bluuebunny/crossref_metadata_2025 huggingface dataset:
“Living with Loss”: A qualitative exploration of existential fears among people with advanced lung cancer in online lung cancer support groups
Authors: Walsh Casey A. , Currin-McCulloch Jennifer , Faris Nicholas R. , Nguyen Thu Suong Thi , Al Achkar Morhaf
Published: February 2024

Objectives

With targeted therapies, people are surviving longer with advanced lung cancer and engaging in online lung cancer support communities. While these groups provide a sense of community, witnessing the death of peers can lead to emotional distress. This qualitative study aims to (1) explore the experience of witnessing death in online cancer support groups; (2) identify factors that contribute to the emotional struggles of witnessing the death of peers; and (3) identify strategies/options for dealing with losses in the cancer community.

Methods

We conducted a cross-sectional analysis of qualitative interviews exploring existential concerns with participants (n = 25) from oncogene-specific online lung cancer support groups. The principal investigator conducted study interviews between August 2018 and March 2019 where participants were asked about their cancer experiences and existential concerns. We used thematic analysis and NVIVO 11 software to examine and store the de-identified interview data.

Results

Participants indicated that they had often witnessed their peers die and felt the pain of the loss. Factors that played a part in their struggle with witnessing others’ death included the closeness of the relationship with the person, the age of the person who died, seeing oneself in the experience of the other dying, disparities in care, and losing touch in the final stages. Participants used varied coping strategies such as celebrating the life of the individual who died, engaging in advocacy efforts, not focusing on the loss, participating in therapy, and bringing self-preserving thoughts.

Significance of results

Our study highlights the importance of addressing existential fears in online lung cancer support groups and incorporating conversations about death in spaces that deal with cancer.
Palliative and end-of-life care practices for critically ill patients and their families in a peri-intensive care setting: A protocol for an umbrella review
Authors: Salins Naveen , Rao Arathi P. , Dhyani Vijay Shree , Prasad Ashmitha , Mathew Mebin , Damani Anuja , Rao Krithika , Nair Shreya , Shanbhag Vishal , Rao Shwethapriya , Iyer Shivakumar , Gursahani Roop , Mani R.K. , Simha Srinagesh
Published: February 2024

Objectives

This umbrella review will summarize palliative and end-of-life care practices in peri-intensive care settings by reviewing systematic reviews in intensive care unit (ICU) settings. Evidence suggests that integrating palliative care into ICU management, initiating conversations about care goals, and providing psychological and emotional support can significantly enhance patient and family outcomes.

Methods

The Joanna Briggs Institute (JBI) methodology for umbrella reviews will be followed. The search will be carried out from inception until 30 September 2023 in the following databases: Cochrane Library, SCOPUS, Web of Science, CINAHL Complete, Medline, EMBASE, and PsycINFO. Two reviewers will independently conduct screening, data extraction, and quality assessment, and to resolve conflicts, adding a third reviewer will facilitate the consensus-building process. The quality assessment will be carried out using the JBI Critical Appraisal Checklist. The review findings will be reported per the guidelines outlined in the Preferred Reporting Items for Overviews of Reviews statement.

Results

This umbrella review seeks to inform future research and practice in critical care medicine, helping to ensure that end-of-life care interventions are optimized to meet the needs of critically ill patients and their families.
An advanced solid-state RF power source maximizing energy efficiency for optimal superconducting RF cavity charging
Authors: Hoang Duc Long , Dancila Dragos
Published: February 2024

This paper outlines an experimental demonstration of an envelope tracking (ET) technique applied to a kilowatt-level single-ended solid-state power amplifier (SSPA), aimed at enhancing the charging efficiency of superconducting radio frequency (SRF) cavities by reducing reflection power while maintaining a high degree of efficiency. The technique is particularly designed for the pulsed operation of the European Spallation Source (ESS) at a nominal frequency of 352 MHz, with a 5% duty cycle and a pulse width of 3.5 ms. The study introduces an optimal charging scheme using a solid-state-based amplifier to maintain high efficiency, allowing for power ramp-up while minimizing reflections from SRF cavities and optimizing SSPA efficiency. A fast envelope tracking power supply (ETPS) system is implemented for the approximately 300 ms charging time required by the SRF cavities at ESS. The ETPS system, demonstrated on a single module as a proof-of-concept with scalability potential to a 400 kW power station, indicates an overall average efficiency of 70% and a 24% energy saving over traditional vacuum-tube based amplifiers. This demonstrates the ET technique’s effectiveness at the kilowatt level for efficient SRF cavity charging with reduced reflection, offering significant efficiency and energy savings.
Impact of soil-residual herbicides on industrial hemp (Cannabis sativa) phytotoxicity and biomass yield in west Texas
Authors: Singh Atinderpal , Saini Rupinder , Kafle Arjun , Singh Manpreet , Singh Sukhbir
Published: February 2024

