bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of prosodic and visual information in disambiguating wh-indeterminates: The case of Korean three-year-olds
Authors: CHO Hye-Jung , KIAER Jieun , CHOI Naya , SONG Jieun
Published: March 2021

In Korean language, questions containing ambiguous wh-words may be interpreted as either wh-questions or yes-no questions. This study investigated 43 Korean three-year-olds’ ability to disambiguate eight indeterminate questions using prosodic and visual cues. The intonation of each question provided a cue as to whether it should be interpreted as a wh-question or a yes-no question. The questions were presented alongside picture stimuli, which acted as either a matched (presentation of corresponding auditory-visual stimuli) or a mismatched contextual cue (presentation conflicting auditory-visual stimuli). Like adults, the children preferred to comprehend questions involving ambiguous wh-words as wh-questions, rather than yes-no questions. In addition, children were as effective as adults in disambiguating indeterminate questions using prosodic cues regardless of the visual cue. However, when confronted with conflicting auditory-visual stimuli (mismatched), the quality of children's responses was less accurate than adults’ responses.
The ‘oldest dated document of the Cairo Genizah’ (Halper 331): The Seleucid era and sectarian Jewish calendars
Authors: KRAKOWSKI EVE , STERN SACHA
Published: March 2021

Halper 331 is the fragment of a codex that has been styled the ‘oldest dated document of the Cairo Genizah’. It preserves the opening of a Jewish legal document dated to the year 1182 (Seleucid era), which appears to have been copied into this codex, probably as a formulary, not long after this date, in the late 9th century. In this article, the text of this fragment, in Aramaic and Hebrew, is edited, and its identification as the beginning of a marriage contract (ketubbah) is evaluated. Its Egyptian provenance is questioned, partly because the earliest evidence for the introduction of the Seleucid era by Jews in Egypt dates from the mid-10th century. The article surveys the history of Jewish dating methods in early medieval Egypt and the Near East, in an attempt to clarify this question. The specific date of the document deviates from the rabbinic calendar, but agrees with that of the contemporary Jewish Near Eastern sectarian groups of Abū ʿImrān al-Tiflīsī and Ismāʿīl al-ʿUkbarī; this document could thus uniquely attest one of these sectarian Jewish calendars.
Psychiatrische Intensivbetreuung
Authors: Rabenschlag Franziska , Schürmann Jan , Trachsel Manuel
Published: March 2021

Was ist zu diesem Thema bereits bekannt?

Um mit Menschen in Krisensituationen in Beziehung zu treten und um sie selber oder andere vor Gefährdung zu schützen, werden im stationären Setting Einzelbetreuungen angeboten und empfohlen: die psychiatrische Intensivbetreuung.

Wie wird eine neue Perspektive eingebracht?

Unmittelbare Begegnung ohne Zweck, Mitgefühl, Zuhören und Da-Sein sind wirkungsvolle Mittel und sollen bewusst eingesetzt werden.

Was sind die Auswirkungen für die Praxis?

Interaktionen, Beziehungsaufbau und „Da-Sein“ kann eine Herausforderung sein und neben spezifischen Methoden als weniger zielgerichtet scheinen. Deshalb sind im Rahmen psychiatrischer Intensivbetreuung Weiterbildung und Supervision wichtig.
Wildfire Smoke Particulate Matter Concentration Measurements Using Radio Links From Cellular Communication Networks
Authors: Guyot Adrien , Pudashine Jayaram , Uijlenhoet Remko , Protat Alain , Pauwels Valentijn R. N. , Louf Valentin , Walker Jeffrey P.
Published: March 2021

The monitoring of wildfire smoke is important to help mitigate impacts on people such as by sending early warnings to affected areas. Received signal levels (RSLs) from radio links have been used as an opportunistic way to accurately measure rainfall and humidity. Radio links provide integrated measurements along their paths and are an exceptional untapped resource to complement air quality stations in areas affected by smoke events, or in developing countries without air quality monitoring capability. This study analyzed radio link signal fluctuations during smoke events associated with the 2019–2020 Australian wildfires. Concurrently, the atmospheric boundary layer was characterized using atmospheric soundings and surface observations, as well as air quality proxies such as particulate matter concentrations less than 2.5 μm (10 μm), or PM2.5(PM10). Observations showed that dry air containing large amounts of smoke within a surface layer above the ground acted as a lid, reducing dispersion, trapping and maintaining high ground‐level concentrations of smoke. These conditions also created anomalous propagation conditions for radio links and operational weather radars. Power‐law relations between signal fluctuations and PM10and PM2.5were derived based on the link data collected and the closest air quality station observations. While there was variability in retrieval performance across smoke events, the best performance determination coefficients exceeded 0.5, with an RMSE on the order of less than 50 μg m−3for concentrations of more than 400 μg m−3. Mid‐range link lengths (5–20 km) provided the best results.
Confronting Racism to Advance Our Science
Authors: Zeitler Peter , Barros Ana P. , Becker Thorsten W. , Davidson Eric A. , Ehlmann Bethany L. , Gruber Nicolas , Hofmann Eileen E. , Hudson Mary K. , Illangasekare Tissa H. , Kang Sarah M. , Malanotte‐Rizzoli Paola , Moerchen Margaret , Nimmo Francis , Parsons Tom , Salters Vincent J. M. , Stevens Bjorn , Trumbore Susan , Wuebbles Donald J. , Zhu Tong
Published: March 2021

