bluuebunny/crossref_metadata_2025 huggingface dataset:
Positive and negative valences of identities: Longitudinal associations of identity content valences with adaptive and maladaptive functioning among Japanese young adults
Authors: Hihara Shogo , Sugimura Kazumi , Umemura Tomotaka , Iwasa Yasuhiro , Syed Moin
Published: March 2021

Erikson's psychosocial developmental theory assumes that valence of one's identity (i.e., identity content valence) defined by positive and negative identity elements is important for understanding patterns of (mal)adaptation. However, previous empirical research on identity and (mal)adaptation has focused on how individuals deal with identity issues (e.g., exploration and commitment), while neglecting identity content valences. In contrast, this study assessed identity content valences in terms of positive and negative identity elements. Theoretically, identity content valences affect (mal)adaptation, whereas individuals’ (mal)adaptation influences their identities. Consequently, this study examined reciprocal relationships between identity content valences and adaptation (i.e., prosocial behaviors) and maladaptation (e.g., externalizing symptoms) in a sample of Japanese young adults, including socioculturally relevant indicators of maladaptation (i.e., hikikomori symptoms and suicidal ideation). This study includes 2,313 Japanese young adults who participated in a three-wave longitudinal study. The cross-lagged panel model and random intercept cross-lagged panel model revealed reciprocal relationships between identity content valences and (mal)adaptation at the between-person level. Negative identity elements positively predicted suicidal ideation. Meanwhile, prosocial behaviors positively predicted positive identity elements, whereas hikikomori symptoms and suicidal ideation positively predicted negative identity elements. These relationships were significant only for socioculturally relevant indicators, suggesting the importance of considering sociocultural contexts.
Cultural Diplomacy and Europe's Twenty Years’ Crisis, 1919–1939: Introduction
Authors: Martin Benjamin G. , Piller Elisabeth Marie
Published: March 2021

Photographs of the German and Soviet pavilions facing off at the Paris International Exposition in 1937 offer an iconic image of the interwar period, and with good reason. This image captures the interwar period's great conflict of ideologies, the international interconnectedness of the age and the aestheticisation of political and ideological conflict in the age of mass media and mass spectacle. [Figure 1] Last but not least, it captures the importance in the 1930s of what we now call cultural diplomacy. Both pavilions – Germany's, in Albert Speer's neo-classical tower bloc crowned with a giant swastika, and the Soviet Union's, housed in Boris Iofan's forward-thrusting structure topped by Vera Mukhina's monumental sculptural group – represented the outcome of a large-scale collaboration between political leaders and architects, artists, intellectuals and graphic and industrial designers seeking to present their country to foreign visitors in a manner designed to advance the country's interests in the international arena. Each pavilion, that is, made an outreach that wasdiplomatic– in the sense that it sought to mediate between distinct polities – using means that werecultural– in the sense that they deployed refined aesthetic practices (like the arts and architecture) and in the sense that they highlighted the distinctive features, or ‘culture’, of a particular group (like the German nation or the Soviet state).
Do fruiting habit traits affect green fruit yield and its component traits in chilli (Capsicum annuumL.)?
Authors: Anilkumar C. , Rao A. Mohan , Ramesh S. , Pathy T. Lakshmi
Published: March 2021

In chilli, farmer preferences for fruiting habit traits, namely fruit orientation (pendant erect) and fruits node−1(solitary cluster), vary from region to region. For increased acceptability by farmers/consumers, cultivars should be bred with preferred fruiting habit traits in high green fruit yielding background. An investigation was carried out to study the influence of fruiting habit traits on green fruit yield and its component traits during the 2016 and 2017 rainy seasons. The F2, backcross populations and near-isogenic lines (NILs) derived from crosses involving parents differing for single or both the fruiting habit traits were grouped into fruiting habit classes (single and cluster fruiting; and clustered erect, clustered pendant, single erect and single pendant). Significance of differences in fruit yield and its component traits between/among different fruiting habit trait classes were examined using ‘t’/‘F’ tests. The significance of ‘t’/‘F’ tests was regarded as pieces of evidence for considerable effects of fruiting habit traits on fruit yield and its component traits. While results-based on F2and backcross generations indicated a lack of effects, those based on NILs indicated significant effects of fruiting habit traits on fruit yield and its component traits. The plants bearing pendant fruits (irrespective of whether they are clustered or single) produced a large number of heavier and longer fruits than those bearing erect fruits. The results are discussed about the strategies to develop high yielding cultivars with farmer preferred fruiting habit traits.
Self‐Similarity of Surface Wave Developments Under Tropical Cyclones
Authors: Kudryavtsev Vladimir , Yurovskaya Maria , Chapron Bertrand
Published: March 2021

