic lupus erythematosus. The V117L variant was associated with increased expression of type I interferons and NF-κB-dependent cytokines in patient plasma and immortalized B cells. THP-1 cells expressing the variant UNC93B1 alleles exhibited exaggerated responses to stimulation of TLR7/-8, but not TLR3 or TLR9, which could be inhibited by targeting the downstream signaling molecules, IRAK1/-4. Heterozygous mice expressing the orthologous Unc93b1V117L variant developed a spontaneous lupus-like disease that was more severe in homozygotes and again hyperresponsive to TLR7 stimulation. Together, this work formally identifies genetic variants in UNC93B1 that can predispose to childhood-onset systemic lupus erythematosus.
Lisocabtagene maraleucel in follicular lymphoma: the phase 2 TRANSCEND FL study
Authors: Morschhauser Franck , Dahiya Saurabh , Palomba M. Lia , Martin Garcia-Sancho Alejandro , Reguera Ortega Juan Luis , Kuruvilla John , Jäger Ulrich , Cartron Guillaume , Izutsu Koji , Dreyling Martin , Kahl Brad , Ghesquieres Hervé , Ardeshna Kirit , Goto Hideki , Barbui Anna Maria , Abramson Jeremy S. , Borchmann Peter , Fleury Isabelle , Mielke Stephan , Skarbnik Alan , de Vos Sven , Kamdar Manali , Karmali Reem , Viardot Andreas , Farazi Thalia , Fasan Omotayo , Lymp James , Vedal Min , Nishii Rina , Avilion Ariel , Papuga Jessica , Kumar Jinender , Nastoupil Loretta J.
Published: June 2024

An unmet need exists for patients with relapsed/refractory (R/R) follicular lymphoma (FL) and high-risk disease features, such as progression of disease within 24 months (POD24) from first-line immunochemotherapy or disease refractory to both CD20-targeting agent and alkylator (double refractory), due to no established standard of care and poor outcomes. Chimeric antigen receptor (CAR) T cell therapy is an option in R/R FL after two or more lines of prior systemic therapy, but there is no consensus on its optimal timing in the disease course of FL, and there are no data in second-line (2L) treatment of patients with high-risk features. Lisocabtagene maraleucel (liso-cel) is an autologous, CD19-directed, 4-1BB CAR T cell product. The phase 2 TRANSCEND FL study evaluated liso-cel in patients with R/R FL, including 2L patients who all had POD24 from diagnosis after treatment with anti-CD20 antibody and alkylator ≤6 months of FL diagnosis and/or met modified Groupe d’Etude des Lymphomes Folliculaires criteria. Primary/key secondary endpoints were independent review committee–assessed overall response rate (ORR)/complete response (CR) rate. At data cutoff, 130 patients had received liso-cel (median follow-up, 18.9 months). Primary/key secondary endpoints were met. In third-line or later FL (n = 101), ORR was 97% (95% confidence interval (CI): 91.6‒99.4), and CR rate was 94% (95% CI: 87.5‒97.8). In 2L FL (n = 23), ORR was 96% (95% CI: 78.1‒99.9); all responders achieved CR. Cytokine release syndrome occurred in 58% of patients (grade ≥3, 1%); neurological events occurred in 15% of patients (grade ≥3, 2%). Liso-cel demonstrated efficacy and safety in patients with R/R FL, including high-risk 2L FL. ClinicalTrials.gov identifier: NCT04245839.