bluuebunny/crossref_metadata_2025 huggingface dataset:
Examining Ethical and Social Implications of Digital Mental Health Technologies Through Expert Interviews and Sociotechnical Systems Theory
Authors: Adams Jonathan
Published: May 2024

This paper aims to understand how science and technology experts working in the digital mental health field interpret the ethical and social implications of its technologies, combining an ‘expert interview’ methodology with insights from sociotechnical systems theory. Following recruitment of experts in science and technology fields who had experience of supporting the development of DMH interventions, 11 semi-structured interviews were conducted and analyzed in accordance with the Framework Method. A single theme of ‘complexity of implications’ is presented here and divided into the categories of ‘implications for users’, ‘implications for healthcare professionals and systems’, and ‘implications for society’. Participants identified a range of ethical and social implications of digital mental health technologies at the three different levels, which this discussion relates to three key aspects of complex sociotechnical systems identified in existing theoretical work. These are ‘heterogeneity’, ‘interdependence’ and ‘distribution’, each of which raises important questions for future research about how complex values, relationships and responsibilities should be negotiated in digital mental health. The paper concludes that this study’s approach provides a model for understanding the implications of digital health more broadly, with participants’ combined experience and knowledge shedding light on key interventions at the forefront of digitalization in healthcare.
Nonlinearities detection in river-tide interaction in Río Negro hydrographic lower basin (Argentina) using higher-order spectra
Authors: García Bu Bucogen Grethel , Huck Gabriel Eduardo , Piccolo María Cintia , Bohn Vanesa Yael , Perillo Gerardo Miguel Eduardo
Published: May 2024

The nonlinear interactions between river discharge, astronomical tidal wave, and local geomorphology during storm passage or water release from upstream dams can produce severe floods in the Río Negro lower basin (Argentina). For this reason, this paper aims to detect and study nonlinear processes in this area. The watercourse hydrodynamics was described using hourly water level data from three limnigraphs during 2003 – 2021 and flow time series. The tide gauge dataset was employed to describe the influence of tidal cycles on the hydrological regimen. Nonlinear processes' impact on the astronomical tidal cycle and river discharge was analyzed using Harmonic Analysis, and Fourier higher-order spectra, also it was complemented with the selection of two study cases. Harmonic Analysis results showed that the tidal wave entry upstream of the Río Negro modulates its hydrological regime, presenting the water column semidiurnal variations. Also, high-order spectral analysis detected nonlinear interactions in the signal in storm conditions with an energetic redistribution among the linear tidal constituents toward shallow water harmonics. Additionally, nonlinear interactions provoked a delay in the tidal ebb phase with a consequential extension of flooding duration time. This type of study contributes to the knowledge of the flood mechanisms activated during a storm.
“Electrical impedance tomography during open heart surgery and on the cardiac icu is feasible to monitor ventilation in children with congenital heart disease”
Authors: Clausen Jan-Christoph , Emeis Michael , Kleine-Brueggeney Maren , Cho Mi-Young , Kneyber Martin , Miera Oliver
Published: May 2024

Alveolar de recruitment is a common problem during general anesthesia and operations. Pediatric cardiac surgery with cardiopulmonary Bypass is associated with interruption of ventilation and might enhance loss of Ventilation compared to other surgical procedures. Electrical impedance tomography (EIT) allows for monitoring of ventilation distribution and can be helpful in detecting pulmonary de recruitment. This case series demonstrates for the first time that EIT is feasible during open heart surgery and in patients with open chest on the ICU using adapted belts in pediatric patients. It might be helpful to monitor changes in tidal volume distribution, to detect loss of Ventilation during surgery and to guide recruitment maneuvers. Study registration: NCT06270485, clincialtrials.gov, 02/02/2024.
New materials of acanthomorphic acritarchs from the Ediacaran Weng'an Biota (South China)
Authors: Wu Junxian , Sun Weichen , Shang Xiaodong , Liu Pengju , Zhu Maoyan , Yin Zongjun
Published: May 2024

The Weng'an Biota from the Ediacaran Doushantuo Formation in Guizhou Province, southwestern China, is known for its three-dimensionally phosphatized acritarchs, multicellular algae, and embryo-like animal fossils. Among these diverse microfossils, acanthomorphic acritarchs have played a significant role in the biostratigraphic subdivision and correlation of the lower-middle Ediacaran System. However, most previous studies on the biostratigraphy of the Doushantuo Formation in the Weng'an area have focused on large acanthomorphic acritarchs (LAAs, vesicle diameter >200 μm), whereas the smaller acanthomorphic acritarchs (SAAs, vesicle diameter <100 μm) from the Weng'an Biota have been largely overlooked. In this study, we examined >500 thin sections and discovered a large number of well-preserved, small (<100 μm) and medium-sized acanthomorphic acritarchs (MAAs, vesicle diameter ranging 100–200 μm). In total, we have identified SAAs in four genera and six species (Tanarium conoideumKolosova, 1991, emend. Moczydłowska et al., 1993;Tanarium elegansLiu et al., 2014;Mengeosphaera membraniferaShang, Liu, and Moczydłowska, 2019;Mengeosphaera minimaLiu et al., 2014;Estrella rectaLiu and Moczydłowska, 2019;Variomargosphaeridium gracileXiao et al., 2014), as well as two types of MAAs (Tanarium tuberosumMoczydłowska, Vidal, and Rudavskaya, 1993, emend. Moczydłowska, 2015;Weissiellacf.W. grandistellaVorob'eva, Sergeev, and Knoll, 2009, emend. Liu and Moczydłowska, 2019). This updated acritarch assemblage of the Weng'an Biota is valuable for correlating the Ediacaran Doushantuo Formation between the Weng'an and Yangtze Gorges areas. It also serves as a tool to test the proposed acritarch biozones in Ediacaran formations of South China and other localities, including Australia, Siberia, and the East European Platform.
Subnanosecond Electromagnetic Pulse Generated by a Long Spark Discharge: Lightning Implication
Authors: Gushchin M. E. , Zudin I. Yu. , Vershinin I. M. , Mikryukov P. A. , Syssoev V. S. , Sukharevsky D. I. , Orlov A. I. , Naumova M. Yu. , Kuznetsov Yu. A. , Shvets N. N. , Mareev E. A.
Published: May 2024