The 2D‐parametric model suggested in the companion paper is used to simulate waves under tropical cyclones (TCs). Set of equations describing both wind waves and swell evolution in space and time, is solved using the method of characteristics. Wave‐ray patterns efficiently chart on how wave trains develop and travel through the TC varying wind field, to leave the storm area as swell systems. Depending on TC main characteristics—maximal wind speed (um), radius (Rm), and translation velocity (V), wave‐train rays superpose to exhibit particular coherent spatial patterns of significant wave height, peak wavelength and direction. Group velocity resonance leads to the appearance of waves with abnormally high energy, further outrunning as long swell systems through the TC front sector. Yet, when the TC translation velocity exceeds a threshold value, waves cannot reach group velocity resonance, and travel backwards, to form a wake of swell systems trailing the forward moving TC. Importantly, the model solutions for TC 2D‐wavefields can be parameterized using 2D self‐similar universal functions. Comparisons between self‐similar solutions and measurements, demonstrate a reasonable agreement to warrant scientific and practical applications. Self‐similar solutions provide immediate estimates of azimuthal‐radial distributions of wave parameters under TCs, solely characterized by arbitrary sets of um, Rm, and V conditions. Self‐similar solutions clearly divide TCs between slow TCs, fulfilling conditions Rm/Lcr > 1, and fast TCs corresponding to Rm/Lcr < 1, where Lcr is a critical fetch. Around the region Rm/Lc = 1, group velocity resonance occurs, leading to the largest possible waves generated by a TC.
Identification of novel locus associated with coronary artery aneurysms and validation of loci for susceptibility to Kawasaki disease
Authors: Hoggart Clive , Shimizu Chisato , Galassini Rachel , Wright Victoria J. , Shailes Hannah , Bellos Evan , Herberg Jethro A. , Pollard Andrew J. , O’Connor Daniel , Choi Shing Wan , Seaby Eleanor G. , Menikou Stephanie , Hibberd Martin , Sallah Neneh , Burgner David , Brogan Paul , Patel Harsita , Kim Jihoon , Tremoulet Adriana H. , Salo Eeva , van Stijn Diana , Kuijpers Taco , Burns Jane C. , Levin Michael ,   The International Kawasaki Disease Genetics Consortium,   UK Kawasaki Disease Genetics Consortium,   EUCLIDS Consortium
Published: March 2021

Kawasaki disease (KD) is a paediatric vasculitis associated with coronary artery aneurysms (CAA). Genetic variants influencing susceptibility to KD have been previously identified, but no risk alleles have been validated that influence CAA formation. We conducted a genome-wide association study (GWAS) for CAA in KD patients of European descent with 200 cases and 276 controls. A second GWAS for susceptibility pooled KD cases with healthy paediatric controls from vaccine trials in the UK (n = 1609). Logistic regression mixed models were used for both GWASs. The susceptibility GWAS was meta-analysed with 400 KD cases and 6101 controls from a previous European GWAS, these results were further meta-analysed with Japanese GWASs at two putative loci. The CAA GWAS identified an intergenic region of chromosome 20q13 with multiple SNVs showing genome-wide significance. The risk allele of the most associated SNV (rs6017006) was present in 13% of cases and 4% of controls; in East Asian 1000 Genomes data, the allele was absent or rare. Susceptibility GWAS with meta-analysis with previously published European data identified two previously associated loci (ITPKC and FCGR2A). Further meta-analysis with Japanese GWAS summary data from the CASP3 and FAM167A genomic regions validated these loci in Europeans showing consistent effects of the top SNVs in both populations. We identified a novel locus for CAA in KD patients of European descent. The results suggest that different genes determine susceptibility to KD and development of CAA and future work should focus on the function of the intergenic region on chromosome 20q13.
The human intermediate prolactin receptor is a mammary proto-oncogene
Authors: Grible Jacqueline M. , Zot Patricija , Olex Amy L. , Hedrick Shannon E. , Harrell J. Chuck , Woock Alicia E. , Idowu Michael O. , Clevenger Charles V.
Published: March 2021

The hormone prolactin (PRL) and its receptor (hPRLr) are significantly involved in breast cancer pathogenesis. The intermediate hPRLr (hPRLrI) is an alternatively-spliced isoform, capable of stimulating cellular viability and proliferation. An analogous truncated mouse PRLr (mPRLr) was recently found to be oncogenic when co-expressed with wild-type mPRLr. The goal of this study was to determine if a similar transforming event occurs with the hPRLr in human breast epithelial cells and to better understand the mechanism behind such transformation. hPRLrL+I co-expression in MCF10AT cells resulted in robust in vivo and in vitro transformation, while hPRLrI knock-down in MCF7 cells significantly decreased in vitro malignant potential. hPRLrL+I heterodimers displayed greater stability than hPRLrL homodimers, and while being capable of activating Jak2, Ras, and MAPK, they were unable to induce Stat5a tyrosine phosphorylation. Both immunohistochemical breast cancer tissue microarray data and RNA sequencing analyses using The Cancer Genome Atlas (TCGA) identified that higher hPRLrI expression associates with triple-negative breast cancer. These studies indicate the hPRLrI, when expressed alongside hPRLrL, participates in mammary transformation, and represents a novel oncogenic mechanism.
Prediction of intrinsic topological superconductivity in Mn-doped GeTe monolayer from first-principles
Authors: Zhang Xiaoming , Jin Kyung-Hwan , Mao Jiahao , Zhao Mingwen , Liu Zheng , Liu Feng
Published: March 2021

The recent discovery of topological superconductors (TSCs) has sparked enormous interest. The realization of TSC requires a delicate tuning of multiple microscopic parameters, which remains a great challenge. Here, we develop a first-principles approach to quantify realistic conditions of TSC by solving self-consistently Bogoliubov-de Gennes equation based on a Wannier function construction of band structure, in presence of Rashba spin-orbit coupling, Zeeman splitting and electron-phonon coupling. We further demonstrate the power of this method by predicting the Mn-doped GeTe (Ge1-xMnxTe) monolayer—a well-known dilute magnetic semiconductor showing superconductivity under hole doping—to be a Class D TSC with Chern number of −1 and chiral Majorana edge modes. By constructing a first-principles phase diagram in the parameter space of temperature and Mn concentration, we propose the TSC phase can be induced at a lower-limit transition temperature of ~40 mK and the Mn concentration of x~0.015%. Our approach can be generally applied to TSCs with a phonon-mediated pairing, providing useful guidance for future experiments.
Correlation between general health knowledge and sanitation improvements: evidence from rural China
Authors: Huang Li , Qiu Meijun , Zhou Mi
Published: March 2021

