bluuebunny/crossref_metadata_2025 huggingface dataset:
¡Casi te caístes!: Variation in second person singular preterit forms in Spanish Children
Authors: BAKER Elisabeth
Published: July 2021

The current study investigates Spanish children's variation between the standard and non-standard forms for second person singular preterit –s (caiste ~ caístes). All second person singular preterit forms were extracted from the spontaneous speech of 78 children in Spain and analyzed for the effects of age, language contact setting, and lexical frequency. Results show that children in contact with Galician and Catalan produce more non-standard than children in non-contact areas like Madrid. Meanwhile, low-frequency verbs (e.g., pillaste) are more likely to occur with the non-standard –s than high-frequency verbs (e.g., fuiste). However, age is not a significant predictor of children's 2sg preterit production. These preliminary findings demonstrate that Spanish children do have the non-standard -s in their speech, and that their 2sg preterit forms are significantly conditioned by language contact and lexical frequency.
Housing, sanitation and living conditions affecting SARS-CoV-2 prevention interventions in 54 African countries
Authors: Brewer Timothy F. , Zhang Mary , Gordon David , Chung Roger Yat-Nork , Dejene Negussie , Fonta Cynthia L. , Grieve Tigist , Halleröd Björn , Harris Richard , Lanau Alba , Leibbrandt Murray , Mekonen Yehualashet , Muguni Bongai , Najera Hector , Nandy Shailen , Heymann S. Jody
Published: July 2021

The feasibility of non-pharmacological public health interventions (NPIs) such as physical distancing or isolation at home to prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission in low-resource countries is unknown. Household survey data from 54 African countries were used to investigate the feasibility of SARS-CoV-2 NPIs in low-resource settings. Across the 54 countries, approximately 718 million people lived in households with ⩾6 individuals at home (median percentage of at-risk households 56% (95% confidence interval (CI), 51% to 60%)). Approximately 283 million people lived in households where ⩾3 people slept in a single room (median percentage of at-risk households 15% (95% CI, 13% to 19%)). An estimated 890 million Africans lack on-site water (71% (95% CI, 62% to 80%)), while 700 million people lacked in-home soap/washing facilities (56% (95% CI, 42% to 73%)). The median percentage of people without a refrigerator in the home was 79% (95% CI, 67% to 88%), while 45% (95% CI, 39% to 52%) shared toilet facilities with other households. Individuals in low-resource settings have substantial obstacles to implementing NPIs for mitigating SARS-CoV-2 transmission. These populations urgently need to be prioritised for coronavirus disease 2019 vaccination to prevent disease and to contain the global pandemic.
Barriers to care in urban and rural dwelling adults with congenital heart disease
Authors: McGrath Lidija , Taunton Marshall , Levy Sheldon , Kovacs Adrienne H. , Broberg Craig , Khan Abigail
Published: July 2021

Introduction:

Adults with congenital heart disease (CHD) face a unique set of medical, psychological, and social challenges, and access to specialised adult congenital heart disease care has been associated with improved outcomes. Rural adults with CHD may represent a uniquely disadvantaged group given additional challenges when accessing specialised care. The aim of this study was to investigate the challenges faced by adults with CHD in accessing outpatient cardiac care, with a specific focus on understanding differences between urban- and rural-dwelling patients.

Methods:

This cross-sectional, survey-based study took place in the adult congenital heart disease clinic at an urban academic medical center. Additional medical information was abstracted in a retrospective manner from the electronic health record. In addition to descriptive statistics, t-tests and Chi-square tests were performed to investigate differences between urban and rural dwelling patients.

Results:

A total of 100 patients participated in the study (mean age 40 ± 13 years, 60% female, 18% rural dwelling). Across the total sample, the median driving distance to clinic was 20 miles (interquartile range 12–77); it was 15 miles for urban dwellers and 77 miles for rural dwelling patients (p < 0.001). The most commonly identified barriers to cardiac clinic visits were financial losses related to taking time off from work (39%), distance of clinic from home (33%), and weather (33%). Compared to urban dwelling patients, on average those who were rural dwelling had a lower level of education (p = 0.04), more difficulty paying insurance premiums (p < 0.001) and copays (p = 0.005), and were more likely to identify the distance from clinic (p = 0.05) and having to go into the city (p = 0.02) as barriers to clinic appointments.

Conclusions:

The financial impact and distance to clinic were the most commonly identified barriers to outpatient cardiac care in this cohort of adults with CHD. These barriers, along with difficulty paying insurance premiums, are more common in rural dwelling patients. Initiatives such as telemedicine visits or providing financial subsidies for travel and treatment could help to expand specialty adult congenital heart disease care and better serve this growing patient population.
Parenting style as a predictor of dietary score change in children from 4 to 14 years of age. Findings from the Longitudinal Study of Australian Children
Authors: Burnett Alissa J , Lamb Karen E , Spence Alison C , Lacy Kathleen E , Worsley Anthony
Published: July 2021

Objective:

To examine associations between parenting style and changes in dietary quality score across childhood.

Design:

This longitudinal analysis included the child’s frequency of consumption for twelve food and drink items reported by mothers of children (aged 4–8 years) and children (aged 10–14 years) during face-to-face interviews biennially. These items were combined into dietary scores based on the Australian Dietary Guidelines. Parenting styles were classified at baseline as authoritative, authoritarian, permissive and disengaged. Multilevel modelling was used to examine changes in diet quality score over time by maternal parenting styles.

Setting:

The Longitudinal Study of Australian Children.

Participants:

A total of 4282 children aged 4 to 14 years.