The effects of generating pulsed radiation by a long spark discharge are important for the development of lightning models and applications related to lightning protection. In experiments with a Marx generator simulating a lightning discharge, we detected the radiation in the form of a single ultrawideband electromagnetic pulse (UWB EMP) about 200 ps in duration, and rising time about 100 ps. UWB EMP generation occurs during the breakdown of a “rod–rod” 4 m long gap. Pulses of almost unipolar shape are observed in more than half of all positive discharges. EMP emission occurs before the main stage, and corresponds to the start of the upward leader from a grounded electrode. In negative discharges, pulses are also observed, but less frequently and with a smaller amplitude. The UWB EMPs, given their large amplitude (more than 100 V/m at a distance of 90 m from the discharge), can be considered as possible new lightning damage factors.
Methanogenic Archaea as Catalysts for Magnetite Formation in Iron‐Rich Marine Sediments
Authors: Lin Zhiyong , Lin Haixin , Strauss Harald , Roberts Andrew P. , Niu Mingyang , Fang Yunxin , Yang Tao , Sun Xiaoming , Birgel Daniel , Peckmann Jörn
Published: May 2024

Fine‐grained authigenic magnetite has been recognized increasingly in iron‐rich marine environments affected by methane seepage and is a major sedimentary magnetization source. However, it is unknown whether this magnetite forms via microbial or abiotic processes. We report here abundant fine magnetite crystals, in close association with goethite, within coarse‐grained sediments from two adjacent methane seepage sites in the South China Sea. The magnetite‐ and goethite‐rich horizons have sharply increased Zr/Ti, Zr/Rb, Ti/Al, and Fe/Al ratios, probably reflecting deposition by turbidity currents. Deeper intervals have elevated pyrite content, positive δ34S excursions of chromium reducible sulfur, and low magnetic susceptibilities, which is consistent with past sulfate‐driven anaerobic oxidation of methane in environments with dynamically variable seepage intensity. In magnetically extracted aggregates (>63 μm), magnetite particles are mainly clustered euhedral crystals with 0.2–0.8 μm sizes, which will likely impact sedimentary magnetic signals. The fine, euhedral crystalline nature of the magnetite suggests formation in sulfide‐free, ferrous iron‐rich sedimentary environments. Based on 16S rRNA gene sequences, anaerobic methanotrophic archaea coincide with pyrite rich horizons. In contrast, two co‐occurring methanogenic archaea groups of the Methanomicrobia class (mainly Methanosarcina and Methanocella) are particularly abundant in turbidites but have low abundance in all other horizons. Increased Methanomicrobia abundances suggest that this class of archaea may be involved in microbial iron reduction in turbidites with abundant goethite as a reactive iron source, and that they apparently trigger magnetite formation. Our findings provide new clues to microbial magnetite formation in iron‐rich marine sediments.
An Isotope Mass Balance Analysis of Evaporative Loss From Lake Turkana, Kenya Using δ18O and δD of Natural Waters
Authors: Saslaw M. , Yang D. , Lee D. , Poulsen C. J. , Henkes G. A.
Published: May 2024

Measurements of oxygen and hydrogen stable isotope ratios (δ18O and δD) in meteoric waters provide insight to overlapping effects of evaporation, precipitation, and mixing on basin scale hydrology. This study of waters collected between 2016 and 2021 in the Turkana Basin, northern Kenya, uses δ18O and δD to understand water balance in Lake Turkana, a large, low‐latitude, alkaline desert lake. The Omo River, a major river system in the Ethiopian Highlands, is historically understood to provide approximately 90% of the water input to Lake Turkana. Discharge of the Omo is prohibitively difficult to measure, but stable isotope ratios in the lake may provide a meaningful method for monitoring the lake's response to changes in input. Precipitation in the Turkana Basin is low (<200 mm/year) with negligible rainfall on the lake's surface, and all water loss from the lake is evaporative. We compare new measurements with previous data from the region and records of lake height and precipitation from the same time period. We show that a Bayesian approach to modeling evaporation using atmospheric conditions and river δ18O and δD yields results consistent with published water balance models. Continued sampling of lake and meteoric waters in the Turkana Basin will be a useful way to monitor the lake's response to regional and global climate change.
Revealing the EMIC Wave Frequency Differences in the Ionosphere via Coordinated Observations: A Case Study
Authors: Ouyang Xin‐Yan , Yue Chao , Wang Yong‐Fu , Ren Jie , Yang Mu‐Ping , Wang Ya‐Lu , Wu Ying‐Yan , Zhang Xue‐Min
Published: May 2024

We study electromagnetic ion cyclotron (EMIC) waves based on observations from the ionosphere, magnetosphere, and ground during a geomagnetic storm recovery phase on 28 August 2018. In this case, multiple ducting EMIC waves in the ionosphere show higher frequencies in the post‐midnight than those in the pre‐midnight. Ionospheric EMIC wave frequency differences in magnetic local time (MLT) are consistent with MLT frequency differences in the equatorial magnetosphere, which are mainly caused by different background magnetic field at different L‐shells. Moreover, we report the first observation of frequency range selections in ionospheric ducting EMIC waves and find that frequency selections depend on the magnetic field intensity in the main part of the ionospheric waveguide, with higher frequency corresponding to larger magnetic field. This study reveals the important role of background magnetic field in regulating ducting EMIC wave frequencies in the ionosphere.
A Pressure Pulse‐Driven Transient Magnetospheric Event
Authors: Sibeck D. G. , Lee S.‐H.
Published: May 2024