As individuals serving on the AGU Advances editorial board, we condemn racism, affirm that Black Lives Matter, and recognize that inequality is built into the systems that have allowed us to prosper. We aim to persistently foster discussion about racism, inequity, and the need to make our community more diverse and inclusive. This will help AGU Advances do a better job in publishing important science that inclusively reflects the ideas and contributions of all in our community.
Counteracting Systemic Bias in the Lab, Field, and Classroom
Authors: Cooperdock Emily H. G. , Chen Christine Y. , Guevara Victor E. , Metcalf James R.
Published: March 2021

Grappling with systemic discrimination and bias in geosciences can be overwhelming to the point that one may feel powerless to fix them. Despite the sweeping nature of this challenge, faculty, principal investigators, and other scientists with leadership roles have unparalleled power to mitigate harm in environments they oversee. Here, we identify ways that scientists in these roles can immediately address bias in three common spaces—the lab, field, and classroom. We highlight key actions that can be taken to improve the quality of life of marginalized students and other trainees quickly, while important but comparatively slow institutional changes proceed.
Combating Racism in the Geosciences: Reflections From a Black Professor
Authors: Morris Vernon R.
Published: March 2021

Racism is part of my lived experience as a Black person in America. Similarly, microaggressions and systemic racism form part of the common experience for BIPOC+ Geoscientists. This commentary is not intended to be fodder for the oppression‐porn industry that stokes the passions of the “recently woke.” I speak with a unique perspective on the geoscience community and provide concrete recommendations for systemic change. It is time that we faced the realities of structural racism and invested in the real work necessary to make the geosciences diverse, equitable, and inclusive. Geoscientists need the entire community to work together to become anti‐racist.
Observational Evidence of Increasing Global Radiative Forcing
Authors: Kramer Ryan J. , He Haozhe , Soden Brian J. , Oreopoulos Lazaros , Myhre Gunnar , Forster Piers M. , Smith Christopher J.
Published: March 2021

Changes in atmospheric composition, such as increasing greenhouse gases, cause an initial radiative imbalance to the climate system, quantified as the instantaneous radiative forcing. This fundamental metric has not been directly observed globally and previous estimates have come from models. In part, this is because current space‐based instruments cannot distinguish the instantaneous radiative forcing from the climate’s radiative response. We apply radiative kernels to satellite observations to disentangle these components and find all‐sky instantaneous radiative forcing has increased 0.53 ± 0.11 W/m2 from 2003 to 2018, accounting for positive trends in the total planetary radiative imbalance. This increase has been due to a combination of rising concentrations of well‐mixed greenhouse gases and recent reductions in aerosol emissions. These results highlight distinct fingerprints of anthropogenic activity in Earth’s changing energy budget, which we find observations can detect within 4 years.
Breaking Up Is Hard to Do, Especially for Continents
Authors: Worthington Lindsay , Shuck Brandon , B�cel Anne , Eilon Zachary , Lynner Colton
Published: March 2021

A decade-long research collaboration has revealed that the split between Africa and North America roughly 200 million years ago was more drawn out than previously thought.
Spin-decoupled metasurface for simultaneous detection of spin and orbital angular momenta via momentum transformation
Authors: Guo Yinghui , Zhang Shicong , Pu Mingbo , He Qiong , Jin Jinjin , Xu Mingfeng , Zhang Yaxin , Gao Ping , Luo Xiangang
Published: March 2021

With inherent orthogonality, both the spin angular momentum (SAM) and orbital angular momentum (OAM) of photons have been utilized to expand the dimensions of quantum information, optical communications, and information processing, wherein simultaneous detection of SAMs and OAMs with a single element and a single-shot measurement is highly anticipated. Here, a single azimuthal-quadratic phase metasurface-based photonic momentum transformation (PMT) is illustrated and utilized for vortex recognition. Since different vortices are converted into focusing patterns with distinct azimuthal coordinates on a transverse plane through PMT, OAMs within a large mode space can be determined through a single-shot measurement. Moreover, spin-controlled dual-functional PMTs are proposed for simultaneous SAM and OAM sorting, which is implemented by a single spin-decoupled metasurface that merges both the geometric phase and dynamic phase. Interestingly, our proposed method can detect vectorial vortices with both phase and polarization singularities, as well as superimposed vortices with a certain interval step. Experimental results obtained at several wavelengths in the visible band exhibit good agreement with the numerical modeling. With the merits of ultracompact device size, simple optical configuration, and prominent vortex recognition ability, our approach may underpin the development of integrated and high-dimensional optical and quantum systems.
Cardiomyocyte electrical-mechanical synchronized model for high-content, dose-quantitative and time-dependent drug assessment
Authors: Fang Jiaru , Wei Xinwei , Li Hongbo , Hu Ning , Liu Xingxing , Xu Dongxin , Zhang Tao , Wan Hao , Wang Ping , Xie Xi
Published: March 2021