Results:

Children’s diet quality score declined over time between 4 and 14 years of age (β = –0·10, 95 % CI (–0·11, –0·08)). There was strong evidence to suggest that change in diet quality differed dependent on baseline maternal parenting style, although diet quality declined for all groups. Children with authoritative mothers had the greatest decline in diet quality score over time (β = –0·13; 95 % CI (–0·18, –0·08)), while children with disengaged mothers had the lowest decline (β = –0·03; 95 % CI (–0·07, 0·01)). However, it is important to note that children with authoritative mothers had a better dietary quality score than children of permissive or disengaged mothers for most of their childhood.

Conclusion:

These findings question the previous assumptions that early exposure to an authoritative parenting style has lasting positive effects on the dietary intake of children.
Creation and Characterization of an Atomically Sharp Single/Trimer Atom Ir/W(111) Tip by Thermal Field-Assisted Faceting
Authors: Kim Kwang-Il , Hwang Junhyeok , Pin Min-Wook , Kwon Jihwan , Lee Ha Rim , Park In-Yong
Published: July 2021

Atomically sharpened tips have attracted much interest in the imaging and manufacturing fields due to their high spatial resolutions. Typically, tungsten (W) is mainly used as the material of such a tip, but when the W tip is used in an oxygen environment, a limit is revealed due to corrosiveness stemming from a reaction with the oxygen gas. To solve this problem, methods of depositing a metal on W that does not react with oxygen have been studied. In this study, we introduce a method of depositing iridium (Ir) directly onto an insulating layer without an additional pretreatment to remove the insulating layer remaining on the W surface, forming an Ir-nanopyramid structure at the apex of the W tip by field evaporation and faceting. Field ion microscopy and atom probe tomography were used to analyze the crystal structure and composition at the apex during the faceting process, and the overall tip shape change after faceting was compared and analyzed with transmission electron microscopy. The proposed method does not have a tip heating step when creating an atomically sharp tip such that it can be made easily with a simpler equipment configuration than in the existing method.
Evaluation of Corrosion of Refractory Materials Using Electron Microscopy
Authors: Vadász Pavol , Medveď Dávid , Plešingerová Beatrice , Labaj Jerzy
Published: July 2021

The interaction of NCC-A (no cement content, with tabular corundum) refractory castable with corrosive refining steel slag CaO–Al2O3–SiO2–MgO–(FeO, MnO) was studied with static crucible corrosion tests. The corrosion process was evaluated using chemical and phase analyses, and the macro- and microstructures on the corrosion boundary of slag–refractory materials were investigated. We describe the corrosion progress and explain the NCC-A corrosion mechanism by oxide metallurgical slags. The alumina refractory material surface was wetted with molten oxide slag (contact angle θ1390°C from 10° to 20°). The slag penetrated through dissolution of the matrix (fine alumina cement), and the Ca–Si–Al slag, enriched with alumina, attacked the corundum grog. Marked changes in the chemical composition of the slag had an impact on the primary crystallization temperature. As the concentration of Al–O complexes increased in the slag, the binding parameters in Si–O complexes changed and complex tetrahedral units (Al–O–Si) and (Al–O–Mg) were created. Analyses of the corrosion interface grog show that calcium ions diffuse through structural defects in the corundum but Mg2+ diffusion was not observed. A sharp interface is observed between the slag and the corroded corundum layer. Differences in the chemical composition of the slag in the corrosion zone affected the convention stream, and formed the concave corrosion profile of the crucible.
Wernicke encephalopathy in a lung cancer patient receiving home medical care
Authors: Ito Hiroshi , Ishida Mayumi , Itami Kumi , Yoshioka Akira , Sato Izumi , Uchida Nozomu , Onizawa Nobuyuki , Onishi Hideki
Published: July 2021

Objective

Cancer patients often want to spend their final days at home, and it is essential that general practitioners have knowledge of and technical skills related to cancer medicine and symptom relief. Recent clinical studies have revealed that Wernicke encephalopathy (WE) is quite common in cancer patients. However, there have been no reports to date on WE in cancer patients undergoing home medical care.

Methods

From a series of cancer patient undergoing home medical care, we reported a patient with lung cancer who developed WE.

Results

An 84-year-old female with lung cancer undergoing home medical care developed an impaired mental state and an attention deficit. Her symptoms fulfilled the diagnostic criteria for delirium. WE was suspected as the patient's food intake had fallen from normal a month previously to somewhere between 50% or just a few mouthfuls. This diagnosis was supported by abnormal serum thiamine and the disappearance of delirium after thiamine administration.

Significance of the results

When delirium occurs in cancer patients undergoing home treatment, it is necessary to suspect thiamine deficiency as a potential cause, as appropriate diagnosis and treatment can prevent irreversible brain-related sequelae.
Juno Waves High Frequency Antenna Properties
Authors: Sampl Manfred , Macher Wolfgang , Oswald Thomas , Plettemeier Dirk , Rucker Helmut O. , Kurth William S.
Published: July 2021

The Waves instrument aboard Juno is a sophisticated radio astronomy observatory investigating Jupiter's auroral radio emissions and plasma wave interactions. Waves records electric field properties using two monopole antennas, which are connected to form a dipole. The receiving properties of the Waves dipole changes quite remarkably over the instrument's frequency range from near DC to 40 MHz. In this contribution we outline Waves' electrical sensor properties above the quasi‐static frequency range and provide detailed directivity pattern and insertion loss figures of the instrument for science application and data analysis.
Test Particle Model Predictions of SEP Electron Transport and Precipitation at Mars
Authors: Jolitz R. D. , Dong C. F. , Rahmati A. , Brain D. A. , Lee C. O. , Lillis R. J. , Curry S. M. , Jakosky B. M.
Published: July 2021