A lack of access to sanitation not only has negative effects on the environment but also results in increased prevalence of disease and adversely affects health outcomes. This paper uses data from a survey in Liaoning Province in China to examine the relationship between general health knowledge and improved sanitation facility access. It also explores the effects of work experience and government subsidies on toilet renovation. Using Logit Regression and Duration Analysis, our results show that general health knowledge had a significant positive correlation with flush toilet use and a significant negative correlation with the average duration of traditional latrine pits use. The results of heterogeneity analysis show that work experience in cities can expand farmers’ horizons, which increases their general health knowledge. However, per capita government subsidies are insufficient and result in no significant impact on general health knowledge. This paper also discusses certain restrictions that prevent general health knowledge from having an effect on toilet renovation. The article finally proposes policy recommendations for rural areas in China to better promote the rural toilet revolution and our results can also provide useful guidelines for drawing up relevant policies in other developing countries.
Prediction of distance visual acuity in presbyopic astigmatic subjects
Authors: Hoshikawa Rie , Kamiya Kazutaka , Fujimura Fusako , Shoji Nobuyuki
Published: March 2021

This study was aimed to determine the effect of the amount of astigmatism on distance visual acuity, and to provide a prediction formula of visual acuity according to astigmatism, in a presbyopic population. We comprised 318 eyes of 318 consecutive patients (158 phakic and 160 pseudophakic subjects) without any eye diseases, except for refractive errors with astigmatism of 3 diopter or less. We assessed the relationship of the spherical equivalent visual acuity (SEVA) with astigmatism, and also provided a regression formula of visual acuity according to astigmatism in such subjects. We found a significant correlation between the SEVA and the amount of astigmatism (r = 0.715, p < 0.001) in the entire study population. We obtained similar results, not only in phakic eyes (r = 0.718, p < 0.001), but also in pseudophakic eyes (r = 0.717, p < 0.001). The regression formula was expressed as follows: y = 0.017x2 + 0.125x − 0.116 (R2 = 0.544), where y = logMAR SEVA, and x = astigmatism. We also found no significant differences in the SEVA for matched comparison among the with-the-rule (WTR), against-the-rule (ATR), and oblique (OBL) astigmatism subgroups (p = 0.922). These regression formulas may be clinically beneficial not only for estimating the visual prognosis after astigmatic correction, but also for determining the surgical indication of astigmatic correction.
Geographically weighted machine learning model for untangling spatial heterogeneity of type 2 diabetes mellitus (T2D) prevalence in the USA
Authors: Quiñones Sarah , Goyal Aditya , Ahmed Zia U.
Published: March 2021

Type 2 diabetes mellitus (T2D) prevalence in the United States varies substantially across spatial and temporal scales, attributable to variations of socioeconomic and lifestyle risk factors. Understanding these variations in risk factors contributions to T2D would be of great benefit to intervention and treatment approaches to reduce or prevent T2D. Geographically-weighted random forest (GW-RF), a tree-based non-parametric machine learning model, may help explore and visualize the relationships between T2D and risk factors at the county-level. GW-RF outputs are compared to global (RF and OLS) and local (GW-OLS) models between the years of 2013–2017 using low education, poverty, obesity, physical inactivity, access to exercise, and food environment as inputs. Our results indicate that a non-parametric GW-RF model shows a high potential for explaining spatial heterogeneity of, and predicting, T2D prevalence over traditional local and global models when inputting six major risk factors. Some of these predictions, however, are marginal. These findings of spatial heterogeneity using GW-RF demonstrate the need to consider local factors in prevention approaches. Spatial analysis of T2D and associated risk factor prevalence offers useful information for targeting the geographic area for prevention and disease interventions.
Author Correction: Controllable deposition of organic metal halide perovskite films with wafer-scale uniformity by single source flash evaporation
Authors: Lee Woocheol , Lee Jonghoon , Lee Hyeon-Dong , Kim Junwoo , Ahn Heebeom , Kim Youngrok , Yoo Daekyoung , Lee Jeongjae , Lee Tae-Woo , Kang Keehoon , Lee Takhee
Published: March 2021

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Explainable machine learning can outperform Cox regression predictions and provide insights in breast cancer survival
Authors: Moncada-Torres Arturo , van Maaren Marissa C. , Hendriks Mathijs P. , Siesling Sabine , Geleijnse Gijs
Published: March 2021

Cox Proportional Hazards (CPH) analysis is the standard for survival analysis in oncology. Recently, several machine learning (ML) techniques have been adapted for this task. Although they have shown to yield results at least as good as classical methods, they are often disregarded because of their lack of transparency and little to no explainability, which are key for their adoption in clinical settings. In this paper, we used data from the Netherlands Cancer Registry of 36,658 non-metastatic breast cancer patients to compare the performance of CPH with ML techniques (Random Survival Forests, Survival Support Vector Machines, and Extreme Gradient Boosting [XGB]) in predicting survival using the$$c$$c-index. We demonstrated that in our dataset, ML-based models can perform at least as good as the classical CPH regression ($$c$$c-index $$\sim \,0.63$$∼0.63), and in the case of XGB even better ($$c$$c-index $$\sim 0.73$$∼0.73). Furthermore, we used Shapley Additive Explanation (SHAP) values to explain the models’ predictions. We concluded that the difference in performance can be attributed to XGB’s ability to model nonlinearities and complex interactions. We also investigated the impact of specific features on the models’ predictions as well as their corresponding insights. Lastly, we showed that explainable ML can generate explicit knowledge of how models make their predictions, which is crucial in increasing the trust and adoption of innovative ML techniques in oncology and healthcare overall.
A proof-of-concept study for the pathogenetic role of enhancer hypomethylation of MYBPHL in multiple myeloma
Authors: Wong Kwan Yeung , Morgan Gareth J. , Boyle Eileen M. , Cheng Alfred Sze Lok , Yip Kevin Yuk-Lap , Chim Chor Sang
Published: March 2021