Cardiovascular diseases have emerged as a significant threat to human health. However, drug development is a time-consuming and costly process, and few drugs pass the preclinical assessment of safety and efficacy. The existing patch-clamp, Ca2+ imaging, and microelectrode array technologies in cardiomyocyte models for drug preclinical screening have suffered from issues of low throughput, limited long-term assessment, or inability to synchronously and correlatively analyze electrical and mechanical signals. Here, we develop a high-content, dose-quantitative and time-dependent drug assessment platform based on an electrical-mechanical synchronized (EMS) biosensing system. This microfabricated EMS can record both firing potential (FP) and mechanical beating (MB) signals from cardiomyocytes and extract a variety of characteristic parameters from these two signals (FP–MB) for further analysis. This system was applied to test typical ion channel drugs (lidocaine and isradipine), and the dynamic responses of cardiomyocytes to the tested drugs were recorded and analyzed. The high-throughput characteristics of the system can facilitate simultaneous experiments on a large number of samples. Furthermore, a database of various cardiac drugs can be established by heat map analysis for rapid and effective screening of drugs. The EMS biosensing system is highly promising as a powerful tool for the preclinical development of new medicines.
Gray matter networks associated with attention and working memory deficit in ADHD across adolescence and adulthood
Authors: Duan Kuaikuai , Jiang Wenhao , Rootes-Murdy Kelly , Schoenmacker Gido H. , Arias-Vasquez Alejandro , Buitelaar Jan K. , Hoogman Martine , Oosterlaan Jaap , Hoekstra Pieter J. , Heslenfeld Dirk J. , Hartman Catharina A. , Calhoun Vince D. , Turner Jessica A. , Liu Jingyu
Published: March 2021

Attention-deficit/hyperactivity disorder (ADHD) is a childhood-onset neuropsychiatric disorder and may persist into adulthood. Working memory and attention deficits have been reported to persist from childhood to adulthood. How neuronal underpinnings of deficits differ across adolescence and adulthood is not clear. In this study, we investigated gray matter of two cohorts, 486 adults and 508 adolescents, each including participants from ADHD and healthy controls families. Two cohorts both presented significant attention and working memory deficits in individuals with ADHD. Independent component analysis was applied to the gray matter of each cohort, separately, to extract cohort-inherent networks. Then, we identified gray matter networks associated with inattention or working memory in each cohort, and projected them onto the other cohort for comparison. Two components in the inferior, middle/superior frontal regions identified in adults and one component in the insula and inferior frontal region identified in adolescents were significantly associated with working memory in both cohorts. One component in bilateral cerebellar tonsil and culmen identified in adults and one component in left cerebellar region identified in adolescents were significantly associated with inattention in both cohorts. All these components presented a significant or nominal level of gray matter reduction for ADHD participants in adolescents, but only one showed nominal reduction in adults. Our findings suggest although the gray matter reduction of these regions may not be indicative of persistency of ADHD, their persistent associations with inattention or working memory indicate an important role of these regions in the mechanism of persistence or remission of the disorder.
COVID-19 and cancer registries: learning from the first peak of the SARS-CoV-2 pandemic
Authors: Lee Alvin J. X. , Purshouse Karin
Published: March 2021

The SARS-Cov-2 pandemic in 2020 has caused oncology teams around the world to adapt their practice in the aim of protecting patients. Early evidence from China indicated that patients with cancer, and particularly those who had recently received chemotherapy or surgery, were at increased risk of adverse outcomes following SARS-Cov-2 infection. Many registries of cancer patients infected with SARS-Cov-2 emerged during the first wave. We collate the evidence from these national and international studies and focus on the risk factors for patients with solid cancers and the contribution of systemic anti-cancer treatments (SACT—chemotherapy, immunotherapy, targeted and hormone therapy) to outcomes following SARS-Cov-2 infection. Patients with cancer infected with SARS-Cov-2 have a higher probability of death compared with patients without cancer. Common risk factors for mortality following COVID-19 include age, male sex, smoking history, number of comorbidities and poor performance status. Oncological features that may predict for worse outcomes include tumour stage, disease trajectory and lung cancer. Most studies did not identify an association between SACT and adverse outcomes. Recent data suggest that the timing of receipt of SACT may be associated with risk of mortality. Ongoing recruitment to these registries will enable us to provide evidence-based care.
FBXO6-mediated RNASET2 ubiquitination and degradation governs the development of ovarian cancer
Authors: Ji Mei , Zhao Zhao , Li Yue , Xu Penglin , Shi Jia , Li Zhe , Wang Kaige , Huang Xiaotian , Liu Bin
Published: March 2021

RNASET2 (Ribonuclease T2) functions as a tumor suppressor in preventing ovarian tumorigenesis. However, the mechanisms underlying the regulation of RNASET2 protein are completely unknown. Here we identified the F-box protein FBXO6, a substrate recognition subunit of an SCF (Skp1-Cul1-F-box protein) complex, as the ubiquitin E3 ligase for RNASET2. We found that the interaction between FBXO6 and RNASET2 induced RNASET2 instability through the ubiquitin-mediated proteasome degradation pathway. FBXO6 promoted K48-dependent ubiquitination of RNASET2 via its FBA domain. Through analysis of the TCGA dataset, we found that FBXO6 was significantly increased in ovarian cancer tissues and the high expression of FBXO6 was related to the poor overall survival (OS) of ovarian cancer patients at advanced stages. An inverse correlation between the protein levels of FBXO6 and RNASET2 was observed in clinic ovarian cancer samples. Depletion of FBXO6 promoted ovarian cancer cells proliferation, migration, and invasion, which could be partially reversed by RNASET2 silencing. Thus, our data revealed a novel FBXO6-RNASET2 axis, which might contribute to the development of ovarian cancer. We propose that inhibition of FBXO6 might represent an effective therapeutic strategy for ovarian cancer treatment.
A novel lncRNA TCLlnc1 promotes peripheral T cell lymphoma progression through acting as a modular scaffold of HNRNPD and YBX1 complexes
Authors: Zhao Ping , Ji Meng-Meng , Fang Ying , Li Xiao , Yi Hong-Mei , Yan Zi-Xun , Cheng Shu , Xu Peng-Peng , Janin Anne , Wang Chao-Fu , Wang Li , Zhao Wei-Li
Published: March 2021