Extreme space weather events can episodically release solar energetic particles (SEPs) that precipitate into planetary atmospheres, leading to aurora and increased ionization. While the induced magnetosphere of Mars does not substantially obstruct SEP protons, the effect on SEP electrons is not known. We use a test particle model modified for relativistic electrons to model transport of 10–200 keV electrons from outside the bow shock and deep in the magnetotail of Mars. We find a substantial influence of curvature and gradient drifts on precipitation, leading to depletions in the bow shock and transport onto closed field lines. The model estimates ∼3% of incident flux precipitates into the Mars atmosphere for a typical SEP event under nominal solar wind conditions, exceeding the estimate from the guiding center path approximation without drift terms. Precipitation is globally patchy. The model estimates 55% of electrons precipitating into cusps along open field lines and 45% precipitating on closed field lines, suggesting drift and nonadiabatic transport mechanisms have a significant influence on precipitation. We also predict that the fraction of precipitating differential flux increases as a function of energy. We discuss how these predictions would be affected by disturbed conditions that tend to accompany the arrival of SEPs and by differing SEP electron spectra hardness and anisotropy. We finally discuss how the simulation predictions compare to observations of diffuse aurora.
Extended follow-up of a short total diet replacement programme: results of the Doctor Referral of Overweight People to Low Energy total diet replacement Treatment (DROPLET) randomised controlled trial at 3 years
Authors: Astbury Nerys M. , Edwards Rhiannon M. , Ghebretinsea Fitsum , Shanyinde Milensu , Mollison Jill , Aveyard Paul , Jebb Susan A.
Published: July 2021

Objectives

To test the long-term effectiveness of a total diet replacement programme (TDR) for routine treatment of obesity in a primary care setting.

Methods

This study was a pragmatic, two-arm, parallel-group, open-label, individually randomised controlled trial in adults with obesity. The outcomes were change in weight and biomarkers of diabetes and cardiovascular disease risk from baseline to 3 years, analysed as intention-to-treat with mixed effects models.

Interventions

The intervention was TDR for 8 weeks, followed by food-reintroduction over 4 weeks. Behavioural support was provided weekly for 8 weeks, bi-weekly for the next 4 weeks, then monthly for 3 months after which no further support was provided. The usual care (UC) group received dietary advice and behavioural support from a practice nurse for up to 3 months.

Results

Outcome measures were collected from 179 (66%) participants. Compared with baseline, at 3 years the TDR group lost −6.2 kg (SD 9.1) and usual care −2.7 kg (SD 7.7); adjusted mean difference −3.3 kg (95% CI: −5.2, −1.5), p < 0.0001. Regain from programme end (6 months) to 3 years was greater in TDR group +8.9 kg (SD 9.4) than UC + 1.2, (SD 9.1); adjusted mean difference +6.9 kg (95% CI 4.2, 9.5) P < 0.001. At 3 years TDR led to greater reductions than UC in diastolic blood pressure (mean difference −3.3 mmHg (95% CI:−6.2; −0.4) P = 0.024), and systolic blood pressure (mean differences −3.7 mmHg (95% CI: −7.4; 0.1) P = 0.057). There was no evidence of differences between groups in the change from baseline to 3 years HbA1c (−1.9 mmol/mol (95% CI: −0.7; 4.5; P = 0.15), LDL cholesterol concentrations (0.2 mmol/L (95% CI −0.3, 0.7) P = 0.39), cardiovascular risk score (QRISK2) (−0.37 (95% CI −0.96; 0.22); P = 0.22).

Conclusions

Treatment of people with obesity with a TDR programme compared with support from a practice nurse leads to greater weight loss which persists to at least 3 years, but there was only evidence of sustained improvements in BP and not in other aspects of cardiometabolic risk.
Genetic contributions to alcohol use disorder treatment outcomes: a genome-wide pharmacogenomics study
Authors: Biernacka Joanna M. , Coombes Brandon J. , Batzler Anthony , Ho Ada Man-Choi , Geske Jennifer R. , Frank Josef , Hodgkinson Colin , Skime Michelle , Colby Colin , Zillich Lea , Pozsonyiova Sofia , Ho Ming-Fen , Kiefer Falk , Rietschel Marcella , Weinshilboum Richard , O’Malley Stephanie S. , Mann Karl , Anton Ray , Goldman David , Karpyak Victor M.
Published: July 2021