Industrial hemp is a multipurpose crop cultivated for fiber, seed, human food, and animal feed. Hemp legalization in Texas creates a considerable potential to increase its acreage in semi-arid conditions; however, knowledge is limited on growing hemp optimally in Texas. Best management practices, including weed control, require evaluation for profitable hemp production. As little is known about the herbicide tolerance of hemp, field studies were conducted to test several soil-residual herbicides with different modes of action for phytotoxicity to two hemp cultivars, ‘Yuma’ and ‘Jinma’. The experimental units were randomized three times in a blocked split-plot design with hemp cultivars in the main plots and soil-residual herbicides in the subplots. Ethalfluralin, the mixture of sulfentrazone and S-metolachlor, prometryn, and S-metolachlor, resulted in 60% to 90% and 73% to 100% weed control as compared to the nontreated control in 2021 and 2022, respectively. The highest hemp germination, stand count, and plant height were observed with ethalfluralin and S-metolachlor herbicides; however, no significant differences were observed for hemp germination and plant height compared to the nontreated control. S-metolachlor, ethalfluralin, fomesafen, and prometryn resulted in similar hemp biomass compared to the nontreated control. Overall, the results indicate that hemp is tolerant to ethalfluralin, prometryn, and S-metolachlor, and these soil-residual herbicides were effective for weed control in hemp. The mixture of bicyclopyrone plus S-metolachlor, metribuzin plus S-metolachlor, and mesotrione should be avoided, as they caused significant injury to hemp plants. Future research is needed to test the efficacy of different preemergence and postemergence herbicides that can be used in industrial hemp grown under different environments, making sure the delta-9-tetrahydrocannabinol content of the hemp is below the legal content restrictions.
Grape seed extract supplementation in non-alcoholic fatty liver disease
Authors: Ghanbari Parisa , Alboebadi Roghayeh , Bazyar Hadi , Raiesi Davoud , ZareJavid Ahmad , Azadbakht Mohammad Karim , Karimi Mahdi , Razmi Hamidreza
Published: February 2024

Abstract: Background: Despite rising non-alcoholic fatty liver disease (NAFLD) prevalence and its impact on liver health, there’s a lack of studies on grape seed extract’s (GSE) effect on oxidative stress and quality of life (QoL) in NAFLD patients. This study aims to fill this gap by the potential benefits of GSE in reducing oxidative stress and improving QoL. Methods: In this randomized clinical trial study, fifty patients with NAFLD were randomly assigned to receive either 2 tablets of GSE containing 250 mg of proanthocyanidins or placebo (25 participants in each group) for two months. QoL was evaluated using the SF-36 questionnaire, and oxidative stress variables (TAC, MDA, SOD, GPx, CAT, and IL-6) were measured at the beginning and end of the study. Results: Compared with the control group, the group supplemented with GSE experienced greater reductions in IL-6 and MDA (3.14±1.43 pg/ml vs. 2.80±0.31 pg/ml; 4.16±2.09 μM vs. 4.59±1.19 μM, p for all <0.05), as well as greater increases in TAC, SOD, and GPx levels (0.18±0.08 mM vs. –0.03±0.09 mM; 10.5±6.69 U/ml vs. 8.93±1.63 U/ml; 14.7±13.4 U/ml vs. 8.24±3.03 U/ml, p for all <0.05). Furthermore, the QoL questionnaire showed that physical limitations, general health, and total physical health were significantly improved in the GSE group compared with the placebo (17.0±42.0 vs. –12.0±37.5; 3.80±14.8 vs. –3.92±9.55; 5.08 5.26 vs. –7.01±13.7, p for all <0.05). Conclusions: GSE can be effective in improving oxidative stress and QoL in patients with NAFLD. More studies are needed to confirm the results of this study.
The Role of Anthropogenic Forcings on Historical Sea‐Level Change in the Indo‐Pacific Warm Pool Region
Authors: Samanta Dhrubajyoti , Vairagi Vedant , Richter Kristin , McDonagh Elaine L. , Karnauskas Kristopher B. , Goodkin Nathalie F. , Chew Lock Yue , Horton Benjamin P.
Published: February 2024

Detecting and attributing sea‐level rise over different spatiotemporal scales is essential for low‐lying and highly populated coastal regions. Using the Detection and Attribution Model Intercomparison Project (DAMIP) from the Coupled Model Intercomparison Project Phase 6, we evaluate the role of anthropogenic forcing in sea‐level change in the historical (1950–2014) period in the Indo‐Pacific warm pool region. We use three models that have at least 10 ensemble members, corresponding to different DAMIP simulations. We determined the changes in regional sea level from both natural and anthropogenic forcings. Our results demonstrate: (a) the emergence of an anthropogenic footprint on regional sterodynamic sea‐level change has a large spatiotemporal diversity over the Indo‐Pacific warm pool region with the earliest emergence in the western Indian Ocean; (b) a significant rise in dynamic sea level (DSL) (up to 25 mm) and thermosteric (up to 40 mm) sea level over the western Indian Ocean due to greenhouse gas forcing; (c) a positive Indian Ocean Dipole‐like pattern in the DSL changes over the tropical Indian Ocean; (d) a significant increase in the halosteric contribution to sea‐level rise in the Indo‐Pacific warm pool region, and (e) a pronounced rise of manometric sea level (up to 20 mm) over shallow oceans and coastal regions in recent decades. These results provide a comprehensive spatiotemporal analysis of the attribution of anthropogenic factors to sea‐level changes in the Indo‐Pacific warm pool region.
Real‐Time Water Levels Using GNSS‐IR: A Potential Tool for Flood Monitoring
Authors: Purnell D. , Gomez N. , Minarik W. , Langston G.
Published: February 2024

Global Navigation Satellite System Interferometric Reflectometry (GNSS‐IR) using low‐cost antennas is a practical solution for monitoring water levels from rivers, lakes and seas that does not require submerging any instruments in water. Here we present a novel method for obtaining real‐time water levels using multiple low‐cost antennas that we validate by comparing with measurements from a co‐located pressure gauge at two sites with variable tides. Additionally, we use survey measurements to show that there is a site‐dependant mean bias in GNSS‐IR measurements up to a few centimeters, but this mean bias can be effectively removed by using a correction for the effect of tropospheric delay. We conclude that GNSS‐IR water level sensors could be a powerful tool for real‐time applications such as flood or storm surge monitoring and water resource management, as well as for improving the spatial coverage of sensors in remote regions.
Increasing Flood Hazard Posed by Tropical Cyclone Rapid Intensification in a Changing Climate
Authors: Lockwood Joseph W. , Lin Ning , Gori Avantika , Oppenheimer Michael
Published: February 2024