Long noncoding RNAs (lncRNAs) play an essential role in tumor progression. Few researches focused on the clinical and biological relevance of lncRNAs in peripheral T cell lymphoma (PTCL). In this research, a novel lncRNA (ENST00000503502) was identified overexpressed in the main subtypes of PTCL, and designated as T cell lymphoma-associated lncRNA1 (TCLlnc1). Serum TCLlnc1 was associated with extranodal involvement, high-risk International Prognostic Index, and poor prognosis of the patients. Both in vitro and in vivo, overexpression of TCLlnc1 promoted T-lymphoma cell proliferation and migration, both of which were counteracted by the knockdown of TCLlnc1 using small interfering RNAs. As the mechanism of action, TCLlnc1 directly interacted with transcription activator heterogeneous nuclear ribonucleoprotein D (HNRNPD) and Y-box binding protein-1 (YBX1) by acting as a modular scaffold. TCLlnc1/HNRNPD/YBX1 complex upregulated transcription of TGFB2 and TGFBR1 genes, activated the tumor growth factor-β signaling pathway, resulting in lymphoma progression, and might be a potential target in PTCL.
miR-23a/b suppress cGAS-mediated innate and autoimmunity
Authors: Yu Qiuya , Chu Lei , Li Yongxing , Wang Quanyi , Zhu Juanjuan , Wang Chen , Cui Shufang
Published: March 2021

Cyclic GMP-AMP synthase (cGAS), a key sensor of intracellular DNA, is essential for eliciting innate immunity against infection, whereas aberrant activation of cGAS by endogenous DNA promotes severe autoimmune diseases. However, it is largely unknown how cGAS expression is regulated during pathogen infection and autoimmunity. Here, we report that during herpes simplex virus type 1 (HSV-1) infection, two microRNAs (miR-23a and miR-23b) whose levels significantly decrease due to their interaction with the lncRNA Oasl2-209 directly regulate the expression of cGAS. Overexpression of miR-23a/b markedly dampens cytosolic DNA-induced innate immune responses, whereas inhibition of miR-23a/b enhances these responses. Mice treated with miR-23a/b agomirs exhibit increased susceptibility to HSV-1 infection. Moreover, cGAS is significantly upregulated in the Trex1−/− mouse autoimmune disease model. Administration of miR-23a/b blunts self DNA-induced autoinflammatory responses in Trex1−/− mice. Collectively, our study not only reveals a novel regulatory mechanism of cGAS expression by miRNAs but also identifies a potential therapy for cGAS-related autoimmune diseases.
Manganese salts function as potent adjuvants
Authors: Zhang Rui , Wang Chenguang , Guan Yukun , Wei Xiaoming , Sha Mengyin , Yi Mengran , Jing Miao , Lv Mengze , Guo Wen , Xu Jing , Wan Yi , Jia Xin-Ming , Jiang Zhengfan
Published: March 2021

Aluminum-containing adjuvants have been used for nearly 100 years to enhance immune responses in billions of doses of vaccines. To date, only a few adjuvants have been approved for use in humans, among which aluminum-containing adjuvants are the only ones widely used. However, the medical need for potent and safe adjuvants is currently continuously increasing, especially those triggering cellular immune responses for cytotoxic T lymphocyte activation, which are urgently needed for the development of efficient virus and cancer vaccines. Manganese is an essential micronutrient required for diverse biological activities, but its functions in immunity remain undefined. We previously reported that Mn2+ is important in the host defense against cytosolic dsDNA by facilitating cGAS-STING activation and that Mn2+ alone directly activates cGAS independent of dsDNA, leading to an unconventional catalytic synthesis of 2′3′-cGAMP. Herein, we found that Mn2+ strongly promoted immune responses by facilitating antigen uptake, presentation, and germinal center formation via both cGAS-STING and NLRP3 activation. Accordingly, a colloidal manganese salt (Mn jelly, MnJ) was formulated to act not only as an immune potentiator but also as a delivery system to stimulate humoral and cellular immune responses, inducing antibody production and CD4+/CD8+ T-cell proliferation and activation by either intramuscular or intranasal immunization. When administered intranasally, MnJ also worked as a mucosal adjuvant, inducing high levels of secretory IgA. MnJ showed good adjuvant effects for all tested antigens, including T cell-dependent and T cell-independent antigens, such as bacterial capsular polysaccharides, thus indicating that it is a promising adjuvant candidate.
Design of buried charged networks in artificial proteins
Authors: Baumgart Mona , Röpke Michael , Mühlbauer Max E. , Asami Sam , Mader Sophie L. , Fredriksson Kai , Groll Michael , Gamiz-Hernandez Ana P. , Kaila Ville R. I.
Published: March 2021