Naltrexone can aid in reducing alcohol consumption, while acamprosate supports abstinence; however, not all patients with alcohol use disorder (AUD) benefit from these treatments. Here we present the first genome-wide association study of AUD treatment outcomes based on data from the COMBINE and PREDICT studies of acamprosate and naltrexone, and the Mayo Clinic CITA study of acamprosate. Primary analyses focused on treatment outcomes regardless of pharmacological intervention and were followed by drug-stratified analyses to identify treatment-specific pharmacogenomic predictors of acamprosate and naltrexone response. Treatment outcomes were defined as: (1) time until relapse to any drinking (TR) and (2) time until relapse to heavy drinking (THR; ≥ 5 drinks for men, ≥4 drinks for women in a day), during the first 3 months of treatment. Analyses were performed within each dataset, followed by meta-analysis across the studies (N = 1083 European ancestry participants). Single nucleotide polymorphisms (SNPs) in the BRE gene were associated with THR (min p = 1.6E−8) in the entire sample, while two intergenic SNPs were associated with medication-specific outcomes (naltrexone THR: rs12749274, p = 3.9E−8; acamprosate TR: rs77583603, p = 3.1E−9). The top association signal for TR (p = 7.7E−8) and second strongest signal in the THR (p = 6.1E−8) analysis of naltrexone-treated patients maps to PTPRD, a gene previously implicated in addiction phenotypes in human and animal studies. Leave-one-out polygenic risk score analyses showed significant associations with TR (p = 3.7E−4) and THR (p = 2.6E−4). This study provides the first evidence of a polygenic effect on AUD treatment response, and identifies genetic variants associated with potentially medication-specific effects on AUD treatment response.
Human cell transformation by combined lineage conversion and oncogene expression
Authors: Sahu Biswajyoti , Pihlajamaa Päivi , Zhang Kaiyang , Palin Kimmo , Ahonen Saija , Cervera Alejandra , Ristimäki Ari , Aaltonen Lauri A. , Hautaniemi Sampsa , Taipale Jussi
Published: July 2021

Cancer is the most complex genetic disease known, with mutations implicated in more than 250 genes. However, it is still elusive which specific mutations found in human patients lead to tumorigenesis. Here we show that a combination of oncogenes that is characteristic of liver cancer (CTNNB1, TERT, MYC) induces senescence in human fibroblasts and primary hepatocytes. However, reprogramming fibroblasts to a liver progenitor fate, induced hepatocytes (iHeps), makes them sensitive to transformation by the same oncogenes. The transformed iHeps are highly proliferative, tumorigenic in nude mice, and bear gene expression signatures of liver cancer. These results show that tumorigenesis is triggered by a combination of three elements: the set of driver mutations, the cellular lineage, and the state of differentiation of the cells along the lineage. Our results provide direct support for the role of cell identity as a key determinant in transformation and establish a paradigm for studying the dynamic role of oncogenic drivers in human tumorigenesis.
Platelet-derived lysophosphatidic acid mediated LPAR1 activation as a therapeutic target for osteosarcoma metastasis
Authors: Takagi Satoshi , Sasaki Yuki , Koike Sumie , Takemoto Ai , Seto Yosuke , Haraguchi Mizuki , Ukaji Takao , Kawaguchi Tokuichi , Sugawara Minoru , Saito Masanori , Funauchi Yuki , Ae Keisuke , Matsumoto Seiichi , Fujita Naoya , Katayama Ryohei
Published: July 2021

Osteosarcoma is the most common primary malignant bone cancer, with high rates of pulmonary metastasis. Osteosarcoma patients with pulmonary metastasis have worse prognosis than those with localized disease, leading to dramatically reduced survival rates. Therefore, understanding the biological characteristics of metastatic osteosarcoma and the molecular mechanisms of invasion and metastasis of osteosarcoma cells will lead to the development of innovative therapeutic intervention for advanced osteosarcoma. Here, we identified that osteosarcoma cells commonly exhibit high platelet activation-inducing characteristics, and molecules released from activated platelets promote the invasiveness of osteosarcoma cells. Given that heat-denatured platelet releasate maintained the ability to promote osteosarcoma invasion, we focused on heat-tolerant molecules, such as lipid mediators in the platelet releasate. Osteosarcoma-induced platelet activation leads to abundant lysophosphatidic acid (LPA) release. Exposure to LPA or platelet releasate induced morphological changes and increased invasiveness of osteosarcoma cells. By analyzing publicly available transcriptome datasets and our in-house osteosarcoma patient-derived xenograft tumors, we found that LPA receptor 1 (LPAR1) is notably upregulated in osteosarcoma. LPAR1 gene KO in osteosarcoma cells abolished the platelet-mediated osteosarcoma invasion in vitro and the formation of early pulmonary metastatic foci in experimental pulmonary metastasis models. Of note, the pharmacological inhibition of LPAR1 by the orally available LPAR1 antagonist, ONO-7300243, prevented pulmonary metastasis of osteosarcoma in the mouse models. These results indicate that the LPA–LPAR1 axis is essential for the osteosarcoma invasion and metastasis, and targeting LPAR1 would be a promising therapeutic intervention for advanced osteosarcoma.
The therapeutic and prognostic implications of immunobiology in colorectal cancer: a review
Authors: Zaborowski Alexandra M. , Winter Des C. , Lynch Lydia
Published: July 2021

Colorectal cancer represents the second leading cause of cancer-related death worldwide. The therapeutic field of immuno-oncology has rapidly gained momentum, with strikingly promising results observed in clinical practice. Increasing emphasis has been placed on the role of the immune response in tumorigenesis, therapy and predicting prognosis. Enhanced understanding of the dynamic and complex tumour-immune microenvironment has enabled the development of molecularly directed, individualised treatment. Analysis of intra-tumoural lymphocyte infiltration and the dichotomisation of colorectal cancer into microsatellite stable and unstable disease has important therapeutic and prognostic implications, with potential to capitalise further on this data. This review discusses the latest evidence surrounding the tumour biology and immune landscape of colorectal cancer, novel immunotherapies and the interaction of the immune system with each apex of the tripartite of cancer management (oncotherapeutics, radiotherapy and surgery). By utilising the synergy of chemotherapeutic agents and immunotherapies, and identifying prognostic and predictive immunological biomarkers, we may enter an era of unprecedented disease control, survivorship and cure rates.
miR-4293 upregulates lncRNA WFDC21P by suppressing mRNA-decapping enzyme 2 to promote lung carcinoma proliferation
Authors: Zhang Qian , Yan Yun-Fei , Lv Qing , Li You-Jie , Wang Ran-Ran , Sun Guang-Bin , Pan Li , Hu Jin-Xia , Xie Ning , Zhang Can , Tian Bao-Cheng , Jiao Fei , Xu Sen , Wang Ping-Yu , Xie Shu-Yang
Published: July 2021