Bursty reconnection models predict that flux transfer events (FTEs) moving along the magnetopause launch fast mode compressional waves into the magnetosheath that push the bow shock outward. By contrast, increases in the solar wind density striking the bow shock should push that boundary inward and launch fast mode compressional waves that propagate across the magnetosheath, drive waves on the magnetopause, and generate transient events in the outer magnetosphere. Multipoint ACE, Wind, THEMIS, and GOES‐11/12 solar wind, bow shock, and magnetospheric observations on 14 October 2008 provide direct evidence for solar wind pressure pulses producing a large amplitude indentation with crater FTE‐like properties on the magnetopause.
Joint effects of traffic-related air pollution and hypertensive disorders of pregnancy on maternal postpartum depressive and anxiety symptoms
Authors: Hu Yuhong , Chavez Thomas , Eckel Sandrah P. , Yang Tingyu , Chen Xinci , Vigil Mario , Pavlovic Nathan , Lurmann Fred , Lerner Deborah , Lurvey Nathana , Grubbs Brendan , Al-Marayati Laila , Toledo-Corral Claudia , Johnston Jill , Dunton Genevieve F. , Farzan Shohreh F. , Habre Rima , Breton Carrie , Bastain Theresa M.
Published: May 2024

Background

Ambient air pollution has been linked to postpartum depression. However, few studies have investigated the effects of traffic-related NOx on postpartum depression and whether any pregnancy-related factors might increase susceptibility.

Objectives

To evaluate the association between traffic-related NOx and postpartum depressive and anxiety symptoms, and effect modification by pregnancy-related hypertension.

Methods

This study included 453 predominantly low-income Hispanic/Latina women in the MADRES cohort. Daily traffic-related NOx concentrations by road class were estimated using the California LINE-source dispersion model (CALINE4) at participants’ residential locations and averaged across pregnancy. Postpartum depressive and anxiety symptoms were evaluated by a validated questionnaire (Postpartum Distress Measure, PDM) at 1, 3, 6 and 12 months postpartum. Multivariate linear regressions were performed to estimate the associations at each timepoint. Interaction terms were added to the linear models to assess effect modification by hypertensive disorders of pregnancy (HDPs). Repeated measurement analyses were conducted by using mixed effect models.

Results

We found prenatal traffic-related NOx was associated with increased PDM scores. Specifically, mothers exposed to an IQR (0.22 ppb) increase in NOx from major roads had 3.78% (95% CI: 0.53–7.14%) and 5.27% (95% CI: 0.33–10.45%) significantly higher 3-month and 12-month PDM scores, respectively. Similarly, in repeated measurement analyses, higher NOx from major roads was associated with 3.06% (95% CI: 0.43–5.76%) significantly higher PDM scores across the first year postpartum. Effect modification by HDPs was observed: higher freeway/highway and total NOx among mothers with HDPs were associated with significantly higher PDM scores at 12 months postpartum compared to those without HDPs.

Impact

This study shows that prenatal traffic-related air pollution was associated with postpartum depressive and anxiety symptoms. The study also found novel evidence of greater susceptibility among women with HDPs, which advances the understanding of the relationships between air pollution, maternal cardiometabolic health during pregnancy and postpartum mental health. Our study has potential implications for clinical intervention to mitigate the effects of traffic-related pollution on postpartum mental health disorders. The findings can also offer valuable insights into urban planning strategies concerning the implementation of emission control measures and the creation of green spaces.
Characteristics of oral health of patients with X-linked hypophosphatemia: case reports and literature review
Authors: Arhar Ana , Pavlič Alenka , Hočevar Luka
Published: May 2024

Background

Oral health is impaired in X-linked hypophosphatemia (XLH), resulting in delayed dental development, malocclusion, and radiographic abnormalities. This study investigates the oral manifestations in Slovenian XLH patients, focusing on enamel and dentin abnormalities and a literature review of spontaneous periapical abscesses in XLH cases.

Objectives

To report XLH patients with specific oral signs and symptoms, histological analysis of affected teeth, and review of reported cases of XLH patients with spontaneous periapical abscesses.

Methods

Case reports: Seven XLH patients from the National Registry of Patients with Rare Diseases underwent a detailed oral examination, including X-ray reviews. The patients who were expected to have tooth exfoliation or extraction were asked to donate their teeth for histological analysis by scanning electron microscopy. Literature search: A literature search of four electronic databases and a manual bibliography search aimed to identify documented cases of XLH with periapical abscesses up to January 21, 2024. Inclusion criteria were confirmed XLH patients with periapical abscesses in English peer-reviewed publications.

Results

Tooth samples from three XLH patients showed reduced dentin mineralisation, affecting one-third to one-half of the outer dentin. Inadequate mineralisation, uneven dentin tubules, and cracks and chipping in the enamel were observed, indicating mineralisation deviations. Similar cracks extended into the dentin and were also present in the root of the examined tooth. Based on the content of the 75 items identified in the search, spontaneous abscesses are not uncommon in patients with XLH.