Enhancer DNA methylation and expression of MYBPHL was studied in multiple myeloma (MM). By bisulfite genomic sequencing, among the three CpGs inside the MYBPHL enhancer, CpG1 was significantly hypomethylated in MM cell lines (6.7–50.0%) than normal plasma cells (37.5–75.0%) (P = 0.007), which was negatively correlated with qPCR-measured MYBPHL expression. In RPMI-8226 and WL-2 cells, bearing the highest CpG1 methylation, 5-azadC caused enhancer demethylation and expression of MYBPHL. In primary samples, higher CpG1 methylation was associated with lower MYBPHL expression. By luciferase assay, luciferase activity was enhanced by MYBPHL enhancer compared with empty vector control, but reduced by site-directed mutagenesis of each CpG. RNA-seq data of newly diagnosed MM patients showed that MYBPHL expression was associated with t(11;14). MOLP-8 cells carrying t(11;14) express the highest levels of MYBPHL, and its knockdown reduced cellular proliferation and increased cell death. Herein, as a proof-of-concept, our data demonstrated that the MYBPHL enhancer, particularly CpG1, was hypomethylated and associated with increased MYBPHL expression in MM, which was implicated in myelomagenesis.
A pioneering study indicate role of GABRQ rs3810651 in ASD severity of Indo-Caucasoid female probands
Authors: Saha Sharmistha , Chatterjee Mahasweta , Sinha Swagata , Mukhopadhyay Kanchan
Published: March 2021

Alteration in gamma aminobutyric acid (GABA), the principal inhibitory neurotransmitter, is speculated to be a potential risk factor for Autism Spectrum Disorder (ASD) due to an altered expression in the brain. Sensory, social, and emotional deficits of subjects with ASD were reported to be caused by an imbalance between excitatory and inhibitory neurotransmission as well as GABAergic dysfunction caused by inadequate receptor function. We for the first time studied association between ASD and a missense coding variant rs3810651 (I478F) in the GABRQ gene, encoding for one of the subunits of GABAA receptors. Stratified analysis on families with ASD probands (N = 251) and ethnically matched control subjects (N = 250) revealed marginally higher frequency of “A” allele and “AA” genotype in female ASD probands as compared to gender matched controls. Female probands demonstrated higher severity for Verbal communication (χ2 = 5.75, P = 0.01), Activity level (χ2 = 7.26, P  = 0.007), as well as Level and consistency of intellectual response (χ2 = 7.83 P = 0.005) in presence of “A/AA” warranting further in-depth investigation on the role of rs3810651 in ASD.
Intestinal helminth co-infection is an unrecognised risk factor for increased pneumococcal carriage density and invasive disease
Authors: Law Alice E. , Shears Rebecca K. , Lopez Rodas Andrea A. , Grencis Richard K. , Cooper Philip J. , Neill Daniel R. , Kadioglu Aras
Published: March 2021

Infection with Streptococcus pneumoniae is the leading cause of death in children and burden of disease is greatest where helminth infections are also common. We investigated the impact of intestinal helminth co-infection on pneumococcal carriage; a risk factor for invasive disease. We used a mouse co-infection model and clinical data to assess the impact of co-infection on carriage density. Co-infection in mice was associated with increased pneumococcal carriage density and dissemination into lungs. Helminth-infected children also exhibited increased carriage density as compared to uninfected children. Anthelmintic treatment may be a cost-effective method of reducing pneumococcal disease burden in lower-income countries.
Association of antidiabetic therapies with lower extremity amputation, mortality and healthcare cost from a nationwide retrospective cohort study in Taiwan
Authors: Chang Hsien-Yen , Chou Ying-Yi , Tang Wenze , Chang Guann-Ming , Hsieh Chi‐Feng , Singh Sonal , Tung Yu-Chi
Published: March 2021

We compared risks of clinical outcomes, mortality and healthcare costs among new users of different classes of anti-diabetic medications. This is a population-based, retrospective, new-user design cohort study using the Taiwan National Health Insurance Database between May 2, 2015 and September 30, 2017. An individual was assigned to a medication group based on the first anti-diabetic prescription on or after May 1, 2016: SGLT-2 inhibitors, DPP-4 inhibitors, GLP-1 agonists or older agents (metformin, etc.). Clinical outcomes included lower extremity amputation, peripheral vascular disease, critical limb ischemia, osteomyelitis, and ulcer. We built three Cox proportional hazards models for clinical outcomes and mortality, and three regression models with a log-link function and gamma distribution for healthcare costs, all with propensity-score weighting and covariates. We identified 1,222,436 eligible individuals. After adjustment, new users of SGLT-2 inhibitors were associated with 73% lower mortality compared to those of DPP-4 inhibitors or users of older agents, while 36% lower total costs against those of GLP-1 agonists. However, there was no statistically significant difference in the risk of lower extremity amputation across medication groups. Our study suggested that SGLT-2 inhibitors is associated with lower mortality compared to DPP 4 inhibitors and lower costs compared to GLP-1 agonists.
Author Correction: Quantifying the distribution of protein oligomerization degree reflects cellular information capacity
Authors: Danielli Lena , Li Ximing , Tuller Tamir , Daniel Ramez
Published: March 2021