Soluble proteins are universally packed with a hydrophobic core and a polar surface that drive the protein folding process. Yet charged networks within the central protein core are often indispensable for the biological function. Here, we show that natural buried ion-pairs are stabilised by amphiphilic residues that electrostatically shield the charged motif from its surroundings to gain structural stability. To explore this effect, we build artificial proteins with buried ion-pairs by combining directed computational design and biophysical experiments. Our findings illustrate how perturbation in charged networks can introduce structural rearrangements to compensate for desolvation effects. We validate the physical principles by resolving high-resolution atomic structures of the artificial proteins that are resistant towards unfolding at extreme temperatures and harsh chemical conditions. Our findings provide a molecular understanding of functional charged networks and how point mutations may alter the protein’s conformational landscape.
Multi-task weak supervision enables anatomically-resolved abnormality detection in whole-body FDG-PET/CT
Authors: Eyuboglu Sabri , Angus Geoffrey , Patel Bhavik N. , Pareek Anuj , Davidzon Guido , Long Jin , Dunnmon Jared , Lungren Matthew P.
Published: March 2021

Computational decision support systems could provide clinical value in whole-body FDG-PET/CT workflows. However, limited availability of labeled data combined with the large size of PET/CT imaging exams make it challenging to apply existing supervised machine learning systems. Leveraging recent advancements in natural language processing, we describe a weak supervision framework that extracts imperfect, yet highly granular, regional abnormality labels from free-text radiology reports. Our framework automatically labels each region in a custom ontology of anatomical regions, providing a structured profile of the pathologies in each imaging exam. Using these generated labels, we then train an attention-based, multi-task CNN architecture to detect and estimate the location of abnormalities in whole-body scans. We demonstrate empirically that our multi-task representation is critical for strong performance on rare abnormalities with limited training data. The representation also contributes to more accurate mortality prediction from imaging data, suggesting the potential utility of our framework beyond abnormality detection and location estimation.
Viral infection of cells within the tumor microenvironment mediates antitumor immunotherapy via selective TBK1-IRF3 signaling
Authors: Brown Michael C. , Mosaheb Mubeen M. , Mohme Malte , McKay Zachary P. , Holl Eda K. , Kastan Jonathan P. , Yang Yuanfan , Beasley Georgia M. , Hwang E. Shelley , Ashley David M. , Bigner Darell D. , Nair Smita K. , Gromeier Matthias
Published: March 2021

Activating intra-tumor innate immunity might enhance tumor immune surveillance. Virotherapy is proposed to achieve tumor cell killing, while indirectly activating innate immunity. Here, we report that recombinant poliovirus therapy primarily mediates antitumor immunotherapy via direct infection of non-malignant tumor microenvironment (TME) cells, independent of malignant cell lysis. Relative to other innate immune agonists, virotherapy provokes selective, TBK1-IRF3 driven innate inflammation that is associated with sustained type-I/III interferon (IFN) release. Despite priming equivalent antitumor T cell quantities, MDA5-orchestrated TBK1-IRF3 signaling, but not NFκB-polarized TLR activation, culminates in polyfunctional and Th1-differentiated antitumor T cell phenotypes. Recombinant type-I IFN increases tumor-localized T cell function, but does not mediate durable antitumor immunotherapy without concomitant pattern recognition receptor (PRR) signaling. Thus, virus-induced MDA5-TBK1-IRF3 signaling in the TME provides PRR-contextualized IFN responses that elicit functional antitumor T cell immunity. TBK1-IRF3 innate signal transduction stimulates eventual function and differentiation of tumor-infiltrating T cells.
Near-room temperature ferromagnetic insulating state in highly distorted LaCoO2.5 with CoO5 square pyramids
Authors: Zhang Qinghua , Gao Ang , Meng Fanqi , Jin Qiao , Lin Shan , Wang Xuefeng , Xiao Dongdong , Wang Can , Jin Kui-juan , Su Dong , Guo Er-Jia , Gu Lin
Published: March 2021

Dedicated control of oxygen vacancies is an important route to functionalizing complex oxide films. It is well-known that tensile strain significantly lowers the oxygen vacancy formation energy, whereas compressive strain plays a minor role. Thus, atomic reconstruction by extracting oxygen from a compressive-strained film is challenging. Here we report an unexpected LaCoO2.5 phase with a zigzag-like oxygen vacancy ordering through annealing a compressive-strained LaCoO3 in vacuum. The synergetic tilt and distortion of CoO5 square pyramids with large La and Co shifts are quantified using scanning transmission electron microscopy. The large in-plane expansion of CoO5 square pyramids weaken the crystal field splitting and facilitated the ordered high-spin state of Co2+, which produces an insulating ferromagnetic state with a Curie temperature of ~284 K and a saturation magnetization of ~0.25 μB/Co. These results demonstrate that extracting targeted oxygen from a compressive-strained oxide provides an opportunity for creating unexpected crystal structures and novel functionalities.
scGNN is a novel graph neural network framework for single-cell RNA-Seq analyses
Authors: Wang Juexin , Ma Anjun , Chang Yuzhou , Gong Jianting , Jiang Yuexu , Qi Ren , Wang Cankun , Fu Hongjun , Ma Qin , Xu Dong
Published: March 2021