Tropical cyclones (TCs) that undergo rapid intensification (RI) before landfall are notoriously difficult to predict and have caused tremendous damage to coastal regions in the United States. Using downscaled synthetic TCs and physics‐based models for storm tide and rain, we investigate the hazards posed by TCs that rapidly intensify before landfall under both historical and future mid‐emissions climate scenarios. In the downscaled synthetic data, the percentage of TCs experiencing RI is estimated to rise across a significant portion of the North Atlantic basin. Notably, future climate warming causes large increases in the probability of RI within 24 hr of landfall. Also, our analysis shows that RI events induce notably higher rainfall hazard levels than non‐RI events with equivalent TC intensities. As a result, RI events dominate increases in 100‐year rainfall and storm tide levels under climate change for most of the US coastline.
Modeling Equatorial to Mid‐Latitudinal Global Night Time Ionospheric Plasma Irregularities Using Machine Learning
Authors: Seba Ephrem Beshir , Lapenta Giovanni
Published: February 2024

This study focuses on modeling the characteristics of nighttime topside Ionospheric Plasma Irregularities (PI) on a global scale. We utilize Random Forest (RF) and a one‐dimensional Convolutional Neural Network (1D‐CNN) model, incorporating data from the Swarm A, B, and C satellites, space weather data from the OMNIWeb data center, as well as zonal and meridional wind model data. Our objective is to simulate monthly global PI characteristics using a multilayer 1D‐CNN model trained on 12 space weather and ionospheric parameters. In addition, we investigate the most influential input parameters for predicting global nighttime PI characteristics. Our findings indicate that non‐equinox months exhibit the highest equatorial PI magnitude over the American‐African longitudinal sector, contrary to the expected higher Rayleigh‐Taylor instability growth rate during equinox months. Winter months display the most intense and widespread vertically and horizontally distributed equatorial PI patterns. We also observe double peaks across geomagnetic latitudes and longitudinally varying wavelike irregularity structures, particularly in May, August, and predominantly in September. Furthermore, north‐south hemispherical asymmetry in PI observed across different seasons. Through the RF parameter importance analysis method, we determine that temporal, geographical, and magnetic disturbance‐related factors play a crucial role in predicting global PI variabilities. These findings emphasize the significance of these variables in controlling the strongest PI characteristics observed in the Atlantic sector, which has garnered considerable attention in PI research. The employed 1D‐CNN model demonstrates exceptional predictive capabilities, exhibiting a strong correlation of 0.98 for global PI characteristics across all months and satellites.
Introducing the new Editor-in-Chief of JGR: Solid Earth
Authors: Schubnel Alexandre
Published: February 2024

Learn about the person taking the helm of JGR: Solid Earth and his vision for the coming years.
APOE genotype-specific methylation patterns are linked to Alzheimer disease pathology and estrogen response
Authors: Panitch Rebecca , Sahelijo Nathan , Hu Junming , Nho Kwangsik , Bennett David A. , Lunetta Kathryn L. , Au Rhoda , Stein Thor D. , Farrer Lindsay A. , Jun Gyungah R.
Published: February 2024

The joint effects of APOE genotype and DNA methylation on Alzheimer disease (AD) risk is relatively unknown. We conducted genome-wide methylation analyses using 2,021 samples in blood (91 AD cases, 329 mild cognitive impairment, 1,391 controls) and 697 samples in brain (417 AD cases, 280 controls). We identified differentially methylated levels in AD compared to controls in an APOE genotype-specific manner at 25 cytosine-phosphate-guanine (CpG) sites in brain and 36 CpG sites in blood. Additionally, we identified seven CpG sites in the APOE region containing TOMM40, APOE, and APOC1 genes with P < 5 × 10−8 between APOE ε4 carriers and non-carriers in brain or blood. In brain, the most significant CpG site hypomethylated in ε4 carriers compared to non-carriers was from the TOMM40 in the total sample, while most of the evidence was derived from AD cases. However, the CpG site was not significantly modulating expression of these three genes in brain. Three CpG sites from the APOE were hypermethylated in APOE ε4 carriers in brain or blood compared in ε4 non-carriers and nominally significant with APOE expression in brain. Three CpG sites from the APOC1 were hypermethylated in blood, which one of the 3 CpG sites significantly lowered APOC1 expression in blood using all subjects or ε4 non-carriers. Co-methylation network analysis in blood and brain detected eight methylation networks associated with AD and APOE ε4 status. Five of the eight networks included genes containing network CpGs that were significantly enriched for estradiol perturbation, where four of the five networks were enriched for the estrogen response pathway. Our findings provide further evidence of the role of APOE genotype on methylation levels associated with AD, especially linked to estrogen response pathway.
Solar ultraviolet radiation exposure, and incidence of childhood acute lymphocytic leukaemia and non-Hodgkin lymphoma in a US population-based dataset
Authors: Little Mark P. , Mai Jim Z. , Fang Michelle , Chernyavskiy Pavel , Kennerley Victoria , Cahoon Elizabeth K. , Cockburn Myles G. , Kendall Gerald M. , Kimlin Michael G.
Published: February 2024

Background

Acute lymphocytic leukaemia (ALL) and non-Hodgkin lymphoma (NHL) are among the commonest types of childhood cancer. Some previous studies suggested that elevated ultraviolet radiation (UVR) exposures increase ALL risk; many more indicate NHL risk is reduced.