Conclusions

XLH significantly affects patients’ lives and requires lifelong treatment. Dental examinations consistently revealed oral problems, including malocclusion. Histological analysis confirmed structural changes, especially in the dentin. Despite continued treatment, XLH patients may have an increased risk of oral pathologies. Further research is needed to understand the impact of XLH and its treatment on dental health.
Comparison of infectious complications with BCMA-directed therapies in multiple myeloma
Authors: Nath Karthik , Shekarkhand Tala , Nemirovsky David , Derkach Andriy , Costa Bruno Almeida , Nishimura Noriko , Farzana Tasmin , Rueda Colin , Chung David J. , Landau Heather J. , Lahoud Oscar B. , Scordo Michael , Shah Gunjan L. , Hassoun Hani , Maclachlan Kylee , Korde Neha , Shah Urvi A. , Tan Carlyn Rose , Hultcrantz Malin , Giralt Sergio A. , Usmani Saad Z. , Shahid Zainab , Mailankody Sham , Lesokhin Alexander M.
Published: May 2024

B-cell-maturation-antigen (BCMA)-directed therapies are highly active for multiple myeloma, but infections are emerging as a major challenge. In this retrospective, single-center analysis we evaluated infectious complications after BCMA-targeted chimeric-antigen-receptor T-cell therapy (CAR-T), bispecific-antibodies (BsAb) and antibody-drug-conjugates (ADC). The primary endpoint was severe (grade ≥3) infection incidence. Amongst 256 patients, 92 received CAR-T, 55 BsAb and 109 ADC. The incidence of severe infections was higher with BsAb (40%) than CAR-T (26%) or ADC (8%), including grade 5 infections (7% vs 0% vs 0%, respectively). Comparing T-cell redirecting therapies, the incidence rate of severe infections was significantly lower with CAR-T compared to BsAb at 1-year (incidence-rate-ratio [IRR] = 0.43, 95%CI 0.25−0.76, P = 0.004). During periods of treatment-emergent hypogammaglobulinemia, BsAb recipients had higher infection rates (IRR:2.27, 1.31−3.98, P = 0.004) and time to severe infection (HR 2.04, 1.05–3.96, P = 0.036) than their CAR-T counterparts. During periods of non-neutropenia, CAR-T recipients had a lower risk (HR 0.44, 95%CI 0.21−0.93, P = 0.032) and incidence rate (IRR:0.32, 95% 0.17–0.59, P < 0.001) of severe infections than BsAb. In conclusion, we observed an overall higher and more persistent risk of severe infections with BsAb. Our results also suggest a higher infection risk during periods of hypogammaglobulinemia with BsAb, and with neutropenia in CAR-T recipients.
Imatinib with intensive chemotherapy in AML with t(9;22)(q34.1;q11.2)/BCR::ABL1. A DATAML registry study
Authors: Gondran Camille , Dumas Pierre-Yves , Bérard Emilie , Bidet Audrey , Delabesse Eric , Tavitian Suzanne , Leguay Thibaut , Huguet Françoise , Borel Cécile , Forcade Edouard , Vergez François , Vial Jean-Philippe , Rieu Jean Baptiste , Lechevalier Nicolas , Luquet Isabelle , Canali Alban , Klein Emilie , Sarry Audrey , de Grande Anne-Charlotte , Pigneux Arnaud , Récher Christian , Largeaud Laetitia , Bertoli Sarah
Published: May 2024

Acute myeloid leukemia (AML) with t(9;22) (q34.1; q11.2)/BCR::ABL1, a distinct entity within the group of AML with defining genetic abnormalities, belong to the adverse-risk group of the 2022 ELN classification. However, there is little data on outcome since the era of tyrosine kinase inhibitors. Among 5819 AML cases included in the DATAML registry, 20 patients with de novo BCR::ABL1+AML (0.3%) were identified. Eighteen patients treated with standard induction chemotherapy were analyzed in this study. Imatinib was added to chemotherapy in 16 patients. The female-to-male ratio was 1.25 and median age was 54 years. The t(9;22) translocation was the sole chromosomal abnormality in 12 patients. Main gene mutations detected by NGS were ASXL1, RUNX1 and NPM1. Compared with patients with myeloid blast phase of chronic myeloid leukemia (CML-BP), de novo BCR::ABL1+AML had higher WBC, fewer additional chromosomal abnormalities, lower CD36 or CD7 expression and no ABL1 mutations. Seventeen patients (94.4%) achieved complete remission (CR) or CR with incomplete hematologic recovery. Twelve patients were allografted in first remission. With a median follow-up of 6.3 years, the median OS was not reached and 2-year OS was 77% (95% CI: 50–91). Four out of five patients who were not transplanted did not relapse. Comparison of BCR::ABL1+AML, CML-BP, 2017 ELN intermediate (n = 643) and adverse-risk patients (n = 863) showed that patients with BCR::ABL1+AML had a significant better outcome than intermediate and adverse-risk patients. BCR::ABL1+AML patients treated with imatinib and intensive chemotherapy should not be included in the adverse-risk group of current AML classifications.
Interfacing exogenous stents with human coronary artery by self-assembled coating: designs, functionalities and applications
Authors: Zhao Feng , Liu Feng , Gao Chenglong , Wang Guoqing , Zhang Yinfeng , Yu Fei , Tian Jiawei , Tan Kai , Zhang Runhao , Liang Kang , Lian Zhexun , Guo Junjie , Kong Biao , Ge Junbo , Xin Hui
Published: May 2024