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Preoperative immune landscape predisposes adverse outcomes in hepatocellular carcinoma patients with liver transplantation
Authors: Yoon Sang-Ho , Choi Seo-Won , Nam Suk Woo , Lee Kyoung Bun , Nam Jin-Wu
Published: March 2021

Immune class in hepatocellular carcinoma (HCC) has been shown to possess immunogenic power; however, how preestablished immune landscapes in premalignant and early HCC stages impact the clinical outcomes of HCC patients remains unexplored. We sequenced bulk transcriptomes for 62 malignant tumor samples from a Korean HCC cohort in which 38 patients underwent total hepatectomy, as well as for 15 normal and 47 adjacent nontumor samples. Using in silico deconvolution of expression mixtures, 22 immune cell fractions for each sample were inferred, and validated with immune cell counting by immunohistochemistry. Cell type-specific immune signatures dynamically shifted from premalignant stages to the late HCC stage. Total hepatectomy patients displayed elevated immune infiltration and prolonged disease-free survival compared to the partial hepatectomy patients. However, patients who exhibited an infiltration of regulatory T cells (Tregs) during the pretransplantation period displayed a high risk of tumor relapse with suppressed immune responses, and pretreatment was a potential driver of Treg infiltration in the total hepatectomy group. Treg infiltration appeared to be independent of molecular classifications based on transcriptomic data. Our study provides not only comprehensive immune signatures in adjacent nontumor lesions and early malignant HCC stages but also clinical guidance for HCC patients who will undergo liver transplantation.
Effectiveness of a digital therapeutic as adjunct to treatment with medication in pediatric ADHD
Authors: Kollins Scott H. , Childress Ann , Heusser Andrew C. , Lutz Jacqueline
Published: March 2021

STARS-Adjunct was a multicenter, open-label effectiveness study of AKL-T01, an app and video-game-based treatment for inattention, as an adjunct to pharmacotherapy in 8–14-year-old children with attention-deficit/hyperactivity disorder (ADHD) on stimulant medication (n = 130) or not on any ADHD medication (n = 76). Children used AKL-T01 for 4 weeks, followed by a 4-week pause and another 4-week treatment. The primary outcome was change in ADHD-related impairment (Impairment Rating Scale (IRS)) after 4 weeks. Secondary outcomes included changes in IRS, ADHD Rating Scale (ADHD-RS). and Clinical Global Impressions Scale—Improvement (CGI-I) on days 28, 56, and 84. IRS significantly improved in both cohorts (On Stimulants: −0.7, p < 0.001; No Stimulants: −0.5, p < 0.001) after 4 weeks. IRS, ADHD-RS, and CGI-I remained stable during the pause and improved with a second treatment period. The treatment was well-tolerated with no serious adverse events. STARS-Adjunct extends AKL-T01’s body of evidence to a medication-treated pediatric ADHD population, and suggests additional treatment benefit.
The digital scribe in clinical practice: a scoping review and research agenda
Authors: van Buchem Marieke M. , Boosman Hileen , Bauer Martijn P. , Kant Ilse M. J. , Cammel Simone A. , Steyerberg Ewout W.
Published: March 2021

The number of clinician burnouts is increasing and has been linked to a high administrative burden. Automatic speech recognition (ASR) and natural language processing (NLP) techniques may address this issue by creating the possibility of automating clinical documentation with a “digital scribe”. We reviewed the current status of the digital scribe in development towards clinical practice and present a scope for future research. We performed a literature search of four scientific databases (Medline, Web of Science, ACL, and Arxiv) and requested several companies that offer digital scribes to provide performance data. We included articles that described the use of models on clinical conversational data, either automatically or manually transcribed, to automate clinical documentation. Of 20 included articles, three described ASR models for clinical conversations. The other 17 articles presented models for entity extraction, classification, or summarization of clinical conversations. Two studies examined the system’s clinical validity and usability, while the other 18 studies only assessed their model’s technical validity on the specific NLP task. One company provided performance data. The most promising models use context-sensitive word embeddings in combination with attention-based neural networks. However, the studies on digital scribes only focus on technical validity, while companies offering digital scribes do not publish information on any of the research phases. Future research should focus on more extensive reporting, iteratively studying technical validity and clinical validity and usability, and investigating the clinical utility of digital scribes.
A role for Dynlt3 in melanosome movement, distribution, acidity and transfer
Authors: Aktary Zackie , Conde-Perez Alejandro , Rambow Florian , Di Marco Mathilde , Amblard François , Hurbain Ilse , Raposo Graça , Delevoye Cédric , Coscoy Sylvie , Larue Lionel
Published: March 2021

Skin pigmentation is dependent on cellular processes including melanosome biogenesis, transport, maturation and transfer to keratinocytes. However, how the cells finely control these processes in space and time to ensure proper pigmentation remains unclear. Here, we show that a component of the cytoplasmic dynein complex, Dynlt3, is required for efficient melanosome transport, acidity and transfer. In Mus musculus melanocytes with decreased levels of Dynlt3, pigmented melanosomes undergo a more directional motion, leading to their peripheral location in the cell. Stage IV melanosomes are more acidic, but still heavily pigmented, resulting in a less efficient melanosome transfer. Finally, the level of Dynlt3 is dependent on β-catenin activity, revealing a function of the Wnt/β-catenin signalling pathway during melanocyte and skin pigmentation, by coupling the transport, positioning and acidity of melanosomes required for their transfer.
The metabolic network of the last bacterial common ancestor
Authors: Xavier Joana C. , Gerhards Rebecca E. , Wimmer Jessica L. E. , Brueckner Julia , Tria Fernando D. K. , Martin William F.
Published: March 2021