Methods

We assessed age<20 ALL/NHL incidence in Surveillance, Epidemiology and End Results data using AVGLO-derived UVR irradiance/cumulative radiant exposure measures, using quasi-likelihood models accounting for underdispersion, adjusted for age, sex, racial/ethnic group and other county-level socioeconomic variables.

Results

There were 30,349 cases of ALL and 8062 of NHL, with significant increasing trends of ALL with UVR irradiance (relative risk (RR) = 1.200/mW/cm2 (95% CI 1.060, 1.359, p = 0.0040)), but significant decreasing trends for NHL (RR = 0.646/mW/cm2 (95% CI 0.512, 0.816, p = 0.0002)). There was a borderline-significant increasing trend of ALL with UVR cumulative radiant exposure (RR = 1.444/MJ/cm2 (95% CI 0.949, 2.197, p = 0.0865)), and significant decreasing trends for NHL (RR = 0.284/MJ/cm2 (95% CI 0.166, 0.485, p < 0.0001)). ALL and NHL trend RR is substantially increased among those aged 0–3. All-age trend RRs are most extreme (increasing for ALL, decreasing for NHL) for Hispanics for both UVR measures.

Conclusions

Our more novel finding, of excess UVR-related ALL risk, is consistent with some previous studies, but is not clear-cut, and in need of replication.
Boosting exciton mobility approaching Mott-Ioffe-Regel limit in Ruddlesden−Popper perovskites by anchoring the organic cation
Authors: Gong Yiyang , Yue Shuai , Liang Yin , Du Wenna , Bian Tieyuan , Jiang Chuanxiu , Bao Xiaotian , Zhang Shuai , Long Mingzhu , Zhou Guofu , Yin Jun , Deng Shibin , Zhang Qing , Wu Bo , Liu Xinfeng
Published: February 2024

Exciton transport in two-dimensional Ruddlesden−Popper perovskite plays a pivotal role for their optoelectronic performance. However, a clear photophysical picture of exciton transport is still lacking due to strong confinement effects and intricate exciton-phonon interactions in an organic-inorganic hybrid lattice. Herein, we present a systematical study on exciton transport in (BA)2(MA)n−1PbnI3n+1 Ruddlesden−Popper perovskites using time-resolved photoluminescence microscopy. We reveal that the free exciton mobilities in exfoliated thin flakes can be improved from around 8 cm2 V−1 s−1 to 280 cm2V−1s−1 by anchoring the soft butyl ammonium cation with a polymethyl methacrylate network at the surface. The mobility of the latter is close to the theoretical limit of Mott-Ioffe-Regel criterion. Combining optical measurements and theoretical studies, it is unveiled that the polymethyl methacrylate network significantly improve the lattice rigidity resulting in the decrease of deformation potential scattering and lattice fluctuation at the surface few layers. Our work elucidates the origin of high exciton mobility in Ruddlesden−Popper perovskites and opens up avenues to regulate exciton transport in two-dimensional materials.
Probing molecules in gas cells of subwavelength thickness with high frequency resolution
Authors: Arellano Guadalupe Garcia , de Aquino Carvalho Joao Carlos , Mouhanna Hippolyte , Butery Esther , Billeton Thierry , Du-Burck Frederic , Darquié Benoit , Maurin Isabelle , Laliotis Athanasios
Published: February 2024

Miniaturizing and integrating atomic vapor cells is widely investigated for the purposes of fundamental measurements and technological applications such as quantum sensing. Extending such platforms to the realm of molecular physics is a fascinating prospect that paves the way for compact frequency metrology as well as for exploring light-matter interactions with complex quantum objects. Here, we perform molecular rovibrational spectroscopy in a thin-cell of micrometric thickness, comparable to excitation wavelengths. We operate the cell in two distinct regions of the electromagnetic spectrum, probing ν1 + ν3 resonances of acetylene at 1.530 µm, within the telecommunications wavelength range, as well as the ν3 and ν2 resonances of SF6 and NH3 respectively, in the mid-infrared fingerprint region around 10.55 µm. Thin-cell confinement allows linear sub-Doppler transmission spectroscopy due to the coherent Dicke narrowing effect, here demonstrated for molecular rovibrations. Our experiment can find applications extending to the fields of compact molecular frequency references, atmospheric physics or fundamental precision measurements.
Specificity, synergy, and mechanisms of splice-modifying drugs
Authors: Ishigami Yuma , Wong Mandy S. , Martí-Gómez Carlos , Ayaz Andalus , Kooshkbaghi Mahdi , Hanson Sonya M. , McCandlish David M. , Krainer Adrian R. , Kinney Justin B.
Published: February 2024