Non-coding RNAs (ncRNAs) involve in diverse biological processes by post-transcriptional regulation of gene expression. Emerging evidence shows that miRNA-4293 plays a significant role in the development of non-small cell lung cancer. However, the oncogenic functions of miR-4293 have not been studied. Our results demonstrated that miR-4293 expression is markedly enhanced in lung carcinoma tissue and cells. Moreover, miR-4293 promotes tumor cell proliferation and metastasis but suppresses apoptosis. Mechanistic investigations identified mRNA-decapping enzyme 2 (DCP2) as a target of miR-4293 and its expression is suppressed by miR-4293. DCP2 can directly or indirectly bind to WFDC21P and downregulates its expression. Consequently, miR-4293 can further promote WFDC21P expression by regulating DCP2. With a positive correlation to miR-4293 expression, WFDC21P also plays an oncogenic role in lung carcinoma. Furthermore, knockdown of WFDC21P results in functional attenuation of miR-4293 on tumor promotion. In vivo xenograft growth is also promoted by both miR-4293 and WFDC21P. Overall, our results establish oncogenic roles for both miR-4293 and WFDC21P and demonstrate that interactions between miRNAs and lncRNAs through DCP2 are important in the regulation of carcinoma pathogenesis. These results provided a valuable theoretical basis for the discovery of lung carcinoma therapeutic targets and diagnostic markers based on miR-4293 and WFDC21P.
Strainberry: automated strain separation in low-complexity metagenomes using long reads
Authors: Vicedomini Riccardo , Quince Christopher , Darling Aaron E. , Chikhi Rayan
Published: July 2021

High-throughput short-read metagenomics has enabled large-scale species-level analysis and functional characterization of microbial communities. Microbiomes often contain multiple strains of the same species, and different strains have been shown to have important differences in their functional roles. Recent advances on long-read based methods enabled accurate assembly of bacterial genomes from complex microbiomes and an as-yet-unrealized opportunity to resolve strains. Here we present Strainberry, a metagenome assembly pipeline that performs strain separation in single-sample low-complexity metagenomes and that relies uniquely on long-read data. We benchmarked Strainberry on mock communities for which it produces strain-resolved assemblies with near-complete reference coverage and 99.9% base accuracy. We also applied Strainberry on real datasets for which it improved assemblies generating 20-118% additional genomic material than conventional metagenome assemblies on individual strain genomes. We show that Strainberry is also able to refine microbial diversity in a complex microbiome, with complete separation of strain genomes. We anticipate this work to be a starting point for further methodological improvements on strain-resolved metagenome assembly in environments of higher complexities.
Rapid discovery of self-assembling peptides with one-bead one-compound peptide library
Authors: Yang Pei-Pei , Li Yi-Jing , Cao Yan , Zhang Lu , Wang Jia-Qi , Lai Ziwei , Zhang Kuo , Shorty Diedra , Xiao Wenwu , Cao Hui , Wang Lei , Wang Hao , Liu Ruiwu , Lam Kit S.
Published: July 2021

Self-assembling peptides have shown tremendous potential in the fields of material sciences, nanoscience, and medicine. Because of the vast combinatorial space of even short peptides, identification of self-assembling sequences remains a challenge. Herein, we develop an experimental method to rapidly screen a huge array of peptide sequences for self-assembling property, using the one-bead one-compound (OBOC) combinatorial library method. In this approach, peptides on beads are N-terminally capped with nitro-1,2,3-benzoxadiazole, a hydrophobicity-sensitive fluorescence molecule. Beads displaying self-assembling peptides would fluoresce under aqueous environment. Using this approach, we identify eight pentapeptides, all of which are able to self-assemble into nanoparticles or nanofibers. Some of them are able to interact with and are taken up efficiently by HeLa cells. Intracellular distribution varied among these non-toxic peptidic nanoparticles. This simple screening strategy has enabled rapid identification of self-assembling peptides suitable for the development of nanostructures for various biomedical and material applications.
Lineage-defined leiomyosarcoma subtypes emerge years before diagnosis and determine patient survival
Authors: Anderson Nathaniel D. , Babichev Yael , Fuligni Fabio , Comitani Federico , Layeghifard Mehdi , Venier Rosemarie E. , Dentro Stefan C. , Maheshwari Anant , Guram Sheena , Wunker Claire , Thompson J. Drew , Yuki Kyoko E. , Hou Huayun , Zatzman Matthew , Light Nicholas , Bernardini Marcus Q. , Wunder Jay S. , Andrulis Irene L. , Ferguson Peter , Razak Albiruni R. Abdul , Swallow Carol J. , Dowling James J. , Al-Awar Rima S. , Marcellus Richard , Rouzbahman Marjan , Gerstung Moritz , Durocher Daniel , Alexandrov Ludmil B. , Dickson Brendan C. , Gladdy Rebecca A. , Shlien Adam
Published: July 2021