Drug-eluting stents are a commonly used treatment for coronary artery disease. However, the coatings used in drug-eluting stents have some limitations such as poor biocompatibility and drug loading capacity. In recent years, self-assembly methods have emerged as a promising alternative for stent coatings. Self-assembled coatings employ biomaterials and offer several advantages over traditional coatings, including thinner thickness, stronger binding capacity, and better biocompatibility. This review discusses the latest research on self-assembled biomaterial-based coatings for drug-eluting stents. We explore how layer-by-layer coatings and composite coating films have been utilized to load and release drugs with high drug loading capacity and biocompatibility, as well as how they promote endothelial adhesion and growth. Additionally, we examine how self-assembled coatings have been used to release active molecules for anti-coagulation and deliver gene therapy. Moreover, we discuss the potential of self-assembled coatings for future development, including intelligent targeted drug delivery, bionic stent coatings, and 3D printed stent coatings. These advancements have the potential to further improve the effectiveness of drug-eluting stents in treating coronary artery disease.
Structural variant calling and clinical interpretation in 6224 unsolved rare disease exomes
Authors: Demidov German , Laurie Steven , Torella Annalaura , Piluso Giulio , Scala Marcello , Morleo Manuela , Nigro Vincenzo , Graessner Holm , Banka Siddharth ,   Solve-RD consortium, Macaya Alfons , Pérez-Dueñas Belén , Jackson Adam , Stevanin Giovanni , de Sainte Agathe Jean-Madeleine , Havlovicová Markéta , Horvath Rita , Pinelli Michele , van Os Nienke J. H. , van de Warrenburg Bart P. C. , Denommé-Pichon Anne-Sophie , Savarese Marco , Johari Mridul , Dallapiccola Bruno , Tartaglia Marco , Pauly Martje G. , Sommer Anna Katharina , Haack Tobias B. , Töpf Ana , Didier Lacombe , Fallerini Chiara , Renieri Alessandra , Chinnery Patrick F. , Natera-de Benito Daniel , Nascimento Andres , Trimouille Aurélien , Munell Francina , Marcé-Grau Anna , Rabah Ben Yaou , Bonne Gisèle , Van de Vondel Liedewei , Lohmann Katja , Ossowski Stephan
Published: May 2024

Structural variants (SVs), including large deletions, duplications, inversions, translocations, and more complex events have the potential to disrupt gene function resulting in rare disease. Nevertheless, current pipelines and clinical decision support systems for exome sequencing (ES) tend to focus on small alterations such as single nucleotide variants (SNVs) and insertions-deletions shorter than 50 base pairs (indels). Additionally, detection and interpretation of large copy-number variants (CNVs) are frequently performed. However, detection of other types of SVs in ES data is hampered by the difficulty of identifying breakpoints in off-target (intergenic or intronic) regions, which makes robust identification of SVs challenging. In this paper, we demonstrate the utility of SV calling in ES resulting in a diagnostic yield of 0.4% (23 out of 5825 probands) for a large cohort of unsolved patients collected by the Solve-RD consortium. Remarkably, 8 out of 23 pathogenic SV were not found by comprehensive read-depth-based CNV analysis, resulting in a 0.13% increased diagnostic value.
Simulation of functional additive and non-additive genetic effects using statistical estimates from quantitative genetic models
Authors: Chu Thinh Tuan , Kristensen Peter Skov , Jensen Just
Published: May 2024

Stochastic simulation software is commonly used to aid breeders designing cost-effective breeding programs and to validate statistical models used in genetic evaluation. An essential feature of the software is the ability to simulate populations with desired genetic and non-genetic parameters. However, this feature often fails when non-additive effects due to dominance or epistasis are modeled, as the desired properties of simulated populations are estimated from classical quantitative genetic statistical models formulated at the population level. The software simulates underlying functional effects for genotypic values at the individual level, which are not necessarily the same as effects from statistical models in which dominance and epistasis are included. This paper provides the theoretical basis and mathematical formulas for the transformation between functional and statistical effects in such simulations. The transformation is demonstrated with two statistical models analyzing individual phenotypes in a single population (common in animal breeding) and plot phenotypes of three-way hybrids involving two inbred populations (observed in some crop breeding programs). We also describe different methods for the simulation of functional effects for additive genetics, dominance, and epistasis to achieve the desired levels of variance components in classical statistical models used in quantitative genetics.
Regional uniqueness of tree species composition and response to forest loss and climate change
Authors: van Tiel Nina , Fopp Fabian , Brun Philipp , van den Hoogen Johan , Karger Dirk Nikolaus , Casadei Cecilia M. , Lyu Lisha , Tuia Devis , Zimmermann Niklaus E. , Crowther Thomas W. , Pellissier Loïc
Published: May 2024

The conservation and restoration of forest ecosystems require detailed knowledge of the native plant compositions. Here, we map global forest tree composition and assess the impacts of historical forest cover loss and climate change on trees. The global occupancy of 10,590 tree species reveals complex taxonomic and phylogenetic gradients determining a local signature of tree lineage assembly. Species occupancy analyses indicate that historical forest loss has significantly restricted the potential suitable range of tree species in all forest biomes. Nevertheless, tropical moist and boreal forest biomes display the lowest level of range restriction and harbor extremely large ranged tree species, albeit with a stark contrast in richness and composition. Climate change simulations indicate that forest biomes are projected to differ in their response to climate change, with the highest predicted species loss in tropical dry and Mediterranean ecoregions. Our findings highlight the need for preserving the remaining large forest biomes while regenerating degraded forests in a way that provides resilience against climate change.
Two noncompeting human neutralizing antibodies targeting MPXV B6 show protective effects against orthopoxvirus infections
Authors: Zhao Runchu , Wu Lili , Sun Junqing , Liu Dezhi , Han Pu , Gao Yue , Zhang Yi , Xu Yanli , Qu Xiao , Wang Han , Chai Yan , Chen Zhihai , Gao George F. , Wang Qihui
Published: May 2024