Bacteria are the most abundant cells on Earth. They are generally regarded as ancient, but due to striking diversity in their metabolic capacities and widespread lateral gene transfer, the physiology of the first bacteria is unknown. From 1089 reference genomes of bacterial anaerobes, we identified 146 protein families that trace to the last bacterial common ancestor, LBCA, and form the conserved predicted core of its metabolic network, which requires only nine genes to encompass all universal metabolites. Our results indicate that LBCA performed gluconeogenesis towards cell wall synthesis, and had numerous RNA modifications and multifunctional enzymes that permitted life with low gene content. In accordance with recent findings for LUCA and LACA, analyses of thousands of individual gene trees indicate that LBCA was rod-shaped and the first lineage to diverge from the ancestral bacterial stem was most similar to modern Clostridia, followed by other autotrophs that harbor the acetyl-CoA pathway.
Inhibiting LXRα phosphorylation in hematopoietic cells reduces inflammation and attenuates atherosclerosis and obesity in mice
Authors: Voisin Maud , Shrestha Elina , Rollet Claire , Nikain Cyrus A. , Josefs Tatjana , Mahé Mélanie , Barrett Tessa J. , Chang Hye Rim , Ruoff Rachel , Schneider Jeffrey A. , Garabedian Michela L. , Zoumadakis Chris , Yun Chi , Badwan Bara , Brown Emily J. , Mar Adam C. , Schneider Robert J. , Goldberg Ira J. , Pineda-Torra Inés , Fisher Edward A. , Garabedian Michael J.
Published: March 2021

Atherosclerosis and obesity share pathological features including inflammation mediated by innate and adaptive immune cells. LXRα plays a central role in the transcription of inflammatory and metabolic genes. LXRα is modulated by phosphorylation at serine 196 (LXRα pS196), however, the consequences of LXRα pS196 in hematopoietic cell precursors in atherosclerosis and obesity have not been investigated. To assess the importance of LXRα phosphorylation, bone marrow from LXRα WT and S196A mice was transplanted intoLdlr−/−mice, which were fed a western diet prior to evaluation of atherosclerosis and obesity. Plaques from S196A mice showed reduced inflammatory monocyte recruitment, lipid accumulation, and macrophage proliferation. Expression profiling of CD68+and T cells from S196A mouse plaques revealed downregulation of pro-inflammatory genes and in the case of CD68+upregulation of mitochondrial genes characteristic of anti-inflammatory macrophages. Furthermore, S196A mice had lower body weight and less visceral adipose tissue; this was associated with transcriptional reprograming of the adipose tissue macrophages and T cells, and resolution of inflammation resulting in less fat accumulation within adipocytes. Thus, reducing LXRα pS196 in hematopoietic cells attenuates atherosclerosis and obesity by reprogramming the transcriptional activity of LXRα in macrophages and T cells to promote an anti-inflammatory phenotype.
MED15 prion-like domain forms a coiled-coil responsible for its amyloid conversion and propagation
Authors: Batlle Cristina , Calvo Isabel , Iglesias Valentin , J. Lynch Cian , Gil-Garcia Marcos , Serrano Manuel , Ventura Salvador
Published: March 2021

A disordered to β-sheet transition was thought to drive the functional switch of Q/N-rich prions, similar to pathogenic amyloids. However, recent evidence indicates a critical role for coiled-coil (CC) regions within yeast prion domains in amyloid formation. We show that many human prion-like domains (PrLDs) contain CC regions that overlap with polyQ tracts. Most of the proteins bearing these domains are transcriptional coactivators, including the Mediator complex subunit 15 (MED15) involved in bridging enhancers and promoters. We demonstrate that the human MED15-PrLD forms homodimers in solution sustained by CC interactions and that it is this CC fold that mediates the transition towards a β-sheet amyloid state, its chemical or genetic disruption abolishing aggregation. As in functional yeast prions, a GFP globular domain adjacent to MED15-PrLD retains its structural integrity in the amyloid state. Expression of MED15-PrLD in human cells promotes the formation of cytoplasmic and perinuclear inclusions, kidnapping endogenous full-length MED15 to these aggregates in a prion-like manner. The prion-like properties of MED15 are conserved, suggesting novel mechanisms for the function and malfunction of this transcription coactivator.
INPP4B protects from metabolic syndrome and associated disorders
Authors: Zhang Manqi , Ceyhan Yasemin , Kaftanovskaya Elena M. , Vasquez Judy L. , Vacher Jean , Knop Filip K. , Nathanson Lubov , Agoulnik Alexander I. , Ittmann Michael M. , Agoulnik Irina U.
Published: March 2021

A high fat diet and obesity have been linked to the development of metabolic dysfunction and the promotion of multiple cancers. The causative cellular signals are multifactorial and not yet completely understood. In this report, we show that Inositol Polyphosphate-4-Phosphatase Type II B (INPP4B) signaling protects mice from diet-induced metabolic dysfunction. INPP4B suppresses AKT and PKC signaling in the liver thereby improving insulin sensitivity. INPP4B loss results in the proteolytic cleavage and activation of a key regulator in de novo lipogenesis and lipid storage, SREBP1. In mice fed with the high fat diet, SREBP1 increases expression and activity of PPARG and other lipogenic pathways, leading to obesity and non-alcoholic fatty liver disease (NAFLD). Inpp4b−/− male mice have reduced energy expenditure and respiratory exchange ratio leading to increased adiposity and insulin resistance. When treated with high fat diet, Inpp4b−/− males develop type II diabetes and inflammation of adipose tissue and prostate. In turn, inflammation drives the development of high-grade prostatic intraepithelial neoplasia (PIN). Thus, INPP4B plays a crucial role in maintenance of overall metabolic health and protects from prostate neoplasms associated with metabolic dysfunction.
CENP-A overexpression promotes distinct fates in human cells, depending on p53 status
Authors: Jeffery Daniel , Gatto Alberto , Podsypanina Katrina , Renaud-Pageot Charlène , Ponce Landete Rebeca , Bonneville Lorraine , Dumont Marie , Fachinetti Daniele , Almouzni Geneviève
Published: March 2021