Single-cell RNA-sequencing (scRNA-Seq) is widely used to reveal the heterogeneity and dynamics of tissues, organisms, and complex diseases, but its analyses still suffer from multiple grand challenges, including the sequencing sparsity and complex differential patterns in gene expression. We introduce the scGNN (single-cell graph neural network) to provide a hypothesis-free deep learning framework for scRNA-Seq analyses. This framework formulates and aggregates cell–cell relationships with graph neural networks and models heterogeneous gene expression patterns using a left-truncated mixture Gaussian model. scGNN integrates three iterative multi-modal autoencoders and outperforms existing tools for gene imputation and cell clustering on four benchmark scRNA-Seq datasets. In an Alzheimer’s disease study with 13,214 single nuclei from postmortem brain tissues, scGNN successfully illustrated disease-related neural development and the differential mechanism. scGNN provides an effective representation of gene expression and cell–cell relationships. It is also a powerful framework that can be applied to general scRNA-Seq analyses.
No hints at glyphosate-induced ruminal dysbiosis in cows
Authors: Billenkamp Fabian , Schnabel Karina , Hüther Liane , Frahm Jana , von Soosten Dirk , Meyer Ulrich , Höper Dirk , Beer Martin , Seyboldt Christian , Neubauer Heinrich , Dänicke Sven
Published: March 2021

Glyphosate-based herbicides are among the most used non-selective herbicides worldwide and inhibit synthesis of aromatic amino acids in plants, bacteria, and fungi. Given the broad usage, controversies concerning potential effects of glyphosate on health and especially on gut microbiomes arose. For cattle, it has been proposed based on in vitro data that glyphosate has detrimental effects on the ruminal microbiome, which manifest as a specific inhibition of bacteria involved in fiber degradation and as an enrichment of specific pathogens. In the present study, glyphosate effects on the ruminal microbiome were analyzed in vivo using glyphosate contaminated feedstuffs with strong differences in dietary fiber and dietary energy content in order to reproduce the proposed detrimental glyphosate effects on the rumen microbiome. While significant impact of dietary factors on the ruminal microbiome and its products are pointed out, no adverse glyphosate effects on ruminal microbiome composition, diversity, and microbial metabolites are observed.
De-escalation of radiation therapy in patients with stage I, node-negative, HER2-positive breast cancer
Authors: Bazan Jose G. , Jhawar Sachin R. , Stover Daniel , Park Ko Un , Beyer Sasha , Healy Erin , White Julia R.
Published: March 2021

In the modern era, highly effective anti-HER2 therapy is associated with low local-regional recurrence (LRR) rates for early-stage HER2+ breast cancer raising the question of whether local therapy de-escalation by radiation omission is possible in patients with small-node negative tumors treated with lumpectomy. To evaluate existing data on radiation omission, we used the National Cancer Database (NCDB) to test the hypothesis that RT omission results in equivalent overall survival (OS) in stage 1 (T1N0) HER2+ breast cancer. We excluded patients that received neoadjuvant systemic therapy. We stratified the cohort by receipt of adjuvant radiation. We identified 6897 patients (6388 RT; 509 no RT). Patients that did not receive radiation tended to be ≥70 years-old (odds ratio [OR] = 3.69, 95% CI: 3.02–4.51,p < 0.0001), to have ≥1 comorbidity (OR = 1.33, 95% CI: 1.06–1.68,p = 0.0154), to be Hispanic (OR = 1.49, 95% CI: 1.00–2.22,p = 0.049), and to live in lower income areas (OR = 1.32, 95% CI: 1.07–1.64,p = 0.0266). Radiation omission was associated with a 3.67-fold (95% CI: 2.23–6.02,p < 0.0001) increased risk of death. While other selection biases that influence radiation omission likely persist, these data should give caution to radiation omission in T1N0 HER2+ breast cancer.
Structural and chemical mechanisms governing stability of inorganic Janus nanotubes
Authors: Bölle Felix T. , Mikkelsen August E. G. , Thygesen Kristian S. , Vegge Tejs , Castelli Ivano E.
Published: March 2021

One-dimensional inorganic nanotubes hold promise for technological applications due to their distinct physical/chemical properties, but so far advancements have been hampered by difficulties in producing single-wall nanotubes with a well-defined radius. In this work we investigate, based on Density Functional Theory (DFT), the formation mechanism of 135 different inorganic nanotubes formed by the intrinsic self-rolling driving force found in asymmetric 2D Janus sheets. We show that for isovalent Janus sheets, the lattice mismatch between inner and outer atomic layers is the driving force behind the nanotube formation, while in the non-isovalent case it is governed by the difference in chemical bond strength of the inner and outer layer leading to steric effects. From our pool of candidate structures we have identified more than 100 tubes with a preferred radius below 35 Å, which we hypothesize can display distinctive properties compared to their parent 2D monolayers. Simple descriptors have been identified to accelerate the discovery of small-radius tubes and a Bayesian regression approach has been implemented to assess the uncertainty in our predictions on the radius.
Optimal band structure for thermoelectrics with realistic scattering and bands
Authors: Park Junsoo , Xia Yi , Ozoliņš Vidvuds , Jain Anubhav
Published: March 2021

Understanding how to optimize electronic band structures for thermoelectrics is a topic of long-standing interest in the community. Prior models have been limited to simplified bands and/or scattering models. In this study, we apply more rigorous scattering treatments to more realistic model band structures—upward-parabolic bands that inflect to an inverted-parabolic behavior—including cases of multiple bands. In contrast to common descriptors (e.g., quality factor and complexity factor), the degree to which multiple pockets improve thermoelectric performance is bounded by interband scattering and the relative shapes of the bands. We establish that extremely anisotropic “flat-and-dispersive” bands, although best-performing in theory, may not represent a promising design strategy in practice. Critically, we determine optimum bandwidth, dependent on temperature and lattice thermal conductivity, from perfect transport cutoffs that can in theory significantly boost zT beyond the values attainable through intrinsic band structures alone. Our analysis should be widely useful as the thermoelectric research community eyes zT > 3.
NLM-Chem, a new resource for chemical entity recognition in PubMed full text literature
Authors: Islamaj Rezarta , Leaman Robert , Kim Sun , Kwon Dongseop , Wei Chih-Hsuan , Comeau Donald C. , Peng Yifan , Cissel David , Coss Cathleen , Fisher Carol , Guzman Rob , Kochar Preeti Gokal , Koppel Stella , Trinh Dorothy , Sekiya Keiko , Ward Janice , Whitman Deborah , Schmidt Susan , Lu Zhiyong
Published: March 2021