Drugs that target pre-mRNA splicing hold great therapeutic potential, but the quantitative understanding of how these drugs work is limited. Here we introduce mechanistically interpretable quantitative models for the sequence-specific and concentration-dependent behavior of splice-modifying drugs. Using massively parallel splicing assays, RNA-seq experiments, and precision dose-response curves, we obtain quantitative models for two small-molecule drugs, risdiplam and branaplam, developed for treating spinal muscular atrophy. The results quantitatively characterize the specificities of risdiplam and branaplam for 5’ splice site sequences, suggest that branaplam recognizes 5’ splice sites via two distinct interaction modes, and contradict the prevailing two-site hypothesis for risdiplam activity at SMN2 exon 7. The results also show that anomalous single-drug cooperativity, as well as multi-drug synergy, are widespread among small-molecule drugs and antisense-oligonucleotide drugs that promote exon inclusion. Our quantitative models thus clarify the mechanisms of existing treatments and provide a basis for the rational development of new therapies.
Ferromagnetism on an atom-thick & extended 2D metal-organic coordination network
Authors: Lobo-Checa Jorge , Hernández-López Leyre , Otrokov Mikhail M. , Piquero-Zulaica Ignacio , Candia Adriana E. , Gargiani Pierluigi , Serrate David , Delgado Fernando , Valvidares Manuel , Cerdá Jorge , Arnau Andrés , Bartolomé Fernando
Published: February 2024

Ferromagnetism is the collective alignment of atomic spins that retain a net magnetic moment below the Curie temperature, even in the absence of external magnetic fields. Reducing this fundamental property into strictly two-dimensions was proposed in metal-organic coordination networks, but thus far has eluded experimental realization. In this work, we demonstrate that extended, cooperative ferromagnetism is feasible in an atomically thin two-dimensional metal-organic coordination network, despite only ≈ 5% of the monolayer being composed of Fe atoms. The resulting ferromagnetic state exhibits an out-of-plane easy-axis square-like hysteresis loop with large coercive fields over 2 Tesla, significant magnetic anisotropy, and persists up to TC ≈ 35 K. These properties are driven by exchange interactions mainly mediated by the molecular linkers. Our findings resolve a two decade search for ferromagnetism in two-dimensional metal-organic coordination networks.
Empirical data drift detection experiments on real-world medical imaging data
Authors: Kore Ali , Abbasi Bavil Elyar , Subasri Vallijah , Abdalla Moustafa , Fine Benjamin , Dolatabadi Elham , Abdalla Mohamed
Published: February 2024

While it is common to monitor deployed clinical artificial intelligence (AI) models for performance degradation, it is less common for the input data to be monitored for data drift – systemic changes to input distributions. However, when real-time evaluation may not be practical (eg., labeling costs) or when gold-labels are automatically generated, we argue that tracking data drift becomes a vital addition for AI deployments. In this work, we perform empirical experiments on real-world medical imaging to evaluate three data drift detection methods’ ability to detect data drift caused (a) naturally (emergence of COVID-19 in X-rays) and (b) synthetically. We find that monitoring performance alone is not a good proxy for detecting data drift and that drift-detection heavily depends on sample size and patient features. Our work discusses the need and utility of data drift detection in various scenarios and highlights gaps in knowledge for the practical application of existing methods.
The Deinococcus protease PprI senses DNA damage by directly interacting with single-stranded DNA
Authors: Lu Huizhi , Chen Zijing , Xie Teng , Zhong Shitong , Suo Shasha , Song Shuang , Wang Liangyan , Xu Hong , Tian Bing , Zhao Ye , Zhou Ruhong , Hua Yuejin
Published: February 2024

Bacteria have evolved various response systems to adapt to environmental stress. A protease-based derepression mechanism in response to DNA damage was characterized in Deinococcus, which is controlled by the specific cleavage of repressor DdrO by metallopeptidase PprI (also called IrrE). Despite the efforts to document the biochemical, physiological, and downstream regulation of PprI-DdrO, the upstream regulatory signal activating this system remains unclear. Here, we show that single-stranded DNA physically interacts with PprI protease, which enhances the PprI-DdrO interactions as well as the DdrO cleavage in a length-dependent manner both in vivo and in vitro. Structures of PprI, in its apo and complexed forms with single-stranded DNA, reveal two DNA-binding interfaces shaping the cleavage site. Moreover, we show that the dynamic monomer-dimer equilibrium of PprI is also important for its cleavage activity. Our data provide evidence that single-stranded DNA could serve as the signal for DNA damage sensing in the metalloprotease/repressor system in bacteria. These results also shed light on the survival and acquired drug resistance of certain bacteria under antimicrobial stress through a SOS-independent pathway.
Coherent control of enhanced second-harmonic generation in a plasmonic nanocircuit using a transition metal dichalcogenide monolayer
Authors: Wu Pei-Yuan , Lee Wei-Qing , Liu Chang-Hua , Huang Chen-Bin
Published: February 2024

Nonlinear nanophotonic circuits, renowned for their compact form and integration capabilities, hold potential for advancing high-capacity optical signal processing. However, limited practicality arises from low nonlinear conversion efficiency. Transition metal dichalcogenides (TMDs) could present a promising avenue to address this challenge, given their superior optical nonlinear characteristics and compatibility with diverse device platforms. Nevertheless, this potential remains largely unexplored, with current endeavors predominantly focusing on the demonstration of TMDs’ coherent nonlinear signals via free-space excitation and collection. In this work, we perform direct integration of TMDs onto a plasmonic nanocircuitry. By controlling the polarization angle of the input laser, we show selective routing of second-harmonic generation (SHG) signals from a MoSe2 monolayer within the plasmonic circuit. Routing extinction ratios of 14.86 dB are achieved, demonstrating good coherence preservation in this hybrid nanocircuit. Additionally, our characterization indicates that the integration of TMDs leads to a 13.8-fold SHG enhancement, compared with the pristine nonlinear plasmonic nanocircuitry. These distinct features—efficient SHG generation, coupling, and controllable routing—suggest that our hybrid TMD-plasmonic nanocircuitry could find immediate applications including on-chip optical frequency conversion, selective routing, switching, logic operations, as well as quantum operations.
CAMSAPs and nucleation-promoting factors control microtubule release from γ-TuRC
Authors: Rai Dipti , Song Yinlong , Hua Shasha , Stecker Kelly , Monster Jooske L. , Yin Victor , Stucchi Riccardo , Xu Yixin , Zhang Yaqian , Chen Fangrui , Katrukha Eugene A. , Altelaar Maarten , Heck Albert J. R. , Wieczorek Michal , Jiang Kai , Akhmanova Anna
Published: February 2024