Leiomyosarcomas (LMS) are genetically heterogeneous tumors differentiating along smooth muscle lines. Currently, LMS treatment is not informed by molecular subtyping and is associated with highly variable survival. While disease site continues to dictate clinical management, the contribution of genetic factors to LMS subtype, origins, and timing are unknown. Here we analyze 70 genomes and 130 transcriptomes of LMS, including multiple tumor regions and paired metastases. Molecular profiling highlight the very early origins of LMS. We uncover three specific subtypes of LMS that likely develop from distinct lineages of smooth muscle cells. Of these, dedifferentiated LMS with high immune infiltration and tumors primarily of gynecological origin harbor genomic dystrophin deletions and/or loss of dystrophin expression, acquire the highest burden of genomic mutation, and are associated with worse survival. Homologous recombination defects lead to genome-wide mutational signatures, and a corresponding sensitivity to PARP trappers and other DNA damage response inhibitors, suggesting a promising therapeutic strategy for LMS. Finally, by phylogenetic reconstruction, we present evidence that clones seeding lethal metastases arise decades prior to LMS diagnosis.
ER – lysosome contacts at a pre-axonal region regulate axonal lysosome availability
Authors: Özkan Nazmiye , Koppers Max , van Soest Inge , van Harten Alexandra , Jurriens Daphne , Liv Nalan , Klumperman Judith , Kapitein Lukas C. , Hoogenraad Casper C. , Farías Ginny G.
Published: July 2021

Neuronal function relies on careful coordination of organelle organization and transport. Kinesin-1 mediates transport of the endoplasmic reticulum (ER) and lysosomes into the axon and it is increasingly recognized that contacts between the ER and lysosomes influence organelle organization. However, it is unclear how organelle organization, inter-organelle communication and transport are linked and how this contributes to local organelle availability in neurons. Here, we show that somatic ER tubules are required for proper lysosome transport into the axon. Somatic ER tubule disruption causes accumulation of enlarged and less motile lysosomes at the soma. ER tubules regulate lysosome size and axonal translocation by promoting lysosome homo-fission. ER tubule – lysosome contacts often occur at a somatic pre-axonal region, where the kinesin-1-binding ER-protein P180 binds microtubules to promote kinesin-1-powered lysosome fission and subsequent axonal translocation. We propose that ER tubule – lysosome contacts at a pre-axonal region finely orchestrate axonal lysosome availability for proper neuronal function.
From basic properties to the Mott design of correlated delafossites
Authors: Lechermann Frank
Published: July 2021

The natural-heterostructure concept realized in delafossites highlights these layered oxides. While metallic, band- or Mott-insulating character may be associated with individual layers, inter-layer coupling still plays a decisive role. We review the correlated electronic structure of PdCoO2, PdCrO2, and AgCrO2, showing that layer-entangled electronic states can deviate from standard classifications of interacting systems. This finding opens up possibilities for materials design in a subtle Mott-critical regime. Manipulated Hidden-Mott physics, correlation-induced semimetallicity, or Dirac/flat-band dispersions in a Mott background are emerging features. Together with achievements in the experimental preparation, this inaugurates an exciting research field in the arena of correlated materials.
Dynamic regulation of small RNAs in anthocyanin accumulation during blueberry fruit maturation
Authors: Li Xiaobai , Hong Yan , Jackson Aaron , Guo Fangqi
Published: July 2021

Blueberry is rich in anthocyanins which accumulate during fruit maturation. Previous studies mostly focus on their translational/transcriptional regulation, but usually underestimate their post-transcriptional regulation, e.g. small RNAs. This study aimed to identify sRNAs and their potential pathways associated with anthocyanin biosynthesis. During three typical phases of fruit maturation (green, pink, and blue), we investigated dynamic changes of sRNA by deep sequencing sRNA and examined the interaction of sRNAs with their target genes by degradome and RLM-PCR. During maturation, up-regulation of VcmiRNA156 and VcmiR393 resulted in down-regulation of VcSPLs and VcTIR1/AFBs, respectively. An important gene of anthocyanin biosynthesis, VcDFR, was substantially down-regulated at both the mRNA and protein levels, and potentially responded to regulation of VcSPLs and VcTIR1/AFBs. Additionally, indole acetic acid (IAA) and abscisic acid (ABA) were involved in the regulation of anthocyanin biosynthesis by interacting with VcmiR393-TIR1/AFBs and VcmiRNA319-VcMYBs respectively. This information provides another insight into blueberry anthocyanin biosynthesis.
Plasmonic mode coupling and thin film sensing in metal–insulator–metal structures
Authors: Andam N. , Refki S. , Hayashi S. , Sekkat Z.
Published: July 2021

Optical sensors based on surface plasmon resonance (SPR) in the attenuated total reflection (ATR) configuration in layered media have attracted considerable attention over the past decades owing to their ability of label free sensing in biomolecular interaction analysis, and highly sensitive detection of changes in refractive index and thickness, i.e. the optical thickness, of thin film adsorbates (thin film sensing). Furthermore, SPR is highly sensitive to the refractive index of the medium adjacent to the bare metal, and it allows for bulk sensing as well. When deposited at the metal/air interface, an adsorbed layer disturbs the highly localized, i.e. bound, wave at this interface and changes the plasmon resonance to allow for sensing in angular or wavelength interrogation and intensity measurement modes. A high degree of sensitivity is required for precise and efficient sensing, especially for biomolecular interaction analysis for early stage diagnostics; and besides conventional SPR (CSPR), several other configurations have been developed in recent years targeting sensitivity, including long-range SPR (LRSPR) and waveguide-coupled SPR (WGSPR) observed in MIM structures, referred here to by MIM modes, resulting from the coupling of SPRs at I/M interfaces, and Fano-type resonances occurring from broad and sharp modes coupling in layered structures. In our previous research, we demonstrated that MIM is better than CSPR for bulk sensing, and in this paper, we show that CSPR is better than MIM for thin film sensing for thicknesses of the sensing layer (SL) larger than 10 nm. We discuss and compare the sensitivity of CSPR and MIM for thin film sensing by using both experiments and theoretical calculations based on rigorous electromagnetic (EM) theory. We discuss in detail MIM modes coupling and anti-crossing, and we show that when a thin film adsorbate, i.e. a SL), is deposited on top of the outermost-layer of an optimized MIM structure, it modifies the characteristics of the coupled modes of the structure, and it reduces the electric field, both inside the SL and at the SL/air interface, and as a result, it decreases the sensitivity of the MIM versus the CSPR sensor. Our work is of critical importance to plasmonic mode coupling using MIM configurations, as well as to optical bio- and chemical-sensing.
Classification of ECG signals using multi-cumulants based evolutionary hybrid classifier
Authors: Dalal Sahil , Vishwakarma Virendra P.
Published: July 2021