The recent outbreak of mpox epidemic, caused by monkeypox virus (MPXV), poses a new threat to global public health. Here, we initially assessed the preexisting antibody level to the MPXV B6 protein in vaccinia vaccinees born before the end of the immunization program and then identified two monoclonal antibodies (MAbs), hMB621 and hMB668, targeting distinct epitopes on B6, from one vaccinee. Binding assays demonstrate that both MAbs exhibit broad binding abilities to B6 and its orthologs in vaccinia (VACV), variola (VARV) and cowpox viruses (CPXV). Neutralizing assays reveal that the two MAbs showed potent neutralization against VACV. Animal experiments using a BALB/c female mouse model indicate that the two MAbs showed effective protection against VACV via intraperitoneal injection. Additionally, we determined the complex structure of B6 and hMB668, revealing the structural feature of B6 and the epitope of hMB668. Collectively, our study provides two promising antibody candidates for the treatment of orthopoxvirus infections, including mpox.
The chromatin landscape of pathogenic transcriptional cell states in rheumatoid arthritis
Authors: Weinand Kathryn , Sakaue Saori , Nathan Aparna , Jonsson Anna Helena , Zhang Fan , Watts Gerald F. M. , Al Suqri Majd , Zhu Zhu ,   Accelerating Medicines Partnership Program: Rheumatoid Arthritis and Systemic Lupus Erythematosus (AMP RA/SLE) Network, Albrecht Jennifer , Apruzzese William , Banda Nirmal , Barnas Jennifer L. , Bathon Joan M. , Ben-Artzi Ami , Boyce Brendan F. , Boyle David L. , Bridges S. Louis , Bykerk Vivian P. , Campbell Debbie , Carr Hayley L. , Ceponis Arnold , Chicoine Adam , Cordle Andrew , Curtis Michelle , Deane Kevin D. , DiCarlo Edward , Dunn Patrick , Filer Andrew , Firestein Gary S. , Forbess Lindsy , Geraldino-Pardilla Laura , Goodman Susan M. , Gravallese Ellen M. , Gregersen Peter K. , Guthridge Joel M. , Gutierrez-Arcelus Maria , Gurajala Siddarth , Holers V. Michael , Horowitz Diane , Hughes Laura B. , Ishigaki Kazuyoshi , Ivashkiv Lionel B. , James Judith A. , Kang Joyce B. , Keras Gregory , Korsunsky Ilya , Lakhanpal Amit , Lederer James A. , Li Zhihan J. , Li Yuhong , Liao Katherine P. , Mandelin Arthur M. , Mantel Ian , Maybury Mark , McDavid Andrew , Mears Joseph , Meednu Nida , Millard Nghia , Moreland Larry W. , Nerviani Alessandra , Orange Dana E. , Perlman Harris , Pitzalis Costantino , Rangel-Moreno Javier , Raza Karim , Reshef Yakir , Ritchlin Christopher , Rivellese Felice , Robinson William H. , Rumker Laurie , Sahbudin Ilfita , Scheel-Toellner Dagmar , Seifert Jennifer A. , Slowikowski Kamil , Smith Melanie H. , Tabechian Darren , Utz Paul J. , Weisenfeld Dana , Weisman Michael H. , Xiao Qian , Rao Deepak A. , Anolik Jennifer H. , Brenner Michael B. , Donlin Laura T. , Wei Kevin , Raychaudhuri Soumya
Published: May 2024

Synovial tissue inflammation is a hallmark of rheumatoid arthritis (RA). Recent work has identified prominent pathogenic cell states in inflamed RA synovial tissue, such as T peripheral helper cells; however, the epigenetic regulation of these states has yet to be defined. Here, we examine genome-wide open chromatin at single-cell resolution in 30 synovial tissue samples, including 12 samples with transcriptional data in multimodal experiments. We identify 24 chromatin classes and predict their associated transcription factors, including a CD8 + GZMK+ class associated with EOMES and a lining fibroblast class associated with AP-1. By integrating with an RA tissue transcriptional atlas, we propose that these chromatin classes represent ‘superstates’ corresponding to multiple transcriptional cell states. Finally, we demonstrate the utility of this RA tissue chromatin atlas through the associations between disease phenotypes and chromatin class abundance, as well as the nomination of classes mediating the effects of putatively causal RA genetic variants.
Inward motion of diamond nanoparticles inside an iron crystal
Authors: Wang Yuecun , Wang Xudong , Ding Jun , Liang Beiming , Zuo Lingling , Zheng Shaochuan , Huang Longchao , Xu Wei , Fan Chuanwei , Duan Zhanqiang , Jia Chunde , Zheng Rui , Liu Zhang , Zhang Wei , Li Ju , Ma En , Shan Zhiwei
Published: May 2024

In the absence of externally applied mechanical loading, it would seem counterintuitive that a solid particle sitting on the surface of another solid could not only sink into the latter, but also continue its rigid-body motion towards the interior, reaching a depth as distant as thousands of times the particle diameter. Here, we demonstrate such a case using in situ microscopic as well as bulk experiments, in which diamond nanoparticles ~100 nm in size move into iron up to millimeter depth, at a temperature about half of the melting point of iron. Each diamond nanoparticle is nudged as a whole, in a displacive motion towards the iron interior, due to a local stress induced by the accumulation of iron atoms diffusing around the particle via a short and easy interfacial channel. Our discovery underscores an unusual mass transport mode in solids, in addition to the familiar diffusion of individual atoms.
Large out-of-plane spin–orbit torque in topological Weyl semimetal TaIrTe4
Authors: Bainsla Lakhan , Zhao Bing , Behera Nilamani , Hoque Anamul Md. , Sjöström Lars , Martinelli Anna , Abdel-Hafiez Mahmoud , Åkerman Johan , Dash Saroj P.
Published: May 2024