γ-Tubulin ring complex (γ-TuRC) is the major microtubule-nucleating factor. After nucleation, microtubules can be released from γ-TuRC and stabilized by other proteins, such as CAMSAPs, but the biochemical cross-talk between minus-end regulation pathways is poorly understood. Here we reconstituted this process in vitro using purified components. We found that all CAMSAPs could bind to the minus ends of γ-TuRC-attached microtubules. CAMSAP2 and CAMSAP3, which decorate and stabilize growing minus ends but not the minus-end tracking protein CAMSAP1, induced microtubule release from γ-TuRC. CDK5RAP2, a γ-TuRC-interactor, and CLASP2, a regulator of microtubule growth, strongly stimulated γ-TuRC-dependent microtubule nucleation, but only CDK5RAP2 suppressed CAMSAP binding to γ-TuRC-anchored minus ends and their release. CDK5RAP2 also improved selectivity of γ-tubulin-containing complexes for 13- rather than 14-protofilament microtubules in microtubule-capping assays. Knockout and overexpression experiments in cells showed that CDK5RAP2 inhibits the formation of CAMSAP2-bound microtubules detached from the microtubule-organizing centre. We conclude that CAMSAPs can release newly nucleated microtubules from γ-TuRC, whereas nucleation-promoting factors can differentially regulate this process.
A combinatorial genetic strategy for exploring complex genotype–phenotype associations in cancer
Authors: Li Shan , Wong Alicia , Sun Huiyun , Bhatia Vipul , Javier Gerardo , Jana Sujata , Wu Qian , Montgomery Robert B. , Wright Jonathan L. , Lam Hung-Ming , Hsieh Andrew C. , Faltas Bishoy M. , Haffner Michael C. , Lee John K.
Published: February 2024

Available genetically defined cancer models are limited in genotypic and phenotypic complexity and underrepresent the heterogeneity of human cancer. Here, we describe a combinatorial genetic strategy applied to an organoid transformation assay to rapidly generate diverse, clinically relevant bladder and prostate cancer models. Importantly, the clonal architecture of the resultant tumors can be resolved using single-cell or spatially resolved next-generation sequencing to uncover polygenic drivers of cancer phenotypes.
Enhanced risk of record-breaking regional temperatures during the 2023–24 El Niño
Authors: Jiang Ning , Zhu Congwen , Hu Zeng-Zhen , McPhaden Michael J. , Chen Deliang , Liu Boqi , Ma Shuangmei , Yan Yuhan , Zhou Tianjun , Qian Weihong , Luo Jingjia , Yang Xiuqun , Liu Fei , Zhu Yuejian
Published: February 2024

In 2023, the development of El Niño is poised to drive a global upsurge in surface air temperatures (SAT), potentially resulting in unprecedented warming worldwide. Nevertheless, the regional patterns of SAT anomalies remain diverse, obscuring where historical warming records may be surpassed in the forthcoming year. Our study underscores the significant influence of El Niño and the persistence of climate signals on the inter-annual variability of regional SAT, both in amplitude and spatial distribution. The likelihood of global mean SAT exceeding historical records, calculated from July 2023 to June 2024, is estimated at 90%, contingent upon annual-mean sea surface temperature anomalies in the eastern equatorial Pacific exceeding 0.6 °C. Regions particularly susceptible to recording record-high SAT include coastal and adjacent areas in Asia such as the Bay of Bengal and the South China Sea, as well as Alaska, the Caribbean Sea, and the Amazon. This impending warmth heightens the risk of year-round marine heatwaves and escalates the threat of wildfires and other negative consequences in Alaska and the Amazon basin, necessitating strategic mitigation measures to minimize potential worst-case impacts.
IL-6 and IL-17 as potential links between pre-existing hypertension and long-term COVID sequelae in patients undergoing hemodialysis: a multicenter cross-sectional study
Authors: Stepanova Natalia , Driianska Victoria , Rysyev Andriy , Ostapenko Tetyana , Kalinina Nataliia
Published: February 2024

Long COVID, characterized by persistent symptoms following acute infection, poses a significant health challenge, particularly for patients with pre-existing chronic conditions such as hypertension. We hypothesized that an increase in the production of interleukins (IL)-6 and IL-17 could serve as a potential mechanism linking pre-existing uncontrolled blood pressure (BP) to the occurrence of long-term COVID sequelae in patients undergoing hemodialysis (HD). This cross-sectional study examined serum IL-6 and IL-17 levels in 80 patients undergoing HD, considering preinfection BP, the presence of long-term COVID sequelae, and the time interval after acute COVID-19 infection, which was either 5 or 10 months. Controlled BP was defined as a 3-month average pre-dialysis BP < 140/90 mmHg and post-dialysis < 130/80 mmHg. The findings suggest that the prevalence of long-term COVID sequelae was significantly higher in patients with uncontrolled BP than in the BP-controlled group. Both IL-6 and IL-17 concentrations were also significantly higher in patients with uncontrolled BP compared with the BP-controlled group. The patients with long-term COVID sequelae had higher IL-6 and IL-17 values than the fully recovered patients at both time points, but their concentrations decreased significantly over time. Further research and prospective studies are warranted to validate these findings.
Patient leaflets on respiratory tract infections did not improve shared decision making and antibiotic prescriptions in a low-prescriber setting
Authors: Plate Andreas , Di Gangi Stefania , Garzoni Christian , Selby Kevin , Pichierri Giuseppe , Senn Oliver , Neuner-Jehle Stefan
Published: February 2024