Every human being has a different electro-cardio-graphy (ECG) waveform that provides information about the well being of a human heart. Therefore, ECG waveform can be used as an effective identification measure in biometrics and many such applications of human identification. To achieve fast and accurate identification of human beings using ECG signals, a novel robust approach has been introduced here. The databases of ECG utilized during the experimentation are MLII, UCI repository arrhythmia and PTBDB databases. All these databases are imbalanced; hence, resampling techniques are helpful in making the databases balanced. Noise removal is performed with discrete wavelet transform (DWT) and features are obtained with multi-cumulants. This approach is mainly based on features extracted from the ECG data in terms of multi-cumulants. The multi-cumulants feature based ECG data is classified using kernel extreme learning machine (KELM). The parameters of multi-cumulants and KELM are optimized using genetic algorithm (GA). Excellent classification rate is achieved with 100% accuracy on MLII and UCI repository arrhythmia databases, and 99.57% on PTBDB database. Comparison with existing state-of-art approaches has also been performed to prove the efficacy of the proposed approach. Here, the process of classification in the proposed approach is named as evolutionary hybrid classifier.
Natural processes dominate the pollution levels during COVID-19 lockdown over India
Authors: Madineni Venkat Ratnam , Dasari Hari Prasad , Karumuri Ramakrishna , Viswanadhapalli Yesubabu , Perumal Prasad , Hoteit Ibrahim
Published: July 2021

The lockdown measures that were taken to combat the COVID-19 pandemic minimized anthropogenic activities and created natural laboratory conditions for studying air quality. Both observations and WRF-Chem simulations show a 20–50% reduction (compared to pre-lockdown and same period of previous year) in the concentrations of most aerosols and trace gases over Northwest India, the Indo Gangetic Plain (IGP), and the Northeast Indian regions. It is shown that this was mainly due to a 70–80% increase in the height of the boundary layer and the low emissions during lockdown. However, a 60–70% increase in the pollutants levels was observed over Central and South India including the Arabian sea and Bay of Bengal during this period, which is attributed to natural processes. Elevated (dust) aerosol layers are transported from the Middle East and Africa via long-range transport, and a decrease in the wind speed (20–40%) caused these aerosols to stagnate, enhancing the aerosol levels over Central and Southern India. A 40–60% increase in relative humidity further amplified aerosol concentrations. The results of this study suggest that besides emissions, natural processes including background meteorology and dynamics, play a crucial role in the pollution concentrations over the Indian sub-continent.
Using 2D video-based pose estimation for automated prediction of autism spectrum disorders in young children
Authors: Kojovic Nada , Natraj Shreyasvi , Mohanty Sharada Prasanna , Maillart Thomas , Schaer Marie
Published: July 2021

Clinical research in autism has recently witnessed promising digital phenotyping results, mainly focused on single feature extraction, such as gaze, head turn on name-calling or visual tracking of the moving object. The main drawback of these studies is the focus on relatively isolated behaviors elicited by largely controlled prompts. We recognize that while the diagnosis process understands the indexing of the specific behaviors, ASD also comes with broad impairments that often transcend single behavioral acts. For instance, the atypical nonverbal behaviors manifest through global patterns of atypical postures and movements, fewer gestures used and often decoupled from visual contact, facial affect, speech. Here, we tested the hypothesis that a deep neural network trained on the non-verbal aspects of social interaction can effectively differentiate between children with ASD and their typically developing peers. Our model achieves an accuracy of 80.9% (F1 score: 0.818; precision: 0.784; recall: 0.854) with the prediction probability positively correlated to the overall level of symptoms of autism in social affect and repetitive and restricted behaviors domain. Provided the non-invasive and affordable nature of computer vision, our approach carries reasonable promises that a reliable machine-learning-based ASD screening may become a reality not too far in the future.
Automated machine learning optimizes and accelerates predictive modeling from COVID-19 high throughput datasets
Authors: Papoutsoglou Georgios , Karaglani Makrina , Lagani Vincenzo , Thomson Naomi , Røe Oluf Dimitri , Tsamardinos Ioannis , Chatzaki Ekaterini
Published: July 2021