The unique electronic properties of topological quantum materials, such as protected surface states and exotic quasiparticles, can provide an out-of-plane spin-polarized current needed for external field-free magnetization switching of magnets with perpendicular magnetic anisotropy. Conventional spin–orbit torque (SOT) materials provide only an in-plane spin-polarized current, and recently explored materials with lower crystal symmetries provide very low out-of-plane spin-polarized current components, which are not suitable for energy-efficient SOT applications. Here, we demonstrate a large out-of-plane damping-like SOT at room temperature using the topological Weyl semimetal candidate TaIrTe4 with a lower crystal symmetry. We performed spin–torque ferromagnetic resonance (STFMR) and second harmonic Hall measurements on devices based on TaIrTe4/Ni80Fe20 heterostructures and observed a large out-of-plane damping-like SOT efficiency. The out-of-plane spin Hall conductivity is estimated to be (4.05 ± 0.23)×104 (ℏ ⁄ 2e) (Ωm)−1, which is an order of magnitude higher than the reported values in other materials.
AgRP neuron cis-regulatory analysis across hunger states reveals that IRF3 mediates leptin’s acute effects
Authors: Heyward Frankie D. , Liu Nan , Jacobs Christopher , Machado Natalia L. S. , Ivison Rachael , Uner Aykut , Srinivasan Harini , Patel Suraj J. , Gulko Anton , Sermersheim Tyler , Tsai Linus , Rosen Evan D.
Published: May 2024

AgRP neurons in the arcuate nucleus of the hypothalamus (ARC) coordinate homeostatic changes in appetite associated with fluctuations in food availability and leptin signaling. Identifying the relevant transcriptional regulatory pathways in these neurons has been a priority, yet such attempts have been stymied due to their low abundance and the rich cellular diversity of the ARC. Here we generated AgRP neuron-specific transcriptomic and chromatin accessibility profiles from male mice during three distinct hunger states of satiety, fasting-induced hunger, and leptin-induced hunger suppression. Cis-regulatory analysis of these integrated datasets enabled the identification of 18 putative hunger-promoting and 29 putative hunger-suppressing transcriptional regulators in AgRP neurons, 16 of which were predicted to be transcriptional effectors of leptin. Within our dataset, Interferon regulatory factor 3 (IRF3) emerged as a leading candidate mediator of leptin-induced hunger-suppression. Measures of IRF3 activation in vitro and in vivo reveal an increase in IRF3 nuclear occupancy following leptin administration. Finally, gain- and loss-of-function experiments in vivo confirm the role of IRF3 in mediating the acute satiety-evoking effects of leptin in AgRP neurons. Thus, our findings identify IRF3 as a key mediator of the acute hunger-suppressing effects of leptin in AgRP neurons.
A parametrically programmable delay line for microwave photons
Authors: Makihara Takuma , Lee Nathan , Guo Yudan , Guan Wenyan , Safavi-Naeini Amir
Published: May 2024

Delay lines that store quantum information are crucial for advancing quantum repeaters and hardware efficient quantum computers. Traditionally, they are realized as extended systems that support wave propagation but provide limited control over the propagating fields. Here, we introduce a parametrically addressed delay line for microwave photons that provides a high level of control over the stored pulses. By parametrically driving a three-wave mixing circuit element that is weakly hybridized with an ensemble of resonators, we engineer a spectral response that simulates that of a physical delay line, while providing fast control over the delay line’s properties. We demonstrate this novel degree of control by choosing which photon echo to emit, translating pulses in time, and even swapping two pulses, all with pulse energies on the order of a single photon. We also measure the noise added from our parametric interactions and find it is much less than one photon.
Photocatalytic toluene oxidation with nickel-mediated cascaded active units over Ni/Bi2WO6 monolayers
Authors: Shi Yingzhang , Li Peng , Chen Huiling , Wang Zhiwen , Song Yujie , Tang Yu , Lin Sen , Yu Zhiyang , Wu Ling , Yu Jimmy C. , Fu Xianzhi
Published: May 2024

Adsorption and activation of C–H bonds by photocatalysts are crucial for the efficient conversion of C–H bonds to produce high-value chemicals. Nevertheless, the delivery of surface-active oxygen species for C–H bond oxygenation inevitably needs to overcome obstacles due to the separated active centers, which suppresses the catalytic efficiency. Herein, Ni dopants are introduced into a monolayer Bi2WO6 to create cascaded active units consisting of unsaturated W atoms and Bi/O frustrated Lewis pairs. Experimental characterizations and density functional theory calculations reveal that these special sites can establish an efficient and controllable C–H bond oxidation process. The activated oxygen species on unsaturated W are readily transferred to the Bi/O sites for C–H bond oxygenation. The catalyst with a Ni mass fraction of 1.8% exhibits excellent toluene conversion rates and high selectivity towards benzaldehyde. This study presents a fascinating strategy for toluene oxidation through the design of efficient cascaded active units.
Robotic versus laparoscopic distal gastrectomy for resectable gastric cancer: a randomized phase 2 trial
Authors: Lu Jun , Xu Bin-bin , Zheng Hua-Long , Li Ping , Xie Jian-wei , Wang Jia-bin , Lin Jian-xian , Chen Qi-yue , Cao Long-long , Lin Mi , Tu Ru-hong , Huang Ze-ning , Lin Ju-li , Yao Zi-hao , Zheng Chao-Hui , Huang Chang-Ming
Published: May 2024