Patient information leaflets can reduce antibiotic prescription rates by improving knowledge and encouraging shared decision making (SDM) in patients with respiratory tract infections (RTI). The effect of these interventions in antibiotic low-prescriber settings is unknown. We conducted a pragmatic pre-/post interventional study between October 2022 and March 2023 in Swiss outpatient care. The intervention was the provision of patient leaflets informing about RTIs and antibiotics use. Main outcomes were the extent of SDM, antibiotic prescription rates, and patients’ awareness/knowledge about antibiotic use in RTIs. 408 patients participated in the pre-intervention period, and 315 patients in the post- intervention period. There was no difference in the extent of SDM (mean score (range 0–100): 65.86 vs. 64.65, p = 0.565), nor in antibiotic prescription rates (no prescription: 89.8% vs. 87.2%, p = 0.465) between the periods. Overall awareness/knowledge among patients with RTI was high and leaflets showed only a small effect on overall awareness/knowledge. In conclusion, in an antibiotic low-prescriber setting, patient information leaflets may improve knowledge, but may not affect treatment decisions nor antibiotic prescription rates for RTIs.
Occurrence and diversity of stem nodulation in Aeschynomene and Sesbania legumes from wetlands of Madagascar
Authors: Manantsoa Faustin F. , Rakotoarisoa Marrino F. , Chaintreuil Clémence , Razakatiana Adamson T. E. , Gressent Frédéric , Pervent Marjorie , Bourge Mickaël , Andrianandrasana Martial D. , Nouwen Nico , Randriambanona Herizo , Ramanankierana Heriniaina , Arrighi Jean-François
Published: February 2024

Legumes have the ability to establish a nitrogen-fixing symbiosis with soil rhizobia that they house in specific organs, the nodules. In most rhizobium-legume interactions, nodulation occurs on the root. However, certain tropical legumes growing in wetlands possess a unique trait: the capacity to form rhizobia-harbouring nodules on the stem. Despite the originality of the stem nodulation process, its occurrence and diversity in waterlogging-tolerant legumes remains underexplored, impeding a comprehensive analysis of its genetics and biology. Here, we aimed at filling this gap by surveying stem nodulation in legume species-rich wetlands of Madagascar. Stem nodulation was readily observed in eight hydrophytic species of the legume genera, Aeschynomene and Sesbania, for which significant variations in stem nodule density and morphology was documented. Among these species, A. evenia, which is used as genetic model to study the rhizobial symbiosis, was found to be frequently stem-nodulated. Two other Aeschynomene species, A. cristata and A. uniflora, were evidenced to display a profuse stem-nodulation as occurs in S. rostrata. These findings extend our knowledge on legumes species that are endowed with stem nodulation and further indicate that A. evenia, A. cristata, A. uniflora and S. rostrata are of special interest for the study of stem nodulation. As such, these legume species represent opportunities to investigate different modalities of the nitrogen-fixing symbiosis and this knowledge could provide cues for the engineering of nitrogen-fixation in non-legume crops.
Semi-automated approaches for interrogating spatial heterogeneity of tissue samples
Authors: Navikas Vytautas , Kowal Joanna , Rodriguez Daniel , Rivest François , Brajkovic Saska , Cassano Marco , Dupouy Diego
Published: February 2024

Tissues are spatially orchestrated ecosystems composed of heterogeneous cell populations and non-cellular elements. Tissue components’ interactions shape the biological processes that govern homeostasis and disease, thus comprehensive insights into tissues’ composition are crucial for understanding their biology. Recently, advancements in the spatial biology field enabled the in-depth analyses of tissue architecture at single-cell resolution, while preserving the structural context. The increasing number of biomarkers analyzed, together with whole tissue imaging, generate datasets approaching several hundreds of gigabytes in size, which are rich sources of valuable knowledge but require investments in infrastructure and resources for extracting quantitative information. The analysis of multiplex whole-tissue images requires extensive training and experience in data analysis. Here, we showcase how a set of open-source tools can allow semi-automated image data extraction to study the spatial composition of tissues with a focus on tumor microenvironment (TME). With the use of Lunaphore COMET platform, we interrogated lung cancer specimens where we examined the expression of 20 biomarkers. Subsequently, the tissue composition was interrogated using an in-house optimized nuclei detection algorithm followed by a newly developed image artifact exclusion approach. Thereafter, the data was processed using several publicly available tools, highlighting the compatibility of COMET-derived data with currently available image analysis frameworks. In summary, we showcased an innovative semi-automated workflow that highlights the ease of adoption of multiplex imaging to explore TME composition at single-cell resolution using a simple slide in, data out approach. Our workflow is easily transferrable to various cohorts of specimens to provide a toolset for spatial cellular dissection of the tissue composition.
Weak evidence of density dependent population regulation when using the ability of two simple density dependent models to predict population size
Authors: Gebreyohannes Demissew T. , Houlahan Jeff E.
Published: February 2024