COVID-19 outbreak brings intense pressure on healthcare systems, with an urgent demand for effective diagnostic, prognostic and therapeutic procedures. Here, we employed Automated Machine Learning (AutoML) to analyze three publicly available high throughput COVID-19 datasets, including proteomic, metabolomic and transcriptomic measurements. Pathway analysis of the selected features was also performed. Analysis of a combined proteomic and metabolomic dataset led to 10 equivalent signatures of two features each, with AUC 0.840 (CI 0.723–0.941) in discriminating severe from non-severe COVID-19 patients. A transcriptomic dataset led to two equivalent signatures of eight features each, with AUC 0.914 (CI 0.865–0.955) in identifying COVID-19 patients from those with a different acute respiratory illness. Another transcriptomic dataset led to two equivalent signatures of nine features each, with AUC 0.967 (CI 0.899–0.996) in identifying COVID-19 patients from virus-free individuals. Signature predictive performance remained high upon validation. Multiple new features emerged and pathway analysis revealed biological relevance by implication in Viral mRNA Translation, Interferon gamma signaling and Innate Immune System pathways. In conclusion, AutoML analysis led to multiple biosignatures of high predictive performance, with reduced features and large choice of alternative predictors. These favorable characteristics are eminent for development of cost-effective assays to contribute to better disease management.
Effects of eliminating interactions in multi-layer culture on survival, food utilization and growth of small sea urchins Strongylocentrotus intermedius at high temperatures
Authors: Hu Fangyuan , Chi Xiaomei , Yang Mingfang , Ding Peng , Yin Donghong , Ding Jingyun , Huang Xiyuan , Luo Jia , Chang Yaqing , Zhao Chong
Published: July 2021

Poor growth and disease transmission of small sea urchins Strongylocentrotus intermedius in summer greatly hamper the production efficiency of the longline culture. Reducing the adverse effects of high stocking density while maintaining high biomass is essential to address these problems. Here, we conducted a laboratory experiment to simulate the multi-layer culture for sea urchins at ambient high temperatures (from 22.2 to 24.5 °C) in summer for ~ 7 weeks. Survival, body size, lantern growth, gut weight, food consumption, Aristotle's lantern reflex, 5-hydroxytryptamine concentration, pepsin activity and gut morphology were subsequently evaluated. The present study found that multi-layer culture led to significantly larger body size than those without multi-layer culture (the control group). This was probably because of the greater feeding capacity (indicated by lantern growth and Aristotle's lantern reflex) and food digestion (indicated by morphology and pepsin activity of gut) in the multi-layer cultured sea urchins. These results indicate that multi-layer is an effective approach to improving the growth efficiency of sea urchins at high temperatures. We assessed whether eliminating interaction further improve these commercially important traits of sea urchins in multi-layer culture. This study found that eliminating interactions displayed greater body size and Aristotle's lantern reflex than those not separated in the multi-layer culture. This approach also significantly reduced the morbidity compared with the control group. These novel findings indicate that eliminating interactions in multi-layer culture greatly contributes to the growth and disease prevention of sea urchins at high temperatures. The present study establishes a new technique for the longline culture of sea urchins in summer and provides valuable information into the longline culture management of other commercially important species (e.g. scallops, abalones and oysters).
Development of thymic tumor in [LSL:KrasG12D; Pdx1-CRE] mice, an adverse effect associated with accelerated pancreatic carcinogenesis
Authors: Liot Sophie , El Kholti Naïma , Balas Jonathan , Genestier Laurent , Verrier Bernard , Valcourt Ulrich , Lambert Elise
Published: July 2021

Pancreatic Ductal AdenoCarcinoma (PDAC) represents about 90% of pancreatic cancers. It is one of the most aggressive cancer, with a 5-year survival rate below 10% due to late diagnosis and poor therapeutic efficiency. This bad prognosis thus encourages intense research in order to better understand PDAC pathogenesis and molecular basis leading to the development of innovative therapeutic strategies. This research frequently involves the KC (LSL:KrasG12D;Pdx1-CRE) genetically engineered mouse model, which leads to pancreatic cancer predisposition. However, as frequently encountered in animal models, the KC mouse model also exhibits biases. Herein, we report a new adverse effect of KrasG12D mutation in KC mouse model. In our hands, 10% of KC mice developed clinical signs reaching pre-defined end-points between 100- and 150-days post-parturition, and associated with large thymic mass development. Histological and genetic analyses of this massive thymus enabled us (1) to characterize it as a highly proliferative thymic lymphoma and (2) to detect the unexpected recombination of the Lox-STOP-Lox cassette upstream KrasG12D allele and subsequent KRASG12D protein expression in all cells composing thymic masses. Finally, we highlighted that development of such thymic tumor was associated with accelerated pancreatic carcinogenesis, immune compartment disorganization, and in some cases, lung malignancies.
In situ electroporation of mammalian cells through SiO2 thin film capacitive microelectrodes
Authors: Maschietto M. , Dal Maschio M. , Girardi S. , Vassanelli S.
Published: July 2021

Electroporation is a widely used non-viral technique for the delivery of molecules, including nucleic acids, into cells. Recently, electronic microsystems that miniaturize the electroporation machinery have been developed as a new tool for genetic manipulation of cells in vitro, by integrating metal microelectrodes in the culture substrate and enabling electroporation in-situ. We report that non-faradic SiO2 thin film-insulated microelectrodes can be used for reliable and spatially selective in-situ electroporation of mammalian cells. CHO-K1 and SH-SY5Y cell lines and primary neuronal cultures were electroporated by application of short and low amplitude voltage transients leading to cell electroporation by capacitive currents. We demonstrate reliable delivery of DNA plasmids and exogenous gene expression, accompanied by high spatial selectivity and cell viability, even with differentiated neurons. Finally, we show that SiO2 thin film-insulated microelectrodes support a double and serial transfection of the targeted cells.