Tumour evolution is driven by both genetic and epigenetic changes. CENP-A, the centromeric histone H3 variant, is an epigenetic mark that directly perturbs genetic stability and chromatin when overexpressed. Although CENP-A overexpression is a common feature of many cancers, how this impacts cell fate and response to therapy remains unclear. Here, we established a tunable system of inducible and reversible CENP-A overexpression combined with a switch in p53 status in human cell lines. Through clonogenic survival assays, single-cell RNA-sequencing and cell trajectory analysis, we uncover the tumour suppressor p53 as a key determinant of how CENP-A impacts cell state, cell identity and therapeutic response. If p53 is functional, CENP-A overexpression promotes senescence and radiosensitivity. Surprisingly, when we inactivate p53, CENP-A overexpression instead promotes epithelial-mesenchymal transition, an essential process in mammalian development but also a precursor for tumour cell invasion and metastasis. Thus, we uncover an unanticipated function of CENP-A overexpression to promote cell fate reprogramming, with important implications for development and tumour evolution.
Near-unity broadband omnidirectional emissivity via femtosecond laser surface processing
Authors: Reicks Andrew , Tsubaki Alfred , Anderson Mark , Wieseler Jace , Khorashad Larousse Khosravi , Shield Jeffrey E. , Gogos George , Alexander Dennis , Argyropoulos Christos , Zuhlke Craig
Published: March 2021

It is very challenging to achieve near perfect absorption or emission that is both broadband and omnidirectional while utilizing a scalable fabrication process. Femtosecond laser surface processing is an emerging low-cost and large-scale manufacturing technique used to directly and permanently modify the surface properties of a material. The versatility of this technique to produce tailored surface properties has resulted in a rapidly growing number of applications. Here, we demonstrate near perfect, broadband, omnidirectional emissivity from aluminum surfaces by tuning the laser surface processing parameters including fluence, pulse count, and the ambient gas. Full-wave simulations and experimental results prove that the obtained increase in emissivity is mainly a result of two distinct features produced by femtosecond laser surface processing: the introduction of microscale surface features and the thick oxide layer. This technique leads to functionalized metallic surfaces that are ideal for emerging applications, such as passive radiative cooling and thermal management of spacecraft.
Vegetation and microbes interact to preserve carbon in many wooded peatlands
Authors: Wang Hongjun , Tian Jianqing , Chen Huai , Ho Mengchi , Vilgalys Rytas , Bu Zhao-Jun , Liu Xingzhong , Richardson Curtis J.
Published: March 2021

Peatlands have persisted as massive carbon sinks over millennia, even during past periods of climate change. The commonly accepted theory of abiotic controls (mainly anoxia and low temperature) over carbon decomposition cannot fully explain how vast low-latitude shrub/tree dominated (wooded) peatlands consistently accrete peat under warm and seasonally unsaturated conditions. Here we show, by comparing the composition and ecological traits of microbes between Sphagnum- and shrub-dominated peatlands, that slow-growing microbes decisively dominate the studied shrub-dominated peatlands, concomitant with plant-induced increases in highly recalcitrant carbon and phenolics. The slow-growing microbes metabolize organic matter thirty times slower than the fast-growing microbes that dominate our Sphagnum-dominated site. We suggest that the high-phenolic shrub/tree induced shifts in microbial composition may compensate for positive effects of temperature and/or drought on metabolism over time in peatlands. This biotic self-sustaining process that modulates abiotic controls on carbon cycling may improve projections of long-term, climate-carbon feedbacks in peatlands.
Environmentally persistent free radicals are ubiquitous in wildfire charcoals and remain stable for years
Authors: Sigmund Gabriel , Santín Cristina , Pignitter Marc , Tepe Nathalie , Doerr Stefan H. , Hofmann Thilo
Published: March 2021

Globally landscape fires produce about 256 Tg of pyrogenic carbon or charcoal each year. The role of charcoal as a source of environmentally persistent free radicals, which are precursors of potentially harmful reactive oxygen species, is poorly constrained. Here, we analyse 60 charcoal samples collected from 10 wildfires, that include crown as well as surface fires in forest, shrubland and grassland spanning different boreal, temperate, subtropical and tropical climate. Using electron spin resonance spectroscopy, we measure high concentrations of environmentally persistent free radicals in charcoal samples, much higher than those found in soils. Concentrations increased with degree of carbonization and woody fuels favoured higher concentrations. Moreover, environmentally persistent free radicals remained stable for an unexpectedly long time of at least 5 years. We suggest that wildfire charcoal is an important global source of environmentally persistent free radicals, and therefore potentially of harmful reactive oxygen species.
Engineering nanomedicine for glutathione depletion-augmented cancer therapy
Authors: Xiong Yuxuan , Xiao Chen , Li Zifu , Yang Xiangliang
Published: March 2021

In this review, we systematically survey the most recent progress in engineering nanomedicine for intracellular glutathione consumption-augmented cancer therapy.
Earth-abundant 3d-transition-metal catalysts for lignocellulosic biomass conversion
Authors: Feng Yunchao , Long Sishi , Tang Xing , Sun Yong , Luque Rafael , Zeng Xianhai , Lin Lu
Published: March 2021