The relative importance of density dependence regulation in natural population fluctuations has long been debated. The concept of density dependence implies that current abundance is determined by historical abundance. We have developed four models—two density dependent and two density independent—to predict population size one year beyond the training set and used predictive performance on more than 16,000 populations from 14 datasets to compare the understanding captured by those models. For 4 of 14 datasets the density dependent models make better predictions (i.e., density dependent regulated) than either of the density independent models. However, neither of the density dependent models is statistically significantly superior to density independent models for any of the 14 datasets. We conclude that the evidence for widespread density dependent population regulation in the forms represented by these two simple density-dependent models is weak. However, the density dependent models used here—the Logistic and Gompertz models—are simple representations of how population density might regulate natural populations and only examine density-dependent effects on population size. A comprehensive assessment of the relative importance of density-dependent population regulation will require testing the predictive ability of a wider range of density-dependent models including models examining effects on population characteristics other than population size.
Perception of temporal synchrony not a prerequisite for multisensory integration
Authors: Jertberg Robert M. , Begeer Sander , Geurts Hilde M. , Chakrabarti Bhismadev , Van der Burg Erik
Published: February 2024

Temporal alignment is often viewed as the most essential cue the brain can use to integrate information from across sensory modalities. However, the importance of conscious perception of synchrony to multisensory integration is a controversial topic. Conversely, the influence of cross-modal incongruence of higher level stimulus features such as phonetics on temporal processing is poorly understood. To explore the nuances of this relationship between temporal processing and multisensory integration, we presented 101 participants (ranging from 19 to 73 years of age) with stimuli designed to elicit the McGurk/MacDonald illusion (either matched or mismatched pairs of phonemes and visemes) with varying degrees of stimulus onset asynchrony between the visual and auditory streams. We asked them to indicate which syllable they perceived and whether the video and audio were synchronized on each trial. We found that participants often experienced the illusion despite not perceiving the stimuli as synchronous, and the same phonetic incongruence that produced the illusion also led to significant interference in simultaneity judgments. These findings challenge the longstanding assumption that perception of synchrony is a prerequisite to multisensory integration, support a more flexible view of multisensory integration, and suggest a complex, reciprocal relationship between temporal and multisensory processing.
The Tuning in to Kids parenting program delivered online improves emotion socialization and child behavior in a first randomized controlled trial
Authors: Burkhardt Susan C. A. , Röösli Patrizia , Müller Xenia
Published: February 2024

Emotion-focused parenting interventions have only rarely been evaluated systematically in Europe. This study investigates the effectiveness of “Tuning in to Kids” (TIK) from Australia delivered online in a randomized controlled trial. TIK is a six-week emotion-focused group parenting program that has shown to improve many aspects of parent emotion socialization as well as child problem behavior in several different countries across cultures. Parents (N = 141) of children between 3 and 6 years of age were included in the study and randomly assigned to an intervention and wait-list control group. The intervention was delivered online due to the worldwide COVID-19 pandemic in spring 2021 (intervention group) and one year later (control group) in Switzerland. Parents’ beliefs about emotions, their reported reactions to the child’s negative emotions, family emotional climate, and child behavior (internalizing and externalizing) improved after the intervention and stayed better until the 6 months follow-up in the intervention group, but not in the wait-list controls. Adherence to the program was very high. This study shows that parent emotion socialization practice is changeable with small effects even on child behavior and even after online delivery. This possibly makes Tuning in to Kids a promising emotion-focused parenting intervention when delivered online as an interactive group webinar.
Severe COVID-19 and long COVID are associated with high expression of STING, cGAS and IFN-α
Authors: Queiroz Maria Alice Freitas , Brito Wandrey Roberto dos Santos , Pereira Keise Adrielle Santos , Pereira Leonn Mendes Soares , Amoras Ednelza da Silva Graça , Lima Sandra Souza , Santos Erika Ferreira dos , Costa Flávia Póvoa da , Sarges Kevin Matheus Lima de , Cantanhede Marcos Henrique Damasceno , Brito Mioni Thieli Figueiredo Magalhães d , Silva Andréa Luciana Soares da , Leite Mauro de Meira , Viana Maria de Nazaré do Socorro de Almei , Rodrigues Fabíola Brasil Barbosa , Silva Rosilene da , Viana Giselle Maria Rachid , Chaves Tânia do Socorro Souza , Veríssimo Adriana de Oliveira Lameira , Carvalho Mayara da Silva , Henriques Daniele Freitas , Silva Carla Pinheiro da , Nunes Juliana Abreu Lima , Costa Iran Barros , Cayres-Vallinoto Izaura Maria Vieira , Brasil-Costa Igor , Quaresma Juarez Antônio Simões , Falcão Luiz Fábio Magno , Santos Eduardo José Melo dos , Vallinoto Antonio Carlos Rosário
Published: February 2024

The cGAS-STING pathway appears to contribute to dysregulated inflammation during coronavirus disease 2019 (COVID-19); however, inflammatory factors related to long COVID are still being investigated. In the present study, we evaluated the association of cGAS and STING gene expression levels and plasma IFN-α, TNF-α and IL-6 levels with COVID-19 severity in acute infection and long COVID, based on analysis of blood samples from 148 individuals, 87 with acute COVID-19 and 61 in the post-COVID-19 period. Quantification of gene expression was performed by real-time PCR, and cytokine levels were quantified by ELISA and flow cytometry. In acute COVID-19, cGAS, STING, IFN-α, TNF-α, and IL-6 levels were higher in patients with severe disease than in those with nonsevere manifestations (p < 0.05). Long COVID was associated with elevated cGAS, STING and IFN-α levels (p < 0.05). Activation of the cGAS-STING pathway may contribute to an intense systemic inflammatory state in severe COVID-19 and, after infection resolution, induce an autoinflammatory disease in some tissues, resulting in long COVID.