Automatically identifying chemical and drug names in scientific publications advances information access for this important class of entities in a variety of biomedical disciplines by enabling improved retrieval and linkage to related concepts. While current methods for tagging chemical entities were developed for the article title and abstract, their performance in the full article text is substantially lower. However, the full text frequently contains more detailed chemical information, such as the properties of chemical compounds, their biological effects and interactions with diseases, genes and other chemicals. We therefore present the NLM-Chem corpus, a full-text resource to support the development and evaluation of automated chemical entity taggers. The NLM-Chem corpus consists of 150 full-text articles, doubly annotated by ten expert NLM indexers, with ~5000 unique chemical name annotations, mapped to ~2000 MeSH identifiers. We also describe a substantially improved chemical entity tagger, with automated annotations for all of PubMed and PMC freely accessible through the PubTator web-based interface and API. The NLM-Chem corpus is freely available.
New insights into structure and function of bis-phosphinic acid derivatives and implications for CFTR modulation
Authors: Bitam Sara , Elbahnsi Ahmad , Creste Geordie , Pranke Iwona , Chevalier Benoit , Berhal Farouk , Hoffmann Brice , Servel Nathalie , Baatalah Nesrine , Tondelier Danielle , Hatton Aurelie , Moquereau Christelle , Faria Da Cunha Mélanie , Pastor Alexandra , Lepissier Agathe , Hinzpeter Alexandre , Mornon Jean-Paul , Prestat Guillaume , Edelman Aleksander , Callebaut Isabelle , Gravier-Pelletier Christine , Sermet-Gaudelus Isabelle
Published: March 2021

C407 is a compound that corrects the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein carrying the p.Phe508del (F508del) mutation. We investigated the corrector effect of c407 and its derivatives on F508del-CFTR protein. Molecular docking and dynamics simulations combined with site-directed mutagenesis suggested that c407 stabilizes the F508del-Nucleotide Binding Domain 1 (NBD1) during the co-translational folding process by occupying the position of the p.Phe1068 side chain located at the fourth intracellular loop (ICL4). After CFTR domains assembly, c407 occupies the position of the missing p.Phe508 side chain. C407 alone or in combination with the F508del-CFTR corrector VX-809, increased CFTR activity in cell lines but not in primary respiratory cells carrying the F508del mutation. A structure-based approach resulted in the synthesis of an extended c407 analog G1, designed to improve the interaction with ICL4. G1 significantly increased CFTR activity and response to VX-809 in primary nasal cells of F508del homozygous patients. Our data demonstrate that in-silico optimized c407 derivative G1 acts by a mechanism different from the reference VX-809 corrector and provide insights into its possible molecular mode of action. These results pave the way for novel strategies aiming to optimize the flawed ICL4–NBD1 interface.
Plastid phylogenomics resolves ambiguous relationships within the orchid family and provides a solid timeframe for biogeography and macroevolution
Authors: Serna-Sánchez Maria Alejandra , Pérez-Escobar Oscar A. , Bogarín Diego , Torres-Jimenez María Fernanda , Alvarez-Yela Astrid Catalina , Arcila-Galvis Juliana E. , Hall Climbie F. , de Barros Fábio , Pinheiro Fábio , Dodsworth Steven , Chase Mark W. , Antonelli Alexandre , Arias Tatiana
Published: March 2021

Recent phylogenomic analyses based on the maternally inherited plastid organelle have enlightened evolutionary relationships between the subfamilies of Orchidaceae and most of the tribes. However, uncertainty remains within several subtribes and genera for which phylogenetic relationships have not ever been tested in a phylogenomic context. To address these knowledge-gaps, we here provide the most extensively sampled analysis of the orchid family to date, based on 78 plastid coding genes representing 264 species, 117 genera, 18 tribes and 28 subtribes. Divergence times are also provided as inferred from strict and relaxed molecular clocks and birth–death tree models. Our taxon sampling includes 51 newly sequenced plastid genomes produced by a genome skimming approach. We focus our sampling efforts on previously unplaced clades within tribes Cymbidieae and Epidendreae. Our results confirmed phylogenetic relationships in Orchidaceae as recovered in previous studies, most of which were recovered with maximum support (209 of the 262 tree branches). We provide for the first time a clear phylogenetic placement for Codonorchideae within subfamily Orchidoideae, and Podochilieae and Collabieae within subfamily Epidendroideae. We also identify relationships that have been persistently problematic across multiple studies, regardless of the different details of sampling and genomic datasets used for phylogenetic reconstructions. Our study provides an expanded, robust temporal phylogenomic framework of the Orchidaceae that paves the way for biogeographical and macroevolutionary studies.
A modality selective effect of functional laterality in pain detection sensitivity
Authors: Zhang Huijuan , Lu Xuejing , Bi Yanzhi , Hu Li
Published: March 2021