Transformation of biomass to chemicals and fuels is a long-term goal in both science and industry. Here, we review the fast development and recent advances of 3d-metal-based catalysts including Cu, Fe, Co, Ni and Mn in lignocellulosic biomass conversion.
The dynamic interplay between intramolecular and intermolecular interactions in mononuclear manganese(iii) SCO complexes
Authors: Qin Chun-Yan , Zhao Sheng-Ze , Wu Hua-Yu , Li Yong-Hua , Wang Zi-Kun , Wang Zheng , Wang Shi
Published: March 2021

Spin crossover in Mn(iii) ions is the most rare event. Changing the size of the anions from PF6−, AsF6−, SbF6− to BF4−, ClO4−, Cl−, Br−, and I− led to a significant change of the overall crystal packing and furthermore the Mn(iii) spin state.
Emergence and stabilization of transient twisted defect structures in confined achiral liquid crystals at a phase transition
Authors: Velez Jose X. , Zheng Zhaofei , Beller Daniel A. , Serra Francesca
Published: March 2021

We report a transient twist observed in common thermotropic, achiral liquid crystals at the transition between the smectic and the nematic phase. This is explained with the combined effect of the change of the elastic constants at the phase transition and of the confining geometry.
Single enzyme electroanalysis
Authors: Vannoy Kathryn J. , Ryabykh Andrey , Chapoval Andrei I. , Dick Jeffrey E.
Published: March 2021

Traditional enzymology relies on the kinetics of millions of enzymes, an experimental approach that may wash out heterogeneities between individual enzymes. Electrochemical methods have emerged in the last 5 years to probe single enzyme reactivity.
Correction: The potential role of borophene as a radiosensitizer in boron neutron capture therapy (BNCT) and particle therapy (PT)
Authors: Qi Pengyuan , Chen Qianyuan , Tu Dong , Yao Songhuan , Zhang Yupeng , Wang Jike , Xie Conghua , Pan Chunxu , Peng Hao
Published: March 2021

Correction for ‘The potential role of borophene as a radiosensitizer in boron neutron capture therapy (BNCT) and particle therapy (PT)’ by Pengyuan Qi et al., Biomater. Sci., 2020, 8, 2778–2785, DOI: 10.1039/D0BM00318B.
Nanosphere [Ag(SR)]n: coordination polymers of Ag+ with a combination of hydrophilic and hydrophobic thiols
Authors: Xu Yan , Dong Su-Li , Yan Xiao-Sheng , Wang Qian , Li Zhao , Jiang Yun-Bao
Published: March 2021

A strategy for building nanospheres is proposed by using a combination of both a hydrophilic and a hydrophobic thiol ligand to form coordination polymers of Ag+ in aqueous solutions.
N-Heterocyclic carbene complexes enabling the α-arylation of carbonyl compounds
Authors: Ostrowska Sylwia , Scattolin Thomas , Nolan Steven P.
Published: March 2021

The considerable importance of α-arylated carbonyl compounds, which are widely used in the pharmaceutical industry, has prompted efficient synthetic strategies for their preparation.
High anticancer activity and apoptosis- and autophagy-inducing properties of novel lanthanide(iii) complexes bearing 8-hydroxyquinoline-N-oxide and 1,10-phenanthroline
Authors: Yang Yan , Zhou Zhen , Wei Zu-Zhuang , Qin Qi-Pin , Yang Lin , Liang Hong
Published: March 2021

This study constitutes the first example of antitumor NQ-phen Ln(iii) complexes inducing autophagy-mediated cell death.
Rapid dissolution of β-chitin and hierarchical self-assembly of chitin chains in aqueous KOH/urea solution
Authors: Huang Junchao , Zhong Yi , Wei Pingdong , Cai Jie
Published: March 2021

β-chitin allows for rapid penetration of solvent molecules, followed by swelling and dissolution. During neutralization, the chitin chains self-assembled into nanofibrils, and even the formation of hydrogels of crystalline α-chitin.
Tissue metabolic profiling reveals major metabolic alteration in colorectal cancer
Authors: Shen Yao , Sun Mao , Zhu Jun , Wei Mengying , Li Huichen , Zhao Pan , Wang Jiajia , Li Ruikai , Tian Lianlian , Tao Yanyan , Shen Peng , Zhang Jian
Published: March 2021

Novel insights into metabolism profiling of colorectal cancer by mass spectrometry-based metabolomics conducted on tissue samples.
N-(5-Amino-9H-benzo[a]phenoxazin-9-ylidene)propan-1-aminium chlorides as antifungal agents and NIR fluorescent probes
Authors: Sousa Rui P. C. L. , Ferreira João C. C. , Sousa Maria João , Gonçalves M. Sameiro T.
Published: March 2021

New benzo[a]phenoxazinium chlorides (λemi ≤ 683 nm, ΦF ≤ 0.24, at pH = 7.4), best MIC 6.25 μM in Saccharomyces cerevisiae, stain vacuolar/perinuclear membranes of cells.
Copper catalyzed five-component domino strategy for the synthesis of nicotinimidamides
Authors: Zhao Yu , Li Li , Zhou Zitong , Chen Man , Yang Weiguang , Luo Hui
Published: March 2021

Copper catalyzed five-component domino strategy to synthesize nicotinimidamides via a CuAAC/ring-opening procedure and generate a highly reactive N-sulfonyl acetylketenimine intermediate.
Composition-dependent phase transformation in side-chain liquid crystalline copolymers with mesogenic groups at different substituent positions
Authors: Pei Jiwei , Wei Wenjing , Li Bian , Huang Jundan , Chen Xiao-Fang
Published: March 2021

The composition and chemical structures have important effects on the evolution of supramolecular liquid crystalline structures in SCLC copolymers.