Robotic surgery may be an alternative to laparoscopic surgery for gastric cancer (GC). However, randomized controlled trials (RCTs) reporting the differences in survival between these two approaches are currently lacking. From September 2017 to January 2020, 300 patients with cT1-4a and N0/+ were enrolled and randomized to either the robotic (RDG) or laparoscopic distal gastrectomy (LDG) group (NCT03313700). The primary endpoint was 3-year disease-free survival (DFS); secondary endpoints reported here are the 3-year overall survival (OS) and recurrence patterns. The remaining secondary outcomes include intraoperative outcomes, postoperative recovery, quality of lymphadenectomy, and cost differences, which have previously been reported. There were 283 patients in the modified intention-to-treat analysis (RDG group: n = 141; LDG group: n = 142). The trial has met pre-specified endpoints. The 3-year DFS rates were 85.8% and 73.2% in the RDG and LDG groups, respectively (p = 0.011). Multivariable Cox regression model including age, tumor size, sex, ECOG PS, lymphovascular invasion, histology, pT stage, and pN stage showed that RDG was associated with better 3-year DFS (HR: 0.541; 95% CI: 0.314-0.932). The RDG also improved the 3-year cumulative recurrence rate (RDG vs. LDG: 12.1% vs. 21.1%; HR: 0.546, 95% CI: 0.302-0.990). Compared to LDG, RDG demonstrated non-inferiority in 3-year DFS rate.
Circular single-stranded DNA as a programmable vector for gene regulation in cell-free protein expression systems
Authors: Tian Zhijin , Shao Dandan , Tang Linlin , Li Zhen , Chen Qian , Song Yongxiu , Li Tao , Simmel Friedrich C. , Song Jie
Published: May 2024

Cell-free protein expression (CFE) systems have emerged as a critical platform for synthetic biology research. The vectors for protein expression in CFE systems mainly rely on double-stranded DNA and single-stranded RNA for transcription and translation processing. Here, we introduce a programmable vector - circular single-stranded DNA (CssDNA), which is shown to be processed by DNA and RNA polymerases for gene expression in a yeast-based CFE system. CssDNA is already widely employed in DNA nanotechnology due to its addressability and programmability. To apply above methods in the context of synthetic biology, CssDNA can not only be engineered for gene regulation via the different pathways of sense CssDNA and antisense CssDNA, but also be constructed into several gene regulatory logic gates in CFE systems. Our findings advance the understanding of how CssDNA can be utilized in gene expression and gene regulation, and thus enrich the synthetic biology toolbox.
Conformations of Bcs1L undergoing ATP hydrolysis suggest a concerted translocation mechanism for folded iron-sulfur protein substrate
Authors: Zhan Jingyu , Zeher Allison , Huang Rick , Tang Wai Kwan , Jenkins Lisa M. , Xia Di
Published: May 2024

The human AAA-ATPase Bcs1L translocates the fully assembled Rieske iron-sulfur protein (ISP) precursor across the mitochondrial inner membrane, enabling respiratory Complex III assembly. Exactly how the folded substrate is bound to and released from Bcs1L has been unclear, and there has been ongoing debate as to whether subunits of Bcs1L act in sequence or in unison hydrolyzing ATP when moving the protein cargo. Here, we captured Bcs1L conformations by cryo-EM during active ATP hydrolysis in the presence or absence of ISP substrate. In contrast to the threading mechanism widely employed by AAA proteins in substrate translocation, subunits of Bcs1L alternate uniformly between ATP and ADP conformations without detectable intermediates that have different, co-existing nucleotide states, indicating that the subunits act in concert. We further show that the ISP can be trapped by Bcs1 when its subunits are all in the ADP-bound state, which we propose to be released in the apo form.
Multiple photofluorochromic luminogens via catalyst-free alkene oxidative cleavage photoreaction for dynamic 4D codes encryption
Authors: Lu Lin , Wu Bo , He Xinyuan , Zhao Fen , Feng Xing , Wang Dong , Qiu Zijie , Han Ting , Zhao Zheng , Tang Ben Zhong
Published: May 2024

Controllable photofluorochromic systems with high contrast and multicolor in both solutions and solid states are ideal candidates for the development of dynamic artificial intelligence. However, it is still challenging to realize multiple photochromism within one single molecule, not to mention good controllability. Herein, we report an aggregation-induced emission luminogen TPE-2MO2NT that undergoes oxidation cleavage upon light irradiation and is accompanied by tunable multicolor emission from orange to blue with time-dependence. The photocleavage mechanism revealed that the self-generation of reactive oxidants driving the catalyst-free oxidative cleavage process. A comprehensive analysis of TPE-2MO2NT and other comparative molecules demonstrates that the TPE-2MO2NT molecular scaffold can be easily modified and extended. Further, the multicolor microenvironmental controllability of TPE-2MO2NT photoreaction within polymer matrices enables the fabrication of dynamic fluorescence images and 4D information codes, providing strategies for advanced controllable information encryption.
A multidimensional selective landscape drives adaptive divergence between and within closely related Phlox species
Authors: Goulet-Scott Benjamin E. , Farnitano Matthew C. , Brown Andrea L. M. , Hale Charles O. , Blumstein Meghan , Hopkins Robin
Published: May 2024

Selection causes local adaptation across populations within species and simultaneously divergence between species. However, it is unclear if either the force of or the response to selection is similar across these scales. We show that natural selection drives divergence between closely related species in a pattern that is distinct from local adaptation within species. We use reciprocal transplant experiments across three species of Phlox wildflowers to characterize widespread adaptive divergence. Using provenance trials, we also find strong local adaptation between populations within a species. Comparing divergence and selection between these two scales of diversity we discover that one suite of traits predicts fitness differences between species and that an independent suite of traits predicts fitness variation within species. Selection drives divergence between species, contributing to speciation, while simultaneously favoring extensive diversity that is maintained across populations within a species. Our work demonstrates how the selection landscape is complex and multidimensional.