The ability to detect environmental changes is essential to determine the appropriate reaction when facing potential threats. Both detection and reaction functions are critical to survival, and the superior performance of motor reaction for the dominant hand is well recognized in humans. However, it is not clear whether there exists laterality in sensitivity to detect external changes and whether the possible laterality is associated with sensory modality and stimulus intensity. Here, we tested whether the perceptual sensitivity and electrophysiological responses elicited by graded sensory stimuli (i.e., nociceptive somatosensory, non-nociceptive somatosensory, auditory, and visual) that were delivered on/near the left and right hands would be different for right-handed individuals. We observed that perceived intensities and most brain responses were significantly larger when nociceptive stimuli were delivered to the left side (i.e., the non-dominant hand) than to the right side (i.e., the dominant hand). No significant difference was observed between the two sides for other modalities. The higher sensitivity to detect nociceptive stimuli for the non-dominant hand would be important to provide a prompt reaction to noxious events, thus compensating for its worse motor performance. This laterality phenomenon should be considered when designing experiments for pain laboratory studies and evaluating regional sensory abnormalities for pain patients.
A tale of shifting relations: East Asian summer and winter monsoon variability during the Holocene
Authors: Kaboth-Bahr Stefanie , Bahr André , Zeeden Christian , Yamoah Kweku A. , Lone Mahjoor Ahmad , Chuang Chih-Kai , Löwemark Ludvig , Wei Kuo-Yen
Published: March 2021

Understanding the dynamics between the East Asian summer (EASM) and winter monsoon (EAWM) is needed to predict their variability under future global warming scenarios. Here, we investigate the relationship between EASM and EAWM as well as the mechanisms driving their variability during the last 10,000 years by stacking marine and terrestrial (non-speleothem) proxy records from the East Asian realm. This provides a regional and proxy independent signal for both monsoonal systems. The respective signal was subsequently analysed using a linear regression model. We find that the phase relationship between EASM and EAWM is not time-constant and significantly depends on orbital configuration changes. In addition, changes in the Atlantic Meridional Overturning circulation, Arctic sea-ice coverage, El Niño-Southern Oscillation and Sun Spot numbers contributed to millennial scale changes in the EASM and EAWM during the Holocene. We also argue that the bulk signal of monsoonal activity captured by the stacked non-speleothem proxy records supports the previously argued bias of speleothem climatic archives to moisture source changes and/or seasonality.
Cooperative partner choice in multi-level male dolphin alliances
Authors: Gerber Livia , Wittwer Samuel , Allen Simon J. , Holmes Kathryn G. , King Stephanie L. , Sherwin William B. , Wild Sonja , Willems Erik P. , Connor Richard C. , Krützen Michael
Published: March 2021

Investigations into cooperative partner choice should consider both potential and realised partners, allowing for the comparison of traits across all those available. Male bottlenose dolphins form persisting multi-level alliances. Second-order alliances of 4–14 males are the core social unit, within which 2–3 males form first-order alliances to sequester females during consortships. We compared social bond strength, relatedness and age similarity of potential and realised partners of individual males in two age periods: (i) adolescence, when second-order alliances are formed from all available associates, and (ii) adulthood, when first-order allies are selected from within second-order alliances. Social bond strength during adolescence predicted second-order alliance membership in adulthood. Moreover, males preferred same-aged or older males as second-order allies. Within second-order alliances, non-mating season social bond strength predicted first-order partner preferences during mating season consortships. Relatedness did not influence partner choice on either alliance level. There is thus a striking resemblance between male dolphins, chimpanzees and humans, where closely bonded non-relatives engage in higher-level, polyadic cooperative acts. To that end, our study extends the scope of taxa in which social bonds rather than kinship explain cooperation, providing the first evidence that such traits might have evolved independently in marine and terrestrial realms.
The difficulty to model Huntington’s disease in vitro using striatal medium spiny neurons differentiated from human induced pluripotent stem cells
Authors: Le Cann Kim , Foerster Alec , Rösseler Corinna , Erickson Andelain , Hautvast Petra , Giesselmann Sebastian , Pensold Daniel , Kurth Ingo , Rothermel Markus , Mattis Virginia B. , Zimmer-Bensch Geraldine , von Hörsten Stephan , Denecke Bernd , Clarner Tim , Meents Jannis , Lampert Angelika
Published: March 2021

Huntington’s disease (HD) is an autosomal dominant neurodegenerative disorder caused by an expanded polyglutamine repeat in the huntingtin gene. The neuropathology of HD is characterized by the decline of a specific neuronal population within the brain, the striatal medium spiny neurons (MSNs). The origins of this extreme vulnerability remain unknown. Human induced pluripotent stem cell (hiPS cell)-derived MSNs represent a powerful tool to study this genetic disease. However, the differentiation protocols published so far show a high heterogeneity of neuronal populations in vitro. Here, we compared two previously published protocols to obtain hiPS cell-derived striatal neurons from both healthy donors and HD patients. Patch-clamp experiments, immunostaining and RT-qPCR were performed to characterize the neurons in culture. While the neurons were mature enough to fire action potentials, a majority failed to express markers typical for MSNs. Voltage-clamp experiments on voltage-gated sodium (Nav) channels revealed a large variability between the two differentiation protocols. Action potential analysis did not reveal changes induced by the HD mutation. This study attempts to demonstrate the current challenges in reproducing data of previously published differentiation protocols and in generating hiPS cell-derived striatal MSNs to model a genetic neurodegenerative disorder in vitro.